This article is part of the 2019 Oncology Special Issue of Natural Medicine Journal. Read the full issue here. 

Tina Kaczor, ND, FABNO, interviews Shauna Birdsall, ND, FABNO, on what clinicians need to know about skin cancers. From preventing squamous cell carcinomas to recognizing melanoma, Birdsall details the essentials of cancer-related dermatology.

This interview includes a broad review of what you can do to help patients prevent skin cancer. Do you remember the ABCDE’s of recognizing melanoma? Where do squamous and basal cell carcinomas usually occur? What is the ideal range for serum vitamin D? What other supplements have evidence for reducing the risk of squamous cell cancers? We cover all this and more in this in-depth discussion between integrative oncology experts.

About the Expert

Shauna M. Birdsall, ND, FABNO, is a naturopathic physician and fellow of the American Board of Naturopathic Oncology. Birdsall graduated from National University of Natural Medicine in 2000. After completing a residency at Cancer Treatment Centers of America (CTCA) at Midwestern Regional Medical Center in 2002, she provided patient care and supervised naturopathic medical students there until 2008. She took on a leadership role at Western Regional Medical Center at CTCA in Goodyear, AZ, in 2008 and was later elected vice chief of the medical staff there. She also chaired the Medical Executive Committee, Credentials Committee, Peer Review Committee, and served as the Medical Director of Integrative Oncology until 2018. Birdsall recently joined Avante Medical Center in Anchorage, AK. One of Phoenix Magazine’s Top Doctors 2014-2018, Birdsall is strongly committed to providing individualized, compassionate, evidence-based care to empower and provide hope to cancer patients.

Transcript

Tina Kaczor, ND, FABNO: Hello. I'm Tina Kaczor, editor-in-chief here at the Natural Medicine Journal. I'm talking today with Dr. Shauna Birdsall about skin cancers, and Dr. Shauna Birdsall has graduated from the National College of Natural Medicine in the year 2000. After that, she went to Cancer Treatment Centers of America, and she has been a specialist in integrative oncology since graduation. She's most recently taken a position at Avante Medical Center in Anchorage, Alaska, where she'll be providing patient care in a hospital-based setting. Shauna, thanks so much for joining me.

Shauna Birdsall, ND, FABNO: Oh, thank you for having me.

Kaczor: Dr. Birdsall, you've recently worked closely with a lot of dermatologists in a dermatologist setting, and you and I got talking about that. I was intrigued by a lot of the things that you learned, and I would like you to elaborate a little bit on how working closely alongside these dermatologists maybe changed your perspective of oncology and skin cancer specifically.

Birdsall: I have to say I was blown away, and this is a bit embarrassing. Working with patients undergoing chemotherapy and radiation for cancers like breast cancer and pancreatic cancer, I had always seen dermatology as more on the periphery. Working with dermatologists showed me how often dermatologists are diagnosing things like melanoma and really saving people's lives. It completely changed my perception around the integral nature of the specialty.

Kaczor: Yeah. I think that's what struck me, because you and I have parallel universes in the idea of our professions. We both graduated in the same year, and we've both been doing integrative oncology. I have to say I haven't worked closely with dermatologists. I share your inclination to say, "Ah, yeah, skin, we can catch that. No problem. We always catch skin cancer," and, I mean, that's despite the fact that of course we've both worked with people with metastatic melanoma.

We'll get to that and the importance of prevention, especially to prevent such tragedies as metastatic disease. I'd like you to give us a primer, and just give us a really basic overview for the clinicians out there on the types of skin cancers that there are, and who they most likely effect as well.

Birdsall: Sure. First of all, skin cancer is the most common type of cancer, and in the United States this year, more than 5 million people will be diagnosed with skin cancers. First and foremost, we like to talk about actinic keratoses. These are also known as AKs, and they are really precancerous lesions. You'll hear, the resounding themes of those that have sun exposure as being at risk for these cancers as I go on, but essentially actinic keratoses are often flaky or scaly patches of skin, and it's important that those are identified and treated, as sometimes they can lead to squamous cell carcinoma.

The most common type of skin cancer is basal cell carcinoma or BCC. This accounts for about 80% of skin cancers, and BCCs usually look like a flesh-colored pearl or bump, or a pinkish patch of skin. All of these skin cancers are going to be more prevalent in patients with fair skin, although patients with skin of all colors can develop these skin cancers.

Then, as I mentioned we're going to repeatedly talk about risk with sun exposure, and that means that the areas of the body that are most frequently exposed to sun such as the face, head, chest, arms and legs are going to be the most prevalent areas that you can see these cancers.

Squamous cell carcinoma is the most second type of skin cancer, and you're going to also see squamous cell cancers on areas like the rim of the ear. You really need to be able to make sure that those are identified, as those cancers can spread more deeply into tissues and cause additional damage, as well as metastasize elsewhere.

Melanoma, as we talked about earlier, is the deadliest form of skin cancer. It's actually been on the rise for the last 50 years. Melanoma in situ annual incidents in the United States is 9.5%, and in the United States melanoma has become the fifth-most common cancer in men and women. Melanoma increases with age, and you do see again the sun exposure and fair skin as common risk factors. I think later on, we'll talk about more risk factors for melanoma.

Kaczor: Yeah. That's an incredible statistic. Nearly 10% incidence for in situ melanoma. Wow.

Birdsall: Yes. Which is why I really started waking up to the issues with skin cancer detection and prevention, working with dermatologists, because I just was blown away, as I mentioned, with how often they were diagnosing either melanoma in situ or melanomas.

Kaczor: That's just checking. I mean, that's just skin checks, not coming in with that complaint.

Birdsall: Yes.

Kaczor: Most of our listeners are practitioners that are primary practitioners. Very few are going to be specialists in skincare, of course. I'd like us to maybe, if you could, go through how to recognize melanoma, and maybe making sure that when we are seeing our patients ... and this could be in a specific skin exam, or it could also just be an incidental finding on their arm or their face or whatever. What are we looking for with melanoma?

Birdsall: Melanomas frequently develop in a mole or suddenly appears as a new dark spot on the skin. If you'll recall, we have the ABCDE warning signs, and I'm just going to go through those just for all of our review. A stands for asymmetry. B stands for border, either irregular, scalloped or poorly defined. C stands for color, varied really from one area to another in the same mole, and you can see shades of tan and brown, black, white, pink, red or blue. I think one of the most shocking melanomas that I saw was a melanoma inside the web of the toes in a patient that just looked like a little pink spot.

D stands for diameter. While melanomas are usually greater than 6 millimeters in size, which is the size of a pencil eraser, when initially diagnosed they can be smaller. E stands for evolving, a mole or a skin lesion that looks different from the rest or is changing in size, shape or color.

What is important to know as well is that melanomas don't necessarily read the textbooks. As I mentioned, they can look like something that, for those of us who are not dermatologists, may not look like something of concern, which is why I became aware of the need for annual skin exams.

Kaczor: Yeah. Yeah. It is remarkable that some of them don't look like much, and I think that erring on the side of caution, especially as our patients get older and older, because aging is a risk factor for all cancers, and I'm assuming skin cancer is included in there. Okay. Is there anything else? Last notes besides ABCD and E, and anything else that people should be looking for clinically before we close that discussion?

Birdsall: An area that's itching, bleeding. An area that opens up and appears to heal over, and then opens up again. Anything like that also needs to be evaluated.

Kaczor: Okay. Yeah. Referral to a dermatologist is simple enough that I think it's ... again, erring on the side of caution seems like a smart thing to do. We talked about melanoma, and experience shows us that of course it's the most likely to go somewhere. It's most likely to spread and become fatal for some patients, but I'm curious. Basal cell and squamous cell carcinoma, what is the risk of any local or metastatic disease with those?

Birdsall: In the majority of patients with cutaneous squamous cell carcinoma or basal cell carcinoma, the disease remains limited to the skin and with appropriate treatment is considered, "cured," which you and I both know we don't get to use that word very often in oncology. It's exciting that something can be cured with appropriate treatment. However, in 3 to 7% of patients with cutaneous squamous cell carcinoma, and rarely in individuals with basal cell carcinoma, local, regional or distant metastases can occur, which increases the risk for mortality or death.

Kaczor: Do you happen to know, is this analogous to melanoma in that the depth of the lesion has anything to do with it? Do you know?

Birdsall: Yes. For both basal cell and squamous cell carcinomas, both the depth and the size can contribute to risk, which is why even though a patient might only have a small spot, why it's important that it be caught early and treated, because left to its own devices, the larger it gets, the more at risk a patient is.

Kaczor: Okay. Well, that makes logical sense. As far as melanomas go, you mentioned in situ is nearly 10%. Are most of them still caught in the early stages, before they go anywhere?

Birdsall: Yes. Yeah. About 85% of melanomas are caught when there's only localized disease, so Stage I or Stage II at presentation, which as you and I both know, that's when you see the best survival rates. At diagnosis, about 15% have regional nodal disease, and only about 2% have distant metastases at the time of diagnosis. We're getting better at diagnosing skin cancers and melanoma, and it's theorized that dermatologists are more likely to biopsy these days because of seeing a higher prevalence.

Kaczor: I see. Okay. Can I ask one question? That is, in some states, including where I am in Oregon, naturopathic physicians can do minor surgery. The question I have ... I know my opinion on this, but I want to hear your opinion on this. It's not uncommon for shave biopsies to happen in-office. This is true of primary care physicians across the board, not just naturopaths. If someone suspects a melanoma, yea or nay on something like a biopsy of that, whether it's a punch biopsy or a shave biopsy?

Birdsall: Nay, and the reason is that there is research that the sooner after initial diagnosis ... so the sooner after initial biopsy ... that patient is able to get definitive treatment for their melanoma, the better. One of the risks, if someone other than a dermatologist or another health professional biopsies melanoma, is that there's then a delay potentially in getting the patient in to the provider that's going to be able to provide definitive treatment for that melanoma. That's one of the risks. Really, you want to see the highest level of specialty if you suspect a melanoma.

Kaczor: Okay. I think that needs to be reiterated time and again, because every once in a while you come across those patients, and your hair stands up when they tell you what first happened to their lesion, and you just hope that it didn't go anywhere. Okay. Let's talk about, again, we're talking to our audience is generally practitioners that are frontline folks, and which patient populations, which types of people, should there be particular vigilance for skin cancers, like higher levels of suspicion, and who exactly?

Birdsall: Okay. I warned you that we'd keep going back to a couple of things. Fair-skinned individuals, particularly those with blonde hair, red hair, lighter-colored eyes, blue eyes, although again, the warning that skin cancers can occur in patients of any skin color, and then that hallmark UV, exposure to UV radiation. More sun exposure, more risk. Also, however, living in sunny climates or higher altitudes, again because you're getting more direct exposure to UV radiation, as well as lower latitudes. Moles, patients that have more than 50 moles are at higher risk, and patients that have had a history of dysplastic nevi nearby or abnormal moles.

Patients with actinic keratoses are at higher risk. Patients with either a family history of skin cancer or a personal history of skin cancer, and immune suppression. I want to just take a moment to talk about immune suppression, because that can include a variety of different patient populations. That can include patients living with HIV or AIDS, or oncology patients that maybe are receiving chemotherapy or maybe their immune system hasn't recovered from prior chemotherapy, and it does include patients on immunosuppressive drugs such as for organ transplants. Patients who've had an organ transplant are at high risk for skin cancers because they're likely to have a lifetime of immune suppression because of those immunosuppressive drugs.

Lastly, exposure to radiation. You and I think of patients that have been exposed to radiation like breast cancer patients, lung cancer patients, et cetera. However, sometimes patients are exposed to radiation for skin conditions like basal cell carcinoma or eczema or acne, just different types of radiation. Then, exposure to chemical substances like arsenic can also increase risk, and then age increases risk. We're just at higher risk, the longer that we're living a lifetime out, being exposed to the sun.

Kaczor: Is it true that childhood exposures can have an effect decades later? Like someone who grew up down in San Diego, for example, but they live in Minnesota?

Birdsall: Yes, especially to melanoma. I am a-fair skinned person and I had an unfortunate history of a couple of different blistering sunburns, and that history of childhood sunburns and history of blistering sunburns can increase risk, especially for melanoma.

Kaczor: Okay. Yeah. That's good to have validated, because I've always heard that. Maybe in our patient intakes, it's something we should put on our intake forms. Not only where did you grow up, but did you get burned, sunburned?

Birdsall: Yes.

Kaczor: Back in the day, of course, there was a time when people intentionally went out there and called a burn halfway to a tan.

Birdsall: That actually reminds me. I don't think of indoor tanning frequently these days, but exposure to indoor tanning and tanning beds. Maybe your patient is very responsible now as an adult, but maybe in their teenage years had a long history of exposure to tanning beds.

Kaczor: Yeah, yeah. It's something that's easily overlooked in an intake. Maybe we should make sure that that's top of mind. Let's talk a little bit about screening and prevention, and how can we make sure that we do catch things early, especially melanoma. What are the current recommendations, even, for skin cancer prevention?

Birdsall: It's interesting. As far as screening, it remains somewhat of a controversy, which surprised me. US Preventive Task Force is considered one of the authorities on screenings, and to date, the US Preventive Task Force hasn't found sufficient evidence either for or against skin screenings. What's interesting is there is a lot of debate amongst other experts in the field. The American Cancer Society actually recommends a cancer-related checkup every three years for patients between age 28 to 40, and then also encompassed in that cancer-related checkup is other kinds of screenings in addition to skin cancer screenings, and then every year for anyone over 40. Interestingly, the American Medical Association really sees it as individualized, and recommends that a patient should talk to their physician about frequency for skin cancer screenings, and those at moderate risk even should see their PCP or dermatologist annually.

The American Academy of Dermatology issued a statement regarding their disappointment over the recommendation by the US Preventive Task Force, and felt that the public should know that that recommendation that was neither for nor against annual skin cancer screening did not apply to individuals with suspicious skin lesions or those with increased skin cancer risk, and does not apply to the practice of skin self-exams. The American Academy of Dermatology recommends that patients really function as their own health advocate by regularly conducting skin self-exams and that if the patients see anything unusual, that they should see a dermatologist. Unfortunately, we all know that there's not always consistency with patients regarding advising for self-exam, and a patient can't necessarily see the back of their neck or their back, that may have had a lot of sun exposure. A number of dermatology providers still recommend annual skin exams, which after working with dermatologists, I'm definitely an advocate for as well.

Kaczor: Yeah. Yeah, that makes sense. All it takes is a few cases. We're all a product of our experience, right? You see a few cases where it could have been prevented, and it seems and it is tragic. What can we do? I guess once we identify patients who are at higher risk, due to either childhood or exposure or fair skin or immune suppression, like what can we do to prevent skin cancers?

Birdsall: Again, not to sound like a broken record, but decreasing sun exposure is the first thing. Interestingly enough, while I was just reviewing the research when I was preparing for our interview, I was looking at the Environmental Working Group and sunscreens, because there are definitely sunscreen ingredients these days that people have concerns about. For a patient that might be more holistically inclined, they might feel somewhat reluctant to put some of the ingredients that are in sunscreens on their skin, and so there's still a number of things that we can recommend. One is the physical sunscreens that are more of a barrier, and zinc oxide and titanium dioxide were considered generally safe and effective by the Environmental Working Group, and those are sunscreens with definitely friendlier ingredients that people may feel a lot more comfortable using and recommending. Secondly, wearing clothing shields our skin from sun exposure. There's some really interesting sun-protective clothing that is coming out as well if people are in the sun more frequently. Just trying to stay out of the sun during the peak periods or during high heat indexes is also something that patients can do as well. Then, doing annual skin exams. Because as you and I talked about, we may not feel concerned about a lesion that a dermatologist may instantly pick up on as something that may need to be further evaluated.

Kaczor: Yeah. On that note, I don't remember when I read this, but years ago I remember reading they did surveys of lesions, and they had primary care physicians and dermatologists assess them and see who was most accurate. Nobody bats a thousand, but it was remarkable how much better the dermatologists were at visually assessing lesions correctly.

Birdsall: Well, what was interesting working with dermatologists is I'd ask them why they were attracted to their field, why they went into dermatology, and they said because it's actually a field of medicine that you visually diagnose. You can visually see what's going on. Internal medicine, you might look at the results of a patient's lab work or a chest X-ray, but dermatology, you can actually see pathology and treat it.

Kaczor: Yeah. How interesting. Yeah, so I guess you're good at that. Some people are better than others, I think. We are naturopaths, and so let's talk a little bit about diet and supplements and other things that we can do. What can we do from a supplement standpoint? Is there anything we can add or anything we should avoid, for that matter, that could lower the risk of developing cancer, skin cancer specifically?

Birdsall: There was a really interesting Phase 3 randomized trial of nicotinamide for skin cancer prevention published in the New England Journal of Medicine in October of 2015, and in the study, 386 participants who had a history of at least 2 non-melanoma skin cancers ... again, that's basal cell carcinoma or squamous cell carcinoma ... in the past 5 years were randomized to receive 500 milligrams of nicotinamide twice daily or placebo for 12 months. They were seen by dermatologists every 3 months.

At the end of the study, the rate of new non-melanoma skin cancers was lowered by 23% in the nicotinamide group, and noteworthy was the fact that there was no benefit after the nicotinamide was discontinued. I would say about 70% of the dermatologists that I was working with recommended nicotinamide to their patients. That's actually compelling data from my perspective in regards to a supplement.

There's another supplement that has less research but is something interesting to watch called polypodium leucotomos, which is a fern from Central and South America. It was actually shown in studies to prevent both UVA- and UVB-induced toxicity and DNA damage. There was a study showing that 240 milligrams of a supplement containing that ingredient twice daily suppressed sunburn, and was found to extend the time outdoors before skin started to tan, so that's another possibility. I think we know as naturopathic doctors that vitamin C, E, zinc, beta carotene, omega-3 fatty acids, lycopene and polyphenols, especially in things like green tea, do also help to prevent free radical damage, which is what the exposure to UV radiation causes as well.

Kaczor: Okay. Yeah. Is there a specific role ... I don't I honestly don't remember where I have this idea from, so you can validate or invalidate my presumption ... about using vitamin A specifically for actinic keratosis?

Birdsall: Sure. There was a study on high-dose vitamin A reducing the incidence of actinic keratosis converting to squamous cell carcinoma, and the study looked at doses ranging from 25,000 IU a day, 50,000 IU a day and 75,000 IU a day. They did indeed find that that did prevent those AKs from turning into SCCs pretty significantly. However, from my perspective, there'd need to be a risk/benefit weighing of that for any particular patient.

Kaczor: Yeah. Because 25,000 to 75,000 IU daily for an extended period is ...

Birdsall: Correct. I had some concern after looking at that.

Kaczor: Yeah. Yeah. Recently, I mean, I generally wasn't too concerned with vitamin A levels as we gave them until ... because we would often use this dose for antiviral effects. Recently I came across a study that did suggest that high doses for prolonged periods actually can lead to or at least are correlated with fatty liver. I was a little surprised by that. I came upon it, of course, by way of patient care and doing a little due diligence. Anyways, that's just a little caveat

Birdsall: Right. I just am looking at that study and thinking about the fact that you would need to be on that long-term. I just had some concerns about using that particular amount of time.

Kaczor: Yeah, yeah. Not just the known, but the unknowns. Okay. Let's turn to vitamin D, because that whole "Do I'd get enough sun for vitamin D, am I getting so much sun that I'm increasing my risk of skin cancer," it seems to be a bit of a conundrum. On the same note and maybe in the context of this, is there a difference between sunburns and suntans and their link to skin cancer?

Birdsall: Okay. I think that there's definitely good evidence to suggest that vitamin D production from sun exposure poses too much of a risk for skin cancer. That's probably not the way that we want to be getting enough vitamin D, and there is more risk with a sunburn. However, suntans, our concept of tanning as being something that adds to our attractiveness, which I think in this day and age has faded with all the concern and the risk. Tanning does pose a risk too. That is still damage to your skin. Actually, as I was reviewing the research and thinking about this interview ... I'm just going to throw this in now, even though it's a little tangential and random ... if you have patients that are worried about the anti-aging, about the appearance of their skin, really the very best thing that they could do is to avoid sun exposure, to apply sunscreen, et cetera, because even that tanning still actually represents damage.

Kaczor: Okay. The vitamin D, what I hear you saying is it's best taken supplementally.

Birdsall: Yes.

Kaczor: Because we have access of doing labs for our patients and such, is there an ideal dose to give, or do we base it on laboratory values? What is your opinion on that?

Birdsall: My opinion is that we need to base it on laboratory values, because there's so much individual variation on intake of vitamin D and the impact of that intake. One patient may consume a lot of dietary sources of vitamin D and actually be at perhaps not an optimal, optimal level, but not be deficient in vitamin D. Another patient may take some vitamin D supplements and actually get to pretty high levels of vitamin D pretty quickly. I think the only thing that we can do for our patients right now is to do lab testing.

Having said that, there is a lot of controversy over what the right values are, what the right range is. Again, when I was doing research just to make sure that I was totally up to date before we talked, it looks like people are in agreement over the fact that a 25-hydroxy vitamin D level below 20 nanograms per milliliter is considered deficient and does need repletion. We have more concurrence over that value.

What's still controversial is what is that optimal range? Is it between 30 and 40? Is it 50? What we do know is that vitamin D can reach toxic levels, and that that's not good either, and that there is more and more data on too high of a level of vitamin D posing risk. I think that that again argues for making sure that we're adequately testing our patients, because say they're deficient, we decide that they need repletion. It's still hard to monitor, without doing that testing, where they're at from a vitamin D level as you're doing repletion.

Kaczor: Sure. Sure. Yeah, I totally agree. I think that laboratory values should be just part of a routine lab for most people, given the many ways that vitamin D adequacy protects us from so many diseases.

My last question is having to do with those who know they have a family history of skin cancers, maybe even particularly melanoma, but skin cancers in general. Is it appropriate, I suppose, for certain patients with a strong family history to look at genetic predispositions and hereditary syndromes that include skin cancer?

Birdsall: That's interesting, again still a little bit of a controversy. We can test for a couple of genetic mutations related to melanoma. People who have a mutation on a gene known as CDKN2A have a higher risk of developing melanoma, pancreatic cancer, or a tumor of the central nervous system. A mutation on the gene called BAP1 means a higher risk of getting melanoma, melanoma of the eye or mesothelioma, and kidney cancer. However, the challenge is that if a patient carries a mutation on one of those genes, their lifetime risk of getting melanoma ranges from 60% to 90%. However, only about 10% of the people who develop melanoma have one of these genes.

What we do know is that we're still evolving our scientific knowledge of genetic mutations, and it's highly likely that there are additional genetic mutations that we just haven't found yet for melanoma. This is a really important conversation for a patient to have with their healthcare provider, or even ideally with a genetic counselor, who can counsel them on the risks and benefits of genetic testing overall.

Kaczor: Yeah. Yeah. Genetic counselors are a great referral for us to have, because we don't need to figure everything out and they have it all either at their fingertips or in their minds, so they're they're great professionals to ally with. All right. Well, I think that that's a really good survey and a nice review of reminders of things we may know, and maybe some things that are definitely new to our listeners. I can't thank you enough for taking some time and sharing your expertise with us today. Thanks, Shauna.

Birdsall: Thanks. Thanks for having me.

Kaczor: Take care.

The mission of the Climate Collaborative is to leverage the power of the natural product industry to positively impact climate change. Their goal is to bring the industry together in an effort to reverse climate change. In this interview, the organization's director, Erin Callahan, describes how they intend to achieve this lofty goal.

Here's more NMJ coverage on how climate change will impact our food supply:

• Climate Change and Food Quality
• More Anticipated Damage to Food Quality from Global Warming

About the Expert

Erin Callahan is the director of the Climate Collaborative, responsible for management and execution of the Collaborative’s work, including all programming, communications, and outreach. Erin has a range of corporate campaigning and sustainability experience. She previously worked for CDP, managing corporate engagement for the We Mean Business coalition’s commitments campaign. In that role, Erin worked with hundreds of the world’s largest companies, industry groups, and investors, supporting them in making leadership commitments on climate change. She has also worked in public relations and international development and earned a master’s degree in international relations and economics from Johns Hopkins University School of Advanced International Studies. She is based in Oakland, CA.

Transcript

Karolyn Gazella: Hello. I'm Karolyn Gazella, the publisher of the Natural Medicine Journal. Today we are tackling the big topic of reversing climate change. My guest is Erin Callahan, who is the director of Climate Collaborative. Erin, thanks so much for joining me.

Erin Callahan: Thanks for having me.

Gazella: Well, first let's have you tell us a little bit about the history of the Climate Collaborative.

Callahan: Yeah. I'd love to. Well, thank you again for having me, I'm really excited to talk about some of our work. So the first thing to note is that we're a relatively new organization. We launched about 2 and a half years ago, just over that, at Natural Products Expo West, which is the largest food show in the US.

And we launched because it did become really clear that within the natural product space, which is the fastest growing part of the food and ag sector and full of innovative companies, who are really helping define their mission and work via social impact and issues related to it, there wasn't yet a convening space for companies to come together on climate change. And we in fact did this study that showed that around 97% of the companies we surveyed really understood the urgency to be doing something on climate change, but almost 80% of them didn't know how to translate that understanding into action. There was a big gap between knowing that they wanted to do something and having the capacity to tackle it within their businesses.

And so we launched to kind of address that gap. We really wanted to create a community of companies within the industry who could learn from each other, move forward together and get the rest of the industry really excited about climate change. And so that's what we've been trying to do for the past 2 and a half years. And I can certainly talk about the ways in which we do that, if that would be useful.

Gazella: Yeah. Let's start with what you've been focusing on since 2017 when you started. So what's been the focus over the last couple of years?

Callahan: Yeah. Well, you know, when Jessica Roth, the founder of Happy Family Organics the baby food company, and Lara Dickinson, the founder of OSC2, they were the cofounders of the Climate Collaborative and they really wanted to launch it as an industry collaboration.

So we're a project of 2 organizations, SFTA and OSC2, and have collaboration deeply built into our model. And so over the past year we've really been working to try and extend that, kind of, baseline of collaboration and understanding that to tackle a problem as big as climate change, we can't act alone. No one in the industry can think that they're going to solve it on their own in a silo, so we've really been trying to build robust industry collaboration.

And we've done that by creating this roadmap of nine commitment areas that represent the key emissions drivers for most companies in the sector. So it's packaging, food waste, agricultural practices, transportation, policy engagement, and we ask companies to make commitments, public commitments, in one or all of those areas. And that sends a message out to the industry that, "Hey. We are taking this seriously, we're setting public goals, and we are working as part of a bigger movement within the industry to do this."

And so we asked companies to make commitments and then we help them on the implementation side. So we host webinars, we connect companies to partners and solutions providers, we try to connect companies to case studies and representations of what best practice looks like within the industry and work really closely with a really wide range of partners. And, crucially, we do this all for free.

We're a nonprofit, so it's really important to us to not have cost, or any other issue, be a barrier to entry for companies. We work mostly with small and medium-sized companies who otherwise might not have the resources to start tackling this stuff. And so we really want to enable companies, regardless of where they're getting started, to be able to get on a pathway to action. And to do so as part of a really whole of industry movement.

So we have everything from farmers and producers, to distributors and food retailers and brands, all working together collectively across the supply chain. Recognizing you need every link to really make change. And so that's been the baseline for the past 2 and a half years has really been building a strong base of companies who are committed to action. Kind of building this movement within the industry, and then starting to go down the road of providing really robust programming that can help them on the implementation side.

You know, our theory of change is commit, act, impact, and we're kind of trying, you know, over the course of years of being around, to move companies from making these public commitments toward acting on them and then ultimately seeing real impact in the industry. And that's been the journey so far.

Gazella: Yeah. I think it's brilliant. I mean, that's really why I was drawn to your organization, because you have this holistic collaborative from start to finish and you're getting commitments from organizations. So how many organizations have made this commitment that you're talking about? You know, you have 9 commitment areas, and they need to commit to 1 or all, how many organizations have done so?

Callahan: Yeah. It's really incredible. We've got over 400. We've got nearly 450 companies signed up. We're at about 440 companies who've made over 1,600 commitments.

And that's, I think, over 2 a day. I did the math recently, since we launched, commitments coming in. And, in fact, our busiest single month ever was this past August 2 and a half years in. And so I think what that shows is that the energy and momentum and sense of importance and value of what we're doing is only picking up as companies see climate change impacting their supply chains more and more and hear their customers talking about it and inherit it becoming a policy issue ahead of the 2020 elections. It's only becoming more important and central to what companies are doing, and that is incredibly heartening to see. We are so happy to see that progress.

And so, yeah, we've got about 440 companies committed. They've made... You know, those represent General Mills and Dannon, really large food companies that everyone here has heard of and probably have their products in the pantry, but also really small startups and everything in between. So we're really happy to work with kind of a really wide range of companies who are at every stage of the sustainability journey and kind of going really deeply on things. Like packaging, in some cases, and, in some cases, trying to tackle everything. And, you know, so we really do have the full spread represented.

Gazella: That's great. Well, congratulations on that progress so far. Now, obviously, your organization feels climate change is a big problem and we here at The Natural Medicine Journal are trying to cover this as well, so how concerned should we be about climate change? You know, what damage can and will occur with climate change if we don't act together, as you're talking about?

Callahan: Yeah. Well, a lot is the short answer. And I think... I feel like everyone, this year especially, something's changed and we're all kind of scared of looking around and seeing... You know, this August, for example, all of us were watching sort of helplessly as the Amazon burned, and Hurricane Dorian just hovered as this slow-moving, giant storm over The Bahamas, and just these great tragedies affecting millions of lives and livelihoods and communities and just not being able to do anything. And, you know, that's a trend that's only worsening.

I'm from the Mississippi/Gulf Coast and grew up watching hurricanes get worse throughout my childhood. And Katrina destroyed my hometown. And so these are very visceral things that I think we're starting to see and not be able to not connect... We can no longer avoid connecting it to climate change, and so I think everyone's sort of feeling it very viscerally.

And then, you know, on the data side, we've got a huge amount of evidence to back up the fact that climate change is happening. It's getting worse. We're already seeing the impacts, and if we don't act quickly and at scale, the problems are going to be tremendous. You know, when we look at UNFCCC Reports, and even an EPA report that came out in November 2018, that showed that absent action, this could slash 1/10 of the US economy by 2100. You know, the UN has showed us that we have about 10 years to act to avoid catastrophic damage. We're on a road to exceed 1.5 degree increase in global temperatures, and we have to stop that. We have to take action to reverse it.

And, you know, I moved to California year ago and within a couple of months was wearing a mask to avoid the smoke and fires, and saw my friends have to pull their kids out of school, and so I... It's a very emotional thing and it's a very practical thing that we have a lot of evidence backing up the risk of inaction. And getting into the health a little bit, it's very clear that climate change is absolutely a public health issue, in addition to an environmental issue and so many other types of issues. And so I think part of the conversation is how do we break this scary complex issue out of a silo of just being isolated to kind of environmentalism? And really focus on how is this having an impact on generations? How is it impacting the lives and livelihoods of the poorest people who are the most vulnerable to climate impacts? The youngest people who are going to bear the brunt of the problems that we see now?

So, you know, I think that that's all becoming increasingly clear and hard to ignore, which is, you know, both heartening and terrifying. It's been really great to see the type of action that happened last week at the climate strikes in New York, right? I think they had to shut down Battery Park because there were so many people gathered. And this is all because of 16-year-old climate activists, Greta Thundberg, who, I think, is just been one person who has created this giant, global movement that gives me real hope. But it also just shows the energy and strength behind how many young people are recognizing the threat to their future that they see.

Gazella: Yeah. I would agree. Well said. And before we get into the practical information, you know in the description of this an interview, I called your goal to reverse climate change lofty. I was actually surprised when I read on your website that the goal was to reverse climate change. What do you think? Is this a pretty lofty goal? And, even more important, is that a realistic goal?

Callahan: Well, yes, it is a very lofty goal. And I think we absolutely can't do it single-handedly, so I don't have any illusions. As much as it would be wonderful if I could work with these 450 companies to single-handedly reverse climate change, I don't think that's possible.

I think what we're trying to do at the Climate Collaborative is highly ambitious, and, essentially, what we're trying to do is create a new model of doing business within the natural product space that is replicable and scalable. And that shows that there is a way that companies can take advantage of the tremendous opportunity that responding to climate change represents. Be first movers on creating new systems and ways of doing business that are an inevitability, I really believe. In terms of new ways of doing agriculture that helps restore carbon in the soil, new types of packaging, reductions in food waste. The shift toward these types of practices is inevitable, and why not have this innovative industry be at the helm of creating those shifts?

And so, you know, that is really... We want to create a model that then cascades across the food sector. And I think... So when you ask, are we looking to really reverse climate change? I think that when you look at the fact that the food and agricultural system accounts for about 23% of global emissions, it's going to be absolutely key to solving climate change and have this huge kind of double-edged sword of being a huge potential opportunity as a solution, through carbon soil sequestration and other mechanisms, but also is a tremendous risk factor if we don't take action. And so I really look towards the types and group of companies that we work with as leaders in creating those new systems.

And so maybe not reversing all of the climate change, but maybe reversing how the food sector responds to climate change. And any company with an agricultural supply chain, how they can shift their practices to really create a new model for the food system. And so I hope we can do at least that much. I still believe that is an incredibly lofty goal, in that there are a lot of structural barriers to getting there. When you look at certain policies that disincentivize the types of practices that our companies are looking to start making or already making, and then the absence of things like a price on carbon and absence of policy and incentives rather than disincentives for farmers to be changing their practices to help restore carbon in the soil and all of that.

So that's why policy is such a crucial piece of what we do as one of our 9 commitment areas. And it's potentially the most important, because every company in our network could get to net zero emissions and it would be the drop in the bucket, when you look at global emissions. So policy has to go alongside whatever action that companies take, and my hope is you can then create a virtuous circle where you have companies acting and proving policy mechanisms can support these actions at scale, and then wider set of businesses taking up these policies and then you kind of create that virtuous circle.

So, that's my hope. But I completely agree, it is still really lofty. But I think we don't have really any other choice but to be ambitious and lofty in our goal setting these days. So, I am hopeful.

Gazella: Well, I agree. And I was going to ask you, "Why the natural health industry?" But you bring up such a good point, if you can create this new model that can then be replicated, you could have that ripple effect and have that, as you mentioned, cascade into the food sector. So to me that makes sense, so now I'm feeling better about my term lofty. Because I think-

Callahan: Oh. Good.

Gazella: Yeah. That makes total sense to me now. So let's get to the heart of the matter. So exactly how is your organization going to reverse climate change? Or, you know, if we put this into more digestible pieces, how is your organization going to create this new model of doing business that can then be replicated?

Callahan: Yeah. Well, the first thing is getting companies to make public events. And I think that... You know, I mentioned before, and kind of getting to your point around why the natural health and products industry, and I think that is because it's almost a quarter of global emissions when you look at the food and land system. There was just a Land Use Report that the Intergovernmental Panel on Climate Change put out that just showed how critical the sector is in responding to climate change, and that kind of double-edged sword of it being a solution and a problem.

So that's why these companies. And, you know, I think that within the food sector, our companies already have a status of first movers. When you look at issues like organic and non-GMO, fair trade, the natural products space, they've been first movers on those. And then have then become standards that we all know, we all shop and look for those labels, and we're all kind of very aware and it's cascaded across the food sectors. So we have model of what it could be and how that scale could work and look, and now we need to make climate that issue.

And that's part of the type of model we've tried to adopt here at the Climate Collaborative. In terms of how we do that on climate, it is predominantly through our commitment areas. So we have these 9 commitment areas. They're focused around carbon farming and regenerative agricultural practices. So it's changing on-farm practices so that you're pulling carbon into the soil and keeping it there, and that things like compost applications and cover crops. Intensive rotational grazing, when you're looking at pastures with animals. So changing your on-farm practices to really help draw down carbon, and that's a huge opportunity.

If, you know, you're familiar with Paul Hawken's Project Drawdown, which is this giant list of climate solutions, that's number 11 on the list. Another one that we work on, number 3 of his solutions, is food waste. And that is, you know, about a third of food is wasted and so we're trying to help at least the corporate part of that, so companies and their supply chains, to reduce food waste. And at source. So not just looking at waste diversion and donations, but really looking at how can we reduce the waste that's produced in the first place and make a more efficient supply chain from producers to grocers selling it to consumers? So we had a big project this year where we did intensive consultations with retailers in the US on reducing their food waste in store.

Packaging is another really big issue that we look at. It's the single biggest challenge for companies, you know? Everyone, I think, has paid attention to the plastic straw bans, and plastic in the oceans, and been very aware... It's a very visceral thing because you hold it in your hands and you see it, and then you throw it in the trash or the recycling and... It was just a very visceral way to be aware of your footprint, I think. And so that has been the single biggest issue and challenge area for the companies we work with and we do a lot to try and help them reduce their packaging impact. And, you know, there's policy, energy efficiency, switching to renewable energy, so we're looking at very concrete practical solutions that are very action-focused.

You know, I would say that for companies it's also really important to take a look at your footprint and say, you know, "Where are my emissions concentrated?" Start measuring and setting goals, and so we do encourage that. And, above all, we want companies to just say, "Okay. Let's start taking action. Let's start doing something and be part of, kind of, a larger community of companies within the industry doing that." So we do that through working groups. We have one on regenerative ag, we have on consumer engagement, one just for retailers and we really try to just kind of get companies able to talk to each other a little bit more about their efforts.

So that's a little bit. I'm happy to go into more detail, but those are a few of our projects.

Gazella: No. I think that's great because what we're going to do is we're going to put a link to the Climate Collaborative website, and I know that you list these 9 commitments. And you have a ton of information on your website, videos and such, so I highly recommend that any manufacturers who are listening, you know, or anybody really, click over to the Climate Collaborative to learn more.

Now, technically our journal is a part of the integrative health community and not necessarily the natural health community, per se, with a lot of retailers and manufacturers and such, but I'm wondering how our readers, are individual doctors, can help with this effort. So what advice do you have for the individual? And, in particular, I mean, our doctors are seeing patients and they're influential, you know? So what advice do you have for them to make an impact in this area of climate change?

Callahan: Yeah. Well, a couple of things come to mind there.

Firstly, we host one day of the year called Climate Day, which is my favorite day of the year. It's where we bring the whole industry together and get a set of thought leadership speakers, and everyone in the room just talking about the biggest issues that we need to tackle on climate change over the next year. And last year one of our keynotes with Yvon Chouinard, the founder of Patagonia, which, I think, if there's a company who's doing just fantastic work on climate change and making their whole mission focused around reversing, it's Patagonia. They've just been real leaders. And he was interviewed by Dr. Zach Bush who some of your listeners might be familiar with. I actually wasn't too familiar with him, but it might be an interesting conversation to reference in this because his whole talk was really around the relationship between the microbiome in all of us and climate, our biome. And what are those connecting, and how does one impact the other, and how does how we manage the climate then filter down to the nutrition and the food that we eat? And, overall, the microbiome and health of our bodies?

And so I just want to reference that, because I think that there's a lot of interesting stuff happening. A lot of interesting research happening there right now that I'm fascinated by and there's a lot to mine there. So, that is one thing. The other thing is, I think when it comes to doctors, or really anyone as an educated, active citizen, 1) voting and advocacy matters. And then, 2) being a really conscious consumer. And asking the businesses that you're purchasing from and working with what their practices are, and asking them questions about their packaging, asking them questions about their footprint. And business is new because of stakeholder action and requests and consumers are such a crucial stakeholder. It's why we're launching this consumer aspect of the product this year.

But I think creating an aware base of people who are talking to these companies, and working with them, in some cases, and shopping for... You know, with their products. Make smart choices but with your dollars. We have a group of fantastic companies that are really piloting new work and it's really important that we acknowledge that through engagement with those companies, through dialoguing. By pushing them farther and getting engaged in their mission, but also just generally when shopping by making really informed choices about the company that you're looking at.

And that's a very hard thing to do. I mean, I'm a consumer and it's really hard to hold the fact that I need something in a certain price point, I need it to be really good, I need it to be exactly for what I'm doing, I need to get it pretty conveniently. And then also, on top of that, I need to care about what's its footprint? Where did they source the ingredients? You know? And then also is it fair trade? Is it... You know, are they using renewable energy? What's the packaging? It's a lot to hold, but I think the more you can be okay and accept that complexity and really try to make informed purchasing decisions, the farther where we're going to go.

And, luckily, we're already seeing real movement. You know, I think 70% of Americans are looking to see more from the companies they're doing from a study that came out last year. I mean, you look at the younger demographics, those numbers get even higher and they really are making their purchasing decisions based on the footprint and choices of the companies they purchase from. So I think the more we can all lean into that, the better.

Gazella: Yeah. I would agree. And I think that's great advice. So, in closing, why don't you go ahead and describe some of your short-term goals moving forward. Say, within the next year or 2, what is your organization want to accomplish in the near term?

Callahan: Yeah. Well, firstly, on the outreach side, we've got an incredible base of companies committed. We're at about 440, like I mentioned, I want us to get to 500 by March of 2020. That is my goal.

It really matters to keep that energy and momentum up, and so I'm looking to bring on new companies. We're really looking to actually move in to a lot of health and nutrition companies and we're going to be at a conference in a couple of weeks talking to them. And, you know, that's kind of a subsector of the industry that we really want more actively engaged, so that's the one thing. And then on the programming side and the work of it side, we're just over a year away from the 2020 elections. Giving our companies pathways toward active engagement on policy issues ahead of that election and getting them informed on what they can be seeking out on and supporting, is a real, real priority of mine. We're working with a great set of policy partners on that front to do that and that's something that we're going to really try to be doing a lot of over the next year.

Outside of that, I mentioned consumer engagement. We are launching a consumer engagement part of the project over the next year, where we're trying to actually create a common set of messages that companies are using to engage in dialogues with consumers. And also to raise awareness on specific issues. Like soil health, like food waste, packaging, and really try to create dynamic, fun, engaging conversations with consumers that are action-focused as well. So we're hoping to really get that off the ground in the next year as well.

And then our rooted community, the regenerative agriculture community that we have, we meet 4 to 6 times a year right now and going to be doing our first on-farm site visit over the next year as well. And I really hope we can be doing more of that, and constantly just trying to roadmap the business case for action. I think a lot of companies understand the altruistic and moral reasons to act, but when you back that up with saying that there are real business cases to be doing certain things like this, especially when you're working upstream in your supply chain with farmers who have very small margins and also really know... They know how best to manage their farms, and so when you have these conversations, what are the incentives we can provide and what data do we have to back that up?

So we're constantly looking to increase the amount of data that we have on that and to connect your companies to it to really help promote these practices within the industry. So, those are a few key priorities. I think, overall, we're also just trying to keep the energy and momentum up in the industry. Climate is a really complex issue with a lot of nuances and not a lot of clear black and white solutions that we can just easily adopt, and so the more we can get companies excited and motivated and willing to work together, which I think they increasingly are, the more opportunity we have to really see transformative change in how the industry at scale is really attacking some of these issues.

So that's my biggest hope. Is that we just keep the energy up, from as wide a group of stakeholders as possible, around focusing on climate and moving forward with real action.

Gazella: Well, those sound like some great goals and it sounds like you're going to be very busy in the coming couple of years.

Callahan: I think so. Yeah.

Gazella: Yeah. Well, I just want to congratulate you on creating the... Well, your founders creating he Climate Collaborative and your work as the director. I really applaud you. I think it's great work. It is lofty and it's huge, but it's so important.

So thank you so much for joining me today and telling us about your work. And I encourage our listeners to go and check out the Climate Collaborative, and thank you, Erin, for joining me today.

Callahan: Thank you so much.

Gazella: Have a great day.

Callahan: You too.

In this interview, Benton Bramwell, ND, discusses the unique Mediterranean herb Arum palaestinum. Listeners will learn about the traditional use of this herb, as well as current research that helps illuminate its modern-day clinical applications including oncology specifically. Synergy, safety, and dosage will also be discussed.

About the Expert

Benton Bramwell, ND, graduated from the National University of Naturopathic Medicine in 2002. He manages a private practice and also provides consulting services to food and dietary supplement industries in matters of scientific and regulatory affairs. He enjoys the wonderful outdoors, especially working the vegetable gardens with his family and going on bicycle rides that allow him to think and exercise at the same time.

About the Sponsor

Hyatt Life Sciences is Putting Science Behind the Tradition™
Headquartered in America’s heartland, Sterling, Kansas, Hyatt Life Sciences continually searches for unique botanical entities and combinations that have been used traditionally in their countries of origin for hundreds of years. Rather than depending only on tradition and legend as many nutraceutical companies do, scientists at Hyatt Life Sciences research, test, and evaluate each herb, root, and component to discover the scientific reason for the ingredient’s benefit. We offer products only after each ingredient has been thoroughly researched for benefit, safety, and purity. At Hyatt, we are committed to Putting Science Behind the Tradition™. Read more.

Transcript

Karolyn Gazella: Hello. I'm Karolyn Gazella, the publisher of the Natural Medicine Journal. Today, we're going to have an interesting discussion about the Mediterranean herb Arum palaestinum. My expert guest is Dr. Benton Bramwell. Before we begin, I'd like to thank the sponsor of this topic, Hyatt Life Sciences. Dr Bramwell, thank you for joining me.

Benton Bramwell, ND: Pleasure to be here, Karolyn.

Gazella: Well, let's start with the basics. Where does Arum palaestinum grow?

Bramwell: Great question. Arum palaestinum grows in the Mediterranean region and is particularly known and used in the Middle Eastern portion of the Mediterranean.

Gazella: Okay. Perfect.

Bramwell: Quite a history to it actually, Karolyn. It's been known in the region for actually, literally, thousands of years. In fact, it shows up on some drawings in ancient Egyptian temples. We believe it was probably brought to Egypt from Canaan in about 1440 BC. It's been there for a while.

Gazella: Yes. Yes. Also from a historical perspective, what conditions was it used traditionally for?

Bramwell: It appears from the historical literature that it's been used for many different kinds of conditions. Primarily for a treatment for cancer, historically, but also as a treatment for infections and open wounds, as a treatment for kidney stones, and even for a worm treatment in animals and humans. Also, it's a way to strengthen bones. This is one herb that has been used in a very diverse applications, perhaps not the least of which because it happens to also be a wonderful food. It made its way from food into medicine. Really that distinction as, of course, you know in a lot of places in the world, there really is no distinction, right? A lot of times the best medicines come from our feed. This is certainly a prime example of that.

Gazella: Yes, exactly. Let's fast forward to today. What are the main clinical applications of this botanical today?

Bramwell: Yes, we're still learning about that in terms of modern application, where it's going to be the best fit. We certainly continue to see it used clinically in the ways that has been used traditionally previously. That's in the Middle East. It's still used as a complimentary supportive adjunctive support for patients with cancer. It's also finding its way into skincare, and I think we're catching up, frankly, in the modern scientific age as to where it should be best used. I think we still have a lot to learn there, but we're learning as we go.

Gazella: That's a pretty diverse list of conditions that this herb can help with, which is kind of common with some botanicals. I'm assuming that's because there's a variety of mechanisms of action. Is that a correct assumption? Can you tell us exactly how this botanical works in the body?

Bramwell: Right. I can tell you what we're starting to see there and understand. There are a variety of mechanisms. Just for a minute, let's focus on where it might fit in terms of something that makes supportive sense for the patient with cancer. What we're seeing is that it may very well, at least in the in vitro models that we're seeing, it may very well help with the cellular process of apoptosis. That's the process by which a cell decides that it's time to basically do itself in. It's programmed cell death, right? There are some interesting mechanisms through proteins that are caspases. I think that we're going to continue to see the literature develop there quite a bit, but I think that's one important mechanism.

It's also important in terms of cell signaling by means of phosphorylation. There are many pathways in the cell which run off messenger systems based on phosphorylation. It seems that Arum palaestinum probably inhibits some of those pathways as well, or at least the compounds from. Those are several of the mechanisms that we see in play.

Gazella: Okay, good. I understand that there's a topical application of this plant. Can you tell us a little bit about the topical application and what that formulation actually looks like?

Bramwell: Yes, I can tell you a little bit about that. I'm glad to see that one coming forward. It's certainly in line with the traditional use. That product, Arumacil, it contains the Arum palaestinum extract, as well as dimethicone and petrolatum. The object there is to help protect the skin, give it a chance to heal, basically. I wouldn't be surprised, and I don't think the literature has necessarily caught up to us here, but one of the main categories of plant chemicals that we're talking about here are flavonoids. Flavonoids are known in the literature to have antiviral effects. Again, a little bit more to learn there, but I wouldn't be surprised at all to find this topical application of good use, clinically for people with cold sores and other minor skin irritations, frankly.

You're going to get a lot of antioxidant action from these compounds, as well as potentially some antiviral, although I think we need to learn more about them.

Gazella: Okay. That makes a lot of sense. From what I've read, this is a pretty complex botanical. It has a lot of different constituents. From the therapeutic perspective, what are some of the key active compounds in the plant?

Bramwell: Well, there are many actually. In the literature where I've spent some time, and from what we can find, there's about 180 phytochemicals that we can at least tentatively be identified at this point in time. Most of those, as I mentioned, are flavonoids of one kind or another. As I look at the list of what's been identified, some of those I would pull out would luteolin, which I think is going to prove to be very important from an anti-inflammatory point of view. That's certainly an active bioflavonoid, in particular, a class of flavonoids called flat bones. I think that's going to, doing the [inaudible 00:07:52] one of the important ones. But there are others as well. There are derivatives of rutin in there, and epicatechin. So I think those are all going to be important.

In addition to the flavonoids, there are also phenolic acids and derivatives of phenolic acids in here as well. Rosmarinic acid is one that pops out, and these are all compounds that I mentioning that when you look at the individual ingredient, it doesn't take you long to find in the literature that these individual ingredients, upwards of between 20 or 30 of them, have a little body of literature of their own, as to their anticarcinogenic potential.

And so, I think what we've got here among the flavonoids, the phenolic acids, and I should mention also some terpenoid derivatives, of course solic acids in there as well as some iridoid derivatives. When you put all those together, and each of them have an anticarcinogenic potential, the complexion of the botanical is one that seems well suited for its historical use.

Gazella: Yes. Especially when you consider a condition like cancer, which in and of itself is so complex. I'm fascinated by the fact that there are all these little compounds, and as you've mentioned, you could probably take one compound, do a scientific literature search and find data to support that one compound, but here we're talking about multiple compounds all within the same plant.

Bramwell: Well, that's exactly right. And actually some of the interesting work that's been done, one of the interesting approaches here is to take some of the compounds that occur in the plant naturally and make a fortified extract, if you will. So, that work's been done in vitro and in vivo and in several different places. They've taken out, for example, linolenic acid, beta sitosterol and isovanillin.

Those are items, constituents that you can get in a water extract of the plant and then made a fortified product from that... material. And when that material has been tested in the in vitro and animal models, it seems to perform superiorly to the raw extract, and I find that very interesting. It seems that Genzada Pharmaceuticals, Hyatt Life Sciences have done a very good job in the work that's been ongoing here showing an increased potential of this fortified extract approach.

Gazella: Yes, that sounds like some pretty cool science. I want to focus, in particular, on a 2018 study that was published in scientific reports. Now in that study, it compared to three different formulations and all of the formulations included Arum palaestinum. What were the results of that study? Tell us a little bit about that particular study and what the objective was and what the results were.

Bramwell: Right. So, this is an approach, again, where a fortified... a number of things were tested. One of the things that they tested was combination of the three plant extracts, Arum palaestinum, curcumin longa, which most people are familiar with turmeric, as well as another from the Middle East peganum harmala, sometimes known as Syrian rue.

So, those 3 botanicals were studied together and then various combinations of a fortified extract, or in one case, a chemical constituent from each of those was mixed together, and that actually looked the most potent as far as it's anticarcinogenic potential. And in that case, isovanillin, which you would find in the Arum palaestinum, was mixed with harmine, which you would find from the Syrian rue and also curcumin from the turmeric and all three of those plant chemicals were used together. And that actually seemed to have a very potent anticarcinogenic effect in the in vitro and in the animal models that we're studying here, in terms of looking at the invasive potential and proliferation, of the cancer cellulars models that we used.

And in this case, the researchers were looking at the head and neck squamous cell carcinoma, which is a very fast growing, aggressive kind of cancer. And, it does appear that the cells that were used here were very sensitive in these models, to that combination.

Gazella: So remind us, which combination then performed the best in this particular study?

Bramwell: Right. In this particular study, the combination of the three phytochemicals, so isovanillin, Arum palaestinum, and harming from the Syrian rue and curcumin from turmeric is what performed the best.

Gazella: Got it.

Bramwell: And again, they were able to show the effect on the molecular signaling cascades within the cell. So, there's some definite believable mechanisms of action here as to why the compounds would have the effect that they do. I think we're going to see a lot more about this one in the future as it becomes translated to human clinical studies.

Gazella: Right. Yes. Based on that study and other research, it sure seems like Arum palaestinum is best used in combination, potentially with other botanicals versus as a single botanical. Is that true? And if it is true, why is that?

Bramwell: That's an excellent question. I think that probably is the case, that either combination of the Arum palaestinium with other botanicals or even compounds, key compounds, from each of several important medicinal herbs. The question is why do we see this additive or even synergistic effect with these compounds or with the botanical blends that seems to manifest in the literature? I don't know all the reasons for that, but I rather think, given as complex as cancer is, being able to affect multiple pathways is probably the breadth of the attack against cancer cells, is probably why we're seeing that synergistic kind of benefit.

One way to attack something is with a very narrow focused approach. A deep attack. Another way is with a multitude of effects together. A nice, you know, cover all the bases. And I think that's potentially what we're seeing as this literature sort of declares itself here.

Gazella: And now what combination or what product, what Arum palaestinum product do you use in your clinical practice?

Bramwell: So right now what I'm using is the Afaya Plus and you can learn about that, consumers, patients, physicians can learn about that at the Hyatt Life Sciences website. But I think that that's the best product certainly than I've seen on the market at this point in time.

Gazella: Mm-hmm (affirmative) great. We'll also provide a link to the website too, so listeners can click right over. So, so far, there's been some compelling in vitro and in vivo and we all know that that's kind of the progression of research as we study these botanicals. What about human clinical trials?

Bramwell: That's the next step really, Karolyn, and I don't know when those are going to be published or what stage we're at, but we're definitely ripe for what would be called phase one and phase two clinical trials here. From what I can see in the literature.

Gazella: Are they underway? Phase one, is this phase one underway or is that still, are we still waiting for them?

Bramwell: I think we're still waiting for that, at this point in time. I hope to hear more about that in the near future. But at this point, following the literature and everything we see we like.

Gazella: Right.

Bramwell: And can't wait for the next human work to actually be published.

Gazella: Yes, I mean, the traditional use combined with the preliminary research sure does seem to be compelling. I'd like to talk a little bit about how it's used in oncology in particular. Do you look at this botanical as an adjuvant to be used with treatment or maybe after treatment? What's the clinical application when it comes to oncology?

Bramwell: Right. Well that's a very good question and because of where we are in the scientific process here, we're still early on. Although I think Hyatt Life Sciences, to be fair, has done much more work than many dietary supplement companies ever do. But we're not there yet in terms of knowing all we want to know. So at this point in time, I don't think anyone would responsibly say that this is a treatment for cancer. What we would say is, traditionally the syrup has been used by patients who have cancer. It's part of our herbal armamentarium historically, and it seems to make supportive sense.

And so, this would be something I would recommend while the patient is going through treatment. Although I tend to leave a space of time between conventional care and herbal therapies, just to make sure that the chemotherapy has time to do its work. So I would tend to leave three or four days, or at least one or two before and after a chemotherapy treatment. I think, from what I see in the literature, at least from the the Middle Eastern region where this is used quite heavily, when oncologists in that area are surveyed, they're not reporting anything really of concern as far as interactions go. But I would still leave a couple of days on either side of treatment, make sure the chemo gets in and does its job.

Gazella: Yes, that, Oh, go ahead.

Bramwell: No, you're fine.

Gazella: Well, I think that that's a good, prudent recommendation and I think that oncologists would agree with that. Now beyond oncology, is the herb safe? You talked about no interactions with chemotherapy that we know of, but are there any other interactions or contraindications that we should know about?

Bramwell: You know, not that we can see at this point in time. The only thing I would point out and highlight there, Karolyn, is that even in traditional use, where this has been used as a food, what's been known for a long time is that it's boiled. It's boiled several times in water and that water is decanted several times, taken off, in the preparation of the herb as a food. Or in this case, before it's a supplement. Don't know all the reasons for that, but part of the thinking has been there that there's a high amount of oxalates in the plant and in order to prevent toxicity, that's an important part of the plants preparation as a food/medicine. So, I would highlight that for you.

Gazella: Yes, that's interesting. Is there any kind of standardization with this botanical?

Bramwell: Yes, it could be standardized. But since we're in the process of learning all that's important about it, I think the closest thing to standardization is the work that was done several years ago with the fortified extract of isovanillin, linolenic acid and beta sitosterol . That complex looked quite promising. And if you wanted to standardize to something, that would be one way to do it, but I'm not aware of a totally standardized extract at this point without fortification, if that makes sense.

Gazella: Okay. Yes. Let's talk a little bit about dosage. So what dosage do you recommend and does that dosage change based on the clinical application or if it's for prevention versus treatment?

Bramwell: I would tend to be more aggressive with a patient who's using this as a supportive. Make it a supportive care during cancer. And the Afaya Plus, two capsules [inaudible 00:23:07] of that is going to give about 900 milligrams, of a combination of vanillin powder, tumeric powder, harmala powder, the Syrian rue and Arum palaestinum. I would tend to go at least two capsules, twice a day on that.

But again, when you're working with a patient with cancer, you're going to have to titrate the need, titrate the dosage that they can take. Some patients going through treatment have a difficult time getting food in. And one thing we always have to remember with a patient with cancer is that we want to feed them first. And we don't want capsules to take the place of food, and so it's going to depend on what the patient can tolerate. But I would start off with a two capsule b.i.d. kind of an approach. And if they can tolerate that well, even up to two capsules t.i.d. As a maintenance kind of thing, for general health, I could see taking a single or two capsules a day, single serving.

Gazella: Do you feel like it has a good application? Like for example, somebody, a patient who may be at high risk of developing a type of cancer. So as a way to kind of help reduce risk, do you feel like there's an application for that?

Bramwell: We don't really know at this point, but I would suspect so. There again, I'm not one to, I don't necessarily subscribe to the philosophy of more is always better. But I think it's something that I would carry in my mind. You know, if dad and grandfather both had prostate cancer and I want to take something and it's kind of a daily maintenance to keep as healthy as I can, to maintain that prostate tissue in a good state, I would think of serving of this a day would make a lot of sense.

Gazella: Okay, great. Now, we talked a lot about oncology, but we also mentioned skincare, infections, kidneys, bones, when you're looking at the clinical potential of this botanical and the clinical application of this botanical, does oncology bubble to the top over everything else?

Bramwell: I think it definitely does. In fact, there are many other applications that we've mentioned here. And we're going to learn more about those over time. I think this is something that naturopathic physicians and other integrated healthcare practitioners are going to learn about as they go. And that's okay, really. We're using something that's been in traditional use for a very long time. But it would be something that for other conditions like skincare, I would just try it clinically and see what we see with it. But I think the biggest, biggest application, Karolyn, is going to be oncology.

Gazella: Yes, I would agree based on what we've discussed today. For sure. Now, Bramwell, I'd like you to pull out your crystal ball and kind of look into the future as a clinician, what would you like to see happen with this botanical as it relates to oncology specifically?

Bramwell: Couple of things and I think already some progress has been made in terms of what formulations are the most effective, but I'd like to see a little bit more work in that regard, with various combinations. I think that we will see, in the next few years, based on what's already been done, phase one and phase two clinical trials. And I hope, based on what's done that that includes work in both patients with prostate cancer, as well as patients with head and neck squamous cell carcinoma and some of the other lines that have shown promise. I mean, there's been some work that's a promising in glioblastoma cell lines as well as lung cancer. So we'll see where it goes in humans first, I hope with patients with prostate cancer and patients with the head neck cancer especially. I also am intrigued, in that 2018 paper that you referenced, there was some work indicating that it may go very well in combination with Cisplatin.

Bramwell: Platinum chemotherapy is very commonly used in colon cancer treatment, as well as other cancers. And boy, if there would be something that would help the platinum chemotherapy be even more effective than it is, I think that would be a wonderful combination and as I kind of look to the future, that one comes to the front of my mind, Karolyn is, is this an adjunctive therapy that could actually make the conventional therapy a little more effective? And I would really hope that the future upcoming human work will really hone in on that and help to answer that question.

Gazella: Yes, and it would also be kind of interesting to see if this botanical could help reduce some of the side effects that come with conventional chemotherapy. I think that would be kind of an interesting... I'm curious as to why prostate and head and neck. I mean, head and neck, that's a tough one and I would love to see it be effective, but why are those two ones kind of standing out in your mind as to where this botanical may help?

Bramwell: Right. Well that's based on the work that's been done so far. So yes, there's going to be a great, great question. The 2018 work was primarily done in head and neck squamous cell carcinoma, and the work before that, in 2015 that was published, was quite focused on prostate cancer cells. So, it makes sense to build on what you have there.

But, you know what? Here's the great thing about Arum palaestinum, from everything I'm reading, it looks like the mechanisms of action, and there are multiple of them, could be applicable across many kinds of solid tumors. So this would be the kind of thing where you can build on your in vitro and animal work and human studies, but you might quickly branch out and other areas of exploration as well. It could be something that could be beneficial to many patients. We don't know yet, I don't think. But, when I read this literature, the question I asked myself is, could this be the next [00:30:30] ? Could Arum palaestinum be that botanical source for a cocktail of phytochemicals that really finds broader use and helps many patients live longer and much better lives. I hope so. Time will tell. Human data will certainly inform things from here, but what we see so far is it's highly encouraging and kudos to the Hyatt Life Sciences for getting this out there.

Gazella: Yes, I hope so as well. It sure sounds like there's a lot of potential here and we're going to definitely, The Natural Medicine Journal, will definitely be following this research on this interesting botanical, Arum palaestinum. Well, once again, thank you Bramwell, for joining me today and I'd also like to thank the sponsor of this topic, Hyatt Life Sciences. So, thank you for the interesting information, Bramwell, and I hope you have a great day.

Bramwell: Well, thank you, Karolyn. Pleasure to be with you.

Natural Medicine Journal publisher Karolyn A. Gazella talked with Kristie Ebi, PhD, from the Center for Health and the Global Environment with the University of Washington. The two discuss Ebi's research using new technology to model growing conditions as they will be in the coming decades if we don't curb climate change.

In this podcast interview, we speak with neuroscientist and physician Leanna J. Standish, ND, PhD, LAc, FABNO, about her naturopathic oncology research. Standish has been involved in original research at Bastyr University since 1987, where she continues to teach and serve patients. We discuss the research she's currently working on—the Canadian US Integrative Oncology Study (CUSIOS)—and its focus on understanding how integrative oncology care affects outcomes for people with certain advanced cancers. In addition, we discuss the use of psychedelic drugs like psilocybin in cancer care—especially for people who have a history of trauma.

About the Expert

Leanna J. Standish, ND, PhD, LAc, FABNO, is a neuroscientist and physician living in Seattle. She has faculty appointments in the University of Washington School of Medicine Radiology Department, the University of Washington School of Public Health, and Bastyr University. She is working toward obtaining approvals to conduct ayahuasca clinical studies in the United States. She uses functional magnetic brain imaging to study brain-to-brain communication and the ‘entangled minds’ hypothesis. As a physician she specializes in naturopathic oncology, with special interest in the treatment of stage 4 cancer.

Standish earned her PhD in neuroscience/biopsychology from the University of Massachusetts in 1978, her ND from Bastyr University in 1991, an MS in acupuncture and Oriental medicine from Bastyr University in 1994, and became board-certified in naturopathic oncology in 2006.

Transcript

Tina Kaczor: Hello, I'm Tina Kaczor, Editor-in-Chief here at the Natural Medicine Journal. I'm talking today with Dr Leanna Standish about ongoing original research in naturopathic oncology. Dr Standish is a neuroscientist and naturopathic physician with a master's in acupuncture and Oriental medicine and board certification in naturopathic oncology. She's been involved in original research at Bastyr University since 1987, where she continues to teach and serve patients. Dr. Standish, thank you so much for joining me. I want to go-

Leanna Standish: Hi, can I just say hi to everybody and especially you, Dr Kazcor, and just express how delighted I am to talk to all of you.

Kaczor: Yes, and so yeah, it's very exciting to have you one on one to get to know a little bit of what's going on in the front lines of research specifically. What prompted this was your update at the recent oncology conference. The Oncology Association of Naturopathic Physicians had their annual conference in February where you spoke. I'd like you to kind of start at the beginning. What was really compelling is some of the research on both non-small and small cell lung cancer as well as breast cancer studies. So, if you could kind of update us about a little bit of what ... update us on what's going on with your research in those areas.

Standish: Yes. Well, since 2009 working at Bastyr University with Paul Anderson, we started collecting data on survival outcomes in our advanced cancer patients and have a big enough database that we can start summarizing survival outcomes, which is I think of great interest to both patients and their physicians. What we found, our first study was in breast cancer, stage 4 breast cancer, that our median overall survival in our patients, they were 54 consecutive women with breast cancer. The median overall survival is 47 months. When I first got those data, I was very upset because it means that half of my patients were dead at 47 months. But then I thought, well, how does that compare to other studies that were being published at the same time that we were doing our work? What we found is that the best study that we could find in terms of median overall survival in stage four breast cancer was an Abraxane trial that happened in the early part of the 2000s. Just getting some tea here, hold on.

That study showed a median overall survival of 36 months. So the conclusion to me was yeah, this is an uncontrolled study. The kinds of patients that we see are the kind of people that are very proactive. They may be survivors just in their very being, but in any sense that you can think about this, that those are pretty good results in advanced cancer. Then we did a similar study in advanced non-small cell lung cancer, and that was with 18 consecutive patients, stage 3 and 4, and the median overall survival there was 43 months. Then we surveyed the literature and did a systematic, I should say systematized review to find that the median overall survival for all the chemotherapy drug trials and even the new immunotherapies that were coming out in just the last say 5 years, the median overall survival of all those studies when averaged together was only 13.3 months. It's kind of astounding to me how poor results in advanced cancer continue to be.

That's the summary. Just one more thing I want to say is that this is why we started the Canadian and US study of integrative oncology outcomes. This is 12 clinics all over Canada and the United States that are doing what we call advanced naturopathic oncology, and we're tracking survival and treatment data from 400 people. That probably will be published, it will probably be at 2 years before that study is published.

Kaczor: Are there any intermediate points where you've looked at that data? Do we have any idea of what's gong on with that study?

Standish: Which study do you mean? CUSIOS?

Kaczor: Yeah, that last one you just mentioned, which I think you called-

Standish: Yeah, we called CUSIOS, so Canadian US Integrative Oncology Study. What we know is that we've been able to recruit. We're about 85% done recruiting the 400 patients. We have a good diversity of the patients that we recruited for, which was stage 4 breast cancer, stage 4 colorectal cancer, and stage 3 and 4 pancreatic cancer, and stage 3 and 4 ovarian cancer. We wanted to narrow our study to those 4 conditions. We're recruiting. We're able to collect death data, and the most exciting and problematic thing is what do you compare our naturopathic oncology survival data to? Here I've just talked about a breast cancer study, 53 women, their median overall survival is 47, but what does that mean? Compared to what?

Right now there is a tremendous amount of intellectual work going on at Bastyr University and also at Canadian College to figure out what the best statistical method is, and fortunately we've been able to collaborate with some very sophisticated big data scientist with statistical ability that have access to this marvelous database in Canada. We will be able to use the SEER database too, and what we're doing is trying to figure out how to match naturopathic oncology cancer patients to patients that are just like them in these registries and then watch them over time with the hard endpoint of date of death.

We're also of course very interested in quality of life. We're also interested of course in what therapies each patient got, not only what they were recommended, but also what therapies they received. For example we're tracking Dr Gurdev Parmar's clinic where they're doing locoregional hypothermia. Another clinic is using mistletoe therapy intensively. Another clinic, such as ours at the Ames Institute in Seattle, we're focusing now on the utilization of what's being called metabolic therapy, which is the idea of the cliché is starving cancer using FDA off label drugs that is all the rage these days, very interesting approach. We're using intravenous vitamin C along with chemotherapy. We've sort of abandoned the idea that as a monotherapy it does much. We're starting to explore the safe use of quercetin as a botanical medicine that really needs to be given intravenously to be bioavailable.

But I think the most important thing we're doing is taking seriously the idea that trauma, childhood trauma in particular, is a risk factor for development of cancer. And I'm referring of course to the famous ACEs study, Adverse Childhood Events study, that linked in a dose-dependent way the number of adverse childhood events like neglect, foster child, abandonment by parents, alcoholism, violence, etc., war, that the number of these events is correlated with the risk of cancer later in life. And so we at Ames Institute are saying well okay, if that is an important causal feature of why we get cancer, then let's get to that. We're using now psychedelic assisted psychotherapy to be able to do the deep work that is required to help people heal from posttraumatic stress disorder, which not only can come from childhood, but just the very experience of having cancer, being diagnosed with cancer, going through cancer treatment produces posttraumatic stress disorder.

What we're hoping is all these therapies combined are going to improve the median overall survival of our patients. That's what we're doing here in my clinic.

Kaczor: Tell me a little bit more about this. Is this low-dose psychedelics? I think we're talking about it here in Oregon from a state level. I think there's going to be actually some kind of referendum vote to see if we can legalize such things here, so I'm curious about this.

Standish: Yes. The initiative that will be happening in Oregon in 2020 is about permitting psychotherapists, certified licensed and fully trained psychotherapists, to utilize psilocybin in the treatment of posttraumatic stress disorder and also in end-of-life care. That's very exciting. But in the meantime, right now there are no legal psychedelic drugs available for physicians with 1 exception, and that is ketamine. Ketamine is a drug that comes from anesthesia. It's been very well studied as both an anesthetic, but in low doses, it produces a state of consciousness that some people would describe as psychedelic with a dissolution of the sense of self, a connection with higher realities, a connection with one's ancestry, an ability to do deep work in the presence of a physician and a nurse who are overseeing the treatment. What we've found is a 3-hour ketamine session that's led and facilitated in an excellent way can help enormously relieving the depression and the anxiety that is part of all of our lives, but especially if you've been diagnosed with cancer, and especially if you have the kind of trauma in your childhood that is a risk factor for cancer.

Kaczor: Is there already clinical data on the use of this?

Standish: On what? I'm sorry, clinical data on what?

Kaczor: On ketamine or psychedelics being used in this fashion.

Standish: No. What there is, this is translational science, and the reason I love naturopathic oncology is that we are people who take science and translate it into other domains of medicine. We know without a doubt now that the state of consciousness, emotional states and brain states associated with those emotional states, have direct effect on the autonomic nervous system, which has direct effects through a cascade of physiology and biochemistry that affects the behavior of cells in the tumor bed. And there's tons of work on that. Is there work on the use of psychedelics for healing cancer? No, but it will be coming, and I hope that we can show some leadership in that area here in Seattle because I think it's an extremely important area.

The reason psychedelics might be important too is that most of them have very strong serotonergic effects. What we've found in immunology is that the kinds of cells that are involved in the immunological response to cancer, T-cells in particular, are loaded with serotonin receptors. It is not a far stretch to imagine that one of our future immunotherapies will be psychedelics, and there's now kind of a rage around doing low dose psychedelics, all of which are considered by the drug enforcement agency to be controlled substances, but there's huge interest in this field. Most of us have probably seen Michael Pollan's new book How to Change Your Mind.

Kaczor: Yes, yeah. It's a fascinating read. It definitely had more data behind the use of it for emotional states than I had ever realized before reading that book. So let me ask you this because our listeners are often clinicians themselves. Sometimes they are the lay public. In any case, if people want to look further to see if they are appropriate to enter a study or they have patients that might be appropriate, because what I hear you saying is some of these tough-to-treat cancers, whether it's stage 4 disease or lung cancer in stages 3 and 4, they're tough to treat, and we all want to help our patients as best we can. So where would someone go to find you or one of the other 14 clinics involved in CUSIOS study? We'll put a link here with the podcast, but otherwise, where do we find you?

Standish: Oh, okay. Yes, please to go the Bastyr University website, and look at the research, and then look for CUSIOS [https://bastyr.edu/research/studies/canadianus-integrative-oncology-study-cusios-advanced-integrative-oncology]. Everything is updated there. It's also listed on the national NIH clinical trials .gov site, and all the clinics are listed there [https://clinicaltrials.gov/ct2/show/NCT02494037].

Kaczor: That's great, and I think what we have is more of a full whole-systems research, outcomes-based research is what I hear you saying. All of these are taking into account large plants, not single agents, which is why we often have weak data when we use single agents in our medicine. Kudos for mastering the complexity of figuring out how to get this data going and inform us.

Standish: Yeah, I think that one of our fundamental hypotheses is that natural medicines, those that are known and those that are not known yet, have a potential when they're used in the correct sequence and at the right time and in the right patient who has the right genetics and the right epigenetics at the time that you see them, that our therapies have a chance of really extending high quality life and making cancer into what we hoped for AIDS in the old days as a chronic manageable condition. I think that that day is coming, and we're certainly not there yet. That's for sure.

Kaczor: Yeah, yeah. I'm excited because I think that we can track the data much better than we have been able to, so that's certainly helps our cause as well. I thank you for carving out some time in your day and speaking with us today and updating us on what's going on. It's all very exciting, and thank you for all of your ongoing work.

Standish: Okay, thank you, Tina. Thanks, everybody. See you soon.

This podcast interview features integrative health expert Russell Jaffe, MD, PhD, CCN, who shares his philosophy about addressing men's health issues in clinical practice. Jaffe discusses hormonal balance, prostate health, gastrointestinal health, cardiovascular health, and inflammation.

About the Expert

Russell M. Jaffe, MD, PhD, is CEO and Chairman of PERQUE Integrative Health (PIH). He is considered one of the pioneers of integrative and regenerative medicine. Since inventing the world’s first single step amplified (ELISA) procedure in 1984, a process for measuring and monitoring all delayed allergies, Jaffe has continually sought new ways to help speed the transition from our current healthcare system’s symptom reactive model to a more functionally integrated, effective, and compassionate system. PIH is the outcome of years of Dr Jaffe’s scientific research. It brings to market 3 decades of rethinking safer, more effective, novel, and proprietary dietary supplements, supplement delivery systems, diagnostic testing, and validation studies.

About the Sponsor

PERQUE Integrative Health (PIH) is dedicated to speeding the transition from sickness care to healthful caring. Delivering novel, personalized health solutions, PIH gives physicians and their patients the tools needed to achieve sustained optimal wellness. Combining the best in functional, evidence-based testing with premium professional supplements and healthful lifestyle guides, PIH solutions deliver successful outcomes in even the toughest cases. If you are interested in delving more deeply into this and other integrative health topics, we invite you to join the PIH Academy.

Transcript

Karolyn Gazella: Hello, I'm Karolyn Gazella, the publisher of the Natural Medicine Journal. Thank you for joining me today. Our topic is men's health, and my guest is integrative health expert, Dr Russell Jaffe. Before we begin, I'd like to thank the sponsor of this topic, who is Perque Integrative Health. Dr Jaffe, thank you so much for joining me.

Russell Jaffe, MD, PhD, CCN: Thanks for the invitation.

Gazella: Well, before we dig into the specific health issues that men face, you believe in a philosophy first approach. I'm sorry, physiology first approach. What do you mean by-

Jaffe: The philosophy is physiology.

Gazella: Exactly.

Jaffe: So, that was appropriate. Yeah-

Gazella: So, what do you mean by that?

Jaffe: Right. It's a high level, brief, 2 words, physiology first. What we mean is, physiology before pharmacology. We mean physiology first because it seeks an upstream assessment of the causes of risk or symptoms, in contrast to most conventional care today, even holistic or not, that remains rooted in downstream symptom management. Physiology first uses global evidence to reduce risks and prevent people from falling into the river of disease. Physiology first uses nature's nutrients in supplements, with enhanced uptake and chaperone delivery, for safer, more effective, essential replenishments, items we must take in since our body doesn't make them.

Physiology first urges organic or biodynamic or locally grown sources of nutrient-dense whole foods, as minimally contaminated as possible. Physiology first focuses on underlying causes. For example, too little of essential needs being met, which are eating, drinking, thinking, doing—those are the 4 headline categories—rather than working back from symptom-reactive case management.

And finally, physiology first uses predictive biomarkers interpreted to their best outcome goal values. Now, this is a paradigm shift for many colleagues but we now can impersonalize predicted, proactive, primary prevention practices, save individuals probably a million a year just by applying physiology first.

Gazella: Yeah. Well, that's exciting so I'm glad that we went over that. Now in general, what should be on the radar of clinicians when it comes to addressing the special health needs of their male patients?

Jaffe: Yes, and here again, now that we've kind of gotten the hundred thousand–foot level, we start and recommend colleagues start with self assessment. This includes transit time, urine pH after rest, hydration, and a sea-cleans as overall global self assessments, very inexpensive. The individual does much of it themselves, brings it to the expert who interprets it so that we get a snapshot of the metabolic or metabolon/microbiome, the digestion and metabolism. You interpret that to best outcome goal values. You use that to inform and inspire and motivate people to put it in effort for the 6 to 7 weeks that it takes to change a habit of daily living and you can add years to life, years of quality life and life to years.

In people with chronic symptoms, well. Take a careful family history although family history is highly relevant if you have the same behavior and environmental factors. If you change your behavior, your habits, your environment, then your family history to a very large extent disappears into the midst of history. If there have been prior treatments and treatment failures, it's important to assess that. We use the predictive biomarkers to help people celebrate when they are at their best outcome goal value and take action when their risks increase.

Now, men and women at all ages need activity, at least 45 minutes a day of walking or equivalent. Sitting is the new smoking. Weight-bearing exercise or cardio exercise 2 or 3 days a week and knowing about it or preaching about it is one thing. It's when you actually do it. I'm glad to tell you that I had just enough glimpse of the consequences of not doing that I do what I'm recommending. Now we want to teach men to prepare for sleep, achieve restorative sleep, using physiology before pharmacology, using salt and soda baths, Epsom salts and baking soda, plus or minus aroma oil, essential oil. The baking soda alkalinizes and relaxes muscles in the pores of the skin, and the Epsom salts, which is magnesium sulfate, allows the magnesium to come in and that's often very helpful. We recommend that teaching people, particularly men who have sleep issues, about abdominal breathing and active meditation and green dichromatic light, along with nature's sources of serotonin and melatonin, which is tryptophan.

We ask about changes in urine stream flow and quality after urination. Is there any dribbling? How many times do they get up at night to urinate? And we make lifestyle suggestions tailored to the individual at their phase of life. We want to be proactive with prostate support nutrients, such as micellized soft gel that contains all of active saw palmetto, [inaudible 00:06:03], lycopene. Free lycopene, not just some ketchup. Hygeium, with 14 or 15% beta sitosterols. Urtica dioica, also known as stinging nettles. Zinc, in the picolinate form. And selenomethionine, selenium in the selenomethionine, healthier, safer form. And all of this micellized in pure pumpkin seed oil to enhance uptake in retention, to improve function. And we think people can be pleasantly surprised at how effective and synergistic the above prostate health support is, available in a single, easy-to-swallow soft gel.

Ask about adult beverages. If they consume more than 5 a week, provide comprehensive liver support and recommend a glass of water above the four quarts or four liters a day that humans need to avoid marginal dehydration—1 or 2 or 3 percent dehydrated is a big stress on every organ in your body. So this is, again, at a headline level, how our comprehensive approach actually works.

Gazella: Perfect. Now I'd like to kind of narrow our conversation and I want to stay on the prostate because you mentioned the prostate. So, what are the roles that testosterone plays when it comes to prostate health and men's health in general?

Jaffe: Right. Both men and women need testosterone. They need a balance of free and bound testosterone. They need good and not bad testosterone. Now, what does that mean? Well, you can measure in saliva or in plasma. The free and the bound, free and total testosterone. You can measure the dihydrotestosterone. You don't want much of that, maybe zero. You can measure oxidized testosterone. You want zero of that. And you want to enhance the good T, the good testosterone and reduce the bad T based on testing results because testosterone is needed for brain and muscle and organ and joint and bowel renewal and many other functions beyond just being a male hormone. You want to enhance healthy testosterone production through healthy microbiome and metabolon functions, especially the family of the central antioxidants. Vitamins, minerals, and cofactors that along with good hydration optimize your healthy testosterone, which is one of the vitality factors in the body and minimize the bad testosterone that causes everything from hair loss to loss of erections.

Gazella: Okay, perfect. So before we leave the prostate, remind us what the significance is of the PSA test.

Jaffe: That's a very important question and I think we're finally, after half a century in laboratory medicine and I've been following the issue all of that time. The PSA test is a measure of prostate repair. So, the PSA goes up if you have prostatitis. For example, if you just sit in your car too long and hold your urine in too long. And the PSA goes up in some but not all prostate cancers, and you can fractionate the PSA, free and bound, and that usually but not always helps distinguish the prostatitis from the cancer risk. If you had concern about the prostate and about PSA levels and have a biopsy, after a single biopsy—often there are multiple biopsies—the future PSA has no interpretable value that I know of except for population, but we're talking about 1 man at a time. And so many review articles that I have seen in the last few years say do other tests of prostate health and don't even do the PSA because if you don't need the test, you wouldn't do the test. If it's a question, it's a gray zone, that's exactly what the test is not very sensitive or specific.

Gazella: What about enlarged prostate?

Jaffe: The first thing I would do and have recommended for many years for enlarged prostate is to take that combination of prostate vitality factors and we have had men whose prostate was double or triple than usual size come back to that of a 40-year-old by following for about 6 months a program that includes the supplements that I recommended just a few minutes ago, along with eating foods that the man can digest, assimilate, and eliminate without immune burden, and that means the lymphocyte response assay test that measures T and B cell function and that then says eat this and don't eat that, take the supplement and don't take that, follow this mental and physical plan because in the 80,000 cases that we put in our database, we've evolved a very personalized approach to, say, prostate size.

Gazella: Okay, perfect. So, let's move on. What does it mean when a man wakes up with an erection or doesn't have an erection? Is that significant?

Jaffe: Oh, absolutely. The headline is that every healthy man should wake up in the morning with an erection. In essence, it's the quality control check of the distinctive male. Too often and very commonly, when a man does not wake up with an erection, that's a sign that they have pregnenolone steal, that they have high stress cortisol levels and low DHEA, which is the antistress hormone, usually with low free healthy testosterone, often with a sluggish thyroid and an exhausted adrenal gland, due to lack of adequate intake of the essential antioxidants, minerals, cofactors that are necessary. In addition to prostate health nutrients, I would recommend checking the thyroid, TSH, 3T3, 3T4. That can be done on a blood spot or in many different ways. But you must, by my recommendation, get the 3T3, 3T4, TSH all at the same time, and the healthy range for TSH is .5 to 2.5, not above. The usual range has too many unwell people. (Usual lab range.)

You want to check adrenal stress hormones, cortisol and DHEA at four times during one day. And at the same time, in the same saliva or plasma specimen, you can measure male and female hormones and their sources, their precursors to see if the body has learned a distress response that steals the healthy progesterone and pregnenolone and produces too much distress hormone cortisol and too little healthy male and female hormones. They come from the same source. You want to get both and in balance.

Now in regard to male sexual performance, there are natural solutions to erectile dysfunction. The following vitamins, minerals, and amino acids work as a team to improve the quality and duration of erections

• B complex. One phrase is 'B complex is for boners'. Keep the urine sunshine yellow and feel the difference comprehensive B complex means.
• C, it is ascorbate vitamin C, always fully buffered, fully reduced and we recommend based on the C cleanse, taking that amount is associated with healthier and the more robust erections.
• Vitamin D is really a neuro hormone and it does a lot of things, including improving cell function and providing cell energy to sustain the generally sixfold increase in blood retention during an erection.
• Then magnesium choline citrate. Magnesium is essential for a lot of different things, including a healthy sexual function, and choline citrate at the same time, say 220 mg of magnesium solves and a teaspoon of choline citrate. That enhances the uptake dramatically. It enhances the retention because it is an alkalinizing, rather than an acidifying source. Most magnesium solves and magnesium products have very low bioavailability and are in the acid form, which makes the magnesium run out almost as soon as it comes in.
• And then last is L-citrulline and L-arginine, and these are 2 amino acids. They both enhance nitric oxide production inside cells, and when you take about a gram of L-citrulline and 500 mg of L-arginine 30 minutes before adult activities, most men notice the difference, especially men over 40. Foods that are rich in these amino acids include nuts, seeds, chickpeas, and other legumes, also known as garbanzos, and meats. Making an avocado and chickpea hummus with some mustard seeds or black and white sesame seeds added plus or minus some toasted pine nuts with fresh ground black peppers and your favored high-quality salt, that can blend into a nutritious, delicious, amorous and traditional food.

Gazella: That's great and it sounds yummy as well.

Jaffe: It is. It should be nutritious and delicious.

Gazella: Exactly, exactly. Well, let's now move onto the gastrointestinal tract. What should practitioners focus here when it comes to their male patients?

Jaffe: Well, in the 21st century it is a pretty fair assumption that the person sitting across a professional has mild digestion dysbiosis, some degree of atrophy known as enteropathy, a long transit time. Transit time should be 12 to 18 hours. We recommend doing that with charcoal. We have an online instruction if folks are interested because you want to assess what's called the microbiome, which is the digestive tract in its fullness, or the GNS, known as the gut nervous system, which is in constant conversation and communion with the reigning central nervous system.

And so we recommend focusing on a full complement of personalized native antioxidant, minerals, and cofactors in their safer higher uptake forms based on the assessments and the predictive biomarker tests that we recommend. We want to pay attention to hydration because even a little bit 1, 2, 3% dehydrated puts a stress on every part of the body. We want to have prebiotics. That is unprocessed fiber from diet or supplements, 40 to 100 grams a day. That's what Dennis Burkitt taught me and the most knowledgeable nutritionists that I know recommend that much fiber a day. Probiotics, 40 to 100 billion healthy by a mixed bacteria, bugs. Then synbiotics, which is really recycled glutamine to energize and repair the lining of the digestive tract. Then you want to eat what you can digest, assimilate, and eliminate without immune burden.

So, you've done some functional immunology testing like LRA, lymphocyte response assay. Take in no empty calories. You are sweet enough as you are. If you feed parasites and pathogens, fungi and yeast, they will grow. Improve the digestion, the microbiome and metabolon, the innate biological detoxification competencies and enhance your digestion by eating what you can digest, assimilate, and eliminate without activating your immune responses. We teach people to stop feeding the pathogens and they disappear as digestion improves, repairs improve, resilience is restored, and habits of daily living are improved.

Then you want to look at the secretory IgA if you're concerned about the interface between digestion and the body. It's called SIgA, secretory IgA. You can measure that in saliva. There should be protected mucins so that if partially digestive materials get near the wall of the body, they don't become foreign invaders if you have healthy mucins and healthy secretory IgA. And there are other elected protected digestive functions that healthy people have that are lost when people lack the essential nutrients or the essential minerals when their cellular metabolism becomes acidic, when their body is reaching out, calling out, actually crying out for repair enhancement essentials, things you have to take in that you can't make in the body.

So, we wanna taper or possibly discontinue medications that impair digestion. We want to use prebiotics, probiotics, and synbiotics, especially in people who have had antibiotics and other digestive-interfering medicines. We want to check transit time, should be 12 to 18 hours. When I have roast beets as a main part of my dinner, I expect to see red in the commode in the morning. But I can tell you after all these years when I see that red, my first thought is never, "Oh, I had beets last night" so that's why we use charcoal. Now, avoid fat-binding medications and supplements that reduce essential fat-soluble vitamin uptake. That's vitamins A, D, E and K. And you need bile from the liver to do that and for that you need phosphatidylcholine-rich foods and/or supplements, and we happen to micellize all of our soft gels with this PC, with this—not politically correct—phosphatidylcholine.

Now, many men have atrophy of their intestinal lining because of stress and toxin exposure and it's the 21st century, and maybe less than perfect eating, breathing, and drinking. So, getting the essential needed nutrients restored may mean intensive supplementation for a few months, followed by maintenance supplementation for a long, healthy life, and I personally plan to be dancing at 120 and I would like you to join me.

Gazella: That sounds perfect. So, you mentioned tests to assess the microbiome and you also mentioned secretory IgA. Are there other tests that you recommend in terms of assessing the microbiome?

Jaffe: Right. So, the transit time we talked about, it's one of the self-assessments, 1 of the 4. Then this SIgA, the secretory IgA, in saliva or serum, with the comprehensive lymphocyte response assay, if there's any indication that the person has shifted from elected protected mode into survival mode, which means all the protective and repair functions are down regulated, that's called chronic illness to happen, or hormone tests that include cortisol and DHEA at 4 different time points, male and female hormones can be measured in their precursors on the same saliva specimen. You can use plasma if you wish.

Adrenal and thyroid adaptogenic supplementation is recommended either based on clinical history or these test results. By all means include some way of determining how much ascorbate that person needs because ascorbate is the maternal antioxidant that sacrifices yourself that all others may be presode.

And then the magnesium with enhanced uptake choline citrate. The choline helps build acetylcholine, an important neurotransmitter and neurochemical. It also helps build the choline-rich biosalts that are more soluble and help get the thicker bile out of the gallbladder and into the digestive tract, where that helps emulsify fat to be taken up into the body. And then based on the urine pH, we would adjust how many doses of the magnesium choline citrate you take. Do a regular hydration assessment and when in doubt, what I recommend is that you have a carafe of water in front of you and a glass. If the glass is full you drink it and if it's empty you fill it, and you just keep doing that. And personally my goal is to go to the bathroom at least every couple of hours and then I cut down the amount of liquid I take in after 7 or 8 PM so then I'm not overhydrated when I go to bed. But underhydration is a much more common and unappreciated problem.

Monitor the breadth of our little chemicals, and this can give very interesting insights that are both diagnosis-specific of mild digestion dysbiosis enteropathies and so forth. But in addition that information often makes it very clear to the individual that this is true for them and not in general.

And the last is a zinc taste test. Developed by Harry Henken, you drop a zinc solution on the tongue. The people who need zinc can't taste it. The people who say the zinc tastes strong have enough. And it's a pretty good one-dollar type assessment of a critical mineral and specifically for men, men need lots of minerals but especially zinc. You lose about 25 mg per every ejaculation.

Gazella: Yeah, that's good. That makes a lot of sense. So, now it's time to discuss inflammation. Is inflammation really repair deficit and how does that change clinical practice? Remind us why that's such a big deal.

Jaffe: Right. Well, we started with the physiology-first concept. Now I'm a doubly board-certified pathologist. I know the 5 aspects of inflammation. I know it's taught as a fire to be fought, something that has to be suppressed with anti-inflammatories. And now I pause and say: Anything that starts with 'anti' is using pharmacology before physiology. Inflammation is repair deficit. What my pathology colleagues see as inflammation is the cumulative lack of repair when your immune defense and repair system is doing too much defensive work because of foreign invaders from the breath or the skin or the gut, and if you enhance the innate immune system's ability to repair, your infrastructure is reborn, your bones get rebuilt, your joints are renewed, your mood is better. Your ability to get restorative sleep and meaningful relationships all are improved when you recognize that repair deficit is an opportunity.

You use the hsCRP test as a predictive and validated biomarker. It's also an all-cause mortality, morbidity marker. The healthy goal value—and this is, again, where we have the reframing. I don't even look at the lab range because that includes too many unwell people. You know the goal value for this test, hsCRP, and it's less than 0.5. Ignore statistical lab ranges unless you're treating statistics, and knowing the best outcome goal value we add ascorbate based on the [inaudible 26:350, magnesium choline citrate based on the urine pH, and other similar kinds of monitoring so that the person gets more safely the forms that are more effective because of their enhanced uptake and retention and therefore the deficits get corrected more quickly.

I mentioned hydration. I keep mentioning it only because every part of your body is healthier and more resilient and more able to repair when you take in healthy water, 4 liters a day or more of either mineral-rich, I happen to have well water but some mineral-rich water that's not contaminated and/or sparkling water. I happen to like Pellegrino but there's also Gerolsteiner and Apollinaris and actually every culture has a mineral-rich water known as a therapeutic or beneficial or health-promoting mineral water. So, you want to drink hard water, so water softeners are not recommended, at least not total home water softeners. If you want to soften the water in the pipes, I don't care, but your blood vessels are not pipes and now I care about the quality of the water that you take in.

Gazella: Perfect. So, I love your perspective about looking at repair deficit as an opportunity. Are there other ways to kind of take advantage of that opportunity to reduce oxidative stress and reign in inflammation?

Jaffe: Yes. And again, in a physiology-first point-of-view in regard to, say, blood fats. Cholesterol and triglycerides and blood fats and [inaudible 00:28:14]. If you keep the oxidation of those fats, if you keep oxidized cholesterol to zero, if you keep oxidized LDL to zero, because you're taking enough antioxidants and especially ascorbate. Now, the fat-related cardiovascular risks just went away. What remains is understanding your hemoglobin A1C, your hsCRP, your homocysteine, your LRA (lymphocyte response assay immune responses), your vitamin D, your first morning urine pH, your omega-3 index, and [inaudible 00:28:51]. Those are the eight predictive biomarker tests and we have online for folks to peruse and/or download or watch on YouTube discussions of why these eight predictive biomarkers cover all of that genetics, which is 92% of your lifetime quality of life and health. And yes, you can blame mom and dad for the other 8%, and yes transgenerational influences on RNA are a big scientific field but not yet ready to measure clinically. Live in the moment, do one thing at a time, practice gratitude and random acts of kindness, breathe abdominally for at least 5 minutes a day, and make enhance repair your practice and banish inflammation.

Gazella: That's perfect. It's a very integrative approach that includes lifestyle as well. I'd like to end with heart disease because heart disease remains the leading cause of death for men in the United States. So, what do you recommend when it comes to protecting heart health for male patients?

Jaffe: Yes, and as I think you know part of my primary research when I was in government service at the National Institutes of Health Clinical Center was collaborating with the Heart Institute on animal models of heart disease. Now, Paul Dudley White in the 1930s was a famous cardiologist. He helped invent the electrocardiogram. He taught when I was a young student that in the 1930s at Mass General Hospital in Boston, Massachusetts if they had 1 heart attack a year, they published the case. And yet 40 years after that, cardiovascular disease was the major killer of Western civilization. That's not a genetic change. It's too quick for genetics. A lot has to do with smoking and sitting, sedentary lifestyle, processing of foods, and all that goes with that.

Jaffe: So, cardiovascular disease. If your heart attacks you, if you have a clog in a blood vessel, an artery, if you have a stroke, you didn't pay attention to the upstream warnings that you would know about if you did the self-assessment, if you did the predictive biomarker tests because these change. Your risk goes up dramatically decades before catastrophe. And if you change your consumption and attitude, if you change the environmental toxin exposures and by the way 80% of the toxins that people have in their body are of recent exposure, and you can dramatically reduce that by certain simple lifestyle changes. Include 1 to 300 mg a day of micellized CoQ10 in 100% rice-brand oil, and no glycose. No antifreeze in your CoQ10. Keep the 8 predictive biomarkers at their best outcome goal value and when they are, when those 8 tests are at their best outcome goal value, you have a 99% chance of living 10+ years, even if you're 100 at that point, and my main teacher Buntey was 110 when he passed and as I mentioned before I plan to be dancing at 120 by following this lifestyle, and I urge anyone who is willing and interested to join me.

Gazella: That's perfect. Well, Dr Jaffe, we covered a lot today. Before I let you go, I'm just wondering if there's any final thoughts or anything else that you'd like to share with our listeners today.

Jaffe: Yes. In essence, the physiology-first, the epigenetics is 92% of your life quality has to do with consumption, which you eat and drink and how you think and what you do. Now whatever season of your life is as a man, that may be different. When you're young and immortal, that's one thing. As soon as you're beyond young and immortal, be prudent. Cardiovascular disease starts in teenage years. Cancer risks goes up dramatically when your innate anti-cancer mechanism is turned down because you're eating foods that are causing too much defense burden in your immune defense and repair system. So, just follow through on this physiology-first approach looking at your individual needs for personalized health promotion and put pay to chronic ill health.

Gazella: Perfect. Well, once again I'd like to thank today's sponsor, Perque Integrative Health, and Dr Jaffe I'd like to thank you for taking the time and sharing so much information with us today.

Jaffe: Well, thanks for inviting me and for making it such an enjoyable time. I hope the listeners will take away much that will be of value, and it's my pleasure.

Gazella: Well, thank you and I hope you have a great day.

Jaffe: You the same, Karolyn. Always a pleasure.

Gazella: Yes, it is. Bye-bye.

This article is part of the 2018 NMJ Oncology Special Issue. Download the full issue.

During this interview, Christopher Shade, PhD, discusses targeted nutrients to support restorative sleep in patients who are struggling with sleep issues. Shade focuses on the neurotransmitter gamma-aminobutyric acid (GABA), key botanicals, cannabidiol (CBD), and tetrahydrocannabinol (THC).

About the Expert

Christopher Shade, PhD, founder and CEO of Quicksilver Scientific, continues to be the driving force of development and innovation. Shade’s vast depth and breadth of knowledge, passion for healing, and intuitive understanding of chemistry and biology are reflected in Quicksilver Scientific’s well-designed detoxification protocols, unique supplement delivery systems, and patented mercury speciation test. Shade earned his PhD from the University of Illinois Urbana-Champaign and his undergraduate degree in Environmental Chemistry is from Lehigh University.

Shade is a recognized expert on mercury and liposomal delivery systems. He has lectured and trained doctors in the United States and internationally on the subject of mercury, heavy metals, and the human detoxification system. Shade's current focus is on the development of cutting-edge, lipid-based delivery systems for nutraceuticals, such as liposomes and micro-emulsion systems, to address the growing need of high-quality, affordable detoxification solutions.

About the Sponsor

Quicksilver Scientific is a leading manufacturer of advanced nutritional systems with a focus on detoxification. We specialize in superior liposomal delivery systems and heavy metal testing to support optimal health. Our advanced liposomal supplements are highly absorbable, and support the body in the elimination of ubiquitous toxins, enabling you to achieve your genetic potential. At Quicksilver Scientific, we are passionate about health and well-being, and are committed to improving the lives of everyone we touch.

Learn more about Quicksilver Scientific LipoCalm.

During this interview Russell Jaffe, MD, PhD, CCN, will share his thoughts on how to safely and effectively enhance and protect bone health. Listeners will learn how acid-alkaline balance impacts bone health, as well as key nutrients that can help support bone density. 

About the Expert

Russell M. Jaffe, MD, PhD, is CEO and Chairman of PERQUE Integrative Health (PIH). He is considered one of the pioneers of integrative and regenerative medicine. Since inventing the world’s first single step amplified (ELISA) procedure in 1984, a process for measuring and monitoring all delayed allergies, Jaffe has continually sought new ways to help speed the transition from our current healthcare system’s symptom reactive model to a more functionally integrated, effective, and compassionate system. PIH is the outcome of years of Dr. Jaffe’s scientific research. It brings to market 3 decades of rethinking safer, more effective, novel, and proprietary dietary supplements, supplement delivery systems, diagnostic testing, and validation studies.

About the Sponsor

PERQUE Integrative Health (PIH) is dedicated to speeding the transition from sickness care to healthful caring. Delivering novel, personalized health solutions, PIH gives physicians and their patients the tools needed to achieve sustained optimal wellness. Combining the best in functional, evidence-based testing with premium professional supplements and healthful lifestyle guides, PIH solutions deliver successful outcomes in even the toughest cases.

Transcript

Karolyn Gazella: Hello, I'm Karolyn Gazella, the publisher of the Natural Medicine Journal. Thank you for joining me.

Today, we're talking about bone health with pioneering integrative health expert, Dr. Russell Jaffe. Before we being, I'd like to thank the sponsor of this podcast who is Perk Integrative Health. Dr. Jaffe, thank you so much for joining me today.

Russell M. Jaffe, MD, PhD: Thanks for the invitation.

Gazella: Well you know when we think of our bones, we often think of osteoporosis. Let's start there. How common is osteoporosis in particular?

Jaffe: Oh, far too common. Depending on how you make the measurements, somewhere between 50 and 100 million Americans are at risk. One in 4 women over the age of 40 will have a fracture of their bones due to the osteoporosis or osteopenia. Maybe 1 in 5 or 1 in 4 men, maybe more, the precision of diagnosis probably understates the issue. The point is that bones, whatever your birth date might be, your bones should be young.

Bones turn over every 10 years, which means no part of any bone that you or I have is more than 10 years old. Remember when we were 10 years old, we could jump around, we could leap around. I don't recommend behaving like a 10-year-old. What I'm saying is, your bones should be resilient, and flexible, and not brittle, and not being leeched by the stress and dietary choices of modern living.

Gazella: Yes. It's hard for me to even imagine a 10-year-old, but it would be fun to have bones like a 10-year-old, for sure.

Now is the DEXA scan still the gold standard for measuring bone density?

Jaffe: Yes. D-E-X-A, DEXA is the "gold standard" reference standard. There are other measures that are coming along. There's N-telopeptides which are a little hard to interpret. There are other measures, but to the best of my understanding, the expert experts in bone say that you can measure DEXA changes over 2years. My colleague, Susan Brown and I did an anecdotal prospective study with 11 people, 10 of whom had between 2% and 10% or 11% new bone growth, unprecedented new bone growth by following this approach to Alkaline Way bone health.

Gazella: Yes. How often do you recommend that patients get a DEXA scan?

Jaffe: Well, let me come at it 2 or 3 different ways. In regard to the usual and customary use of the DEXA scan, it's a 2-year waiting period. Now many doctors will do a DEXA after one year and try to compare, and interpolate, God bless. Other people will use other measures, including bone mineral protein and how much of that there is in say the urine.

You asked the right question, which is what is does the measure that almost everyone agrees, or that about which there is reasonable agreement and consensus. The answer there, DEXA. Until something better is really validated and yes, new things come along all the time, but I'm seeing a lot of them go 'cause as you know, my PhD was in collagen and elastin cross-linking, and how you regulate that. That was half a century ago and learned a lot since then. But collagen has a lot to do with bone health and bone turnover.

Then there's certain other unique characteristics contributed by the liver that allow the minerals, not just calcium, but all of the minerals that are necessary to align properly to form what we call a bone.

Gazella: When it comes to bone health, what do you mean when you say physiology before pharmacology?

Jaffe: Well I mean the fact that bone is piezoelectric, which means when you walk, when you move, actually stimulating tiny electrical flows that say to the bone rebuilding cells, the osteoblast and osteoclast, "Do your job." Moving is a good thing, at least 45 minutes a day of walking. Yes, sitting is the new smoking, but if you get up at least 5 minutes an hour, you can undo most of the adverse effects of cutting off your circulation when you sit in most chairs.

Now if you happen to have one of these recliner chairs or something like that, more power to you, but you still have to get up out of the chair. Walk for at 45 minutes a day. [inaudible 00:05:24], to the extent that he had a doctor was me, and [inaudible 00:05:29] very active now, they both agree. Now walking is a terrific way of human beings stimulating bone growth because of this "piezoelectric" or tiny electrical flow that nurtures and nourishes the bone. That's an example of physiology before pharmacology.

Gazella: A great example. When it comes to your integrative approach, I want to dig into certain aspects of how we can enhance or protect bone health. You often talk about the acid alkaline balance. How does acid alkaline balance impact bone health?

Jaffe: Well in essence when your diet or your environment contributes acid, your bones melt slowly away and sometimes not so slowly. On the other hand, when you have a mineral rich environment that bathes the cells and renews the cell's mineral buffering abilities, now you build new bone. We want to build new bone. We don't want to melt the existing bone.

Gazella: Right. That makes a lot of sense. Let's stay on this topic for a bit because I know that most of our listeners understand how to support the acid alkaline balance, but what are some of your foundational aspects when it comes to supporting proper acid alkaline balance?

Jaffe: Well as you know, we start with the self-assessments. The assessment we want to start with measuring the pH, that means how much acid or how much mineral is in your urine after 6 or more hours of rest. It's the one time of day when you get a meaningful measure in a non-evasive way of the cellular mineral status, 'cause after 6 hours, the fluid in the bladder equilibrates with the lining cells, and lining cells, if they need magnesium then they put the extra acid into the urine.

If it's below a pH value of 6.5, then you're too acid. You're deficient in minerals, particularly magnesium at the cellular level. You should take 2, 3, 4 more doses a day of magnesium, but enhanced uptake magnesium with choline citrate. It must be choline citrate, it cannot be choline bitartrate. Try to fool mother nature and she'll come back and slap you on the tush.

You want to enhance the uptake and chaperone delivery of magnesium based on [inaudible 00:08:14] chemistry, and for your listeners who are technical, these are inverted [inaudible 00:08:20] droplets. I really am a biochemist. What that means is tiny little droplets that are taken up by [inaudible 00:08:28], that easily enhance the uptake. In recent studies near 100% comes in and then goes to the cells that are [inaudible 00:08:37].

Gazella: You know it seems like bone broth has been the rage for a while now. What are your thoughts on bone broth as a way to boost bone nutrition?

Jaffe: Well I'm a big advocate for broth, but not bone broth. Why not bone broth? Bone broth turns out to be far too rich in glutamate, and why is it rich in glutamate? You wouldn't think there's much glutamate in bone, it's glycine, and proline, and something else. No.

What the industry calls bone broth includes skin, it includes things that have no other commercial value that are left after you "render" the animal, or the chicken, or the whatever, [inaudible 00:09:27] bone. Bone broth, no. But meat broth, vegetable broth, fish broth, broth you make at home, or broth that's organic or biodynamic, yes, yes, yes.

Broth is a very good source of minerals, and I mean vegetable broth, fish broth, meat broth if you want, but real meat made into a broth, which means you very slowly simmer it until it falls apart, and then you have more or less a broth, especially if you either whisk it or put it in a blender. Broth, yes. Bone broth, no.

Gazella: Okay, good. That's a good distinguishing factor. Now we also hear about MSM and hyaluronic acid for bones and joints. I'm wondering what you think about these 2 ingredients when it comes to bone health.

Jaffe: Well MSM is a sulfur source. Sulfur sources are very important in protecting and enhancing bone vitality and renewal. Now we recommend that physiology before pharmacology approach, which we use garlic, ginger, onions, brassica sprouts and eggs. G-G-O-B-E, garlic, ginger, onions, brassica sprouts. All sprouts are good, but broccoli sprouts, brassica sprouts especially, and eggs.

Why not MSM? 'Cause it's pharmacology. It is water soluble DMSO. DMSO makes you smell like a fish. Not a very healthy fish or a decomposing fish actually. MSM is a supplement that's been around for 20 plus years. It has a certain [inaudible 00:11:04] that comes and goes, but it's pharmacology. We want to start the physiology, the G-G-O-B-E, garlic, ginger, onions, brassica sprouts and eggs. Then if a particular practitioner feels that additional MSM is helpful, I think they make the final decision along with their client.

As you can hear from my comments, we want to use nature's pharmacy, which means you generally have to cook the food the way it's traditionally done. If you just chop up an onion, the cell walls will prevent you from getting the good stuff. But if you sauteed the union until it's clear, now you have a nutritious and delicious detoxifying physiologically helpful bone joint and vitality enhancing material that you can make into any broth you want. However, you want to eat the foods you can digest, assimilate and eliminate without immune burden. If your body reacts to one or more of the G-G-O-B-E foods, then substitute with the other 4.

Thomas Jefferson said they should be stables in the diet, not condiments. I'm a Jeffersonian democrat, which means I'm a grieving optimist. I believe that we should make these staples in our diet again.

Gazella: Yeah, that makes a lot of sense. What about hyaluronic acid?

Jaffe: I'm glad you asked that too. Hyaluronic acid is different. It is physiologic, so when you take ... I'm a pathologist, [inaudible 00:12:40] certified pathologist. When you look under a microscope at a joint, more than at bone, but at the joints you do see what are called water absorbing compression-friendly molecules, hyaluronic acid among them.

Hyaluronic acid goes back to the early '80s, when a Canadian company thought that this was going to be the answer to joint erosion, to the kind of bone-on-bone pain that very commonly occurs to people who haven't walked enough, and have sat too much, or have been on planes too much, as I have been from time to time. Hyaluronic acid has a medical application. It's an injection.

I think after you use nature's pharmacy, after you engage, when you eat and think, drink and do in a comprehensive and holistic way, that injections in hyaluronic acid in the right hands, in experienced hands, are an option. It does provide relief to some people for a period of time while other renewal should be engaged in.

Gazella: Okay, that makes a lot of sense. Now let's dig into some of your other go-to nutrients for healthy brains. I'm sorry, health ...

Jaffe: Bones.

Gazella: Bones. Yeah.

Jaffe: That applies to brains too.

Gazella: Yeah, yeah. That's good. When it comes to bones, what are some of the nutrients that you like to recommend?

Jaffe: Well in regard to the nutrients, there are over a dozen and a half. You can divide these into vitamins, minerals and co-factors. It's mostly about a family or a symphony of minerals. Remember a symphony has many different instruments, each of whom plays a slightly different tune. We recommend, in addition to vitamin K1 and K2, in addition to vitamin D3, we recommend biotin necessary for healthy bone. We recommend half a dozen forms of calcium, half a dozen forms of magnesium. Specialized bio available forms, low contaminant forms of zinc and magnesium, and chromium and selenium, methionine. Copper is the sebacate, iodine and iodide, you need both.

Boron, acid citrate, vanadium, which balances out blood sugar and chromium. Silica, but from horsetail. Stable strontium is the gluconate, and fiber, croscarmellose fiber to enhance the easing digestibility making it food-like. Those are the over 18, 19, 20 essential bone building nutrients. Now vitamin D should be the D3. There should be some vitamin C to keep everything reduced and happy.

Gazella: 'Cause this does seem like a big list. These all work synergistically?

Jaffe: And they're all essential. If you lack any one, your bones won't renew properly. It's amazing how many co-factors, how many minerals and necessary nutrients that allow for bone health. But Dr. Susan Brown and I published an article a decade ago, we're working on an update now, which basically says the more tonic, or soda, or acid beverage you consume, the more quickly your bones will dissolve, the more quickly your bones will melt away.

Then on the other hand, when you have a healthy traditional diet, rich in minerals, the Alkaline Way, the joy of living the Alkaline Way, documented by morning urine pH, keeping it in the 6 ½ to 7 ½ range, that's green rather than sandy color which is acid, or blue which is too alkaline, you want to keep it in the green zone. It's Goldilocks scenario. Not too much, not too little. Just right is just right.

Gazella: Now before I move on, I want to talk about this combination of vitamins, minerals and co-factors. Are these in one product? What will be ...

Jaffe: Oh, yes. This is what Dr. Brown and I used in our prospective study. When I say gaining 2% to 11% new bone, by DEXA in just 2 years, I'm saying people taking this formula and also following a healthy lifestyle of foods they can digest, assimilate and eliminate.

Gazella: Okay, great. What's the name of this product and what's the recommended dosage of this product?

Jaffe: Well the recommended dosage is 4 tabsules a day to build, 2 tabsules a day to maintain, 6 tabsules a day if you have osteopenia or osteoporosis.

Gazella: Okay, so 4 per day, 2 per day. Then, I'm sorry, that was 6 per day if there is osteoporosis or osteopenia? Dr. Jaffe?

Jaffe: Oh, I'm back. Sorry.

Gazella: Okay, perfect. The dose for osteoporosis or osteopenia is 6 per day.

Jaffe: Yes, that would be 6 per day. What I would say would be 3 in the morning, 3 in the evening, so a twice a day dose of 3 tabsules, these are fully active, fully available, and they contain all of these different nutrients, each one of which is necessary, and together they form a symphony or a bone building team.

Gazella: Okay, perfect. Great. Now I want to switch gears a little bit. What's your view of bone morphogenic proteins and the long-term effect on bone status?

Jaffe: Well you're absolutely up to the minute. Bone morphogenic protein is being studied as we speak. It's promising, but we really don't, in my opinion yet, have enough information. What we know is it's built upon something called 2-Beta Coxatene, for those of you who are technical. This is bone mineral protein precursor.

Dr. Brown and I are, at this moment in time, encouraged by what we have heard about this. She and I are collecting information as we speak, and stay tuned for bone [inaudible 00:19:21], as they say.

Gazella: If we were going to look into the future when it comes to integrative health and bone support, bone building, is this where we're headed with the morphogenic proteins? Is this an exciting area?

Jaffe: Well yes, definitely an exciting area. The question is, how much do you need for each person because, as you can imagine, given that you started with a really healthy organic or biodynamic bone, and then you somehow got out of it, this magic complex, how much do you need, and how much does it cost, and how long will it take before you really confirm what is asserted by some clinicians based on their observations? The observations are encouraging, but stay tuned for the bulletin.

Gazella: Okay. Perfect. Now I want to dig into diet and lifestyle. I want to circle back with your G-G-O-B-E, the garlic, ginger, onions, brassica vegetables and eggs. Explain it again or in more detail as to why these 5 dietary items are foundational for you.

Jaffe: Right. They're foundational because in traditional societies they are sulfur rich. You can think of sulfur as a fire that burns away bad stuff and toxins. That's a metaphor, but biochemically it's not far from the case.

For those of you who are technical, they form thioethers. This makes compounds that would otherwise be free radical generating harmful compounds more water soluble and less harmful, so once they're complex, what these sulfur rich foods, or the sulfur in the foods, then they can be treated in urine, sweat and stool more safely and effectively, and it's been used for millennia in traditional societies. We just have rediscovered it in recent times.

Gazella: Perfect. Well I want to stay a little bit with eggs because I've done a lot of writing about eggs, and I had the belief that eggs have gotten a bad rap. I personally eat eggs almost every morning. Explain to us about why eggs got the bad rap, and why eggs are actually good for us. Just remind us of that.

Jaffe: Yes, eggs got a bad rap because Levy and Fredrickson had the idea of the diet-heart hypothesis that the amount of fat or cholesterol you ate was determinative or it actually determined how much blood fat you have. Now it turned out to not be the case, but Levy ran the Heart Institute and Fredrickson ran the NIH. They had the dominant ... in their time.

At that time, there was a man named Olson, and he pointed out that eggs are the perfect food when you combined the white and the yolk, when you make a gently coddled or gently cooked egg you have a near perfect food in regard to easy to digest, assimilate and eliminate for people that have healthy digestion.

Now implied in what you said, I think, is getting a healthy egg. My preference today are goose and duck eggs, or quail eggs because they haven't been messed with very much. If you put in front of me a biodynamic chicken egg, or a home harvested fresh egg, I'll be delighted. Commercial eggs I'm not so sure of. I'm concerned about what the chicken ate the got into the egg and that's what she wrote, as they say.

Gazella: I would have that same feeling as well. Let's talk a little bit about what we should not eat if we're trying to protect and enhance bone health. What do you tell your patients not to do from a dietary standpoint?

Jaffe: Well as you know, I don't have a private practice. I get to influence other doctors and their probable cases, but what I do recommend is stay alkaline. Stay alkaline means eat foods that are mineral rich, eat foods that are antioxidant rich, eat foods that are nutrient dense and rich, and you are sweet enough as you are, do not add sugar to your diet, do not use edible oils. I think edible oils is an oxymoron. What I mean by that is you avoid packaged goods, shipped foods, crisp foods, extruded foods, things that have been processed because processed means you lost the good stuff and you gained the bad stuff.

Do a makeover in your kitchen, eat the foods that are whole, eat more fruits and vegetables that are vying ripe. If you want to have healthy fat in your diet, have an avocado, a whole one. Once you separate the oil from the seed, you know, like the olive oil, once you separate the oil from the seed the protective material is now gone and what you have are dense calories. Fat are dense calories, but those fats, those edible oils are easily oxidized, damaged and rancid. Then they get masking agents to make sure that your tongue and your brain get addicted to wanting those rancid processed fats.

I don't think that's a good idea. I can tell you lots of reasons why [inaudible 00:25:15], who taught me about this in the early '80s, late '70, [inaudible 00:25:19], why Patty Deuster is so correct about these issues, but slowly we turned in regard to nutrition [inaudible 00:25:26].

Gazella: Let's talk a little bit about lifestyle factors. Now you mentioned movement and exercise in a scientific literature is so clear that that's protective of bone health. What about other lifestyle factors, like if we're looking at stress, or sleep, or just other things that we do? What do you tell your doctors to tell their patients?

Jaffe: Well what I learned from [inaudible 00:25:52] and the Dalai Lama was that afflictive responses, that is the traumas of early life or the traumas of daily living that contribute stress hormones, afflict us, they erode us, they reduce new bone formation. By the way, no one gains from any of that.

In the famous words of Bobby McFerrin, "Don't worry, be happy." I don't mean live by denial. What I mean is practice relaxation response. Know that your breath is a refuge and know that stress hormones only come out when you feel under attack. You may have heard about fight or flight, but there's also fortitude, there's also gaining the resilience to know that when you go to your breath, you can stay at ease even if everyone around you is hysterical. I can tell you from personal experience, in my family, if you didn't shout, no one paid any attention to you because everyone else was shouting. They just didn't know it.

Gazella: Yeah, that's true. The relaxation ... Stress is a big deal. What about sleep? I know often times, sleep and stress go hand in hand, and one can lead to the other, and vice versa. What's your philosophy on sleep?

Jaffe: Yes, my philosophy on sleep is that it's really important, restorative sleep, and how do I prepare for restorative sleep? Well I take a salt and soda bath. I put half to a cup of baking soda and Epsom salts in a warm tub of water, and get in for 20 minutes. First 5 minutes I breathe like a baby into my abdomen, the next 15 minutes I pray that my heart won't attack me, and whatever active mediation you want to do, then I get out and I dry off before I get into bed, and I stretch when I'm in bed before I fall asleep.

Then I might even ask myself a question that I would like my dreams to answer if I'm inclined to do that. [inaudible 00:28:03] dreaming myself. In the morning I wake up and I stretch. I got to bed early enough that I get up early enough that I don't need an alarm clock. There is no screen, there is no clock, there's no unnatural sound.

Occasionally I'm woken up by a wind chime or by a bird, but that's a nice thing to get woken up by. Then I stretch before I get out of bed, and then I get in the shower and I stretch when I'm in the shower, 'cause if you're not stretching a lot, you'll contract. Look at most old people, they slow down and contract. I am how you say old, but not that old, and I'm not yet contracted.

Gazella: That's a good thing.

Jaffe: That's a good thing. I'm working on it.

Gazella: It's perfect. What would you like to be the most important bone health message that our listeners of health care professionals receive today? What's the most important thing that you want to get across?

Jaffe: Most important is that bone health is a choice. It is about what you eat and drink, think and do. When you put it together in this proactive way, you have healthy bones for life. If you follow the "Conventions of modern living and pharmaceutical pill-based solutions," you end up slowing the loss but creating brittle, more fragile bones. In the famous words of Mel Brooks, the 2,000 Year Old Man, "Don't do that."

Gazella: Right. Yeah, the physiology before pharmacology, I think, is such an important message.

Well this has been very interesting, Dr. Jaffe. Once again, I would like to thank the sponsor of this topic, who is Perk Integrative Health. Dr. Jaffe, once again I'd like to thank you for joining me today.

Jaffe: Pleasure to be with you as always.

Gazella: Yes. Have a great day.

Jaffe: You have the same.

Research is confirming that there is a direct link between the gut and the brain. In this interview, probiotics expert Ross Pelton, RPh, will describe the research associated with probiotics and brain health. The focus of the interview is on cognition and mental health issues such as depression and anxiety and how probiotics may help patients with brain issues.

Approximate listen time is 31 minutes

About the Expert

Ross Pelton, RPh, CCN, is Essential Formula's director of science, in addition to being a practicing pharmacist, clinical nutritionist, and health educator in Southern Oregon. Pelton earned his bachelor of science in pharmacy from the University of Wisconsin. A certified clinical nutritionist, Pelton was named as 1 of the Top 50 Most Influential Pharmacists in the United States by American Druggist magazine for his work in natural medicine. Pelton teaches continuing education programs for healthcare professionals to use natural medicine and integrate it into their practices. He also has authored numerous books, including The Drug-Induced Nutrient Depletion Handbook, which is a gold-standard reference book for health practitioners.

About the Sponsor

Essential Formulas Incorporated (EFI) was established in 2000 as the sole US distributor of world-renowned microbiologist Dr. Iichiroh Ohhira’s award-winning probiotic dietary supplements and skin care products. Always an innovator, EFI introduced REG’ACTIV in 2015, containing ME-3, a probiotic catalyst that produces the “master’” oxidant glutathione inside the body's cells. A family-owned and operated business, EFI was founded on the philosophy of providing high-quality preventative, supportive, and comprehensive pro-health products for the entire family. EFI continues to flourish and grow through a strong company and product integrity and the knowledge that they’re providing scientifically proven products that positively impact the health and well-being of their customers.

Transcript

Karolyn Gazella: Hello, I'm Karolyn Gazella, the publisher of the Natural Medicine Journal. Today we're talking about the gut-brain axis and how probiotics can help with brain function, including mental health issues and cognition. Before we begin, I'd like to thank the sponsor of this topic who is Essential Formulas Incorporated. My guest is probiotics expert and registered pharmacists, Ross Pelton. Ross, thank you so much for joining me today.

Ross Pelton: Hi, Karolyn is really nice to be with you and your audience again. Appreciate it very much.

Gazella: Yeah, this is a really interesting subject. We've covered it a little bit in the Natural Medicine Journal, but I'm really anxious to kind of dig in a little bit more deeply with you. So let's just jump right in. How much do we know about the connection between what's going on in the gut and how that can influence the brain?

Pelton: Well, we're starting to learn a lot more about it and I would say that we're still in the infancy of this learning curve, but we now understand why we call the gut your second brain. There's an enormous amount of neurons in your gut. There's over a hundred million neurons and your probiotic bacteria and the compounds they produce, interact with those neurons in your gut and send signals to your brain up what's called the vagus nerve, and so that's how the gut communicates with the brain, through this super highway of nerves called the vagus nerve. It's the longest nerve in the body. What's really interesting to me, Karolyn, is that they've figured out that about 20% of the vagus nerves are sending information from the brain into the stomach or the gut. But 80% of these nerve fibers in the vagus nerve are sending information from the stomach to the brain. So the majority of this information, this communication between the gut and the brain is really the gut communicating with the brain.

Gazella: Wow. That's pretty cool. So let's talk a little bit about the scientific literature then. What does the scientific literature tell us about the link between the gut microbiome and mental health issues like depression and anxiety?

Pelton: That's getting to be a big topic also and there's a tremendous amount of work being done in that area. In the cover, on the cover of the magazine Psychology Today, in April, 2014 their lead article was the psychobiotic revolution, how your gut bacteria control and influence your emotions and your state of mind. So a mainstream journal, Psychology Today, is referring to what they call a psychobiotic revolution. There's more and more studies that are starting to tease out how this happens. One study I found that was very interesting, mice who were infected with a very small of a toxic bacteria called campylobacter, but it was such a small dose, it did not cause any immune system activation. So the body really didn't know it was there. There was no immune alarm reaction.

However, several tests revealed at the mice exhibited greater levels of depression and anxiety-like behavior. So the brain knows, even though the body wasn't responding with an immune reaction, the brain could tell that there was some bad bacteria, very small amount in the gut. In a human trial, it was chronic fatigue patients. It was a placebo controlled trial so some of the chronic fatigue patients were getting probiotics and some were getting a placebo and they did stool samples and they did a number of tests of depression and anxiety and the people taking probiotics were calmer, had less anxiety and claimed they were better able to cope, they got better sleep and they had fewer heart palpitations. So animal studies and human trials are also kind of combining to give us more and more information about this gut-brain communication.

Gazella: Great. Now what about other brain issues like cognition and concentration? Does the gut-brain axis cover those issues in the scientific literature as well?

Pelton: Well, it really does and it starts at birth and there's a real strong and important relationship between the early microbiome and child cognitive development. You find out that when children are born with a Cesarean birth, the mother has to give a C-section birth, then there's a difference in the microbiome. They've studied infants between C-section births and healthy natural vaginal births and they find out that the infants that are born via C-section for cognitive development through the ages of 4 through 9 is what this particular study looked at and they called it a cognitive gap. So it's just more information that's detailing that an infant's microbiome plays a real critical role in cognitive development.

Now, we're learning more and more about the relationship between microbiome and psychology and neuroscience and normally you'd think that the fields of psychology and microbiology are not really connected, but now they're starting to be strongly connected because we're finding out how strongly microbiology and the influence of your bacteria communicate with your brain and affect your mental, emotional states. So gut health affects mental health is the stronger and stronger message that's coming out from the scientific community.

Gazella: Yeah, it's really true. I have to tell you, there was an interesting study that I read while I trying to prepare for this interview and it was involving traumatic brain injury. Now, I understand that that connection is preliminary, but it's pretty promising to make the connection between traumatic brain injury and the gut. How can probiotics help someone who has experienced traumatic brain injury?

Pelton: Well, there's several studies that have been done on this now. The gut-brain axis is a communication between the gut and the brain and it's the nervous system that does the communication, and when you upset the nervous system, you're going to upset the communication between the gut and the brain. So the gut microbiome has a central role in this pathway of humidification and it's really altered. They find out that the gut microbiome is significantly altered following a brain injury. It reads to more inflammation in the central nervous system and that affects the brain. You get brain inflammation. So that's 1 of the studies that talked about this traumatic brain injury microbiome relationship.

In animal studies, it's not nice to talk about these studies because they do some nasty things to the animals, but that's the way we learn about a lot of these things. So they took some male rats and divided them into 2 groups. One group received a brain injury and the other didn't. But they looked at their microbiome before and after and they started a pre-traumatic brain injury incident and then they rechecked the microbiome in day 2, day 7, and day 14. They found that the mice that had received the traumatic brain injury, there was a definite significant change in the composition of their microbiome and it got worse as time went on. They started looking at the microbiome before the injury and then checked it at 2 hours after the injury and then 1 day, 3 days, and 7 days afterward. The change in the microbiome continued to worsen after that traumatic brain injury. So when we learn more about this, we see that the faster you can intervene, the more help that you can provide in this type of a situation.

Gazella: So the scientific literature is clear that in cases of brain function, mental health, like depression, anxiety, and even in cases of traumatic brain injury, that the gut microbiome is altered. Does the scientific literature tell us that a probiotic intervention can reverse, change or influence the gut microbiome in such a way that the brain will be positively influenced?

Pelton: Well, yes. That's what we're learning is that if you supply probiotics, you will change the gut and you change the electrical and chemical communication between the gut and the brain and you can influence the brain in positive ways. There's a number of researchers that are really documenting the changes in the brain from microbiome probiotic administration. There's a scientist by the name of [Christine Tillich 00:09:11] and she does brain imaging scans on people, these are human clinical trials. She had a group of women who had no previous gastrointestinal complaints and no previous psychiatric problems. She gave them probiotics twice a day for 2 weeks and she conducted functional MRI brain scan on these women and they were looking at the brain activity when the volunteers were viewing faces that contained different emotional expressions and they found changes in the brain regions that control the central processing of emotions and sensations.

So this is a placebo controlled trial. Some of the women who were taking something but wasn't a probiotic and then the other women had probiotics and the women that had probiotics, they found positive changes in the brain areas that process emotions and sensations. So really interesting work that's being done.

Gazella: Yeah. Very exciting to know that we have this intervention. Now, last year I read about a very small study that got some publicity and it was actually negative towards probiotics and it stated that probiotics can actually cause brain fog. I'm not sure if you had a chance to read that study or what's your take on this issue if it's come up in your pharmacy practice that probiotics can actually cause negative brain issues?

Pelton: Well, I'm familiar with that study and my take on that is that this has to do with SIBO, small intestinal bacterial overgrowth. When people have SIBO, then yes, probiotics can cause a problem because SIBO is a situation were bacteria that are normally resident in the large intestine and the colon have translocated. They backed up into the lower portion of the small intestine. So it's not necessarily bad bacteria, but it's just bacteria that are now in the wrong geographical location in the GI track. Those bacteria can digest the fibers in food and cause gas and bloating and a great deal of discomfort. They produce a compound called D-lactate and that can produce brain fog.

But the scientist that reported this, I think, really didn't report it correctly, or at least how I would like to report it because he's just saying that taking probiotics cause brain fog. Well, you have to understand that this is in SIBO and many people with SIBO should not be taking probiotics because the bacteria will digest the fibers and cause a great deal of gas and bloating and discomfort. So SIBO is a unique situation and needs to be dealt with separately.

Gazella: Yes. Now, that makes a lot of sense. I'm glad that you clarified that. So when it comes to using probiotics in clinical practice for brain health, do you recommend probiotics as a sole treatment or as a part of a more comprehensive protocol? How can clinicians best use probiotics in clinical practice for this particular application?

Pelton: Well, I'm always in favor of a more comprehensive approach to health, so I wouldn't advocate just probiotics. It's really important to understand how important a healthy diet is and exercise and good sleep. I also advocate a wide range of different types of nutritional supplements. But probiotics are 1 of the things I do recommend on a regular basis and it's kind of like insurance where you might not need it, but if you get in this situation where you need it, you're darn happy that you have it. I would say that there's certainly a range in how important probiotics are to people. Some people can maintain a microbiome when they're eating a healthy diet and they do pretty well long term and they might be less in need of probiotics on a regular basis.

But I would say the majority of Americans, in fact, I've got 1 study that said that 90% of adults and children in America do not consume the recommended amount of fiber in their daily diets and fiber is what feeds your good bacteria. So if you're not getting adequate fiber in your diet, then you're not supporting the growth of your microbiome and your need probiotics. But I really emphasize the people, Karolyn, probiotics alone are not enough. You have to feed your probiotics well, otherwise they won't thrive and survive. So it's a combination of a fiber rich diet with lots of fruits and vegetables, especially the multicolored vegetables. That fiber will feed your microbiome and promote growth and proliferation of a more diverse microbiome. So it's probiotics plus fiber in the diet.

Gazella: How do you counsel your patients about getting more fiber in the diet? Because I think you're right. I think that this is a big issue and the statistics are pretty clear that people aren't getting enough fiber and fiber and probiotics go hand in hand. How do you teach them to get more fiber in their diet?

Pelton: Well, I encourage people to Google my YouTube video. It's an 8-minute youtube video, just Google Ross, R-O-S-S, and and salad buzz, B-U-Z-Z. It is an 8-minute video that I teach people how to save a lot of time making salads. One of my theories is that people don't eat salads often enough because they're time consuming. But I teach to process all the vegetables all at once and then the secret to the whole process is squeeze a lemon over all of your processed vegetables and toss that lemon and lemon juice in your vegetables and the vitamin C in the lemon juice will preserve your precut vegetables. So I put it in a Tupperware and it stores easily for a week and then every night when my wife and I have our big salad, I take a handful of lettuce and a handful of vegetables that I've already processed and put some wild caught salmon on there. It takes me like a minute to make supper. So it's a way to get a wide range of vegetables because I've got about 14 different types of vegetables in my salad mix and it saves time in the process.

Gazella: Yeah, it's a great idea. I'm sure that practitioners may want to share that with their patients. So that's Ross salad buzz. Go ahead and search that. So now let's talk about probiotics. I mean, this is a field where there are a lot of different types of probiotic products. So what do you feel clinicians should look for when choosing a probiotic to recommend to their patients?

Pelton: Well, that's a really broad topic, Karolyn, and there's a lot to talk about there. Turns out that humans have somewhere between 500 and a thousand different species of bacteria in their GI track and we're just beginning to learn what these are and there's a wide range between your microbiome and my microbiome. But generally you want to have a strain that has been prepared well in manufacturing so they good shelf life. That's a critical factor whether or not they need to be refrigerated. But 1 thing I'd like to talk about is what I call the new frontier in microbiome science. This is the term postbiotic metabolites. Now, some of your listeners might not be aware of this term, but it's really in 1 of the most important new understandings about probiotic bacteria and the microbiome.

We're starting to learn that it's not so much the bacteria that are important, but it's the compounds they produce and we call these compounds postbiotic metabolites. So the process goes like this. You ingest fiber rich foods, your probiotic bacteria break down those fibers and produce secondary compounds that we call it postbiotic metabolites. These are the compounds that are the master health regulating compounds for the entire body. These postbiotic metabolites influence the functioning of every single organ system in the body, especially your immune system in your brain. I use the analogy of NASA's mission control center, controls our space flights. There's dozens and dozens of scientists and engineers but it's really the hundreds of computers making millions of decisions every second that guide and regulate our space flights.

So in my analogy, your probiotic bacteria are kind of like the scientists and engineers, but it's your postbiotic metabolites that are really doing all the work, controlling and regulating all the signals that are having an effect on virtually every single organ system in your body. So that's the real important message and the new frontier and the microbiome, learning what bacteria produce these compounds, what strains of bacteria are more efficient at producing some of these compounds and as we get farther into this whole topic, science will start to tell us what types of fibers and what types of food will primarily or preferentially feed different types of bacteria.

We know that diversity is important for a healthy microbiome and that means a wider range of different types of bacteria. The way to get a wider range of different types of bacteria is to consume a wider range of different types of fiber. So it's not just the quantity of fiber, it's also the the different diversity, different types of fiber is what's required to get a diverse microbiome.

Gazella: Now give us some examples of the postbiotic metabolites that are produced that are so important to our health.

Pelton: That's a big topic and I'm glad you've asked me because it's fascinating to me. Our probiotic bacteria are fascinating little chemical factories and so some of the postbiotic metabolites, all the B vitamins are produced by your probiotic bacteria. Several of the amino acids, they make a lot of the neurotransmitters and lactobacillus fermentum ME-3 produces glutathione. Some of the strains produce hydrogen peroxide, which is active against some of the things like Candida yeasts and short chain fatty acids are 1 of the big, most important categories that we know about. These short chain fatty acids are active against pathogens. They rebalance the acid base level. They have antiinflammatory activity. So that's why these postbiotic metabolites are so important because these are the compounds that have all the activity to regulate the microbiome ecosystem.

So again, it's not just the bacteria, it's all these compounds that they produced. These compounds are produced during fermentation. The bacteria ferment foods to get access to the fibers and then they change these fibers into these secondary metabolites, the postbiotic metabolites. So fermentation is the process that creates the postbiotic metabolites. For years, and in fact for centuries, fermented foods have been a primary way that we preserved foods and it's the postbiotic metabolites, especially the short chain fatty acids that are produced during fermentation that create an acidic environment to suppress the growth of pathogens. So that's how fermentation works and that's an important part of your immune system because in your gut, the bacteria go through fermentation process and produce these short chain fatty acids that will suppress the growth of pathogens.

Gazella: Yeah. When you're describing this, you're describing this combination of fiber plus bacteria. So you're actually describing more than a probiotic. You're describing more of a whole food extract or what's sometimes called a symbiotic. Is this where we're headed? It seems like there's not a lot of probiotic products that have fiber rich foods combined with the bacteria to create this whole food combination, which then creates the posts by attic metabolites. So it seems like this is unique.

Pelton: Well, you're right. Although you will see some probiotic products that have a prebiotic in them, like fructo-oligosaccharides or FOS. I mean, some of them had things like inulin in them. But keep in mind, we want to strive for a diversity of fibers and so these products just have one type of fiber or 1 or 2 types of fiber. A product that I'm very familiar with because I'm the scientific director with Essential Formulas is called Dr. Ohhira's Probiotics. They're made in a fermentation process. It takes years to produce the product. They have large fermentation vats where they start out with 12 strains of bacteria then they had dozens of different types of organically grown foods and the bacteria are given 3 to 5 years to break down and ferment all of these foods, and during the process they're producing a wide range of postbiotic metabolites and scientific research has determined that Dr. Ohhira's Probiotics contain over 400 different postbiotic metabolites.

So Dr. Ohhira's is really not primarily a probiotic. It's primarily delivering postbiotic metabolites directly and it's a much faster way of effecting change in the microbiome because if you just take probiotic bacteria, those bacteria, when they reached the gut have to find fibers and begin the process of breaking those fibers down and transforming them into the postbiotic metabolites. But Dr. Ohhira's is directly delivering these postbiotic metabolites so you get a really rapid microbiome restoration because they immediately, as soon as they hit the gut, they start to produce the antiinflammatory effects and accelerates the regrowth of healthy new cells that line the GI track. It's just a really unique fast way to create change and correct things like dysbiosis.

Gazella: So you mentioned that there are dozens of forwards in the Dr. Ohhira's product that are fermented and combined with the 12 strains. What are some of the types of foods that are in that product?

Pelton: They have a wide range of fruits and vegetables and mushrooms and seaweeds, all healthfully raised. They have different standards in Japan, so they're not what we would call organically grown by our standards because they just don't have those standards. But they're healthfully grown. They use pure spring water. There's no pesticides and insecticides and artificial fertilizer or anything, and they're allowed to grow naturally and then there are harvested at their peak of ripeness. So the nutritional content is at its peak and then they shred these foods and add them to the fermentation vats so that the bacteria can start to break them down and do the fermentation process that allows them to produce the postbiotic metabolites.

Gazella: Now you mentioned that you don't have to refrigerate Dr. Ohhira's. I mean, as a consumer, I actually find that really appealing, but some practitioners are pretty focused on the refrigerated probiotic products. Why don't you have to refrigerate Dr. Ohhira's?

Pelton: Well, Dr. Ohhira's, this fermentation process that I've spoken about, the bacteria learn to thrive and survive in the fermentation vats at room temperature. So they have adjusted to survive in a room temperature and then the capsule for Dr. Ohhira's Probiotics is a patented capsule design that's as hard in the harsh acidic environment in the stomach and then preferentially releases all the contents in the small intestines. So it's a user-friendly product where food is not an issue, it could be taken on an empty stomach or with food and refrigeration is also not an issue.

Gazella: Then what's the dosage of the Dr. Ohhira's if you're just going with regular maintenance and there's not really a therapeutic application? You just want to recommend it to your patient for optimal health.

Pelton: Sure. The recommended dose is 2 capsules daily on a ongoing regular basis.

Gazella: Perfect. So I'd like to talk a little bit about the future because it sounds like what you've just described with this whole food extract and this fermentation process at room temperature and the paste that's created and it's put into this special gel cap that can survive the stomach. It sounds like that we're headed to the future. So bring out your crystal ball and tell us 2 things. First of all, what does the future hold when it comes to probiotic research and advancement and then what does the future hold when it comes to this gut-brain axis and where we're headed with that?

Pelton: Okay. Well, I think that in the future we'll see more and more recognition of the benefits of these postbiotic metabolites. I think more companies will start to try to develop products so that they can directly deliver postbiotic metabolites. In fact, the pharmaceutical industry also sees the handwriting on the wall. I've looked at a number of different reports where pharmaceutical companies are starting to develop new products that contain postbiotic metabolites. The pharmaceutical industry realizes that rather than trying to develop more antibiotics, they can start to develop products that contain postbiotics and these new products will be less expensive to produce. They'll have fewer side effects because these are compounds that are naturally produced in the human body. So it's a new frontier for the pharmaceutical industry also. The postbiotic metabolites is a new frontier all the way around.

Your other part of your question is how do I see the whole industry of probiotics going? We'll continue to discover new strains of bacteria, but I think there will be more emphasis focused on trying to discover what are the compounds, these postbiotic metabolites, the different strains of bacteria produce. So it's not so much trying to just discover different strains of bacteria and name them, but what are these compounds that they're producing and which strains of bacteria are more effective at producing these compounds for us. I think we'll also get into in the future much more personalized microbiome understanding so that different people will react differently or more favorably to different types of probiotic products and even different types of postbiotic metabolites will probably be more effective and more important for different types of individuals with different types of problems.

Gazella: Yeah. I have to say that this does lend itself to that personalized medicine that practitioners and researchers are talking about. So I would agree. I think that's a great direction to go in. Now when it comes to the gut-brain axis, I know a lot of the research that we talked about today is a bit preliminary. Are you expecting to see some more formalized larger clinical trials, human trials, double-blind, randomized placebo-controlled trials in the area of mental health, potentially dementia, Alzheimer's, concentration, maybe chemo brain? I mean this is just such a big topic.

Pelton: Well, yes, Karolyn. That's another huge frontier for the microbiome. Some studies are calling the microbiome the missing link in the gut-brain axis and they're starting to focus more on the microbiome's role in the link between gastrointestinal health and mental health. So we'll see a lot of that happening in the future. I can share 1 study with your listeners that's really quite amazing that talks to the mental health issue and the relationship between the microbiome and mental health. Scientists started out with 2 strains of mice. One strain of mice is specifically bred to be highly timid and anxious and the second strain of mice are bred to be highly courageous, bold, and exploratory. So then the researchers just took the bacteria from the GI track of each strain of mice and implanted them into the opposite strain.

It completely reversed their behaviors, just by changing the bacteria and their microbiome, taking it from the bold, courageous exploratory mice and transplanting those gut bacteria into the strain that was timid and anxious. It just totally changed the behavior from being bold and exploratory to being timid and anxious and did the reverse in the opposite of mice. So fascinating information to see how just the gut bacteria have this direct influence on behavior and emotional activity and so forth. I'm sure we'll see many more studies in the future that are starting to unravel how this all works for us.

Gazella: Yeah, I would agree. This is going to be fun to keep an eye on and to follow because it's really exciting and it can really make a difference in patients' lives. So once again, I'd like to thank the sponsor of this topic was Essential Formulas Incorporated, of course, the distributors of Dr. Ohhira's Probiotics. Thank you, Ross, for providing us with such a great amount of interesting information for us to consider. Have a great day.

Pelton: Okay, Karolyn. Nice to be with your listeners. I want to just encourage everybody, every time you eat, you're feeding 100 trillion guests, so feed your probiotics well.

Gazella: Absolutely. That's great ending advice. Thank you.

Pelton: All right.

The Centers for Disease Control and Prevention has called insufficient sleep a public health epidemic. And yet, many of the commonly prescribed medications are not helping most patients. In this interview, John Neustadt, ND, explains why an integrative approach to treating insomnia provides a much more effective alternative to commonly used sleep medications.

About the Expert

John Neustadt, ND, received his naturopathic doctorate from Bastyr University. He was founder and medical director of Montana Integrative Medicine and founder and president of Nutritional Biochemistry, Inc. (NBI) and NBI Pharmaceuticals. He’s a medical expert for TAP Integrative, a nonprofit organization educating doctors about integrative medicine. He has published more than 100 research reviews and was recognized by Elsevier as a Top Ten Cited Author for his work.

Neustadt’s books include A Revolution in Health through Nutritional Biochemistry and the textbook Foundations and Applications of Medical Biochemistry in Clinical Practice. Neustadt is an editor of the textbook Laboratory Evaluations for Integrative and Functional Medicine (2d Edition). He was the first naturopathic doctor ever voted Best Doctor among all physicians in his area.

Neustadt received 15 Orphan Drug Designation by the US Food and Drug Administration for the use of natural products for the potential treatment of rare diseases.

About the Sponsor

Nutritional Biochemistry, Inc. (NBI) formulates and manufactures products that give results. Started by John Neustadt, ND, in 2006 when he couldn’t find formulas he needed to help his patients and family, NBI products solve 2 problems he was having. Existing products didn’t contain the dose or combination of nutrients used in clinical trials and actually shown to work. Equally frustrating, other companies would cite studies on their websites, but then use lower amounts of nutrients than what was used in the study, or use entirely different nutrients that weren’t supported by the research.

Neustadt’s latest creation is Sleep Relief. NBI’s Sleep Relief is a breakthrough in sleep technology. Its bi-phasic, time-release technology delivers NBI’s proprietary formula with clinically validated nutrients in two stages—a quick-release first stage and a slow-release second stage to help you gently fall asleep, stay asleep and wake refreshed and ready for your day. NBI's Osteo-K delivers the clinical dose of nutrients shown in more than 25 clinical trials to grow stronger bones and reduce fractures more than 80%.

NBI is and always has been a family-owned company. We don’t manufacture anything we wouldn’t take ourselves or give to our own family. No matter what we do, our promise to physicians using our products is to help their patients, and to customers purchasing directly from NBI, is uncompromising quality.

NBI is a name you can trust. But don’t take our word for it. Spend some time on our website, learn about our products, and educate yourself on the hundreds of research citations and studies that they’re based on.

Transcript

Karolyn Gazella: Hello. I'm Karolyn Gazella, publisher of the Natural Medicine Journal. Thank you so much for joining me. Today, our topic is the integrative approach to insomnia. During this interview, we will learn that insomnia is a significant problem for many patients that can have far reaching physical, mental and emotional health ramifications. We will also learn how to successfully treat this condition by using a combination of diet, lifestyle recommendations, and dietary supplements.

My expert guest today is Dr. John Neustadt. Dr. Neustadt received his naturopathic doctorate from Bastyr University and he was the founder and medical director of Montana Integrative Health.

Before we begin, I'd like to thank the sponsor of this topic who is Nutritional Biochemistry Incorporated, or NBI, manufacturers of high-quality dietary supplements for health care professionals.

Dr. Neustadt, thank you so much for joining me today.

John Neustadt, ND: Thank you for having me on.

Gazella: Well, so the Centers of Disease Control and Prevention calls lack of sleep a public health epidemic. Now, that seems pretty significant so today we're going to talk specifically about insomnia. How common is insomnia in particular?

Neustadt: Well, the CDC is absolutely correct. It is a public health epidemic. Up to 80% of people struggle at some point with what's considered transient insomnia, less than two weeks of duration and insomnia effects 10 to 15 percent of the general population.

In primary care settings, it's estimated that up to almost 70 percent of primary care patients have insomnia so it is incredibly common.

Gazella: Oh, yeah that is. So how does lack of sleep impact a patient's overall health from like a physical, mental, emotional standpoint?

Neustadt: It has devastating impacts. There are two ways to think of it. One is short-term impacts and the other are the long-term impacts. So, short term it can impact decreased job performance, impact social and family life by creating greater fatigue. I mean, just you're more tired during the day. Decreased mood and depression, increases in anxiety and stress. Decreased vigor and just not being able to cope with the demands of daily life and be able to complete tasks. That's only short term. Devastating just in the short term.

But in the long term, it can be a killer. There, if people are sleeping an average of less than six hours per night, it can increase the ... or decrease the quality of life at the same magnitude of a similar condition such as congestive heart failure and major depressive disorder. It's an early symptom for Alzheimer's Disease and Parkinson's Disease and Huntington's Disease and there's a sweet spot for sleeping of about eight hours. That research shows is the healthiest, and if you're sleeping less than six, or longer than nine hours, it increases your risk for diabetes, metabolic syndrome, and death and, in fact, for metabolic syndrome, there's a 45 percent increase in risk compared to people who are sleeping seven to eight hours a night.

Gazella: Wow, so yeah, so this is a very important topic for clinicians to have on their radar. So, when you're evaluating a patient with a sleep disorder such as insomnia, how do you approach the work up?

Neustadt: Well, insomnia's really a qualitative diagnosis. It's how are they ... how do they feel that they're sleeping? How do they feel that it's impacting their health? Now the DSM official diagnosis, there is a quantitative or a couple of quantitative aspects to that and that is it's occurring at least three nights per week, and present for at least three months. So understand the difference between transient insomnia, less than two weeks, versus the diagnosis, official diagnosis, needs to be going on for greater than three months.

So there's a huge discrepancy there and in time periods and clinically it's important to be aware of that because these detrimental and dangerous effects of insomnia and sleep deprivation definitely are occurring in shorter than three months period of time. They're happening pretty quickly if someone's not getting enough sleep and even over a few days the short term consequences.

And so what I ask people about is how many hours, on average, do they think they're sleeping a night? Do they have any difficulty with falling asleep or staying asleep called sleep phase delay or sleep phase advance? Are they waking refreshed in the morning? What's going on with them psychosocially? Are there any stresses going on at work or in relationships or financially that's increasing their anxiety and could be impacting their sleep? Are they are risk for any hormonal abnormalities or imbalances because the research is clear that low estrogen, low or high testosterone, elevated TSH, those are all things that can create insomnia. Abnormal progesterone, as well.

And then looking at medications because there are some medications that can impact sleep, as well.

Gazella: Yeah, let's talk about the medications that can impact sleep. What are some of those medications that can impact sleep?

Neustadt: Well, prednisone, that can cause hyper-arousal, or can cause somebody to not sleep, not be able to fall asleep, or have fragmented sleep. Beta-blockers, very common heart medications, can decrease melatonin production. So we know what the mechanism of action ... their interaction of sleep is they decrease melatonin and can cause poor sleep.

Some antidepressants, actually, can cause poor sleep. Antidepressants can, depending on the antidepressants, can either cause somebody to not be able to sleep enough or can cause hypersomnolence, somebody to be sleeping too much. So looking at those, looking up ... it's very easy to look up whatever medication they're taking quickly and see, besides the ones that I mentioned, could it be potentially interfering and impacting with their sleep.

Gazella: So I've been hearing about hyperarousal, or the hyperarousal hypothesis, which I find quite fascinating. What is the hyperarousal hypothesis and how can it affect what is recommended to patients?

Neustadt: Great question. So the hyperarousal hypothesis I like to refer to as "wired-but-tired." And it occurs to people typically who are under a lot of stress, they have elevated cortisol, and when they end up trying to fall asleep they just can't turn their mind off, or even if their mind isn't racing, they just can't calm down. Their body can't relax and settle into sleep. They're staring at the ceiling, it can cause fragmented sleep. And that wired-but-tired, again, typically occurs in people who are under chronic stress.

Gazella: Yeah. And you know the other day when you and I were talking as it related to the hyperarousal hypothesis, you were telling me about something else that was new to me and it was called social jet lag. Talk a little bit about social jet lag and the research associated with social jet lag.

Neustadt: I'm so happy you brought this up because I love this as well. Fitbit, that maker of the wearable tracking devices, and tracking people's sleep as well, they had access, because of their users, to over six billion data points of sleep. And they looked at those. And they looked at the data and determined that the biggest predictor of healthy sleep, restful sleep, is going to bed at about the same time every night. Basically training our body that it's bedtime, getting that routine.

Social jet lag occurs when people are going to bed at about the same time every night during the week but then the weekend comes. Friday night they go out, hang out with friends, stay out late. Saturday night maybe do the same thing, and then Sunday comes around and they try to go to bed again at their weekday, or their work week time, and they can't fall asleep. And essentially what they've done is it's as if they've flown to another time zone and their body thinks that it's not time to go to sleep yet. And they've induced their own jet lag called social jet lag.

And so one of the things that Fitbit found, and I think one of the most impactful things, is showing that getting that regular bedtime, being in that routine, going to bed at about the same time every night is one of the best things people can do for improving their sleep.

Gazella: And even on the weekend, and I'll tell, you, when you put this on my radar I, of course, had to do a little research and there's a lot of studies on this that actually show that the physical effects that you talked about with sleep deprivation earlier also occur with this social jet lag. So I think it's really important for clinicians to be aware of that. So thank you for bringing this to my attention.

So now doctors often prescribe benzodiazepine or benzodiazepine-like drugs to help patients sleep. What are some of the potential risks of these particular medications?

Neustadt: Well, the potential risks are very well documented and they increase risk for falling, dizziness, light-headedness, those risks are increased in people who are 60 years or older because their ability to metabolize the drug tends to decrease. And so because it increases the risk for falls and dizziness and light-headedness, it then increases the risk for fall-related injuries, such as osteoporotic fractures, such as concussions, such as death, even. But even beyond those risks associated with increased risks for falling, the research has shown that cancer risk is actually increased in people who take over about 132 doses of benzodiazepine a year. So that's even ... that's less than half of a year worth.

And in fact some of these risks are increased with very small and limited exposure. So you know from half a dose to 18 doses per year, the hazard risk for death is increased 3.6 times. 18 to 132 doses, the hazard risk for death increased 4.43 times in a study that looked at this. And for greater than 132 doses, it increases 5.32 times. That's 532 percent greater than somebody not taking these medications for death. And the research has shown to actually get one benefit, the number needed to treat, to have one patient benefit is 13 patients. But the number to treat to create harm is only 6 patients.

Gazella: Yeah, that's problematic. So what about the newer class of medications, like the orexin receptor antagonist Belsomra?

Neustadt: Belsomra came on the market in 2015, it's a schedule 4 drug and it's a CNS depressant. So, like other CNS depressants, like benzodiazepine, it can have similar adverse effects. Some of the benzodiazepine drugs like Lunesta or Ambien can also cause, like Belsomra, can cause daytime impairment including impaired driving skills, risk of falling asleep while driving, abnormal thinking and behavioral changes are part of the adverse events spectrum, including amnesia, anxiety, hallucinations, other neuropsychiatric symptoms, even complex behaviors like sleep-driving. I mean, you're driving while not fully awake, after taking the hypnotic. Or other complex behaviors have been documented, like preparing and eating food, making phone calls, or even having sex, without remembering it.

And so the drug has some serious risks, including worsening of depression and suicidal ideation, and the benefits of that, it can increase ... or the benefits of the medication, because all medication, it's a risk-reward calculation ... it can decrease sleep latency, that is, the amount of time to fall asleep by about eight to 10 minutes and increase sleep duration by 17 to 20 minutes.

So at the most beneficial end of that, maybe it's 30 extra minutes of sleep. But you get all of those risks associated with it.

Gazella: And are patients getting good sleep when they're on these prescription and over-counter medications? Are they getting good quality sleep?

Neustadt: Well, you raise a great point. That's one of the problems with all of these medications is they tend to increase sleep duration, sleep quantity, but they're not increasing sleep quality. They're not getting patients into that deep, restorative phrases of sleep, the slow-wave sleep, phase 3 and into phase 4, to get that good, restorative sleep.

So the quantity of the sleep may be increased but the quality has not been shown to be increased.

Gazella: So you've made a pretty compelling case that a more integrated, holistic approach is needed. And integrative practitioners often recommend melatonin for insomnia with their patients. Can you talk a little bit about melatonin and why for some patients, many even many patients, it may not be enough?

Neustadt: Melatonin is one of the first things I find that people with whom I speak, they've tried. They've reached for that. If they're going to try a natural product, they've reached for the melatonin, you know, first, almost universally.

The challenge with melatonin is that it's got a very short half life, 40 to 50 minutes. And so while melatonin is considered a circadian modulator, meaning it helps the body recognize day from night, and it is a natural hormone, a natural product that our body uses to help us fall asleep, it's not really used for sleep maintenance. And so when somebody takes melatonin to help them fall asleep, because it's got such a short half life, well 50 percent of the melatonin is eliminated from the body in less than an hour, so let's just be generous and say an hour for easy calculations. So common doses out there is a 3 mg dose. So in an hour, they've got a one and a half milligrams left. An hour later they've got .75 milligrams left. And on down.

And so 3, 4 hours later, essentially most of that melatonin is out of their body and they wake up again. I hear so often people who take melatonin, they end up waking up in the middle of the night, still. And so what do they do? Well, they might need more melatonin. And so they keep taking higher and higher doses until they're sleeping through the night and then they wake up feeling drugged in the morning. Groggy, hungover and it takes them hours to actually feel fully awake.

So the natural rhythm of melatonin in our body is that the rise in melatonin occurs around 10 PM and then it peaks at about 2 AM in the morning, and it declines at approximately 6 AM, it's declined back to baseline. And that makes sense because that's sort of the rhythm of when we start to fall asleep and when our body then starts to wake up. Of course melatonin is balanced with other hormones as well that the body is producing during sleep, but the immediate release of melatonin that people are taking is not mimicking the body's cycle of melatonin production during the night. And it's also not a complete solution because it's not dealing with the other phases of sleep, we're looking at the other hormones in sleep, GABA for example. Or the other variables that can impact sleep such as poor blood sugar. When blood sugar can drop, hormones are secreted like cortisol and epinephrine to increase the body's blood sugar and we wake up.

And so that's why melatonin for a lot of people doesn't work, because it's just not a complete enough solution.

Gazella: I think that's a really good point, that it's not a complete solution for many people and that's why you use such an integrative approach. So I'd like to really dig into your integrative approach, I'd like to talk about dietary supplements, diet, and other lifestyle factors. So as long as we're talking about melatonin, let's keep on that subject and talk about dietary supplements. Are there specific dietary supplements that you use in your clinical practice specifically for insomnia?

Neustadt: There are and it depends typically on the clinical picture. So for example if somebody has muscle aches or tight muscles that's keeping them from sleeping, magnesium can help, that can be a gentle muscle relaxant. If there's some anxiety that may keep them from sleep, well, glycine is an amino acid that's also an inhibitory neurotransmitter, that can be helpful. GABA also an inhibitory neurotransmitter used in the body available as a dietary supplement. That can be helpful. Botanical extracts such as alphianine increases alpha-wave production in the brain which is associated with calming, alert calmness. Then there are some sedative botanicals that can be helpful such as hops or skullcap, also called Scutellaria. And others.

So that's part of it and for potential, looking at decreasing the response to stress, I like using, if they're under a lot of stress, some adaptogenic herbs like ashwagandha, or jujube, magnolia bark extract. If there is vaso ... if there's an issue with hot flashes and perimenopause, pine back extract. There's a clinical trial on that showing that it improved sleep quality and sleep quantity.

And so I typically, you know, this monotherapy approach of one symptom, 1 pill, it really doesn't work when we're looking at complex pathologies like insomnia or many other chronic issues. And so I tend to like products that combine those different nutrients shown in clinical trials to work that target the underlying pathology, the underlying biochemical pathways at work and sleep and affected by insomnia in a time release or a biphasic time release delivery system because it more closely mimics the body's natural rhythm of the 2 major categories of your sleep. One is helping somebody fall asleep, you know how do we do that, and the other, over ... you know, the subsequent 6, 7 hours later after they've fallen asleep, how do we help them stay asleep?

And so that's how I conceptualize it and that's the overall approach with dietary supplements when they're indicated.

Gazella: So before I move on to diet, I know that you helped formulate and create a specific sleep supplement. I want you to tell me the name of that supplement but I also want you to tell me why you created it, because let's face it, there are a lot of sleep supplements in the market. So why did you want to create the supplement that you created?

Neustadt: So the name of the product is NBI's, my company, NBI's Sleep Relief is the name of the product. And I created it for a couple reasons.

One, just like all the products that I've created in NBI and formulated, I couldn't find the combination of nutrients or the dose and form of nutrients in a product shown in clinical trials to actually work. And I personally suffered from insomnia for years and years. And I tried a lot of different things. It wasn't helping me. I'd work with a lot of my patients trying to different things, having to dispense different bottles of products, in addition of course to working with diet and lifestyle and other psychosocial factors involved. And I couldn't find something that worked consistently.

And so I started digging into the sleep research, the pathophysiology of sleep, the clinical trials, what are the underlying mechanisms affecting sleep. And after over a year of research and formulating and working, trying over a dozen different combinations and doses, that's when I created Sleep Relief.

Gazella: Okay perfect, Sleep Relief. So now let's talk a little bit about diet. What are some of the things that you recommend to your patients when it comes to sleep, associated with diet that may not be on the radar of some practitioners?

Neustadt: So one of the big things that I see over and over is a lot of people have, may have acid reflux and they don't know about it. And because maybe it's not ... maybe they have a cough when they lay down, maybe they are just not aware that that's going on. And so evaluating for that because that can wake people up.

The other thing that I find with diet that's very important, and with acid reflux, you know, that can be diet related. There are 5 most common foods that can contribute to that and interrupt sleep, that's raw garlic and onion, chocolate, coffee, and citrus. Although other things can do it for other people. An infection can do that, H. Pylori can cause that as well. And then if they have a hernia, a hiatal hernia, that can cause it as well. So looking at that, looking at those underlying potential causes if that is involved.

The other thing is poor blood sugar control which I already mentioned. And one of the things I like to ask that can indicate if they might have poor blood sugar control is if they get that afternoon, postprandial tiredness. You know, about 3, 4 o'clock in the afternoon, a couple hours after lunch do they just get that energy slump. And that can be an indication that they're having a little bit of blood sugar control issues. Or are they waking up at the same time every night. Both of those questions can give clues.

And if that does seem to be involved, one thing that I love to try with patients ... it doesn't work very often but when it does, it's really a home run, and that is ask them to eat 8 to 10 grams of protein before bed. Protein's one of the best ways to regulate blood sugar. And so if they do that and it stabilizes their blood sugar and they then are sleeping through the night, well, again, it's a home run. I mean, there are no pills, no powders, it's just natural doing it with food and it also opens the door for even more discussions with helping them understand how they can improve their diet during the day to help, to eat, to promote ... to help them understand how they can eat, changes they can make to eat, the promote their health for the rest of their life.

Gazella: Yeah, those are some great suggestions when it comes to diet. Now let's talk a little bit about lifestyle. What are some things that may not be on the radar of some practitioners when it comes to lifestyle aspects?

Neustadt: So we talked about going to sleep at about the same time every night, that's really important. The other thing is ... and most practitioners, or hopefully all of them have heard of sleep hygiene. The research shows that about the 69 to 70 degrees for most people is the ideal temperature for sleep. Some people who, if they're in a relationship with their partner, they may like different temperatures may be most comfortable for them.

So there are wonderful things out there now, it's call the ChiliPad, that you can get, it's a pad you can put on your bed, where you can control the temperature on each side of the bed. So that can be really helpful.

Stress of course is a big issue in our society, a lot of people are under chronic stress, so anything that we can do to help people decrease their stress or better deal with stress is really important. And a fantastic study came out recently that showed that a lot of the impact of stress is not the actual event happening to us, it's how we view it. So if people view stress as a good thing, meaning "I gotta learn something from it and what can I take from this," the health impacts from stress are mitigated. If somebody sees a stressful event and they're internalizing it and they're not seeing it as a growth opportunity, then it magnifies the negative stress impacts.

So, A) getting them to just understand that mindset is really important, just when it comes to stress happening, and then what can they do to have more control over those events that may be causing them stress to decrease that stress. And that could mean creating healthy boundaries for themselves. That could mean doing any yoga or mind-body techniques. You know there's lots of things that we can offer to patients that can be incredibly, incredibly helpful.

Gazella: Yeah, I would agree. And now your approach focuses on diet, lifestyle, and dietary supplements. How important is it to focus on all 3? So some practitioners might be really focused on the person's diet, or some might be looking at their stress level, and some might be focused on just melatonin. Why is it so important to look at this from an integrative standpoint?

Neustadt: Well I think if we want to do the best job we possibly can for our patients and give them the best results, looking at it through a more integrative approach is important. And I like the approach of trying dietary supplements to give people benefit quickly. So if somebody is sleep deprived, it's gonna increase their tendency to reach for those comfort foods. I think we've probably all experienced that. And especially because what happens with insomnia and sleep deprivation, it decreases mood. It can cause depression. And sugary foods, for example, when we reach for those, it can increase our serotonin production and temporarily lift mood. But it causes this rollercoaster of insulin and blood sugar that's hard to get off of.

So just getting people sleep can help improve their mood. So I like the dietary supplement approach for triage to get them feeling better so they can make healthier decisions, have a more present mindset, be more proactive instead of reactive, while I'm working with them also on improving their diet. Transitioning to a healthier way of eating, which, the research has shown, unambiguously is the Mediterranean pattern of eating. And also stress reduction and exercise and those things as well.

Gazella: Yeah, I mean that all makes a lot of sense. And this is a very important topic and I want to thank you, Dr. Neustadt for a very interesting conversation and once again, I'd also thank today's sponsor, Nutritional Biochemistry Incorporated, or NBI. Thanks again, Dr. Neustadt, for joining me.

Neustadt: Thank you for the opportunity.

Gazella: Have a great day.

Neustadt: Thank you.

Gazella: I'd like to remind readers of the Natural Medicine Journal that we now offer free continuing education credits for naturopathic physicians. Our list of podcasts and research guides that have free CE credits is growing. For more information, just click the Continuing Education tab at the top of our Natural Medicine Journal website.

Statistics indicate that hearing loss is on the rise. In this interview, board certified otolaryngologist Dr. Ford D. Albritton IV describes the magnitude of the problem, as well as the research associated with key nutrients that can help reduce the risk of hearing loss. It's critical that all practitioners, not just hearing specialists, put this topic on their radar so they can help patients who already have hearing loss and those who are at risk.

About the Expert

Ford D Albritton IV, MD, FACS, is the director of sinus surgery at the Sinus and Respiratory Disease Center at the Texas Institute for Surgery. He has served as chairman of the board of directors at the Texas Institute for Surgery and chairman of the Department of Otolaryngology-Head & Neck Surgery at the Texas Health Presbyterian Hospital of Dallas. Innovation and creative solutions to long standing problems in his field have been a focus of his practice since completing his training at the Emory University School of Medicine. He holds patents in the fields of nutritional compounds for targeting prevention of sensorineural hearing loss based on research initiated in the early 2000s. He also holds patents and expertise in the field of sinus disease and surgery with several publications to his credit. He remains active in clinical research and has been requested as a lecturer on the subject for surgeons domestically and internationally. Current interest exists in linking dietary methods of hearing preservation to cognitive function maintenance in patients with hearing disability, defining intervention strategy, and establishing modes of prevention.

Transcript

Karolyn Gazella: Hello, I'm Karolyn Gazella, the publisher of the Natural Medicine Journal. Today we have a fascinating topic. We'll be talking about how certain nutrients can help reduce the risk of developing hearing loss, and we have the perfect expert to help us with this topic. Dr. Ford Albritton, IV is a board certified otolaryngologist with the Sinus and Respiratory Disease Center at the Texas Institute.

Dr. Albritton, thank you so much for joining me.

Ford Albritton, IV: It's my pleasure, Karolyn. Thanks for having me.

Gazella: Yeah. So, how common is hearing loss, and have we actually seen an increase over the past decade or so?

Albritton: Hearing loss is incredibly common, and it's been pretty consistent if we look at the prevalence. The National Institutes of Health actually has its own group that looks at communication disorders, and they estimate the prevalence of about 15% of residents in the US having a diagnosis of hearing loss, and currently that puts us at about 38 to 40 million.

And you asked the question has there been an increase, and it's sort of a tricky answer. Yes, there's been an increase, but so has the population increased. In 1971, that number was 13.2 million and basically one third the current number.

So, why are we seeing such an increase? Well, it's a combination of population growth and the basic dynamics of our population age. If we look at aging as a criteria for hearing loss, we can compare people that are between the ages of 45 and 54. Only about 2% of those people are going to have a diagnosis of hearing loss, but if we go up to 75 years or older, almost one half to two thirds of the population will be having a hearing loss diagnosis depending on the studies you look at. And the World Health Organization has currently estimated hearing loss at about 466 million, but by 2050 they do predict that number should hit 900 million.

So, there's certainly an increase, but it's tricky to say that that's because of something changing in the environment or our susceptibility is increasing, and their point of fact is a few years ago, pediatrics journals documented that adolescents were having an increased rate of hearing loss from comparing data between '94 and 2006. They reviewed that data again in 2010 and found that that was just simply a statistical error and that they had erroneously just compared two points of data instead of contiguous and that actually the rate of hearing loss has not increased in that age group.

Gazella: Okay, that's interesting. So, what is considered a normal hearing range, and at what range does there begin to be a problem?

Albritton: The way we measure hearing is using something called an audiogram or audiometry, and it measures sound intensity. The official measurement unit is called the decibel, which is a logarithmic measurement of sound intensity, and we define normal hearing as a threshold where a subject can recognize a presented tone at a specific frequency less than 20 decibels. So, if you're presented a tone at a low frequency or a high frequency and you can perceive it, recognize it at a sound energy level quieter or equal to 20 decibels, that's normal.

Furthermore, we use some tricks of averaging and statistics to have some simple ways of measuring. Like we will average two tones or three tones or pitches on the hearing test and come up with a number of sound intensity, and we consider anything less than 20 normal, and anything above 25 we start to believe is abnormal and probably would benefit from some sort of intervention.

Gazella: Okay, great. So, let's talk a little bit about risk factor. Who's at risk of developing hearing loss?

Albritton: Probably a number one factor is family history. So, genetics play a larger role than we really can appreciate at this point in our mapping of the human genome, but family history is probably the most important question we ask patients into mapping their risk for hearing loss.

The second one would be noise exposures, people with a high occupational noise exposure. OSHA measures that as greater than eight hours exposed at 90 decibels, so noise exposure at that rate can cause hearing loss.

And then drugs; certain chemotherapy agents, some antibiotics are notorious for being toxic to the inner ear. Certain infections; one of the great benefits of immunizations and the reason we recommend immunizations is to prevent some of these preventable causes of hearing loss. Maternal infection of mumps, measles, rubella, for instance, can have devastating consequences on a fetal ear development and could have consequent hearing loss.

And then finally, sort of our chronic illnesses, diabetes, hypertension, heart disease can compromise blood flow and health to the inner ear causing problems. Inflammatory conditions such as rheumatoid arthritis, certain inner ear inflammatory conditions can also cause problems.

So, it's a pretty broad area of the things that can cause hearing loss, but the biggest risk, again, being family history.

Gazella: So, when we think of hearing loss, it's understood that it obviously affects communication and how we communicate with each other, but does hearing loss have any physical impact on a patient's life?

Albritton: That's an interesting question, and I think that 20 years ago we probably would not have directly thought so. It obviously does affect sense of wellbeing and ability to interact with others, but it can affect a lot of other things.

An interesting study from last February demonstrated a correlation of hearing impairment severity and the incidence of fractures to the radial forearm, to the hip, to the spine, and it showed that patients with severe hearing impairment actually had an increased risk of fracture that was greater than the normal hearing group, and basically you had 1.4 to 1.6 greater risk of having one of those types of fracture from a fall if your hearing was severely affected. There's lots of further digging that needs to be explored such as severe hearing loss also contribute to injuries to the balance system. That's sort of outside the scope of the research at this time.

But really the most newsworthy research in the past decade is focused on the correlation of hearing loss, severity of the hearing loss, with cognitive impairment and dementia. In 2013, a paper out of Johns Hopkins authored by Dr. Lin out of their department of otolaryngology and his colleagues demonstrated in just under 2000 patients that patients with a pure-tone average, that's that average we discussed earlier, of several frequencies of over 25 decibels, they had rates in decline in their cognitive function testing that was 30% to 40% greater than their normal hearing peers. And not only that, there was a linear relation between the hearing loss severity and the degree of decrease in their cognitive function test scores.

So, that data really set off alarm bells, and health organizations throughout the world, the British health system, the French health system, Danes, Italians began looking at their population, and probably the most robust examination has been the English, many thousands of patients, have agreed with this information. They put a cognitive impairment risk of 1.6 times greater than normal hearing population with hearing impairment.

Interestingly, some of these studies took the next step and tried to assess, well, if we do something for the hearing, such as a hearing aid or a Cochlear implant, something that will restore hearing, does that make a difference in the cognitive impairment testing? And it actually does.

An Italian study was one of the preliminary studies to look at this, and they demonstrated that either a hearing aid or a Cochlear implant could actually reverse some of this cognitive impairment seen on the testing with improved scores. The French study was pretty astounding in terms of its result. Greater than 80% of their lowest scoring cognitive impairment patients tested, they showed improvement after the Cochlear implant, which was quite surprising.

So, there's a question as to how hearing loss, how is this leading to dementia? And I don't think we fully understand that yet, though there are some hypotheses, and Dr. Lin laid out about four of these. First one being is there some common physiologic pathway that's contributing to both brain damage and inner ear damage? Something like blood pressure elevations where we see some chronic ischemic changes to the brain on MRIs or diabetes or something along those lines.

The second theory is something called the cognitive load theory. Basically, it surmises that the effort of constantly trying to comprehend what is being heard takes memory resources, whether it be a neurotransmitter or other nutritive resources, and the chronicity and cumulative nature of this leads to issues and errors in ongoing brain function, the ability to maintain memories in an ongoing manner.

A third theory is that hearing loss may affect brain structure. We do know that in brains of patients without stimulation, stroke patients, et cetera, that there's certain areas of the brain that shrink, and it isn't necessarily that we lose cells there, but there are some changes in the simple [inaudible 00:11:38] of those cells and that hearing loss patients do appear to show some of those similar findings on their MRIs.

And then finally, social isolation. We know that social isolation happens with hearing loss, and we also know that social isolation is a known risk for cognitive impairment. One theory that a lot of fellow ENTs and otolaryngologists specializing in ear have known about since the '90s is that if we fit a patient with hearing aids earlier, they do better long term, and a large study in the VA looking at World War II veterans in the '90s established that patients that obtained hearing aids earlier did better with those hearing aids long term. They were able to accurately repeat words presented to them at a higher rate than their peers who had not obtained a hearing aid and had similar hearing test results. They would have basically the same level of hearing loss, but their ability to interpret speech was impaired, and the ability for the hearing aid to function with those patients was just suboptimal and were not able to get the same level of functionality from their hearing aid.

And what the theory was is that the stimulation of certain areas of the cortical brain kept those areas healthy and functioning and that the old use it or lose it hypothesis, the patients who weren't using it did not maintain that brain and it therefore degenerated, never to really fully improve.

This takes it to another level and seems to suggest that it's not just those areas of brain corresponding to speech recognition; it's rather the brain as a whole that is suffering from the lack of input.

Gazella: Yeah. Early intervention is always best, so that makes a lot of sense. Now, you mentioned social isolation. Are there other areas that are affected with hearing loss that negatively impact the quality of the life of the patient?

Albritton: Well, I'm sure that there are, and I'm sure that we're going to discover more, but I think the most obvious is isolation and its consequential potential for depression. People that can't hear, they eventually will isolate themselves in social situations because it just becomes too embarrassing or futile for them to continue trying to participate in a conversation they can't hear. And I think we all can appreciate what that feels like. If we've ever been to a noisy restaurant and we can't hear the conversation across the table or slightly away from us, we tend to withdraw. Imagine that for patients with significant hearing loss being a daily ongoing issue, and that ends up contributing to further self-isolation, but depression, and several studies have demonstrated that there is an increased incidence of associated depression with hearing loss.

Gazella: Yeah, that makes a lot of sense. Now, you mentioned genetics. So, what is the difference between hereditary hearing loss and age-related hearing loss?

Albritton: I would suggest that almost all forms of hearing loss that we attribute to age probably have some genetic component. As we look at just genetic programming for your resilience, your resilience of your skin, your eyes, your hair, your ears, all of those things are sort of pre-programmed, and most people accept multi-hit hypothesis to hearing loss. In other words, that it's not one thing; it's a multitude of things over time that lead to the cumulative and irreparable damage and that there are certain susceptibilities imparted by our genetics.

So, we would guess that most age-related hearing loss does have some genetic, if not total genetic, predisposition, and the fact that it's not 100% of patients over the age of 75 with hearing loss, rather one half to two thirds, sort of backs that up.

But in terms of congenital or hereditary hearing loss, there are certain conditions and syndromes which we know are hearing loss related, and we can diagnose those fairly young. It's the patients over the age of 40, 50, 60 that we're less able to determine. And there are some studies, though, that have looked at what we term age-related hearing loss and looked at their genetics and have identified some mutations that are fairly specific for a family group but not universally represented in other genomic studies, and they show up in certain areas of the gene pool where we know that genes dedicated to hearing messaging are present.

So, there's probably a multitude of issues with mutations over our family histories that does lead to the age-related hearing loss, so I would look at them mostly in the same way.

Gazella: Yeah. It'll be interesting to see how that research kind of plays out from an epigenetic standpoint.

Now, there's early evidence showing that antioxidants, specifically beta-carotene, vitamins A, C, and E and magnesium can be protective. Tell us about that research.

Albritton: Sure. I want to add one more little point to the last question as it'll tie into this. We do know that insulin-like growth factor 1 is something that's important in our homeostasis and our ability to fight off reactive oxygen species or free radicals, and some studies have demonstrated that this decreases with age, and some other studies have taken it a step further and looked at does this have a role in some of the age-related hearing loss, and it does appear to have some role in that.

So, it's been a natural thing for antioxidants to have been targeted as a potential therapeutic arm against the aging of the ear. You mentioned vitamin A, C, E, magnesium, and I would caution drawing conclusions to these individual compounds at this time because the data is really all over the place.

There are numerous studies in mice that have demonstrated some general improvements using a group of different antioxidants versus control groups. Some of those antioxidants include things like cysteine or acetylcarnitine. Longitudinal studies, though, looking at humans with vitamins A, E, C, B12, folate have showed different results. For instance, in men, they didn't find any difference with any of those vitamins used except in men over the age of 60 they did note that folate may have given some protective benefit. In women, they found that vitamin A and folate also helped not necessarily an age dependent result, but this is interesting; vitamin C, which has been shown to be helpful in some animal models, was actually harmful and actually worsened things in some women studies.

We know that folate is an effective cofactor. We know that it helps balance out homocysteine levels, which can protect ischemic vascular damage, so that makes sense to us that it would work. The roles of vitamin C are just straight antioxidant properties, so that suggests that there's something more than just straight antioxidant benefits.

One interesting study in Finland that was done about 10 years ago, and they call it the disco study, and it wasn't a very large study; about 20 people were given either an antioxidant vitamin or a placebo. They had their hearing tested before a night exposed to loud music and then they had their hearing tested short term and long term afterwards, and they definitively showed that the group with the antioxidants had less impact from the noise exposure than the control group.

Gazella: That's interesting. I like they called it the disco study. That speaks to the era or the timing of that study, I think. So, when we're talking about studies, the research that I read I believe also included magnesium. What would be the connection with magnesium and why would magnesium help our ears? Am I correct? Was magnesium a part of that study?

Albritton: Magnesium's a part in several of these studies, and magnesium and the metals probably have a bigger role in enzymatic cofactor, enzymes that can control either the release of certain natural antioxidants or enzymes that have some role in keeping a biochemical process in its favorable state as opposed to going to its unfavorable state. Those metals are essential to these enzymes functioning theoretically, and yes, in some military studies, the use of magnesium has been shown to be effective.

Gazella: Now, you mentioned a lot of nutrients, A, C, E, just talked about magnesium. Is the combination of nutrients important and are there other nutrients that you wish researchers would be looking at?

Albritton: Now, you're getting to what my interest is. I think yes. I think very much there is combination therapy that makes a difference. I think we're still trying to figure out what that precisely is.

There are a host of readily available organic compounds that are something we may have picked up through ethnobotany or traditional Chinese medicine or just from the vitamin industry at large, but we have found that several of these compounds do appear to help in the protection of the inner ear, the heart, the kidney, et cetera.

One of those is N-acetylcysteine in rat models, which has proven to be effective at protecting the outer hair cells of the inner ear, and one of the methods we think it works is just by scavenging the free radicals, but it does turn on the body's natural production of glutathione synthesis. So, it doesn't just target the free radicals with its own ability to neutralize them. It actually turns on the body's ability to keep producing those free radical fighters.

But there's something else that goes on. It seems to regulate the nitric oxide in the inner ear, and one of the things that nitric oxide can do is, depending on its concentrations, it can trigger a cell to commit cell suicide. We call that apoptosis. In damage that may be sublethal, damage that shouldn't cause a cell to destroy itself, sometimes that misregulation allows the nitric oxide to get so high that it ends up allowing that cell to die. And as you may or may not know, these cells can't regenerate at this time, and so that regulation of the nitric oxide is one unexpected benefit of the N-acetylcysteine.

And that's something we see in several other compounds. Some compounds, for instance ... I'm just going to give you a brief list. Resveratrol. We know resveratrol as a miracle compound that has some anti-aging properties in animals, turns on some anti-aging genes, but we found in several studies that it has a highly effective role in reducing inner ear damage in animal studies. It has not been studied in humans to date. We believe that's a real key chemical.

CoQ10 has been also very effective in guinea pig models. We know that the mitochondria stabilization appears to be important, and CoQ10 is important in the function of our energy production in the mitochondria. Replacement does appear to have beneficial effects.

One independent observation as I see patients in my office all the time with a balance disorder that we can attribute to a medication being used for their high cholesterol, and a class of medications HMG-CoA reductase inhibitors, such as the statin drugs, are notorious for depleting the body's natural production of CoQ10. So, replacement of that in patients has helped with balance preservation, and anything that helps balance preservation we can assume is also working in other areas of the inner ear as well.

There are a number of elements and compounds that we discussed. We put together in 2006 a group of compounds we thought were going to be important that included the resveratrol, the N-acetylcysteine, N-acetyl-carnitine, alpha lipoic acid, green tea extracts, flavonoids from citrus, the CoQ10, B complex, and the trace minerals such as selenium, manganese, magnesium, and have found that to be effective in some pilot studies that we have performed on patients with their hearing loss showing some actual improvement in their hearing using the compound versus not using the compounds.

We've not had the opportunity yet to complete a double blinded study at this time, but there is certain promise with this. I think the holy grail is a compound that would be able to be taken on a daily basis that would offer protective benefits to the whole body, not just the inner ear.

Gazella: Right, and when you're talking about protection, you're even talking about protection in a patient that has some hearing loss; that it can also work in that patient population.

Albritton: Yes. In fact, our pilot study really only targeted patients with hearing loss. We compared patients that had many years of hearing loss, and we had multiple hearing tests on them and then started therapy with them and measured several hearing tests on the medication, were able to compare their hearing test pre and post, and were able to make those comparisons based on a preexisting condition. And so we did see some improvements in patients with existing hearing loss.

Gazella: What about reversal? Is that on the radar or is that a little bit too pie in the sky to actually reverse damage, to have a hearing be regained?

Albritton: There's research being done in terms of hair cell regeneration. That's several decades away at best. That, if it does prove possible, would reverse it.

Now, in terms of nutritional therapy, that's an unknown. We don't have the data yet to determine that. I think it is promising that we can see improvements in cognitive function with hearing aids and with Cochlear implants, but we can't know that by correcting some of the metabolic issues or protecting the interior from damage from its own physiologic stressors or noise exposures whether that's going to actually reverse the hearing loss that has occurred. I think that's probably pretty hopeful on our parts, but never rule anything out.

Gazella: Yeah. Yeah, that's for sure. Now, given how common hearing loss is, it's likely that the readers of our journal have patients in their practice who are at risk. So, in addition to the nutrients that you mentioned, what else should doctors be recommending to their patients to help protect hearing?

Albritton: I think first and foremost is recognize how common of a condition this is and screen for it. Ask patients, "Have you had any problems hearing? Has your spouse indicated that you may be having trouble hearing you?" It's interesting that spouses tend to be the ones that send patients for hearing tests more often than the patient seeks testing on their own. And it's a known fact that only one in five patients with hearing loss is going to seek help for it on their own typically. It can take 10 years or so before patients seek help for the symptoms.

So, it can lay dormant, it can be hiding and be attributed to mumbling or volume not being turned up loud enough before a patient truly begins to embrace there may be a problem they need to evaluate.

Refer patients for hearing tests if there is a presumed hearing loss or if there's a family history of hearing loss. Any patient that is on those medications, chemotherapy drugs, certain types of antibiotics, those patients should be monitored.

One other thing that I think is very important and I think most practitioners are very good about doing, but let's remind them that noise exposure can be prevented. If you can't prevent the noise exposure, then protect yourself from it and that people that have hobbies or occupational risks should be wearing some degree of hearing protection, and just like smoking cessation's important for us to counsel, the use and adoption of protective devices should be something we continually discuss at our meetings with these patients.

Gazella: Yeah, it's such a good point that you bring up that one in five seek help on their own and a lot just kind of let it go, let it go, and yet early detection, the earlier it's caught, the better off they'll be. So, I'm so glad that we're putting this on the radar of the doctors who are reading our journal. This has been very interesting, and I really appreciate you for joining me today.

Albritton: Well, thank you. It's been a pleasure.

Gazella: Have a great day.

Albritton: You as well.

In this podcast episode, we speak with Ross Pelton, RRh, CCN, about the variety of mechanisms of action that probiotics have when it comes to reducing cancer risk. Pelton also talks about colon cancer, H. pylori, and probiotic safety and dosage. Finally, he describes how to support a healthy microbiome with a healthy lifestyle.

(Approximate listening time is 32 minutes)

About the Expert

Ross Pelton, RPh, CCN, is Essential Formula's director of science, in addition to being a practicing pharmacist, clinical nutritionist, and health educator in Southern Oregon. Pelton earned his bachelor of science in pharmacy from the University of Wisconsin. A certified clinical nutritionist, Pelton was named as one of the Top 50 Most Influential Pharmacists in the United States by American Druggist magazine for his work in natural medicine. Pelton teaches continuing education programs for healthcare professionals to use natural medicine and integrate it into their practices. He also has authored numerous books, including The Drug-Induced Nutrient Depletion Handbook, which is a gold-standard reference book for health practitioners.

About the Sponsor

Essential Formulas Incorporated (EFI) was established in 2000 as the sole US distributor of world-renowned microbiologist Dr. Iichiroh Ohhira’s award-winning probiotic dietary supplements and skin care products. Always an innovator, EFI introduced REG’ACTIV in 2015, containing ME-3, a probiotic catalyst that produces the “master’” oxidant glutathione inside the body's cells. A family-owned and operated business, EFI was founded on the philosophy of providing high-quality preventative, supportive, and comprehensive pro-health products for the entire family. EFI continues to flourish and grow through a strong company and product integrity and the knowledge that they’re providing scientifically proven products that positively impact the health and well-being of their customers.

Transcript

Karolyn Gazella: Hello. I'm Karolyn Gazella, the publisher of the Natural Medicine Journal. Today, our topic is reducing cancer risk with probiotics. Before we begin, I'd like to thank the sponsor of this interview who is Essential Formulas Incorporated. My guest is integrative pharmacist and nutritionist Ross Pelton who is an expert on the topic of probiotics and health. Ross, thank you so much for joining me.

Ross Pelton, RPh, CCN: Hi, Karolyn. It's really nice to be with you. I enjoy our conversations.

Gazella: Yes. Now, first of all, how does the scientific literature stack up when it comes to probiotics and cancer prevention? Are there published human clinical trials?

Pelton: Well there's really not a lot of human clinical trials, but there's really quite a bit of research that has been conducted looking at cancer with probiotics. Human clinical trials are lacking, but there's a lot of work that has been done, cell culture studies and animal studies. There's a lot of work being done in this area. We just don't have the longterm human clinical trials which are very expensive to do. I think there's a lot to talk about because we've got substantial studies that have been published on the relationship between probiotics and cancer.

Gazella: Right. So I'd like to begin by having you give us an overview of exactly how probiotics influence the microbiota to reduce cancer risk. Now, there are several mechanisms of action. So go ahead and fill us in.

Pelton: Sure. Well some of your probiotics produce compounds that have antioxidant activity. Some of them have anti-inflammatory activity. They help to regulate detoxification. A lot of these functions are due to the fact that your probiotic bacteria produce secondary compounds or secondary metabolites that are called postbiotic metabolites. This is really the new frontier in microbiome science, starting to learn more about the compounds that your probiotic bacteria produce when they digest and ferment the food that you give them. Remember, these compounds have anticancer activity or protectant mechanisms that help protect against cancer.

Gazella: So I'd like to focus on these mechanisms of action as they relate to reducing risk of cancer. So let's begin with a more well-known mechanism and that is, as you mentioned, probiotics influence immunity. Describe what the scientific literature tells us about probiotics and the immune system.

Pelton: Well we know that 70% to 80% of the cells in your immune system reside in the gut. So it's really critical to have a healthy microbiome, a healthy gastrointestinal tract because that is the bulk of your immune system cells. One thing a lot of people don't realize is in the first 6 months of life, the primary function of your probiotic bacteria is to train your immune system. So it's really critical that kids get a good start in life with a vaginal delivery and adequate breastfeeding and for kids that don't, that's a compromised immune system. The gut is the seat of the immune system, and your probiotic bacteria are what trains the immune system.

Gazella: So now, what about maybe a little less known activity which is, as you mentioned, the antioxidant potential of probiotics? This may not be on the radar of some practitioners. Describe this mechanism of action.

Pelton: Sure. We know that free radical damage causes DNA damage and can increase your cancer risk. In a highly inflammatory condition in the gastrointestinal tract, there's a lot of free radicals being produced and a number of your probiotic bacteria have antioxidant activity and they also produce compounds that have antioxidant activity. There's 2 things going on here. Some of the bacteria themselves are antioxidants, but more importantly, they produce compounds that have direct antioxidant activity. In that respect, they're reducing free radical damage and reducing cancer risk especially for colon cancer which is a site of a lot of the free radical activity in a highly inflamed colon.

Gazella: Yeah. We're going to definitely talk about colon cancer, but now, when it comes to this influence on immunity and antioxidant potential, are there research studies in vivo or in vitro studies indicating probiotics, which probiotics can help with immunity and antioxidant potential?

Pelton: Sure. There's both some of the lactic acid-producing bacteria, Lactobacillus strains, and also some of the Bifidobacteria, bacteria that reside primarily in the large intestine and colon. One of the classes of antioxidants that they produce, they're called exopolysaccharides. That's a big word for people, but it just means that there are chains of sugars that the bacteria produce and then they excrete them and they have antioxidant activity. So this is just one of the mechanisms of action by which both Lactobacillus and Bifidobacteria are able to produce antioxidant compounds that reduce cancer risks.

Gazella: So the research tells us that probiotics can influence gene expression. Tell us how this impacts cancer risk reduction.

Pelton: Well various different strains of probiotic bacteria can influence gene expression. They can influence apoptosis, which is the rate of cell death. They can influence metastasis. They can influence cancer stem cells. They can up-regulate tumor suppressor genes. So a number of different ways that probiotic bacteria and the compounds that they produce, these postbiotic metabolites can influence gene expression which ultimately is going to influence cancer risks.

Gazella: So now, there's a significant amount of evidence and research showing that toxins can increase risk of cancer. What role do probiotics play in neutralizing some of these toxins or in supporting the detoxification of some of these toxins?

Pelton: Sure. This is actually a pretty broad category. There's a lot of different ways that probiotics can have detoxification capabilities. Some strains of bacteria can detoxify or decrease the absorption of a cancer risk factor called bisphenol A. There's a lot of studies on that substance now that show that it increases cancer risk. This is a compound that's in a lot of products that are on the market, especially baby products.

Some strains detoxify some of the agricultural pesticides. One of the Essential Formulas' products, Reg'Activ, contains a strain of bacteria called Lactobacillus fermentum ME3, and that strain of bacteria up-regulates a group of enzymes called paraoxonase enzymes. Those enzymes directly detoxify things like organophosphates, which are one of the commonly used pesticides in the agricultural industry.

Other strains can directly bind some of the heavy metal toxins like mercury and lead and cadmium. They also decrease the absorption of these heavy metal toxins when they bind them up so they don't get absorbed into your system. They get excreted. Some strains actually metabolize cancer-causing food preservatives like sodium nitrate, and Bifidobacteria are able to degrade and detoxify a very serious compound called perchlorate. We get exposed to perchlorate from fertilizers in the environment and a lot of that in the agricultural industry.

Heterocyclic amines are frequently caused by cooking meat at high temperatures. So our middle America, meat and potato people, they're out there with their barbecues and they're producing these heterocyclic amines. Some of the Lactobacillus organisms reduce the toxicity from heterocyclic amines. That's just a number of the different ways that your probiotic bacteria function as detoxifying agents in the gastrointestinal tract.

Gazella: Yeah. It's a long, impressive list. Now, I want to get back to the ME3 that you mentioned. Are there scientific studies on that particular-

Pelton: There are.

Gazella: ... strain, the ME3?

Pelton: It is a really, really fascinating topic because Lactobacillus fermentum ME3 synthesizes glutathione. Glutathione is the master regulator of your detoxification throughout your system and every cell produces glutathione, but it's hard to boost your levels of glutathione because, when you take it orally, it gets oxidized, it gets broken down and destroyed so you don't absorb it. But now we've got a strain of bacteria, this Lactobacillus fermentum ME3, where the bacteria actually synthesize glutathione.

Yes, we have human clinical trials showing that the antioxidant activity of glutathione produced by the ME3 probiotic bacteria will reduce levels of oxidized LDL cholesterol so you're reducing your cardiovascular risk, and it does a good job of increasing detoxification throughout your whole body. The human clinical trial, people taking ME3 had an astounding 49% increase in the ratio between oxidized glutathione to reduced glutathione with the reduced glutathione is the active form. A 49% increase in the ratio of the reduced to oxidized glutathione is a huge, huge meaningful marker.

This is really a revolution in healthcare and medicine to be able to boost your glutathione levels on a regular basis because, as I mentioned, glutathione regulates your detoxification. It's also called the master antioxidant and probably protects more of your body than all the other antioxidants combined. This is one area that is just really astounding both in terms of antioxidant protection and detoxification capabilities.

Gazella: That's great. So I'd like to switch gears and I'd like to talk about specific cancers. When I think about probiotics and cancer, I often think about colon cancer. You mentioned that previously. What role can probiotics play in reducing the risk of colon cancer?

Pelton: Well there's a number of ways that this can happen. Pathological bacteria will convert bile acids into secondary metabolites that promote cancer. When you have the proper acid-base balance in the GI tract, there's a dramatic reduction in the conversion of these bile acids into the more cancer-causing secondary metabolites. So maintaining the proper acid-base balance, which is what the probiotic bacteria do when they produce things like short-chain fatty acids and organic acids and nucleic acids, they create the proper acid-base balance which reduces the conversion of bile acids into secondary cancer-causing metabolites.

Your probiotics can also inhibit the activity of carcinogenic enzymes. They suppress growth of bacteria that produce enzymes that deconjugate carcinogens. What I mean by that is that a lot of carcinogens get bound up and they're supposed to be excreted when you have bowel movements, but if you don't have good elimination and so things stay in the colon too long, those cancer-causing things that are bound up can get released and reabsorbed. So probiotics can actually suppress the growth of bacteria that produce these enzymes that are deconjugating these carcinogens. Good bacteria are actually keeping these carcinogenic byproducts bound up so they get eliminated from your body.

Gazella: Well speaking of bacteria, it's widely known that there's a connection between H. pyloriand cancer. Can you describe that connection and tell us how probiotics can help prevent or even reverse H. pylori?

Pelton: Sure. That's another big topic because now that H. pylori has been discovered and understood, we realize it's the primary cause of stomach cancer and cancers in the upper small intestine. This is an interesting bacteria. It's got kind of a corkscrew tail on it, and it can just burrow its way into the lining in the stomach or the lining in the small intestine. When that happens, you've got a hole in your intestinal wall. Then you get the acids and the digestive enzymes leaking through, creating inflammation, and you end up with a higher incidence of cancer.

If you have a good, healthy microbiome and adequate numbers of your good bacteria, you suppress the growth or the overgrowth of H. pylori. There's a little bit of a controversy about whether people should try to totally eradicate H. pylori. Some people, some of ... Martin Blaser is one of the leading scientists that's exploring this and saying maybe we shouldn't totally eliminate H. pylori, but people that have H. pylori overgrowth certainly do have increased risk to gastric cancer and small intestinal cancers. It's having a good microbiome and adequate numbers of your good bacteria that will keep the H. pylori in check and not get overgrown so you reduce your cancer risk.

Gazella: What are some of the symptoms of H. pylori overgrowth? I mean how does a doctor recognize this in their patient population?

Pelton: Well as I described, the bacteria has this corkscrew tail that burrows through the unprotected mucus lining in your stomach or your small intestine. When you get that hole in the lining, you've got an ulcer. It's painful. Your digestive acids, your stomach acid, and your bile acids and small intestine. Then they go through the mucus membrane which is your protective barrier, and they come into direct contact with the cells that line your GI tract. When that mucus protective layer is breached, then those acids contact those cells that line the GI tract and it's painful. You've got an ulcer and you say "Oh, man. This is sore." So people actually oftentimes stop eating because every time they eat, they get more digestive juices in that ulcerative location. You need to heal that ulcer. Getting rid of H. pylori is one thing, but you also have to take time to heal the ulcer.

Gazella: Yeah, that makes a lot of sense. Now so far, we talked about colon cancer, stomach, upper GI. Are there any other cancers when it comes to using probiotics? I mean do you pretty much recommend probiotics as a risk reduction strategy across the board?

Pelton: I do because your immune system is so directly related to cancer risk factors. A lot of people don't realize that probiotics have an effect outside the intestinal tract. We now know that things like short-chain fatty acids get absorbed into your system and can actually reduce the risks of liver cancer. It's a whole body effect. These bacteria are not just a local effect in the gastrointestinal tract. I kind of use the analogy of Mission Control at NASA where those computers are controlling your space flights. Well your probiotics and the postbiotic metabolites in your small intestines and your colon are really Mission Control for all health-regulating effects in your whole body.

There's a new study that I wanted to share with you, Karolyn, published just recently in a journal called Oncotarget. It's a cancer journal. It says cancer killers in the human gut microbiota. One of the things they're reporting here is that they identify intestinal bacteria that exhibit potent antimalignancy activities on a broad range of solid cancers and leukemia. So this is a relatively new paper just published in July of 2017, identifying that postbiotic metabolites and your probiotic bacteria are helping to reduce both solid cancer tumors and leukemia. It's just an exciting new report giving more emphasis on the anticancer capabilities of your probiotic bacteria.

Gazella: Yeah. I think this area of research is going to just really explode. Now, a lot of patients go into their doctor's office and they say "Oh, well I'm fine. I don't need a probiotic supplement because I eat yogurt everyday," or something like that. How easy or difficult is it to get the probiotics we need from diet alone?

Pelton: It depends on what you mean by diet. If people are eating fermented foods, that's a really good source of probiotic bacteria, but most people aren't eating sauerkraut and kimchi and tempe and things like that. Most foods don't have probiotic bacteria. People think about yogurt, but commercial yogurts have a lot of sugar which actually promotes the growth of your pathological bacteria and yeast like candida. So commercial yogurts are generally not a good idea either in terms of just not getting a good source of probiotic bacteria. You're really working against the health of your gastrointestinal tract and your microbiome.

If people produce their own yogurts, there are some good ones. Yes. But you're really not getting a diverse level of bacteria in yogurt, and a healthy microbiome is a diverse microbiomes which means you want to get a lot of different types of strains of bacteria. The best way to do that is to consume a diet that has many different types of fiber-rich foods, especially the multicolored vegetables. That's the number one food source for your bacteria.

Gazella: Right. We have to feed those good bacteria.

Pelton: That's right.

Gazella: So now, you represent a specific type of probiotic, the Dr. Ohhira's brand. Why do you recommend that specific brand of probiotic?

Pelton: Well I'm glad you asked that. I'm the scientific director of Essential Formulas, and Dr. Ohhira's Probiotics is our primary product line. Dr. Ohhira's Probiotics are made differently than every other probiotic in the world. In fact, it's kind of confusing, but Dr. Ohhira's Probiotics is really not primarily a probiotic. It is primarily a fermented food.

The Dr. Ohhira's Probiotics are produced in a fermentation production system. We have large fermentation vats in a warehouse, and we start with 12 strains of probiotic bacteria. Then at seasonally appropriate times throughout the year, we shred and harvest dozens of different types of organically-grown foods. There's fruits and vegetables and mushrooms and seaweeds. Then the bacteria get to digest and ferment these foods for 3 years before the product is finished.

During that fermentation process, the bacteria are breaking down the foods and producing this wide range of compounds that we now refer to as postbiotic metabolites. As I mentioned earlier, these are the master health-regulating compounds in our system. So Dr. Ohhira's Probiotics have been tested and we find out there are over 400 postbiotic metabolites in Dr. Ohhira's Probiotics. We are not primarily just delivering probiotic bacteria. We're delivering over 400 of these postbiotic metabolites that rapidly create change in the GI tract. You rapidly reduce inflammation, rebalance the acid-base level, promote the growth of healthy new cells that line the GI tract, cell signaling and gut-brain communication directly with postbiotic metabolites.

We get what we call rapid microbiome restoration or rapid microbiome repair. Other companies are just giving you bacteria in a capsule. That's kind of like a starter culture. Those bacteria haven't done any work yet. Our bacteria have been working for 3 years producing postbiotic metabolites by the time you ingest them. That's the big difference. Dr. Ohhira's Probiotics is different than every single other probiotic in the world. The new science in the microbiome, the new frontier in microbiome science is starting to realize that it's these postbiotic metabolites that have the master health regulatory effects in the gastrointestinal tract and health-regulating effects for the entire body. So by directly delivering this postbiotic metabolites, we get rapid improvement in the microbiome in the gastrointestinal tract for people who take Dr. Ohhira's Probiotics.

Gazella: Now, I know this particular product does not have to be refrigerated. Why is that?

Pelton: Well these bacteria learn to thrive and survive at room temperature during the 3 years of fermentation. They don't need to be refrigerated, which makes them very user-friendly. Also they are in a patented capsule that stays hard in the harsh acid environment in the stomach. Then it preferentially releases the contents in the small intestine. So it doesn't make any difference if you take it with food or on an empty stomach. Any way you take it, just the main thing is 2 capsules once a day. Get Dr. Ohhira's in on a regular basis and you'll be maintaining a healthy microbiome.

Gazella: Yeah. I'd like to talk a little bit about dosage because honestly it seems like you can ask 3 different experts about dosage and they'll give you 3 different answers. When it comes to dosage specific to cancer prevention, is that the 2 caps per day? What does that deliver in terms of CFUs or different strains for that two caps per day?

Pelton: Well 2 capsules a day is the recommended dosage. One thing we emphasize, we're not concerned about how many million or how many billion bacteria we have. There's a numbers game that is really a misconception by people when we're talking about probiotics that they call the bacteria that are available CFU which stands for colony forming units. It really means just the number of viable bacteria, but people have a misconception that more is better. They say "Mine has 30 billion. Mine has 50 billion. Oh, mine's got 100 billion." They think more is better.

One of the most critical factors in a healthy microbiome is balance. If you take massive doses even as a healthy strain of bacteria, you're not working in favor of balance. You're actually working against creating balance in the microbiome. So it's not important to have high strains of, high dosages and high numbers. It's better to have a multistrain probiotic, a lot of different strains but at lower dosage levels.

I really talk in my lectures and seminars against the high-dose probiotics. I'm not saying they're never appropriate. A product like VSL3, which is a prescription probiotic, I think it has 112 billion bacteria per dose. Those people have some good research and have documented benefits from their high-dose probiotic, but I don't think high-dose probiotics are appropriate on a longterm maintenance basis. You want to strive for balance and diversity.

Gazella: Yes, I would agree with that. How many strains are in the Dr. Ohhira's product?

Pelton: Dr. Ohhira's has 12 strains. We start out with 12 strains in the manufacturing process. We are a multistrain probiotic. I'm not sure, but Dr. Ohhira may have been the first scientist in the world to understand the concept and the importance of a multistrain probiotic because he created Dr. Ohhira's Probiotics 30 years ago.

Gazella: Yeah. So let's talk a little bit about safety. When it comes to cancer prevention, are probiotics safe for the majority of patients or is there any patient or group of patients who should not take probiotics to help reduce cancer risk?

Pelton: No, everybody should take probiotics. One of the most important things for health is a healthy microbiome. We now understand that a healthy microbiome is the foundation of health. I think it's important for everybody to realize that supporting and maintaining a healthy microbiome is a critical factor for health regulation. There's no contraindications.

I do want to mention briefly, Karolyn, there are 2 studies that were recently published in the journal Cell that have gained a great deal of publicity because they cast doubt on the effectiveness of probiotics. The scientists who conducted these studies stated that their results suggested probiotics are almost useless. There's been a lot of pushback after the publication of these studies. It turns out there was some methodological shortcomings in the way they set up their studies, and there were a very low number of people. I think there was only 8 to 12 people in these studies.

What's more disturbing is that it has been learned that the scientists that conducted these studies, they have a personalized approach to probiotics that they promote in their studies. Turns out that they have a vested interest. They have financial interest in this company that's promoting this personalized approach. So it's a very serious flaw and their conclusions should not be generalized of the whole field of probiotics. Allowing studies to be published in which the authors state that probiotics are almost useless is really grossly misleading and a disservice to the general public.

Gazella: Yes, I would agree. Now, I often like to ask experts to grab their crystal ball and look into the future. In your case, I'd like to have you tell us what you'd like to see happen when it comes to probiotic or postbiotic metabolite research in the future. What do you want to see happen as we go into this next phase? Because I'll tell you, there's a lot of exciting stuff happening. There's a lot of different directions we could go into.

Pelton: You're absolutely right. It is a very exciting field and rapidly evolving. As I've talked about these postbiotic metabolites, the compounds that your probiotic bacteria produce, in the future, we will learn a great deal more about the health-regulating effects of these compounds that your bacteria produce and we'll learn more about which strains of bacteria are more effective at producing some of these health-regulating postbiotic metabolites.

I think in the future, we'll probably make a great deal of inroads and progress in designing personalized probiotic programs for people. We'll be able to assess your own innate microbiome and be able to know more accurately how to promote and enhance the growth of your own innate what we call your probiotic fingerprint, the bacterial population that you've developed early in life. I think we'll get into more of a personalized microbiome and personalized approach to probiotics to help promote health in individuals.

Gazella: When you think about cancer specifically and reducing cancer risk, I mean now obviously, it's estimated that 1 in 2 men and 1 in 3 women will develop cancer in their lifetime. I mean this is now reaching near epidemic proportions. How critical is it that we look at things like probiotics when it comes to reducing cancer risk?

Pelton: Well again, I go back to the immune system. It's absolutely essential that people have a healthy microbiome so that they have a healthy immune system. This is really where it starts. Your gastrointestinal tract and your microbiome are literally the foundation of your health for everything that happens. It is the number 1 thing that people need to be aware of and it's not just the microbiome.

As we mentioned earlier, you have to learn how to feed your probiotic bacteria well. This is another key message of mine. This is why diet is so important because you're not eating just for yourself. You're eating to feed 100 trillion guests. It's a pretty big party that's going on down there. Every time you eat, you have to realize that you're feeding your microbiome, and your microbiome is the center and the foundation of your health and your immune system and your anticancer activity. So people need to realize how important it is on a regular basis to eat a wide range of different types of fiber-rich foods, especially the multicolored vegetables, because a more diverse fiber-rich diet will promote the growth of a more diverse microbiome which means your bacteria will produce a wider range of these health-regulating postbiotic metabolites and you will be a healthier person with a stronger immune system.

There's a recent study that was just published that shows that, reports that people that consume more probiotics take less antibiotics. That's just another insight into probiotics being able to support your immune system. So these people using probiotics more have a stronger immune system. They have less need over time for antibiotics.

Gazella: Yeah. That antibiotic issue, that's something that we ... That could be whole other topic for us.

Pelton: It's a big one.

Gazella: But as an integrative pharmacist, you share a philosophy with our listeners who are, most of them are integrative practitioners. It's not just about giving a pill and calling it a day. It's a very comprehensive approach, and I like the fact that you focus so heavily on diet and using a healthy diet to feed the probiotics and the bacteria and that you use probiotics hand-in-hand with that comprehensive lifestyle approach which I'm assuming, beyond diet, you counsel people to exercise and get enough sleep and those other lifestyle factors as well.

Pelton: Absolutely. Those are critical factors. There are studies now that show that your probiotic bacteria respond to exercise. Exercise needs to be emphasized. So it's diet and exercise, lifestyle. All these healthy things go into creating and maintaining a healthy individual and having a healthy aging process. It's not just probiotics and it's not just diet as you mentioned. It's exercise and sleep and learning how to avoid environmental toxins. There's lots of things that go into it.

Gazella: Right. Treat your microbiome well and it will serve you for a long time to come.

Pelton: It will work for you. Absolutely.

Gazella: Well great. Well Ross, this has been very informational as per usual. I want to thank you for joining me. Once again, I'd like to thank Essential Formulas Incorporated for sponsoring this topic. Thanks so much, Ross. Have a great day.

Pelton: Nice to be with you, Karolyn. Always enjoy speaking with you.

In this podcast, we take a guided journey with noted professor and neuroscientist, Jane Foster, PhD, as she explains how animal models have elucidated the complexities of the gut-brain axis and role of gut microbes in mood and mental wellbeing. From a sound scientific footing, we join practicing psychiatrist, Scot Bay, MD, as he shares his experience with the integration of a mood-targeted probiotic blend in challenging cases and complex therapeutic interventions.

Approximate listening time: 35 minutes.

About the Experts

Scot Bay, MD, is board certified in adult psychiatry. He was educated at the University of Rochester and New York Medical College. He completed his residency in psychiatry at St Vincent’s Hospital in New York City. Bay specializes in the evaluation and management of mood, anxiety, and thought disorders and has special interests and expertise in psychopharmacology. He has extensive experience with numerous psychiatric medications and has lectured all over the Southeast regarding practical and innovative uses of psychiatric medications.

Jane Foster, PhD, joined the McMaster University faculty in 2003. She holds a research appointment with the University Health Network in Toronto, Ontario, Canada, as well as a scientific position with St Michael’s Hospital.

Foster is an active researcher with 2 translational networks, The Province of Ontario Neurodevelopment Disorders Network (POND) and the Canadian Biomarker Integration Network in Depression (CAN-BIND). Her research focuses on the role of immune-brain and gut-brain interactions on neurodevelopment, behavior, and brain function.

About Klaire Labs

Since 1969, Klaire Labs™ has been dedicated to developing clean, efficacious nutritional supplements to ensure optimal outcomes for the most sensitive individuals. It is this dedication to purity, potency, and performance that has guided the development of our legacy formulations including the highest selling professionally distributed probiotic brand in the United States, Ther-Biotic, as well as our novel, indication-targeted probiotic products such as Target gb-X™ (gut brain axis) and Target b2™ (breast and baby).

Transcript

Karolyn Gazella: Hello. I'm Karolyn Gazella, the publisher of the Natural Medicine Journal. Today, we will be discussing the gut/brain axis as it relates to mood and mental health. I have 2 experts joining me today, researcher Dr Jane Foster and clinician Dr Scot Bay. Before we begin, I'd like to thank the sponsor of this interview who is Klaire Labs.

Gazella: Dr Foster, I'd like to start with you and then I'll switch gears and get a clinical perspective from Dr Bay. Dr Foster, how does the human microbiota communicate with the brain?

Jane Foster, PhD: The human microbiota actually covers all of the surface of our bodies. However today I'm going to talk mostly about gut microbiota. That's a key component of the gut/brain axis. There are several pathways of communication between gut microbes and the brain. Neural connections are very important. In particular, the vagus nerve, which is a bi-directional nerve that can communicate from the gut to the brain but also from the brain to the body, that includes communication with the immune system and the gut, has a well-established role as a communication pathway between the gut and the brain.

The enteric nervous system, which is the mini-nervous system that wraps the gastrointestinal tract, responds to signals from microbiota in the lumen of your gut, and this influences both the host physiology at the level of the gut but also communications with the central nervous system.

These neural pathways are important, but there's also humoral pathways that are important. We know, and we have for a long time, that the brain can influence gut function and microbiota through the production of hormones such as cortisol. The interaction between stress and our microbiota is actually where a lot of the work that currently goes on started. But in the past decade we've been learning a lot more about how microbiota participate in bottom-up communication through the immune system and through other systems. But by influencing immune cells themselves or by influencing the immune molecules produced by the peripheral immune system such as cytokines and other molecules, the microbiota can influence this immune cascade signal to the brain.

One of the big areas of interest in the field is metabolism. Gut microbiota influence metabolism through the composition and function of gut has been shown to influence things like tryptophan metabolism bot locally and across the body, which may influence mood through modulation of central serotonergic systems.

And finally if we think about the microbes themselves, microbes can produce neurotransmitters and their lack of molecules. Although the role of microbiota-produced neurotransmitters might just be in the local area of the gut between microbes themselves and some of the gut tissue, there's a big interest in understanding how these might influence microbiota brain communication. Microbes also ferment dietary fiber, and through this fermentation they produce short-chain fatty acids including things like acetate, butyrate, and propionate. These short-chain fatty acids are important for crosstalk between microbiota themselves and promote healthy gut physiology.

Some of the evidence suggests that short-chain fatty acids can communicate beyond the gut, and in the case of propionate it's very important in the portal vein system and communication with the liver. In the case of acetate there's evidence that it can systemically communicate to the brain.

Gazella: That's fascinating. Why is it so important for us to understand this complex communication that's taking place?

Foster: Evidence from both pre-clinical studies and clinical studies supports a role for the microbiota-brain axis in these communication pathways in both physical and mental health. From the mental health perspective there's several potential benefits for understanding these connections. First, there's a great interest in the potential use of interventions that may target the microbiome, such as probiotics or prebiotics, but also diet and exercise and how these interventions might improve mental health.

Second, understanding the molecules and some of the signal transception pathways that mediate microbe/host or host/microbe interaction may actually provide novel targets for drug development outside of these microbiota-related therapies.

And finally one of the most interesting things from my perspective is the remarkable interpersonal differences in microbiota composition such that in fact between you and I our differences are in the range of 90% at the level of our microbiota composition. And such it seems that each person's microbiota is their own. This feature is really interesting when we think about heterogeneity and psychiatric illnesses or mental health in general. As the field moves toward more precision medicine approaches where we really do need to identify biomarkers that will help understand how individual biological differences might influencing what treatment might be best for each person.

Gazella: You mentioned the research. Can you describe some of the more significant studies that indicate how microbes influence brain function and mood?

Foster: Yeah. The foundation for our understanding of how microbiota influence brain function and mood has really come from a long history of animal studies that manipulated microbiota both in early life and in adulthood to show how connections between microbiota and behavior exist and also in these studies identify key signaling systems in the brain that are influenced by the microbiome but include things like our stress circuitry, our fear circuitry, systems that influence anxiety and depressive like behavior.

One of the ways that people have taken this animal work and started to think about are these systems actually operating in people has been to actually do the fecal transplant experiments where they've actually taken fecal samples from depressed patients and put them in rodents and demonstrated that rodents that received that depressed fecal sample actually have an increase in depressive-like behaviors and in sometimes anxiety-like behaviors.

That just supports this connection between microbes and the behavior, but a small collection of studies so far has also examined the composition of that microbiota in healthy and depressed individuals and shown that there are actually differences in the microbiota composition in depressed individuals when compared to healthy volunteers. A few of these studies have actually taken that a little bit farther and showed a direct association between specific taxa and clinical symptoms and disease severity.

If I can just highlight a couple of things about that that really are interesting and the sort of observations that I think will move the field forward. In a study by Chang in 2015 and colleagues, they shed a reduction in a very abundant bacteria called faecalibacterium. A reduction here was associated with an increased severity in depression. What's interesting about that is this is it's an abundant bacteria in healthy adults and a major producer of that short-chain fatty acid I mentioned butyrate. A reduction in this bacterial taxa has also been reported in other studies in depression but also in individuals with gut functional disorders. Suggesting this link between gut dysfunction and mood could be related to some of these key taxa.

If I can just tell you one more study that really links the bacteria to the brain is the work that comes of Kirsten Tillisch's group and Emeran Mayer's group at UCLA where they've shown some key taxa in healthy individuals are actually associated with brain connectivity using both DPI and structural imaging and then have also shown that the same taxa might actually be involved in emotional response using functional imaging. These sort of studies really do start to connect specific bacteria to brain function and behavior.

Gazella: Yeah. I think it's fascinating. When we're trying to target a microbiome to change the composition, you mentioned that there are some key factors that can influence gut health and therefore hopefully influence brain health. You mentioned probiotics, prebiotics, diet, lifestyle. Can you tell us some more specifics about how we can influence this gut/brain axis connection?

Foster: There are several factors that influence the composition and the function of gut microbiota. There's a lot of interest in the field to determine how both genetics and the environment and that interface influence the microbiome and how those interactions might influence both physical and mental health. A key factor that influences the microbiome is genetics. There's a whole series of twin studies that provide evidence for a role for host genetics or the DNA that we inherit influencing your microbiome.

The first evidence that showed this was this observation that monozygotic twins that have exactly the same DNA have more similar microbiomes than dizygotic twins but not perfectly matched suggesting that while genetics is an important role other things might also be important. There's extensive literature both in animals and in humans that looks at the importance of genetics but also highlights the influence of these other environmental factors. Some of those are important to consider in mental health.

Age, for example, influences microbiota composition and function. Our relationship with our microbiomes happens very early in life as we travel down the vaginal tract and are colonized by the bacteria. The dynamic changes that occur in early life really do influence all sorts of health outcomes, including risk of particular allergic responses, but also potentially mental health. Age-related changes that occur later in life also could have a direct impact on gut health and brain health.

Another big factor to consider is diet. There's a direct impact of diet on gut health and brain health but also understanding which specific taxa are influenced by the diet and how the related molecules and signaling systems that influence the interaction between diet, microbiome, and mental health really has to be addressed in a very systematic way.

The final factor, I think, that we all know about and pay attention to are the impacts of drugs on the microbiome, the most obvious being antibiotics. There's one large epidemiological study that suggests exposure to antibiotics increases risks of anxiety and depressive disorders, but recent evidence actually shows that both antibiotics and non-antibiotic drugs have direct effect on microbiota composition. The impact of the influence of these different drugs on the microbiome and how that bottom-up mechanisms might influence the side effects or the direct action of drugs is very important.

Gazella: What about probiotics? You mentioned prebiotics and probiotics. What role can they play in influencing the microbiome and then influencing mood and brain function?

Foster: There's enormous public and scientific interest in probiotics and other psychobiotics as you mentioned such as prebiotics but also naturally fermented foods, which have been around for a long time, to improve mental health. There is extensive preclinical literature that demonstrates benefits of probiotics in mood and brain function. Interestingly within this literature even when it's a challenge in an animal model that has nothing to do with mental health outcomes, the addition of a probiotic tends to improve some of the emotion-related behavior such as anxiety-like behaviors in these animal models.

The first evidence to support microbes can influence and probiotics specifically can influence brain function came from a whole series of probiotic studies in healthy adults. These studies administered probiotic cocktails or single probiotics to healthy individuals for a period of usually a month or longer. The benefits included things like reduced inflammation, reduced stress hormones, and improved anxiety and depressive measure, and that's in healthy individuals.

A key report in this area that actually launched some of the interest of Dr Bay who we're going to speak to later was a randomized control trial conducted by Laura Steenbergen and colleagues in the Netherlands that showed that this particular probiotic cocktail, Ecologic BARRIER, which is now in the US as Target gb-X, reduced cognitive reactivity to sad mood and reduced ruminative thoughts in those healthy individuals, suggesting again this link between microbes and a benefit on mood. But there's only been to date maybe 1 or 2 but 1 particular randomized control trial by Akkasheh and colleagues in 2016 that showed probiotics administration in depressed subjects reduced depressive scores and was accompanied by reduced inflammation and reduced serum insulin.

The field is certainly supporting the hope for therapies such as probiotics and prebiotics influencing mood.

Gazella: Perfect. Your last question Dr Foster. When it comes to gut/brain research, what would you like to see emphasized in the future? What more do we need to learn? I would imagine it's a long list.

Foster: I have a long list, and in fact the interesting thing about this field is its multidisciplinary nature and that as a neuroscientist in the field I also get the great advantage of associating with microbiologists who have never considered mental health in their research. I think this crosstalk between these different disorders helps us try to define what is a healthy microbiome, which is actually a critical step of the field right now, before we can figure out how alterations in the microbiome influence illness, whether it be physical illness or mental illness.

One of the things that I think is needed from a research perspective is actually, particularly in mental health, it's some longitudinal studies so that we can understand how dynamics of the microbiome and perhaps perturbations of it over time influence mental health. And also we need more studies examining the microbiome in psychiatric populations, paying attention to some of these individual differences that we know are emerging that might influence the gut/brain axis's impact on mental health.

If I go back to an earlier comment I made, if we think about the field in general and the researchers that have advanced some of our technology, the field's really very interested in functional readouts of the microbiota-host interactions. A lot of studies have looked at the composition of the microbiome. Knowing who's there is just the first step along the path of understanding how these communication pathways impact health. In particular, people are now using shotgun metagenomics to get a more comprehensive profile of what the functions of the microbiome are using genomics to look at the genes that are being expressed and metabolomics in both fecal, urine, and plasma samples to understand what the functional outcome of these different taxa have within our whole system.

This is a great advantage to psychiatry because depression and anxiety are really very heterogenous disorders. Understanding how the microbiome and the related signaling systems are linked though, clinical presentations of these disorders is important. What might be very important is understanding using these sophisticated tools, how individual differences in these microbiome readouts or proxies for the microbiome can identify a microbiota-brain signature that might actually allow us to cater treatments to individuals based on their own microbiome and their own depression or anxiety symptom profile. That way the trial-and-error component of treating individuals with psychiatric illness may be improved.

Gazella: Yeah. That's a great goal, and it's going to be exciting to watch this area of study as it evolves.

Okay, Dr Bay, it's now your turn. Dr Bay, much of your work has focused on psychopharmacology. What prompted your interest in the gut/brain axis?

Scot Bay, MD: I've always been looking through the literature for new and interesting developments in the field both to stay current on the latest developments in case you care but also because I had a weekly mental health–related podcast for many years and I was looking for new and interesting topics to discuss on that. Over the past several years I've been seeing more and more articles documenting research studies about the effects of probiotics in mood and also as Dr Foster mentioned even the effects of certain fermented foods in things like anxiety and also depression. That really struck a chord with me because I've always observed that there's a lot of promorbidity between states of anxiety and depression and gastrointestinal disorders. And again Dr Foster very elegantly laid out how the gut and brain are connected, so that always made perfect sense to me that people who have mental health problems are likely as not to have also gastrointestinal issues. It's just one of many ways I think that mental health problems affect the body physically.

People with depression but also especially with anxiety almost always have some kind of somatic or physical symptoms that are a manifestation of their disorder. Having gastrointestinal-related symptoms is a very common manifestation of the things that we psychiatrists treat on a daily basis, the depression, anxiety, and other adverse mood states.

Gazella: What type of GI issues are you seeing in your practice in people who have mental health issues?

Bay: Things like irritable bowel syndrome, which could either be prime persistent constipation or diarrhea or switching from one to the other, bad reflux, gastroesophageal reflux disease, and also other just non-specific functional bowel complaints that may not have a particular diagnosis associated with them but nonetheless affect people's gastrointestinal functioning.

Gazella: That is an interesting connection between mental health issues and the GI issues. Were there others that you wanted to mention?

Bay: Gastroparesis is another one. It's commonly associated with certain medical conditions especially diabetes but can also be affected by mood. And then there's also the other consideration being many psychotropic medications can affect motility of the intestines, so there's that consideration as well.

Gazella: I'd like to talk a little bit about treatment resistance because you have been focusing on psychopharmacology. How common is the issue of treatment resistance, and why is that such a challenge for many clinicians?

Bay: Right. I would say the treatment-resistant patients, in other words people who I guess by some definition had failed trials of 4 or more psychotropic medications, this is a very difficult problem because when you have people who don't respond to the normal typical treatments, it's very difficult to get them any symptomatic relief whatsoever. There's only a limited number of treatment alternatives to consider. The other part to that is when people wind up seeing psychiatrists, they've often cycled through several treatments already through their primary care physician. There are too few psychiatrists, so people often don't start their treatment of their mental health problems with us. It's usually started with primary care, so by the time they get to see us they've already struggled to not get any relief with the treatments they've been getting. It's even more difficult by the time that they see us.

The way I see it, we have patients who have their experience of their illness and all of them are as unique as their individual DNA, but the illnesses that we treat are not so unspecific that any treatment would be effective. For example, if someone has a bacterial infection it's very cut and dried. You send it for a culture. You know exactly what antibiotics will or will not kill it. You pretty much know what results you're going to get when you give the patient the treatment.

But when it comes to psychiatric problems, we just don't have a way of knowing in advance what treatments will work or not. When people don't respond to several treatments, that unfortunately indicates often a guarded prognosis. Another reason why I'm always looking around for other additional ways to help people who don't respond to the standard psychiatric medication treatments.

Gazella: That makes a lot of sense. I'd like to switch gears a little bit and talk about probiotics specifically. What are the clinical applications of using probiotics in patients who have mood issues like depression, anxiety, or other mental health disorders?

Bay: So far what I've been doing is adding this to the regimen of medications that I have my patients on. Initially what I did was to have people add the probiotic who were already on medication but still having symptoms to see if it would do two things, address their gastrointestinal symptoms and also bring about further improvement in mood.

When I first started doing this I had a limited supply of Ecologic BARRIER, which is the version made by the original manufacturer in Netherlands, Winclove. The company was kind enough to shoot me some samples. Initially since I had a limited supply I was just saying let me try this out on the people who are really bad off, maybe chronic, severe, treatment-resistant conditions, very complex regimens of medications, or polypharmacy and see how they respond because they're the people most in need of relief. Sure enough they all saw at least slight improvements in mood, and in many cases very rapid relief from their gastrointestinal symptoms.

But since the product is now available in the States and has been for quite some time under the name Target gb-X, I'm expanding that to people who are not necessarily only treatment-resistant as far as their depression and/or anxiety to people who aren't necessarily on complex regimens of medication with polypharmacy, even who may not necessarily have co-morbid gastrointestinal symptoms to see how this would help people.

I often get the question as far as another potential applications, I'm not getting support yet, but when I've discussed this with other clinicians I get the question, "Have you ever tried to give this to people to help them get off their psychiatric medication?" I haven't because initially the issue is helping people feel better who are only getting partial relief from their medication. But that's definitely something I plan to explore in the future.

Gazella: I definitely want to talk about some of your specific patient outcomes, but first can you please tell us the name again of the product and also tell us why you chose that particular product because there are a lot of probiotic products out there. Tell us the name of the product and why you chose this one.

Bay: Right. It's called Target gb-X, and it was originally only available through the original manufacturer in the Netherlands, Winclove. The reason I chose it going back to my always scanning for articles in the mental health field and looking for new developments and seeing the literature about probiotics, the study that Dr Foster mentioned earlier by Dr Steenbergen, that really caught my eye. This is what really, I think, initiated my getting involved in using probiotics in my clinical practice. As Dr Foster explained, Dr Steenbergen and her colleagues found that this particular probiotic helped reduce cognitive reactivity to sad mood and the aggressive negative ruminative thinking that is common in states of major depression even though in the study there were healthy adults, not depressed.

That really caught my eye when I saw the article about that study. I said to myself, "Wow. If this probiotic will do that, I need to get some of that and get some of my patients on it because so many of my patients are dealing with symptoms like that." I reached out to Winclove. They were kind enough to respond very readily and quickly. Kind enough to ship me some samples, and when I saw the results in my patients, that's when I realized that this could be very helpful.

To get back to your question why this one, the main reason is that because I saw the research study documenting that this particular one had benefits for those types of symptoms that I commonly see in my patients. But then also looking at the specific species that are contained in this particular probiotic, Bifidum bacterium species is one of them, and also Winclove really dialed down to not the specific subspecies in terms of which bacteria they included in their product. I have seen other studies besides Dr Steenbergen's in the literature mentioning probiotics that contained Bifidum bacterium species as far as helping with mood.

That's really why I said this probiotic seems to have the species that I've seen in literature can help with psychiatric symptoms and there's a study to back up that it treats symptoms that are common in depressed patients. That's why I said this one definitely has value as far as helping psychiatric patients.

Gazella: Yeah. It's always good to use the exact product that was used in the study. I think that's a really important factor. Before I get to the outcomes of your patients, it seems like dosing is always challenging. Do you dose the same with all of your patients and what dose do you typically prescribe to your mental health patients.

Bay: Right. The dose that's recommended by the manufacturer is the one that I typically prescribe, which is one sachet it's called, really just a packet of powder, in several ounces of tepid or lukewarm water once a day on an empty stomach. On occasion, I have suggested to patients that if they did not respond to one packet a day to try one packet twice a day. I've made that recommendation in the case of people who have especially severe gastrointestinal symptoms as well as mood symptoms or in people who they only had a very modest response to one packet a day or maybe not much of a response. But the vast majority of the patients that I've had try the Target gb-X have only been taking it once a day, and they have found that very effective.

Gazella: Okay, perfect. Describe some of the outcomes you've achieved in your practice using this particular probiotic.

Bay: In the original case series that I did when, again, I only had the samples shipped from the Netherlands, there were about 8 patients. They all had very rapid and thorough relief from their gastrointestinal symptoms such as irritable bowel syndrome symptoms, whether that was constipation or diarrhea. One older lady had this chronic severe diarrhea despite being on 2 antidepressants that are notorious for causing constipation. That was especially puzzling, but on the probiotic her diarrhea stopped.

I had another male patient with just very, very severe treatment resistant depression. He had tried multiple antidepressants of all different classes of drugs. No relief whatsoever, and he was only able to tolerate a very low dose of a much older generation antidepressant. But also he had chronic, severe, unremitting diarrhea. This man literally wore out his gastroenterologist's office and was not able to get any relief from it. The diarrhea stopped almost immediately upon staring the probiotic. That was amazing, and he was quite surprised, too.

These are the types of outcomes that I've seen as far as the GI symptoms. As far as mood symptoms, they were not as immediate or as dramatic, but usually after months, sometimes after 2 months, patients were able to look back and say you know what, I do think my mood is at least somewhat better than it was before I added this. It definitely has been successful as far as bringing about improvement in mood symptoms as well as improvement in gastrointestinal symptoms.

Gazella: Yeah, that's great. This as been a lot of great info, and once again I would like to thank the sponsor of this interview who is Klaire Labs. And I would like to thank you Dr Foster and you Dr Bay for joining me today.

Foster: Thanks very much, Karolyn.

Bay: Yes, you're very welcome. Thank you. It's been a pleasure.

Gazella: All right. Have a great day.

In this interview, Ross Pelton, RPh, PhD, CCN, describes the new science associated with postbiotic metabolites and their impact on health. Listeners will also discover what postbiotic metabolites are and why they are so important to the human microbiome.

About the Expert

Ross Pelton, RPh, PhD, CCN, is Essential Formula's director of science, in additino to being a practicing pharmacist, clinical nutritionist, and health educator in Southern Oregon. Pelton earned his bachelor of science in pharmacy from the University of Wisconsin and received his PhD in psychology and holistic Health from the University for Humanistic Studies in San Diego, California. A certified clinical nutritionist, Pelton was named as one of the Top 50 Most Influential Pharmacists in the United States by American Druggist magazine for his work in natural medicine. Pelton teaches continuing education programs for healthcare professionals to use natural medicine and integrate it into their practices. He also has authored numerous books, including The Drug-Induced Nutrient Depletion Handbook, which is a gold-standard reference book for health practitioners.

About the Sponsor

Essential Formulas Incorporated (EFI) was established in 2000 as the sole US distributor of world-renowned microbiologist Dr Iichiroh Ohhira’s award-winning probiotic dietary supplements and skin care products. Always an innovator, EFI introduced REG’ACTIV in 2015, containing ME-3, a probiotic catalyst that produces the “master’” oxidant glutathione inside the body's cells. A family-owned and operated business, EFI was founded on the philosophy of providing high-quality preventative, supportive, and comprehensive pro-health products for the entire family. EFI continues to flourish and grow through a strong company and product integrity and the knowledge that they’re providing scientifically proven products that positively impact the health and well-being of their customers.

Transcript

Karolyn Gazella: Hello. I'm Karolyn Gazella, the publisher of the Natural Medicine Journal. Today, we have a fascinating topic. We'll be talking about post-biotic metabolites with probiotic expert Dr Ross Pelton who is also an integrative pharmacist. Before we begin, I'd like to thank the sponsor of this interview who is Essential Formulas Incorporated. Dr Pelton, thank you so much for joining me.

Ross Pelton, RPh, PhD, CCN: Hi, Karolyn. It's nice to be with you.

Gazella: Well the research regarding the human microbiome is really exploding. Why is this so significant?

Pelton: Well I like to give people a little historical overview which I think gives us an understanding of how and why this incredible acceleration of research into the microbiome has taken place. I'd like to go back to the Human Genome Project. It took 13 years and billions of dollars to sequence the first human genome. After sequencing the human genome, one of the primary goals of that whole scientific endeavor, they thought once they sequenced the human genome we would be able to get cures for many of our chronic degenerative diseases.

That primary goal of the Human Genome Project was a total failure. We did not get any cures for human diseases from the Human Genome Project, but one important thing that we did get was the development of incredible technology and incredible equipment that allowed for much faster and much cheaper sequencing of genomes. That's when scientists started to use this new technology to sequence the genomes of bacteria in the human gastrointestinal tract. They were astounded with what they found, this whole massive population of organisms in the human gastrointestinal tract. Fortunately, our government then went on to fund the Human Microbiome Project. The funding for the Human Microbiome Project coupled with the incredible technology developed in the Human Genome Project allowed scientists to make tremendous progress in exploring and identifying many of the different species and strains of bacteria in the human microbiome.

Now, a little historical overview. Bacteria were discovered several hundred years ago, and scientists like Louis Pasteur had a major impact on the development of microbiology and the study of bacteria. But Louis Pasteur was responsible for the gene ... Excuse me. The germ theory of disease. He solved most of the serious diseases of his time. He developed vaccines for them and taught people how to avoid them or limit their problems. He was a global rock star in his lifetime because he solved most of the common diseases of his time. It would be similar if one person today solved Alzheimer's disease and cancer and diabetes and autism or something. It's amazing what he did, but he set in motion this germ theory of disease. For a couple of centuries, most people had the concept that germs or bacteria were bad. They're causing disease and we need to eradicate them.

Well another thing that happened along the way is that the only way scientists could study bacteria was extract them from the body, put them on what's called a Petri dish on an auger plate that allows the bacteria to grow, and then they watched them and observed it. A couple hundred years, that's the only way we could study bacteria, but we've recently learned that over 99% of your bacteria are anaerobic which means they can't stand oxygen. For a couple of hundred years, scientists would extract bacteria, put it in the lab to look at it, but it would get exposed to oxygen and die. For several hundred years, we could not study over 99% of the bacteria in our microbiome, but the development of this incredible technology from the Human Genome Project allowed scientists to start to dive into this new area and sequence the genomes of the bacteria and start to learn what they are and how they function. That's what started to kind of explode the research into the human genome, the human microbiome.

Also a very interesting thing happened. There's a thing that I refer to as the genome complexity conundrum. This is a fact that, when the human genome was sequenced, we found out that humans have about 23000 genes which is significantly less than scientists thought they would find, but the conundrum is that the common rice plant has around 45000 genes. Scientists are scratching their heads. How could we as evolved beings as we are have only 23000 genes and the common rice plant has over twice as many genes as we do? The answer to this conundrum is the fact that, although we only have 23000 genes, the bacteria in our microbiome have millions of genes. In fact, over 99% of the DNA in your body is the DNA of your bacteria.

This starts to open up an understanding of how important it is to create and maintain a healthy population of these bacteria in your microbiome so that they are doing good work for you. Because if you have pathological bacteria, their DNA and their genes are creating bad compounds that cause inflammation and poison you and create all sorts of diseases. This ... We're starting to understand why it is so important to create and maintain a healthy microbiome because your bacteria in your gastrointestinal tract are controlling and regulating vast amounts of your health.

Gazella: Well I have-

Pelton: It's kind of a little overview for starters.

Gazella: Yeah. I have to say I love that historical perspective because it provides the perfect backdrop for today's conversation. Thank you. It was very thorough.

Pelton: Sure.

Gazella: Now today, I'd like to focus on post-biotic metabolites because, as you have referred to in your recent presentation, this really is a new frontier in probiotic science. Remind us. What are post-biotic metabolites?

Pelton: This is another fascinating area, Karolyn. It's just starting to be explored, but it's extremely important when it comes to microbiome science. [inaudible 00:06:39] say in my lectures and seminars the reason probiotic bacteria is important is because of the work they do. The work that they do is that their metabolic processes digest the food that you give them and break it down and, in turn, their metabolic processes produce a wide range of compounds that we're referring to as post-biotic metabolites. What's really important for people to understand is it's these compounds that the bacteria produce that regulate vast amounts of your health, not the bacteria themselves.

We're shifting our focus a little bit from putting all our research efforts and all of our money into just identifying and naming different strains of bacteria. Now, we're starting to realize it's probably more important to identify what are the compounds that these bacteria produce, what are the health regulatory effects of these compounds, which strains of bacteria are more efficient and more effective at producing some of these compounds. That's the new frontier in microbiome science. Two months ago, I gave a presentation at the International Probiotic Association's annual convention in Miami. The title of my presentation was Post-biotic Metabolites: The New Frontier in Microbiome Science. This is what we're starting to explore and understand now.

Gazella: Yeah. It sees like it's taking this science ... It's giving it a whole new level of complexity. Let's talk a little bit about practical things like what functions do these metabolites serve as it relates to the human microbiome and health in general.

Pelton: Sure. That's a good segue here. I'm emphasizing these post-biotic metabolites. What do they do? Well they have a vast number of functions, and in fact, a very highly respected author and scientist in the microbiome arena—his name is Dr Emeran Mayer—wrote a book called The Mind-Gut Connection. In his book, he tells us that your bacteria with their millions of genes will digest your food and produce hundreds of thousands of metabolites. We're just beginning to understand what all these metabolites, these post-biotic metabolites are. Some of their functions, they have antiinflammatory activity. They adjust the acid-base balance in the GI tract. They have cell signaling capabilities. They have detoxification capabilities. They can directly fight and kill pathological bacteria. There's just a wide range of functions.

Let me just mention one major class of these post-biotic metabolites. They're called short-chain fatty acids. This is a class of really important post-biotic metabolites produced by your probiotic bacteria. Since they're acids, short-chain fatty acids, they're weak acids, but they create the proper and optimal acid-base balance in the gastrointestinal tract. The optimal acid-base balance is just slightly acidic, but when people have dysbiosis ... That's the term for different types of gastrointestinal problems or you have gas or bloating or diarrhea or constipation or inflammation or pain or whatever. Dysbiosis is the term for these general conditions. When people have dysbiosis or gastrointestinal problems, the acid-base balance goes anywhere from 10 to 100 times too alkaline. If you're going to get the GI tract back to good health, you have to bring it from it's alkalinity back down to its slightly acidic condition, and these short-chain fatty acids produced by the probiotic bacteria readjust and create that optimal slightly acidic acid-base balance.

Short-chain fatty acids also have antiinflammatory activity. If you have dysbiosis and gut problems, you've got inflammation. They'll help to dampen that inflammatory fire. Also another really important part of this in the story with the short-chain fatty acids is the fact that the cells that line your gastrointestinal tract have the most rapid rate of turnover of any cell in the human body. People don't realize this. Most people don't, but you create a whole new digestive tract every 6 to 10 days. It takes an enormous amount of energy for the body to continually generate these new cells in the lining of the gastrointestinal tract, and you do not get the energy to produce these new cells from your blood supply. The energy comes from short-chain fatty acids like butyric acid that are produced by your probiotic bacteria, these post-biotic metabolites.

These are just some of the ways one class of post-biotic metabolites, the short-chain fatty acids, contribute to a wide range of health-related things related to your gastrointestinal tract.

Gazella: Now, can you expand a little bit more on the mechanisms of action and how these metabolites kind of work on our behalf? I mean the short-chain fatty acids is a great example.

Pelton: Sure. Again, there's a wide range of these different compounds, and so there's different mechanisms depending on what post-biotic metabolite the particular strain of bacteria are producing. This gives me a chance to emphasize a really important point, Karolyn. A healthy microbiome is a widely diverse microbiome. By diversity, I mean a lot of different types of probiotic bacteria. It's not enough just to have high numbers but only a few different types. You want to have lower numbers but a wide range of different types of bacteria. If you have diversity of bacteria, you'll have a lot more bacteria producing different types of health regulatory compounds, and the way to create a diverse microbiome is to consume a diverse diet.

You have to consume a wide range of different high-fiber foods because these are the foods that your bacteria require. The fibers in multi-colored vegetables especially, that's the number one food group for your probiotic bacteria. Then there's also multi-colored vegetables and various other types of foods that are high in fiber, but our human body cannot digest these fibers. They go through your system into your colon, your large intestine, and that's where your probiotic bacteria start to digest them. That's the food for your probiotic bacteria. Yes, it's important to take probiotics, but you have to learn how to feed your probiotic bacteria well. If you don't, they will not thrive and survive.

Here's a couple of examples of some other mechanisms and how they work on our behalf. Some probiotic bacteria produce a wide range of compounds called antimicrobial peptides. Scientists just abbreviate these as AMPs, but antimicrobial peptides are very small amino acid chains or I describe them as small fragments of proteins. They specifically have antibiotic effects, but they have a narrow range of effectiveness. They are only damaging to pathological bacteria. They don't harm your good bacteria whereas prescription antibiotics are called broad-spectrum. They kill everything, your good and your bad, but the natural antibiotics produced by your microbiome and your probiotic bacteria as antimicrobial peptides are only going to function or be active against pathologic organisms. It's an important part of your immune system. These natural antibiotics being produced in a healthy microbiome are sometimes suppressing the growth of any bad bacteria that happen to be resident in your gut.

Another example, there's lactobacillus fermentum ME-3. It's a very unique strain of probiotic bacteria that synthesizes glutathione. Glutathione is a post-biotic metabolite of that particular strain of probiotic bacteria. I could go on and on. There are many different types of post-biotic metabolites. Just a couple of general classes, your probiotic bacteria are little chemical manufacturing plants. They make all the B vitamins and Vitamin K and some of the critical amino acids. They make some of our most important nutrients. That's really a source of some of our nutrition. That's a little overview of some of the things and some of the ways that some of these other post-biotic metabolites are helping us.

Gazella: Yeah. Those are some great examples. I have to say, when I knew that I was going to talk to you about this topic, I jumped online to do a literature search and I was actually quite surprised at the amount of research specifically about post-biotic metabolites. Can you tell us about some of the more recent studies that you have enjoyed reading about in the scientific literature?

Pelton: Sure. Well I'm very excited having learned that a strain of bacteria called lactobacillus fermentum ME-3 can produce glutathione. Glutathione is one of the most important compounds in the human body. We call it the master antioxidant. It's produced in every cell in your body, and glutathione probably protects more of your body than all the other antioxidants combined. Glutathione also is the master regulator of all your detoxification. Being able to boost your glutathione levels by taking a strain of probiotic bacteria everyday is really a breakthrough in health and medicine. That's a pretty unique, new understanding of one particular strain of probiotic bacteria.

Another thing that's very exciting to me is that, last year in Japan, there was some independent research done on Dr Ohhira's Probiotics which is a brand of probiotics that's produced in a fermentation process that's different than all other types of probiotics on the market. The fermentation process used in the production of Dr Ohhira's Probiotics allows the final product to contain over 400 post-biotic metabolites. This is a real interesting, new viewpoint and insight into how probiotic bacteria work where you've got a probiotic, Dr Ohhira's Probiotic by brand name, that's produced in a multi-year fermentation process -- and I'll explain that in just a moment -- but the end product contains 400 of these post-biotic metabolites.

Let me explain this fermentation process and how these post-biotic metabolites are produced. We start out with big fermentation vats in a sterile warehouse. They start out with 12 strains of probiotic bacteria. Then they, at seasonally appropriate times, harvest and shred dozens of different types of organically grown foods: mushrooms, vegetables, seaweeds, fruits, and so forth. Then the bacteria get to grow and digest and ferment these foods for 3 years before the product is ready for encapsulation. During that 3-year fermentation process the bacteria in those fermentation vats are breaking down the food and producing this wide range of post-biotic metabolites.

With Dr Ohhira's Probiotics, we are not so much impressed by the probiotic bacteria we're delivering. We're really focusing on the delivery of these post-biotic metabolites. We get what we call rapid microbiome restoration because we're not just supplying somebody with bacteria in a capsule. We're directly delivering these post-biotic metabolites. Other companies that supply probiotics, you have a capsule with bacteria in it. Those bacteria haven't done any work yet. It's like a starter culture. When you take those bacteria, they have to go into your system, start to try to find the proper foods that they need so that their metabolic processes can begin to start to produce some of these post-biotic metabolites that are responsible for improving the health of the gastrointestinal tract.

But with Dr Ohhira's, we're directly putting in over 400 post-biotic metabolites. We quickly readjust the acid-base balance and suppress inflammation and start to heal the leaky gut or intestinal permeability problems and have some detoxification capabilities and start to work against some of the allergies that might be present in the GI tract. It's a very fast, rapid way of addressing gastrointestinal problems.

Gazella: Yeah. I'll disclose to our listeners that I actually have been taking the Dr Ohhira brand of probiotics for a lot of years actually now. I have been impressed with the product. You're telling me something very, very new though. I had no idea about the 400 post-biotic metabolites and this delivery of all these post-biotic metabolites. I've always loved the fermentation process and all the organic foods that are put in there in a 3-year period, and there's just so much that I love about the product. This kind of adds a new level of complexity to this particular product. I'd like to stay on the Dr Ohhira product just because I always like to clarify dosages and ... Now, how many strains, again, are in the Dr Ohhira product?

Pelton: There's 12 strains that we use to start the process, but again, I want to kind of emphasize that our product is really what we call a complete microbiome product because it doesn't just have probiotic bacteria. It's got probiotic bacteria plus some of the prebiotic food supply that was present in the fermentation process, and most importantly, it's got this wide range of post-biotic metabolites.

We just redesigned the packaging for Dr Ohhira's Probiotics, and on the new package, there are 3 different arrows that go in a circular direction. The 3 individual areas, the words inside the arrows say probiotics, prebiotics, and post-biotics. The post-biotic arrow is right front and center on the package. We're trying to emphasize to people the importance of this topic of post-biotic metabolites and Dr Ohhira's specifically delivering post-biotic metabolites. There is no other probiotic in the world that we know of that is produced in this multi-year fermentation process that allows the direct delivery of post-biotic metabolites.

Gazella: So as a result, do you dose this differently than you would a typical probiotic? Am I able to maybe use less? How do you handle the dosing of this?

Pelton: Sure. The recommended dosage is 2 capsules daily. I'll give just a little recommendation on some other uses of it. If people have food poisoning and it's very common when people travel, get some bad food, and get sick pretty quickly, then I advise them to bite and squeeze the contents out of Dr Ohhira's and swallow it that way because the capsule in Dr Ohhira's is a patented delivery system where the capsule actually stays hard in the harsh acid environment in the stomach and then it becomes porous in the more alkaline pH in the small intestine. So it preferentially releases the contents in the small intestine. But if you've got food poisoning, if you've got bad bacteria directly in your stomach, you want to bite the capsules, squeeze the contents out so it gets directly into your stomach and start to fight the bacteria locally in the stomach. I have people who chew 5 to 10 capsules and do it every 20 or 30 minutes, and it clears food poisoning out very quickly for most people.

Another thing to emphasize is that, in the fermentation process, the bacteria learn to grow and thrive and survive at room temperature. Dr Ohhira's does not need to be refrigerated. That's a very nice user-friendly part of Dr Ohhira's. Also because of this patented capsule design, you don't have to worry about food. It can be empty stomach, can be with meals, after meals, makes no difference. Main thing is everyday get them in. If I'm working with somebody that has Crohn's disease or colitis or irritable bowel syndrome, some of these really serious GI problems, I personally suggest they try taking 5 to 10 capsules daily, maybe 5 capsules twice a day for a period of 10 days or longer until you start to get improvement because you want to power these post-biotic metabolites and start to accelerate the change.

Some relatively new information, SIBO is a condition that is getting a lot more press these days, becoming more recognized as a fairly widespread condition. SIBO stands for small intestinal bacterial overgrowth where you have bad bacteria that normally reside in the colon, but they backed up into the small intestine and then they digest foods there. They're in the wrong location in the GI tract. They produce a lot of gas and bloating and diarrhea. So a lot of people with SIBO can't tolerate probiotics, but with Dr Ohhira's Probiotics, we're not primarily delivering probiotic bacteria. We're delivering the post-biotic metabolites. Many people on SIBO will find that Dr Ohhira's is very helpful.

Gazella: Interesting. An interesting note too, it doesn't taste bad. I've actually opened up the capsule and put it on a little part of my gum.

Pelton: I'm glad you brought that up, Karolyn, because that's another recommendation I make. There are a couple of dentists that make this recommendation, and I myself do it personally. Several nights a week at bedtime, I will take one capsule and bite it in my mouth and squeeze the contents out and swish it around in my mouth before swallowing it. This helps support a healthy oral microbiome. It helps to suppress gingivitis and periodontal disease and things like that. We're not calling it a treatment for these conditions. You're just trying to support the health of your oral cavity and a good healthy oral microbiome.

Gazella: Yeah, absolutely. Probiotic supplementation and probiotic science has really come a long way. There was a time when we thought that all you had to do is eat a little yogurt and you're good to go. Then there was the exciting research regarding prebiotics and synbiotics. Now, there's this topic of post-biotic metabolites. What does the future hold when it comes to this exciting area of study that seems to be moving quite rapidly?

Pelton: Well I think the future is in post-biotic metabolites because ... In fact, even pharmaceutical companies, drug company industry is starting to look at post-biotic metabolites and realizing that there's potential for them to develop new drugs on these naturally occurring compounds that are produced by your probiotic bacteria. These are compounds that are natural to the human body. It's not like they're putting a foreign chemical into your body.

As I mentioned earlier, Dr Mayer, in his book The Mind-Gut Connection. He's telling us that your probiotic bacteria produce hundreds of thousands of metabolites. I think the future will be less emphasis on just trying to name and identify strains of bacteria, but learn more about what are the compounds, what are the post-biotic metabolites that these bacteria make, what are the health regulatory effects of these compounds, which bacteria are more efficient at producing these compounds.

I think that's really the new area, new era, new frontier of microbiome research. It really is very exciting because we're really starting to understand that the microbiome is the foundation of your health at all levels. There's a physician by the name of Alessio Fasano who discovered the primary cause of leaky gut and intestinal permeability which happens when you have inflammation, it opens up your tight junctions in your GI tract and allows toxic things to leak into your system. Dr Fasano says that 2 main causes of inflammation and leaky gut are gluten and bad bacteria. I recommend that everybody be on a gluten-free diet. Then we need to clean the gut up.

I did a presentation a month ago at the American Association of Antiaging Medicine Conference, and my topic was Natural Therapies for ADD and ADHD. One of my primary messages is scientists are looking for the answers for autism and ADD and ADHD in the brain. Don't look in the brain. The answer is in the gut. We have to heal the gut and heal this intestinal permeability problem because if you have leaky gut, you have leaky brain. We mean your blood-brain barrier is leaky and some of these toxins are getting into your brain. You have gut inflammation. You have brain inflammation.

We have to focus on the gut, and one of the most serious worldwide health dilemmas right now is the rapid rise in antibiotic-resistant bacteria. Many of the people listening to this probably are familiar with MRSA, methicillin-resistant Staph aureus. There's hardly any antibiotics that are effective against it anymore. Now, we've got antibiotic-resistant [inaudible 00:29:33] and antibiotic-resistant tuberculosis on the rise. We have to understand that we have to reduce our reliance on antibiotics and increase our reliance on good bacteria. We need more bugs, not drugs.

The rise of antibiotic-resistant bacteria is a global health crisis, and you don't want to have a weak immune system and wait until you get sick because scientists are talking about a post-antibiotic era where antibiotics are not going to be effective anymore. We won't be able to have Cesarean births and we won't be able to have our appendix out or our teeth cleaned because, if you get an infection, you're dead. The answer to the problem is to have a good healthy diet with lots of fiber-rich foods to create a diverse microbiome which gives you a healthy immune system. That's the way to stay away from all these antibiotic prescriptions. That's my little rant on that topic.

Gazella: No. It makes a lot of sense. I have to say that human microbiome research is fascinating and so important. This new research on post-biotic metabolites resulting from probiotics just really adds a lot to the conversation that we need to have about -- excuse me -- the human microbiome. Don't you agree?

Pelton: I agree totally. I think this is the next level of understanding of how and why the microbiome is important and gives people a little bit more insight into why it's so important to learn how to create and maintain a healthy microbiome so you can have many different types of bacteria producing all these health regulatory post-biotic metabolites so that, in turn, you will have a healthy immune system.

Gazella: Absolutely. Well this has been a great interview with a lot of great, important information. Once again, I'd like to thank the sponsor of this interview who is Essential Formulas Incorporated. Thank you, Dr Pelton, for joining me today.

Pelton: My pleasure. Nice to be with you, Karolyn.

Gazella: Have a great day.

Pelton: You bet. Bye-bye.

This paper is part of NMJ's 2018 Microbiome Special Issue. Download the full issue here.

In this interview, naturopathic physician and probiotic expert Donald Brown, ND, discusses the role of probiotics in supporting the gut microbiome. Brown also describes the mechanisms of action and clinical applications of probiotics, as well as strains, dosages and potential contraindications.

About the Expert

Donald J. Brown, ND, is one of the leading authorities in the USA on the safety and efficacy of dietary supplements, evidence-based herbal medicine, and probiotics. Brown currently serves as the director of Natural Product Research Consultants (NPRC) in Seattle. He is a member of the Advisory Board of the American Botanical Council (ABC) and the Editorial Board of The Integrative Medicine Alert. He was a member of the Board of Directors for the International Probiotics Association (2008-2010) and its Scientific Advisory Board (2006-2008). He has also previously served as an advisor to the Office of Dietary Supplements at the National Institutes of Health. Brown is the author of Herbal Prescriptions for Health and Healing (Lotus Press, 2002) and was a contributor to The Natural Pharmacy (Prima Publishing, 2006), the A-Z Guide to Drug-Herb-Vitamin Interactions (Prima Publishing, 2006), and The Textbook of Natural Medicine (Churchill Livingstone, 2006).

About the Sponsor

Founded in 1979 by molecular geneticist Stephen Levine, PhD, Allergy Research Group® is one of the very first truly hypoallergenic nutritional supplement companies. For nearly 40 years Allergy Research Group® has been a leading innovator and educator in the natural products industry. Our dedication to the latest research about cutting-edge nutritional supplements continues to this day.

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Transcript

Karolyn Gazella: Hello. I'm Karolyn Gazella, the publisher of the Natural Medicine Journal. Today we are exploring the impact that probiotics can have on the gut microbiome. Before we begin, I'd like to thank the sponsor of this topic who is Allergy Research Group.

My guest is naturopathic physician and a leading probiotic expert, Dr. Donald Brown. Dr. Brown, thank you so much for joining me.

Donald J. Brown, ND: Hi Karolyn. It's a pleasure to talk to you. It's been a long time.

Gazella: I know.

Brown: How are you?

Gazella: I'm doing great. I know. This is like old times. And you know, before we dig into this topic, I have to tell you that I am just fascinated by the human microbiome, and it seems like the research in this area has really exploded. Why is that?

Brown: Well, I think, again, it's ironic as a naturopath talking about it because we've always talked about the impact that the intestinal tract has on health in general. Immune health, skin health, so forth and so on, and I think that what's happened is that particularly probiotic research has led us to realize that there's these microbes on our body. And we have a tendency in probiotics to focus on bacteria, but what's exploding in this area is that we have resident microbes that are viral microbes. We have fungal microbes that are natural inhabitants of our body.

So looking at this, we're really talking about 40 trillion microbes, predominantly bacteria, and sort of the balance that we have with these microbes which are part of our body. And it's funny because the research [inaudible 00:01:54] dramatic, and we have 10 times more microbes on us and in us, mainly in us, than we have cells. And the new data is really indicating that that's not the case; it's about 1.3 to 1.

So people who get itchy when they think that they have more bacteria on them than cells, it's not quite as dramatic as we thought. Again, I think it gets back to the fact that we're recognizing the fact that these things play such an interesting part in our health and our wellness, and when it tips in the wrong direction, our illness too. So expanding it out so we're not just looking at the microbes in the GI tract, but the microbes in other parts of our body as well.

Gazella: Yeah, I think that's really some of the most interesting parts of this research is that it does expand beyond the intestinal tract. So as it relates to the human microbiome, remind us of the mechanisms of actions that probiotics have. How and why do probiotics even work?

Brown: Well, probiotics ... When you think about the GI tract, the analogy I like to use, especially when I'm talking to the public ... talking to healthcare professionals here ... is it's sort of like a busy parking lot. And you have organisms that are health promoting, and then you have organisms that are potential pathogens, and they're looking for parking spots. Remember that bacteria ... viruses are the same way ... have to adhere to cells to be able to be either health promoting or disease promoting.

So that's one of the first things that probiotics are doing is they're competing for spots. And once they actually set up house, they then start creating a micro-environment that is inhospitable to potential pathogens, producing things that are anti ... compounds that are antimicrobial. They alter the pH slightly to make it inhospitable for these microbes and really create a situation where, "Hey, this is our home. This is our neighborhood, and you're not welcome here" kind of a thing.

The other thing that should resonate with most of the doctors on the phone is the whole idea of leaky gut and intestinal barrier function, too. It's one of the things that probiotics do once they set up house is they're also helping to produce mucin and to sort of keep those tight junctions in the intestinal tract, the cells healthy and intact. And that's very, very important.

The other thing that they do is they also, in the colon, are producing short-chain fatty acids which are associated with reducing risk of cancer as we age. Production of short-chain fatty acids act to help with digestive health as well. And then one of the really interesting things that's really been discovered over the last, I would say, eight to 10 years, is that when these little bacteria actually bind, they're communicating through the intestinal wall with what are called dendritic cells which are funny-looking, little, sort of odd-looking starfish type things that send little feelers up through the ... into the epithelial cells. And the probiotics are actually communicating with them to sort of modulate the immune system. So they produce a little bit more of this, produce a little less of this. Inflammatory responses are also modulated through it.

And then the last thing and one of the really, really interesting things right now is we're beginning to realize that the intestinal tract is communicating with the brain. So the gut-brain axis is what that's called, and we know that stress, for instance, can actually negatively impact the probiotics in the GI tract, the healthy bacteria in the GI tract, and in turn, through the vagal nerve going up to the hypothalamic-pituitary axis, actually modulates that response.

So we're now finding out that probiotics may actually be involved in ... I'm sure you've done interviews where you talk about the HPA axis and stress response. We're now finding out that the GI tract is very, very directly involved in that. So it could be negatively impacted by stress but can also positively impact the HPA axis, which is a whole new mechanism of action which is wild.

So we've got gut health, digestive health. We have immune health based on responses with the GI tract. Now we're finding out that there's actually effects on mood, stress response, that sort of thing. And that's not even covering the female genitourinary tract which has its whole population of probiotics that are positively affecting genitourinary tract health as well, so it's big. It's a vast influence on the body.

Gazella: Yeah. There is a lot going on here with probiotics. I think that's why I like the topic so much because there's just so much to talk about.

So when we're looking at the scientific literature and the research, what conditions have the most compelling research in terms of improved outcomes? I realize that this may be a pretty long list, given the mechanisms that you've just described, but take us through that list from a research perspective.

Well, I think what I like to do is I like to start with the things that are accepted by the larger medical community. And one of those is the fact that we've known for a long time that probiotics have a positive effect on prevention of antibiotic-associated diarrhea. So I would put that probably at the top of the list of, hey, if I'm in a room and I've got people who are skeptical of alternative medicine, integrative medicine, that's always a good starting point because we have really solid data that antibiotics definitely are good at preventing that.

My background is in pediatrics, and I think another area that has sort of reached a critical mass is actually ... it's fascinating ... is the prevention of atopic dermatitis in children who are potentially at risk. The studies started ... First one was in the Lancet in early 2000s, and basically the studies are looking at mom particularly but also whoever the partner is, and risk of ... that have a background of atopic diseases, allergic diseases, and actually starting to give mom probiotics during the second half of her last trimester. And then once the baby is born, if mom's nursing, continuing to give the probiotics to the mom until she stops. And then, anyway, it varies on the study, but usually then the infant starts to take the probiotics.

What they're finding is that it's reducing the incidence of atopic dermatitis by about 50%. That's amazing to me because if you look at sort of tracking the use of the antibiotics in children on a graph and you look at the increase in atopic diseases, so you're looking at eczema, atopic dermatitis. You look at asthma. They track almost exactly if you look at from 25 years ago to now, they track almost exactly. And also cesarean births contributing to that as well where the microbiome, so that's really fascinating to me.

I would say the other area, sort of shifting gears, that I think has reached a critical mass is also adjunctive use of probiotics in female genitourinary tract health. So treatment using standard treatments for things like bacterial vaginosis would probably be the top area, but also prevention of recurrence of urinary tract infections.

We're, particularly in the bacterial vaginosis area, I think really reaching a point where we have enough data to sort of suggest that, hey, using these things really can help with prevention. And then I would probably put the last one, as we move into the immune system and we really have reached a critical amount of data. Not a lot of pediatric data but adult data now that suggests that routine use of probiotics seems to reduce the incidence of upper respiratory tract infections. So, again, I could go on and on and on.

Gazella: Right. Yeah.

Brown: There's a lot of stuff. There's a lot of stuff that's emerging and that we're sort of on the edge.

But one of the things I think the listeners need to know about is the fact that I think we like to think about alternatives too, but one of the great things about probiotics is that adjunctive use. Obviously it's antibiotics, but Helicobacter pylori, for instance. The standard treatment of that is very rough on people. Recurrence rates are really high, so one of the themes that I always like to talk about when I talk in my lectures to healthcare professionals is that remember that a lot of the treatments that we use for ... Let's take urinary tract infections. E coli are really good at setting up what are called biofilms that are these little bits like taking a Visqueen sheet and putting it over themselves so that you can get to use the antibiotics. You can get to the ones that are not underneath the protective shield, but the ones that are under there don't get affected.

So one of the things that probiotics are great about is going in and helping to break up that biofilm and actually make standard treatment perform better, and then continuing to use the probiotics actually reduce recurrence rates. So, and there's reduced recurrence rates, and there's a whole litany of examples of areas where if we use probiotics. I mentioned helicobacter pylori but also UTI's, bacterial vaginosis, where probiotics actually help the treatment go better, outcomes are better, and then really reduces recurrence rates.

Gazella: Yeah. That's such a good point and you know, you mentioned antibiotics and how they disrupt gut flora and how probiotics can help reverse that dysbiosis. Are there other medications that kind of do the same thing as antibiotics where they disrupt that gut microbiota diversity and that probiotics may be able to help reverse that?

Brown: We're thinking that some of the more aggressive inflammatories that people take may have an affect. That's still sort of in the early phases. One of the early ones, interesting ones that there's still a limited amount of data, but I actually reviewed it, was a study with a proton pump inhibitor, so things that we're using for reflex and that sort of thing, having a very negative effect on the microbiome. So, we're sort of still in the early stages of learning what specific drugs and the effects are. Obviously antibiotics would the be the easiest case study, because we can actually look at the what affects. They've done studies with people who are getting the triple therapy for helicobacter pylori and realizing that during that therapy, the healthy bacteria in the G.I. tract can be reduced by as much as 80%. If we use probiotics, during that treatment, it reduces that to 40 to 50% and then if we continue to use it after, people tend to bounce back quicker. There are other drugs that we know are beginning to emerge that have negative effects, but stay tuned on that one.

Gazella: Right. Right. Now, let's switch gears and talk little bit about strains, because I know that that's a hot topic. So, specifically for the conditions that you mentioned in helping to restore gut microbiota that's been disrupted by medications like you were just talking about, what are the more common strains used for these types of clinical applications?

If you don't mind my backing that up, I am very, very disturbed when I hear people lecturing who say that strains don't matter. I go to a lot of international conferences. I sit on committees that set standards, international standards for probiotics and it is something that experts who know a lot more about this area than I do are upset about, because there are people out there who are saying that it's species specific and strains don't matter. I beg to differ.

I think that it's very, very important that health care professionals realize that, particularly health care professionals realize that ... and Karolyn, you've known me for a long time. We've done interviews about [bontanical 00:16:20] medicine that I'm an evidenced based person. I like to see the ... particularly if we're talking about treating a condition. And so when we go from species level where there's very little research to strain level, we emerge into an area where we know what the dosage was, that was used in the study. Particularly when we talk about pediatrics, we talked about people who might be immune compromised. We talked about older folks like myself. It's important also to ... safety is pertinent too and that's one of the areas that is a little bit of a red flag for me with the whole probiotic area. Particularly on the commercial side where we have this race to do all these different things and some of the species level stuff that's being sold has not been clinically studied.

And so, very, very important that people realize that some of the standards that go around a strain or viability is the lack of bacillus or the bifidobacterium strain that you're using shown to be viable. Does it actually adhere in the intestine is one of the things that we now have the ... within the persons body, but we now have technology that can actually show that these things sort of do adhere, and how long they adhere, and how long they stick around.

Another thing that's really important that I've given many lectures to health care professionals is they don't think about is that we also don't want these strains, what's called trans located, we don't want them to go from the intestine to the blood stream. And they're having case studies. There was a paper published a number of years ago on people who were really severely immune compromised where the probiotic that was being ... it was a specific strain actually trans located into the blood stream and caused sepsis. People then had to be treated with very aggressive antibiotics. So, we don't want them to go from the intestinal tract into the blood stream.

Another one that's [inaudible 00:18:39] ... we're talking about antibiotics, I always chuckle when I remiss on this one is also we realized that hey, probiotics are good for people who are taking antibiotics, but we also want to be sure that the probiotics strain has been tested for not blocking the ability of the antibiotic to do it's job. So, it's called antibiotic resistance. And it can be transferable. They have run into organisms that we think are probiotics that actually have a negative effect on an antibiotic doing it's job, so that's important.

I already talked about safety and efficacy. I'm all about that. A silly one that I just want to toss in that's talked about internationally, that I still bump into in the U.S. more so than in other areas is the fact when we talk about being a probiotic supplement, we want to look at the label, and we want to be sure that these stability, or the shelf life of the product is actually been proven to the time expiration. There are still a lot of probiotic products that are sold in the United States that actually declare their potency at the time of manufacture, which is like, well okay, but I have a vitamin C product. They told me the potency when it was manufactured, but it says it has a two year shelf life. Have they actually tested that? Has that actually been proven? And so, remember, these are living organisms. Very, very important that stability or shelf life be proven for these as part of the choice of picking a supplement. 

Gazella: Well, I was just going to say, do you have some go to strains that you like to focus on when it comes to recommending probiotics?

Brown: I think there's a lot of them right now, actually. That's another area where we could probably go on and on about. There are what I like to call legacy strains that have been around for a while that have a lot of research on them that have ... and we also understand their mechanism of action really well. The one that people probably know the most is lactobacillus GG, which is a rhamnosus strain that was discovered by a couple of guys in Boston. I always like it when they give their own name to the strains. It was Gorbach and Goldin I think were their names, so they named it lactobacillus GG. But anyway, that one has been around for a long time. A lot of really, really excellent research. Some of the bifidobacterium strains from Japan from [Morinaga 00:21:24] is the name of the company, have a lot of research, particularly in the pediatric area. Been around really since the ... lactobacillus GG, since the early '60's, the Morinaga [inaudible 00:21:38] really since the '50's. The Japanese were doing isolation in human studies long before we were doing them here in the U.S.

Brown: Another one that I really like is lactobacillus acidophilus DDS-1. It's an interesting strain that was discovered by a guy named Dr. [Shahani 00:21:56]. By the way, all of these strains that we're talking about are derived from humans. These are human derived strains and this one was actually discovered and isolated first in 1959. And like the lactobacillus GG and some of the Morinaga strains has a lot of clinical research. It also ... in vitro research that shows that it adheres, that it survives. And then human trials, actually looking at it's ability to treat things like travelers diarrhea, prevent antibiotic associated diarrhea, those sorts of things.

When I look at products, I always look at what's the indication? What's been studied? There's commercial strains the lactobacillus, I'm sorry rhamnosus HN001, for instance, in the atopic dermatitis prevention area that has phenomenal studies. And so there are a number of strains out there that have reached that critical point of whether its specific to one condition or have been looked at in other areas that have really excellent data. And again, being somebody whose background was in pediatrics, I'm always also looking at what's your safety data as well. That would be an example of a few strains that I think have really excellent data.

Gazella: Yeah. That's good. And you know, not that long ago, we were seeing maybe just one or two species, one or two strains. Now we're seeing multi species, multi strains in these formulations, sometimes six, nine, twelve different species or strains in one formulation. Is that a good thing?

Brown: Sometimes it's a commercial thing. Here's my theory and I could easily be misproven [inaudible 00:23:58], but or unproven. Are you misproven or unproven? Which-

Gazella: I'm not sure.

Brown: Called out for my lack of proof. My answer to that, when I get asked that, and it's more common when I'm lecturing to the public or to managers of supplement sections is that probably for wellness purposes. So if I'm taking a probiotic or if I'm a doctor and I'm recommending a probiotic supplement to be taken daily, I probably would use something that's a little bit more of a multi strain. Sort of a balance between the lactobacilli family and the bifidobacterium family. That's a sort of my go to. And as you get into the senior population, seniors have a tendency to have a drop in the bifido. That's probably dietary related, because fiber and that sorts of things, they like to feed on ... They're probably eating less fiber in their diet.

But anyway. Having a balance of a number of strains, is there a magical number of strains? I don't think so at this point. I don't think anybody's proven that. I think the difficulty ... what I say to people is, is that when you shift, it's much easier to talk about a single strain or a combination of a couple strains. You know, in irritable bowel syndrome, inflammatory bowel disease, BSL-3 has eight different strains in it. I mean, that's a lot of strains. It's been around for a long time. They use very high doses, but its easier to look at disease endpoints when we do a clinical trials, because we have very clear outcomes that we're looking for compared to what's a placebo, for instance, Wellness studies are really hard to do, so I don't know that there's an easy answer to your question because I don't know if the company after I ... know a lot of them, and some of them have a lot of ... have deep pockets. I don't know who's gonna do a wellness study that shows that, "Hey, if you do this many strains at this potency, that it works better than if you only do one strain at this potency, or if you do nothing." 'Cause those are expensive studies to do.

Gazella: Yeah. Totally. And I'm gonna ask you another unfair question, and it's regarding dosage. You know that can be somewhat controversial, still debatable. How do you dose probiotics or recommend ... What's your philosophy on the dosage?

Brown: Well, I always start with what is the clinical. If I'm treating a specific condition and I'm using an evidence-based strain I dose it at the dose. And it's interesting, 'cause there's extremes and that's one of the issues when we look at meta-analyses that have been done, so stuff like say, not only was there this cacophony of strains that were used, going from one strain to five strains. That sort of thing. But the dose, the potency and we measure the potency of probiotics, what are called colony forming units so we talk about milligrams or gram amounts of these things. So I always try to look up with what the research showed.

Again, leading back to wellness and sort of, regular use. I have a patient who's take a multi-vitamin, who's taking fish oil every day and I say, "Hey, one of the things you should think about is keeping your intestinal tract healthy and probiotics are gonna contribute to that, keeping your immune system healthy." I don't have an easy answer for that.

I typically use multi-strains and I'll probably usually go in the 10 to 50 billion CFU per day. Is that correct? Is there clinical data to back that up? The answer is no, I don't know for sure. But that's sort of how I think.

The one thing that I can tell you is that I remember a client who decided to go high potency and high potency is definitely [inaudible 00:28:23] was like 25 billion CFUs per instance, it was like a shot across the balance. It was 12 years ago. And I'm freaking out because [inaudible 00:28:33]. You can't go run 5 billion CFUs per day or people gonna be having a [inaudible 00:28:41] reaction or getting thrown out of dinner parties 'cause they're farting and having to go to the bathroom all the time.

So what I can tell you is that we have enough data now in healthy people that if we go to, even, 100 billion CFUs per day that we're not seeing any adverse effects. We're usually with this ... How much of that is actually ... adhering how much of it is actually having an impact versus 40 billion, 50 billion or even 10 billion for that instance. So that's another one that's gonna be interesting to see how that evolves. There's obviously, particularly on the retail side in this race to see who can come out with the highest potency with most strains and we'll see how that goes.

Gazella: Right, yeah. Well, I think that was a difficult question and you answered it brilliantly. So now it seems like many probiotics on the market are actually synbiotics because they combine pro and prebiotics. Now, what's your view about this combination and why are more companies going in that direction? And am I right, are companies going in this direction?

Brown: Well, here's my criticism of that and I like synbiotics. I think the whole concept is an interesting one. On the retail commercial sense, it's been difficult for consumers to wrap their head around a probiotic and then also there's this concept called prebiotics and then again for people who are listening, a prebiotic is basically something that acts as a food for probiotics to feed on and grow and encourage growth even on their own.

The issue that I have with a lot of products that combine probiotics and prebiotics, whether it's FOS, GOS, XOS now is another one that's used. Now these are basically complex sugars. Really, for all intents and purposes, kind of fibers. All of the FDAs now said that they are probably not gonna qualify to make the cut.

The problem is that if you look at the studies on the prebiotics, the dosages are way higher than what you're gonna put into a capsule.

There are some probiotic products that I've seen that have ... that are powders or that are in the sachets where you can actually get the prebiotic up to a dose that actually has any meaningful effect clinically.

So remember with prebiotics, we're rack out a low of a gram and many of the studies were as high as 10 to 15 grams. So again, really important to sort of ... And I know this is a challenge for people who are in clinical practice because they're trying to treat some patients with what they think is the best, but it's really an issue of, again, getting back to sort of ... Does the company make an attempt to sort of match up the dosage of the prebiotic that actually showed an effect, a positive effect on probiotics? And that's a challenge. That your delivery yet [inaudible 00:31:50] in capsules, it's under dose. You don't get enough of the prebiotic.

Gazella: Yeah, that's really interesting because I was not aware of that. So, that's a good heads up there. Now you talked about safety, but are there any contraindications that clinicians should be aware of? Direct contraindications that says, "This patient should not be on probiotics"?

Brown: The area that I'm most cautious about ... I used to think it was premature infants, very low growth weight infants, but there's been enough research. When you ask, probably why the other thing too, that would be our [inaudible 00:32:24] list of things that have really reached critical masses, prevention of what's called Necrotizing Enterocolitis and in very low growth rate entrance ... fascinating and it worked. It's basically saving lives is what we are talking about. The death rate from that is quite high. So used to saying, "Hey, these kids are born ... GI tracts not really developed." That's a potentially dangerous use in that population.

The answer to that is "No, actually. It's actually good." I would still continue to encourage on healthcare professionals to be very selective in strains that they use in people ... HIV positive, AIDS, people with really severe immune deficiencies. Cancer patients who ... technically more advanced cancer. Be very selective and try to get to the best of their possibility, look at the data and say, "Okay, this is strain that actually was used in that population and works." That would not ... Those two populations are ... that collection of population severely immunocompromised people is not one that I could, probably just use any probiotic supplement. Particularly multi-strain, high potency without doing any sort of research.

I'm very selective and usually do one strain or two strains in that population that I feel have enough safety data.

Gazella: Yeah, that's good advice. Anything else that you'd like to add on the topic of probiotics for listeners that you'd like to leave them with?

Brown: Again, I just think that it very, very important to first and foremost, and I'm repeating myself. First and foremost look at if you're using it for specific use. We didn't even get into female genital urinary tract health nursing. Really amazing stuff going on in that area. Your oral use of probiotics to actually, finding that they're populating in the vagina and that you're getting significant effects, which is amazing. We used to think you'd have to use everything with ... through a vaginal, pessary type of an effect. So that's it.

I think again, trying as much as possible to deal with companies that are trying to ... that are working with strain suppliers or strain suppliers that are manufacturing products for them that are looking at the essentials that we talked about at the beginning. It's really, really important to me. And also again, trying to insist that companies refer back to the data on specific strains as opposed to just saying "It doesn't matter, you can use anything you want." I'm horrified when I go to professional lectures and I hear ... For instance, medical doctor getting up and saying that it's [inaudible 00:35:14]. So it goes against every thing that is accepted in the probiotic world. So, again, a lot of white noise in this area. Healthcare professionals are going to be as susceptible to it as consumers are but that's a couple of areas where I think you can sort of cut through that and try to get to what really has been shown to be effective and safe.

Gazella: Yeah. I mean, it's a big topic for sure. We're going to have you back to dig in a little bit more deeply on some of these topics, but I want to thank you for definitely shedding some light on this important topic, and helping us get through it. And I'd also like to once again thank the sponsor of this topic, who is Allergy Research Group. So Dr. Brown, thank you again for giving us all this wonderful information and I hope you have an awesome day.

Brown: Thank you Karolyn.

This paper is part of NMJ's 2018 Microbiome Special Issue. Download the full issue here.

In this interview Natural Medicine Journal's editor-in-chief, Tina Kaczor, ND, FABNO, and Steven Sandberg-Lewis, ND, DHANP, discuss the integral role of the gut microbiota in mood and cognition. A review of how the gut and brain communicate through both the nerves and gut microbial metabolites is discussed. They also talk about how intestinal permeability and brain permeability are associated and what you can do about it. As a naturopathic clinician with over 40 years' experience, Sandberg-Lewis shares some clinically useful pearls along the way. 

About the Expert

Steven Sandberg-Lewis, ND, DHANP, has been practicing since 1978, teaches gastroenterology at National University of Natural Medicine and has a private practice at 8Hearts Health and Wellness in Portland, Oregon. He lectures, presents webinars and interviews on issues of digestive health.

He is the author of the medical textbook Functional Gastroenterology: Assessing and Addressing the Causes of Functional Digestive Disorders, Second Edition, 2017. His column Functional Gastroenterology Bolus appears regularly in the Townsend Letter.

Within gastroenterology, Sandberg-Lewis has special interest and expertise in inflammatory bowel disease, irritable bowel syndrome, small intestine bacterial overgrowth (SIBO), hiatal hernia, gastroesophageal and bile reflux (GERD), biliary dyskinesia, and chronic states of nausea and vomiting. He lives in Portland with his wife, Kayle. His interests include mandolin, guitar, writing, and lecturing.

Transcript

Tina Kaczor, ND, FABNO: Hello, I'm Tina Kaczor with the Natural Medicine Journal. I'm speaking today with Dr. Steven Sandberg-Lewis and our topic is the gut-brain axis. Dr. Sandberg-Lewis has been a practicing clinician for over 40 years now and he is the author of Functional Gastroenterology: Assessing the Causes of Functional Gastrointestinal Disorders, and that has come out in a second edition as of March 2017. He's also adjunct full professor at the National University of Natural Medicine. Dr. Sandberg-Lewis, thank you so much for joining me today.

Steven Sandberg-Lewis, ND, DHANP: You're welcome.

Kaczor: Alright, so I think our talk about the gut-brain axis is extremely timely because of the media attention now given to the bacteria and the effect of our microbiome on our physical ailments and I think it's beginning to look at how it effects the brain both cognition and mood as well.

And so, what I'd like to do is really start at the beginning and can you just give us a quick overview of what exactly do we mean when we talk about the gut-brain axis?

Sandberg-Lewis: Yeah, naturopathic medicine seems to always be at least 30 years ahead of the rest of medicine. We've been talking about this a long time but now we have a lot of research to back up what we talk about. So, the gut-brain axis probably has many more players than we're aware of but the ones we know about are, of course, the microbiota, a lot of people call that the 'microbiome'. But it's the bugs. About 100 trillion of them and they are, of course, not just in the colon but in the small bowel, in the stomach, which is not sterile and the oral and esophageal areas.

The true meaning of microbiome is the genome of the gut floor which has way more, at least 100X more genes than the human genome, which is 26,000. And when you put the two together, you call it the 'holobiome', which is the human genes and the microbial gene. But really, you need to do that because they interplay so much and the bugs really control our genome so intensely.

Then there's that whole genetic piece then there's all the, what we call the metabolon. What the bugs and the enteric cells make, all their metabolic products and that includes secretory IGA, short chain fatty acids, lipooligosaccharide, bacterial hormones and neurotransmitters and cytocinesis. We can talk about all those kind of details.

And then of course there's the enteric nervous system speaking to the vagus and the vagus speaking back. And there's the HPA axis and then there's the immune system and the gut. So, it's huge. It's so much talk it's deafening crosstalk.

Kaczor: It is interesting and one of the pleasures, I think, I've been practicing nearly 20 years and I know that you've been practicing over 40 eyras so, it's quite a long time to watch the evolution of thought processes in medicine as well as the population at large.

And in some of the folk medicine even, naturopathic medicine, but good old folk medicine, an apple a day and staying regular and keeping the bowels moving, it's amazing how that comes back at us and now we're talking about it in scientific terms which is fascinating to watch the pendulum swing.

Okay so, when we talk about how they communicate, you gave a little overview of some of the ways, when you mention the vagus system, what do you mean exactly?

Sandberg-Lewis: On every new patient, I like to have them open their mouth, stick out their tongue, take a look at their palatal arch and their uvula and then have them say 'ah'. When they phonate, we've all done this, check the vagus nerve. The place you can check the vagus nerve directly is there in the palate because the levator palatini muscles on either side raise the palate when you say 'ah' and when you phonate.

So, I'd like to see both arches go up symmetrically and not an asymmetrical rod. Occasionally you see nothing. The patient says 'ah', nothing happens. There's no palatal rise and you can have them do it over and over and nothing happens. So, that's a sign that the vagus isn't really firing the way it's supposed to and there are lots of ways to try and improve vegul tone. But that's a good thing to know about your patient.

The next thing is the vagus nerve gets sensory information from the enteric nervous system and the neuroendocrine cells in the gut as well as the epithelial cells. It gets input in actually 90% they assume, 90% of the crosstalk is from the enteric nervous system to the Brian through the vagus.

So, it's mostly the gut talking to the Brian and then the brain through the vagus talks back about 10% of the time. So, there's direct transmission through the nerves and then there's all the cytocinesis and other factors and neuro peptides that also speak through the humoral method.

Kaczor: So, what you're saying is the gut itself is sending signals through the vagus nerve to the central nervous system and effecting what exactly?

Sandberg-Lewis: So, yeah. It's pretty interesting what the gut is interested in talking about. Yeah, you wonder, what does my gut have to say? What does it care about? So, what the gut is saying, the 90% of impulse is going from the gut to the brain, it's talking about the shape and the consistency of the bowless of food moving through and scraping up against the ... rubbing up against the mucosa. The sheering forces of the bowless against the mucosa. That's stimulating serotonin locally but there's also this ... That's what the gut's interested in. Is, what kind of food is it, what's the shape, what's the consistency and what does it feel like as it rubs against the enteric cells?

This seems to stimulate taste receptors on the antero endocrine cells that are scattered throughout the mucosa and give information about the composition of the food, there's, again, there's all these neuro peptides and hormones, GI hormones that are released as well. But directly through the vagus nerve, we think it's mostly the gut talking about it's scratchiness of the food and the size and the consistency and the kind of food.

Kaczor: Okay. And I have to clarify for my own self, when you say 'taste receptors', you're going beyond the tongue? Is that what I hear you saying? Is this "taste receptors" that you say along the GI tract, how does that work?

Sandberg-Lewis: Air quotes, well, our genius in our midst, Paul [Calmens 00:08:18], he's been telling me for years that there are taste receptors throughout the entire gut. And especially most pronounced is the bitter, bitter receptors. And I've tried to go into the research and find out what exactly they do. We don't know a lot about what they do but we know that bitter receptors are not just in the tongue and the mouth, they're throughout the whole gut and they seem to trigger the release when they're stimulated. They trigger the release of ghrelin and glucagon peptide one which have to do with blood sugar balance and hunger and my guess is, Flip Wilson used to say, "The devil made me do it" when he did something that he thought was nasty.

But I really think that in many ways, the GI flora and the food that we eat interact to create cravings so that the body can get what it needs. And if you get more ghrelin, you get hungrier. And certain other, like GLP, maybe you're gonna create more sugar.

It's really important, of course, to eat food ... I think this is why Indies think it's so important to eat foods that's close to nature because once you get these synthetically modified foods or their consistency and their flavor and their compositions is altered, it probably throws off these natural mechanisms that tell us when to eat, when not to eat, when our blood sugar is fine, when it needs to go up or down. So, these are really finely tuned things.

Kaczor: Yeah, it's interesting in context, again, of traditional medicines because it automatically makes me think of Ayurvedic medicine and other traditional practices that naturally balance the flavors on the plate, that's a big part of making sure each meal is healthy in that tradition. So, let's talk about the microbiotas some more.

You mentioned briefly that its metabolites are part of the talk between the gut and the brain, can you elaborate on that?

Sandberg-Lewis: Yeah. First of all, I wanted to mention that the metabolic byproducts, the products of the microbiota, it's huge, it's huge. And Emerson Mayor's book, the gut-brain connection, he makes a quote that 40% of the metabolites in human blood are derived from gut flora, which blew my mind completely.

And so, I said, "Where is he getting that?" And I looked, I found it in two or three different articles. And so, to me, that means 40% of our blood chemistry is derived from the intestinal flora. And that makes sense since there are at least 10-to-1 more of them than there is of us in terms of cells. But I never really put that together.

So, there's these metabolites in our blood derived from the flora that do fine tuning of eating behavior, mod, blood glucose, digestive secretion, absorption, motility, just it's mind blowing. It's so important and it makes sense. You can understand that when you go ahead and even just take a broad spectrum antibiotic, we know that greatly increases the risk of kids and even adults, getting inflammatory bowl disease, especially Crohn's.

Just so many effects on immunity and the balance within the body if we knock down the bacteria or alter them or decrease their diversity. So, pretty important, pretty major stuff that everybody's been messing around with since the 1920s and '30s with antibiotics.

Kaczor: Mm-hmm (affirmative). Yeah and you mention a metabolite that caught my attention because I think it's at least in our naturopathic circles, we're paying a lot of attention to the role of that lipopolysaccaride and the LPS, for short. Can you talk a little bit about that? Because I feel like that's, as far as I can see, getting a bit of attention these days in how the gut and brain effect one another.

Sandberg-Lewis: Yeah well, I'm glad it's getting attention, it deserves it. You know, every physician knows about LPS in one particular way and that is, it is the cause of septic shock. It kills people if the LPS is high enough. What we don't usually hear about and we're starting to get more and more research on is, what about physiological levels of LPS when it's not super high?

Sandberg-Lewis: LPS is used in research, they inject it into lab animals to activate the NF kappa B pathway of inflammation and there's a tremendous amount of it. These are from the gram-negatives. The gram-positives also have an inflammatory precursor like this, which is the peptidoglycan. But, mostly we talk about the gram-negative because it's so potent and there were a million copies or so of LPS in each gram-negative microbe and it's not just something that gets emitted when the bug dies, it's also just when it's replicating or if you take an antibiotic and weaken it a little bit, they don't have to die to give off LPS.

And it's thought that in the adult human gut, you have up to a gram of LPS, a thousand milligrams at any one time. So, it's a major player. There's a lot of it and it can trigger the Zonulin pathway, which leads to intestinal permeability, hyperpermeability, which we know is related to autoimmunity and allergies.

Obese humans have up to a three fold increase in LPS compared to lean and maybe some of that also dove tails with the fact that obese adipose tissue has 10X as many macrofacies. So, you got a lot of esocine activity, a lot of TNF alpha.

Kaczor: Mm-hmm (affirmative).

Sandberg-Lewis: And different types of enteric flora have different amounts of LPS. Or even different potentiates. So, antero bacter are thought to have some of the most potent LPS that can be up to 1,000X more potent than some of the other gram-negative bacteria.

So, this is a major toxin, it's a major provoker of inflammation and pre radical activity in all kinds of changes.

Kaczor: So, how does LPS effect the brain directly? Since, I hear what you're saying and I know even in experimental animals LPS is a common way to reliably instill an inflammatory process in a lab animal. So, it's clearly a very potent, inflammatory molecule. How does it effect the brain?

Sandberg-Lewis: So, the bacteria, we get some bacteria trans locating into the blood but they usually get called out after they travel through the portal vein to the liver by the cooper cells. At least if the liver's working well. You're not gonna have a lot of bacteria in the blood but the bacteria can still effect the central nervous system, even if they don't cross the blood brain barrier and never even get there.

First of all, one mechanism is that LPS and the inflammatory cytocinesis that it induces include interleukin one, interleukin six and I mentioned TNF alpha and they can actually up regulate the transcription of these cytocinesis in certain discrete areas of the brain.

And then one of the things that happens with that is, within the brain you get an up regulation of indoleamine dioxygenase, which is that enzyme that converts tryptophan to kynurenine and that can move further to quinolinic acid, which is neurodegenerative. Although, there's quinolinic acid, which is also has a positive effect.

So, depending on how it goes through the pathways, you can have neuro degeneration up regulated. And studies show that depression, anxiety and insomnia can issue from high levels of quinolinic acid. So, there's that.

There's also cognitive deficits and in my book, very important, is increased visceral sensitivity. All the functional disorders of the GI tract, there is increased visceral sensitivity meaning, people perceive their own motility and movement within the gut as pain or strong discomfort. And man, those patients are strong to treat because if you start to activate their GI tract and get it moving again after it's been atonic for years, then they're complaining that they're up all night with abdominal pain. And that's a tough one, we're trying to learn more about how to deal with visceral hypersensitivity.

But, it's thought that LPS is one of the things that triggers that too.

Kaczor: So, I have a two part question. I guess, in our clinical assessment of LPS, is there a means, I mean, I know that we could do testing for small intestine bacteria overgrowth through breath testing but, is there any blood test, I guess is what I'm thinking? Can you tack on any blood test to gauge LPS levels and the second part of this question is, what do we do about it?

I suppose treating the gut in a totality dysbiosis present, is the short answer. Any clinical pearls are certainly welcome.

Sandberg-Lewis: Yeah. So, you can, this is available, you can measure LPS. You can measure LPS binding protein, I believe as well. And you can, in your patients, you can, of course, measure zonulin, which gets up regulated by LPS. So, yeah. By all means, start experimenting with that and then see if you can get the levels down.

Now, yeah. I'm known for spearheading along with some other really busy physicians and researchers. The treatment and in our case, more the natural treatment, of small intestine bacterial overgrowth, you just can't get away from it. It's so key to, we used to say, "Death begins in the colon" when I was in school in the 1970s and now, I think it makes sense to say, "Disfunction and autoimmunity begins in the small intestine". It's just associated with so much and that includes neurodegenerative diseases, like Parkinson's as well.

A practical thing, yeah. Learn how to test for, interpret and treat ... Use your testing and learn how to treat SIBO. Both the hydrogen, methane and hydrogen sulfide types. And don't throw out the yeast with it either because they often go together and get that metabolite base 40% of the blood. Get it into a functional mode instead of a dysfunctional mode.

Kaczor: Mm-hmm (affirmative). Mm-hmm (affirmative). Yeah. And I know, I will say that, you lecture and write a lot on the clinical aspects of this. So, anyone who wants further information can certainly start Googling you and find lots and lots to followup on. I do want to ask another question because this issue that we are in for the Natural Medicine Journal this month is a special on the microbiota and the microbiome. How do probiotics specially effect the gut-brain axis?

Sandberg-Lewis: I don't know that we have enough yet to really have a great answer. Although, there are some docs out there that really have a strong handle on the strain specific effects of probiotics and people like Jason Hawrelak who is a ND and teaches at Western States and practices in Australia, he has totally got that covered. So, I would highly recommend looking at his website Jason Hawrelak, Hawrelak. But I mean, we know that there are studies that show that fermented foods significantly reduce anxiety, especially social anxiety.

And there's a lot more research going on on strains, specific things that show that there are specific effects on anxiety and depression. But it's still really early so, I can't say I have a really good picture of that. When people ask me about probiotics, I usually say, "I don't know anything about probiotics". They don't believe me but, yeah.

Kaczor: So, is it accurate to say that you advocate the whole foods diet, plenty of prebiotics in the form of fibers and resistant starches and things like that and then trust that if that is done well and consistently and then, of course if there is other treatments to kill undesirable bacteria etc. but complimenting ... I mean, the way to encourage the good bacteria is to give the prebiotics more in your view?

Sandberg-Lewis: Well, the problem is a lot of my patients, because they have overgrowth, they can't tolerate prebiotics and fiber. So, when I first start working with them, we can't really use those things except very specific types. We know that partially hydrolyzed program seems to be actually beneficial for people who have overgrowth, sometimes used along with rifaximin in treatment of hydrogen SIBO and it increases the effectiveness of that.

But, there's some GOS's that that may also be well tolerated. But that's a problem in the beginning because if you have overgrowth and then you feed them with a prebiotic, then it just increases symptoms and problems. So, it's a fine balance, it's a fine balance. But, yeah. I really encourage my patients to eat whatever fermented foods, probiotic foods that they tolerate.

So, we use lactose-free, fermented dairy products, we use pickled items like kimchi or sauerkraut, the real stuff not the fake stuff. The refrigerated kind. Or homemade. And things like that. I think all traditional groups of people around the world have their own probiotic foods. Some of them pretty hard to even relate to, like haggis in ... where is that? Scotland. Where they eat the goat stomach that's fermented. Fish and rotten fish in the northern areas of Europe.

There are some really interesting things you'd think, "Why the hell would people ever invent that food?" But these things have tremendous fermentative capabilities. And one thing that I'm sure NDs understand this but it comes up a lot with patients asking, they'll say, "So, you don't want me to eat any fermented food, right? Because I already have ... You want me on a low fermentation diet". And I say to them, "Well, no that's not what I want you to do". Unless you have a histamine sensitivity and you can't handle foods that are fermented, I want you to use those things because if you eat a high fermentation diet that has carbohydrates that are easily fermented, that produces gases. Hydrogen, carbon dioxide, maybe ethanol, methane, hydrogen sulfide in the gut and causes distention and pain and changes the stools and can cause bloating.

But if you eat a food that is a fermented food, the gases have already come off into the atmosphere in the process of fermentation and now you're just getting all the bacteria and the great metabolites without the gas that causes the symptoms. I think that's an important differentiation.

Kaczor: Well, yeah that's a great way to put it. To help them and us understand it a little bit. One last question, we'll end on a fun question, when you hear the term 'gut reaction to something', because we're talking about the gut-brain axis and someone says, "I used my gut" or gut instinct, gut reaction, what do you think?

Sandberg-Lewis: Well, I'll bet physicians with different backgrounds have different ways of interpreting that but clearly if 90% of the input in the gut-brain axis is coming from the gut and if you think about it, if virtually every neuro peptide and GI hormone that's produced in the gut effects insulin and blood sugar and we know the brain suffers within minutes from blood sugar that's too low whereas the other organs may not care for quite some time and oxygen as well, of course, to the brain within three minutes.

There are major effects on life and death related emotions that take place when the gut is feeling like something is wrong and it's gonna make more jittery molecules instead of more serotonin and gaba.

And that's gonna have very rapid effects on the mood and on the functioning of the person's nervous system.

Kaczor: Mm-hmm (affirmative). Alright well, I sure do appreciate the time you took to talk to us today about this. It is a huge topic and I am excited, as a naturopath that everything is coming back to a source, the GI tract, I mean and we've always been taught that we have to remedy the gut and get that in order before we can really keep someone in an optimal health state.

So, sometimes that's harder than others and I do appreciate the time it took to enlighten us today with the gut-brain axis and it look forward to talking to you probably in the realm of gastroenterology again in the future.

Sandberg-Lewis: Great, let's do it.

Kaczor: Alright, take care.

Sandberg-Lewis: Alright, bye.

In this interview Nigel Brockton, PhD, describes the most recent expert report produced by the American Institute for Cancer Research (AICR). The AICR is a highly-respected non-profit organization leading the charge against cancer globally. This latest report provides a blueprint that practitioners and patients can use to help reduce cancer risk.

About the Expert

Nigel Brockton, PhD, is the director of research for the American Institute for Cancer Research. A two-time cancer survivor, he likes to bike to work every day.

He is a keen skier, cyclist, and cancer research advocate leading the research at AICR to focus on the links between diet, weight, physical activity, and cancer throughout the cancer continuum—prevention, treatment, and survivorship. He combines all of his passions to encourage active lifestyle in the community and support people affected by cancer.

Brockton has been interested in cancer prevention since he was diagnosed with Ewing’s Sarcoma at age 18 (1989) and again at age 21 (1992).

He has a PhD in genetic epidemiology of colorectal cancer risk (Aberdeen, Scotland). Before coming to AICR, he spent 10 years as a Cancer Researcher in Alberta, Canada

About the Expert

Sidney Baker, MD, is a Yale Medical School graduate and former assistant professor of medical computer sciences, Peace Corps volunteer, family practitioner, Gesell Institute director, founder of Defeat Autism Now!, Linus Pauling Award recipient, and associate editor of integrative medicine. He is the author of Detoxification and Healing, The Circadian Prescription, and, with Jon Pangborn, Autism: Effective Biomedical Treatments, and various journal articles. He practices functional medicine in Sag Harbor, New York.

In this interview, naturopathic physician Carrie Decker, ND, describes some of the actions she takes with patients to help reduce the risk of developing dementia and cognitive decline. Her integrative approach includes nutritional and lifestyle assessment, assessment for common risk factors or other potential exposures, and nutritional supplementation to meet her patients' individual needs.

About the Expert

Carrie Decker, ND, is a certified Naturopathic Doctor, graduating with honors from the National College of Natural Medicine (now the National University of Natural Medicine) in Portland, Oregon. Decker sees patients at her office in Portland as well as remotely, with a focus on gastrointestinal disease, mood imbalances, eating disorders, autoimmune disease, and chronic fatigue. Prior to becoming a naturopathic physician, Decker was an engineer, and obtained graduate degrees in biomedical and mechanical engineering from the University of Wisconsin-Madison and University of Illinois at Urbana-Champaign respectively. Decker continues to enjoy academic research and writing and uses these skills to support integrative medicine education as a writer and contributor to various resources. Decker supports Allergy Research Group as a member of their education and product development team.

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Transcript

Karolyn Gazella: Hello, I'm Karolyn Gazella, the publisher of the Natural Medicine Journal. Today we're talking about maintaining healthy brain function with naturopathic physician, Dr. Carrie Decker. Before we begin, I'd like to thank the sponsor of this podcast who is Allergy Research Group. Dr. Decker, thank you so much for joining me.

Carrie Decker: Thanks Karolyn, I'm glad I'm able to be with you today.

Gazella: So we're going to start by having you remind us of the medical definition of dementia, and then tell us how common these conditions are.

Decker: Yeah, so dementia basically is the mental decline and associative changes in memory, mood and even personality which can occur from an acute incident, such as a vascular event or head injury, or be the progressive changes we see with conditions such as Alzheimer's and Parkinson's Disease, or even alcoholism. There are other less common causes of dementia as well.

Not surprisingly, many of these conditions can overlap, particularly vascular and Alzheimer's dementia. The main difference with vasculars and Alzheimer's dementia, is that with a vascular event there will be a more sudden decline and then a fairly stable period compared to the typical slow decline of Alzheimer's disease. With a vascular event you might see a sudden change in personality, mood, language or even motor symptoms. Personality, mood and motor changes also may occur with Alzheimer's disease, but are generally in the later stages and occur gradually.

Vascular or stroke related dementia accounts for 10 to 20% of dementia in the US and Europe. And the most common type of stroke is ischemic stroke which represents roughly 80% of all strokes in the US. There actually is a region in the US known as the stroke belt in the Southeast, which I was unaware of. Multiple studies have found a higher incidents of stroke in this region. Even in well characterized populations such as healthy male physicians and patients born there. There are many subcategories of ischemic stroke and, of course, all are associated with conditions such as a clot or vessel disease which leads to obstruction and reduced blood flow. And with this oxygen, the nutrients to a focal region of the brain.

With a hemorrhagic stroke, which is often associated with hypertension and trauma, blood leaks into the brain and locally increases pressure in the surrounding region. Changes with a hemorrhagic stroke may occur somewhat gradually over minutes or hours, where the intracerebral hemorrhage are very suddenly with a subarachnoid hemorrhage.

Clinically, the course of events helps to diagnose which type of stroke someone had, but brain and vascular imaging is required for diagnoses. Incidents of cognitive impairment in dementia after stroke ranges from six to 32% which becomes clouded with factors contributing to other types of dementia the longer the patient is followed.

Alzheimer's dementia is most common type of dementia. In the age specific incidents ranges from less than 1% in an individual 65 to 70 years of age, to as high as 8% in individuals 85 years in age and older. Early onset Alzheimer and dementia can occur in individuals as young as 30, however this is far less common and usually genetically related or many misdiagnoses and other conditions which can cause cognitive changes.

Gazella: Perfect. So what I'd like to do, is I'd like to focus on Alzheimer's a little bit, because it is the most common form of dementia as you mentioned. So what are some of the hallmark changes that take place in the brain, that can indicate Alzheimer's has set in?

Decker: So all this again is pretty gradual, but the key things that occur in the brain with Alzheimer's dementia, which many people ... the physicians out there, at least will remember from cramming for pathology tests, are extra cellular deposits to amyloid beta peptides near fibrillary degeneration and associated tangles and neuritic plaques.

These are not specifically seen with imaging, but analysis techniques and tracers are constantly being developed that can help us see these changes more specifically. Additional biomarkers that assess for changes in markers related to tau and amyloid beta in the cerebral spinal fluid are also being developed to help determine the risk of cognitive decline and assess for Alzheimer's disease, but are not yet recommended for routine diagnostic purposes.

Brain imaging with an MRI is indicated in the evaluation of dementia and is capable of identifying alternative diagnoses such as the cerebral vascular types of events. Contrast may be used, excuse me, to help visualize the regions of vascular compromise or even an altered blood-brain barrier.

Structural changes seen in an MRI with Alzheimer's dementia include general and focal atrophy, as well as white matter lesions; however, these findings are non-specific.

The most characteristic finding with Alzheimer's disease is reduced hippocampal volume, or medial lobe atrophy, which must be evaluated relative to one's age, as a decrease in volume is normal with aging, as well.

At times, there might be a dramatic reduction in hippocampal volume of over 40%. Positron Emission Tomography, which is commonly called a PET scan, with amyloid tracers can help us determine if there's an amyloid burden on the brain and this helps rule out the likelihood of Alzheimer's dementia if they're not found. But, it's not diagnostic if they are found, because you still have to rule out other types of pathology.

Gazella: Okay, perfect. Now what are some of the symptoms of Alzheimer's disease?

Decker: As most people ... even an untrained non-professional would know, the cognitive impairment is one of the most common signs that we see. Especially, initially, with Alzheimer's dementia. But it may be accompanied by executive disfunction and visual spatial impairments.

Executive disfunction may manifest as difficulties in things like problem solving, multi-tasking, and abstract reasoning. Visual spatial impairment can manifest as changes with difficulties with reading, discriminating form and color, perceiving contrast, and detecting motion.

For the most part, these deficits and changes manifest insidiously.

The memory changes with Alzheimer's dementia involve significant deficits and declarative episodic memory, that is the memory of events occurring at particular time and place, which relies heavily on the hippocampal function.

Memories for recent events are also impaired early in Alzheimer's disease, whereas the ability to recall something that's mentally rehearsed, like an address, is kind of spared early on.

Longer term memories, which have been consolidated and in essence kind of rehearsed over years, are also spared because they don't rely on the hippocampal function. The deficits in immediate recall of rehearsed items, as well as semantic memory, the knowledge and facts we accumulate through our lives, gradually develop with time.

Procedural memory, like knowing how to tie your shoes, can become affected in the later stages. Generally, the earlier changes are described overall, as recent memory impairment. Kind of avoid confusion and language that's often over a patient or caregiver's level of understanding.

Also, with this we might see neuropsychiatric changes, particularly in the mid to late stages of the disease. This can include apathy or depression, irritability or related disengagement.

More severe behavioral disturbances, such as aggression, wandering, and psychosis or hallucinations, also can be seen but really should be evaluated for further other possible causes, such as infection or medication-related toxicity, which is also more common in the elderly.

It is not uncommon for patients to underestimate their deficits and offer alibis or explanations for them when they're pointed out, which kind of contributes to some of the mood-related symptoms, such as irritability for people.

Loss of insight also occurs with time. And, interestingly, those with more insight into their condition are more depressed. While those with less insight are more likely to become agitated, experience psychotic features or perform actions like leaving the house, wandering in their pajamas. Which, if someone had the insight, they were less likely to do.

Seizures may also occur in 10 to 20% of individuals in the later stations of Alzheimer's disease. The seizure type isn't so much a motor one, it's more of a focal non-motor seizure which manifests with impaired awareness, confusing amnesia spells, unexplained emotions, and experience of a metallic taste.

Sleep disturbances are also common with Alzheimer's disease and may occur early in the disease process. This includes the fragmented sleep. It also may manifest as longer sleep. Sleep time generally decreases by 30 minutes per decade, starting at mid-life. So some sleep changes are also normal with aging. Poor sleep also happens to be a risk factor for cognitive decline and dementia, which is important to note.

Gazella: Yeah, it's a devastating diagnosis, there's no question about it. And today we're talking about reducing risk. How do we even know that's possible?

Decker: Whenever I think about risk for any type of disease, I think about, "Well, what are the risk factors?" And if we can associate it with a risk factor, if we deal with those risk factors then we're reducing your risk.

So, from the Alzheimer's disease, specifically risk factors are hypertension, dyslipidemia, and altered glucose metabolism. Each, of course, is treatable. Individuals who are physically active have a reduced incidence risk of Alzheimer's disease and cognitive decline. Exercise, of course, also reduces the risk of these other things; the hypertension, dyslipidemia, and hyperglycemia. So we really can't say enough about that.

Long-term use of certain medications, such as benzodiazepines, anticholinergics, antihistamines, opioids, and proton pump inhibitors, may be associated with increased risk of Alzheimer's disease. So working with patients to discontinue these, if not needed, may really benefit brain health.

Exposure to environmental pollutants, including air pollution, second-hand smoke, or pesticides may put someone at increased risk for Alzheimer's disease.

Chronic infections, such as Lyme disease, also may put someone at risk for developing dementia. That can be mistaken for Alzheimer's disease, but the inflammatory aspect of any type of chronic condition also may play into something that may later manifest as Alzheimer's.

Cigarette smoking contributes to cardiovascular disease and hypertension, both of which are risk factors for Alzheimer's disease.

The high-sugar diet, of course, contributes to the development of diabetes and hyperinsulinemia, which increases the risk of Alzheimer's.

Excessive alcohol use contributes to dementia in its own right and affects memory acutely. Chronic use of alcohol in excess also contributes to hyperglycemia and the nutritional deficiencies, which may also be contributing factors to longer-term memory problems, as well as Alzheimer's.

So, with so many things that are risk factors that are associated with Alzheimer's disease, correcting them inevitably reduced the risk. And then when we start to eliminate many of these factors that are known risk factors for Alzheimer's disease, or at least associated with it, the reduction in risk, of course, compounds as well.

Genetically, there are definitely some things that we're unable to change, per se, but we can still influence the phenotype by addressing environment, nutritional, and other factors which impact it.

Gazella: Well, that's great. And I would like to talk about nutrition and specific diet. You mentioned high-sugar diet as being a possible risk factor. When it comes to reducing risk, what do you like to emphasize and why?

Decker: For me, really that's one of the biggest places to start. Reducing the high intake of high glycemic foods, like the breads, pastas, desserts and sugary snacks, often is one of the first changes that most people need to make.

So often, people are grabbing these things for a quick energy fix because they're easy. And they also come with a blood sugar spike and then a blood sugar crash. Good brain food really includes foods that provide the essential vitamins and minerals, proteins, and healthy fats. Eating a diet that has lots of color, and not the artificial variety, helps people to take in the necessary vitamins and minerals, as well as many other phytonutrients found in fruits and vegetables.

Nuts like walnuts, which provide healthy fats, protein, Vitamin E, as well as other nutrients and salmon, which provides a lot of Omega-3 fatty acids, are particularly good things to routinely include in the diet.

A higher total intake of Omega-3 fatty acids, particularly DHA, is associated with a reduced risk of Alzheimer's disease. DHA helps reduce the amyloid beta peptide accumulation, as well as oxidative damage, which also is a contributor to Alzheimer's.

One more part of that, when you dial really into the diet more, on an individual basis there might be other things that come up, things like the food sensitivities, the allergies, different types of things that cause inflammation. And for some sensitive people, even things that are high in histamine might be something to reduce. Histamine is an inflammatory mediator, which released from basophils and mast cells in the body, like when we have an allergic response, but it's also found in certain [inaudible 00:11:40] like fermented meats and wine. People can become more sensitive to foods like this when the lining of the gut is damaged, or if they have certain genetics related to the breakdown of histamine. Histamine increases the blood-brain barrier permeability, which can contribute to neuroinflammation and neurodegeneration.

Gluten absolutely should be out of the diet for people with celiac disease, as it's been determined in this population, specifically, to contribute to cognitive impairment, as well as nutritional deficiencies. But, not only them, the people who are not affected by celiac disease also can have an inflammatory response and with this foggy thinking, however we don't have research that I'm aware of that specifically connects it with Alzheimer's yet.

Gazella: Okay, so it sounds like a really solid anti-inflammatory diet. In addition to diet, you mentioned exercise. You mentioned sleep. But what other lifestyle factors are critical to look at when it comes to reducing risk of dementia in the patient population?

Decker: Yeah, like I said, exercise is one of those things that just is important for so many aspects of metabolic health, but also has other ways that it improves cognitive function. It's something that supports the levels of brain-derived neurotrophic factor in the body. We shorten that up, calling it BDNF. And that improves neurogenesis and cognitive pathways in the brain. Exercise also has been shown to increase hippocampal and total brain volume, which we already talked about as being something that happens with Alzheimer's disease.

Cognitive stimulating also benefits cognition, and that's been shown in studies. Just something people talk about. So whether this includes reading a book, playing a game of cards, or learning a new musical instrument or other skill, it's important to include.

Eliminating smoking and excessive alcohol intake also should be a part of a dementia protocol. But, also general health promoting advice.

Healthy sleep is important for cognitive function and preventing dementia. So working with lifestyle to make adaptations, such as new blue light or other stimulating things at least an hour before bed might come into play with people if the sleep is poor.

Gazella: So Let's talk a little bit more specifically about nutritional factors and how they might contribute to cognitive decline in Alzheimer's disease.

Decker: Nutritionally, deficiencies or lower levels of certain vitamins, minerals, or other essential nutrients have been shown to be associated with Alzheimer's disease. This includes the B vitamins; B-12 and folate, Zinc, Vitamin D, as well as tocophorols, and tocotrienols. Lower levels of CoQ10, which our body produces, have also been shown in some studies to be associated with an increased risk of dementia.

I believe it's critically important to start with the necessary nutrients, such as these, because their impact in the body extends far beyond just the brain.

Zinc has a critical function in the brain and lack of zinc can cause neuronal death. Low zinc levels are associated with a poor ability to smell and depression. So if these symptoms are also mentioned, screening should be considered.

Homocysteine levels have been observed to be significantly higher in patients with Alzheimer's disease and also can be deficiencies in the B vitamins; folate, B-12, or riboflavin. Homocysteine elevation also is commonly seen in cardiovascular disease and depression. So if these are also an issue for a patient, and even if not really, this should also be considered.

Vitamin D access in your [inaudible 00:14:45] hormone and also impacts genetic expression. Vitamin D levels should be at least 30 nanograms per milliliters and I would recommend even higher, really around 50 nanograms per milliliters. Low levels of vitamin D are also often seen with cardiovascular disease and should be a part of screening for that.

Tocophorols, tocotrienols, and CoQ10, they're all fat-soluble, neuroprotective antioxidants and they're also cardio-protective. They support not only a healthy brain, but they reduce the risk of cholesterol oxidation and they support health vessel function, which can help reduce the risk of the vascular dementia, which we talked about earlier as well

Gazella: What about other botanicals or natural substances? Are there any others that have evidence supporting cognitive function and helping reducing risk?

Decker: Yeah. There's so many that I kind of got into thinking about some of them and there's way too many to discuss. But, I'm looking at ... I wanted to talk about some of them with the biggest evidence that I've seen.

So because inflammation plays a role with Alzheimer's disease, we talked about that with diet. Some different therapies, which can help reduce inflammation like oxidative shots, can be helpful. But some other mechanism-like things like essential fatty acids also may improve dementia.

When we talk about managing inflammation with natural substances, curcumin, the active compound found in tumeric is often at the top of the list. And it comes into play here, too. Curcumin has been shown to improve working memory, attention, and reduce cognitive decline in healthy elderly patients. Curcumin has clinical evidence it helps reduce depression, as well. Which, again, is common with Alzheimer's disease.

Mechanistically, it has been shown to reduce oxidative stress and accumulation of the beta amyloid plaques, at the same time reducing our increasing levels of protective antioxidants, such as superoxide dismutase.

Of course, making sure the curcumin is bioavailable is very important. The best data I've seen comparing a lot of the [inaudible 00:16:35] curcumin preparation suggests that the best bioavailable can be obtained with a molecular dispersion process that then answers the water solubility and dispersion of fat-soluble ingredients, like curcumin.

With this type of preparation, it's been shown to be even six times higher absorption than the more commonly used curcumin phytosome that's found in many supplements.

Another one that has a lot of evidence behind it is Huperzine A. Huperzine A is an extract from the club moss and it acts as an acytlcholinesterase inhibitor, which also happens to be one of the mechanisms of many drugs which address dementia. Huperzine A also may help reduce dementia by regulating production of beta amyloid precursor protein, protecting the cells from oxidative stress, mitochondrial disfunction, as well as damage associated with glutamate induced toxicity.

Glutamate's an excitatory neurotransmitter in the brain, and when in excess, it promotes some of this neuroinflammation and neurodegeneration that we see with a lot of chronic nervous system diseases.

There've been multiple randomized, placebo-controlled trials looking at the impact that Huperzine A has on both Alzheimer's disease, as well as vascular demential. It's been shown to significantly improve cognitive function in patients with mild to moderate vascular dementia and significantly improve cognition, mood, and activities of daily living scores in patients with mild to moderate Alzheimer's disease.

The benefits of Huperzine A have also benefits in other populations with findings of enhanced memory and learning in adolescence and improved recovery in elderly patients from general anesthesia.

Ginkgo Biloba has been studied in many clinical trials, as well as in the studying of dementia. As a botanical, we always think of it as being this go-to for supporting microcirculation, kind of in the fingertips, the toes, the eyes, the kidneys, but the brain is also a part of that. Ginkgo's protective, in part, due to its antioxidant effects and supports circulation in the small vessels by reducing platelet activation and aggregation, as well as stimulating the release of endothelium-derived relaxation factor.

In double-blind, randomized, placebo-controlled studies in patients with mild cognitive impairment, Ginkgo has been shown to improve cognitive function and reduce dementia conversion rate, improving episodic memory and even improving activity challenged gait, which is something that can be an issue with people with dementia.

In a double-blind, randomized, placebo-controlled study in patients with mild to moderate Alzheimer's or vascular dementia who also had the neuropsychiatric aspect of that, Ginkgo was shown to significantly improve cognition, neuropsychiatric symptoms, functional abilities, and the quality of life in patients, as well as their caregivers.

In healthy populations of middle-aged and older volunteers, Ginkgo has also been observed to positively impact memory, improving recall performance, as well as speed of processing abilities.

Lipids are also very important for the brain, which is not very surprising, as the brain is very fatty tissue. Brain cells are especially rich in phospholipid choline, which the body can synthesize from a substance called citicholine, also known as CDP choline. Citicholine and phospholipid choline both support the integrity and functionality of the neuronal membrane, as well as the mitochondria.

Citicholine provides choline, and enhances the synthesis of acetylcholine, the neurotransmitter that plays a significant role in memory and learning. Citicholine has been studied in multiple clinical trials with populations experiencing memory-related issues ranging from mild cognitive impairment to vascular dementia and Alzheimer's disease.

A Cochrane review assessed the effectively of citicholine in 14 double-blind, randomized, placebo-controlled trials in patients with cognitive impairment due to chronic cerebral disorders, which can include both the vascular and Alzheimer's disease and found that, in patients with cognitive impairment due to these disorders, that citicholine has positive effects on memory and behavior in at least short to medium term and they recommended that studies of longer duration be conducted. Significant improvements in mental performance have even been seen in patients with early-onset Alzheimer's disease treated with citicholine, as well.

In a population of patients with the apolipoprotein protein, E epsilon four allele, which increase the risk of dementia, including that of the early-onset dementia as well as vascular dementia, citicholine has been shown to significantly improve cognitive performance, also improving the parameters of cerebral blood profusion in brain bioelectrical activity patterns. In patients who had their first recent ischemic stroke, citicholine was shown to improve attention, executive function, temporal orientation, cognitive status, as well as quality of life, many of which often decline in this post-stroke period.

Lion's mane mushroom is another one that's worthy of mention in a discussion of dementia, as well as in the other changes that occur with aging. Lion's mane has a long history of traditional use for supporting nerve growth and we now know it induces the secretion of nerve growth factor. In recent randomized, double-blind, placebo-controlled studies, lion's mane has been shown to significantly increase cognitive function scores in patients with mild cognitive impairment, as well as reduce depression and anxiety.

In animal models, lion's mane has been shown to improve spatial short-term and visual recognition memory impairments induced by amyloid beta peptide.

Peripheral neuropathy is not uncommon at all in the aging population, whether it be due to diabetes, nutritional life deficiencies, or idiopathic in nature, and lion's mane can also be a benefit for this, because of the fact that it promotes nerve growth factor again. Lion's mane, like many of the medicinal mushrooms, also may have protective effects against certain forms of cancer.

Gazella: I was gonna say, there's a long list here.

Decker: I know. I just have to throw this last one in.

French maritime pine bark extract also is another one that's been the topic of several clinical studies related to cognitive function. Although, this one hasn't been studied in the population with Alzheimer's or the decline already, it's been studied in several different healthy population ... in different clinical studies. In population ages ranging from kids to older adults, even including 60 years in age and above, it was repeatedly shown to improve cognitive function, as well as additional memory retention, mental performance, and working memory in some of the studies.

And beyond cognitive function, it is also one of these that can positively impact blood pressure, cholesterol balance, blood sugar, and has positive impacts on these other diabetes-related microvasculature complications. So it's really excellent for use in individuals who also experience these other challenges.

Gazella: So that is a long list. You've identified lots of choices when it comes to nutrients and botanicals. Now, are there any safety issues or contraindications associated with this long list that you've just mentioned.

Decker: Yeah. Well for the nutrients, of course, some of them such as zinc and vitamin D are appropriate only if there's a deficiency. As an excess, they can cause problems. But, things like CoQ10, tocotrienols, and essential fatty acids are really very safe and are used in part to help reduce cardiovascular disease risk, as well.

The side effects that some people might experience with agents that help increase blood flow to the brain, like Ginkgo, is a slight headache. And, of course, if this occurs the dosage should be diminished or supplement discontinued if it doesn't subside.

Some people might find cognitive support formulas, and even things like CoQ10 and phospholipids alone, to be somewhat stimulating. Not like the jitters type of thing, life coffee, but feeling like a little supercharged. A little of this sounds positive. It can be really problematic if you're not able to do something with that energy or need to go to sleep.

I've also seen people have more vivid dreams when taking something like Huperzine A, and that tends to usually be more transient. But if it's troubling and doesn't dissipate with time, an alternate supplement should be selected.

I generally instruct people to start with low dose, especially if you using combinations of these nutrients, because they really can be very potent. Although some of the nutrients can be taken at night, I generally tell people to take anything that's intended to support cognitive function in the morning. Because we really want it to be something that helps us fly through the day and be as productive as we can be. But really, with all supplements, it is important to screen them with your doctor to make sure they don't have interactions with other medications you may be taking and to make sure they're something for you, individually, that is correct.

Gazella: Yeah, that makes a lot of sense. And, it occurs to me that you mentioned formulas for brain health ... probably a lot of these ingredients that you mentioned are used in combination to be more effective. So there's a synergistic effect. Is that accurate?

Decker: Yeah. Some things more than other. Different supplement companies put different combinations together and a lot of the companies look to the research, just like I'm talking about today, and see what might be appropriate to put together. When I work with things, I often use a B vitamin complex or other specific combinations meant to address homocysteine elevation, if that's an issue.

Essential fatty acids and moderate doses of vitamin E, if not part of the diet routinely, should also be included.

CoQ10, Vitamin E, and essential fatty acids - the fish oils, sometimes you can find those in combination because they're all a fatty substance. They often combine very well.

Vitamin D and zinc tend to be single nutrient therapies that people are on because we use them for all sorts of things, including immune support as well as mood. So those will be things, individually, people take.

Generally, if someone's healthy and not experiencing cognitive decline, that's kind of a good combination package of nutrients to just prevent the nutritional decline-related issues. But, some of the combinations ... I've seen a combination that has the lion's mane mushroom, the phospholipids, citicholine, as well as a substance called coffee fruit extract that really supports cognitive health quite well on both a short-term and long-term basis.

The coffee fruit extract, which contains less than 1% caffeine, has been shown in multiple studies to increase levels of brain drive neurotrophic factor, which I kind of talked a little bit about with exercise. The brain drive neurotrophic factor promotes neurogenesis and is naturally increased in the brain when someone's working on learning something.

I like the combination again, because it's so potent and it's something that someone feels the effects of in the day they take it, yet it has long-term benefits because of the fact that both lion's mane mushroom and coffee fruit extract have of promoting neurogenesis. It also contains American ginseng, and that in combination with the phospholipids, has a pretty dramatic on energy levels as well.

You know, we see a decline in energy with aging populations, which also can be an issue.

I've also found this combination to be really helpful with patients with depression, which makes sense. There's a common overlap with some of the things we talked about in many ways with depression. So you might want to consider it for that, as well.

Gazella: Yeah, sounds like a good combination. Well this has been packed full of great information, but I'm wondering if you have any other advice for practitioners who might be listening, who are trying to help protect cognition in their patients.

Decker: Yeah, and this one doesn't maybe fit in with everything I've been talking about, but I'm a naturopath and I think about things in a very whole-minded fashion ... and I live in Portland, so maybe that influences it as well, but I think it's really necessary to look at the impact of community and how being happy can really impact the overall health of our patients. Particularly in older patients, a lot of them might be alone and if they get stuck in grief ... say they have the passing of a loved one or so many people pass the more we age, and often that will be people in the family. A partner. A spouse. And that contributes to loneliness and these things don't really just eat away at the mood, but they bleed into the health in so many other ways.

Community really gives people life. It gives them purpose and meaning. And being active and finding community, which someone resonates with, really serves a far greater purpose than just being an event on their schedule. And with the elderly or aging population, whether this is a local community center, a church or some other group, it can really help people find a fulfillment and happiness and that goes far beyond just that. It improves the mood and the health of the brain, as well.

Gazella: Yeah, that's such an important point and I'm glad that we're ending with social support, because it has far reaching benefits. Well, once again, I would like to thank the sponsor of this topic, who is Allergy Research Group. And I'd like to thank you, Dr. Decker, for this wonderful information and joining me today.

Decker: Yeah, it was great to be able to do so.

Gazella: Well have a great day.

Decker: Thank you, you too.

In this interview with Natural Medicine Journal's publisher, Deborah Yurgelun-Todd, PhD, and Perry Renshaw, MD, PhD, MBA, discuss the research they are conducting at The University of Utah in the Neuroscience Department. They specifically describe research associated with the safety and efficacy of supplemental citicoline, as well as evaluate emerging research in this area.

Approximate listening time: 30 minutes

About the Experts

Deborah Yurgelun-Todd, PhD, is director of the Neuroscience Initiative and a USTAR Professor of Psychiatry at the University of Utah School of Medicine. Her research focus is on identifying the neuropsychological and neurobiological bases of human behavior. Yurgelun-Todd is an expert in the application of structural and functional magnetic resonance imaging, the administration and analysis of neurocognitive tests, and the integration of the results obtained by these multiple modalities. She has examined the etiologic bases of neural models of dysfunction in psychiatric disorders including depression, bipolar illness, substance misuse, and schizophrenia. She is also recognized for applying imaging techniques to study cortical changes during development in healthy children and adolescents, and during treatment intervention in adult patients.

Perry Renshaw, MD, PhD, MBA, is a USTAR Professor of Psychiatry at the University of Utah School of Medicine and a Medical Director of the VISN 19 Mental Illness Research, Education and Clinical Center (MIRECC) at the Salt Lake City Veterans Affairs Medical Center. His training as a biophysicist and psychiatrist has led to a primary research interest in the use of multinuclear magnetic resonance spectroscopy (MRS) neuroimaging to identify changes in brain chemistry associated with psychiatric disorders and substance abuse. Current clinical trials are focused on the use of citicoline as a treatment for methamphetamine dependence, creatine as a treatment for depression, and uridine as a treatment for bipolar disorder. Renshaw’s recent work focuses on brain chemistry changes that may increase depression and suicide for people living at high altitudes.

Transcript 

Karolyn Gazella: Hello, I'm Karolyn Gazella, the publisher of the Natural Medicine Journal. Today, I'm thrilled to be joined by two highly respected brain researchers from them University of Utah Neuroscience Department, Dr. Deborah Yurgelun-Todd and Dr. Perry Renshaw. Now, before we begin and dig into today's topic, I'd like to have each of you describe the focus of your research. So let's start with you, Dr. Yurgelun-Todd.

Deborah Yurgelun-Todd: Yeah. Well, my research is initially started to focus on cognitive function and the neuropsychological, or brain, pathways that mediate how we think and how we feel. And then I became very interested in the application of brain-imaging to help us understand exactly how those pathways worked and give us some insights into how the brain does things well, and how it does things less well.

Gazella: Perfect. Now, Dr. Renshaw, how about you? Can you please describe your research focus?

Renshaw: Well, sure. Well, I'm sort of confused soul. I'm a psychiatrist/biophysicist, and the way in which I merged these techniques together is to do brain-imaging studies that focus on, how is brain chemistry altered in, particularly, diseased states that psychiatrists might be interested in. And based on identifying unusual patterns in brain chemistry, my research group likes to focus on identification and development of novel treatment strategies. One of which is a molecule, I guess we'll be talking about today, CDP-choline or Cognizin.

Gazella: Perfect. And you're absolutely correct, I'd like to talk about citicoline in a lot more detail. Now, Dr. Yurgelun-Todd, why did you become interested in citicoline for the brain, and why did it catch your attention?

Yurgelun-Todd: Well, they've done some work looking at why the brain was not working very well in mood disorders, and why attention, in particular, was a problem in individuals who had depression and other mood disorders. And when citicoline was brought to my attention, there seemed to be interesting potential for that to alter attentional systems. So I became very excited at the possibility of that becoming a treatment for individuals who may not have optimal brain functioning.

Gazella: Perfect. I love the fact that attention actually is what caught your attention, so that's brilliant. That's brilliant. Now, Dr. Renshaw, what does the scientific literature tell us about the safety of citicoline, and are there any contrary indications or risks associated with its use orally?

Renshaw: You know, that's a great question because we have a really well established answer that citicoline has been used millions of times around the world. In some countries, particularly where they use it as an intravenous administration as a drug. In other countries like the US and Canada, it's a nutritional supplement.

We've done studies, or rather, Dr. Yurgelun-Todd has done studies looking at the effects of citicoline on adolescents and she can describe what she saw. But, by and large, you have to take a whole lot of citicoline before you notice anything adverse. And in the few instances where we've seen that, it's been people feeling like they've had too much Starbucks coffee and that goes away over about a half an hour.

Gazella: Yeah, and I would like to hear about the studies on children, Dr. Yurgelun-Todd. What does your research tell you about safety, especially in that population?

Yurgelun-Todd: It's very interesting because we, as I mentioned, I was interested in potential ways to improve thinking and so we decided we would look at the developing brain in individuals who were adolescent. And we found that when we supplemented with citicoline, they actually improved their attentional span and could do—and had some improvement in their psychomotor function as well. So this was in healthy adolescence, rather than anyone who actually had a documented impairment. The fact that you could see improvement in cognitive functioning and psychomotor functioning in healthy individuals without a documented impairment was actually quite remarkable.

The other thing that was remarkable was that the dosing was very low, and in fact, this was a new area to explore. How low could we dose and still see an effect on the brain? So we were quite enthusiastic about those finding and think they have important implications. With regard to safety, we also were very rigorous in the documenting potential side effects associated with the administration of citicoline and we really saw essentially no side effects in the side effects profile that we did document. Looked very similar to the placebo, in fact, was not statistically different between placebo and the treatment arm. So we were really reassured that even with the rigorous assessment for side effects, there was nothing that was documented in this trial.

What's really compelling, however, is that most treatments for cognitive changes or for any neurologic disorder, neuropsychiatric disorder do end up having side affect issues, some of them being more visceral, like stomach or headache or things like that, but also some of them actually diminishing your cognitive functioning. So this was rather remarkable that we could enhance cognitive functioning with no side effects.

Gazella: Yeah. I mean, it's good to hear that the safety profile is good. And I may want to come back on that topic of children, but Dr. Yurgelun-Todd, I'm going to stick with you here. There's a wide variety of brain functions and cognitive issues that have been researched associated with the use of citicoline, like focus, attention, dementia, and other issues. Which area, presently, has the strongest, and most compelling research?

Yurgelun-Todd: Well, that's a very interesting question because there's a biased based on what science you happen to love. I think some of the most compelling research has been associated with the fact that there's a repair mechanism associated with the administration of citicoline, that is, cellular biochemistry is actually altered and phospholipid synthesis is improved when you have an administration of citicoline, therefore, individuals who have neurological insults, such as strokes or mild traumatic brain injury, things like that can see rapid repair in their cells with citicoline administration. That is the area that's more involved in the patient or the real neurological insult area.

Within the healthy individual, I think the most compelling research really falls on two ends of the lifespan, that is the elderly or middle-age and above, and also then some of the work we talked about in adolescence, where both when your brain is growing rapidly and also when your brain is aging, it seems as if the supplement with Citicoline can make a substantial difference.

Gazella: Yeah, that's interesting. Now, Dr. Renshaw, there's preliminary research demonstrating that citicoline may be able to help with cocaine dependence and addictions. I find that pretty fascinating. How promising is that research, and do you see that as a viable application in the future?

Renshaw: Yeah. No, that's a great question. Citicoline, broadly speaking, has 2 effects. One that Dr. Yurgelun-Todd just touched on. Brain repairs is probably more well established and been investigated for probably 30 or 40 years. Our work, to a first approximation, looks at the effects of citicoline in terms of increasing the levels, brain levels, of neurotransmitters, particularly dopamine and norepinephrine in the brain.

When someone is using cocaine or methamphetamine, they often have a depletion of dopamine within their brain, as well as, in the case of methamphetamine, some damage related to decreases in blood flow. From that perspective, citicoline is almost a perfect fit in terms of what it can do an active user, increasing the level of dopamine in the brain, makes them feel, I think, more intact and, perhaps, less inclined to continue using drugs. And the brain repair mechanism because the mechanism on which stimulants cause brain damage is often related to ischemia. It's just a really good fit.

Where we're going now in this research, is that we've broadened our scope from cocaine to methamphetamine to stimulants that are used to treat ADHD. In fact, we are in the middle of finding a study supported by the National Institutes on Drug Abuse, we're working with in Salt Lake City and Seoul, South Korea. And what we're looking at is adolescents who are using stimulants, not necessarily as a drug of abuse, as a way to approve their attention, focus, and do better on very rigorous South Korean college entrance exams. Some estimates suggest that close to a quarter of all high school students in South Korea are taking stimulants, which is probably not good or the long-term outcome of which is not good. We think citicoline may be a way to help people feel better and get off the use of stimulants. Which is better avoided, unless you have a really good reason for continuing treatment with that class of medication.

Gazella: Yeah. That's actually one of the questions I was going to ask. When you're talking about using citicoline in healthy children, I was curious ... and Dr. Renshaw, I'll stick with you on this one ... I was curious, I have not read any studies using citicoline for children with ADHD, but I think what you're saying is you're evaluating whether or not this could be a viable alternative to the pharmaceuticals that are being used for ADHD. Is that what I'm hearing?

Renshaw: There's a real divide, at least in the United States, between things that are approved as natural products, nutritional supplements, and pharmaceutical agents. The natural product industry lives in fear of having their products considered to be drugs because the amount of testing, and safety monitoring, and efficacy, and evaluation that goes into getting something onto the market as a drug is really very expensive and onerous.

So for us, any research that we do, we have to have it paid for itself. It's been a lot easier to look at the use of citicoline in healthy populations, and certainly the sponsors of the work that we've done, which have been certain large natural product companies, who are much, much happier without us in approach. That's said, if I take off my sort of business man's hat and put on the scientific garb, what we believe is that, in fact, citicoline would likely have good effects for treating ADHD.

In Europe, it's been used as a drug to treat Parkinson's disease with good outcomes, and Parkinson's disease is, as you may know, is also a disorder associated with decreased dopamine in the brain. The ability to increase focus and attention is generally quite good. The difference between citicoline and the stimulant per se, is the effect of citicoline is to increase the brain's concentration of dopamine, that you're encouraging the brain to make dopamine when it otherwise might not do so. Stimulants just release dopamine from the brain and tend to deplete it, so they are very different mechanisms, and there's every reason to think that they'd both be affective. They probably have different safety profiles.

Gazella: That's fascinating. And Dr. Renshaw, I'm going to stay with you one more time. What about autism, autism spectrum? There's numerous conditions that are in that category. Any preliminary research in that or are we pretty much leaving that alone for now?

Renshaw: We haven't been involved in that research. There was a company we did some research with in the Boston area, that was very interested in a related compound from the treatment of autism. They got involved in a big patent dispute with the University of California in San Diego that was resolved in UCSD's favor. So I don't think there's ever been a trial. But, there certainly is a suggestion in the autism literature to treat with pyrimidines, as the effect of either cytidine or uridine on the brain might help some individuals with autism spectrum disorders, but I think in fairness, it's really quite preliminary and that we'd have to do studies to understand what the effects were likely to really be to a population.

Gazella: Yeah. That makes a lot of sense. Now, Dr. Yurgelun-Todd, I'd like to stay on this topic of exciting new research in the area of citicoline use. Another area of research that's pretty interesting, and could be significant, is the use of citicoline for appetite control. I mean, obviously we have an issue with obesity in this country. Is it too early to tell is this may be a promising application of citicoline in the future?

Yurgelun-Todd: You know, I don't think it is. We've noticed some years ago that in looking at the response to food cues, individuals who had received the supplementation of citicoline actually showed significant decreases in appetite and that this was related to dose of citicoline that they'd received. And the thing that was interesting about that data, was it wasn't just that the individual said, "Oh, I feel like I have a reduced appetite." They actually showed differences in the way their brain responded to the cues, such as food items, ice cream, donuts, things like that when they viewed them in the magnet.

So we had documentation that neural activation was altered in food-processing related areas of the brain, as well as having a decrease in appetite, which really suggests that there is some mediation of brain responses to appetitive cues, which is really one of the problems with obesity. And within weight control, that's just sort of having an over-reaction to these kinds of cues.

And thinking about it further, it didn't really surprise us because it goes back to what Dr. Renshaw just mentioned about the dopamine system, the dopamine system in addiction are part of the reward system in the brain and the ... although we initially focused on the impact of citicoline on cellular function and phospholipid metabolism, we recognized as we thought about it further, that the concentration of dopamine is being changed with the supplementation of citicoline as well. So we're changing neurotransmitter balance in the brain and that had a really positive affect in terms of response to food items. I don't know if Dr. Renshaw wants to comment.

Renshaw: No, I think that's right. When stimulants have been used for this purpose, in fact, that's why many of them were developed initially, but they sort of force the brain to release all the dopamine that it's already made. What we really like about citicoline or pyrimidines as a strategy for increasing brain dopamine is that A, it's really encouraging the brain to speed up synthesis, which is sort of what you'd like to do, and again from a safety perspective the latter approach should be much safer for individuals taking a supplement or another medication over time.

Yurgelun-Todd: To go back to your question on is it too soon. I don't think so because I think most studies that we hear about are really just using self-report and don't have the documentation of a brain response. You couldn't really fake a brain response in terms of metabolic activations, so that is a really, I think, robust piece of research that will support this as an appetite moderator.

Gazella: That's fascinating. Now, I want to stick with you, Dr. Yurgelun-Todd because I do want to go into dosage. But specific to appetite control, what was the dosage used?

Yurgelun-Todd: 2,000 milligrams in the study that we did. Although, we did not ... we've not had the opportunity to see how low we can go to have this effect. And this was in middle-aged individuals. So we were looking at people, 40 to 60 years old, and they were looking at the extent to which having a 6-week supplementation could impact the brain. And that's what we saw.

Gazella: And 2,000 milligrams, is that divided doses?

Yurgelun-Todd: Yes, it was. It was morning and evening.

Gazella: Okay, perfect. Now, Dr. Renshaw, I want to dig a little bit deeper into this issue of dose. Now, does the dose of citicoline vary depending on the application or is there a consistent dosage range that is affective across most conditions?

Renshaw: That's a great question, and citicoline has a funny history that was used most extensively first in Europe. And there, after an injection of citicoline, they had a lot of trouble showing that there was any citicoline or cytidine in the bloodstream. When they went to oral ingestion, that became an even bigger problem. And it turns out, that the stomach plays tricks with citicoline, it turns the cytidine, that's part of it, into a molecule called uridine, which is the predominate pyrimidine in the human central nervous system. Because of that, it's been a wide spectrum on the views on how bioavailable, that is how much citicoline gets used by the body. It turns out that if you measure uridine, essentially all the citicoline is absorbed and gets distributed across the body, but it took a long time to figure that out. This was sorted out by a scientist at MIT, Richard Berkman, who's also studied citicoline extensively.

If you look at the clinical indications, a lot of the ones we look at, mood disorders, attention-deficit disorder, probably require lower doses. In the United States, the most recent trials have really looked at serious brain injury conditions, like stroke, and so there have been trials that are conducted with oral administration of citicoline to treat stroke. The problem there is that in the context of someone who's found out a real metabolic stress affecting the brain and the body, it just sort of absorbs things effectively from your stomach, plus you've got a problem with the area you want to impact has got decreased blood supply due to the stroke. And doses went up to something like four grams a day in those instances.

We've been ... most of our indications using somewhere between 500 and 2,000 milligrams of citicoline. The effects of citicoline last for about two, or three, or four hours just depending on the individual. So taking it twice a day works reasonably well. There is, for many normal people, a self-correcting mechanism, which if you're taking more than your body needs, you will feel anxious and jittery. That's relatively uncommon. Anyone taking less than 2,000 milligrams a day is unlikely to have side effects. This is obviously important in figuring out what to do. Studies in children, for example, as Dr. Yurgelun-Todd has done. Children come in a variety of shapes, sizes, and weights. It's probably going to be important to adjust the dose to reflect the weight of the child.

Gazella: Yeah. I think one of the fascinating things for me with citicoline, is that it does, in fact, have efficacy at what could be considered a fairly low dose, even as low as 250 milligrams. But even at 500 milligrams, that's a pretty low dose, and it's still showing affect, correct?

Renshaw: That's right. From that perspective, it's really important to recognize that one of the most established effects of citicoline is to speed up membrane synthesis, and this is true in every cell in the body, and we all travel around with CDP-choline in our cells. For that reason, because it's highly important in controlling this fundamental process, the body tends to keep the concentration of CDP-choline low. So that relatively low doses, especially for natural product, work much more effectively than is true of almost any other type of natural product. And again, we think that that has a lot to do with the fact that it's a really important regulatory control molecule within the body.

Gazella: Right. Now, Dr. Yurgelun-Todd, we've talked about a lot of different conditions, and application, and some pretty exciting emerging research associated with the oral use of citicoline. Out of all of that, what do you feel shows the most promise?

Yurgelun-Todd: I think I'm going to relate that to where I think there's a great deal of need. And that is in our children, and our adolescents, and young adults. And specifically, I think the fact that we can provide a very safe, minimally, essentially no side effect treatment to improve attention, and you touched on this earlier, I think is very significant. We've not done studies in ADHD or populations, such as a diagnosed ADHD population, but I'm quite sure that this would be a supplement that would make a significant difference for many of those and not have any long-term or short-term side effects. So I think that's a very important point.

The other thing that hasn't been as well explored, but I think is important, is the area of concussion or sports injury. Where, I believe, because of the data that we've seen in stroke, and in other neurologic disorders there's every reason to believe that citicoline could actually provide a preventative capacity, like in a sports drink or a bar, something to that effect, prior to concussion. And then also supplementation during the season could be very helpful. So I think that ... well, that hasn't been an area that we've focused on so much. I think given the attention now in the sports of our children and college students, that this would be an area that could be really important.

And then, of course, my original reason for wanting to get into this work, which is mood disorders. I think that we hadn't really capitalized on the impact of Cognizin on improving mood disorders. And I think there are many individual, particularly, in the perimenopausal age group who have found that this has been a very important supplement in their life and has helped them significantly in feeling that they can think more clearly and feel better overall. So those are my favorite areas to think about.

Gazella: Yeah. That concussion, that is really fascinating and it would be great if there could be some studies done there. Dr Renshaw, do you agree? Anything to add to that list?

Renshaw: Yeah. There's a substance abuse investigator at the University of Texas Southwestern in Dallas, Sherwood Brown, who did a study of the individuals who had both, cocaine dependence and bipolar disorder. And what he found was citicoline was actually much more effective in treating the bipolar disorder than the cocaine dependence in the patients that he was working with.

We have a colleague here in Utah, Doug Hondo, who looked at that and said, "Why would something like citicoline be effective in treating bipolar disorder?" And he's developed a theory that suggests that citicoline may have a really potent antisuicidal effect. And it shares, to an unbelievable degree, many of the same effects on the human brain that both lithium, which is known to antisuicidal and ketamine, which is the antidepressant for those of us in psychiatry. So he's about to begin a study looking at whether or not, and this has been funded by the Veterans Administration, Citicoline reduces suicidality with treatment for only the first week. This is very exciting, and is something that will get underway, it's a 4-year study, in a couple of weeks. And if that's really true, and you could get the same protective effect without having to take Lithium or Ketamine, both of which have pretty significant side effects, that would be a real advance. The compound that Doug will be using in the study is uridine, which is the major metabolite that citicoline provides through the body in [inaudible 00:25:19].

Gazella: Dr. Yurgelun-Todd, because we're talking about bi-polar mood disorders, a lot of these folks are on some heavy duty medications as Dr. Renshaw just mentioned. Do we know anything about interactions? I don't know that there's been any studies, but if somebody is on a Prozac, or an antidepressant, or some of these other, Lithium and whatnot, can citicoline be taken with that or is that a no-no?

Yurgelun-Todd: Thus far, I don't know of a clinical trial that examined that specific question, however, everything that we know about citicoline would suggest that because this is found in normal diets and is a part of the human body, that it would not have any interaction effect with the treatments that have been provided. So it should be perfectly safe.

Gazella: Yeah. That makes some logical sense.

Yurgelun-Todd: But with the caveat that we don't have that empirical data.

Gazella: Right. You're basing that on logic and mechanisms of action and ...

Yurgelun-Todd: Exactly.

Gazella: Now, Dr. Renshaw, I'm going to put you on the spot here, but this is your area of expertise, your background is with addiction. I would love to hear your thoughts on our present opioid epidemic. I realize that this is a huge topic. This might be an unfair question, but can you give us a snapshot from your perspective as a researcher with this type of expertise, what needs to happen to get this issue, this opioid epidemic under control?

Renshaw: Boy, if I knew the answer to that question, I'd have a really high profile job. We're very interested in addiction as you know, we live in the Rocky Mountain states, and so one of the things we study is, what happens when someone moves from a lower altitude to higher altitude, and what we find is that people often get more depressed and more anxious and, curiously, use more different kinds of drugs of abuse. So I guess you could say, flatten out the Rocky Mountains states, but that's not actually our strategy. We're looking for molecules like citicoline that may have an effect in changing brain chemistry in ways that are effective in treating some of these high altitude related conditions.

The fact that this is something you can do that changes the use of drugs across a broad variety of categories suggests that these may be molecules that are really valuable in treating a range of different addictive disorders, but clearly you've figured out by now, that I'm sort of waving my hands because I think there are a lot of very smart people who are struggling with the question of how do you prove the problems of opiate dependence in this country. And it's really shocking how we have a problem that's occurred over a short period of time.

Gazella: Right. We've covered it in the Natural Medicine Journal, so it's definitely in our radar as well. Now, I think we covered everything, but Dr. Yurgelun-Todd, is there any final thoughts that you'd like to add on this subject?

Yurgelun-Todd: Yeah, just one final thought, which is that I think that the impact of citicoline and particularly Cognizin citicoline has not been fully appreciated yet. It's come a long way since we began working with it and I think we've appreciated that it has multiple types of impact on the human brain and body, but I think we have even more potential to see it improve the quality of our lives. So I'm excited to continue working with it.

Gazella: Yeah. That's kind of why I wanted to focus on the emerging research because I think that that's very exciting, and I think that this can be a really positive clinical tool for healthcare practitioners. Dr. Renshaw, anything else to add to that?

Renshaw: Just one comment and then a tantalizing tidbit if you will, we can edit this out, I guess. But one of the things that we think is going be an important trend, is the combination of citicoline with other natural products as a way to boost its efficacy. And that's something that hasn't happened yet, but we have some combinations that we're exploring now. One of the things that Dr. Yurgelun-Todd didn't share with you, is she has, across 3 different studies, evidence that citicoline also improves complexion. It has effects on skin tone, which makes some sense when you think that both the brain and the skin are rapidly turning over cells. So that's an area that's a little bit outside our area of clinical expertise that merits investigation as well.

Gazella: Wow. Yeah, that is pretty interesting because that could then ... it could be a topical ingredient.

Yurgelun-Todd: Right. Exactly.

Renshaw: Exactly.

Gazella: Yeah. Wow. That's pretty interesting. Well, I want to thank you both for joining me. This has been fascinating and information-packed. I'm so pleased that you took time out of your schedule to join me today. And I hope you have an awesome day.

Yurgelun-Todd: Well, thank you so much. We were delighted to join you.

Renshaw: Yeah, you too, Karolyn.