Natural Medicine Journal Podcast

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Aug 14, 2018

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 Brown

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

Allergy Research Group

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.

Our purpose is to provide customers with products they can use to improve their patients’ quality of life, through scientific based innovation, purity of ingredients, education and outstanding service.

ARG is proud to be a sponsor of the Clinical Education LinkedIn Forum, a closed peer-to-peer group on LinkedIn where healthcare professionals can ask clinical questions and receive evidence-based and clinical-based responses by experts in their field.

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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.

Aug 14, 2018

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

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.


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.

May 15, 2018

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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Allergy Research Group

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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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.

May 15, 2018

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

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

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.


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.

May 2, 2018

In this podcast episode, we talk about cardiovascular labs with naturopathic cardiology expert, Daniel Chong, ND. Chong discusses the use of cholesterol panels and other tests he uses in practice. He dispels some common myths about how to interpret different lab results.


About the Expert

Daniel Chong, ND

Daniel Chong, ND, has been a licensed naturopathic physician, practicing in Portland, Oregon, since 2000 and focusing on risk assessment, prevention, and drug-free treatment strategies for cardiovascular disease and diabetes, as well as general healthy aging, and acute and chronic musculoskeletal injuries. Chong has also completed certificate training in cardio-metabolic medicine from the American Academy of Anti-Aging Medicine and is an active member of the Society for Heart Attack Prevention and Eradication (SHAPE). In addition to his clinical work, Chong serves as a clinical consultant for Boston Heart Diagnostics Lab.

Tina Kaczor, ND, FABNO: Hello I'm Tina Kaczor editor-in-chief at the Natural Medicine Journal. I'm speaking today with my friend and colleague Dr. Daniel Chong a naturopathic physician and specialist in cardiology specifically. Dr. Chong is a founder and lead consultant at as well as a consultant for the cardiology industry. Dan, thanks for joining me today.

Daniel Chong, ND: Hello Dr. Kaczor, it's nice to be here.

Kaczor: We have talked informally, and I thought this would be a great opportunity to talk specifically for our audience, about the use of cholesterol panels, and we'll go into specifically some breakdown of the usefulness of common cholesterol panels, and then break that out into more particular cardiology panels. There's a lot out there right now about whether cholesterol is or isn't even linked to heart disease, so let's just start at the beginning. Can you give us a little bit about the roots of the cholesterol theory? We'll branch off from there.

Chong: I can try. It definitely is a relatively long-standing theory now. As I understand it, the first thoughts as to whether or not cholesterol had anything to do with cardiovascular disease came in the early 1900s on animal research with rabbits, but at that point it was dismissed because people were still not clear whether or not you could make any correlations between findings in rabbits and extrapolate out to humans.

The major real focus on the connection between cholesterol and heart disease started more in the mid-1900s almost simultaneously in a way with Ancel Keys and the Framingham study, so they started around the same time. Ancel Keys was one of the first people to really make a point of saying, "We should really research this because we repeatedly are seeing this potential connection," and so he was one of the first people to really start trying to splice it out. Then, the Framingham study started simultaneously. They don't come out with any of their more definitive conclusions until a little later than him with that. That's where it all began as far as I understand it.

Kaczor: In the Framingham study specifically I know that there has been ... The broad interpretation in the professional world has been high cholesterol equals risk of heart disease, LDL being the "bad cholesterol," in general. Is there particular subpopulations that this is more true for? In other words, can we say if you are a 40 or 50 something-year-old male this is more true than if you're a 80-year-old male, or a female? Is there any way to delineate that with just looking at broad generic cholesterol levels, nothing too specific yet?

Chong: Hopefully, it will be answering your question by saying this, but to me one of the most fascinating pieces of information I heard come out of the Framingham study in particular is that over the course of however many years ... this was a statistic we heard about maybe five or so years ago. The Framingham study had been active for well over 50 years and they had well over 50 years of data on how many thousands of people, and the statement was made by the former director of the Framingham study, so it was certainly legitimate. Essentially what they said was, one of the key pieces of information that they saw in terms of the relationship between at least total cholesterol and cardiovascular disease was that it appeared as though if a person's total cholesterol was at or below 150 naturally, so throughout their lives without necessarily an intervention with a drug or whatever, just the people in the study who had naturally low cholesterol did not get heart disease period.

Of course, you can't then take that and make any truly definitive statements, but there is, in terms of a general viewpoint that was one of the things that came out. In other words, nobody with cholesterol under 150 naturally got a heart attack in their study. Again, there would still need to be more done to splice that out and figure out what exactly is going on there and why that is, but there's definitely something to be said. You can see the same exact type of finding if you look at epidemiological research on different cultures of people in history who did not get heart disease or got very little heart disease, all of those people regardless of where they were on the planet, what types of specific foods they were eating, even to some extent what their lifestyle was some of these people smoked, et cetera, the cultures of people who were known and found not to get cardiovascular disease all had cholesterol at or below 150.

Kaczor: You're talking about total cholesterol?

Chong: Correct.

Kaczor: Let's move over to talking about the bad cholesterol. LDL-

Chong: Can I pause you for one quick second?

Kaczor: Yeah.

Chong: Just to say one other thing about that. There's a lot of questions that would be immediately raised from those statements that I just made. One other way that I look at things is, and I know we'll get into it more, but cholesterol in of itself, I will say right from the beginning, has to be involved. It is not a worthless thing to measure, it is not something to just disregard and only focus on information. Time and again it has to be involved, technically it has to be involved. You can't make plaque without it, but it's just an important way to think about it. It's just whether or not it's the primary causative factor and we'll get into that.

Kaczor: Yeah, that's an important point. I don't see many people with total cholesterol below 150, but we'll put that aside. It's pretty uncommon. I don't know about other people. Let's break it down-

Chong: In modern times it absolutely it is.

Kaczor: Let's talk about LDL specifically and just start out with there's a lot of more specific labs that are looking at LDL particle size rather than total LDL. Just a brief primer, if you would, on the difference between LDL-

Chong: I like your emphasis on brief.

Kaczor: Yeah.

Chong: Sorry, go ahead.

Kaczor: On LDL calculated as it is in a common cholesterol panel and the particle size as it is measured by several different labs now.

Chong: I'll do two separate simple ways that I look at it. One is technically LDLC or "LDL cholesterol" measurements that are most commonly done in the average physicians' offices et cetera is technically measuring the mass or total amount of cholesterol being carried around on LDL molecules. Just as a reminder to people, these LDL molecules are protein-based particles that are essentially like cargo ships carrying around different substances, one of the main ones being cholesterol.

When you are getting an LDLC you are getting an estimate of the mass of the total amount of cholesterol being a carried around by all of the LDL particles in the system whereas, an LDLP is specifically getting a count of the LDL particles floating around in any one measurement of blood. From an analogy perspective it's like you're counting either the cargo that's being ... The Pacific Ocean has a certain amount of cargo ships out in it carrying cargo and LDLC is like, "Okay, what's the estimate of total cargo being carried around by all of those ships?" Whereas an LDLP would be like, "Okay, we're going to go into the ocean, we're going to count each one of those ships and see how many there are."

Depending on some different factors this is why you could theoretically ... Let's say a cargo ship could technically carry 100 pounds of cargo, you could technically have two ships carrying 200 total pounds of cargo or you could have 20 ships carrying 10 pounds of cargo each. In both cases the LDLC would be the same and yet one, there's 20 ships and the other there's two ships, if that makes sense. The reason why that's so important to make the distinction is that what we know now is that risk specifically goes up with ship count or particle count—not necessarily total mass or total cargo. If you have a way of identifying, "Aha, there is actually only two ships in this ocean versus 20," that can significantly impact risk level.

Kaczor: Looking at the LDLC, which is the calculated one, it may or may not correlate with cardiovascular disease is what I'm hearing you say, and LDLP we can use as a more specific correlation with cardiovascular disease.

Chong: Right, that is correct. In the grand scheme of things when we're also potentially considering other factors like inflammation, and oxidative stress, et cetera, it's still relative ... we're just talking about cholesterol-related markers and their impact on risk, so there are obviously ... I don't want to discount the fact there are other factors involved here, but when we're just talking about the cholesterol and its impact on future risk or not the particle count is what trumps everything. Again, just in the realm of the cholesterol markers.

Just for an example, there's a research study I've seen where they looked at 16-year survival, from year 0 to 16 and measured LDLP and LDLC in each person. This is a very large study, and what they saw is a distinct difference between particle count and future event risk for cardiovascular disease. In other words, you had a distinct increase or higher rate of survival in people who have low particle counts regardless of what their LDLC or mass was. Whereas the people with worse outcomes all had high particles even though some of them technically had low LDLCs or low amount of total mass or cargo.

Kaczor: It's been-

Chong: It's been clearly seen that there's a distinct difference. It's also important to mention here, it is unfortunately true that there are some people out there who are still saying, "If I have large puffy LDL (i.e., my LDL particles are loaded with a lot of cargo per particle) and yet not necessarily ..." If you have a high LDLC, but all of your LDLs are large and puffy, and you also have a high LDL particle count you will still have an increased risk. There are some people out there who are under the misconception that if LDL particles are large and fluffy or large and puffy enough they can't cause problems, that's totally inaccurate. Bottom line, when we're talking about LDL, particle count trumps everything.

Kaczor: Let's move on to HDL. That's really good points on the LDL because I do know that the size and the type, the fluffy or the dense, that idea is very much part of the verbiage that patients use when they come through the door-

Chong: I'm sorry, I will say one other thing quickly about that. I don't mean to say that it's worthless to check LDL particle size because it's still true that LDL particle size, the smaller the particles the higher the potential is for future risk, but it's not just because of the mechanism itself. It's like just because there is a strong relation between what causes LDL particle sizes small and what causes cardiovascular disease. As an example, typically people with poor insulin sensitivity, or insulin resistance, diabetes, et cetera tend to have smaller particles, so it's still important to look at particle size because it does add to the predictive value of the test you're running. I don't mean to say that it's worthless or anything like that, you just can't say, "If my particles are large and puffy, I don't care how many there are."

Kaczor: Got you. Okay. Let's go back and just come back to HDL, the high density lipoproteins. This we don't harp on as much, the drugs aren't targeted towards it as much. We tend to know that higher is better. How do you use HDL in your interpretations?

Chong: One of the reasons why the drugs aren't targeted as much is because they keep trying and failing. Pretty much every study that's ever been done on a drug that it raises HDL shows that they clearly work and then oftentimes the people die sooner, so they have to stop. The bottom line is it's not a cut and dry direct simple relationship where the higher the HDL the better necessarily. Especially if you make a change in somebody, so like diet, lifestyle, et cetera, and their HDL goes up it is absolutely not a guarantee that they are getting better or that they are more cardio protected than they were beforehand. It might be the case, but it's not a certainty.

From that perspective, at least personally, when I'm looking at HDL I'm always looking at the whole picture. If I see a relatively low HDL and yet this person might happen to be one of these lifelong naturally low in total cholesterol, naturally low in LDL people I'm not as concerned about that low HDL as I am in somebody who has really high LDL, really high total cholesterol, insulin resistance, et cetera, and they have low HDL. There's a definite difference.

Those two people might both have the same HDL number, but one is way more concerning than the other one, and it just has to do with the role of these particles, these molecules, and what are they doing for us? If you really simplify it down HDL does a lot of complicated things, we still don't even know everything that it does, but definitely one of its main job is reverse cholesterol transport where it's helping to remove excessive cholesterol deposited in the periphery so to speak. I like to look at it as a garbage truck or a garbage collector. It is very true that if you do have a lot of "garbage" in the system, you have a high total cholesterol, a high LDL there's lots of cargo, or garbage, or whatever you want to call it being shipped outward you would hope to see the body responding to that by increasing garbage truck count to pick up the extras.

You commonly see that on people who go onto low-carbohydrate, high-fat diets. Oftentimes you will see, hopefully, an elevation in HDL as the body is literally just adapting to the additional load on the system that you're putting on it. It does not, however ... Unfortunately, you can't take that response and then conclude that the low-carbohydrate diets are cardioprotective because they cause HDL to go up. It's not that cut and dry, it's more just that the body is responding and having to increase its HDL to adapt and make up for the extra amount of cholesterol in the system, if that makes sense.

It's quite complicated. You do see HDL go up for that reason. The other thing is sometimes you'll see high HDL in somebody who's got disease, especially if they're inflamed or they have chronic inflammation. In those situations, in all likelihood, what's going on is that inflammation is known to hinder HDL function. The body always trying to adapt, always doing the best that it can to deal with the cards it's being dealt, if it has poorly functioning HDL it's going to spit out more of them in an effort to continue doing the job that needs to be done. If the HDL are dysfunctional as a result of oxidative stress, inflammation, et cetera in the system if the person has the capability you may sometimes see HDL production go up or HDL number go up on the person's lab because each one is not working as well as it should.

Kaczor: That's an interesting idea, that it's a reaction.

Chong: Absolutely. It's a fluid, functional system. Again, people just think, "Oh, HDL went up, that's good," or whatever. It's not like that. You have to think about why is the body doing that? What is the response going on? The body's always trying to maintain homeostasis, which would include not having cholesterol collect in the walls of the arteries.

Kaczor: That's awesome. I appreciate that perspective. I think it's really helpful for us because we want the quickest most linear path to a conclusion, so it's good to remember to step back once in a while.

Chong: For sure.

Kaczor: We don't have time to go into labs, other labs in great detail, but what other laboratory parameters would you consider must haves? I'm going to give you a typical case, a patient comes to your office, they themselves have no history of cardiovascular disease. They have both sides lots of cardiovascular risk, so they believe that maybe there might be something going on there. What's your bare minimum of labs? What would you do?

Chong: Especially in today's world where we're not necessarily billing insurance or whatever personally, for me, if I'm trying to get the most bang for my patient's buck in the realm of cholesterol I'm going to measure an apo A1, or apolipoprotein A1, I'm going to measure an apolipoprotein B, which for those people that aren't fully aware it's essentially like getting more precise HDL and LDL. Apo A1 is like getting a bit more precise HDL count and apo B is like getting a more precise particle count. Again, that's the name of the game, especially looking at the ratio between those two.

I'm also going to measure a lipoprotein a, which has its own independent impact on things and is not necessarily going to be responsive to medications or dietary changes that do impact these other markers. It's a very important marker to assess and you can never really predict whether or not somebody's going to have high levels of that or not, but definitely the potential goes up with a strong family history.

Then, beyond that in the realm of inflammation I'm at least going to want to see an HSCRP, I'm at least going to want to do some fundamental blood sugar metabolism related markers. I personally like to check a fasting insulin, and then potentially a hemoglobin A1c as well, although that sometimes has some questionable value depending on each patient. Beyond that, it starts getting a little bit more spliced out and potentially, depending on each patient, what you might go from there. I do check vitamin Ds pretty often, I check ferritin, and iron binding capacity pretty often at least screening that once to make sure there's no hemochromatosis going on. Those are probably the main ones I'm going to want to see. I will definitely do a CBC as well.

Kaczor: The one I didn't hear you say, and I'm curious if you do, is homocysteine.

Chong: Sorry, thank you Dr. Kaczor. Yes, absolutely homocysteine as well. Again, whenever I have the opportunity especially if there is a strong history and there's good reason to want to delve more deeply than average there are definitely some other markers I would typically run with people, but those would be a great starting point.

I don't know if we're going to talk later about going outside of blood tests, but just long story short I don't consider an assessment truly complete without some type of imaging at least on the high risk population.

Kaczor: By that, you mean?

Chong: Sorry, carotid ultrasound, IMT, or a coronary calcium score.

Kaczor: I can vouch for that. I've had several patients with cholesterols that didn't look too impressive, but their coronary calcium scores came back very, very good, and so they didn't have any [inaudible 00:24:42].

Chong: I will say one pearl type of information about that, the value of coronary calcium scores specifically goes up with age. The value of risk assessment using that test goes up with age. In other words, occasionally if a person is still relatively young, typically under about 55, you may have a situation where that person has a decent amount of soft plaque that has not been calcified yet and it will make their calcium score looks pretty good, but then if you check a carotid ultrasound it doesn't look so good. I have seen some mismatches in that regard with some of the slightly younger people, so my tendency is to measure carotid ultrasound, IMT tests with the understanding, obviously, that you're not checking the coronary arteries, but there's an over 90% correlation between the two. To me, a carotid ultrasound is a little pickier, a little more fine-tuned than the other one, but absolutely the high calcium score is a very powerful risk predictor. It's just whether or not you're going to catch everybody that way.

Kaczor: Great. Dr. Chong, thank you so much for joining me today, I appreciate your expertise, taking the time. I think this is a to be continued type of thing because we didn't talk about what to do.

Chong: I would love to keep talking, yes because I feel like we just started scratching the surface. Happy to delve more into some of these other details because there's a lot of other things to consider.

Kaczor: We'll talk about treatments and we can talk a little bit more about imaging techniques next time. Thanks again.

Chong: Super, yeah. Thank you.

Apr 4, 2018

In this interview, nutrition expert Jolie Root describes the health benefits of the Mediterranean diet and how practitioners can enhance compliance with their patients. Listeners will learn how to effectively utilize this diet in clinical practice.

Approximate listening time: 32 minutes

About the Expert

Jolie Root

Jolie Root, LPN, LNC, is a nutritionist, health educator, nurse, medical journalist and well-known radio personality. She travels North America attending medical conferences and educating the public about the roles of nutrition in integrative medicine. She also spreads the word through informational articles published in magazines and newsletters across the country, including Alternative Medicine, Whole Foods, Taste for Life, and Senior Living. In addition, she hosts a weekly talk show called “Food for Thought,” which can be heard Fridays at 10:00 a.m. Eastern Time on AM 1160 WVNJ.

About the Sponsor

Carlson Laboratories

Since 1965, Carlson has produced pure, quality, award-winning vitamins, minerals, omega-3s, and other nutritional supplements. Carlson began with a single vitamin E product, helped launch the omega-3 market in North America in the early 1980s, and now offers a product line with more than 200 nutritional supplements. Carlson is most renowned for the high quality of their award-winning omega-3s, and now they’re available in a premium olive oil. Olive Your Heart® blends cold-pressed Greek Terra Creta extra virgin olive oil with premium Norwegian marine oil sourced from deep, cold-water fish and is available in basil, lemon, garlic, and natural flavor. Each serving provides 1,480 mg of omega-3s, including EPA and DHA. Olive Your Heart® is mild and smooth, and makes it easy and delicious to add heart healthy nutrients into your diet.


Karolyn Gazella: Hello. I'm Karolyn Gazella, the publisher of the Natural Medicine Journal. Today, we are going to explore the efficacy of key components of the Mediterranean Diet. We'll also be talking about enhancing patient compliance to this diet. Before we begin, I'd like to thank the sponsor of this topic, who is Carlson Laboratories. My guest is nutritionist Jolie Root. Jolie, thank you for joining me.

Jolie Root, LPN, LNC: Oh. It's a pleasure to be with you, Karolyn. Thanks for the opportunity.

Gazella: Well, this is a great topic. We've actually written about this topic a lot in our journal, and I am a big fan of the Mediterranean Diet. I think most practitioners know what makes up the Mediterranean Diet, but can you remind us what the key components of the diet are that contribute most to its health promoting aspects?

Root: Yes. It is a diet that is high in plant foods, so that means fruits, and vegetables, and whole grains, and whole grain breads, legumes, and nuts, and seeds. They also use hefty amounts of extra virgin olive oil, and it may or may not include moderate amounts of red wine, and also fish, and poultry, dairy, and eggs are featured, and red meat is minimized. It's only very occasionally that there will be red meat in this diet. It's a plant-based diet with a variety of fruits and vegetables, fresh foods, and whole grains, legumes, nuts, and seeds, and olive oil.

Gazella: Now, let's talk about the olive oil, because it seems like the healthy fats are a big component of this diet. What are some examples of the healthy fats in the diet, and why are these fats better for patients?

Root: Well, I think that you could say that part of the overarching benefit of walking away from unhealthier fats and towards healthy fats in the diet has to do with inflammation. We know in Western culture that we have an imbalance of fats that promote inflammation relative to an inadequate intake of fats that help to balance inflammation, so specifically I'm saying that one of the really I think imminent qualities of the Mediterranean Diet is that it relies on olive oil and then omega-3s from nuts and from fish, and it's low in omega-6s. That's the problem when you contrast that to the Western pattern diet, which is much higher than it should be in omega-6 relative to omega-3, and in the US, in North America, people rarely use olive oil as their main cooking oil.

Here in the West we eat a diet that promotes inflammation, and it's not just inflammation. It also promotes an unhealthy level of clotting in the blood and constricted blood vessels, so the result of that is high blood pressure and arterial stiffness. The Mediterranean approach, using olive oil and omega-3s from nuts and from fish oil, relaxes the blood vessels, helps to govern excess inflammation, and promotes health in areas from heart disease all the way to cognitive function.

Gazella: Now, I'd like to continue to deconstruct the diet a bit more, but let's stick with the conditions that you just mentioned, and I'd like to talk about first prevention and then treatment. Let's talk first about prevention. Purely from a preventative standpoint, which conditions benefit most from the Mediterranean Diet? You mentioned heart conditions, but can you expand on that a little bit more?

Root: Well, cardiovascular disease, so disease of the heart and the blood vessels, so that would mean not just heart disease with its inherent health risks, but cardiovascular death as an endpoint is something that has seen reduction in the double-blind, randomized, controlled studies and even in single-blind, controlled studies with the Mediterranean Diet, so the Lyon Heart Diet Study and the PREDIMED Study are studies that practitioners can look up and read. They saw a reduction in heart disease and a reduction in heart disease deaths as an endpoint, but along with that we also see blood vessel issues, so hypertension and endothelial function as components of heart disease, are improved on the Mediterranean Diet, because some of the elements in the Mediterranean Diet relax the blood vessels, and that allows for supporting blood pressure in a normal range.

The other thing is when you look at the heart, before we have heart disease, we may have diabetes or metabolic syndrome, conditions leading up to sometimes an increased likelihood of an endpoint of heart disease. The Mediterranean Diet helps with blood sugar stability and some of the issues that contribute to the metabolic syndrome, such as derangement of lipids, so cholesterol numbers that are not where we want them, triglycerides that are elevated, and that blood sugar control, and higher than what would be optimal inflammatory markers, and then that's metabolic syndrome, which also sometimes we might call pre-diabetes, but also diabetes itself is something that we have seen benefit in reducing risk of with Mediterranean Diets.

That's kind of in the cardiovascular realm, but if you want to go to the cognitive realm, we have seen improvement in cognition in elderly people who followed a Mediterranean Diet with either additional nuts or additional olive oil, and we have even seen some changes in some of the suspected markers of Alzheimer's risk, things like amyloid deposits and amyloid protein. So, earlier in life we're concerned about heart disease. We're concerned about metabolic syndrome, diabetes. Later in life we start thinking about dementia and ultimately with the worst endpoint there, which would be Alzheimer's.

Gazella: Yeah. I mean, that's a pretty broad range of conditions. I'm curious. When we switch over to treatment intervention, can the diet be used as a treatment intervention for many of these same conditions?

Root: Well, I wouldn't go so far as to say that it would be a treatment for Alzheimer's. We don't generally find that treating Alzheimer's works particularly well once that disease itself has set in, although I would urge practitioners to look up Dale Bredesen and the work that he's doing. However, the cardiovascular disease? Yes. I would recommend the Mediterranean Diet as a treatment if someone were to come to me and ask for a recommendation, because of the ability to change the inflammatory markers, the lipid balances back to a more favorable profile.

There is, for example, one of the elements ... I know we're going to talk about this in more depth as we go forward, but think about resveratrol, which is known to enhance nitric oxide production, and that means relaxing blood vessels and promoting endothelial health. In those cases, people that are in pre-diabetes, metabolic syndrome, or actually know that they have cardiovascular disease are looking to improve these factors, and Mediterranean Diet has shown to do exactly that.

Gazella: Before I leave this subject, are there any studies on obesity? It seems like obesity can increase the risk of so many things, not only heart disease, but also some cancers, and of course diabetes, and metabolic syndrome, and some of the other things that you've mentioned. Are there any studies showing that the Mediterranean Diet will help people lose weight?

Root: Yes. They weren't looking at that as an endpoint, so I'm not aware of studies, Karolyn, where they were specifically looking for weight loss as an endpoint in the study, but they have seen, as an aside, the additional benefit in some of the big studies of Mediterranean Diet of weight loss, although that wasn't really what they were after or what their intent was. People do seem to lose weight when they follow, when they adhere to a Mediterranean Diet. There's the key.

Gazella: Right.

Root: You know, that's the key in everything that we do, either successfully or not, when we talk about integrative health. But the weight loss factor seems to be more pronounced than in people who follow something like a low fat diet. I think that it's a happy additional benefit of following a Mediterranean Diet.

Gazella: Well, that's good. Now, is there anybody who should not be on the Mediterranean Diet? Are there any contraindications or safety issues?

Root: I can't think of any. I thought about that. I expected you to ask me that question, and I thought about that. I can't think of any, because the factors in Mediterranean cooking and following that approach are varied enough that if you had ... Let's say, okay, one caution is always what if you have a really strong food sensitivity or food intolerance, so a gluten issue, or what if you have a real sensitivity to nightshades? You could avoid those foods and still follow a Mediterranean approach, so there's enough variety I think in the foods in a Mediterranean lifestyle, a Mediterranean Diet, that I can't think of anyone that really would be a problem.

If you choose to be a vegetarian, omit the fish and include more olive oil and nuts for healthy fats. If you are avoiding gluten, then don't eat the gluten containing foods that are part of the diet. There's no hard and fast rule that says that you absolutely must include every element of the diet. If you have an issue with alcohol, you do not have to have the red wine. But as far as just a strict avoidance, I can't think of anyone.

Gazella: You know, I would agree. I have not seen anything ... I mean the diet is so fluid and so varied, so I think that that's definitely one of the benefits. I'd like to continue to kind of deconstruct this diet a bit more. You know, you mentioned healthy fats. You mentioned resveratrol. This diet includes a lot of key nutrients. It comes from the spices and the other foods that are featured in the diet. Can you give us some more examples of the specific polyphenols and other compounds that we can find when we break down this diet?

Root: Definitely. Let's say tomatoes, which are certainly something that people in Italy, and people in Spain, and France, and most of the Mediterranean countries enjoy, so with tomatoes we have lycopene, and lycopene is one of the dominant antioxidants in the bloodstream when people do eat a Mediterranean Diet. Lycopene itself has been associated with protecting the prostate health in men, reducing certain aspects of risk factors for health disease. So, lycopene from tomatoes is an example.

If you look at the leafy greens that are in the diet, then we can talk about lutein and zeaxanthin, and we'd also have to talk about the magnesium that is a very strong element benefit of leafy greens, and the carotenoids, the betacarotene, but lutein has been shown to be very beneficial for the retina. You know, dating back to the 90s, more lutein, even a single serving of spinach a day, reduced macular degeneration by more than 40% in men who were eating a healthy diet including spinach on a daily basis. Lutein is there in the leafy greens.

Think about garlic. You've got allicin, and you've got a lot of phenolic compounds in the garlic. Garlic is a benefit for being, first of all, an antioxidant, but also an antifungal. It's just a very healthy food. It also helps to normalize lipids. It helps with blood vessel expansion, so garlic is another element. I mentioned the resveratrol in the red wine. You wouldn't need to do red wine. You could get resveratrol from the purple grapes and from other red foods that are in the diet. If you eat blueberries, you could get pterostilbene, which is another very potent blood vessel health supporting antioxidant.

Let's not even get started on the dark chocolate, which is one of the elements, and we love that part, in moderation, meaning about an ounce a day of a good dark chocolate, full of flavonoids, beneficial for the blood vessels. Turmeric, so in the spice cabinet we have the turmeric, which provides us with the curcumin, which is an antioxidant, protects the lining of the blood vessels, associated with benefits in the brain, associated with a reduction in the amyloid deposits. You know, those are just some that come to mind.

Then the olive oil, which is certainly a big part of this. There's the oleuropein. There's the oleocanthal. These are antiinflammatory. When you get a good olive oil, you get a little sting in your throat if it's a really good one. Antioxidant, antiinflammatory. We're always a little reluctant to talk about cancer, but anti-proliferation. There are some studies that have shown the biological activity of oleuropein too, and that's an olive oil compound, antimicrobial, antiviral. So, you could apply that to heart disease, absolutely, diabetes, but also neurological diseases. There are just so many mechanisms from the specific compounds that would benefit almost the entire lifespan. I can't think of ... Even children would benefit from having these very nutritionally potent foods as the centerpiece of their diet, rather than pop tarts.

Gazella: Yeah. Exactly. It is a long list. I have to say that I've only heard one complaint about the Mediterranean Diet from a clinical perspective, and that is that sometimes practitioners feel like it's not specific enough. You know, the DASH Diet and some of the other diets, they have very specific directions on how to follow the diet, X number of this and X number of this. Now, how do you describe the Mediterranean Diet in very specific terms to ensure proper adherence to the diet?

Root: Well, I try to describe the things to include and the things to avoid in order to hopefully be following it quite well. So, we don't include added sugar, for example. I say get rid of that. I talk about limiting and hearty limits on red meats, and instead fish, and also feel free to have days where you don't have an animal protein or the animal protein might be cheese or eggs, but that we keep eggs even limited somewhat. What we're doing is changing out saturated fats for unsaturated fat. I'm not one of these that thinks that saturated fats are all bad, but this is a diet that emphasizes olive oil, rather than butter.

When we start to make these changes and we begin to develop a taste for these more natural and less processed foods, your taste buds change, and you begin to find it easier to embrace this more ... It's a simpler approach to cooking, so very few things from boxes, for example, in the Mediterranean Diet. People always say, "But what about pasta?" I say, "Well, what about whole grains? What about exploring using bulgur wheat? If you're going to do a pasta, do something like a couscous. You know?" Fewer things from boxes, fewer things from cans, although tomatoes from cans I think are okay. More fresh herbs, less salt, and more fresh herbs and seasoning as spices.

As far as adherence goes, I recommend cookbooks, Karolyn. I think that it's easier to take a kitchen table approach to this. I find a lot of times when diets are specified very strictly, people get very frustrated and overwhelmed with the weights and measures of it all. How do we actually keep ourselves to 200 milligrams of cholesterol in a day, for example? How many milligrams of cholesterol are in an egg? I take a different approach as far as specificity and try to encourage a variety of colors of fruits and vegetables, less canned and boxed and more fresh.

Shop more often, not less often, so that you're going and you're getting some fresh produce, and you're going home and having it in the next couple of days. Several meals a week that don't feature meat. At least two or three meals a week that do feature fish, so that you're getting those omega-3s. If you're going to do the eggs, get the omega-3 eggs, because those are full of a very absorbable form of DHA, and also lutein, and other nutrients, the choline that your brain needs.

I take more of a Food Network approach to it than I do an American Medical Association approach to it, and I recommend cookbooks. I have a favorite cookbook. It's the Complete Mediterranean Cookbook, and it's done by the people that do Cooks Illustrated Magazine, so it's America's Test Kitchen. I got it from Amazon. It's got 500 recipes in it. I haven't found one that I haven't liked.

Gazella: I love that kitchen table approach. You bring up so many good things. When you're describing it to patients, you're talking about ... Just by telling them what to avoid, it's going to automatically be including healthier options in their diets, you know, like swapping out butter for olive oil and shopping more often. That's a great piece of advice as it relates to a Mediterranean Diet. I think those are some great tips. Now, in addition to describing the diet in those specific terms, is there anything else that healthcare professionals can do to improve compliance?

Root: I think there is. I think it brings up a piece of the Mediterranean Diet that we don't talk about enough, and that is imagine yourself in the South of France. Imagine yourself on the Island of Crete. Think about the way that they approach their day, their meals, their habits. These are people that are moving at a slower pace than we do here, so it's not as much about convenience as it is about community. The meals are a point of shared experience for the family, the extended family, your neighbors, people that you ... Even when you're doing business with people, you bring them to your table, and you break bread, and you have a glass of wine. It's a much more relaxed, chill approach to things than in our zooming from point A to point B, and running into the deli, and grabbing something, and running back out kind of approach to life.

You saunter through the market with a basket over your arm and pick up some fresh veggies, and some fresh fruit, and maybe a nice piece of fish, and maybe they've just baked some crusty bread, and you're going to take that home and break the bread, and dip it in some of that olive oil, which you've ground some seasoning and some spices in, maybe a little balsamic vinegar. You take a very slow approach to that meal. Maybe you're all cooking it together and having it a little bit at a time, but there's this sort of attitude, and this piece of mind, and this slow approach that they take. I think that that is as important to adopt that mindset as it is to be aware of the nuts, and the bolts, and the mechanics, and the ingredients of the diet.

Gazella: I am so glad that you brought that up, because you're right. A big part of the Mediterranean eating is social and communal. Honestly, I don't hear a lot of doctors talking about that benefit. I would agree with you. I think that does add to the health promoting aspects of the diet. Yeah. I think that's a great thing to emphasize to patients. Now, for those people who are having difficulty consistently following the Mediterranean Diet, do you recommend dietary supplements. If you do, take us through some of ... I know this might be kind of an unfair question, because it's not a one size fits all, but are there maybe your top three recommendations that would probably be good for 90% of the people?

Root: Well, of course, you know, I have my favorites, but fish oils, so a good, high quality omega-3 supplement. Obviously you want a trusted company, because you want it purified. These days, with the omega-3s we are taking the approach of reaching an optimal intake, and that's measurable now. There's actually a little finger stick blood test that we can do now to see where you stand as your omega-3 score is concerned. For most adults we actually need a little more than what had been the recommendation. High quality fish oil that provides somewhere around 1,500 milligrams of the active components, the EPA and the DHA, is one thing, fish oil and with olive oil as your main cooking oil.

There's even a functional food supplement now that is even a combination of the two that you don't actually heat up to cook with, but you could use it for salad dressing, or you could use it to do that dip the bread in thing that I described, which is the first course of so many Mediterranean meals. So, that's a place to start is a good, high quality omega-3 or a combination omega-3/olive oil supplement.

Then I think something that not enough people are taking that more people probably would benefit from is a good curcumin supplement. It's made from turmeric. The curcumin itself is not really well absorbed, so you want to take it at mealtime. Get one that is CurcuWIN or one of the trademarked turmeric supplements, because the manufacturers have helped with the absorption. Always in a meal with fat is the best way to take either a fish oil supplement or the curcumin supplement. Those are the first two things that come to mind.

Then if I were going to pick a third thing for Mediterranean Diet, it would probably be a resveratrol or a pterostilbene. Those are things that maybe people aren't getting enough of in their diet, and especially teetotalers. If you're not drinking red wine, then you may not be getting much resveratrol, and there really does seem to be some longevity associated with that.

Gazella: Yeah. I was going to ask you about resveratrol, because even if you are drinking maybe a glass or two, I think that enhancing the resveratrol amount in the diet is probably a good idea. It's such a powerful nutrient.

Root: Me too. There are a lot of people that a glass or two is absolutely as much as they ought to do, women. Really you've got to keep alcohol at a small to moderate level, because extra is so bad. So, we've just seen a look at early onset dementia with chronic, heavy drinking, and it was much worse in men, but that's because men are more likely to be the chronic, heavy drinker, but it was scary when I was reading about it, because these men that it's four to five drinks a day ... So, this is a see something, say something for family members. If you know somebody that's drinking that much, it's intervention time. It takes 20 years off of their life. With the resveratrol a little bit of red wine, great, but I wouldn't do more red wine in order to meet my resveratrol goal. I would take a resveratrol supplement.

Gazella: Yeah. That's such a great point. Well, before we wrap up, Jolie, I'm wondering if there's anything else that you'd like to share to our listeners about the Mediterranean Diet and how they could or should be using it in their clinical practice.

Root: I would encourage physicians to use any kind of teaching tool that they can. There is now the ... I'm drawing a blank on this. The Department of Agriculture makes dietary recommendations, and they actually have one now that talks about Mediterranean Diet, and they help people follow it, a Mediterranean style diet, but there is a wealth of information on the internet from trusted sources that can help with sort of the guidelines for the Mediterranean Diet.

I think Oldways has a Mediterranean Diet pyramid. Maybe even keep some good cookbooks in the office, and hold them up, and say, "Here is a great way to get started," and they can order them, or you can give them a gift or something. People need practical advice, and remind them of the community benefit, the gathering the family around the table, because that's not just about the Mediterranean Diet. That's something that really is missing in our busy culture, and everyone I think would be healthier if they were able to do more sharing over meals.

Gazella: Yeah. I would agree. I think the Mediterranean Diet is such a powerful clinical tool that practitioners can use. Well, once again, I'd like to thank today's sponsor of this topic, Carlson Laboratories, and I'd like to thank you, Jolie, for joining me today and sharing this information with us.

Root: It was a treat, Karolyn. It was so nice to talk to you.

Gazella: Yeah. Well, great. You have a great day.

Root: You too.

Mar 13, 2018

Sponsored by Perque Integrative Health

By Natural Medicine Journal

There is a significant link between lack of sleep and hormonal, inflammatory, and immune system health. In this interview, Russell Jaffe, MD, PhD, describes the connection and then provides information about his comprehensive, integrative approach to sleep issues.

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

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.


Karolyn Gazella: Hello, I'm Karolyn Gazella, the publisher of The Natural Medicine Journal. Today, I have one of my favorite guests, Dr. Russell Jaffe, with me. Our topic is sleep. But before we begin, I'd like to thank the sponsor of this interview, who is PERQUE Integrative Health.

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

Russell Jaffe, MD, PhD: A pleasure to be with you, Karolyn.

Gazella: Yes, it's always a pleasure. This is an important great topic. Now, the CDC has said that lack of sleep is a significant national health problem. It's reached epidemic proportions. Now, why do you think so many people today don't get enough quality sleep?

Jaffe: Well, first I commend my colleagues at the Center for Disease Control for waking up. Yes, sleep deprivation in our time, in this 21st century, it is at least epidemic, and it may be endemic. Endemic means beyond epidemic. If it becomes so usual that it's like the normal, we don't notice it.

Fortunately, CDC has noticed that sleep deprivation causes all sorts of "tsuris." That's a Yiddish word for problems. It causes all sorts of amplifications of dispositions to ill health. Not necessarily the sole cause or the single bullet in the problem that a person has, but anything you have will be made better by good restorative sleep. Anything, any health challenge you have, any performance issue, any life quality issue, will be made better by good quality of sleep and worse by a lack of restorative sleep. The emphasis here is on restorative, not just on being unconscious.

Gazella: Right, I would agree with that. I want to dig into some of the technical aspects of sleep. Can you first explain to us the intricacies of the hormonal regulation of sleep? What's going on?

Jaffe: Well, half a step back if you permit me, which is in biology, in life, it's always about proportion, or ratios, or balance or imbalance. We can, and I'm happy to talk about the hormones and the neurochemicals, and the sources of these neurochemicals that are amino acids. The sources of some of these neurohormones that are either a vitamin or a fatty acid, a dietary source again.

As Hippocrates said several millennia ago, "Let your food be your medicine. Let your medicine be your food." If you start with a healthy, all foods diet that you can digest, assimilate and eliminate, you will then take in a healthy balance of the precursors to all of these neurochemicals, neurohormones, et cetera, and the body will figure out how to utilize them in an efficient and effective way.

Now I know that's a kind of high level view. But when we talk about these rhythms, which sleep is a particular example of biological rhythms in action, we do know certain things. There are four phases to sleep. At the end of the fourth phase is the time when a release of growth hormone, a release of neurochemicals, a release of neurohormones occurs, and abnormal cells are identified and eliminated. It's called apoptosis for those of you who speak Greek. But it means that everybody makes abnormal cells, abnormal cells you could hear as cancer. But everyone makes abnormal cells every day. The reason we don't all have cancer is because at night we have a restorative and reparative system that also identifies abnormal cells and eliminates them.

Now I mentioned the importance of rhythm, and you asked me about hormones, which is the right question to ask for sure, one of them. One of the hormones we know in relation to stress resilience, and stress adaptation and stress response is cortisol coming out of the adrenal under the stimulation of the pituitary, which in turn is controlled by the pineal, and we'll get upstream at some point.

When cortisol goes up because we're under stress, if DHEA, the companion molecule on the other side, the source of the androgens and estrogens, if DHEA goes up in proportion to the cortisol going up, we're fine. It's when the stress hormone cortisol goes up and the DHEA is exhausted and cannot go up, that's when we have a first level of problem. That's when people feel invincible, but they're not. They're cruising for a bruising, but they're not aware of it because the cortisol overrides the commonsense of the DHEA and those androgen and estrogen compounds.

There are other hormone ... Go ahead.

Gazella: Yeah, that makes a lot of sense, and I was going to ask you, but are there hormonal connections, so please continue.

Jaffe: Oh. If I may, there are other modulators. One important balance point or ratio is the cortisol to DHEA. But then there are others including the adrenaline to serotonin. Now adrenaline derived from the amino acid tyrosine, derived from our dietary protein, adrenaline says, "Go and you can persevere until the success shall be won." In contrast, serotonin says, "Now hold on there. Maybe we don't have the fuel to go all the way to the end. Maybe we should be a little more sensible here and not get exhausted."

Now serotonin comes from tryptophan just like adrenaline comes from tyrosine. Both of these come from the proteins we eat. If we're a carnivore, we'll have more of those amino acids. If we're a vegan or a vegetarian, we'll have less. If you think your engine is burning too hot because of too much adrenaline, if you think that it would be better for you to be more on the calm than on the assertive side, my suggestion is try a plant based diet.

You might not want to be a vegan or a strict vegetarian cause I think you should have a wide variety of foods that you can digest, assimilate and eliminate without immune burden, and I'm not making any political statements about ... Although my personal preference is a more plant-based diet cause I think that's healthier. I think that's less polluted. I also think that's better for the planet.

But I put my little advertisement in, and now I'll get back to the fact that tryptophan becomes not just serotonin, the soothing counterbalance to adrenaline, but serotonin becomes melatonin in the pineal, this deep control center. We've learned about the pituitary as the master gland, but the mistress or the master of the master gland is the pineal, modulated through the thalamus and the hypothalamus. We can get into all those tracks if you want cause I really am a biochemist and a neuroanatomist.

But the point is that amino acids derived from our diet become the neurochemicals whose balance we express in our personality, in our resilience, or in the way in which we're distressed. The people who have mood issues, the people who have endurance issues, the people who are concerned that sometimes they, maybe either overreact, or they're just not in tune with what's going on and people misunderstand. In any of those situations, you have an imbalance of cortisol to DHEA and/or an imbalance of adrenaline to serotonin.

Gazella: Right, that makes a lot of sense. I love how you brought adrenaline and serotonin to life. That was perfect. I want to stick with the topic of amino acids here. You know, I've heard varying views about tryptophan versus 5-HTP regarding sleep. Can you clear up that confusion for us?

Jaffe: I absolutely can. There was a time when tryptophan was the favorite approach, the more natural approach to sleep, to sleep enhancement, sleep quality. Then it fell under a cloud because of something called Eosinophilia–myalgia Syndrome. At that time ... This was the late 80s, early 90s ... there was voluntary recall of tryptophan. At the same time, interestingly, that serotonin reuptake inhibitors were being advocated on the pharma side.

Tryptophan fell under a cloud until it became clear that due to a change in production techniques, one company called Takeda had inadvertently, not intentionally, but they had changed the way in which they produced tryptophan. It was cheaper for them to produce large bulk of tryptophan. But they also included what turned out to be something called Peak E, which was a dimer. It was two tryptophan molecules bridged by a small carbon bridge. The consequence was induction of pain, myalgia, muscle pain, and an allergic-like response, eosinophilia. The FDA, out of an excess of caution, asked the industry to voluntarily recall tryptophan and they did, which was the right thing to do, in my opinion.

At the same time, my group published a clinical observation, which is we had uncontaminated tryptophan, and we gave it to people with this Eosinophilia–myalgia Syndrome, and it helped them get better, and we published that. If tryptophan was the real culprit, then giving them tryptophan would have made them worse, and it made them better, and we published that.

Now the agency, the FDA did not yet know about the contaminate now known as Peak E, this dimer of tryptophan that somehow jangles things up or messes things up. In fact, we do know how it does that. It bridges across two receptors in a way that makes the cell very unhappy.

Out of an excess of caution, the FDA asked the industry to withdraw tryptophan. In the absence of tryptophan, 5-HTP became popular because it's a tryptophan derivative. That sounds okay. Until you learn that it most often goes to quinolinic acid, and a series of excito-neurotoxin consequences that are not so good. You don't get as much of the serotonin to melatonin conversion when you go through 5-HTP. It's actually better to go directly from tryptophan to melatonin and bypass the 5-HTP.

5-HTP is a supplement. It is available in health food stores and online today. It is not my preferred form because I always believed in tryptophan. I still believe in tryptophan. My recommendation is enhanced uptake tryptophan. Because it turns out when you have a little B6, a little B3, a little zinc, a little of the right fiber, then you double, triple or quadruple the uptake from the intestines into the body so you get smoother uptake and better total absorbability, or what we call bioavailability. That is basically what we recommend.

Gazella: Interesting. With the tryptophan, is there a dosage range for sleep that you typically recommend?

Jaffe: Well yes, in regard to the tryptophan ... And I do recommend the enhanced uptake and the chaperone delivery. But for the tryptophan itself, it's anywhere from 500 milligrams of free amino acid to 1,000, maybe even 2,000. It is absolutely safe for people to start at the lower end, which would be one capsule, say 500 milligrams, and go up anywhere from two to four, depending on their body mass, depending on their situation.

Then often people ask me the question, "Well, what if I get up in the middle of the night?" "Well, why did you get up in the middle of the night? If you got up to go to the bathroom, go to the bathroom and get back to bed. If you want, you can take a second dose of the tryptophan because the peak occurs at 30 minutes. It has really done its job after four hours. If you are in a deep sleep and you stay restorative in your sleep, you don't need more. But if you get up, for whatever reason, my suggestion is take another dose. Take another one, two, three, four capsules, whatever dose works for you, 500 to 2,000 milligrams per dose. You can take that two or three times in a night."

Now occasionally, people do tell us that if they take more than 500 milligrams, they sleep really soundly. But when they get up, they're a little bit groggy before they really get going. That feels, to me, like a little too much. "Metabolism does play into this individuality," as Roger Williams told us. Biochemical and individual natures of our metabolism, how robust is our liver, how effective is our spleen and kidney at any moment in time, these are important variables.

Gazella: Yeah, and I'm glad that you mentioned that about the breakthrough insomnia, because I think that a lot of people are affected by that, where they will wake up at 2:00 in the morning and then they're frustrated, so that's good to know about the tryptophan. Now are there any-

Jaffe: Well, let me add if I can jump in on that, cause it is very, very common. It is also very common in people who are more creative, more sensitive and more aware. Why? Because they're worrying. I think you know this, but the Dalai Lama is my daughter's godfather. One of the things he said to me is, "Don't worry."

Gazella: Good advice.

Jaffe: Good advice, hard to do. You have to practice it and that's the point. Sometimes two, three, four o'clock, maybe even five o'clock in the morning, it may feel early, but that's the preferred time for monks to meditate. They go to bed early, but they get up early.

If you're one of those people ... And I'm in that phase of my life. I tend to go to bed early now, and I tend to get up early. I find those few hours before dawn a delicious time to either relax, or stretch or meditate, or just have a few quiet moments to myself where the phone doesn't ring.

Gazella: Yeah, I would agree. Now are there any other amino acids that can be helpful with regulating sleep and mood?

Jaffe: Well, yes, and there's two parts to this discussion. There are the amino acids related to detoxification. Then there are the amino acids related to mood stability. If I can take those in reverse order, in regard to mood, it turns out that glycine, the simplest amino acid, is also a neurotransmitter. It's a soothing neurochemical. If the nerves are excited, glycine calms them down. If the nerves are exhausted, glycine provides an energy source to wake them back up. Glycine's really very important in the brain, also important in the gut nervous system.

In addition, if you combine glycine with methionine, a methylating detoxifying amino acid, and combine those two with magnesium aspartate, an amino acid that in its own right has been studied as a mood modulator, as an antidepressant. But when combined with the detoxifying methionine and the neuro-balancing glycine, that's a very interesting combo of simple amino acids that in combination with the tryptophan can give even deeper and more restorative sleep.

Gazella: Perfect. Then now you mentioned the detox side of things?

Jaffe: Right. Now the other side is there are three phases to detoxification, phase one, phase two, phase three. Within the detoxification system, you want sulfur containing amino acids like cysteine, C-Y-S-T-E-I-N-E, you want methionine, but you might want a little phenylalanine because in order for sleep to occur, you must have enough adrenaline in the deep brain sleep center so that the adrenaline falls at the same time that the serotonin rises. That's called going to sleep at the cellular, molecular, biochemical level.

Now what happens if the serotonin rises cause you're tired, and your body wants to go to bed, but there isn't enough phenylalanine-derived adrenaline to fall, you'll be exhausted, but you'll still be awake. What about the other side? What if the adrenaline falls, but you didn't take in enough tryptophan so the serotonin doesn't rise? You'll be groggy, but you won't have restorative sleep. We need to have the fall of adrenaline and the rise of serotonin at the time when we're horizontal, not vertical.

Gazella: Right. I want to kind of circle back to what's going on when we're sleeping because you mentioned previously when we're sleeping, the body is really quite active. I've read studies associated with inflammation for example. If you get six hours or less in just one night, you put your body in an inflamed state. We know that there's a strong connection between the immune system and the inflammatory system. What's going on with those two systems in particular, and why is it so damaging if we're not getting enough sleep?

Jaffe: A profound, important question, and a question for our time, our 21st century challenging time. There is so much that occupies people today, so many screens, so many calls, so many distractions, so many attractions, that most people do not appreciate that sleep is essential for quality of life. If you want to add life to years and you want add years to life, you must have a quality of sleep.

Most of us, at some point, we become tired and/or exhausted. We do get into bed. Most of us even take our clothes off before we do that. But most people ... And I'm the exception here and I would advocate being the exception. Most people do not have a roughly half an hour or so during which they prepare for a restive, restorative, rehabilitative sleep time. They might even dream. They might even be able to solve a problem and bring a solution back into waking time. It turns out you can do things called lucid dreaming if you're inclined towards that.

But the bottom line is that sleep, preparation for sleep, and appreciation of the importance of sleep has been massively devalued in our society. Where we're supposed to go as close to 24/7 as we can and sleeping is somehow either depreciated, deprecated, or seen as a sign of sloth.

Now when I was a young doctor in the academic medical world, I can tell you that I slept so little that when Rebecca and I got together ... Cause she's a fine artist who values her sleep, and she's a terrific human being if she gets 10 to 12 hours of sleep a day. At the time, I was sleeping about four hours a day and thought that was just fine, which meant we had to choreograph being together, but we figured it out.

My point is that very often the very people who would benefit from mindfulness and restorative sleep don't "have the time." They can't fit it in. They're too driven to succeed. Or, as the Dalai Lama says, "They sacrifice their health to gain wealth. Then they give back their wealth to regain their health and they are so busy living in the past or ruminating about the future, that when they pass in the moment, they have barely lived."

That's a classic Buddhist perspective. I'm not particularly Buddhist, although I've done of lot of mindfulness myself. I have found that it helps to not just to feel that I've indulged in sleep, but to know that with wisdom and more years, having the ability now to go to bed early and get up early is delicious. I don't miss going out to the Kennedy Center as much.

Occasionally, I still want to go out and socialize. I have friends over. I prefer to cook for them than to go to a restaurant cause when I cook, I know what they're going to eat. I know we're going to sleep better because it's going to be food you can digest, assimilate and eliminate without any burden. I'm even going to take into account what their biochemical individuality might be and sometimes I get it right, sometimes I don't, but I always try.

Sleep is our friend. Sleep is to be appreciated for the positive side, not for the absence of usual consciousness.

Gazella: You know, I want to get back to specific nutrients cause we've already talked a lot about amino acids. But before I talk about other nutrients, I'd like to talk about sleep medications. There are some pretty potent prescription sleep medications. There are over the counter sleep medications. Do you have an overarching view of these sleep medications and if they're helpful or if you think it's better to try to get patients off of these sleep medications? What's your view?

Jaffe: Well, actually it's interesting. My view is more or less the same as the FDA. The FDA's official view is if you can do without them, please do. If you can possibly do without them, do. Because the adverse effects are clearly known. The benefits are also statistically defined. If you absolutely need them, they are beneficial at least within the reductionist frame of our scientific method.

But while I agree with the FDA, I often find that if people will follow through on what we're talking about. Including, having a diet that's appropriate for them, that they can digest, assimilate, and eliminate without a burden.

When they have enough of the essential vitamins, include vitamin D, which is really a neural hormone and other essential nutrients. So that their cells can deal with the challenges and stresses of the day without being so overexcited or overexhausted, those are two extremes which we want to avoid. Being overexcited or overexhausted.

We want to be resilient, we want to be in the middle. Sleep is just really important for all of that. Now with regard to prescriptions, the most common question I get is, can we approach this nature, nurture, and wholeness approach to sleep ... these amino acids and these fatty acids that are the precursors for these complicated molecules.

Can I increase nature's sleep balancing, stress balancing molecules? The answer is yes, although in many cases—especially, in the cases of Ambien and other serotonin reuptake inhibitors—when you bring in nature's team, the full valet or symphony of life, very often you can taper the pharmaceutical hypnogogic sleep medicines.

Taper them, eliminate them slowly. The importance of that is that it's known and it's been proven in many scientific studies. That you do sleep, however you don't dream and you don't have the normal sleep rhythms phase one, two, three, four. You don't have the normal release of growth hormone, which is so important to identify abnormal cells and eliminate them.

So sleep prescriptive medicines are benefits with a cost. I usually find that when we bring in the essential nutrients that people can't make. That they must take in from their diet or supplements, that they can then taper safely and effectively, the pharmaceutical sleep medications.

Gazella: Yeah, that's good to know. Certainly long-term use is definitely not indicated with those pharmaceuticals. Talk a little bit about those specific nutrients that practitioners who are listening can use to help improve sleep quality.

Jaffe: Well, we've talked about amino acids, so I'd like to note turn towards the fats. Those essential fatty acids, the omega-3 and omega-6 fats are the sources for the prostaglandins. They're the sources for the thromboxanes, which are the really active but short lived molecules inside the body.

We can measure the balance of omega-3 to 6 in laboratories. Neil Harris has devoted decades to validating the omega-3 index. My colleague, Artemus Simopolous, has looked at the NHANES National Health and Nutrition survey data.

She says that Americans now, instead of having a balance of omega-3 to -6, because of edible oils, and fats in our diet, and these foods that are crisped, and chipped, and so forth. It's typical for Americans to have 20, 30, 50, 80 times more omega-6 than omega-3, which is pro-inflammatory.

That makes you feel worse faster. That makes you more inflamed, and creaky, and uncomfortable faster. Folks like me no longer use edible oils. We cook with wine, or we cook with broth, or we cook with beer, and whole foods.

When you do that, you can restore a typical four to one ratio and not be so pro-inflammatory. Many people that I meet today look, feel, and function as if their body is under assault, inflammatory assault as if it's not repairing itself.

Inflammatory is really repair deficit. When your body can repair itself, you don't have inflammation. So we don't want to have zero omega-6 intake, but we don't want to have 50 times omega-6 to omega-3.

There is an omega-3 index test. It's one of the eight predictive biomarkers. It can help you take in the sources of fat that are essential and good. By the way, there is good fat. Omega-3 and omega-6 fats are good unless they're damaged by air and oxygen, in which case they're bad.

So you want them distilled under nitrogen. You want them in whole food sources. You want them in the healthier forms so that your body can convert the omega-3 fats into the prostaglandins that repair you while you still have a little bit of omega-6 to activate the system. But not so much that it creates repair deficit commonly known as inflammation.

Gazella: Perfect. Now in addition to the EFAs, before I move on to my next question, are there any other nutrients that you'd like to highlight?

Jaffe: Well, yes and it's in the broad category of, life is connected at every level with every thing. But when we think about, say sleep, and how the systems that convert these amino acids or these fats into the quality of sleep molecules that we're looking for.

We must have enough antioxidant ascorbate in the cell to donate electrons and prevent free radical oxidative harm. We must have enough magnesium, choline, and citrate. We advocate advanced uptake in chaperone delivery of magnesium using choline citrate.

So that you can correct the acetylcholine/bile salt deficiency at the same time you've energized and alkalinized the cell, while bringing magnesium into the cell. When very often, there's too much calcium and too little magnesium.

In fact, calcium channel blockers are a major category of pharmaceuticals because there is a relative excess of calcium. But there's an absolute deficiency of magnesium. Magnesium in the diet, Dr. [Rah Aleem 00:06:51] has shown, has dropped half, by 50 percent in the last 50 years.

While the need for magnesium ... because of stress and medicines that waste magnesium. Like, proton pump inhibitors and H2 blockers, and many chemotherapies, and even hypertensive medicines like diuretics are known to waste minerals including magnesium. So, as my grandmother used to say, the rents are going up and the ceilings are coming down.

Gazella: It's true. So, you know the conversation between the patient and the doctor is an important one. I'm wondering for the Healthcare Professionals who are listening, what type of tips do you give patients to help them get a good night's sleep?

I know you believe that it's not just a matter of handing somebody a pill and calling it a day. It's a very comprehensive approach that you have to health. So, what type of advice do you give to people who are struggling with sleep?

Jaffe: Thanks for asking and yes, as important as I believe diet and supplementation are in the 21st century, it's about what you eat, drink, think, and do. So, let's talk about the doing part of preparing for sleep.

Here's what I do, I set aside the half an hour before I'm gonna get into bed. During that half hour, I want to get as much value as I can. So I set a salt and soda bath. I put a half to one cup of Epsom salts and a half to one cup of baking soda.

My skin isn't dry, but if my skin was dry, I might put in a drop of Rosemary or some other Emollient oil, an aromatic. I soak in there for about 20 minutes. While I'm soaking, I do five minutes of deep abdominal breathing.

If you want to know what abdominal breathing is like, get a video of a baby or watch a baby because they all do it correctly. They breathe abdominally. Then, do about 15 minutes of mindfulness practice, or active meditation, or whatever is your preference to let go of the day.

Very often, people fall into bed, reasonably tired and exhausted. But thinking about the stresses of the day and they bring that into the bedroom. In my bedroom, we actually have no screens, we have no clocks, we have no alarm clocks, we have no phones. I know this is hard to believe, but I actually when I go to bed, I don't need to hear the emails coming in on my phone.

I believe, if you can, at the place where you sleep should be a place of serenity. That you should give yourself a half an hour to let go of the day and really let it go. Then, have an active time of restoring yourself through sleep.

If you want the bonus round, it's the green dichromatic light that I learned about from [Banti Darmawarh 00:09:56]. A rather extraordinary monk. Green dichromatic light is known to go directly from the retina to the pineal gland. In the pineal gland, it says everything is okay.

Green is the harmonizing color. This has nothing to do with vision. It has everything to do with the retinal / pineal direct connection, which has been reconfirmed by others. As [Banti 00:10:25] said, well wisdom, new things, millennia ago, and science is catching up and that's a good thing.

Gazella: I have not heard of the green light. That's fascinating to me.

Jaffe: No, it is fascinating. You may have heard about light boxes. There are people with what's called Seasonal Affective Disorder or SAD?

Gazella: Sure.

Jaffe: Norman Rosenthal and NIHMINH, showed that if you stay in front of these fluorescent light boxes for three hours a day, it boosts your pineal, and you get a little more melatonin, and you're less depressed. Banti said, people don't have time for that 20 minutes twice a day in front of the green. That's what we recommend.

Gazella: Wow, that's awesome. What about other hygiene aspects? Like the temperature of the room? Light in the room? Are those valid?

Jaffe: Thanks for asking. The answer to the second question in regard to light. It should be as dark as possible. Now if for some reason, it is not pitch black in the room where you sleep, please get a comfortable eye mask.

You should not have photons of light hitting the retina while your eyes are closed during sleep. If that requires an eye mask, please. They're not expensive, they can be comfortable. Take a flight on the Air Singapore, they'll give them to you. At least in business class. That's the question of dark.

Now, the nature of the room itself, should be comfortable, cool, this is a situation where warm is not your friend. What I have is a latex mattress which is very firm and lets me float. That's a nice thing. I have a duvet, so I have ... Some goose donated some feathers and somebody sewed this together.

In Germany, this is routine. You have this light Duvet on top of you. You have a mattress that will support you. It's cool in the room, you don't want it warm. Does that address your question?

Gazella: Absolutely, absolutely. Those are some great tips that our Practitioners can keep in mind when talking to their patients. I'm just wondering, we're about ready to wrap up, is there anything else that you'd like to talk about sleep for our listeners today?

Jaffe: No. I thank you for the opportunity to come at it in this way. Restorative sleep is one of essentially components of a life well lived. As someone who didn't think that sleep was important for many decades of my life, I can tell you it was a mistake.

I'm correcting that now. But I do also believe there are different phases to a life. I think if you're an adolescent, you have a different sleep rhythm. My understanding today is that young people actually do go to bed later and get up later, although they may or may not be able to do that and still graduate from schools.

But I do think at different seasons of our life, we have different relationships between wake and sleep. I want both my wake time and my sleep time to be as productive as possible because this is the only life that I know I have at this time. Therefore, every moment to me is precious.

Gazella: Yeah, absolutely. Great point, great way to end. So once again, thank you Dr. Jaffe for joining me. I'd also like to thank the sponsor of this interview, Kirk Integrative Health. Thank you and have a great day.

Jaffe: Thank you, Karolyn. A pleasure.

There is a significant link between lack of sleep and hormonal, inflammatory, and immune system health. In this interview, Russell Jaffe, MD, PhD, describes the connection and then provides information about his comprehensive, integrative approach to sleep issues.
Feb 6, 2018

Skin conditions are common in many clinical practices. In this interview, dermatologist and researcher Raja Sivamani, MD, describes how an integrative approach can help improve outcomes, especially with difficult to treat dermatological conditions.

About the Expert

Rava Sivamani

Raja Sivamani, MD, CAT, is a board-certified dermatologist and an associate professor of clinical dermatology at the University of California, Davis, and director of clinical research and the Clinical Trials unit. He is also an adjunct sssistant professor in the Department of Biological Sciences at the California State University, Sacramento. He engages in clinical practice as well as both clinical and translational research that integrates bioengineering, nutrition, cosmetics, and skin biology. With training in both allopathic and Ayurvedic medicine, he takes an integrative approach to his patients and in his research, with a focus on the gut and skin microbiome and lipidome. He has published over 80 peer-reviewed research manuscripts, 10 textbook chapters, and a textbook titled Cosmeceuticals and Active Cosmetics, 3rd Edition. He has a passion for expanding the evidence and boundaries of integrative medicine for skin care.

About the Sponsor

Dermveda Leaders in Dermatology Education

Dermveda is an integrative skin care, beauty, and wellness site dedicated to inspiring and empowering people to develop a healthier, more holistic relationship with their skin. We provide skin education tools and personalized, science-reviewed health content for both consumers and practitioners. Membership is free at

Dermveda's continuing medical education site, LearnSkin, was developed by leading dermatologists and integrative medicine practitioners to support integrative dermatological education throughout the healthcare community. The goal is to share the latest in scientific research and treatment options in dermatology for both Western and Eastern medicine. We aim to meet the growing demand for high-quality, evidence-based education that bridges conventional and alternative medical approaches. The first eczema series will begin in March at

Later this year, Dermveda will be hosting the first annual Integrative Dermatology Symposium in Sacramento, CA, from October 19-21, 2018. Experts from around the world in the practices of Western, Naturopathic, Ayurvedic, and Traditional Chinese Medicine will come together for this special event. The Symposium will feature educational sessions, clinical content, targeted industry trends, practical takeaways, and best practices related to all aspects of skin care. Registration opens in March at


Karolyn Gazella: Hello. My name is Karolyn Gazella and I am the publisher of the Natural Medicine Journal. Today our topic is integrative dermatology and my guest is Dr Raja Sivamani, an integrative skin care expert.

Before we begin, I'd like to thank the sponsor of this topic who is Dermveda.

Dr Sivamani, thank you for joining me today.

Raja Sivamani: Thank you so much for having me. It's a pleasure to be here.

Gazella: Well this is an interesting topic and I have to say that we have not covered this a lot in our journal so I'm super excited to talk to you today.

So, let's start with a very basic question. How do you define or describe integrative medicine specifically as it relates to dermatology?

Sivamani: Karolyn, I agree with you, this is actually a really exciting area when we think about integrative dermatology.

So, to answer the question that you're asking, you know, how does integrative medicine specifically relate. Dermatology really has many facets to it and by in large, many times when you go to see a dermatologist the appointment can be a little rushed and typically you're in there for about 15 minutes or so and many times the conversations will be focused on things like the diagnosis, which is super important and then some basic treatment plans and maybe a surgical treatment plan.

When we start thinking about integrative approaches, really then you start to take into all the other aspects of dermatology that are so vital to providing good care when it comes to anything skin related. So things like psychology, preventative approaches, diet, what you're putting on your skin, daily habits. All these things comes together and so, when I think about integrative approaches to dermatology it really is about a team approach and some of that team can be deployed by the practitioner but many times I also think about this expanded team that's working together in a way that, you know, maybe one practitioner's able to provide certain aspects and then another practitioner is able to provide other aspects of care and then them working together. So, that's how I view integrative.

And integrative, just as an add-on but I do want to talk about is, is not to say its separated from conventional medicine. I think bringing in conventional medicine, making that just as an equal part of the conversation, I think is really important.

Gazella: I would agree and that fits perfectly with the focus of our journal so this is great now.

So, what are some of the more common skin conditions that practitioners are faced with in clinical practice?

Sivamani: It turns out dermatology is so common. A lot of people see people with skin conditions. They did a study at the male clinic where they looked at how often and what kind of skin conditions, sorry, what kind of general conditions come in and skin conditions were really high.

The ones that are common and they tend to be pretty prevalent in the general population are things like acne, of course, these all depend on different age groups as well but, acne is very, very common. When we talk about eczema specifically, atopic dermatitis, that's another one that's common but there's also other conditions that may not be as common as those two but are still pretty common. Things like psoriasis and there's also seborrheic dermatitis, rosacea so, there's quite a few things that come up over and over again.

And, another sub-set of eczema, not atopic dermatitis, which is more dealing with pediatric population, and that does extend into an adult population but then there's also just common irritations that come up on the skin on a day-to-day basis that anyone can get. Things that mean to us as contact dermatitis either from irritation or an allergy.

Gazella: Now out of all of the skin conditions that are out there and, there are a lot of them, what are some of the more difficult to treat skin conditions that practitioners are faced with and, why are they so difficult to treat?

Sivamani: Karolyn, this is such a great question. I really like this question for a couple of reasons. When we talk about difficulty I really break that up into two modes, two facets to what makes a skin condition difficult to treat.

Firstly, a skin condition can be difficult to treat just because it's a rare condition and it will require some treatments that sometimes aren't always well studied because it's rare. And so, you can have conditions that just don't happen that often and when they do often and sometimes you know this condition can be auto-immune or other facets to them that really make it more difficult.

I think there's a second facet, though, that really is a challenge as well. And that's conditions that are chronic and that require constant management. We really have to integrate in lifestyle and other approaches and symptom management isn't enough. So, you have conditions like acne that, you know, they just won't cure on their own, you need to have some sort of active management to that in a very, what I believe, holistic conversation and things like eczema require so much activity from, you know, if you're a patient and you're taking care of eczema that's one thing but, if you're a baby, then you're really dependent on caregivers and so then it becomes a conversation with the caregivers and managing how they are approaching the treatment.

And so, I think that that second group where you have chronic conditions that don't necessarily have a cure but, if you can get really good management then it can make a huge difference. I think that is also a pretty big difficulty because it requires constant conversation and a lot of education. I think education is key in those kinds of situations.

Gazella: Yeah, that would make a lot of sense.

Now, I find it interesting that you have training in both allopathic and Ayurvedic medicine. I'd like to focus a bit on Ayurvedic medicine. So, for our listeners, what is Ayurvedic medicine?

Sivamani: Yeah, so, Ayurvedic medicine is, it was born from a tradition that's very rich in India. It's over 5,000 years old and their approach is really looking at homeostasis, meaning when you're in balance. Just to simplify it, is when are we in balance and when are we in a state of imbalance? And so Ayurvedic medicine has some tendance in how it measures what it means to be imbalanced, what is your imbalance state and I'll just use a couple of cavular terms. One is, prakriti which is your state of balance or what they say your original constitution but then you also have this notion of what's known as Vikrity which is your imbalance state and they use the three doshas which are known as vata, pitta, and kapha in a very broad manner to identify what those imbalances are and, a lot of approaches including lifestyle approaches, dietary approaches, what you put on your skin, believe it or not, you can even describe western medicine from an Ayurvedic perspective and the idea is, can you take this imbalance and move it back towards balance?

What I really like about Ayurvedic medicine is that it can really go well in an integrative approach. So, you clearly have conventional approaches that tend to be focused much more on symptom management and then Ayurvedic medicine gives you tools, and I think that's really important, just having this ability to have this conversation to what it means to be in balance so you have these tools to talk about what are different lifestyle changes you can make or what would be an appropriate dietary change that you could make.

If I may add, one of the fun things I think about Ayurvedic medicine is that it gives you the opportunity to personalize and in conventional medicine they're really good about research studies that will study a large group of people and then in many ways you get kind of an average outcome and then you can apply that to each patient.

So, if you bring the two together you have this really powerful system where Ayurvedic medicine allows you to personalize a little bit more on top of what you're going to do and then conventional medicine gives you the ability to have broad-stroke approaches that might give you a good starting point, especially for symptom management.

But, Ayurvedic medicine is really rich on the personalization aspect.

Gazella: I think that's important. That really has become a big emphasis, it's no longer one size fits all. I would assume, especially in the area of dermatology and these difficult to treat skin conditions.

Can you give us a few examples of how you apply Ayurvedic medicine to dermatology in clinical practice?

Sivamani: Sure, you know, that is one of the funnest parts and really interesting parts of my practice. I feel like I get to know my patients better. If I may say, from one of the really key aspects of Ayurvedic medicine is, I have to get to know the patients habits much more and understand what kind of things are they doing in their daily life. That in and of itself gives me a greater connection.

So, for example, if I have a patient coming in with eczema and Atopic dermatitis, we're talking about different management approaches. One of the things that can sometimes come up is if we're just taking a pharmacological approach and we're talking about steroids, a lot of people want to know, am I going to be doing these steroids for the rest of my life, is there any sort of way that I could do management that doesn't require the steroids to be used?

So then you have this rich knowledge in Ayurvedic medicine about all these different oils and how oils are used on the skin and, there's a rich, rich literature, rich history on different oil therapies and what they call oliation and what's known as abhyanga, so self massage or massage with oils. And it really opens up a conversation because you can start talking about moisturization but bringing in the science of natural oils and, this is an area that's started to really grow in dermatology, what's the role of coconut oil, what's the role of olive oil, what's the role of sunflower, safflower oil, this has now started to hit the medical literature.

What Ayurvedic medicine does is it goes one step further and you can do herbal infused oils and I have these conversations with my patients. I tell them, you know, why don't we talk about maybe some simple ways to make a herbally infused oil where you can have a moisturizer that is really based on an oil therapy.

And what starts happening is, people start to become very engaged with themselves. Their skin becomes a part of them that they're not afraid of anymore and they're used to touching themselves in a way that's actually very therapeutic and then, you know, funny thing is, when I have these conversations then they realize that there's a holistic approach and then they're okay with using the steroids and they understand why we're using steroids and then it's part of a bigger picture approach to managing their symptoms.

So that's one example that comes up very frequently in my practice.

Gazella: And now give us an example of a herbal infused oil. Like which herb would you put with the oil for which condition? Is it that simple?

Sivamani: It's a little bit more nuanced.

Gazella: Okay.

Sivamani: What you have is you have different dosha imbalances and different oils, there can be, some oils that are warming in tendency or they can be cooling, I mean, you have to balance that with the doshas but, I'll give you one example, which I think is a pretty good one.

Coconut oil is widely used now as a moisturizer and sometimes what we can do is we can infuse, there's a herb called neem. Neem has both anti-bacterial and anti-fungal properties and we've been studying it. Actually, I have a basic science laboratory as well and we've been looking at neem specifically. But, one thing you can do is you can create an infused oil that has coconut oil as the base with a neem infusion and what that does is it gives you this oil that's not only going to be helpful for bolstering the skin barrier and nourishing the skin and, from that aspect but you also get that extra little antibacterial effect.

Now, I don't want to claim that it's an antibacterial like something that's been studied through the FDA but that being said, in eczema, sometimes, its smaller shifts in the microbiome and one of the things that we try to do is think about, from a practical perspective, can be infusing oil that might be able to touch upon those kind of aspects and then eventually it would be nice if we could start studying them in controlled studies and really looking at how, what is it doing to, for example, the microbiome?

But that's one of the examples of an infused oil that we might use.

Gazella: Yeah, that's a great example.

Now what advice do you have to healthcare professionals who may be struggling to treat some of these difficult to treat skin conditions in their clinical practice?

Sivamani: This is such a fantastic topic to talk about.

When it comes to treating conditions that are a little bit more difficult, I think it's important to realize that there's a team available and there's also the patient perspective. But I think the team approach is really important.

You're not alone and, what I mean is that, if you have someone that has a really bad itch, for example, we can do our best as a, myself, as a dermatologist, I can talk to them about what are some of the things they can do to help their skin not be as dry or are there some treatment options to help reduce the itch even from a pharmacological perspective. But then, I think it's really helpful to start thinking about the psychology of itch. What are the other approaches that we can take so then, if we can get them to one of my colleagues in, for example, traditional Chinese medicine and they can take an approach where maybe they look at acupuncture, and that can channel in on a different aspect to itch and, you know, focusing a little bit more on some of the other approaches, I think that's where it really becomes important.

When you're struggling to treat a more difficult condition that may even be chronic, it's to start thinking about a team approach and I feel like that's the essence of integrative approaches anyway and so if we can start developing teams and developing good partnerships with other healthcare professionals then as a healthcare professional we won't feel alone and as a patient, the patient won't feel alone either and they see that there's a team working for them.

Gazella: Yeah, absolutely, and that definitely is in line with the integrative approach that you described in the very beginning.

Now, you are an advisor to the company Dermveda. Why did you want to work with Dermveda and how is it different from other skincare companies?

Sivamani: What I really like about Dermveda is it's focused on education and, if you look at the founding team, the founding team consisted of people that are really dedicated to dermatology, they're very good teachers and lecturers and, also they have a good education background and, I like education first approaches because I think if you can teach people to start thinking more deeply about their condition, and when I say deeply, not just about maybe the molecular mechanisms or some sort of cellular pathway but really understanding that that's important but, it's also important to think about things that may be affecting you emotionally or psychologically and allowing people the space to see that these are also important and by opening them up to have better conversations with themselves and their practitioners.

That's why I'm so passionate about this company. I'd personally really dedicated to education, I like education in all of its aspects and I think its really important to empower patients and practitioners and so, because of that approach, I really am drawn to the Dermveda's approach and also, the holistic and the integrative approach allowing us to learn about, not just conventional medicine but also thinking about Ayurvedic medicine, traditional Chinese medicine. Our naturopathic colleagues have such great insight into the botanicals and into plant based approaches but I think that, giving a platform for this open discourse that's honest and credible is super important so that's why I'm so interested in this whole approach.

Gazella: Yes, I was thrilled to see that Michael, Dr Michael Traub is on your team. He is a friend of the Natural Medicine Journal and on our editorial board. A very top-notch doctor so, that was exciting for us to see that as well. And now, Dermveda is also hosting an integrative dermatology symposium this October in Sacramento, California. Can you tell us a little bit more about that symposium and why you feel it may be important for practitioners to attend.

Sivamani: We are so excited about the symposium, the integrative dermatology symposium is going to be the first time where we're going to get all the different perspectives into the same room and have a good open discourse and really start talking to each other ina way that we can start building relationships.

This symposium is going to really feature a wide variety of things. You mentioned Dr Traub, he's going to be one of the speakers there.

I still remember one of the first lectures that I saw with him and I was really impressed by, not only was he able to talk about the pharmacological approaches but it was so nice that he put in things about, and this was with eczema, we were talking about treating eczema, he had a lecture on that and, he put in things about a humor and what does that do for a child at the end of the night when they're about to go to bed, if you can have some way of getting them to laugh, does that make a difference?

I think its important to talk about these aspects and what we'd like to do in the symposium is really put that into a situation with all come together in a focused way where we have this combined goal of just making it better for each other to treat our patients and leaning what's new and what's coming out that's in the new literature and realize that any one perspective isn't the full approach.

And, if you can start taking a different perspectives it really makes a difference and, I'll give you an example. So one of the things that we're going to be talking about is like one of the lectures is going to talk about emerging approaches to eczema and there'll be conversations about all these new medications that are now coming out but then there's also going to be conversations about what is the latest science on the oils that are being used for eczema. Which oils seem to be the best, which one's may not be the best.

And then from there, they'll also swing into a conversation about diet and so, I think one of the things that sometimes we miss out on in just the medical education that we might go through is that you might get pieces and bits but when we start thinking about continuing education, you want to start really have good, honest discourse about all the aspects because that's really what the patient really wants. They want to have a good, holistic conversation about everything. They want to know what can I do with diet or, what can I do with my lifestyle approaches.

So, this is going to give practitioners, that attend, the chance to be empowered to understand what is the latest in that but not only that, I think the most exciting part about it is, we're going to get everybody in the same room and you just never know what's going to develop in those kind of situations. What kind of partnership and friendships are going to come out of that and I think that's the way to really push the boundaries of medicine so that when we talk about integrative medicine it really just becomes medicine and it's just the approach that we all would want to take with any patient that comes in.

Gazella: Yeah, that's a very good point and it sounds very comprehensive and we have a link to the conference. So, for our listeners who want to learn about more information about the integrative dermatology symposium, you can just click on that link and then you'll be able to find out more information.

Well, once again, Dr Sivamani, thank you so much for joining me and I would also like to once again thank our sponsor, Dermveda.

Sivamani: Thank you so much and it's been a pleasure to be here with you.

Gazella: Great. Have a great day.

Jan 25, 2018

In this video interview, Christopher Shade, PhD, describes the diverse clinical applications of cannabidiol (CBD) oil. Also included is information about safety, dosage, and other issues associated with this somewhat controversial natural substance.

About the Expert

Christopher Shade, PhD

Christopher W. Shade, PhD, founder and CEO of Quicksilver Scientific, specializes in the biological, environmental, and analytical chemistry of mercury in all its forms and their interactions with sulfur compounds, particularly glutathione and its enzyme system. He has patented analytical systems for mercury speciation (separation of different forms of mercury), founded the only clinical lab in the world offering mercury speciation in human samples, and has designed cutting edge systems of nutraceuticals for detoxification and antioxidant protection, including advanced phospholipid delivery systems for both water- and fat-soluble compounds. Quicksilver Scientific is recognized globally for innovating on behalf of the pharmaceutical and nutraceutical industries. Dr. Shade is regularly sought out to speak as an educator on the topics of mercury, environmental toxicities, neuroinflammation, immune dysregulation, and the human detoxification system for practitioners and patients in the United States and internationally.

About the Sponsor

Quicksilver Scientific

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.

To purchase Quicksilver Colorado Hemp Oil as a Practitioner, please access Consumers, please access


Karolyn Gazella: Hello. I'm Karolyn Gazella, the publisher of the Natural Medicine Journal. Today we have a fascinating and somewhat controversial topic to talk about. We're going to be talking about the therapeutic effects of CBD oil from cannabis. Before we begin, I'd like to thank the sponsor of this podcast, who is Quicksilver Scientific. My guest today is Dr. Christopher Shade. Dr. Shade, it's always a pleasure.

Christopher Shade, PhD: Always a pleasure.

Gazella: And I have to ask you first of all, is there a reason that CBD oil would be controversial? Am I right in that?

Shade: Much ado about nothing.

Gazella: Maybe.

Shade: You know, is there a reason for controversy? Controversy's built out of us evolving as a society in which we had instituted cannabis prohibition, and we all had this reefer madness fear around the THC side of cannabis, the psychoactive high-inducing side. But CBD is coming from industrial hemp, which is the THC is bred out of it, and you're left with another component that is big in the resins of cannabis, and it's called cannabidiol. It's chemically different than THC, and its physiological effects are vastly different, and they seem almost magical when you look at so many ... At the variety of things that they do for you, but they don't get you high. They have an effect of balancing and calming the mind, but they have so many different therapeutic benefits, and it's really just getting people out of the fear of the evil weed, into this wonderful, medicinal plant and all the uses it has.

Gazella: I want to get into the mechanisms of action and all the science associated, but first, and I know that you're not a legal expert, but is it available freely? Is CBD oil available for purchase, or are there limitations because cannabis is not legal in many states?

Shade: Yeah. The entrance of CBD into use in the US was made possible by the 2014 Farm Bill, which was allowing the use of industrial hemp for various uses in trade in the US. In those uses came the use of the extracts. Now, by some interpretations, well, that's still cannabis, and that's still scheduled as a drug. Certain parts of the government are saying, "Hey." Like the DEA. "Hey, that should still be scheduled. We didn't say that's okay." Whereas other parts of the government are saying, "Hey, that's all right. That comes underneath the Farm Bill." Most of the states have rolled with this being under the Farm Bill, and being an allowed substance. It's gained so much widespread use, and a lot of that use is from very impaired people that rely on it heavily for their health.

Most places are reluctant to step in and go against the Farm Bill. Certain states, however, Indiana notably, recently the Attorney General said, "No. We're not doing this, except for under certain exemptions. If you have a certain type of a ..." It was probably a seizure disorder, "Then you can get a permit to use this." Missouri, I don't know the extent of their laws, but they're kind of difficult. Most people don't sell it in Missouri. Then other states are taking a tack of trying to adopt it into a state cannabis law. Making it like THC, where it's regulated by the state, just like Colorado regulates THC. It does not regulate CBD independently, but for instance, the State of Florida is trying to bring CBD into their medical marijuana world. We'll see how it rolls in Florida, but right now the places to stay out of are Indiana and Missouri. This is such a moving target that this might change in a month.

Gazella: Right. Now, just to clarify, though, CBD oil or hemp oil does not have THC in it.

Dr. Shade: No. In most of the extracts of industrial hemp ... Industrial hemp is defined in the Farm Bill as a plant that, on a whole plant basis, has less than 0.3% THC. When the Colorado Department of Agriculture goes and certifies a crop here for being harvested and processed, it will take representative plants and analyze them for this threshold of THC. Now, these plants usually have, oh, 7% to 9% to 10%, upwards to peak around 15% CBD as well. There's some residual THC along with the CBD. One of the concerns originally was, "Well, when we concentrate that up, will there be enough THC for people to get high?"

Now, processors who are trying to stay very clean with the law will use extraction technologies and post-extraction purification technologies that minimize the THC. For instance, in our CBD oil, there's virtually indetectable THC. Whereas some oils will have a 20-to-1 CBD to THC ratio, ours is around 500-to-1. It's super clean, and that's nice because a lot of people that want to use the oil have THC testing programs that they're in, if they're firefighters, or policemen, or airline pilots. A lot of the commercial extracts have enough THC that if you're using large amounts to be really therapeutic against something like pain, you will probably have enough THC to tip the scales on some of the analytical techniques looking for THC.

Gazella: Got it. Thanks for that clarification. Now, let's get into the science, which is your area of expertise. What's going on from a mechanism of action standpoint? How does CBD oil work inside the human body?

Dr. Shade: Well, it works on a number of different levels, and when we were describing this, we used to chase after one thing or another. We'd say, "Oh, it's antiinflammatory." Or, "Oh, it helps GABA-glutamate balance." As we go forward, we look at it more and more in this symphony, and this symphony, I call neuro-endo-immune poise, or balance. Neuro means neurotransmitters. Endo is endocrine or hormone, and immune is obvious. It's the immune system. Neurologically is how we used it the most, for damping neuro-inflammation. When I lecture to doctors, I say, "This is the most exciting supplement for us in the last 30 years in functional and integrative medicine."

Because we're treating a lot of people with [mole 00:07:45] toxicity, Lyme disease, mercury toxicity, and all these have as part of their symptomology neuro-inflammation, where you become ... Your autonomic nervous system becomes sympathetically dominant, you've got overactivity of glutamate receptors, there's activation of the immune system in the brain called the microglia, and they're sort of at war with the glutamate receptors. That's causing anxiety first, then brain fog, then a disruption with the autonomic nervous system. You're moving resources and blood in wrong ways throughout the body, and this acts to just stabilize all of that. It will block the excitation of the microglia. It will stabilize the glutamate receptor. That will result in a neuro-stabilization. Your neurotransmitter balance between glutamate and GABA gets balanced. Your autonomic nervous system balance between parasympathetic and sympathetic gets balanced.

But that starts cascading down even farther into the body, and we start to look at really what homeostasis or balance of the biology is, and it's a set of reactions that all have these yin-yang poles, which you want to sit in the middle of and take forays in the yin or yang as needed to handle different perturbations, but you always want to come back to the poise of the center, and CBD is always bringing that back to the middle. In hormones, in women, the organ with the greatest amount of cannabinoid receptors? The uterus. I always pair CBD with bitters, and guess what's in the ovaries, but bitter receptors. We find such a stabilization of the female cycle by taking those things together. Then the immune system. You want inflammation when you need to kill things, but then when it gets stuck on, and it won't turn off, you get things like development of chronic inflammatory states. These can be cardiovascular complications. These can lead to cancer. These are problems, so where's the switch to bring it back? The CB-2 receptor, the cannabinoid number two receptor, and where's that located through the body but on the peripheral immune cells of the body.

CBD lubricates your endo-cannabinoid system. Why would you have cannabinoid receptors if you didn't make cannabinoids. The two main cannabinoids you make are 2-Arachidonoylglycerol and anandamide, and the reason you make them is to zip together the neural system, the endocrine system, and the immune system have that neuro-endo-immune poise, and CBD helps you build more of those endo-cannabinoids and helps potentiate those CB-2 receptors. At the same time, it's up-regulating chemo-protective and antiinflammatory genes and down-regulating pro-inflammatory genes. There's really no one thing that helps you create that poise, that essential homeostasis. Nothing does it like CBD oil does, and that's why it seems like a panacea, because it helps so many things.

Gazella: That was actually my next question, because when I was researching for this interview, I found such a diverse amount of conditions that it was being effective for, so because it works on these multiple pathways, that's why you're saying it works for such a variety of conditions. Do you give practitioners who say, "Wait a minute. That's a little bit too good to be true. How can it be that good for that many things?"

Dr. Shade: Well, then I give them the neuro-endo-immune poise story.

Gazella: Exactly.

Dr. Shade: And as soon as you said neuro-endo-immune poise, they go, "Wow."

Gazella: That's right.

Shade: Because what are the disorders? There's some part of you in that yin-yang balance that's stuck over here, or stuck over there. Anything that helps you zip together so many fundamental processes, everything just starts to come back together again. I mean, it runs through all of our different protocols, because it's that X-factor for zipping it all up again.

Gazella: Right. Now, there's got to be some conditions that bubble to the top, and that was the other thing that I was so impressed with, with the research, is the amount of research associated with CBD oil has grown dramatically. But what conditions? As you're looking through the research and you're kind of identifying the strength of the research, what conditions are bubbling to the top, to say, "Yup, that's really what it's going to work for"?

Shade: Right. In our world, we deal with detoxification, and so we're dealing with people who have various problems that are associated with toxins. Autism is a really big one. That's always ... Unless they're just totally exhausted, autistics, always bringing CBD into that, because of that neurological stabilization. Then we're dealing with various mole toxicity, Lyme disease, and the neuro-inflammation that comes from that, the different metal toxins. All of our detoxification protocols, especially when they're neuro-detoxification protocols, involve the use of CBD. Then in distinct disease states, the big ones, MS, Parkinson's, any kind of tremor. Of course, everybody knows seizure disorders. Those are all crying out for some application of CBD.

But then since I understood the endocrine side of it, women who are having endocrine destabilization or hormone imbalance, we're always recommending CBD along with the bitter herbs to them, and we get great ... You might not think, "Premenstrual syndrome: CBD." But it's fantastic for that. Those are the main ones that we use. Oh, any chronic inflammatory pain. That's a really big one. Cardiovascular complications. That's really big, too. We've seen some great data emerging on the use of CBD, including some doctors who have used ours to get preliminary data, on the health of the inside of the vascular system, and you'll see those cells on the inside of the vascular system all getting less stress, increased poise, and so we recommend it in those cases as well.

Gazella: Now, what about mental health? You've now just listed some conditions that are related to our physical health, but what about some conditions associated with mental health?

Shade: Anxiety's just hands down the biggest one, because anxiety results from over-excitation of the glutamate receptors, and boom. CBD stabilizes that immediately. It's very, very fast around that. Now, it's interesting, for much more complicated problems, like schizophrenia, here you've got one plant, two chemicals, THC, CBD. THC is like putting the fast forward button on schizophrenia. It's really bad for a schizophrenic, where CBD has fantastic data around stabilizing schizophrenics, so there it's useful as well.

Even in depression. Depression, you think, "Okay, well anxiety, you're really stimulated, and that calms you down." But depression is also often cycling with anxiety, and so depressive disorders, there's been a lot of data around use of CBD too, and most of my favorite integrative psychiatrists like Kelly Brogan, they've showed very clearly that depression is a neuro-inflammatory disorder, and so you've got different reactions to antigens in your food, in your environment. You're having these constant allergic states and cytokines, these pro-inflammatory states that are contributing to depression, and CBD is working against all that, creating that balance again so it can be used in anxiety and depression.

Gazella: Yeah. It's fascinating.

Shade: Yeah.

Gazella: I'd like to talk about safety, because I have to tell you that I've read some conflicting statements associated with safety. Based on your interpretation of the scientific literature, is it safe? Are there any interactions, contraindications that we need to be worried about?

Shade: On its own, without you having to stick something else into your body like a heart pressure medication, CBD is inherently incredibly safe. We've found a couple of people here and there that seem to have an allergy to the plant, and they just feel unhappy on it, but the issue around CBD and safety is that it interacts with some of the cytochrome P450 system, which are metabolizing drugs. If you're taking a drug for blood pressure, CBD may either lower its breakdown, so increase its circulating levels, or increase its breakdown, and thereby decrease their circulating levels. If you're on a lot of pharmaceuticals, you usually have to do a little bit of research and see if there's some interaction between the CBD and the pharmaceutical that you're on. There's starting to be good lists online of the potential interactions. They've got to get a little bit better at where these are really relevant interactions, and where they're not relevant interactions. But this will be one of the things that we come up with in the future, is nice, clear guidelines on whether something's going to positively reinforce a drug, or work against the activity of the drug.

Gazella: I mean, the case that I read was specific to antidepressants, and that's where it was very conflicting. Some reports were, "Yes, it will react," as you describe, and some were, "It will not."

Shade: Because it's not antidepressants. It's, "This list of chemicals."

Gazella: Exactly. Yeah.

Shade: They just happen to be antidepressants to your body that get metabolized down different pathways according to their chemical nature. Your breakdown doesn't care whether it's an antidepressant or whether it's testosterone. It's got a chemical nature, and it's got to fit into the cytochrone that breaks it down. You get a list of antidepressants, they have different chemical natures, and they go into different cytochrome P450 enzymes to break down, and CBD interacts with two or three of those enzymes. If the antidepressant interacts with the same enzyme CBD does, then there could be an interaction, and if it doesn't, then there's no interaction. It's not about antidepressants.

Gazella: Yes, and nothing is ever clearly black and white when we're talking about this type of chemistry.

Shade: No.

Gazella: I'd like to talk a little bit about the product that you specifically formulated, Colorado Hemp Oil. What makes your product unique or special compared to other CBD oil products that are on the market?

Shade: Quicksilver Scientific specializes in delivery systems, ways to get the compounds into little, lipid-based carrier spheres that are so small that they passively diffuse through mucosal membranes, like your oral mucosa, the sublingual space, as you're swallowing, through the stomach, the upper GI. It's the rapid and complete absorption of these little nano-spheres which is what we do, and when we stick CBD in there, there's a very fast uptake, there's a high total uptake, and it's a very rapid uptake. One of the things that's a problem with CBD is there's only net about 10% uptake of all the CBD you swallow. That's a very expensive molecule, as you know, and so you're throwing away a lot of that and not getting a lot. The stuff you do absorb is absorbed over the whole transit time of the GI, so if we look at uptake versus time, you have a very gradual, slow movement into the blood. The blood levels, the peak blood levels never get very, very high.

Now, a lot of what CBD does, it does through interacting with receptors, and gene triggers, like nuclear transcription factors, like NRF-2, which turns up all your glutathione genes. Now, the receptors and those transcription factors react to peak doses. Level versus time, here's a regular CBD oil. Here's ours. You get a very high transient peak dose. You saturate the system. You're able to work very well on the brain. You're able to hit all of those transcription factors. You're able to interact with all of those membranes, and everything happens very quickly, and you get a very strong effect.

The total absorption is anywhere from four to sixfold higher than a regular pill, but even if you took four to six times as much, you don't get as much of an action, because you don't have that peak dose to really induce everything, ring the bell of those receptors. What happens when you hit receptors, you trigger a whole cascade of different proteins to be made, which is affecting the metabolism of the body. That transient peak dose really creates the effect that you're looking for.

Gazella: Now, your label says that the patient needs to hold it in their mouth for 30 seconds. How important is that, and is that all a part of the enhanced absorption of the product?

Shade: It is, because this is a nice space in the oral cavity. Interacting with the oral musoca is a space where your spheres that you've made have not had to interact with stomach acids or bile, so there's nothing modulating them or modifying them, changing their shape, their size. It's a nice, pure space where all the capillaries are very close to the surface, and you can get a whole bunch in. Now, that being said, for some of our products that are water-core, that are liposomes, those are a little bit more sensitive to the GI conditions, and a little bit more important that you do that oral holding. The nano-emulsion that we make, like the CBD, you have an oil core with a membrane around it. These are more resistant against change in the GI tract, and they will make it through, and you'll get the absorption anyways, but it'll be a little bit slower, and a little bit less efficient.

The more you can do the oral hold, the better, but it is not a game-breaker. That's important for a lot of the people that are very taste-sensitive, or if you're working with autistic children, and they won't do that, or you're giving it to your dog or something, goes right down.

Gazella: I don't know. My dog is pretty smart.

Shade: Yeah. You just say, "30 seconds."

Gazella: That's right.

Shade: "No. Five seconds more."

Gazella: It's interesting. I would like to stay on dosing. Is it complicated to dose from a practitioner's standpoint? Because you do have such a diverse offering of conditions that it can help. Is the dosing-

Shade: Yeah. It's really titration dosing. You start at a low amount. One of the doctors in town here, Joe Cohen, goes with two pumps three times a day as a sort of basis dosing for an adult, and then they'll add more as they need it. If you're not getting the effects, how about three pumps three times a day? Then four pumps three times a day? Titrate up until you get the required effect. You can even start down at one a day, like if you're dealing with kids and you want to start low and slow, but just keep titrating up until you get the effect you want, and often once you induce the effect and start training the body into the healthier state, you can bring the doses back down. Just start low and work up until you get what you need.

Gazella: Great. Now, before I talk about the future, because you know I like to talk about the future, I'd like to have you predict the future, is there anything else that practitioners need to know about CBD oil when it comes to using it in their clinical practice?

Shade: No. Don't be afraid to use it for a wide variety of conditions. Work your dosages up until you get the effects that you want. Let people know, especially if they've never had anything like this, the feeling that they have in the first couple of days may be more intense than it will be later, but it's not ... Most of the other supplements, there's more tricks around it and things to watch out for. Not so much with this.

One thing, though, you will, if you're using it alone, you will start to generate detoxification reactions through two mechanisms. One is NRF-2 up-regulation, that nuclear transcription factor that's turning up the glutathione system, and the other is the autonomic balance, bringing yourself over to a parasympathetic state, and detoxification doesn't happen in sympathetic states, because it's a luxury, and you're trying to survive when you're in sympathetic autonomic dominance. This will bring you over to parasympathetic. It'll help turn up these genes, so some people will start to have detoxification reactions. If they start getting headachey, or a little lower back stress, or rashes, give them good quality bitters, like the BitterX that we make, and maybe a little bit of GI binder, like our ultra-binder, or charcoal clay capsules, and that will help them detoxify.

Gazella: Oh, good. That's good to know. Now, the future.

Shade: The future.

Gazella: What excites you the most when it comes to CBD oil research?

Shade: Yeah. It's CBD not being just a standalone, but being an integrated ingredient in formulas, where it's doing this part of it, maybe the autonomic balancing, or the brain balancing, where the other things are doing other parts, and finding which things are synergistic together, which things are antithetical together. We'll find out how to blend it with other things, and really make it work better. Even if we're just working within the cannabis plant itself, there's the essential oils of the plant called the terpenes, very strongly affect the modulation of how CBD and THC work within the body. The science on the terpenes will be worked out, then the science on other nutriceuticals playing in with those will be worked out, and we'll start to see some really beautiful formulas come.

Gazella: What about when we began, we talked about the availability. Do you see things loosening up a little bit?

Shade: That part of the future. It's funny. There seems to be two forces at work within the United States around CBD. There's a liberalization movement that is not necessarily ... It's not coming out of Boulder County in California. It's coming from within the government, where they want to focus on real issues, like narcotics use, prescription pain med addiction, real drugs, heroin, cocaine, and they want to get away from talking about this. On the other side, there's other people who are just ... Some part of them are just working out what's already been started, where they're just really going to want to try to enforce this. We're starting to hear much more sophisticated language from the state departments of health about CBD, and that's towards a contractive thing. And who knows where that's really coming from? I mean, you have pharmaceutical companies getting into this now, and that may be the long, dark arm of the pharmaceutical companies.

There's two things now, contraction and expansion, happening at the same time. Hopefully the light wins and we expand out, and we're able to use this in a broad scale, and do all the research that's really necessary to put this to the best use.

Gazella: I would agree. I think that the therapeutic efficacy of CBD oil is really ... We're shining a light on it in the scientific literature. Even though it seems that it's preliminary, uncertain cases, it just seems like it's growing more [inaudible 00:28:22], it really should be something that we look harder at.

Shade: Oh, it absolutely is, and I can always gauge it by when I'm on a plane, when little old ladies start talking to me about it, or my aunt came over from Florida, and she had a bottle of it, and it's made its way out to the masses. They need it. They want it. We hope it's here to stay.

Gazella: I do too, and you know, we haven't even touched on the pain aspects, because right now we are in the midst of an opioid crisis in this country.

Shade: Oh, yeah.

Gazella: Is there an application for [crosstalk 00:28:57]?

Shade: Oh, absolutely. Maybe little smidges of opioids along with CBD. CBD, and what we'll find is what we can blend with it nutriceutically to increase its effect at stopping pain, but it's got all the right aspects for that, and for some pains, it's magic. For other ones, it doesn't work as well. Well, maybe we'll find certain blends, but it will always, if you're taking it with opioids, it will always lower how much you need of the opioids, and that's one of the most beautiful things to come out of the legalization of medical marijuana in various states. They've seen a lowering of opioid use.

Gazella: Right. It sure seems like CBD oil, hemp oil, is a valuable tool that clinicians can use in their clinical practice.

Shade: Absolutely.

Gazella: Great. Well, Dr. Shade, as per usual, this has been very interesting. Thank you so much for joining me today, and I would also like to thank the sponsor of this interview, who is Quicksilver Scientific. Thank you everybody for joining us. Have a great day.

Dec 4, 2017

In this interview, Natural Medicine Journal Publisher Karolyn Gazella discusses the challenges and solutions associated with enhanced integrative care for cancer survivors with integrative oncologist Dr. Matt Mumber. More than 15.5 million cancer survivors are currently living in the United States, with more than two-thirds alive five years after their diagnosis. And yet, most survivors report side effects long after treatment and many experience significant distress and fear of recurrence. Mumber describes how an integrative approach can help all practitioners serve the special needs of cancer survivors in their practice.

About the Expert

Matt Mumber, MD, is a board certified radiation oncologist with the Harbin Clinic in Rome, Georgia. He received his medical doctorate from the University of Virginia and he also did a fellowship in integrative medicine with the University of Arizona. He is the coauthor of the book Sustainable Wellnessand the editor of the textbook Integrative Oncology: Principles and Practice. Mumber is the director of medical affairs of the iTHRIVE Plan.

About the Sponsor

iThrive Plan Integrative Cancer Care

iTHRIVE is an online web application that creates personalized wellness plans for cancer survivors that focuses on five key areas: diet, movement, environment, rejuvenation, and spirit. Cancer centers, hospitals, and clinics can license the iTHRIVE Plan to help meet the special needs of their cancer survivors. iTHRIVE also helps cancer centers meet the Commission on Cancer Mandate. For more information, visit


Karolyn Gazella: Hello, I'm Karolyn Gazella, the publisher of the Natural Medicine Journal. Today our topic is cancer survivorship. My guest is radiation oncologist, Dr. Matt Mumber, who's also the editor of the textbook, Integrative Oncology. Before we begin, I'd like to thank the sponsor of this podcast, who is iTHRIVE Plan. That's Dr. Mumber, thank you so much joining me.

Matt Mumber: Oh, thanks for having me. It's always good talking with you.

Gazella: Yeah, well, you know I've been reading research clearly showing that cancer survivors say they have unmet needs and they have special needs. Take us through what some of those needs are, specific to cancer survivors.

Mumber: The diagnosis of cancer is really a whole-person diagnosis. People wonder about, first thing they wonder, "Gosh, am I to somehow blame for this diagnosis?" I think people think about that. Of course, various levels of lifestyle and choices they've made throughout their life. Whether they're smokers, how they've generally eaten, what environment they live in. What their family history is, so they think about all of that, obviously. Then stress weighs in on it. When people get the diagnosis, they have a lot of stress. Then people maybe even think about compounding the fact their lives are stressful, well maybe my stress caused the cancer. That type of thing. That all impacts them and then the physical aspect of it. Of course, we're all, as whole people, we have a physical body that we inhabit.

We have our minds and our spirits, our heart, our emotions, and pretty much all of those are impacted by cancer diagnosis. The physical aspects, people can feel different, they can have symptoms related to the cancer or actual problems. Bleeding, pain and other issues that are outside of normal function. Then, for example, just the fatigue that comes along with having a cancer diagnosis, because fatigue is multifactorial, too, and tends to weigh on people emotionally. Then that has a physical ramification.

The stress and so forth can cause problems with how we eat, drink, move. How we sleep at night. How we relate to others. Different things like sexuality and other aspects that we take for granted as just people walking around being healthy. One of my teachers says that he really enjoys, every now and then, takes time to enjoy the fact that he doesn't have a toothache, because when he has a toothache, it's kind of all-encompassing, so we can be happy our non-toothacheness. I think people with cancer often feel that way. "Gosh, if I could just get a break from having cancer," because once you have cancer you're kind of a cancer patient and you're a cancer survivor, so it really does define who you are.

It's a very much of whole person oriented type of thing. Of course there's all the practical matters, financial, social, and so forth. It really does affect people in a multifactorial way. Perhaps because of the general stigma that's associated with a diagnosis of cancer, for then has been for decades, perhaps more than most of other types of chronic illnesses.

Gazella: I think you may be right, and then there's this issue of fear of reoccurrence. I read in one study saying that upwards of 90% of cancer patients, even if it's not valid, they're afraid. They're so afraid of a reoccurrence of getting cancer again.

Mumber: That's right. No doubt.

Gazella: You've just mentioned a lot of factors. Is this the reason why the American College of Surgeon created the Commission on Cancer Mandate, and you can talk to us a little bout about that Commission on Cancer Mandate?

Mumber: The Commission on Cancer is a wonderful organization, their real mission is to make all of the hospitals that participate in their system as good as they can be. First things they start with were very conventional, let's make sure we have accurate data. Let's make sure people are being treated in facilities that have up-to-date conventional types of processes and that they're recorded and they're followed over time so we can then get feedback and learn and grow with regards to how we're doing in the conventional care of cancer patients.

Then about the time that the Institute of Medicine started to branch out and look at things like cancer survivorship and psycho-social screening, and integrative approaches ... what I would call integrative approaches. They started saying, "Gosh, this is just as important as the conventional. We've got that under control. We've got that to the point where we have standards, we really need to create some standards that affect more of this whole person, outside of the what we do to people," type of scenario. That's really when they started to build these criteria, starting with patient navigation, trying to identify access to caring disparities that people face. Then moving on to actual distress screening, so that we can find a way to identify the stress, almost like another vital sign. Recognize distress and then intervene early before it becomes a problem.

Then moving past when we've gone through active treatment and people that have been treated definitely and curatively and they've done active treatment. Like I said, they're always cancer patients. Cancer survivors now. How do we address that survivorship such that we can make sure they're getting appropriate screenings, that they understand what's been done to them and ultimately what they need to do in order to stay connected, to try to decrease recurrence rates and to function in a way that gives them the best chance of surviving long term.

Gazella: Speaking of these special needs, it certainly seems that because of the sheer number of cancer survivors, pretty soon there's going to be 20 million cancer survivors alive in the United States alone. It certainly seems like their care is spilling out into other medical disciplines, well beyond oncology. I'm wondering what role can general practitioners or integrative practitioners play when it comes to meeting the special needs. Physical, mental, emotional, special needs of cancer survivors.

Mumber: Medicine, I think is evolving. Medicine has evolved from being purely focused on the downhill, what we do to somebody, and has really become more of a partnership where we are able to focus on the commonalities that make us all human and to do so in a way that is therapeutic. For the physician, the physician can bring the power of themselves as they are, what they do to help stay healthy. They can bring in a compassionate way to the doctor patient interaction. Primary care has led the way in this, with the primary care patient center medical home concept. That's now actually something that's billable and is paid for through Medicare, where you can get a group of people together and you can give them ideas and ways to help prevent certain illnesses, for example diabetes, heart disease. Haven't done it so much with cancer yet, because that hasn't filtered into the primary care mechanism, but it's happening and it's a good way for that to happen, because there's only so many oncologists available and there's a much larger pool of primary care doctors.

Prevention has really been in the purview of primary care physicians. There's really 3 types of prevention. Primary prevention in order to try to prevent diseases before they come up. Secondary prevention to prevent disease when people are high risk group, for example prevent heart disease or lung disease from people that are already smokers. Then finally tertiary prevention, which means when people already have an illness or have a diagnosis, for example, cancer, we try to decrease the chance of that recurring or having it again. The primary care center medical home is mainly focused on the primary prevention, somewhat in the secondary prevention and then it also filters over into the tertiary prevention.

In each of those groups, one of the foundational principles that I found to be true in my life is that there's tremendous power in getting groups of people together with similar experience. It's kind of like if I went, no matter how compassionate I am, if I went and tried to sit down with a group of pregnant women and talk with them about what it's like to be pregnant and to be able to have a baby and so forth, I would just be ... There's no way I would add anything that would mean anything to anybody, but if you get a group of pregnant women together, they're going to be able to speak a language that women who have gone through that experience will have. I think that's a very powerful thing and that's filtering into medicine more and more, it's getting reimbursed by Medicare through the primary care patient center medical home.

It's filtering into oncology care. Certainly there are specialty oncology medical homes, as well. However they tend to focus more on what to do during therapy, how to support patients during therapy and it really hasn't filtered over into the tertiary prevention model. I think as a field, medicine in general is evolving a very positive way, mainly it costs so much to have illness, right?

If we can prevent it, the ounce of prevention, right? I think that's a good thing. I do think that's the wave of the future. How it's going to filter into oncology versus primary care, with regards to that tertiary prevention piece, I think that's still to be worked out.

Gazella: Yeah, I would agree. We're making progress though. It is all about serving these special needs of cancer survivors. Now you are the lead investigator on a study that combined patient navigators with an online tool. Can you tell us a little bit about that research and what the outcomes were?

Mumber: Yeah, yeah, so my research is mainly focused on the application and implementation of integrative approaches, especially those that focus on people being able to make and embrace long-term change, kind of what I think of as the difference between translation, which is just giving people information and hoping that they'll understand it. Maybe apply it, versus transformation, which is being able to actually apply information in one's life and make a major change in life. Initially, we started looking at, can we approach this with physicians, for example with integrative medicine approach. We did a study about a dozen or so years ago that was a computer-based educational program, did it in conjunction with the University of Arizona and the Georgia Center of Oncology Research and Education and GSSACO, Georgia's State Society of the American Society for Clinical Oncology.

Basically, we did a prostate cancer where they did integrative medicine, educational module, to educate physicians and provides, nurses, other providers associated with prostate cancer about different complementary alternative methods associated with prostate cancer. We found that that web based educational intervention was very successful. Kind of fast forward to this most recent study, the next logical step would be is there anything we can do to improve upon the ability of this translational information delivery to move more towards a transformational approach. Or what people think of is generally a transformational approach.

The study that we did was, basically, a randomized trial, a small pilot trial. We had 24 people, 24 patient navigators in the state of Georgia that were randomized in this trial to give 1 of either 2 arms. One was an educational, web-based modality that looked at educating about integrative oncology for a patient navigators. We had a bunch of didactic presentation. We had a weekly video presentation that people could watch with regards to how they eat, drink, move, manage their stress, based upon our sustainable wellness book that we had ... Heather Reed and I had written.

Then there were a variety of materials that were present. There was the ability to chat online. That was one arm of the study. The other arm of the study was to do all that, but to also to have the opportunity to do a residential retreat, which I've been facilitating those types of educational types of retreats for years. Focusing more on a variety of contemplative practices and a personal experience and providing those contemplative practices with people that have similar experience. In this case, patient navigators.

The word contemplative is often kind of confusing. It sounds kind of mysterious and mystical. Contemplative is a good way of thinking about, contemplative practice when we can be in a position in which our body and our mind and our heart are in the same place at the same time. That's likely a contemplative practice. One of the features of it are that the result of that is that it brings about a certain level of awareness. It brings about a sense of communion and it brings about a sense of connection.

We would sit with people. We had a three day residential retreat that Heather and I facilitated and basically just experienced a variety of things, like yoga, meditation, massages. Everybody loves massage. We did some creative art therapy, like picture drawing and interpretation of those things. We randomized the trial and the outcome measure was do people learn better when they have this in person interaction, then they do when they have more of an online interaction.

It was a very small study. The numbers hint that there's a slight increase in educational benefit with the in person interaction, in addition to the online interaction. However both interactions resulted in, just like our previous study, significant learning and ability to actually apply these integrative modalities. It was the next step in research with a more focused group. I do think that's it a pretty exciting trial, because it does show the value of somehow having that link to that group of similars. Now whether or not that needs to be based in person or whether it could be based online, with like an online chat that's real active, that's kind of another question, research question, but it was an interesting study.

Gazella: Yeah, sounds very interesting. You know the point with some of the emerging research is to reduce the burden of care. It reminds me of research that was presented at this year's ASCO [American Society of Clinical Oncology] with Dr. Hess from Switzerland, who used the web-based modification tool for cancer survivors and she demonstrated that distress was significantly reduced and quality of life significantly enhanced without a face to face visit. I'm just curious, is this in part the way of the future?

Mumber: I think it could be. I think, of course, that intervention what they did was really more of a psychologist or psychiatrist doing counseling with the individual. They did a good bit of that. They tried to, instead of having to take the patient's time because there's some access to care and disparity issues, in that study, 70% of the patients had an online presence. They were open to using that modality. The counselors would basically do counseling with the patient, instead of them being in a room, basically do it online.

I think as time goes on and as people have more penetrance and more of an online life, I do think that that's going to become more applicable. The current ... It depends on where you are, I guess. It depends on the age of your population and penetrance of internet use and so forth, but I do think that's a positive study. I do think it addresses some of the barriers that can occur, relative to actual time for both the therapist and for the patient, to actually sit down and do it, it's a heck of a lot easier than if you have to travel. Let's say you had to travel 45 minutes. There's also a stigma, I think, to especially the psychological counseling piece where people say, "Gosh, I've got to go to a counselor." It's almost like they're admitting some kind of a weakness.

That gets over that barrier as well. I do think it's going to have applicability in multiple methods. Just in the research that we did, relative to the many uses of the internet and how they pertain to educating people and bringing along. There's absolutely no doubt that the internet has revolutionized the ability to educate people, there's no doubt about it. It makes perfect sense that it would have the ability to be applied in this specific situation, to reduce the stress, to do things with cancer patients that require, in the past, that required face to face interactions, but to do so in a way that's much more practical and less costly, ultimately, than actually having to take the time to do that. Yeah, I think it has significant potential benefit.

Gazella: Yeah, I would agree. I'd like to talk briefly about the iTHRIVE Plan, which is an online tool. Now you in your clinic, the Harbin Clinic in Georgia, you're using the iTHRIVE plan in conjunction with a nonprofit called Cancer Navigators. I'm wondering what your experience has been with the patients who are using the iTHRIVE plan, in particular.

Mumber: Yeah, I think the folks that are using it really enjoy it. Basically, it's a plan that when we set them up, we just basically say, "Look, this is a plan that's written by cancer survivors for cancer survivors." What it does is it evaluates you in 5 different domains of your health, how you eat, how you drink, how you move your body, your spirituality and then how your environment affects you and what things in your environment may be lurking that you're not even aware of that could potentially influence you.

Basically, it's written in a way that there's a nice melding of really good, hard science that each one of the little action steps that are given, are discrete action steps. It's really hard for a patient, when they sit in a room for 15 minutes at a follow up visit where we're talking about, "Well, gosh, you got to do your screening here. You've got to come back for this appointment. Got any questions? Okay, hey, by the way, make sure to eat better, drink pretty of fluids. Exercise. Manage your …" It's such a big elephant, it's hard to bite off. What you do is you start off with one discrete action step. Each of those steps, to the extent people happen to have like a little scientific citation with them. It's very, very valuable.

The people that have been involved in it, they may not like every one of the steps, because everybody's different. Everybody has their own way of doing things. People have different expertise and so forth, but what I tell them is, "Gosh, if you have a set of action steps and one or two really hit home, that's a big deal," because just think about the difference between saying, "Oh, go ahead, eat better, drink better, move better, etc. Handle your stress," and then giving people an option of let's say 30 different steps that pertain to one of those topics. They can go around, in their own time, on their phone and look at each one of those steps and say, "I'm going to try that." It might really hit home and it might stick with them for the rest of their life.

It's a really beneficial thing. The feedback we've gotten has been very good. It has helped us, as well, in identifying people that are in distress that we wouldn't have known otherwise. As a part of that, they'll take a 15-minute survey that evaluates them in those 5 domains. Then one of the domains ... Then it has different symptom complexes like fatigue and pain and so forth. If they reach a certain threshold, then our nurse is identified. Our nurse calls them up and what that's done is it's allowed us to get them to specific services they would not have gotten to otherwise. It's a very beneficial thing on multiple levels. On the patient navigation level, to go back to the COC, well, what a great tool for being able to intervene and educate and identify access to care and disparities issue.

Some of those could be a person can't travel to do various things, so this is a great way of addressing that. The second piece, distress screening, we can identify distress, and appropriately manage it. The third thing, of course, this is a survivorship piece. Really the weakest part of survivorship, in the COC platform, has been that tertiary prevention piece. How you take care of yourself in order to decrease the chances of them coming back.

Gazella: Right, and I'd like to talk a little bit about that, because you and I and Dr. Lise Alschuler wrote a paper that was published in the Natural Medicine Journal that shined a light on emerging research that's showing that survivorship care plans that only focus on the treatment summary and the follow up care are actually causing more distress, because they're not focusing on proactive prevention strategies that can empower the patient. What do you think is the solution to that, because that's kind of troubling, that even after the mandate, these SCPs are causing more distress?

Mumber: I think what's happened is that they've followed the general history of the medical model, ultimately. That is that we figure out what needs to be done and in our infinite wisdom, we then deliver it. We deliver it in the best way that we can, unfortunately the initial way we deliver almost everything in medicine is from the top down. From somebody who knows something better to somebody that doesn't know anything.

Somebody who needs help to somebody's who's going to be stronger and has the ability to get the help. Somebody who's broken to somebody who's going to get fixed. It's not unusual, it's a normal part of the evolutionary process of the way medicine is delivered over time. In the initial part of this, it's very important for us to get the conventional part right. It is very important that people get to their screenings, to make sure that people understand how important it is to eat well, to drink well, to manage your stress, to understand what radiation and chemo they got. How that might place them at greater risk, etc. those are all very important pieces of the puzzle.

However, if all we do is try to deliver information downhill and to a person that literally, all they know is what we're telling them, for the most part, it's going to create distress. It's going to create more distress than if we didn't tell them anything. It's almost like ignorance is bliss to a certain extent. When we overload people with information, without any real applicability of how it means something in their life, it tends to cause more distress. I think it's very important and over time, I think what we'll see is a progression for engaging the patient, engaging the patient in their own care. Engaging the whole person in their own care. That's where I think that it's going to evolve over time, naturally.

Gazella: I would agree with that. What would you like to see happen in the future, when it comes to getting these special needs met? Physical, mental, emotional needs met for cancer survivors in the future?

Mumber: Well, I think from a standpoint of Medicine. Medicine with a big 'M'. Not just medicine that we use to fix people, but medicine that serves the needs of all the participants that are involved. Not just the patient, doctor, community member, all aspects of the community in general. All people involved in it at all levels of their being. Physically, mentally, emotionally, spiritually, and all levels at which they experience life. As an individual person, as a family member, as a community member, etc. That's an integrative approach, a whole approach that addresses everyone at all levels of their being and experience.

That, again, that's a huge elephant. What we're starting with is the ground foundational stuff of what's the science of all these things. What do we need to make sure people have done in order to have just a basement, foundational understanding of what's required for basic science survivorship. Basic science 101. That's the level we're at right now. Going from not doing that at all to doing that is a big step. That's a big step. We don't want to minimize that. It's going to take time. However, ultimately, what's going to happen is that it's going to evolve over time and it's going to progress to the point where we look at the person not just as a patient and as a body, but we look at the patient as somebody who's a responsible participant in their care.

We take therapeutic advantage of their physical presence. Their emotional presence. Their mental and spiritual presence. We optimize their environmental existence such that it impacts everybody in the system. That is where medicine, that's what I'd like to see. I guess to say I'd like to see that is maybe a little self-centered. I think everybody would like to see that, right? It's just a matter of patiently, one step at a time, applying tools that we have that are capable of making incremental change at each of those areas.

For me, I have a lot of people, a lot of colleagues say, "Gosh, I'd look to do some kind of integrative approach." I think starting small and then growing organically with it makes sense and using tools that apply to yourself as an individual, as well as the patient, is a good place to start. Using systems that are in place that can increase communication, break down some of those access to care disparity barriers and move things forward in a way of increasing patient responsibility and participation in their health.

Gazella: I think that's great advice to practitioners who are looking to have a more integrative approach. Well, once again, I would like to thank the sponsor of this interview, which is iTHRIVE Plan. That's Dr. Mumber, I'd like to thank you for joining me today.

Mumber: Happy to be here. Thanks a lot.

Gazella: Have a great day.

Mumber: Alright, you too.

Nov 7, 2017

In this interview, Christopher Shade, PhD, discusses the many factors that can block effective detoxification and how clinicians can address these issues. Cholestasis, endotoxins, estrogen, oxidation, and other detoxification disruptions are explained, as well as key nutrients and botanicals that can be used to help push toxins out and prevent re-absorption. Shade goes into detail about the detoxification protocol he has created.


About the Expert

Christopher Shade, PhD

Christopher W. Shade, PhD, founder and CEO of Quicksilver Scientific, specializes in the biological, environmental, and analytical chemistry of mercury in all its forms and their interactions with sulfur compounds, particularly glutathione and its enzyme system. He has patented analytical systems for mercury speciation (separation of different forms of mercury), founded the only clinical lab in the world offering mercury speciation in human samples, and has designed cutting edge systems of nutraceuticals for detoxification and antioxidant protection, including advanced phospholipid delivery systems for both water- and fat-soluble compounds. Quicksilver Scientific is recognized globally for innovating on behalf of the pharmaceutical and nutraceutical industries. Dr. Shade is regularly sought out to speak as an educator on the topics of mercury, environmental toxicities, neuroinflammation, immune dysregulation, and the human detoxification system for practitioners and patients in the United States and internationally.

About the Sponsor

Quicksilver Scientific

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.

Oct 24, 2017

About the Interview

Tina Kaczor, ND, FABNO, recently sat down with Dugald Seely, ND, MSc, FABNO, director of the Ottawa Integrative Cancer Centre, to discuss several ongoing studies in integrative oncology. Studying integrative oncology has unique study design challenges. They talked about how these challenges are met and how current study designs are attempting to accurately reflect complex in-office care. Seely covered a broad range of topics, from details of specific studies to an overview of the current landscape of collaborating with peers in integrative oncology. He also offered some tips on how private practice clinicians can begin to participate in research.

The Thoracic POISE Trial

One of Seely’s current research endeavors is the Thoracic Peri-Operative Integrative Surgical Care Evaluation (POISE) Trial. Seely says it’s probably the most interesting and complex study his team is currently working on. The goal of this trial is to explore the impact of naturopathic medicine in addition to conventional usual care at the hospital for patients who have thoracic cancers and are eligible for surgery.

The researchers are randomizing a group of these patients into receiving standard usual care at the hospital only, or getting usual care plus an integrated approach delivered by a naturopathic doctor before surgery and for a year after surgery. They’ll be looking at a whole battery of different outcomes, including adverse events related to surgery, quality-of life-measures, immune function, inflammatory changes, cost-effectiveness, and, ultimately, long-term survival and recurrence rate over 5 years.

Seely sees this study as an opportunity to investigate the effectiveness of truly holistic, whole-person care. To do that, they’ll be employing interventions in 4 domains:

  • Targeted natural health products
  • Nutritional approaches
  • Fitness improvements (particularly pulmonary fitness)
  • Mind and body medicine and psychological well-being

At the end of the study, Seely expects to be able to say whether, as a whole, naturopathic medicine in this setting can make a difference in outcomes related to survival or adverse events related to surgery. 

Canadian/US Integrative Oncology Study

Another study Seely is working on is called the Canadian/US Integrative Oncology Study. This is being done in partnership with Bastyr University. The other principal investigator is Leanna Standish, ND, PhD, LAc, FABNO.

This study, which will be conducted over a 6- to 7-year period, will recruit and observe the interventions given to patients with 4 types of late-stage cancer. The researchers will look at the naturopathic care interventions given to these patients at 11 different clinics across North America.

Seely and the research team are looking at clinics with the most innovative and useful therapies in naturopathic oncology. They’ll document the interventions and follow the patients to observe effects on survival rates. In addition, they’ll be looking at cost and quality of life.

In the end, Seely hopes the CUSIOS trial will shed light on the outcomes we see with patients who go through these advanced integrative oncology clinics.

How Can Clinicians Get Involved in Research?

For clinicians interested in getting involved in research, Seely offered this guidance: Build relationships. For him, doing graduate work was key because it automatically caused him to engage and collaborate with others. If you’re interested in research, start by connecting with people at academic institutions and begin the dialog.

If you’d like to learn more about the sites currently involved in integrative medicine research, visit

About the Expert

Dugald Seely

Dugald Seely, ND, MSc, FABNO, leads the clinical practice and cancer research program for the Ottawa Integrative Cancer Centre. In addition to his clinical role as a naturopathic doctor, he also serves as the executive director of research & clinical epidemiology at the Canadian College of Naturopathic Medicine, affiliate investigator for the Ottawa Hospital Research Institute, and vice president for the Oncology Association of Naturopathic Physicians. Seely completed his master of science in cancer research at the University of Toronto and is a fellow of the American Board of Naturopathic Oncology. As a clinician scientist, Seely has been awarded competitive grant and trainee funding from the Canadian Institutes of Health Research, the Canadian Breast Cancer Research Alliance, the SickKids Foundation, the Lotte and John Hecht Memorial Foundation, the Ottawa Regional Cancer Foundation, and the Gateway for Cancer Research Foundation.


Tina Kaczor, ND, FABNO: Hello. I'm Tina Kaczor with the Natural Medicine Journal. I'm speaking today with naturopathic physician and researcher, Dugald Seely. Dr. Seely is the founder and executive director of the Ottawa Integrative Cancer Center in Ontario, Canada. He has led numerous research projects including the largest integrative naturopathic cancer care clinical trial ever conducted in North America. He has more than 50 MEDLINE indexed peer-reviewed publications. Last but not least, among his many accolades over the years, he has most recently been awarded the Dr. Rogers Prize, which is a prize awarded in Canada for excellence in complementary medicine. Dr. Seely, thanks so much for joining me today.

Dugald Seely, ND, FABNO: Thanks so much for having me on to talk, Tina.

Kaczor: There are so many things that we could talk about in the realm of research. You're also a practicing clinician, so there's lots we could discuss. I want to start off with a couple projects that are currently ongoing for you, maybe that you're knee-deep in. If you could just start us off with a couple research projects that you have going on these days.

Seely: Yeah. Sure. One of the ones that you mentioned, the integrative oncology study, is a big study that we're doing. That's probably the most interesting and complex study that we're running right now. I say running a little bit loosely because we actually haven't started it yet. We're waiting on final ethics approval. We're nearing the runway anyways. This is the Thoracic POISE Trial, which is the Thoracic Peri-Operative Integrative Surgical Care Evaluation Trial. The goal for this trial is to explore the impact of naturopathic medicine in addition to conventional usual care at the hospital for patients who have thoracic cancers and are eligible for surgery.

What we're doing in this study is we're going to be randomizing a group of these patients into receiving standard usual care at the hospital only, or getting usual care plus an integrated approach delivered by a naturopathic doctor prior to their surgery and for a year after the surgery as well. We have a whole battery of different outcomes that we're exploring, including adverse events related to surgery. We're looking at quality of life measures. We're looking at some biological surrogates, including immune function, inflammatory changes in the body, and we're looking at some cost-effective outcomes and, ultimately, long-term survival and recurrence rate over 5 years. This study is a long study. It's going to take us probably, by the end of the whole thing, maybe 12 years. We're starting off with a feasibility component to explore the interventions and how effective they can be applied before we move into the randomized component with a much larger population.

Kaczor: That brings up a question in my mind. That is, when you talk about the feasibility aspect, are you designing it such that the intervention will be standardized across the patients, or will this be more naturopathic in it being more personalized per patient in a systems-based approach?

Seely: Yeah. That's a great question. We've struggled a lot with how to develop the intervention in a way that could be representative of naturopathic medicine in the field. Then, also scalable and standardizable in a way that it could be replicated in another trial. I think we balanced it as much as we can from both ends. It depends on who you speak to I suppose around that. The goal is truly holistic or a whole-person care. We have components that relate to the use of targeted natural health products that we've standardized for this population. We've got a nutritional approach that we've standardized to some degree. We have interventions related to improving fitness and pulmonary fitness in particular. Then we have interventions related to mind and body medicine and psychological well-being. Those four domains comprise the types of interventions that we have.

Within each of those, we developed specific interventions that we detailed how this would be applied, and under what conditions, to these patients so that this can be clearly documented. There is a standardized approach that we're using. There is some flexibility in terms of the patients and how they represent in terms of making changes to the intervention. For example, if someone presents with diarrhea, they will be provided with probiotics as well as their core interventions. If they have weight loss, they would get whey protein as well. If they're experiencing mucositis or neuropathy, we'll apply glutamine. There are some things that we can tweak based on symptoms that the patient has.

Initially, at least, everyone in the study is going to get a course of intervention that everyone will receive similar. We don't know what is going to be providing what effect. That's the nature of a pragmatic study like this. We'll be able to say, at the end of the day, that this whole-person approach, what effect does it have on the outcomes that we're looking at. These are important outcomes for these patients regardless. It's a bit of a black box at the end of the day. We won't be able to identify what specific intervention has what effect, but we can say, as a whole, naturopathic medicine in this setting can make a difference in outcomes related to survival or adverse events related to surgery. Things like duration of hospitalization after surgery, so we'll have information on that.

Kaczor: This particular trial is being done in conjunction with area cancer centers and your center specifically. This is site-specific. Is that right?

Seely: It is initially. The feasibility study, which won't be randomized, is going to happen with the Ottawa Hospital as the hospital site. Then, the Ottawa Integrative Cancer Center (OICC) will be the site where the naturopathic care will be delivered. Once we have run in a few of them, when we do the randomization, we do plan on having at least 2 additional sites across the country. We have a couple places identified that will be good sources for recruitment. It will take place in other sites as well.

Kaczor: Great. I like the idea of it being a whole-systems approach because that's one of the things that we run into in naturopathic medicine is that the reductionist view of a single agent being studied is never reflective of what we're actually doing. That's great. My understanding is you have another study that has multiple locations. Is that correct?

Seely: Yeah. We're doing another study, which is quite different. It's an observational study called CUSIOS. It's the Canadian/US Integrative Oncology Study. This is being done in partnership with Bastyr University and the other co-PI is Dr. Leanna Standish. Really, we're looking at in this study over a 6- to 7-year period to recruit and observe the interventions that are given to patients with late-stage cancer, 4 types of late-stage cancer. We're looking at what the naturopathic care interventions are being given to these patients at 11 different clinics across North America—5 in Canada and 6 in the United States. Each of these clinics are being led by what one would consider to be a naturopathic oncologist or someone steeped in naturopathic oncology.

We're tying to look at clinics that have some of the best therapies, the most innovative and useful therapies, in the naturopathic oncology realm being given to these patients. We want to look at what those interventions are and we're documenting that using REDCap. Then, we're going to be also following these patients to see what the survival rate is amongst these patients. Then, we're also doing a substudy within that looking at cost and quality of life. Their experience through the care as well in a more of a qualitative kind of a way. Again, a lot of outcomes that we're trying to track, it is observational so it won't have the same sort of subjective biases for sure. It'll give us, I think, a lot of really good information about what the practice of naturopathic oncology is ostensively at its best, and what are some of the outcomes that we're seeing patients go through these advanced integrative oncology clinics.

Kaczor: Yeah. Let me ask you this as far as time horizons. These are both pretty lengthy studies. I have a 2-part question. One, when can we look forward to preliminary results or the first publications coming out of either of these trials? Two, are they registered such that, regardless of how the data shakes out, positive or negative, that it will be published? I understand that once trials are registered in a certain way, the data has to be published at some point.

Seely: Yes. For sure, we will publish regardless of what the outcomes are. The CUSIOS study is ongoing. It is registered under Thoracic POISE is not yet registered because we haven't got it through ethics yet. We will be establishing that soon. We will be publishing those, no question. We actually have submitted one publication so far and it's been peer reviewed. This is looking at the intervention development process that we used for thoracic POISE, which is really a collaborative effort with physicians at the hospitals, at the hospital pharmacists, the naturopathic doctors as well. That's being submitted for publication.

We also have information related to the survey. When you survey the whole profession through the Oncology Association of Naturopathic Physicians (OncANP), we wanted to know what were the best interventions, what were people using. That really helped influence the interventions that are being chosen for this study. That's also being submitted for publication. Hopefully, we'll see those out in the literature in the next few months.

Kaczor: Great. I'm going to switch gears just a little bit. You mentioned pharmacists and other doctors at these cancer centers. I guess one question to us out there, whether we're clinicians or we're in the research realm, is collaboration and creating those bridges that are required to really study integrative oncology. My question to you is, how to go about that? Maybe just let me know if, over the years, has it changed? It seems like it would be easier now than say 10 years ago, or even 15 years ago. Can you speak on that a little bit?

Seely: Yeah. I think it has gotten easier. There's more of an openness to doing the evaluations and the studies. We're seeing more interest in research, I would say overall, into naturopathic and complementary approaches to care. There's still certainly resistance that exists. Academics and researchers are much more open to looking at these questions typically than clinicians may be. The interest is really in trying to figure out what works from a research perspective. I do believe it's getting more easy to collaborate in that way. Funding opportunities are not easy for sure. I think that, within the naturopathic community, we know that we have a lot of low-lying fruit from our own intervention palate that it should be researched. There's good reason for it, and there's a lot of [inaudible], and there's some early evidence of benefit. [inaudible] have not been researched adequately in many cases.

In terms of building relationships and trying to engage with others, I found doing graduate work was really helpful. There's an automatic process that you engage with others. There's an expectation to be collaborative, and reaching out to people who are doing research at institutions to say, "You've got a good idea about an intervention that might have some effect." I think people are surprised when there's really a good openness for those questions. I think finding people in academic institutions that have a focus on research is a good place to start and to try to start a dialogue and a relationship really.

Kaczor: Yeah. Let me ask you one last question. That is, if people are interested either in your area geographically or they want to look up the centers that are involved in the US/Canadian collaboration trial, where should they look for more information?

Seely: will list all the different sites that are involved in the trial. I think there's more information related to that probably on our website, Yeah, will have the information related to that.

Kaczor: Okay. Great. As far as getting funding, this is usually in collaboration. I mean, you have a research background and a masters degree and such, so your advice to clinicians who just have their clinical degree is to collaborate basically and find others who are of the same passion for whatever question is being asked and maybe try for grants in that direction? Is that correct?

Seely: Yeah. I think trying to become part of a team, reaching out to different groups that are involved in research techniques through the colleges. They often have research departments and may have some information related to that. Talking to universities and people there. A really great place to start, I think, in terms of doing research too is publishing case reports. There's more of a drive for case reports in [inaudible]. That's something that is ... I know that the AANP is trying to support more case reports. I think that diving into that and writing up a case report that really clinically just gets someone steep into what the evidence is in the literature around the topic and leads to more investment. It's a more accessible entry point into research I would say.

Kaczor: That's a great bit of advice. We, as clinicians, are always ... Everybody has a few cases that are extraordinary over the years, so that's a good bit of advice, especially within integrative oncology when extraordinary cases do happen. It would be great to document that and see if there's commonalities and create studies like yours around those treatments. That would be incredible. I really appreciate your work, your time with me today. I hope we get to talk again in the near future. Thanks, Dugald.

Seely: Thanks so much, Dr. Kaczor. I totally appreciate the journal and what you're doing with it. Thanks for having me.

Kaczor: Take care.

Oct 4, 2017

Sponsored by Quest Diagnostics

In this interview, gastroenterologist and leading irritable bowel syndrome (IBS) expert Christine Frissora, MD, describes how to effectively diagnose and treat this common disorder. Frissora also discusses the conditions that need to be ruled out when IBS is suspected.

About the Expert

Dr. Frissora

Christine L. Frissora, MD, is a leading physician in gastroenterology and hepatology. She has extensive experience in IBS and other gastrointestinal disorders including gastroesophageal reflux disease, celiac disease, colon cancer and polyps. Frissora has been board certified as a diplomat of the American Board of Gastroenterology since 1998 and has been in practice for more than 20 years.

Frissora has acted in the role of principal investigator, collaborator, and consultant for various research studies including the areas of symptom management for IBS with constipation, minimally invasive interventions for IBS with diarrhea, and clinical trials for various pharmacologic IBS treatments.

She has developed and directed several courses in the field of gastroenterology and has delivered over 50 noteworthy presentations.

Frissora has authored nearly 20 articles in peer reviewed medical journals since 1992 spanning the fields of gastroenterology and hepatology. She currently practices at a nationally recognized hospital in the greater New York City area, and she continues her involvement in research within the field.

About the Sponsor

Quest Diagnostics

Quest Diagnostics is the world’s leading provider of diagnostic testing services with a medical and scientific staff of more than 650 MDs and PhDs, an extensive network of convenient patient locations and laboratories and a range of complementary diagnostic products. Our advanced health information technology solutions enable better healthcare decisions today, and our support of clinical trials is helping to find the cures of tomorrow. Quest Diagnostics is driven to discover and deliver diagnostic insights and innovations that help to improve human health

IBS affects as much as 20 percent of the population, however, many cases remain undiagnosed–often because patients believe their symptoms are trivial or due to secondary factors like diet, stress, or anxiety.

For those who ultimately do seek medical help, diagnosing IBS has always been an arduous and expensive diagnosis of exclusion. IBSDetex™ blood test can help confirm post-infectious IBS-D (diarrhea-predominant IBS) or IBS-M (IBS with diarrhea and constipation) in as little as 72 hours from the time the specimen is received in our laboratory. This simple non-invasive test can provide answers to millions of IBS patients much quicker thus ending their years of suffering and frustration. Learn more about IBSDetex.

Sep 7, 2017

If you work with patients with small intestinal bacterial overgrowth (SIBO), Crohn's disease, colitis, or food intolerances, you've probably heard about the elemental diet. But there's a lot of confusion about what the diet is, when it's appropriate, and how it can be used most effectively. In this interview, digestive health expert Lela Altman, ND, LAc, explains how the elemental diet allows the gut to rest and repair. She offers practical information for patients and practitioners about how to choose an elemental diet or how to make your own. In addition, she outlines the steps she takes to reduce the risk of relapse after coming off the diet. And she reveals the one question every practitioner needs to ask to identify a major red flag that would contraindicate the elemental diet.

About the Expert

Dr. Lela Altman

Lela Altman, ND, LAc, began working in the medical field in 1998, first as a nursing assistant, then as a medical assistant. This experience inspired her to pursue an education in the natural health sciences. Altman earned her bachelor of science degree from The Evergreen State College where she focused on ethnobotany, biology, and chemistry. She then earned her doctorate in naturopathic medicine and masters of science in acupuncture at Bastyr University in 2011. She went on to complete a 3-year residency at the Bastyr Center for Natural Health. While working as a chief resident, she completed additional training in evidence-based medicine and carried out diabetes research. She recently created the Digestive Wellness clinic at the Bastyr Center for Natural Health, which she currently supervises. Additionally, she teaches full time at Bastyr University and has a private practice.

About the Sponsor

Integrative Therapeutics




Integrative Therapeutics is focused on helping integrative medicine professionals cultivate healthy practices—from the development of science-based nutritional supplements to innovative, actionable resources and professional insights that have the power to inspire and enrich you, your patients, and your practice.

We take pride in our evidence-based approach and meticulous process, and we focus on investing time and resources into developing formulations that have the support of today's scientific community—not the latest 'nutritional craze.' This process includes months of research, rigorous ingredient testing, and quality assurance testing before a product is ready to be released.

Other resources include


Tina Kaczor: Hello, I'm Tina Kaczor with the Natural Medicine Journal. Before we begin, I'd like to thank the sponsor of this podcast, Integrative Therapeutics. Today we're talking about the elemental diet, which is a specialized diet sometimes used in patients with inflammatory bowel disease or small intestinal bacterial overgrowth, better known as SIBO. My guest today is naturopathic doctor Lela Altman, from Bastyr University. She's a specialist in gastrointestinal medicine and has used the elemental diet to improve her own health. Dr Altman, thank you so much for joining me.

Lela Altman: Thank you so much for having me.

Kaczor: So, let's jump right in. I'd like you to start us out with a definition. In doing a little research for this interview, I noticed that the elemental diet or, the words "elemental diet" have been around for decades. So maybe you can just start us out with just a simple definition of what is an elemental diet and what does that term exactly mean?

Altman: Sure, so a true elemental diet is a formula, it can be used in place of meals, and it proves all the nutrition that you need in its most basic, easily absorbed form. And that allows the gut to rest and repair. So, for example, instead of having proteins you would have individual amino acids, which are the building blocks of proteins. Instead of having fibers or starches it would contain simple sugars, which can be easily absorbed. And it also the essential vitamins, minerals, nutrients you need to survive. Fiber isn't typically included in an elemental formula because it can feed gut bacteria so that's something that we wanna look at and make sure it doesn't contain. There are a lot of formulas on the market that kind of market themselves as elemental diets that do have full proteins in them. And so it's not that those are bad formulas, but they're not necessarily totally an elemental formula. So it is important to know what you're looking for when you're evaluating formulas to determine whether or not they're elemental.

Kaczor: Okay, so we'll get into the diet specifics but it sounds fairly regimented in that, when I looked online I saw that there were a lot of various forms. There were homemade recipes and then there were products for sale, like you mentioned. And I guess ... the patient experience, can you tell me a little bit about the patient experience? I mean, is there a breadth of options for the patient where if they wanted to use their own kitchen they could do this diet themselves at home all the way to here's the pre-packaged thing? So what should a patient expect when they're put on this?

Altman: Yeah, absolutely. So you can make your own. Dr. Allison Siebecker has a great website,, that has a recipe for a homemade version and there are also various other forms. So there are supplement companies that make them, there's, I mean, pharmaceutical-type versions of them. So there's a lot of range of what you can purchase and there's a lot variation in price based on that range. So it really depends on whether the patient wants to make their own and save a little bit of money or finds the convenience more important and maybe the taste more important and is willing to buy prepackaged option. Not all of the prepackaged options taste good but there are some that taste better than others.

Kaczor: So in, I guess ... Well it may depend on condition but is this something that people typically do for days, weeks, months, how long are we talking for patients?

Altman: It does really depend on the condition. So for SIBO it's typically done for 2 to 3 weeks. And an elemental diet, again, it's used in place of food. So you're not typically eating food with the elemental diet, you're only doing the formula. So for SIBO, that would be the formula only for 2 to 3 weeks. It can be used really anywhere from a few days for a few months depending on what you're not using it for. Or, sorry, not a few months, a month. So, if you wanna do a little bit of bowel rest you maybe would be on a elemental for 3 to 5 days. If you have maybe Crohn's disease and are using the elemental diet for treatment of an acute, really severe flare of Crohn's disease then you might be on that for up to 4 weeks. Also, sometimes I'll use the elemental formula for people who have a lot of food intolerance or allergies and are unable to maintain their weight, as a way to provide antiallergenic calories. And in that case they are eating food in additional to the elemental formula and so they may be on the formula for months while they're recovering their weight.

Kaczor: And in that, just to clarify, in that scenario they're doing it as an add-on to an otherwise tailored diet for them.

Altman: Right. Typically, if the elemental diet is being given completely alone without any other food it doesn't exceed more than 4 weeks.

Kaczor: Okay, and so what conditions exactly ... I know you mentioned food intolerances so just so are we are complete, what other conditions do you use the elemental diet for?

Altman: The big three that I use the elemental diet for is for treatment of SIBO, also for, again, as I mentioned, addition of calories in people who are underweight and have a lot of food intolerances. And then also just for a short term bowel rest, which might be needed in a Crohn's or colitis flare. There is some research on multiple other conditions though that elemental diets or sub-semi elemental diets have been used to treat. So eosinophilic esophagitis is one, cystic fibrosis, AIDS-related diseases, acute pancreatitis, sometimes rheumatological diseases. So there's a number of different conditions that we are looking at elemental diets to treat. My focus is mostly on the gastrointestinal diseases.

Kaczor: Okay, and so because it's void of fiber completely I'm guessing that the microbiota of the gut changes dramatically without those fibers. So how do people come off of this diet? In other words, how do they step off it without having a massive reaction to fiber from foods?

Altman: Yeah, so, I mean, the first part of that question really is kind of addressing the lack of fiber issue. These diets are not health long term. The elemental diet wouldn't be health long term, nor would necessarily the low-FODMAP diet or something like that. So when I take people off of the elemental diet, I usually have them start with homemade low-FODMAP broth. And if they are tolerating those well on the first day then I'll have them add some well-cooked, low-FODMAP veggies and they can even puree that into a soup to help break it down a little bit more. And if all is going well, the next day I will have them eat lightly cooked low-FODMAP veggies like steamed or lightly sauteed. And they can add some grains if they tolerate grains, though not everybody does. Meat, eggs, those things need to be well tolerated and fairly easy to digest after the elemental diet. And then on phase 3, I kind of transition back to a low-FODMAP diet, that's the diet I'm typically using. Some people are on a SCD [specific-carbohydrate diet] or SIBO-specific diet. I kind of transition them back to whatever diet they were on before that was working for them.

And then when their gut stabilizes, then we start to challenge food. So, for example, we would start challenging low-FODMAP foods to see what they can tolerate and what they can't. The idea is once the SIBO is cleared they shouldn't have to stay strictly adherent to one of those diets.

Kaczor: Okay, so that brings up a question because it seems like there's a lot of relapse in SIBO that a lot of ... there's a lot of talk in the chat groups about what does one do after they feel like they've exhausted many protocols. Do you find in your practice that there is a lot of relapse and a lot of people end up with a recurrence of it?

Altman: Yeah, definitely, so there's one study that shows the recurring aftertreatment with Rifaximin that's about 50% at 6 months. We don't have specific studies looking at different types of treatment and whether the recurrence rate changes, say, for somebody treated with Rifaximin versus somebody treated with an elemental diet. This is why, in my practice, I implement a lot of other things to help prevent recurrence like maybe long-term antimicrobial herbs, prokinetics, maybe a modified diet or a low-FODMAP diet. So, unfortunately, we don't have studies showing what if we do all of these other things too then what is the recurrence rate? But in my practice I think it's lower when we add in those things. And unfortunately, for years SIBO's just been treated with Rifaximin and follow-up testing wasn't even necessarily done and then that's it. And so the studies that we have are based on that type of treatment.

Kaczor: Okay, so, yeah, that answered one of my questions. I didn't know if this was a diet people had to go on intermittently but it sounds like if one can get to the root cause of what's going on and kind of get the gut into a healthier place and perhaps do a few things like longer-term antimicrobial herbs or prokinetics ... And just out of curiosity, prokinetics, when you say that in the naturopathic realm, what are you talking about exactly?

Altman: So, prokinetics can be in various forms. They can be pharmaceutical and they can be herbal and I use both, sort of depends on the person and what they respond to and sort of what level of prokinetics they need. So a prokinetic is essentially something that makes the gut move, it increases motility of the small intestine, which can be a really big problem, particularly in the autoimmune type of SIBO. And so naturopathically I'm generally starting with herbal options, which may include things like ginger and 5-HTP, bitter herbs, things like that.

Kaczor: Yeah and that brings up another question I have and that is with that idea of the lack of peristalsis within the small intestine that seems to be implicated in SIBO and those prokinetics working for those people, it seems to me, and correct me if I'm wrong, that stress has a lot to do with this. That people who maybe have more anxiety or anxiousness and we say they hold it in their gut kind of thing. Is that true in your experience? Do you notice stress having any effect on SIBO or on their GI symptoms?

Altman: I would definitely say so. I have a few patients whose only known risk factor for getting SIBO has been going through a very stressful event. And actually it's those people are the ones that tend to have fewer recurrences or not have recurrence at all because there's not an anatomical or motility issue that you have to deal with. Essentially once you clear the SIBO it's more stress management that helps keep it away. So yeah, that is definitely true. Also, if we think about the sympathetic versus parasympathetic nervous systems, so in the sympathetic nervous system is the fight or flight. And in the fight or flight nervous system, we shunt blood away from our digestive system to our limbs so that we can run. In a parasympathetic nervous system, that's the rest and digest, and so we're shunting blood to the digestive system to help break down food. And so if you're stressed you're kind of constantly in this sympathetic, fight or flight state and you are not shunting blood toward your digestive system to function properly. So that's a really concrete example of why stress would make this worse.

Kaczor: Yeah, yeah, that makes perfect sense. And then, I guess, kinda sticking to the mind-body idea and how the physiology is functioning, I guess, one question I had for you as a practitioner. Do you find that sometimes doing dietary restrictions like an elemental diet, especially when there is a lot of concentration, a lot of time and effort on eating the right things and making sure that the wrong things don't go down, and all of that, have you ever found that there's some trigger for relapse in those who have a prior eating disorder? Especially people, young women, and they might be in high school or college, they had bulimia or anorexia and here they are in their 50s and maybe they have to go through either an elemental diet or more likely the other diets you were talking like the FODMAP diets or the specific carbohydrate diets, very restrictive diets. And they get into kind of a neuroses about food is basically what I'm asking. Have you found that to be true at all?

Altman: Yep, unfortunately I have found that people having eating disorders by trigger them through giving them an elemental diet. So no, it wasn't in the history I was aware of and then they went on the elemental diet and then suddenly this history of an eating disorder became an issue because the elemental diet did trigger that. And that's also true for, I think, any restrictive diet. So a history of or current eating disorder for me is a relatively strong contraindication to an elemental diet or any other type of restrictive diet. I think, I agree with you, I think it's a fine line between treating SIBO and having disordered eating. So when you feel poorly every time you eat and every time you eat you get more bloated, it created a negative feedback pattern associated with food and over time that can cause bigger problems like fear of eating almost anything. You know that anything you eat is gonna make you feel poorly and I think that's something to be really careful of if you have SIBO or if you are treating a lot of SIBO.

Kaczor: Yeah, and thanks for saying it because I think that's a big heads up for everyone who is looking at using this diet. Especially practitioners, that's a very simple thing to have on an intake form so it doesn't have to be too deep of a probe with the patient. It can be very simply asked. So on that note, are there any other contraindications, any other patient populations that we should be aware of that we should be especially careful with this diet?

Altman: Well, you need to think about it, I think, really on a case by case basis. Anybody could have something that could be a contraindication. One of the biggest concerns people have is about weight loss or low BMI. I find that's a relative contraindication. A lot of people think of the elemental diet as a fast, which it's really not. You have all of the calories and nutrition you need and you can increase the amount of formula somebody's taking as needed to meet their caloric requirements. So I've actually had several patients who are really malnourished, had a lot of difficulty maintaining weight, actually gain weight on the elemental formula because it was providing nutrition for them in a way that they could actually absorb and utilize in their bodies. So, I mean, that's something to think about. Diabetes for me is some concern, especially with the insulin needs and blood sugar dysregulation. The elemental diet, as I mentioned in the beginning, the carbohydrates come in the form of sugar and so it does have some potential for blood sugar dysregulation if you're drinking it really quickly. You can really mitigate not a lot by drinking it slowly over time but that would be another concern.

Fungal overgrowth can definitely be exacerbated by an elemental diet, again, because of the sugar content. I initially, when I started using it, thought that maybe kidney disease would be a concern. But I looked it, wasn't really able to find anything that verified that there was any issue with giving an elemental diet in somebody with kidney disease. And actually there was one study I found that showed improvement in kidney function in people with chronic kidney disease on an elemental diet. You might wanna be a little bit more careful in somebody with compromised liver function because amino acid metabolism can lead to ammonia production and build up in their liver and so that might raise liver enzymes. But again, if you're only doing this for 2 weeks or so that really shouldn't make a big difference. And then, as I already mentioned, really that history of the eating disorder is a big red flag for me and then contraindication.

Kaczor: Well that's ... I know this has been incredibly helpful from a practical perspective. I think that in less than 20 minutes we've touched on a few things that are definitely what I would consider clinical pearls for our listeners. So I really appreciate you taking the time of your schedule and offering up your expertise for our listeners. So thanks for being here with me.

Altman: Oh, it's been a pleasure. Thank you.

Kaczor: And once again, this is Tina Kaczor with the Natural Medicine Journal. And I'd like to thank the sponsor of this podcast, Integrative Therapeutics.

Sep 7, 2017

In over half of all cases of hospitalization for a cardiovascular event, the first symptom is the event itself. So anything we can do to get any early indicator that something is going wrong in the cardiovascular system can have a huge impact. Erectile dysfunction is one such early signal. According to cardiovascular health expert Daniel Chong, ND, identifying sexual dysfunction is essential for improving cardiovascular outcomes. 

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Approximate listening time: 30 minutes

About the Interview

It may seem counterintuitive to interview a cardiologist, and not a urologist, on the topic of erectile dysfunction (ED). But we now know that ED is a result of endothelial cell dysfunction and ED can be an early warning sign of systemic atherosclerosis. Looking at ED from a cardiovascular perspective is essential.

That’s why we invited cardiovascular expert Daniel Chong, ND, to talk to us about ED’s connection to heart health. In this interview, Natural Medicine Journal’s editor-in-chief, Tina Kaczor, ND, FABNO, asks Chong about the complex interplay between vascular function and sexual function.

According to Chong, cardiovascular disease always has some degree of contribution—potentially a major one—in ED. That’s in part because blood flow is the key facet to obtaining a full erection. Cardiovascular dysfunction, including plaque in the arteries that regulate that blood flow, can therefore have an impact on ED. Even before plaque development becomes a problem, endothelial dysfunction in the inside walls of the arteries can play a role in erectile function.

In this enlightening interview, Chong explains the different issues that can contribute to ED, including anatomical, physiological, and psychological problems. It’s an important listen for any practitioner who sees men, since beyond being a problem in and of itself ED can be an early signal of other serious health concerns.

About the Expert

Daniel Chong, ND

Daniel Chong, ND, has been a licensed naturopathic physician, practicing in Portland, Oregon, since 2000 and focusing on risk assessment, prevention, and drug-free treatment strategies for cardiovascular disease and diabetes, as well as general healthy aging, and acute and chronic musculoskeletal injuries. Chong has also completed certificate training in cardio-metabolic medicine from the American Academy of Anti-Aging Medicine and is an active member of the Society for Heart Attack Prevention and Eradication (SHAPE). In addition to his clinical work, Chong serves as a clinical consultant for Boston Heart Diagnostics Lab.


Tina Kaczor, ND, FABNO: Hello. I’m Tina Kaczor for the Natural Medicine Journal. Today, we’re going to be talking about erectile dysfunction and cardiovascular disease with Dr Daniel Chong. Dr Chong is a naturopathic physician with a private practice in Portland, Oregon for the past 17 years. He specializes in what he likes to call "vascular wellness optimization." He’s also the founder of the web-based consulting company, the Healthy Heart Project which offers a number of educational and direct consulting options for both the general public as well as healthcare practitioners on how best to assess and reduce risk for cardiovascular disease. Dr Chong also lectures and serves as a clinical consultant for Boston Heart Diagnostics Lab.

Thanks so much for joining me today, Dr Chong.

Daniel Chong, ND: You're welcome, Tina. Good to be here.

Kaczor: As I mentioned, our topic today is erectile dysfunction. At first, it may seem odd to our listeners that I’m talking to a cardiology expert and not a urologist or men’s health expert but we now know that erectile dysfunction is a result of dysfunction of endothelial cells and in fact, this can be an early warning sign of systemic atherosclerosis. Dr Chong, can you start us out with a brief overview of how erectile dysfunction and cardiovascular disease are related?

Chong: Sure. I can do my best there. There’s definitely going to be different circumstances that can contribute to erectile dysfunction. Some of which may not be actually anatomical, so to speak, or physiological from the cardiovascular perspective but I would say the majority is at least indirectly affected because even if we’re talking, for example, about a psychological contributor which we may touch on later, if somebody has dysfunctional arteries down there in the penis, they’re going to be more vulnerable to effects from psychological aspects than they would be otherwise. In other words, a young teenager may get stressed out in an early sexual experience but that’s not going to affect function as much as it could a 50-year-old man.

Anyways, in general, we could just say that cardiovascular disease is going to have some degree of contribution and potentially major. Obviously, blood flow is the key facet to obtaining a full erection and certain arteries are going to be more vulnerable to impacts from the development of cardiovascular disease but even so, the arteries in the penis may or may not actually have plaque in them but they can still dysfunction. Typically, we know, and we’re going to talk about this later, in cardiovascular disease, the preceding step prior to actual anatomical change or plaque development is endothelial dysfunction or dysfunction in the inside wall of the arteries and even that going on without any actual plaque having developed yet can affect erectile function and not to be noticeable by the person.

All in all, I guess you could say they’re intimately intertwined because you have to have good blood flow. It may or may not have plaque. Plaque may or may not be actually playing a role yet but it will in some cases and cause really significant dysfunction, but even minor dysfunction is going to be at least the partial result of the arteries starting to misbehave for various reasons that hopefully we’ll touch on.

Kaczor: Yeah. I actually came across some mention of erectile dysfunction in that whole idea of plaque formation. One author said that it could signify in some patients, or at least it should be followed up to see if it signifies subclinical atherosclerosis.

Chong: Correct.

Kaczor: Yeah. Atherosclerosis being pretty much asymptomatic in people until there’s larger consequences. On that note-

Chong: Right. Yeah. Sorry to cut you off. Sadly, it’s been shown that in over 50% of cases of hospitalization for a cardiovascular event, the first symptom is the event and that’s over half of all of them, so anything we can do to get any early indicator of something in this, so to speak, before, for example, erectile dysfunction, is hugely important for us because we are not doing a very good job at least conventionally in identifying early on what’s going on with people.

Kaczor: Yeah. I look forward later in this discussion to talk to you about how to assess it, to find early markers besides just the symptom of erectile dysfunction but let’s start with the larger picture in conventionally recognized erectile dysfunction and cardiovascular disease risk factors. Can you talk a little bit about like when we’re, as clinicians, who walk into our office, who we should suspect it in or at least engage in the conversation because many patients won’t bring it up themselves unless they're directly asked?

Dr Chong: Yeah, absolutely, so, certainly age. The older a man gets, the more potential there's going to be for all kinds of different changes going on physiologically. Some people are well aware of testosterone production, how crucial that is and that certainly begins to change as a man ages. But certainly, very standard, interestingly enough, it’s the same standard risk factors you might consider for cardiovascular disease in general in terms of high blood pressure, diabetes, certainly, smoking.

Conventionally, you're going to see high cholesterol as a stated contributor but we can certainly talk in more detail about that because I know that some people out there in the functional medicine world, naturopathic world, et cetera, consider high cholesterol as a past tense risk factor for cardiovascular disease which it really is and it’s just more complicated than that. Obesity, lifestyle factors in terms of exercise and then certainly, psychological factors, depression and anxiety, et cetera are all going to be key things.

I also want to make a just brief mention even though this is kind of a topic in and of itself, when we talk about erectile dysfunction, obviously, we’re talking about men but it should be very clearly stated that the same potential processes are going on in women as they age. Women with difficulty with sexual activity or orgasm, et cetera, may in fact be having their own version of “erectile dysfunction” with the clitoris as essentially an analogous structure in a woman and all of these blood flow issues can occur in women as well. It’s important to really kind of make mention to that. I say men, I keep saying men, as men age, blah, blah, blah, but it really should be looked at as both sides of the coin, so to speak.

Kaczor: That’s actually an important point. Thank you for mentioning that.

Chong: Sure.

Kaczor: I want to do a follow-up on that cholesterol thing that you just mentioned because I think that that’s kind of top of mind. I think it’s important to give voice to any new data on looking at cholesterol because I'm with you on it being much more complex and it’s more complex than I understand. I'm happy for you to kind of flesh it out for us.

Chong: Yeah. I mean, I guess anybody that says that cholesterol has nothing to do with cardiovascular disease is not really thinking about the fine details of the situation. You can't have a plaque form without cholesterol and lipoprotein particles being involved because they are what are the sort of primary components to the development of the plaque.

What I don’t agree with conventionally is the idea that high cholesterol, in and of itself, is just going to definitively contribute to cardiovascular disease because obviously, there are many people out there who have relatively “high cholesterol” who don’t get cardiovascular disease. There's certainly something else going on that’s playing a role as to whether or not high cholesterol is going to lead to that issue in some people versus others.

Long story short, I consider cholesterol and related markers to be secondary factors. They are absolutely involved but they are not … There's going to be other things that help sort of determine the likelihood or lack thereof of the high cholesterol sort of turning into cardiovascular disease. That’s a really fun discussion in and of itself. It could be another hour or so by itself but hopefully, that kind of answers your question, at least preliminarily.

Kaczor: Well, it brings up another question which is-

Chong: Certainly, keep going with that. Yeah.

Kaczor: Yeah. If cholesterol is considered a secondary factor, and I see what you're saying, cholesterol is not … needs to be present but can't be causative because there's not a cause and effect 100% of the time.

Chong: Correct.

Kaczor: If it’s secondary, what are you looking at as primary?

Chong: Well, to me, the absolute most important thing that’s going to contribute to the potential or lack thereof of eventual cardiovascular disease development or i.e. plaque, development is the health and vitality of the walls of the artery and how well they're functioning. In other words, the healthier, more nutritionally replete the walls of the arteries are themselves and the better they're being sort of manufactured in the first place by the body, are going to be the primary factor that leads to vulnerability or not.

If you imagine like … I would like to use analogies. On a coastline, you may have, let’s say, in Hawaii versus somewhere else on the mainland. Hawaii is made up of volcanic rock which is, tends to be a little bit more brittle and it can sort of erode more easily. If you have waves crashing into the wall, into a wall of rock in Hawaii, it may erode more quickly. Then, an analogous wall somewhere else in the world that’s made up of a different, harder, more resilient material, the waves are still crashing into them with the same potential force but one’s going to erode more quickly than another.

If we then relate that to the vascular system, somebody who has poor nutrition and tons of inflammation, oxidative stress, et cetera, and especially long-term poor nutrition, they're not going to be able … especially if we’re talking about collagen production, they're not going to be able to manufacture the sort of strong, resilient vascular walls that they should which will inevitably be, if they are stronger, will inevitably be more resistant and resilient to the impact of the turbulence of the flow of blood.

There are certainly other things that are going to impact that as well especially the turbulence itself and the viscosity of the blood. That’s going to make for essentially like stronger waves crashing in which obviously, the stronger the waves is crashing into the area, the more potential there is for erosion as well. To me, long story short, the primary situation that’s going to lead to the potential development of plaque is a combination of two primary factors. That’s the vulnerability of the wall of the artery and the stress that is being placed on the wall of artery.

Kaczor: By-

Chong: If you look at every single risk factor we know of, they are impacting one or both of those factors.

Kaczor: Okay. When you say stress, you mean mechanical forces, as well as chemical?

Chong: Chemical. Absolutely.

Kaczor: As in oxidative stress?

Chong: Correct. That would be one of them. I mean, even environmental toxins, different types of infectious organisms and certainly mechanical stress as well or what we call blood viscosity which is impacted by a variety of factors. Primarily, probably the main ones for blood viscosity would be hydration and like even iron levels or high sort of … basically, concentrated solid substances in the blood and then also, cloudiness of the blood, how high is fibrinogen levels and things like that are going to impact the viscosity of the blood. Then, the classic risk factor of high blood pressure is going to be too, more or less, stress on the wall of artery.

Kaczor: Let’s-

Chong: Sorry. One other thing. I mean, one of the ways that high cholesterol may be contributing to things is it’s known that the higher the cholesterol is, the stronger the impact on the vascular wall is. It actually causes … High cholesterol itself can contribute to endothelial dysfunction or stress on the function of the wall of the artery.

Kaczor: Doing mechanical forces, you're saying, to the viscosity of the blood.

Chong: Right, and more technical reasons, like it literally messes with certain aspects of how the wall, the endothelium is supposed to be functioning. It’s not just that it gets into and becomes part of the plaque. The higher your cholesterol goes, the potentially worse the endothelial function initially.

Kaczor: Okay. Let’s switch gears a little bit. If we’re talking about endothelial dysfunction as the commonality between erectile dysfunction, atherosclerosis, cardiovascular disease, it’s all about a healthy endothelium.

Chong: Right.

Kaczor: It’s interesting, in that same paper I mentioned before, I came across a term that I had not seen before. It was the endothelium as a single organ which I thought was a really interesting concept like, “Oh,” thinking, “I'm sure it’s different, in different tissues,” but just the idea of overall health of it being a singular thing was interesting to me.

Chong: Right. People look at the blood vessel as like these tubes that are just allowing for the passage of blood flow. There's so much going on at the wall of the artery physiologically. It is absolutely an entire organ.

Kaczor: Let me ask you this. As far, for us as clinicians, what are either biomarkers or assessment tools, how do we gauge endothelial function in a patient?

Chong: Well, technically, when we’re specifically talking about endothelial function, there's only a few ways to directly assess that. Clinically, they're going to involve some way, shape, or form of actually testing, in-office, the function of the arteries themselves. There's a general … There's a few … There's basically two main machines that I'm aware of. One is called an EndoPAT and one is called the EndoTherm that are designed to directly assess endothelial function.

The way they basically work is they … You have your fingers in some type of device that’s monitoring either blood flow or temperature at the fingertips. Then, you basically occlude the artery and the arm like you would with the blood pressure cuff. You have to do that for about 5 minutes which is not enjoyable for the patient because, as you can imagine, it isn’t feel very good to have your blood occluded for 5 minutes. Then, prior to doing that though, you're doing a general assessment on blood flow and temperature of the fingers. Then, you occlude the blood flow and then you let it out all at once.

When the blood comes, as you might imagine, rushing back into the extremities in the fingers, you should get some degree of expansion of the arteries. Normal function would lead to the arteries, as the blood really rushes in there, would lead to the arteries expanding to a certain extent. People that have endothelial dysfunction, their blood vessels will not expand appropriately. The machines are designed to sort of read that, sort of the tip, where your tips of your fingers are sitting, the machines is detecting, is there a significant enough change in temperature and or blood flow.

There's also something called arterial pulse velocity which basically, there's a smaller device called an iHeart like an iPod but it’s iHeart. I'm not connected to any of these companies or anything like that but that is a newer device that’s being developed that checks sort of indirectly the same thing. It looks kind of like a pulse oximeter but it’s actually detecting arterial pulse wave velocity and literally how quickly a pulse rate is moving down the arterial tree.

If you might imagine, the sort of left compliant and arterial, an artery is, the quicker the pulse rate is going to move down it. That’s generated by heart, a heartbeat. Those are the only ways that I'm aware that are … Those are the only things that I'm aware that are being used in-office to directly assess endothelial function. There is a lab test that can be measured with people called ADMA. It stands for asymmetric dimethylarginine. That is considered a surrogate or indirect assessment of endothelial function. The higher the ADMA is, the higher the potential for endothelial dysfunction because it’s a direct sort of inhibitor of nitric oxide production.

Kaczor: All right. Well, that leads us into our next little piece, doesn’t it? Nitric oxide production being integral to the whole relaxation of the smooth muscle and the endothelium to allow for blood flow whether we’re talking about the fingertips or the penis. Can you talk a little bit about nitric oxide? Maybe briefly mention how an assessment can be made, the ADMA being one of the means of assessing that as far as the blood test and anything else that might be accessible to a general physician or clinician that might be seeing these patients.

Chong: Well, I mean, endothelial function is, to me, the ideal way to get an assessment of that because I'm a big proponent of the idea that we want to check end of point factors as often as we can. Classic example of this is looking at the different impacts of certain dietary changes on cholesterol markers and making conclusions about whether or not that is good for the vascular system or not, certain changes like HDL going up, for example, after the implementation of a certain diet did not guarantee by any stretch of the imagination that you're having a positive effect on the vascular system so I like to use endpoint markers or end, sort of, functional markers as much as possible so far and away still, the best way to me to assess nitric oxide levels is via those endothelial function tests that we mentioned already.

Other ways to sort of try to get an assessment of it, the only other way that I’m really aware of is if you've seen … You've been to enough conferences, I know. You’ve probably seen this company that has this little saliva test that you can use to check basically nitrate levels in the saliva. That’s going to be … Nitrate is a crucial factor, nitric oxide production as well, so some people are using these little saliva tests to check what a person’s typical nitrate intake is and then recommending dietary or supplement interventions based on that. Those are really the only ways that I’m aware of to sort of really truly get an assessment on that other than, obviously, history and talking to a person, seeing how well things are working, so to speak.

Kaczor: Can I ask you a question? I don’t mean to put you on the spot and I do not know the company that’s offering nitrate levels in saliva but is this something that’s been validated or is it with any rigor or is this one of those early adoption things that happen?

Chong: Right. You're asking me if something has been validated with scientific tests or research? Can you restate?

Kaczor: Or at least … Yeah.

Chong: You do that with everything which is great. That’s why I like you so much but I don't know for sure. This is … In all honesty, I haven’t really looked too deeply into that method of assessment with people, so I wouldn’t be able to say with any certainty at all. I know that they’re quite widely used and it’s not a very complicated, technically complicated test so I think it’s pretty straightforward. I do recall seeing literature being made available by these companies but I have not looked that in-depth at that at this point.

Kaczor: Well, I appreciate your honesty. When you're on the cutting edge, early adoption of new technologies is part of our … We get to do that. We get to be right there doing, instituting things but it’s important, I think, for us all to go at a pace that has some, at least reproducibility, if not rigor.

Chong: Absolutely. The other thing that I would say to add to that is like using different angles of assessment is also crucial, not just relying on one piece of information whether it be cholesterol. That’s why the classic conventional mistake is like, “Okay, we’re going to check and see if you have a high risk for cardiovascular disease. Let’s check your lipid panel. There’s so much more beyond that that can be done to assess and evaluate people and get a much clearer picture. That’s a classic idea, just sort of not settling on one thing, not just using the newest thing, whatever it is. Use as many tools as you can within reason to get the clearest picture.

Kaczor: Yeah. I want to continue on the molecular biology of this and specifically, we have just a few minutes left, really talk about-

Chong: Time flies when you're talking about erectile dysfunction.

Kaczor: What’s that?

Chong: I said time flies when you're talking about erectile dysfunction.

Kaczor: Well, oxidative stress, being something that you mentioned and it’s just something that we’re … That inflammation is kind of always at the forefront of anyone who’s doing integrative medicine or optimal wellness or however you want to term it. I guess my thought is this. In a concise way, can you tell me if you use any actual blood markers that are widely available and what are some of your favorite ways of, kind of across the board, addressing oxidative stress issues, which even beyond erectile dysfunction, it becomes part and parcel with that but it’s also just part of life and part of being alive, is creating oxidation?

Chong: Right. In the realm of assessment, especially if we were going to so far as to separate out inflammation in oxidative stress because obviously, they aren’t exactly the same thing, when we’re talking inflammation, the primary markers that I’m measuring with people certainly are high sensitivity CRP as our sort of general global marker of inflammation or lack thereof. When we’re talking about the vascular system, I’m also typically going to be checking something called Lp-PLA2 or what’s also known as the PLAC test. That is more specifically an inflammation marker for the vascular system so it’s going to actually reveal immunoactivity and inflammation going on in the wall of the artery whereas a high CRP is not going to be able to definitively determine that or not. MPO or myeloperoxidase is a later stage, nonspecific but frequently correlated marker for late stage vascular inflammation for a vulnerable vascular system.

In the realm of oxidative stress, the 2 primary markers that I might look at is actually … number 1 is actually oxidized LDL so it’s pretty hard to have moderately elevated LDL levels and a high amount of oxidative stress and not see a relatively increased level of oxidized LDL in the bloodstream. That is sort of a good, what you'd call extracellular oxidative stress marker, but we can also get intracellular oxidative stress for different reasons.

For that, you can also check something called 8-oxoguanine which is an actual, actually a urinary test. Not too many labs run that. I’m not sure if we’re supposed to name names here but that is an … If you just Google 8-oxoguanine test or something like that, you can probably find the labs that run that but that’s going to give you more of an assessment of intracellular oxidative stress. Then, beyond that, you can, in all honesty, get a pretty good idea whether or not somebody is going to be a candidate for high oxidative stress just by talking to them and looking at them and that type of thing as well.

Kaczor: Yeah. A lot of those other markers for cardiovascular disease like obesity, even the aging process, certainly smoking, all-

Chong: Right. Absolutely.

Kaczor: Obviously, we would take into account for oxidation. Can you let me know or let the listeners know your top three? Someone looks at you and they’re like, “Listen. I do everything right. I exercise. I eat well. My BMI is normal. I don’t drink. I don’t smoke. What are the three supplements you …” You only get to see them once. They’re going to leave your office.

Chong: These people are eating well, you said, in my opinion?

Kaczor: Okay. That brings up the point. What would that look like in your opinion?

Chong: No, no. I’m sorry. I’m just-

Kaczor: We only have 2 minutes left but what would be an ideal guy in your opinion and then-

Chong: No, no, no, no, no. I’m sorry. I was just clarifying the question. If these people are already eating well like they’re eating lots of fruits and vegetables, et cetera and I’m just talking about supplements, the 3 main ones I’m going to recommend are going to be vitamin C, magnesium, and then probably some type of concentrated plant-based antioxidant. As a naturopath, herbal medicine trained, I have an affinity to hawthorn but also, I frequently recommend hibiscus tea to people.

Kaczor: Nice. Hibiscus being, you're also from Hawaii so that’s-

Chong: Good point. You could certainly go beyond that and complement it with things like arginine, citrulline, and then there are a number of nitric oxide precursor type of products that are high in dietary nitrates.

Kaczor: Well, Dan, I really appreciate this. I feel like we could have a whole part 2 where we go into the therapeutics and more details into all of this but I think the listeners have gotten good overview today and I really do appreciate the time you've taken and your expertise, and best of luck with your Healthy Heart Project.

Chong: Thank you, Tina. It was good to talk to you and happy to help as I can.

Kaczor: All right. Take care.

Chong: All right.

Sep 7, 2017

One in four men over the age of 65 has urinary incontinence, according to the Centers for Disease Control and Prevention. In this interview, men's health expert Ronald Morton, MD, FACS, describes how urinary incontinence is diagnosed and treated. He also provides detailed information about the key medical devices that are available to treat this condition.

Approximate listening time: 14 minutes

About the Interview

Although urinary incontinence is not as common in men as it is in women, it is more prevalent than many people think. According to the Centers for Disease Control and Prevention, one in four men over the age of 65 suffers from it.

The underlying causes are often similar in both genders: aging and weakening of the pelvic floor muscles. However, pelvic trauma or prostate disease or surgery can also contribute to the problem in men.

Urinary incontinence creates significant quality-of-life issues, so finding effective treatments is very important.

In this interview with urologist Ronald A. Morton, Jr., MD, FACS, Natural Medicine Journal’s publisher Karolyn A. Gazella discusses the prevailing treatment options for male urinary incontinence. For some men, pelvic floor exercises alone can provide relief. For others, diet and weight modification are necessary. Others may opt for more advanced interventions, including surgery.

Surgical options range minimally invasive to extensive. On the simpler end of the spectrum is the basic urinary sling. In this quick procedure, a sling is inserted to replicate the support lost in previous interventions or trauma. On the other end of the spectrum is an artificial urinary sphincter, which regulates urine flow through a pump.

Of course, surgical interventions are not without risks and side effects. Morton addresses those and discusses how to determine whether a patient is a good candidate for surgery.

Listen to this interview to learn more about the current treatment options for male urinary incontinence, as well as Morton’s predictions for the future of incontinence treatment.

Scroll down for the full transcript.

About the Expert

Ronald A. Morton, JR, MD, FACS, is the vice president of clinical sciences for the Urology and Pelvic Health division of Boston Scientific, a position that he has held since August 2015. Before joining Boston Scientific, via acquisition, Morton worked for Endo International plc as chief surgical officer, American Medical Systems. Previously, he worked for GTx, a biotech company in Memphis, TN, as chief medical officer. Prior to joining GTx, Morton was chief of urology at Robert Wood Johnson Medical School and director of urologic oncology for the Cancer Institute of New Jersey. He also held an endowed chair position as director of the General Clinical Research Center. Morton holds a BA in natural sciences from The Johns Hopkins University and received his medical doctorate from The Johns Hopkins University School of Medicine. He has board certification as a diplomat, American Board of Urology.


Karolyn: Hello, I'm Karolyn Gazella, the publisher of the Natural Medicine Journal. Today our topic is male urinary incontinence and my expert guest is Dr. Ronald Morton. Dr. Morton, thank you for joining me.

Dr. Morton: Hi, Karolyn, and thank you for having me today.

Karolyn: Well great. Well, let's just start with the basics. How is urinary incontinence diagnosed in men?

Dr. Morton: Karolyn, urinary incontinence is not as common in men as it is in women, although it does happen more commonly than people think. The main causes are as it is with women, aging and weakening of the pelvic floor muscles. But more importantly, and the reason for many of the interventions that we have for urinary incontinence in men is it can be due to trauma to the male pelvis and/or surgery for diseases of the prostate. When I say disease of the prostate I mean both benign conditions like BPH, which many men suffer from and are aware of, and then also prostate cancer, which is a very common cause for surgery on the male pelvis.

Karolyn: And then what's considered the gold standard of treatment for this particular men's health condition?

Dr. Morton: There are many ways to treat male incontinence, as there are many ways to treat female incontinence. The usual approach that will be taken by a urologist is to go from the least invasive to more invasive solutions until the patient is happy. I think that one thing that always has to be kept in mind is that this is really a quality of life issue for most men, especially since urinary incontinence in males is generally a disease of men who are older. The median age of diagnosis of prostate cancer is about 63 years of age or so. Since operations on the prostate are the common cause for this, they're generally older men and it's a quality of life issue.

What one male will find satisfactory control of the urinary incontinence might be totally unsatisfactory to another. So the general approach would be to start with exercises, commonly called Kegel exercises. The same exercises that we suggest that women do who have a mild degree of urinary incontinence and see if that won't help. If Kegel exercises won't help and it's not something that can be helped with diet and weight modification, then we go into more invasive treatments for male urinary incontinence.

The first level of invasion is a procedure that only takes a few minutes, really, less than a half an hour called a male urinary sling. It's much like the slings that are used in women. It  supports the male urethra and holds it up, providing support that has been lost due to the previous surgical intervention or pelvic trauma in hopes that that will correct the incontinence.

Fore more severe degrees of incontinence we often times need to move towards what is really considered, as you say in your question, the gold standard for severe incontinence, which is the artificial urinary sphincter [AUS]. In that procedure, a cuff is placed around the urethra and this cuff is connected to a pressure-regulating balloon, which controls pressure in the cuff, keeping the urethra closed and preventing leakage of urine and also a pump, which is placed in the scrotum. When it's time to urinate, the male can just activate the device. The fluid leaves the cuff and goes into the pressure-regulating balloon, opening the urethra. The male can then urinate and then after a period of lock-out time, the cuff will refill, returning him to a state of continence.

Karolyn: So let's talk about these two, the sling and the sphincter. What determines whether or not a patient is severe enough for the sphincter versus the sling? What's the difference between those two patients, the one that gets the sling and the one that gets the sphincter?

Dr. Morton: Good question because again, it has a lot to do with personal preference. But there are some general guidelines that one can go by. When we measure incontinence and it can be a difficult thing to put a number on, but most men who have incontinence will use urinary pads in their shorts in order to trap urine leaking. A good gauge of to what degree a male leaks is how many times they have to change that pad. Now, some men will as soon as there's a small amount of urine because of the discomfort it will cause will change that pad right away. Some men tend to allow the pad to get very, very soaked before they'll change it. Everyone behaves a little bit differently.

A way to get a handle on exactly how much leakage a man has it to do what we call the pad weight test. So we'll give them all the pads that they might need for a day and a bag that can prevent evaporation and they just collect the pads that they use for the day, put it in this bag, and everything is pre weighed, and then we weigh it to see what the volume of urine leakage is.

A rule of thumb, if they're leaking around five pads or 300cc of urine a day, that's severe and is more likely to be treated with the artificial urinary sphincter. Degrees of urinary leakage that are less than that can be and generally might be recommended that they be treated with the sling procedure.

Karolyn: Now are there are any contraindications associated with each of these options, the sling or the sphincter? So in other words, are there men who would not be a good candidate for either of these options?

Dr. Morton: Well, they have to be able to undergo a surgical procedure, and while the sling procedure is relatively short, it does require at least a regional anesthetic. The artificial urinary sphincter procedure is a little bit longer and requires a general anesthetic so they have to be fit for the surgery. The sling is generally not recommended for men if they have been treated for prostate cancer with radiation. The outcomes there haven't been as good as they have been with the artificial urinary sphincter so in that setting we generally would recommend a sphincter as opposed to a sling, even if they were otherwise a good candidate for a sling.

Karolyn: What about side effects? Are there any side effects associated with either of these devices?

Dr. Morton: I'll take that question separately for each of the two devices. The side effects associated with the sling are that if you don't choose the patient in the best way, two things can happen. One, the patient can not have their incontinence adequately treated. A second issue is if you put a sling in a patient whose major problem is not one of the urethra but is a bladder issue, and that can be sorted out ahead of time with uro dynamics, but if you did you may render that patient obstructed or in urinary retention. The problem doesn't have to do with external sphincter deficiency for that patient.

For the artificial urinary sphincter what we're doing is we're placing this cuff around the urethra. It does over time potentially compromise some of the blood supply to the urethra in that area and you can get what's known as atrophy of the urethra in the area of the cuff. When you get atrophy in the area of the cuff there can be a return to urinary incontinence. Of course for both of these procedures, since you're putting a foreign body in, there's a risk of infection, although infectious problems with these devices have been relatively low.

Karolyn: Okay, that makes a lot of sense. Now, I'm just curious because you have a certain expertise in this area as chief surgical officer of American Medical Systems. What general advice do you give to physicians who are treating men with urinary incontinence?

Dr. Morton: One, most of the advice that I have is for physicians who have men with incontinence but aren't necessarily the experts in treating them. There's a couple of things. One of the things that our research has shown us is that many men who are subjected to surgery for prostate cancer, for example, and who then suffer from incontinence don't recognize, or aren't made aware that there are treatments for it and they suffer in silence we like to say. So, if we can get anything out to the many physicians listening to this podcast it would be don't let this happen to any of your patients. Make sure they understand that if they do get incontinence after, for example, radical prostatectomy, there are options and there are potential solutions for this.

The second message is I spend a lot of time working with the engineers and we're constantly looking at ways to come up with a better mouse trap if you will. What can we do to avoid the complications we spoke of earlier? What can we do to help physicians identify the proper patients so we don't use a sling in a patient who should've had an AUS, or an AUS in a patient who should've had a sling? And what can we do to make the functioning of the AUS a little bit easier so that in this elderly population of men they are always candidates for the device?

Karolyn: Yeah, that makes a lot of sense and I'm glad that you brought that up about suffering in silence and information. Obviously, a well-informed patient is the best patient to have. So letting that patient know his options is absolutely critical.

So one final question for you Dr. Morton. What is on the horizon when it comes to devices for this particular issue with men? Do you see existing devices just being improved? Do you see new devices? Are we kind of where we should be? Look into your crystal ball and tell me what the future holds for this.

Dr. Morton: I don't know if I'm the best person to predict the future, but I think that our efforts are to make sure that A, these are the right solutions. We are constantly looking at, are there other options? Are there other ways to manage urinary incontinence? Could we come up with a less invasive way to place the sling or a less invasive device would replicate the great performance of a sling?

On the urinary sphincter side of things it's a mechanical device, so can we simplify that mechanism so that it's easier for the patient to implement? Remember there's a patient interface with the AUS. Most devices that we implant, like when a cardiologist implants a pacemaker, there's no patient interface. The patient doesn't have to decide whether or not their pacemakers work. It's in and it just works. For our device, at least for the artificial urinary sphincter, there's that patient interface. So if we can improve that patient interface with the device and make it as reliable as possible, that's what we're looking to do in order to improve the overall performance of the device and have men have a greater satisfaction with their quality of life.

Karolyn: Yeah, that makes a lot of sense. Well, this has been very informative. Once again, thank you, Dr. Morton, for joining me today.

Dr. Morton: Karolyn, thank you for having me.

Karolyn: Have a great day.

Jul 19, 2017

By Natural Medicine Journal 

The FDA recently held a meeting (July 10-11, 2017) to discuss ways to decrease the frequency and patterns associated with opioid misuse and abuse. In this interview, pain management expert, Beth Darnall, PhD, talks about the crisis of opioid addiction and how to create safe, effective non-opioid pain management strategies.

About the Expert

Beth Darnall, PhD

Beth Darnall, PhD, is clinical associate professor in the department of anesthesiology, perioperative and pain medicine at Stanford University. Past roles include president of the Pain Society of Oregon and cochair of the Pain Psychology Task Force at the American Academy of Pain Medicine. Her NIH-funded research investigates mechanisms of pain catastrophizing, cognitive behavioral therapy for pain, and a targeted intervention she developed. She is also investigating the impact of an online psychological intervention she developed on postsurgical pain and opioid use in various surgical populations, including cancer and orthopedic trauma. Finally, she is investigating effective opioid tapering strategies in community-based outpatients with chronic pain.

Darnall is author of The Opioid-Free Pain Relief Kit and Less Pain, Fewer Pills: Avoid the dangers of prescription opioids and gain control over chronic pain, and the forthcoming book from the American Psychological Association titled Psychological Treatment for Chronic Pain. She is owner of Optimized Psychology Consulting. Her work and viewpoint has been featured by multiple media outlets, including the San Francisco ChronicleNew York MagazineMORE magazine, Forbes, and Scientific American. For more information visit her website at

Jul 5, 2017

By Natural Medicine Journal


While vitamin C may seem like a straightforward topic, it's actually rather complicated. In this interview, leading integrative medical expert Russell M. Jaffe, MD, PhD, describes some of the clinical complexities associated with this popular nutrient. Jaffe describes the different forms, dosages, and synergy with other nutrients. He ends with a description on how ascorbate helps with toxic mineral removal. 

Approximate listening time: 18 minutes

About the Expert

Russell Jaffe

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

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.

Jun 5, 2017

Leading integrative medicine pioneer, Russell Jaffe, MD, PhD, CCN, describes his philosophy regarding hard-to-treat thyroid conditions. Jaffe starts with proper diagnosis and then takes listeners through to the environmental impact, alkalinizing the body, and using targeted nutrients to provide an individualized approach.

Approximate listening time: 21 minutes

About the Expert

Russell Jaffee

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

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.


May 1, 2017

Lyme disease can be a challenging condition to treat. In this interview, integrative medicine expert, Russell Jaffe, MD, PhD, CCN, describes his treatment approach and also explains the important connection between Lyme disease and small intestinal bacterial overgrowth (SIBO).

Approximate listening time: 20 minutes

Play Now

About the Author

Russell M. Jaffe, MD, PhD, CCN, 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

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.

Apr 17, 2017

People who currently and have historically struggled with eating disorders often have many eating disorder-related symptoms that respond positively to an integrative approach to treatment. Just like many other chronic health conditions, with appropriately selected interventions, recovery from an eating disorder can be further facilitated with holistic support. Nutritional support, and natural support for mental health and digestive issues are just a few of the topics that we discussed during this interview with naturopathic expert Carrie Decker, ND. 

Listening time: 33 minutes

About the Author

Carrie Decker, ND, is a certified naturopathic doctor who graduated with honors from the National College of Natural Medicine (now the National University of Natural Medicine) in Portland, Oregon. Decker also holds graduate degrees in biomedical and mechanical engineering from the University of Wisconsin-Madison and University of Illinois at Urbana-Champaign respectively. Decker sees patients at her office in Portland as well as remotely. Her practice focuses on gastrointestinal disease, eating disorders, allergies, mood imbalances, autoimmune disease, chronic fatigue, thyroid disorders, and skin conditions. The primary modalities Decker employs are clinical nutrition, botanical medicine, homeopathy, biotherapeutic drainage, and counselling. Decker also supports integrative medicine education as a clinical education thought leader with Allergy Research Group and by writing for various other educational resources. More about her practice may be found at or

About the Sponsor

Allergy Research Group

Founded in 1979 by molecular geneticist Stephen Levine, PhD, Allergy Research Group® is one of the very first truly hypoallergenic nutritional supplement companies. For over 30 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.

Our purpose is to provide customers with products they can use to improve their patients’ quality of life, through scientific based innovation, purity of ingredients, education and outstanding service.

ARG is proud to be a sponsor of the Clinical Education LinkedIn Forum. A closed peer-to-peer group on LinkedIn where healthcare professionals can ask clinical questions and receive evidence-based and clinical-based responses by experts in their field.

Visit for more information & to sign up for free!

Visit for more information on ARG and our products.

Apr 17, 2017

In this interview Tieraona Low Dog, M.D., discusses the state of micronutrient deficiencies in America. Vitamin D, vitamin B6, magnesium, omega-3 fatty acids, and even vitamin C are deficient in tens of millions of Americans. Tieraona Low Dog, M.D. also discusses what can be done to identify and treat what she calls a “hidden epidemic of micronutrient deficiencies.” 

Tieraona Low Dog, M.D. will be speaking at the AANP Annual Conference, which will be held July 12-15, 2017, at the Arizona Biltmore in Phoenix.

Approximate listening time: 23 minutes

About the Author

Tieraona Low Dog, M.D., began her exploration of natural medicine and its role in modern health care more than 35 years ago while studying midwifery, herbal medicine, massage therapy and martial arts before earning her medical degree from the University of New Mexico School of Medicine. She served as the Fellowship Director at the University of Arizona Center for Integrative Medicine, where she oversaw the training of more than 500 physicians and nurse practitioners in integrative medicine and is currently the Fellowship Director for the Academy of Integrative Health and Medicine. An internationally recognized expert in integrative medicine, dietary supplements and women’s health, Tieraona Low Dog, M.D. was appointed by President Bill Clinton to the White House Commission on Complementary and Alternative Medicine Policy, and has served as Chair of the US Pharmacopeia Dietary Supplements and Botanicals Expert Information Panel. Learn more about Tieraona Low Dog, M.D.

Apr 4, 2017

In this interview, Ronald Hoffman, MD, discusses how he uses the specific carbohydrate diet (SCD) to treat inflammatory bowel conditions. Hoffman recently wrote an Abstract & Commentary on the efficacy of the SCD in children with Crohn's and ulcerative colitis. In this interview, he describes techniques to enhance compliance and outcomes with the SCD. He also compares and contrasts the SCD with the Paleo and low-FODMAP diets. Hoffman draws on his clinical experience in this area to give practitioners advice on how to manage difficult-to-treat cases of inflammatory bowel conditions.

Approximate listening time is 15 minutes.

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About the Author

Ronald Hoffman, MD, is a physician in private practice of integrative medicine in New York City. He is a graduate of Columbia College and Albert Einstein College of Medicine. Since 1984, he has served as Medical Director of the Hoffman Center in Manhattan. Hoffman is past president of the American College for the Advancement of Medicine (ACAM).

Hoffman is the host of Intelligent Medicine, a nationally syndicated radio program, and he produces the daily Intelligent Medicine podcast. He is a certified nutrition specialist (CNS) and the author of several books, including How to Talk with Your Doctor (About Complementary and Alternative Medicine).

Mar 7, 2017

Christopher Shade, PhD, is a globally recognized expert on the topic of human detoxification. In this interview he describes his testing and treatment protocol that effectively cleanses the system of mercury and other toxins. Shade also discusses dietary supplement liposomal delivery technology.

About the Expert

Christopher Shade, PhD, obtained bachelor of science and masters of science degrees from Lehigh University in environmental and aqueous chemistry, and a PhD from the University of Illinois where he studied metal-ligand interactions in the environment and specialized in the and analytical chemistries of mercury. During his PhD work, Shade patented analytical technology for mercury speciation analysis and later founded Quicksilver Scientific, LLC, to commercialize this technology. Shortly after starting Quicksilver Scientific, Shade turned his focus to the human aspects of mercury toxicity and the functioning of the human detoxification system. He has since researched and developed superior liposomal delivery systems for the nutraceutical and wellness markets and also specific clinical analytical techniques for measuring human mercury exposure. He used his understanding of mercury and glutathione chemistry to design a unique system of products for detoxification that repairs and then maximizes the natural detoxification system.

About the Sponsor

Quicksilver Scientific is a CLIA-certified laboratory and health supplement wholesaler located in Lafayette, CO, specializing in superior liposomal delivery systems and blood metals testing for human health and detoxification. We use state-of-the-art technology, including patented mercury speciation, for the most accurate and reliable testing available today. Our liposomal supplements incorporate our Quicksilver Delivery System which brings the power of intravenous therapy to oral delivery and dramatically increases absorption and effectiveness, to restore the body’s natural detoxification system and re-establish natural health and optimum functioning. Our tiny particles encapsulate health-supporting compounds that absorb directly through the mouth into the bloodstream, bypassing the harsh digestive process that destroys or excretes most pill-form supplements. Smaller and faster, Quicksilver Scientific's Etheric Delivery™ systems are clearly superior to other products on the market.

Jan 4, 2017

In this podcast, Danielle Citrolo, PharmD, describes how a unique combination of L-glutamine and L-alanine can enhance electrolyte and water absorption in the intestines, stimulate glycogen synthesis, inhibit muscle protein breakdown and promote the synthesis of muscle protein. This dipeptide compound has also been shown to help protect the integrity of the gastrointestinal tract, contributing to better nutrient absorption.

About the Expert

Danielle Citrolo, PharmD, is manager of technical services at Kyowa Hakko, where she provides technical, scientific, and regulatory support. She also acts as liaison with regulatory authorities in the United States, Canada, and Latin America. Before joining Kyowa, Citrolo was the clinical coordinator at The Hospital for Special Surgery in New York City. She has experience in developing clinical research protocols and managing clinical trials. She earned her bachelor of science in biochemistry and bachelor of arts in chemistry from North Carolina State University and her doctorate in pharmacy from Albany College of Pharmacy in New York. She is licensed by the New York State Board of Pharmacy.

About the Sponsor

Sustamine®  L-Alanyl-L-Glutamine is an excellent choice for use in clinical nutrition because it does not have the problems of poor stability and low solubility that are associated with free-glutamine. Glutamine begins to degrade when mixed with liquids, but Sustamine®  is a unique dipeptide form of glutamine that’s been designed for maximum stability. This means patients get the amount listed on the label when they add it to water or their favorite beverage. Sustamine®  is tasteless, colorless, odorless and dissolves completely in hot or cold liquids – so there is no gritty texture. Manufactured exclusively by KYOWA HAKKO BIO CO., Sustamine® L-Alanyl-L-Glutamine is also ultra-pure, vegetarian and allergen-free.

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