Natural Medicine Journal Podcast

Natural Medicine Journal's interviews with thought-leaders in the field of natural and integrative medicine dig deep into the most important topics in the field. Whether it's a one-on-one with top researchers in integrative medicine or a conversation with a practitioner about treating hard-to-tackle conditions, each episode promises to provide trusted, cutting-edge, evidence-based knowledge about natural medicine that you won't find anywhere else.
RSS Feed
Natural Medicine Journal Podcast






All Episodes
Now displaying: May, 2018
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.

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.

Visit for more information & to sign up for free!

Visit for more information on ARG and our products.


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.