Functional Medicine for the Brain and Thyroid: A Clinical Conversation with Datis Kharrazian, PhD, DHSc, DC, MS, MMSc, FACN, and Robert Rountree, MD

Alternative and Complementary TherapiesVol. 25, No. 1 Open AccessCreative Commons licenseFunctional Medicine for the Brain and Thyroid: A Clinical Conversation with Datis Kharrazian, PhD, DHSc, DC, MS, MMSc, FACN, and Robert Rountree, MDDatis Kharrazian and Robert RountreeDatis KharrazianDatis Kharrazian, PhD, DHSc, DC, MS, MMSc, FACN, is an Associate Clinical Professor at Loma Linda University School of Medicine, in Loma Linda, California, a Research Fellow at Harvard Medical School, in Boston, Massachusetts, and a Research Fellow at the Department of Neurology at Massachusetts General Hospital, in Boston, Massachusetts.Search for more papers by this author and Robert RountreeRobert Rountree, MD, practices family medicine in Boulder, Colorado.Search for more papers by this authorPublished Online:29 Jan 2019https://doi.org/10.1089/act.2018.29202.dkhAboutSectionsPDF/EPUB Permissions & CitationsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail Dr. Kharrazian obtained his Doctor of Chiropractic degree from Southern California University of Health Sciences. He has an MS in Human Nutrition from the University of Bridgeport and a PhD and Doctor of Health Science from Nova Southeastern University. His PhD was in Health Science with concentrations in immunology and toxicology. Dr. Kharrazian completed his postdoctoral training at Harvard Medical School and Massachusetts General Hospital. At the same time, he completed a Master of Medical Sciences degree in Clinical Investigation from Harvard Medical School. Dr. Kharrazian is now a professor, research scientist, and functional medicine healthcare provider. In healthcare, he develops evidence-based models using diet, nutrition, lifestyle, and neurological exercises for various chronic diseases. He is an Associate Clinical Professor at Loma Linda University School of Medicine, a Research Fellow at Harvard Medical School, and a Research Fellow at the Department of Neurology at Massachusetts General Hospital.Robert Rountree: Can you start by telling us a little bit about your early motivators, and a bit about yourself?Datis Kharrazian: I grew up in San Diego, California. When I was growing up, a family member was very sick. She was going from doctor to doctor, just trying to get better. The only person who really made a difference in her life was a chiropractor who practiced nutrition. At that point, functional medicine was not a concept. The chiropractor recommended a few things and, in his opinion, immediately knew what was going on. For the first time in 20 years, she actually started to feel better. After seeing many experts, it was shocking for our whole family. This person made a huge difference in my family member's life.This experience got me interested in being a chiropractor, and then also a nutritionist. Years later, I had several shoulder dislocations, and I went to see the same man. He made some changes to my diet. In the end, I did not need to go in for surgery anymore. My shoulder stopped dislocating, and I thought about how powerful this all was. I really wanted to learn how to do this. This was the motivating event for me to go into chiropractic, not really so much for spinal adjusting but more for a lifestyle and nutritional approach.I eventually went to the Los Angeles College of Chiropractic, which is now Southern California University of Health Sciences. Soon after, I got to meet Dr. Aristo Vojdani, PhD. I got to know him pretty well, and I eventually told him about my family member. He suggested that we check her blood. We checked everything, even things that were not commercially available. She had antibodies to different neurotransmitters, such as serotonin and dopamine. There is no published information on individuals with antibodies to their own serotonin. She had significant adverse reactions to many different antidepressant medications.So, 20 years later, I decided I really wanted to get my PhD in immunology. I got into a PhD program at Nova Southeastern University in Fort Lauderdale, Florida. Dr. Vojdani became my mentor in that program. He was one of my PhD advisors for the university. We worked with the department of health science there, and we come up with a proposal of trying to look at how chemicals can become new triggers if they bind to proteins. Under his mentorship and guidance, I was looking at how chemicals bind to proteins and become new antigens, developing new epitope sites for binding called neoepitopes.When I look back, I realize how much the experience with my family member had to do with where my career went. These experiences as a child really guided me in my adulthood. I was not aware of all these things as I was going through the process. I was just thinking that I should learn about this.Once I finished my PhD, I got an opportunity to do a postdoctoral fellowship at Harvard Medical School. I started in 2015 in the Department of Neurology at Massachusetts General Hospital with another great mentor, Dr. Martha Herbert, MD, PhD, at the TRANSCEND lab. She has done some great work with autism and is really one of the main leaders around how the environment can impact the development and progression of autism. While I was doing my postdoc, I was also enrolled in a Master of Medical Science and Clinical Investigation program at Harvard Medical School. I was in a class with 12 people, all studying how to do clinical research. We trained with some of the best researchers, clinical trialists, statisticians, and epidemiologists in the field of medical research. I was picked for this program because they wanted diversity and different perspectives. They wanted people in the program who had some background in science, who had published but had also come in from a completely different point of view. So, I was their alternative medicine person. They wanted all of us to work on projects together and think together while working with these brilliant researchers.It was interesting coming into a program like that. I was able to point out the alternative medicine approach to many things. What I found at Harvard Medical School was that they were so open-minded. Over the years, I have taught at various medical, naturopathic, and chiropractic schools. My experience at Harvard Medical School made me realize that the reason they have major breakthroughs is because they want to have completely different perspectives coming in and analyzing everything. At the end of the day, data are data, and they realize that their own biases can get in the way of seeing real data and real treatment.In the program I was in, Clinical Investigation, we had some of the major statisticians and researchers sharing publications and research, and showing everything we are all doing wrong with data analysis in the field of medical research. We had a gentleman named Dr. Miguel Hernan, MD, DrPH, at the Harvard T.H. Chan School of Public Health, who I would say is one of the major game-changers in the world of medical research. He has published about how clinical trials are being done incorrectly, and the limitations in the way we are looking at endpoints. Harvard Medical School was very aware of the limitations of medical research and how it is being done. So, even though they are very proud that they have been the number one medical research university for the past 80 years in a row, they also realize how they are doing research incorrectly and where research and data analysis models need to evolve.Dr. Rountree: One of the things that Dr. Vojdani talked about in our last interview forAlternative and Complementary Therapies1 was that when he first started doing antibody testing to environmental toxins, he could not get his data published because no one believed his findings. Has that been your experience as well?Dr. Kharrazian: Absolutely. That is a real thing. And I think that is a big problem. Dr. Vojdani is so far ahead of everyone, they do not even comprehend what he is doing. When you submit a paper to a journal, you are sending it to some random reviewers. The random reviewer may not have the capacity to understand the next level of research or breakthrough research concepts. So, what gets published is essentially what reviewers all decide makes sense, the information that follows the paradigm shift. What I found, with having great publications with Dr. Vojdani, is that many different reviewers would just immediately reject the paper without any useful commentary other than they did not believe the outcomes or concept of the study. Our data or analyses were never scrutinized. Our laboratory methods were never scrutinized. It was just that they did not understand the possibility of novel concepts, so they rejected it.That is real bias. It is unfortunate. Many times, especially in some of the medical journals, you have good data and laboratory science submitted, but then you have a physician or other reviewer who does not have a background in data analysis or laboratory methods. They just reject the paper because they were the reviewer on the print journal.So, we have that frustration with trying to get some of those studies published. However, many of them have been published, and many more manuscripts are in the process. It is just that with every new submission, three reviewers have to approve, and one rejection means starting all over again.Dr. Rountree: When you were doing your clinical research fellowship at Harvard, did you feel like you were able to move the needle a little bit with regards to acceptance?Dr. Kharrazian: Many people at Harvard were already doing breakthrough research. They were breaking paradigms in their own way. There were different groups of people. There were people who were working with established clinical trial methods, with the drug companies, and publishing major studies. Then there were other researchers, such as Dr. Herbert, who was doing phenomenal breakthrough research with autism and the environment and other factors.But overall, there was just a general attitude of openness that I had never been involved with before in my entire career. When I first went there, I thought it was going to be the most conservative, strict, and anti-alternative medicine environment that I had ever been in. However, it was just the opposite. I found out that they were studying the microbiome, the gut–brain axis, intestinal permeability, and many of the topics so important to us in a functional medicine model. The School of Public Health is also doing great research in various fields of nutrition. There is an entire department at the School of Public Health looking at how environmental compounds in our buildings are making people sick. What I realized was that they were conducting some of the most important functional medicine research of our time and that was very exciting. The focus of research was not just on large pharmaceutical clinical trials.In fact, the people who were in charge of the School of Public Health made sure that there was a diverse list of healthy foods in the cafeteria that everyone could eat. I was expecting regular hospital and cafeteria food. These people understand the importance of diet, nutrition, and lifestyle. And of course, they are leaders in nutritional medicine as well.Dr. Rountree: What new insights did you come up with after working with Dr. Herbert? Did you have your own sense of what you think autism is about?Dr. Kharrazian: I think the problem with autism research is that there are so many variables that are involved with the disorder, the development of any type of clinical trial is very difficult. So, what we were really looking at was the role of “N of 1” clinical trials. With these trials, we can do Bayesian statistical methods, where you look at what is called a posterior probability test. You look at how multiple variables are used to treat a person and then look at different biomarkers throughout their treatment. Then those biomarkers are analyzed to see if a personalized multi-treatment protocol has an impact on the patient's outcomes.This type of research allows us to collect all the data on each patient. After looking at the same biomarkers in a group of patients, we can combine the results, and do a type of meta-analysis. It is really the only way that we can look at personalized lifestyle medicine. This was one of the key things I learned while working with Dr. Herbert.As an example, let us say we are looking at hemoglobin A1c and other endpoints. We look at different treatment variables, and we see which endpoints change for them. Then, we can statistically calculate these and compare them while on treatment or without treatment. Then we can come up with a very accurate treatment model that is personalized to one individual.N of 1 clinical trials are getting a lot more support in research publications. With a clinical trial, the focus is on generalizability to the entire population and not on individuality. Also, there is a limitation to only one treatment approach. In a real clinical setting, we do multiple treatment approaches because we are trying to do many different things to make the patient feel better. We get patients to change their lifestyle, maybe try to sleep more, as well as change their diet, and take a few supplements. We are not doing these one at a time for 12 weeks and then measuring a primary outcome. There is a lot of difficulty in establishing a clinically realistic model with a standard clinical trial for complicated conditions that have a lot of diversity in their pathophysiology. For example, we really cannot design an accurate clinical trial with so much variability with each patient who suffers from autism. Each patient has a unique set of physiological parameters that makes the standard clinical trial approach an ineffective model because of the wide range of uniqueness that cannot be accounted for in a group study despite the power of randomization.Dr. Rountree: Can you discuss how you use this in your clinical practice? When people come to see you, don't you typically spend several hours with them?Dr. Kharrazian: I have patients send me their medical history and all of their laboratory tests before they come in for their first visit. I might spend a couple of hours reading their file and their past history. I spend some time on PubMed doing some research. Then, when the patient comes in, I can organize my exam in the best order for them. I might need the day just to examine them. Then I will probably need another few hours to put all my notes together, and maybe another day or two to put together a treatment plan.For me, it is one patient at a time, trying to figure it out. I work as long as it takes to get it done. Going back to my own personal experience of having a chronically sick person in my family and seeing what it really took to turn them around was really a motivating factor for me. I think there are only going to be a few people who really have the motivation to do this. This allows me to figure out a few insights into something that might be new.Dr. Rountree: One thing I have noticed from your lectures is that you are doing some pretty elaborate testing to try to determine the problem. If someone has cognitive impairment, for example, you do functional neurological testing in order to really try to understand where his or her problem is originating in the brain. Can you describe the discipline of functional neurology and how you use it to make recommendations?Dr. Kharrazian: Functional neurology is a clinical model that incorporates a standard neurological exam. However, the idea is to look for all the subtleties in their exam. We are looking for neurological function, not just obvious hard neurological signs found with progressed disease.For example, while doing the Romber's test for neurological function related to balance, when patients close their eyes, they might not fall to the ground, but they might have significant sway to one side. That tells us something about what is going on with their brain and the vestibular integrity on that side. So, in our case, we are looking for the subtleties. We then try to triangulate the area of the brain that is involved. In order to do that, we have to know the examination findings and exactly which pathways are being checked. We can add up all the different exam findings to come up with a potential conclusion. If we think a certain area of the brain is being affected, we can try to do some stimulation to that area. Maybe it could be eye movements because we are trying to activate the frontal eye fields with saccades. Or it could be doing some rotations in the chair to activate the vestibular ocular reflex and cerebellum. Then, if we see some of the exam findings change immediately after stimulation, this becomes our therapy. The goal is to try to develop plasticity in regions of the brain that are not functioning ideally.The field of functional neurology is really growing. We organized the International Association of Functional Neurology 10 years ago. There are about 1000 members right now in approximately 40 countries. We have developed several 150-hour programs, everything from childhood development to neurological rehab for the brain and vestibular dizziness programs for practitioners to learn about. It is a growing field, and it is becoming more and more multidisciplinary. Although it was initially started with mostly chiropractors, we are now getting functional medicine practitioners, physicians, physical therapists, optometrists, and all types of healthcare professionals who are working with patients suffering from various neurological and developmental disorders.Dr. Rountree: Based on your experiences, you wrote a book about problems that affect the brain. What was the main focus of the book?Dr. Kharrazian: Yes, the book, Why Isn't My Brain Working, is really a functional medicine approach for the brain.2 I wrote it to try and share an approach of how to support the brain from a nutritional model. We look at circulation, neurotransmitter pathways, brain barrier access. We present clinical symptoms and patterns to walk through it.I had 3000 peer-reviewed references in the book when I first wrote it. The reference section was bigger than the whole book. I cut out a lot of the references to reduce the bulk of the book. However, there are still 1000 scientific citations because I wanted to make sure that I referenced everything, so that everyone would have some confidence recommending that book to their patients, and I could help them connect the latest research with the clinical approaches I was recommending in my book.Dr. Rountree: Do you have a sense from your research and clinical experience as to how a neuro-cognitive disorder develops?Dr. Kharrazian: I will give you a great example. Last week, I had a patient with some cognitive decline and focus and concentration issues. She was in her late 30s, and she had suffered with this all the way through high school and college. She scores off the charts with IQ testing. So, she is very intelligent; she just does not have the ability to focus and concentrate. On top of that, her brain function goes down throughout the day, meaning that she cannot perform. She was not able to finish a master's program because of her impairment and brain function, despite her intelligence.She came in to see me. From the exam, every finding was normal, even in the functional perspective. We essentially checked the function from the front of the brain to the back, and from the top of the brain down. We spent about two hours doing a detailed neurological exam with her. It really came down to the fact that she was suffering from more of a brain endurance issue. She was not getting fuel to her brain. During the examination, we found that she had a history of mitral valve prolapse. She had thrombocytopenia, and her hemoglobin and hematocrit were really low. She had poor circulation with white nail beds. Her tissue saturation was off. She was just not getting oxygen to her brain.We realized that we had to improve her hemoglobin and hematocrit, so that she could carry oxygen to her brain. There are many publications on thrombocytopenia, and how antioxidants can dampen the inflammatory reaction that impacts red blood cell function.3 So, we put her on a cocktail of antioxidants for support. We gave her things to improve her endothelial and nitric oxide pathways, such as vinpocetine. We got her to do some quick five-minute burst exercises while she was breathing oxygen. There was a huge difference in her function. So, here was an example of a patient who had focus/concentration issues and cognitive decline, but it was really related to a mechanism of improper oxygen getting to her brain from genetic issues. She had been on a cocktail of pretty much every supplement for the brain, but until you do an exam and find the mechanism, you do not know what the appropriate treatment is for the patient. General supplementation might work for many people. But then you get the patients who are frustrated because they need more specific direction, specific to their own unique physiology.Dr. Rountree: I heard you once say something to the effect of the earliest sign of brain degeneration is brain fatigue. Can you tell us a little more about what that means? How do you know the difference between brain fatigue and body fatigue?Dr. Kharrazian: For me, one of the most useful clinical tools to distinguish between the two is just to ask the patient when they notice their fatigue kicking in. If they notice their fatigue kick in after they do a task that involves the brain, such as reading or driving or being on a computer, it strongly suggests that it is brain fatigue. On the other hand, if they wake up every day and they are exhausted and cannot do anything, that is really suggestive of a metabolic fatigue. Of course, some people have both.Often, patients come in with a chief complaint of fatigue or a diagnosis of chronic fatigue syndrome. While working with them, I find that their fatigue happens toward the second hour of the day, when they are actually engaged in cerebral tasks. They wake up okay. Then during an examination, some areas of the brain are not functioning well. In some cases, there are patterns of early neurodegeneration, such as early Parkinsonism or dementia, or perhaps they had an earlier brain injury that has caught up with them over time. They may have done many different things to treat their fatigue from a metabolic point of view, such as supporting their adrenal glands or trying to detox, but there was no effect, and no one really spent any time trying to improve their brain function.We will do some brain exercises to improve plasticity for the brain. We will also develop a specific protocol to address their brain needs nutritionally. In many cases, we have some good clinical outcomes that may have been overlooked if there was not an understanding that sometimes fatigue is really an early sign of a neurodegenerative process taking place. One of the key things is to activate the brain so we can develop mitochondrial biogenesis and plasticity. A functional neurology approach involves activating the brain, meaning we have to fire specific neurons for the specific regions of the brain that are impaired. We use various exercises that fire receptors and induce post-synaptic changes in the necessary regions of the cortex, such as balance therapy, eye movement exercises, sensory exercises, and so on. When you activate specific neurons through receptor stimulation, that is when you actually have neurons connect with each other. There is a lot of research on mitochondrial biogenesis and plasticity using nutrients, but it is not actually showing the change in mitochondria quantity or axon branching. This research is only showing various nutrients can turn on the cellular messengers to activate mitochondria and neurogenesis.4–7 I think we have to be careful when we look at the available research related to mitochondrial biogenesis because transcriptional factors can turn on all the time for various things. But does that mean these supplements are actually increasing the mitochondria in humans? We know that direct stimulation of a neurological pathway can increase the actual quantity of mitochondria.8 Brain activation is similar. If we activate the brain, neurons can connect to each other and also increase the mitochondria within the healthy cells. For many patients with brain impairment, they need the nutritional support their brains, and they need to activate their neurological pathways directly. They need to dampen the mechanisms that promote neurodegeneration, such as inflammatory reactions in the brain and so forth. That is where the functional neurology approach comes in and addresses these mechanisms. As an example, if someone has a weak and atrophied muscle from being in a cast, you can't just give them supplements to have them regain their arm function. You actually have to have the person move their arm and activate their ascending and descending motor pathways in their brain in order to promote both peripheral and central mitochondria biogenesis. The brain responds in the same manner; it has to be activated so it can connect and branch and have mitochondrial biogenesis.Practicing functional neurology in a functional medicine community, we see a lot of patients with brain-based fatigue who have not responded to a functional medicine model. We isolate the areas of the brain involved, and try to activate them and develop plasticity in those areas through activation with various types of exercises. The exercises might involve color therapy or vestibular therapy. They might involve focus and attention, concentration exercises, or various other things. We can sometimes see dramatic changes in their chronic fatigue syndrome. In the end, their chronic fatigue syndrome is an early sign of neurodegeneration related to brain impairment.Dr. Rountree: There is a general agreement that exercise is generally a good thing—that everyone should engage in physical exercise on a regular basis. We know that will help with Alzheimer's, heart disease, and so on. You are saying that we need to go beyond that general recommendation—that we need to get very precise in what areas of the neuromuscular system we are activating. Can you elaborate on that?Dr. Kharrazian: Exactly. General physical exercise such as jogging or riding a bicycle increases growth factors and brain-derived neurotrophic factor.9 These are essential for us to have neurons connect to each other. The specific brain exercises that we suggest for our patient might be to turn their head to the left, close their eyes, and touch their finger to their nose 10 times. This may seem trivial to most of us. However, for people who have a parietal lobe injury, it is the most difficult thing in the world. After 5–10 of those, the heart rate jumps up because the brain is fatiguing. Then we have to stop, wait a minute or two, and try again. It really depends on the region of the brain that is involved. Most of the brain therapies we do can appear trivial, but they are very specific to the neurons and functions that they are involved with.A lot of people have been approaching the concepts of brain plasticity and mitochondrial biogenesis through activation with different models. The brain responds to stimulation; however you find it and get it there is critical to recovery.Dr. Rountree: Can we jump to functional endocrinology? This is also an area that you are deeply involved in. Are endocrinologists treating Hashimoto's hypothyroidism correctly? I ask because I have many patients who feel better with a consistently low or high thyrotropin (TSH)—even when those levels are outside of the “normal” range according to thyroid specialists.Dr. Kharrazian: I would say endocrinologists are treating Hashimoto's hypothyroidism correctly for their scope of practice. Their scope of practice is to identify and diagnose the condition and then to make sure that the patient is receiving adequate hormones for their physiological needs. They put the patient on thyroid replacement and make sure they are not in a thyroid deficient state by monitoring TSH.However, the issue with the condition itself is that most hypothyroidism is really due to an autoimmune pathophysiology involving Hashimoto's. This is where diet and nutrition, lifestyle, and other factors can have an impact on it.So, most patients with hypothyroidism should definitely be working with a conventional physician or endocrinologist to make sure that they are not in a hypothyroid state. But diet, nutrition, and lifestyle changes to modulate the expression of their autoimmunity are also really important for them. I can understand the hesitation with the traditional endocrinology model because there is not a lot of published information of this personalized, individualized approach to a thyroid condition.Ultimately, I think the patient makes the final choice as to who they work with and what works best for them. The thing with TSH is that it fluctuates all over the place. It can change with the amount of thyroid hormone replacement someone has, but there is also a thyroid receptor sensitivity that has to be taken into account. When thyroid replacement is prescribed, it should be noted that thyroid replacement also suppresses both TSH and TSH releasing hormone (TRH). TRH is a major stimulator of autonomic pathways in the brain stem.10 So, if you completely suppress TRH release, you get autonomic dysfunctions and impairments in gut function, enzyme release, and so forth.There are patients who are not feeling well because they are fatigued and their metabolism is slow. They are working with someone who only knows to keep increasing the dose of replaceme