The Dr. Hedberg Show

Human herpesvirus 6 or HHV-6, is a herpes virus just like Epstein-Barr Virus, Cytomegalovirus, Chicken pox (varicella zoster), HHV-7, HHV-8 and Herpes simplex 1 and 2.  There are two types of this virus including HHV-6A and HHV-6B. 100% of human beings get infected with HHV-6B by the age of three which results in fever, diarrhea and a rash called roseola. In rare cases it can cause seizures and encephalitis.  There are many infection connections to autoimmune diseases like Hashimoto's disease and in this article I'll cover the connection between HHV-6 and Hashimoto's disease.

Less is known about HHV-6A which was found in a small study in 50% of adults.  HHV-6A is said to be the most problematic of the two types and it is the type found inside the thyroid glands of some people with Hashimoto’s thyroiditis.

Just like other herpes viruses, HHV-6 can reactivate (occurs in the thyroid gland, GI tract, brain, heart, kidneys, uterus, and lungs) later in life when the immune system is compromised resulting in a variety of conditions including:

Hashimoto’s thyroiditisSjogren's syndromeLupusRheumatoid arthritisSarcoidosisGuillan-BarreMultiple SclerosisInfertilityChronic fatigue syndromeFibromyalgiaHIV progression to AIDSEpilepsySeizuresImmune suppressionCertain types of cancerKidney, liver, lung diseaseHeart diseaseEncephalitisColitisTransplant recipient issuesBone marrow suppressionAutoimmune hepatitis

What is the link between HHV-6 and Hashimoto’s disease?

Here are some studies supporting the connection between HHV-6 and Hashimoto's disease:

Rizzo et al. in 2016 found a direct connection among natural killer cell activation, thyroid antibodies, and HHV-6 in patients with Hashimoto's disease.  This study found that the HHV-6 virus causes an increase in natural killer cells against the virus which causes an ongoing inflammatory process in the thyroid gland that correlates with thyroid peroxidase and anti-thyroglobulin antibodies.  This means that an active HHV-6 infection in the thyroid gland drives the elevation of thyroid antibodies and increases inflammation in the gland resulting in increased damage to thyroid tissue.

A study published in 2012 entitled "Virologic and Immunologic Evidence Supporting an Association between HHV-6 and Hashimoto's Thyroiditis" by Caselli et al. found that a high percentage of patients in the study with Hashimoto’s disease have active HHV-6A infections inside the thyroid gland.  This increases inflammation in the thyroid gland since the immune system is concerned about Human herpesvirus 6 and due to antibodies against the thyroid gland.

A follow-up study by Caselli et al. in 2017 entitled "HHV-6A in vitro infection of thyrocytes and T cells alters the expression of miRNA associated to autoimmune thyroiditis" also found a connection between HHV-6 and Hashimoto's disease.

Sultanova et al. in their 2017 paper entitled "Association of active human herpesvirus-6 (HHV-6) infection with autoimmune thyroid gland diseases" found a statistically significant higher level of persistent HHV-6 infection in those with Hashimoto's disease compared to the control group.  They also biopsied thyroid tissue of patients with Hashimoto's disease compared to a control group without Hashimoto's disease, and they found a statistically significant higher level of HHV-6 in those with Hashimoto's disease compared to the control group (18/44 (41%) vs. 1/17 (6%)).

Seyyedi et al. in their 2019 paper entitled "Human herpesvirus 6A active infection in patients with autoimmune Hashimoto's thyroiditis" consisting of 242 patients found 57 out of 151 (38%) of patients with Hashimoto's disease had active HHV-6A infections.  5 out of 59 (8%) patients with non-autoimmune thyroid disorders had active HHV-6A infections.  And 0 out of 32 (0%) patients with normal thyroid function had active HHV-6A infections.

Why does it reactivate in some people?

For the same reasons that other herpes viruses reactivate in people including physical or emotional trauma, stress, hormone imbalances, other infections, poor diet, gut dysbiosis etc.  Herpes viruses are opportunistic when your immune system is compromised so anything that stresses your immune system can cause reactivation.

Reactivation occurs in about 20-25% of the adult population with much more severe symptoms than in infants.  Reactivation can create a “mono-like” illness in adults resulting in fatigue, fever, swollen lymph nodes, enlarge liver and spleen, or encephalitis and mental changes.

Human herpesvirus 6 seems to be more drawn to the brain and nervous system resulting mainly in problems associated with these areas of the body.  HHV-6 mainly resides in the salivary glands and it is transmitted through saliva from person to person.

What is the best way to test for Human herpesvirus 6?

Testing is tricky with this virus for a few reasons. Antibody tests can “cross-react” with other viruses such as Cytomegalovirus.  It is recommended to always test for Cytomegalovirus along with HHV-6 so you can be sure your positive test is accurate and not just a cross-reaction.

IgG antibodies are positive for life but if you see a four-fold increase in these levels then this can indicate reactivation. IgM antibodies will tell you if it is a recent reactivation however these can be elevated even when the virus isn’t active.  Additionally, IgM antibodies usually don’t elevate in adults who have reactivation of the virus.  If testing for IgG and IgM antibodies, be sure to use IFA testing rather than ELISA.

PCR testing can find the DNA of HHV-6 in the blood to confirm it is present and reactivated. However, this does not rule out infection inside a gland, it only rules out presence in the blood.  So it may be active in a gland or body tissue, but not present in the blood. For more detailed information about all the different types of tests check out the HHV-6 Foundations chart.

How is HHV-6 treated?

Conventional medicine doesn’t mention much about treatment other than perhaps trying acyclovir which is used for genital herpes.

Alternative methods are the same for HHV-6 as they are for the other herpes viruses like Epstein-Barr Virus and CMV.  Here are the compounds that can work well for all herpes viruses:

MonolaurinCordycepsReishiCurcuminBerberineVitamin C (Intravenous is very effective)EGCGBlack Cumin Seed OilQuercetinResveratrolLicoriceBaicalinNAC

As stated in my other articles about treating herpes viruses, simply taking one or a number of these compounds will not yield success in the long run.  This is because the underlying reasons for reactivation of the virus must be corrected in order to keep the virus deactivated.  This is why you should work with a functional medicine practitioner to fix all the underlying causes of reactivation so that your body can keep the virus at bay for life.

Human herpesvirus 6 and Hashimoto’s disease summary

Testing in adults is useful if you see an increase of IgG levels greater than 4x the normal range which can indicate reactivation.  If testing shows that there could be chronic viral activity, then I will target the virus.  The treatment for all herpes viruses is the same, so if we are treating the Epstein-Barr Virus, then we will also be targeting HHV-6 for example.

Your functional medicine practitioner will get your body back in balance so your immune system can control HHV-6 and target it if necessary.  I get excellent results when we have an infection connection to Hashimoto’s disease such as HHV-6.

In this episode of Functional Medicine Research, I interview Dr. Joe Mather and Dr. Jeffrey Moss about Covid-19 immune strategies.  We had a great discussion about the immunology of Covid-19, diet, lifestyle, supplements, as well as Dr. Mather's first-hand clinical experience with Covid-19.

Watch the video podcast:

Below is a full transcript of the interview on Covid-19 immune strategies:

Dr. Hedberg: Well, welcome everyone to Functional Medicine Research. I'm Dr. Hedberg. Really excited today to have two very special guests. We're gonna be talking about COVID-19.

And the first guest is Dr. Joe Mather. He's a MD. He also has a Master's in Public Health and Tropical Medicine. He's a board-certified Family Practice Physician. He graduated from Tulane University School of Medicine and Tulane University School of Public Health and completed his Family Medicine Residency in 2014. And he did actually travel to Malaysia to do infectious disease research and became interested in the role of intestinal infections and their impact on health. He also worked in a rural New Zealand clinic and he was the Medical Director of an Urgent Care and working as a Concierge Physician at the Center for Longevity and Wellness. Dr. Mather strives to deliver evidence-based individualized medicine to his patients. He does have a functional medicine practice in Louisiana where he works with a variety of patients with a specific interest in complex chronic disease and helping patients to optimize their health and longevity.

Now, interestingly, I just learned that, in 2013, Dr. Mather worked on a medical mission, and this was in Nicaragua where he provided healthcare to the remote mountainous region of Nicaragua and helped 2,400 patients and 5 villages. And he also has additional experience in infectious disease, he actually conducted a research project on tuberculosis treatment among Burmese refugees in Malaysia. So that's one of the reasons why I was really excited to have him on because of his deep infectious disease research and also because he's the only one of the three of us who has direct experience with COVID- 19.

So, Dr. Mather, welcome to the show.

Dr. Mather: Thank you so much. Happy to be here.

Dr. Hedberg: Great.

And then our other guest is Dr. Jeffrey Moss. He's the founder of Moss Nutrition. He graduated from the University of Michigan dental school where he employed clinical nutrition and his dental practice. He still has a small clinical nutrition practice today. He founded Moss Nutrition 27 years ago, providing high-quality research-based products and excellent education on how to use these products as well.

And so Dr. Moss has been involved in functional medicine for over 30 years, and he's been writing monthly newsletters, providing commentary on controversial and cutting-edge topics.

Dr. Hedberg:  Dr. Moss also established a online course on organic acids and amino acids testing, and he's a frequent speaker, teaching seminars across the country, and he's been a featured guest on many radio shows.

So, welcome Dr. Moss to the show.

Dr. Moss: Thank you. Thank you for having me.

Dr. Hedberg: So, COVID-19 is a really interesting times and I put together just some basic immunology of what I've been reading about what's going on with this virus. And I think the three of us, I know I've talked to Dr. Moss about this. The three of us were hesitant to put anything out about COVID-19 in the beginning, mainly because of a lack of experience with the actual virus, but also, it was more of a cautious and wait-and-see type approach and we wanted to make sure there was enough available data to start making some valid conclusions. And again, as I mentioned earlier, you know,

There are many digestive enzyme supplements out there but which ones are the best and what is the best way to use them? In this article, I’ll be covering my 3 favorite digestive enzyme supplements and the way I use them in my practice. I’ll also dispel some of the myths and misconceptions about digestive enzyme supplements.

Digestive enzymes are an important part of my practice because most of my patients have gut issues that are connected to their thyroid and autoimmune problems. I have found them to be a vital part of my gut healing protocols. Let’s jump in and cover the details of each product I recommend.

Betaine HCL

Supplemental betaine HCl helps to optimize hydrochloric acid levels in people with low stomach acid and can help to improve digestive function and comfort in patients of all ages. Many symptoms of digestive distress such as acid reflux, heartburn, gas, bloating or nausea after eating may be due to abnormally low or non-existent gastric acid secretion (hypochlorhydria and achlorhydria, respectively.) Endogenous HCl production naturally decreases with age but other factors such as illness, highly processed and acidic diets, overuse of antacids and high stress physiology in general may impair the body’s ability to generate healthy HCl levels. In addition to impaired digestion, hypochlorhydria has been associated with bacterial overgrowth, enteric infection, low vitamin B12 levels and an increased risk of gastric neoplasms.

Hydrochloric acid is secreted by parietal cells in response to the presence of food in the stomach. HCl activates the conversion of pepsinogen to pepsin, an enzyme required for the digestion of proteins. Gastric HCl also works directly on protein molecules to assist in their breakdown and helps to separate nutrients from their carrier compounds (e.g. releasing vitamin B12 from protein molecules, and cleaving calcium from carbonate.) By helping to support efficient breakdown of proteins, betaine hydrochloride can help to prevent large peptide molecules from entering the intestines where they may contribute to inflammation and leaky gut pathologies.

Adequate HCl levels in the stomach also help to minimize food sensitivities. In one study, 25% of patients taking acid-lowering drugs for dyspeptic disorders exhibited increased IgE formation towards commonly ingested foods. The same study suggested that food allergenicity could be reduced up to 10,000-fold by enhanced gastric digestion.

Gastric hydrochloric acid plays a role in immune defense by destroying foodborne pathogens and microbes such as Helicobacter pylori, implicated in the pathogenesis of stomach ulcers. Although stomach ulcers are typically associated with excess acid production and treated with acid-blocking drugs, insufficient gastric HCl may, in fact, be a predisposing factor in ulcerative pathology. H. pylori is, of course, only one biological organism that multiplies in the absence of sufficient gastric HCL levels. Many species of bacteria and fungi overpopulate in the high gastric pH environment caused by low hydrochloric acid production, contributing in turn to a variety of metabolic and dysbiotic symptoms both within and beyond the digestive tract.

Based on molecular weight, Betaine HCl is composed of 76.26% betaine and only 23.74% HCl. Hence we propose that the betaine component of the supplement may play a key role in its functionality. Nutritionally, betaine (also known as trimethylglycine) is obtained from beets and other sources—either as betaine directly or as synthesized endogenously from choline-containing foods. By serving as a methyl donor, betaine helps to support proper liver function, cellular replication and liver detoxification. Betaine also serves as a critical cofactor in the conversion of homocysteine to methionine. Betaine is well known to help reduce high homocysteine, associated with increased risk of Alzheimers and cardiovascular disease.

Patients with sub-optimal thyroid function may also benefit from supplementation with Betaine HCl, since thyroid hormones play an important role in the regulation of methyl group and homocysteine metabolism. Research suggests that decreased hepatic betaine-homocysteine S-methyltransferase, the betaine-dependent enzyme that catalyzes folate independent remethylation of homocysteine, may be a cause of T(3)-mediated hyperhomocysteinemia. In addition, high cortisol levels have been negatively associated with plasma betaine concentrations while increased dietary betaine intake has been suggested to reduce systemic inflammation.

I usually have patients take 1-2 capsules with each meal. Some patients do best taking 3 with each meal as long as this doesn’t cause any burning or stomach discomfort.

Pancreatin Select

Pancreatin Select provides synergistic support for enhanced digestive function with meaningful levels of pancreatic enzymes and lipase plus Betaine HCl, Ox Bile and two high quality researched and traditional herbal bitters: Artichoke and Gentian. This suite of ingredients works together to help support the complete digestion of proteins, carbohydrates and fats, and to help promote digestive ease, comfort and functionality within both gastric (stomach) and intestinal environments.

Of the many factors that contribute to compromised digestive capacity, insufficient stomach acid and diminished pancreatic enzyme production are two of the most common and widespread. Age alone is a primary cause in most people. Achlorhydria and pancreatic insufficiency are associated not only with digestive discomfort but with complications such as malnutrition and small intestine bacterial overgrowth (SIBO). The ingredients in Pancreatin Select can help boost the body’s natural ability to break down and metabolize food in the critical early stages of digestion, directly following a meal, to help promote healthy nutrient absorption, inhibit the growth of pathogenic microbes and improve overall digestive comfort.

PANCREATIN 4X is a concentrated blend of pancreatic protease, lipase and amylase intended to help facilitate the breakdown of proteins, fats, and carbohydrates, respectively. Supplemental pancreatic enzymes help to offset reduced enzymatic output by the exocrine pancreas, an organ which is strained by modern diets high in processed foods and low in enzyme-rich raw and fermented foods. Diets high in sugars and starches similarly overstress the endocrine pancreas, which must constantly produce hormones needed to balance blood glucose levels. Pancreatic insufficiency, common in celiac disease and other digestive disorders, is a major cause of nutrient malabsorption. Taking pancreatic enzymes augments the body’s natural output, promoting the thorough breakdown of nutritional components in chyme entering the duodenum. Additional LIPASE enzyme is added to help support complete and enhanced fat digestion. The Lipase and Pancreatin 4X concentrates used in Pancreatin Select are true, animal-based enzymes derived from natural porcine pancreas.

OX BILE provides a BSE-free source of bile acids. Bile, which is naturally synthesized from cholesterol in the liver before being stored and concentrated in the gallbladder, enables healthy fat emulsification and absorption. Bile acids have been suggested to help regulate fat metabolism by stimulating the production of active thyroid hormone within fat cells. Supplemental conjugated bile acid has been shown clinically to help increase both fat absorption and calcium absorption. Taking ox bile may be of particular benefit to people whose gallbladder has been removed, people with compromised liver or gallbladder function and people taking medications that sequester bile acids.

ARTICHOKE & GENTIAN are bitter herbs that help to stimulate digestive function by increasing saliva production and promoting the secretion of gastric acid, bile and digestive enzymes. Research suggests artichoke extracts offer significant benefits to digestion, particularly when bile production is low due to liver or gall bladder malfunction. Gentian has been shown to stimulate cephalic and gut receptors, positively influencing gastric phase digestion.

As with Betaine HCL, I usually recommend 1-2 capsules with each meal but sometimes certain patients with compromised digestion need 3 with each meal.

Digest Select

Digest Select offers a comprehensive, potent blend of vegetarian digestive enzymes to help support and strengthen healthy digestive function. The eleven distinct enzymes in Digest Select work together to help support the complete breakdown and assimilation of proteins, carbohydrates and fats in a range of pH environments—from the acidic upper stomach down through the more alkaline intestinal tract.

Many people today suffer from compromised digestive capacity. Causes range from diets high in sugar and processed starches to lifestyles high in chronic stress, as well as the diminishing ability of the pancreas to produce sufficient enzymes required to break down food, a natural result of aging.

Pancreatic insufficiency also is common in people with gluten intolerance and other digestive disorders of an inflammatory nature. Low pancreatic enzyme levels may result in uncomfortable feelings of fullness after eating, excess gas and bloating. Insufficient digestive enzyme production and activity also may lead to decreased absorption of food nutrients, malnutrition and GI complications such as increased intestinal permeability or small intestinal bacterial overgrowth (SIBO).

Digest Select contains plant-based digestive enzymes intended to help supplement the body’s own production of pancreatic enzymes to help promote digestive comfort and the thorough breakdown and assimilation of nutritional components. It features three specific protease enzymes plus peptidase to work on a variety of proteins and peptides including gluten, lipase to help support complete and enhanced fat digestion,

The connection between iodine and Hashimoto’s disease has been one of the most requested topics that I cover, so I’d like to present the research on this topic, so we can set the record straight. Please be aware that none of this is my opinion but rather a detailed analysis of what the scientific literature currently presents.

Your body has about 15 to 20 mg of iodine and 70 to 80% of it resides in the thyroid gland. Iodine is transported into the thyroid gland through the sodium-iodine symporter or NIS. The thyroid peroxidase enzyme oxidizes iodine which is then integrated into thyroglobulin resulting in the production of thyroxine (T4) and triiodothyronine (T3). Thyroid stimulating hormone (TSH) regulates this process.

Your thyroid only needs 150 to 250 micrograms a day of iodine to function properly. Once iodine intake exceeds this range, hypothyroidism and autoimmune thyroid disease may occur in some individuals.

How Much Iodine do the Japanese Consume?

The first issue I want to briefly clear up is the false idea that the Japanese consume 13.8 mg of iodine per day from their diet. This is actually a mischaracterization of a single study by Nagataki et al that I will clarify. Here is what the literature shows:

Aceves et al state that, “This element (iodine) has been associated with the low incidence of benign and malignant breast disease in Japanese women (iodine average consumption in the Japanese population is 5,280 μg/day versus 166-209 μg/day in the UK and USA, respectively).” 5,280 ug/day equals 5.28 mg/day.

Cann et al agree in their paper stating, “Japan has a comparatively high iodine intake with an average urinary iodine concentration of 3400 μg/L (approximately 5,280 μg/day) as determined in a recent study of 4138 men and women in Sapporo, Japan.”

Tajiri et al state that, “...the average daily iodine intake was 1-5 mg in the remaining 10 patients, equivalent to the ordinary intake of normal Japanese.”

Kapil et al state, “Iodine Intake in Japan: Average daily intake of iodine in Japan has been reported to be 3000 micrograms, which is 20 times more than the RDA value of 150 mcg in India.”

According to a report on iodine from the FAO/WHO Expert Consultation on Human Vitamin and Mineral Requirements, the following is stated about the daily iodine intake in Japan: “The amount of iodine intake by the Japanese is in the range of 2-3 mg/day.”

And finally, let’s clarify the Nagataki study. Nagataki states, “...the dry weight of such food as ‘tangle’(Laminaria) contains 0.3% iodine...” “...the average daily intake of seaweed was 4.6 g (wet weight).”  The well-known doctors who make this claim of 13.8 mg made a major mathematical error. 0.3% of 4.6 g does in fact equal 13.8 mg, but they confused dry weight and wet weight. The issue is that the paper is referring to dry weight in the above quote but the second quote refers to wet weight.

A follow-up paper in 2008 by Nagataki further clarifies the question of how much iodine is ingested by the Japanese on a daily basis. In this paper, Nagataki states, “The average of dietary iodine intake due to the ingestion of seaweeds is 1.2 mg/day in Japan.”

Alan Gaby, MD, also picked up on this in an editorial from The Townsend Letter for Doctors and Patients entitled “Iodine: A lot to swallow,” states the following: “The idea that Japanese people consume 13.8 mg of iodine per day appears to have arisen from a misinterpretation of a 1967 paper. In that paper, the average intake of seaweed in Japan was listed as 4.6 g (4,600 mg) per day, and seaweed was said to contained 0.3% iodine. The figure of 13.8 mg comes from multiplying 4,600 mg by 0.003. However, the 4.6 g of seaweed consumed per day was expressed as wet weight, whereas the 0.3%-iodine figure was based on dry weight. Since many vegetables contain at least 90% water, 13.8 mg per day is a significant overestimate of iodine intake.”

Does Iodine Cause Hashimoto’s Disease or Make it Worse?

Let’s begin to dig into the research to answer this question.

Konno et al in 1994 evaluated thyroid health by measuring TSH and thyroid autoantibodies in 1061 adults living in five coastal areas of Japan. Konno et al state, “These results indicated that 1) the prevalence of hypothyroidism in iodine sufficient areas may be associated with the amount of iodine ingested; 2) hypothyroidism is more prevalent and marked in subjects consuming further excessive amounts of iodine, and 3) excessive intake of iodine should be considered an etiology of hypothyroidism in addition to chronic thyroiditis in these areas.”

And in a previous paper in 1993, Konno et al analyzed 4110 apparently healthy people (2931 men and 1179 women) for thyroid dysfunction via evaluation of serum TSH, thyroid autoantibodies, and urinary iodine. All resided in the city of Sapporo, a city in northern Japan where iodine intake is high. The authors state: “The prevalence of unsuspected hyperthyroidism as defined by suppressed TSH values was 0.61%, of which 64% was diagnosed as Graves’ disease based on positive thyrotrophin receptor antibody results. The prevalence of unsuspected hypothyroidism, as evidence by supernormal TSH, was 0.68% for males and 3.13% for females with an age-related increase. Of those with hypothyroidism, 45.5% were autoantibody positive.”

The above study also required the subjects to restrict their iodine intake and made the following conclusions:

“When iodine intake was restricted for 6-8 weeks for hypothyroid subjects, the elevated TSH and thyroglobulin and low free T4 levels were reversed in the autoantibody negative but not in the positive group.” “This study provides further information on the prevalence of thyroid dysfunction and autoimmune thyroid diseases in an iodine sufficient area. In addition, it suggests that more than half of the patients with unsuspected hypothyroidism were negative for autoantibodies and that the excessive iodine intake may be involved in causing latent hypothyroidism.”

Now let’s examine some research on the connection between the addition of iodine to the food supply to eliminate iodine deficiency and how this impacts the prevalence Hashimoto’s disease.

Zois et al has published two papers on iodination of the food supply in Greece. In the first paper, Zois et al conclude, “In conclusion, silent iodine prophylaxis has resulted in the elimination of iodine deficiency in Greece, and this has been accompanied by an increase in the prevalence of autoimmune thyroiditis.”

In a follow-up paper, Zois et al state, “At diagnosis, thyroid peroxidase antibodies (TPOAbs) were positive in 25 children (86%) and became positive in all children during follow-up. Thyroglobulin autoantibodies (TgAbs) were positive in 17 children at diagnosis (59%) and became positive in 3 more children (69%). Both antibody types increased by the end of the observation period (P<0.005). Regarding thyroid function, 7 children (24%) at diagnosis had subclinical hypothyroidism that persisted and 4 more children developed subclinical hypothyroidism during the study period (38%). Only 5 of these children (45%) had positive TgAbs. There was an increase in thyrotrophin (TSH) so that at the end of the study all children had TSH greater than 2.5 mU/L but none developed overt hypothyroidism.”

In conclusion, “Thus, after the elimination of iodine deficiency of northwestern Greece, the development of autoimmune thyroiditis appears to be a persistent and progressive phenomenon.”

Bastemir et al found similar results after an iodinization program in Turkey:

“In conclusion, iodine supplementation in Turkey has resulted in the elimination of iodine deficiency in the Eastern Black Sea Region, and this has been accompanied by an increase in the prevalence of autoimmune thyroiditis and thyroid dysfunction.”

Gaberscek et al studied the effects of iodine fortification of table salt from 1953 to 2009 in Slovenia and found that the incidence of Hashimoto’s thyroiditis more than doubled after iodine was added to table salt.

Camargo et al studied the effects of excessive iodine fortification in a population in Sao Paulo, Brazil from 1998 to 2003. Table salt in Brazil was increased to 40-100mg/kg iodine concentration for this five-year period and the prevalence of chronic autoimmune thyroiditis was analyzed.

TSH, Free T4, thyroid peroxidase antibodies (anti-TOP), urinary iodine concentration, and thyroid volume were measured through ultrasound. The authors found that the rate of chronic autoimmune thyroiditis was 16.9% compared to a previous rate of 9.4% in 1994 based on a study finding by Tomimori et al. Brazil decreased the salt iodine content to 20-60mg/kg based on these findings.

The authors conclude, “Five years of excessive iodine intake by the Brazilian population may have increased the prevalence of chronic autoimmune thyroiditis and hypothyroidism in subjects genetically predisposed to thyroid autoimmune diseases. Appropriate screening for early detection of thyroid dysfunction may be considered during excessive nutritional iodine intake.”

Does this mean that iodine fortification should be avoided? Papanastasiou et al do not believe so in their paper “Thyroid autoimmunity in the current iodine environment.” The benefits of correcting iodine deficiency outweigh the risks from a large population perspective. They state: “It seems that both iodine deficiency and iodine excess should be avoided because of increased morbidity that might be induced. Iodine prophylaxis and treatment programs remain even nowadays important for iodine deficiency correction, but follow-up over time and continuous control of iodine intake must be sustained. Although iodine-induced thyroid autoimmunity in the current iodine-sufficient environment is of scientific interest, it seems that it is a transient and/or subclinical phenomenon. Thus, the suspicion for increased prevalence of iodine-induced thyroiditis in

In this episode of the Functional Medicine Research podcast, I interview Dr. Nirala Jacobi in a discussion about the Bi-Phasic SIBO Diet.  I have successfully used the Bi-Phasic SIBO Diet with many of my patients so I was excited to cover this topic with Dr. Jacobi.  We discussed the specifics of the diet including the various phases, oxalates, salicylates, FODMAPs, vegetarian options, candida, histamine, fermented foods, MCAS (Mast Cell Activation Syndrome), SIFO (Small Intestinal Fungal Overgrowth), DAO, hydrogen sulfide, hypnotherapy, DNRS and much more.  If you have SIBO or are a practitioner working with SIBO patients, this is one interview you don't want to miss.

Dr. Hedberg: Well, welcome everyone to Functional Medicine Research. I'm Dr. Hedberg. And I'm really excited today to have Dr. Nirala Jacobi on the show. Dr. Jacobi is a board-certified naturopathic physician. She graduated from Bastyr in 1998 and practiced primary care in Montana for seven years before arriving in Australia. She's one of Australia's leading experts in the treatment of SIBO, which we're gonna be talking about today. And she's also the medical director for SIBOtest. And that's an online testing service for practitioners. She's very passionate about educating practitioners so much so that she founded The SIBO Doctor. This is an online professional education platform for functional digestive disorders. She lectures nationally and internationally about the assessment and treatment of SIBO. And she's the host of the popular podcast which I listened to, it's called The SIBO Doctor podcast. And she's the medical director and senior naturopathic physician at The Biome Clinic. It's center for functional digestive disorders in New South Wales. She's one of the co-founders of the Australian Naturopathic Summit. This is a biennial event that aims to promote and showcase the art and science of naturopathic medicine in Australia. She's also a member of the Gastroenterology Association of Naturopathic Physicians and the Natural Path and Herbalist Association of Australia. So, Dr. Jacobi, thanks for coming on.

Dr. Jacobi: Thanks for having me.

Dr. Hedberg: Great. So, we're gonna be focusing a lot today on treatment and approaches to SIBO and let's go ahead and begin with your bi-phasic SIBO diet. This is something that I've used in practice for years now and it's very, very effective. So why don't you walk us through the bi-phasic diet and why you created this for people at SIBO?

Dr. Jacobi: Well, first of all, thanks for that introduction and to let me know that it's working so well for you because it's always wonderful for me to hear from successful practitioners like yourself that it is indeed a really useful tool that I've created. So, that's really good for me to hear. So, the bi-phasic diet came about, because ultimately, I needed a little bit more... As a practitioner, I wanted to give more structure to a dietary approach rather than just this sort of spectrum of foods, some of which you should avoid and some of which you shouldn't avoid, which is of course, the FODMAP diet. And also what I found is that many people that were on FODMAPs, the Monash FODMAP diet, still had symptoms of SIBO. So, what I wanted to do was structure it and I used the SIBO-specific food guide, which is from Dr. Allison C. Becker, which is based on the FODMAP diet as well as the SIBO-specific... Sorry, the SCD, the Specific Carbohydrate Diet. And so what I wanted to do is take all of that information and put it in a format that allows practitioners to structure their treatment approach.

And so basically, phase one is about six weeks long. It depends on the practitioner, how long they want to extend that diet, but typically four to six weeks. And really, it's about reducing pretty much any fermentable food which includes grains and potatoes and all of the vegetables that we know that are fermentable. And the idea was, we do this before we actually start antimicrobials. So, the aim was to reduce bacterial fermentation so that when we do introduce the antimicrobials, they won't be such a tremendous die off. And then phase two is a little bit more generous where we start to see the reintroduction of certain grains and potatoes and so forth. So, really, it helped me not just structure the diet, but also the treatment in terms of what supplement I wanted to use during which phase so that people weren't leaving with 20 different products per visit. So that really was the inception for me of the bi-phasic diet, and what's come out of that is also now the newly added vegetarian version. And what we wanted to do, I co-authored that with Anne Criner who's a naturopath here as well as a nutritionist and we wanted to not just take the meat out of the bi-phasic diet, we really wanted to offer a lot more to our vegetarians and vegans. So, that's also a good adjunct to the regular bi-phasic diet if people don't want to eat that much meat. And then thirdly, we have the last part of the collection of the bi-phasic diet which is the histamines SIBO bi-phasic diet because I found a lot of people were very histamine intolerance, so that's sort of has now evolved into these three different types of diets.

Dr. Hedberg: Excellent. So, that first four to six weeks, we're removing many foods that are pro-inflammatory that can ferment very easily by the bacteria. And that's going to reduce a lot of their symptoms and inflammation. Is there anything you want to add there as far as why you are removing those foods in that initial period?

Dr. Jacobi: Yeah. And as many practitioners know, when you first see a patient where you don't know if it's SIBO, you don't know if it's LIBO or Large Intestine Bacterial Overgrowth, or SIFO, which is Small Intestinal Fungal Overgrowth, or any of the myriad of other functional issues that we face when we see a patient that ultimately has some form of IBS or dysfunction that's a functional in origin. So, what I did was the first part of the diet, phase one actually has two sub-categories where the first part is the restrictive part and the second part is the semi-restrictive. So, patients sort of self-died themselves through phase one and increase their fermentable foods or slightly more fermentable foods when their symptoms have really improved. And what I found with this approach is really, most people will already have a tremendous improvement in their symptoms not just because of anti-inflammation and less bacterial fermentation, but it's also sort of like a hypo-allergenic part of the diet where we remove dairy, we remove gluten, and many of the things that people are reactive to. So, I find that it's just a wonderful way to calm the gut before we then add in much more sort of caustic agents in some cases like oregano oil or essential oils to kill bacteria and fungi, or in other cases, antibiotics.

So, for me, that really showed me that improving the gut before you even get to the antimicrobial part was really effective in terms of patient outcomes. So, that, I just... You know, because it's such an accessible resource, we've now had it used by thousands and thousands of practitioners worldwide and we get just great feedback from it. And sometimes, you know, and there's always some cases that have either been on super-restrictive diets for a long time already. You and I know those kinds of patients that only eat, like, five foods because they react to everything. And that may not be then appropriate to start them there. So, it's really a basis for individualizing each patient but, it's a good starting point for many practitioners and their patients.

Dr. Hedberg: Yeah. And I've run into a few issues regarding the restricted versus the semi-restricted and that's mainly related to energy especially in women. I've noticed that a lot of my female patients, if we do the full-restricted, their energy just drops too low so we have to add in some rice and possibly some kenoa to try and get their carbs up, their energy up. Have you found that as well?

Dr. Jacobi:  So, what I've seen is anything from improved energy for those people that are... You know, there's always some metabolic individualization that we have to consider where if people really are energy depleted and have a low basal metabolic sort of rate as well as just a underweight and things like that, they are going to respond differently than somebody who does not have those sort of roadblocks in metabolism. So, I think that that's one of the reasons I really individualized it and said to practitioners, "Look, you might need to start with rice. That's totally fine." That's up to the practitioner to decide on a case by case basis. But for the most part, I find if I just have somebody, a patient that has never really... Maybe they've reduced gluten or dairy just because they have continued gut symptoms and they're just fresh, you know, they haven't read anything about SIBO, they haven't been diagnosed. I don't really get those patients anymore because I see very complex patients now. But every now and then I get somebody who doesn't know about SIBO and starts the diet and I am re-acquainted with the fact that, "Wow. It is really effective for those that have never really done any other dietary restrictions."

Dr. Hedberg: Right, right. And so after that first phase, and then they go into the second phase, we're just adding some more variety. And I found that some patients we don't even need the herbal antibiotics, just following this diet, they seem to do pretty well without having to take anything. Probably with the more complex cases like you said, you're not seeing that as much, but have you seen that in the past where there was just no need for antimicrobials?

Dr. Jacobi: Well, the way I do it and the way I... The reason I structured it this way is because I imagined a patient arriving in the practitioner's office and, you know,...

In this episode of Functional Medicine Research, I interview Dr. Robert Hedaya about overcoming PTSD.  Post-traumatic stress disorder is an extremely difficult condition to manage but Dr. Hedaya and I discuss multiple approaches that can help patients with PTSD get well.  We discussed how PTSD is defined, how it changes the brain, QEEG guided laser, neurofeedback, loneliness, social isolation, social media and much more.  I always love having these kinds of conversations with psychiatrists and other mental health professionals because I believe it is the most overlooked aspect of functional medicine today.

Below is a transcript of the interview on overcoming PTSD:

Dr. Hedberg: Well, welcome, everyone to "Functional Medicine Research." I'm Dr. Hedberg and really looking forward to today's conversation with Dr. Robert Hedaya. I first heard him speak at the Institute for Functional Medicine last year on PTSD and so I wanted to have him on the show to talk about that. He is a medical doctor. He's been on the cutting edge of medical practice, psychiatry, and psychopharmacology since 1979. With the publication of his first book, understanding biological psychiatry, in 1996, he pioneered the use of functional medicine in the psychiatric field and he is now pioneering the use of G-guided laser treatment of neuropsychiatric disorders.

Dr. Hedaya is a clinical professor of psychiatry at Georgetown University Medical Center where he's been awarded the teacher of the year on three occasions while teaching courses on affective disorders, cognitive therapy, and one of my favorite topics, psycho-neuro-immuno-endocrinology. Since 1983, he's on faculty at the Institute for Functional Medicine, the author of two additional books, "The Antidepressant Survival Guide," and "Depression: Advancing the Treatment Paradigm," and he's the founder of the Center for Whole Psychiatry and Brain Recovery. Dr. Hedaya is an editorial volunteer for Advances in Mind-Body Medicine and Alternative Therapies in Health and Medicine. He's been featured in local and national media on things like "20/20", "60 minutes," "Vogue," "The New York Times," and "The Washington Post" on many occasions. And he's a frequent nationally and internationally recognized speaker. His website is wholepsychiatry.com. Dr. Hedaya, welcome to the show.

Dr. Hedaya: Thank you very much for having me.

Dr. Hedberg: Excellent. So, like I said, I heard you speak at IFM last year and was really interested in your research and studies on PTSD. Why don't we start by you just talking about how your career evolved from traditional psychiatry into functional medicine and now using some cutting-edge treatments for treatment-resistant depression, dementia, PTSD, chronic fatigue, and technologies like laser?

Dr. Hedaya: Okay. Well, it's been a long arc and I would say that the main thing is that I always try to follow where the science guides me, what's the truth that as far as I can best make it out to be. So, rather than being afraid of stepping outside of the box, you know, I just feel it's my responsibility, as a clinician, helping people to always try to do the right thing, and the right thing for me means doing what the science dictates, and sometimes it's benched to bedside science. Sometimes, you know, like translational medicine, sometimes you have the studies, but following the principles of biology and physiology and sometimes you have to take a leap because you can't wait until the studies are there.

So, the way it started for me was, 1983 about, I was treating a woman with panic disorder and she was not really recovering. And panic disorder is pretty easy to treat. Whether you use cognitive behavioral therapy, which I was using, or medications or combination of the two. So, it was about a year and she wasn't getting better and she paged me, I had a beeper back in those days, on a Saturday night, I was at a wedding and dancing and my beeper went off and looked and there was a number and I went to find the phone booth and called her and she was having a panic attack and I was like, what is going on with her? You know, this should have been over a long time ago.

Anyway, I went into the office early Monday morning to see, look it through her chart, see if I can find any clues. And I saw that the size of her red blood cells in the mean corpuscular volume was a little bit larger than the...a little bit outside the range. The reference range was about 101, the normal range is 80 to 100. I was trained to think, well, it's just really not that far out of the norm, so ignore it. And to be frank, I didn't really know what it meant, anyway, so I have ignored it. Well, I did a little research and it turns out that, as you know, is a marker for B12 deficiency, macrocytic anemia, she had a little bit of anemia. So, anyway, I treated her, I did a Schilling's test to double-check my hunch, treated her with B12 and with the first injection the panic disappeared.

At that point, I was like, "Whoa." You know, the head is connected to the body by this thing called the neck and I gotta figure out, what else am I missing? You know, because as you may know in psychiatry, there's a very, very high percentage of people who don't get well. Now, I think it's over 60% of psychiatric patients are on at least three medications. So, it wasn't like that back then, but there was a revolving door phenomenon. So, one thing leads to another and, you know, I've learned over the course of years always trying to understand what's going on. You know, you learn more and more and more and more and before you know it, you know, you're really...I'm practicing psychiatry and neurology, but also doing immunology, endocrinology, gastroenterology, you know, the whole functional medicine thing.

And then that, in the last 2 or 3 years, really since in 2009, I reversed my first case of dementia and in the last 3 or 4 years, I have been treating a lot of neurodegenerative disorders using functional medicine and using other technologies now like hyperbaric oxygen or light treatments to the brain, etc. So it's been a long path but basically, I follow...The principle is that I would say is you have to follow where the science takes you and what the logic of the process is and not really be so worried about sticking with, you know, the traditional approaches because that's what the evidence base shows because the evidence base is skewed. We know it's skewed by the pharmaceutical companies. We know it is...and that's not to say medication is bad, but it's certainly skewed. And we know that there are limitations on who's gonna do what studies if there's not a profit in it. So, now, this idea of evidence-based medicine is nice in theory, but in practice, it has its limitations. So, you have to use logic and common sense. And that's really the main idea.

Dr. Hedberg: Let's dig into PTSD because this is an area of your expertise and I think a lot of practitioners and people as well may look at PTSD as a single event, you know, say a car accident or sexual trauma, something like that. But there can also be ongoing issues, say, with a parent, or teacher, you know, loved one, things like that. Can you talk a little bit about how you define PTSD and the variables involved in trauma that's not just a single adverse event?

Dr. Hedaya: Yeah, sure. So, PTSD really, there's a trauma, the actual post-traumatic stress disorder actually is a repetitive assault on the mind, on the body, the spirit, and this repetition of re-experiencing the trauma over and over again as if it were really happening at this point in time leads to very, very serious consequences in the body. I mean, it's really a whole mind, body, soul event. And, you know, the studies are very clear that PTSD is not a psychological problem per se. It's actually a whole-body problem. It affects...I think there are four studies that show that gastrointestinal ulcers are associated with PTSD, there's type two diabetes is associated with PTSD, there's certainly earlier mortality. Seven out of 10 studies show that there's a 29% increased risk of mortality. Inflammatory markers are up in PTSD, like interleukin 6, 1-beta CRP. Telomere length, which is associated with biological aging, kind of a marker of biological aging, in all of the studies that we've done, six studies, consistently show that people with PTSD have shortened telomeres. So, PTSD puts the person at risk for many, many disorders and it needs to be conceptualized as such. And so, to me, the body is under siege continuously and repetitively in PTSD.

Dr. Hedberg: And childhood trauma, adverse childhood experiences, the ACE scores and things like that, is that going to make the patient's PTSD more severe as an adult? The more childhood trauma they have, the more severe the PTSD as an adult or is that highly variable depending on the patient?

Dr. Hedaya: Well, it's a vulnerability factor. So, if you take a hundred people who have had childhood trauma and there is to some degree, a dose-response, right? The more trauma you've had, the more vulnerable you are. But it is overlaid on other factors. So, how much support does the person have? What's the genetic makeup of the person, you know, the child? There are a variety of genes, which I talked about at the presentation that you were at, but we can think of them as resilience genes. That's the NR3C1, FKBP5, corticotropin-releasing hormone-binding protein, and corticotropin-releasing hormone receptor 1 and 2. These are all associated with the risk for PTSD. And so, if a person has, a child has a high compliment of these variants in these genes, then essentially what it is, is that their stress response, their resilience to stress is reduced, and they have increased risk for PTSD, for immunological problems, for depression, and even suicide. So, it's really a combination of factors that are at play.

Dr. Hedberg: One of the things that was most interesting to me in

In this episode of the Functional Medicine Research podcast, I interview Dr. Scott Antoine in a discussion about overcoming PANDAS.  Dr. Antoine shares a personal story about PANDAS and his daughter which sparked a deep interest in this disorder that is misunderstood by conventional medicine.  We discuss PANDAS, PANS, IVIG, OCD, and Dr. Antoine's Fully Functional practice model.  You'll also learn how to find a practitioner who is well-versed in PANDAS and the associated disorders discussed in this interview.

Below is a full transcript on Overcoming PANDAS with Dr. Scott Antoine

Dr. Hedberg: Well, welcome everyone to "Functional Medicine Research". I'm Dr. Hedberg and I'm really looking forward to my conversation today with Dr. Scott Antoine. We're gonna be talking about PANDAS today. And Dr. Antoine is an osteopathic physician and after medical school, he completed an emergency medicine residency and emergency medical services fellowship at Albert Einstein Medical Center in Philadelphia. He also has completed a fellowship in metabolic, nutritional and functional medicine through the Metabolic Medical Institute. And he was 1 of only 121 physicians nationwide to achieve board certification in integrative medicine through the newly formed American Board of Integrative Medicine. And he also holds a certification in functional medicine through the Institute for Functional Medicine.

He and his wife currently run a busy functional and integrative medicine practice in Carmel, Indiana where they focus on helping patients who are hopeless and overwhelmed, find the root causes of illness and recover their lives and vitality.

Dr. Antoine, welcome to the show.

Dr. Antoine: Thank you very much. I'm glad to be here.

Dr. Hedberg: Great. So this is a topic I haven't covered previously and you have a particular interest in also not just PANDAS but also mycotoxin illnesses and mold exposure and you have a personal story about that with your daughter who had developed PANDAS in 2013. And it sounds like that's what kind of propelled you into functional medicine. Do you wanna talk a little bit more about that background?

Dr. Antoine: Sure. That's certainly true. So I have a daughter. Her name is Emma. She's 18 now. But five or six years ago, she came to my wife and I one day and said, "I don't think God is happy with me. I think I'm a bad person." And she was having some intrusive thoughts. Shortly thereafter she developed some compulsive handwashing. She had issues with terrible insomnia and bladder control. And we weren't really sure what was going on. At the time, we were both physicians. My wife and I had been physicians for years and so we hit the books to try and figure this out. And one night at about 10 p.m. my wife Ellen came to me and she said, "I think I know what's wrong with Emma. I think she has PANDAS."

I wasn't really sure what that was but I hit the books and said, "Sure enough. That sounds exactly like what she's got going on." PANDAS is pediatric autoimmune neuropsychiatric disorder associated with strep infection. So these kids get a run of the mill infection, maybe a sore throat or a cold, something that involves the strep bacteria, and the antibodies they make to fight it which is what your body's supposed to do, cross the blood-brain barrier and then cause inflammation in the brain and produce all of these characteristic symptoms. These kids become very defiant. They can develop facial tics which my daughter had as well.

So once we figured that out, I figured now we have a direction to go in. So I called the infectious disease...head of infectious disease at our local children's hospital and he got on the phone with me and said, "Well, PANDAS doesn't exist. There's nothing to do here." And it was very frustrating. And I ended up...we went back, tried to figure this out. And my wife and I had remembered hearing a lecture by a guy from New York named Dr. Kenny Bock who had worked with kids with autism and several other difficult disorders, ADHD. And my wife even remembered that he had given a lecture on PANDAS once. And so I sent them off. They got on an airplane and went. And he said, "That's right. She has PANDAS and she needs intravenous immune globulin, IVIG." It's a blood product these kids get and it can be dramatic improvement. So I said, "Great." They came back. And I called a pediatric neurologist here who I knew used IVIG for other children for other reasons and told him all of her symptoms and told him what was going on and he basically said, "Why don't you just put her on antipsychotic medicine and put her into a mental institution?" You know, not my kid. I wasn't having it.

And we kept looking. Finally found someone in Chicago. It was the closest we could find. There was no one at that point in Indiana that did this work and gave her IVIG. And so we went up there on a fieldtrip, Emma and I, and she got IVIG and four days later her symptoms were gone.

So just amazing. And what then developed out of that is we had already opened our functional medicine office at this point but that was a pivot for me and I ended up seeing these kids which is hard. It's always a little bit of PTSD for me in a way when I see them just remembering how bad Emma was, but giving those folks hope and then seeing recovery sometimes with IVIG and actually sometimes without. There are other things you can do to avoid using IVIG but the recovery is really great. And it's a bit of a problem because mainstream medicine and pediatrics even doesn't really believe much in PANDAS. And there's another form of it calls PANS. So PANDAS is associated with strep but some kids get this neuro-inflammation from other infections. What we do know is that you can get it from mycoplasma infection. Also with influenza and there's a strong suggestion that Lyme disease may also cause this and when it's not due to strep we call it PANS, pediatric acute onset neuropsychiatric syndrome.

Dr. Hedberg: And so this is caused by streptococcus and a few other microbes that you mentioned and these have been around for thousands of years. So is this something that is a recent phenomenon or are there any hints of this in any writings or literature that goes back hundreds of years or even thousands of years?

Dr. Antoine: So the answer is yes and no. We know that Sydenham's chorea is an autoimmune encephalitis associated with strep infection that occurs a few weeks to a few months after a strep infection. And we've known about that for years and also known that you can treat that with IVIG. That's usually very severe. The kids don't typically have behavioral changes but they have severe tics, whole body tics, difficulty walking and we've known about that for many years. Interestingly enough, with the facial tics and some of these kids have a lot of throat clearing and defiance, it's suggestive that Gilles de la Tourette, the gentleman that found Tourette syndrome, that many of the kids in his original series probably had PANDAS based on the writings and the case description.

And I say yes and no because we now are seeing this much more commonly and so these folks are cropping up everywhere and I sort of have theories as to why that's the case, similar to why you see an uptick in allergies among kids and mental health in general and autism as well. I don't subscribe to the theory with autism for example that, well, we're just recognizing autism more now. If you look in 2008, autism was maybe 1 in 188 children. Now it's about 1 in 63 the last I checked and the definition of autism between 2008 and now has not substantially changed. So we're definitely seeing an increase in neuro-immune inflammatory brain disorders.

Dr. Hedberg: So for any of the parents listening, we're looking at symptoms of things like obsessive compulsive disorder, facial tics, loss of bladder control, insomnia, defiance. I do remember when oppositional defiance disorder, people started talking about that I think about 14 or 15 years ago. Anything else that people should look out for to identify this condition?

Dr. Antoine: So there is a neurobehavioral unit associated with the National Institute of Health and that's the folks that have done a lot of the work on this and they've published in the Journal of Adolescent and Child Psychology some really extensive articles dealing with their research and definitions of PANS and PANDAS as well as some treatment options. When, you know, to use IVIG, those types of things. And I always say, you know, "If I had have known then what I know now, I would've asked one of those physicians, you know, why did they have an inpatient unit in Washington, DC for these kids and they're using IVIG and high dose rituximab and other immune suppressants."

But definition wise, the classic definition that's been published has been children between the ages of three and puberty, sudden onset of either obsessive compulsive disorder or restrictive eating. So there are a subset of these kids, they're my least favorite to treat because they refuse to eat either due to the texture of the food or most often they are convinced that they're going to choke if they eat.

And so commonly when I see those kids and they come to me, they've had an extensive GI workup, they've been scoped and people have said, you know, we think you have eosinophilic esophagitis or some other digestive disorder or maybe reflux, and to no avail and when you really put the picture together, so it's either OCD or restrictive eating, and then there's a host of minor criteria that you have to have at least two or three of. Some of them you had mentioned which was defiance. So defiance, defiant type behaviors, facial tics. You can also see sensory integration issues, kids that suddenly won't put their shoes on, a common presentation. They just wake up one day for school and will not wear any shoes in the house....

In this episode of Functional Medicine Research I interview Dr. Kara Fitzgerald about her book, "The Methylation Diet" and a preview of her upcoming study on The Methylation Diet.  We had a great discussion about topics like methylation and diet, MTHFR, COMT, SAMe, methylated folate and B12, homocysteine, epigenetics and much more.

The Methylation Diet with Dr. Kara Fitzgerald Interview Transcript

Dr. Hedberg: Well, welcome everyone to "Functional Medicine Research." I'm Dr. Hedberg, and I'm really looking forward today to my conversation with Dr. Kara Fitzgerald. She's a naturopathic physician and a real thought leader in the functional medicine arena. She got her doctorate in naturopathic medicine from National College of Natural Medicine. And she did postdoctoral training with the Metametrix Laboratory, which is now in Genova. And she's also certified through the Institute for Functional Medicine, and she's on faculty at the Institute for Functional Medicine. So, she's been published in a lot of papers and she's been involved in various publications and peer review journals that she's written. She's contributed to functional medicine textbooks, and she recently wrote a chapter for the new "Integrative Gastroenterology" book. And that's Dr. Gerry Mullin's book on gastroenterology. And she's also co-authored an e-book, it's called the "Methylation Diet and Lifestyle." And we'll be talking about methylation today. So, Kara, welcome to the show.

Dr. Fitzgerald: Thanks, Nick. It's nice to reconnect with you. I was just dialoguing with you. I'll tell your audience that we knew each other way back when I was doing my post doc. I think you were one of our early folks to really become an expert in the specialty testing we were offering. So, anyway, it's nice to reconnect.

Dr. Hedberg: Yes, yes, it's great. So, some really interesting things to talk about today. And, as I mentioned, we're going to talk about methylation. And so, why don't we just start with some bedrock information for our laypeople and practitioners about, you know, what is methylation, and if you could just give us a basic overview of what it is and how it works.

Dr. Fitzgerald: Yeah, sure. Listen, if you've got any serious sort of biochemistry history geeks, it was actually...our ability to methylate compounds, to detoxify them was first discovered in 1887, if anybody needs a cocktail party factoid. But it was long after that before the methylation cycle was actually characterized and S-Adenosyl methionine was discovered. You know, it was in the 20th century when all of that was teased out. So, methylation is really quite simply, as you know, either we're putting a methyl group, which is a carbon and three hydrogens, either we're adding it to a compound, or we are removing it from a compound, or we are producing S-Adenosyl methionine, which is the co-factor that carries that methyl group that can be put on compounds.

So that's what methylation is. And it's everywhere. You know, an internet lord [SP] says, those folks talking a lot about methylation say it's happening in every cell all of the time. And I would argue that it's probably pretty close to that. I mean, it's interesting to me that we use this addition of a methyl group or the methylation cycle which interfaces, as you know, intimately with the folate-vitamer cycle and sulfuration. But, you know, it's interesting that we use these in such important fundamental processes, you know, body-wide.

Just to give you a couple of ideas, Nick, of its importance, you know, three of the four DNA bases require a functioning folate/methylation cycle for production. Three of the four bases. And that fourth base, which is cytosine, is the base that in DNA methylation gets methylated. So, for gene expression, fundamentally for gene expression, we have to have good methylation. And for DNA repair, we need good methylation. So just think about it. To make DNA, to regulate DNA expression, to repair DNA all requires really, you know, high-functioning methylation. And so, just as I've been into this more, and more, and more, you know, from an evolutionary perspective, I just ponder how interesting it is that we use it everywhere. And then, additionally, a lot of the folks interested in methylation know, for instance, that we're detoxifying hormones, toxins, histamine clearance, neurotransmitter synthesis, phospholipid synthesis. Like, you know, choline is a really methyl donor demanding process. We use it to make creatine, you know, in muscle energy. And, you know, and kind of on and on.

Stem cells. So, here's another really interesting thing, going back to that epigenetic regulation or the regulation of DNA expression. Our stem cell fate is determined by our DNA methylation patterns. So, gametogenesis and embryogenesis, high methylation activity time, very much so. So are you going to be a brain cell, or a lung cell, or a gut cell, etc., etc. Those pluripotent stem cell rules are defined through DNA methylation patterns. And prior to that, you know, the DNA methylation patterns from mom and dad, you know, in the sperm and egg, those are mostly wiped clean and then new patterns are laid down. They're not completely wiped clean. And so, the heritability of DNA methylation is actually established in this really early time. And I know you're paying attention in this arena, I don't know how much you're focusing in it, but I know that you're a really smart guy with a broad area of interests. So, you know, the epigenetic heritability is in this arena. The fact that we don't completely erase all of the DNA methylation patterns from mom and dad, or grandma and grandpa, and, you know, generations prior, and they're carried forward. So, it's extraordinary. This whole area has become quite interesting to me. But I'm going to stop for a minute.

Dr. Hedberg: Right. I mean, so with so many connections to methylation, since it's kind of at the core of what's going on in the cell, it has to be difficult at times to figure out if it is truly connected to the patient's condition.

Dr. Fitzgerald: Good question. Yeah.

Dr. Hedberg: How do you approach the need or, you know, the interest in looking deeper into methylation in particular patients? Are there any particular conditions that really stand out?

Dr. Fitzgerald: Well, that's a really good question. Arguably, we all need to be addressing methylation, and arguably we want to be doing it really upstream. So, you know, there are certain times we're going to be leaning on it more heavily, like preconception planning, when women who are pregnant, we want to be leaning on it more heavily. I know there are hosts of conditions that, you know, some of us in our arena have associated with methylation defects more obviously, and probably the best evidence is around depression and, you know, other neuropsychiatric conditions. Certainly in autism we commonly see methylation defects. But I guess I want to say that my...so a big practice changer for me has been thinking much more upstream and globally about methylation and really putting a lot of attention on epigenetic methylation. And I want to give you a little bit of the backstory, Nick. Interrupt me if I'm going on too long, but let me just talk about that. And that I think this will kind of elucidate where I'm coming from.

So, you know back in the lab, you know, years ago, we were looking at methylation all the time, looking at amino acids associated with the methylation cycle. Of course, we always look at homocysteine, etc. We're looking at sulfuration. And so, we've been thinking about it for a long time. And then we started to layer in single-nucleotide polymorphisms, and, you know, in the hopes that we would get sort of a deeper, more useful clinical picture. Arguably, we didn't. I don't know that MTHFR status always lends much clarity to a patient's condition. You know, I would say it's actually the exception that it really game changes how we approach patients. So, we had the organic acids and the various biomarkers there. We layered in the single-nucleotide polymorphisms, and, you know, maybe a little benefit, not that much.

So, you know, flash forward, epigenetic research starts really, really pouring out over maybe the last eight years or so. I mean, extraordinarily so. And for me, in about, I don't know, 2012, 2013, enough studies on epigenetics and cancer were moving across my desk that I realized I needed to dive in. Like, I needed to start to understand this in a deeper way. Honestly, you know, it was yet another omics investigation, and I had a little bit of omics fatigue at that time. And I was like, "You know, here's just another really complicated kind of arcane physiologic process going on that I need to understand. Damn it." But I did dive in and the bulk of the research is in, you know, the epigenetics cancer. And, by and large, you know, the most important epigenetic mark appears to be DNA methylation. And as I unpacked it, it became a practice game changer for me.

So, the background in it is that in cancer, so the tumor micro-environment is very effective at harnessing our own epigenetic machinery and taking over DNA methylation for its own, you know, nefarious ends. So, when we hypermethylate a promoter region of a gene, that gene is effectively turned off. When we hypomethylate it, when either there's an absence of methyl groups on the gene or those methyl groups are removed, that gene is allowed to express. So, the tumor micro-environment can very efficiently hypermethylate tumor suppressor genes.

And so, the first question for me as a functional medicine doctor, looking at methylation, prescribing B vitamins, high dose B-12, folate, all of the time was, "Geez, you know, do I need to stop doing that in my patients who I'm suspecting cancer in, or who are in, you know, an age range of an increased risk, or who have cancer, etc.?" You know,...

In this episode of Functional Medicine Research, I interview Dr. Bruce Hoffman, who’s a board certified physician and he has a fellowship in Anti-Aging as well as a Master’s degree in Clinical Nutrition. He is also a certified functional medicine practitioner. Speaking with Dr. Hoffman was extremely educational, we spoke about mast cell activation syndrome and how exactly the condition is diagnosed. Dr. Hoffman covers how he first got interested in the disease and the progress that he’s made working with several other doctors working to understand the implications of mast cell activation syndrome. Dr. Hoffman explains how some conditions overlap and indicate mast cell activation syndrome; such as fatigue, brain fog, and even GERD.  You should come away from this interview with a much better understanding of mast cell activation syndrome, how it’s diagnosed and what lab tests are beneficial in assisting in this diagnosis.

Below is a transcript of the interview on Mast Cell Activation Syndrome:

Dr. Hedberg: Well, welcome everyone to "Functional Medicine Research." I'm Dr. Hedberg. And I'm really looking forward to today's conversation with Dr. Bruce Hoffman. He's a board certified physician, and he has a Fellowship in Anti-Aging, as well as a Master's Degree in Clinical Nutrition. He's a certified functional medicine practitioner. And one of the really interesting things about him is that, in addition to his clinical training, he studied with many of the leading mind-body and spiritual healers of our time. So people like Deepak Chopra, Paul Lowe, Osho, Ramesh Balsekar, and one of my favorites, Jon Kabat-Zinn.

So, Dr. Hoffman, you shared the stage with Dr. Deepak Chopra, Dr. John Demartini. And he continues to spread his inspiring vision of healing and wellness with audiences and patients around the world. So Dr. Hoffman, welcome to the show.

Dr. Hoffman: Thanks very much, Nikolas. I'm glad to be here. Thank you.

Dr. Hedberg: Great. So I'm really looking forward to this discussion on mast cell activation syndrome. It's something I haven't seen a lot of in my practice. I have heard a number of lectures on this and read quite a bit about it. And it seems to be an area of your expertise. So why don't we jump right in and just talk about what mast cell activation is, and how is this condition diagnosed?

Dr. Hoffman: Sure. I first got interested in mast cell activation syndrome when I started to work with a cancer patient advocate by the name of Dr. Mark Renneker out of San Francisco. And he alerted me to the connection between cancer and mast cell activation syndrome, particularly in gynecological cancers. And then put me in touch with Dr. Lawrence Afrin, who leads one of the major sort of advocacy groups for mast cell activation syndrome as opposed to systemic mastocytosis, which I'll explain in a bit.

And so I've been for the last three to four years working with Dr. Lawrence Afrin's group and learning to understand the implications of mast cell activation syndrome in most of the patients that we see. Which are chronic multisystem, multisymptom patients who, as you know, have been everywhere and remain frustrated with the one disease, one drug paradigm that we learned at medical school. So, what I learned over time was how to separate between two specific conditions, one called systemic mastocytosis and the other called mast cell activation syndrome.

But before I begin with that, I'd like to say that mast cells are part of a...they're produced in our bone marrow, and they're part of our immune system. And they make up a very small percentage of it. And they act as defense structures against incoming invading pathogens. So anything that comes into our environment or into our biome, mast cells are often at the first line of defense. And they were actually discovered a long time ago, 1878, I believe, by Paul Ehrlich. And he called them mast cells because they were fat and puffy.

And the word mast in Greek means breast or the German means masticate. So, this is how the name mast cell got generated. Just for your North American readers, I say mast, and most people don't know what I'm saying. So it is mast in North America. People often don't know mast cells, what I'm saying.

So, these were originally discovered by Paul Ehrlich when he developed specific staining for them. And since then, they sort of lingered on in the literature. They were linked early on to cancer, but that sort of faded out of the picture and sort of just resuscitated by some Italian researchers who now are doing massive amounts of work on mast cell activation syndrome and cancers. And then it really sort of resurfaced in the 1990s and didn't really gather steam until about 2007, when two, you know, researchers and clinicians put together sort of a consensus statement on what constitutes mast cell activation syndrome.

There are two different schools of thought and they do tend to conflict with each other in terms of the diagnostic criteria. But basically, mast cells being part of the immune system, and regulating many of the incoming so-called antigens or toxins tend to be distributed in almost all tissues, but nowhere quite as much as on mucosal surfaces: so eyes, mouth, skin, GI tract, bladder, etc. They're also found in other tissues, you know, lungs and heart tissues, and brain, many mast cells activated in the brain.

And so when they get triggered, they do tend to release many, many mediators of inflammation. And it was estimated that there were over 200 mediators of inflammation that get released by these mast cells. But Dr. Afrin in a very recent post, as of last night, said that he's now changing his opinion that he believes there are over 1,000 mediators released by mast cells. All these inflammatory mediators like histamine, like proteases, prostaglandins, leukotrienes, all these inflammatory mediators that then set up this multisystem inflammatory response, which can confuse diagnosticians particularly if you have been trained in single organ, you know, specialties.

So that leads to the sort of difficulty with the diagnosis as people present with many different symptoms. And unless you have an understanding of mast cell activation syndrome, and a method of sort of sifting through the multiple systems they can present, you can often get very confused and misled. So the recent, you know, people speaking about mast cell activation syndrome is an attempt to bring some coherence to this somewhat disorganized field. And hence, establishing criteria for the diagnosis, lab tests, and then treatment protocols. So now it's coming into its own and I think you're gonna hear a lot about it in the years to come.

Dr. Hedberg: Mm-hmm, so we're talking about illnesses that may be so-called mystery illnesses, and multifactorial presentations like gut issues, skin, brain, and things like that. Can you just let everyone know some of the overlap that you see in various conditions in your practice that would specifically indicate mast cell activation syndrome?

Dr. Hoffman: Yeah. So mast cells, when they release the inflammatory mediators, can present locally or systemically. So a local condition would be something like hives, urticaria, or interstitial cystitis. Or it can be systemically like people can present with often cognitive symptoms. So they'll have fatigue and brain fog, and associated GI symptoms, like GERD. GERD is a potentially very big diagnostic category for mast cell activation syndrome or, you know, the irritable bowel syndrome. Even the autoimmune diseases of Crohn's disease and ulcerative colitis have been linked to mast cell activation syndrome.

Asthma is another one. Asthma, you know, if you analyze all the triggers of an asthma response, and you identify them, like, for instance, mold, allergy or mold inflammation, which are two different criteria, and you remove the trigger and downregulate the mast cell activation potential, I can't tell you how many cases of asthma have been absolutely shut down when you treat the mast cell activation. It's very rewarding. The same goes for GERD, the same goes for irritable bowel syndrome. The same goes for anxiety and cognitive decline. When you target the triggers and downregulate the mast cell activation, it's very rewarding to treat these patients, and they're very grateful. Angioedema, another, canker sores another one, there's many, many symptoms in all the organs that can present with this syndrome.

Afrin has written a chapter in a book. The book is called "Mast Cells," the editor is David Murray. The chapter is chapter...I think it's chapter 6, and it's called Presentation, Diagnosis and Management of Mast Cell Activation Syndrome. And at the back, he gives a long, long list of every organ that can be affected from ophthalmic, to lymphatic, to pulmonary, to cardiovascular, and just goes through all the systems, even fibromyalgia, even osteoporosis, headache, all the mood disorders, dysmenorrhea, endometriosis, many of the hematological conditions, the immunological conditions. There's a huge long list of different organ systems that can be affected that present as isolated diagnosis to specialists, but often they miss the overriding pathophysiological basis to the condition.

And our training as MDs makes us very aware of what is called systemic mastocytosis, which is when the mast cell from a clonal perspective within the bone marrow becomes amplified. There's actually a mutation of the KIT gene. And the mast cells become very high in numbers. So there's increased numbers of mast cells, which is systemic mastocytosis, which is very different from mast cell activation syndrome, which is an abnormal reaction of the mast cells, not an increased number.

So I can't tell you how many patients come back to me after having got the diagnosis of mast cell activation syndrome by myself with the criteria I use go to the specialties, go to the hematologist,...

“All disease begins in the gut.” --Hippocrates

Was Hippocrates right over 2,000 years ago? I would have to agree with him a majority of the time when it comes to chronic diseases. A healthy digestive system begins with excellent digestion so let’s go over some tips to help you improve your digestion naturally. Firstly, I’d like to briefly cover the reason why your digestion may be out of balance.

What causes bad digestion?

Eating very quickly while on the run and not completely focusing on your meal will result in poor digestion. You must be in a parasympathetic dominant state which is your “rest and digest” branch of your nervous system. Many people are sympathetic dominant when they eat which is the “fight or flight” branch of your nervous system.

 

Stress is a major cause of bad digestion which puts you in a sympathetic dominant state. When your sympathetic nervous is revved up, your body produces adrenaline which takes blood away from your stomach and lowers stomach acid so you won’t digest food very well. Sympathetic dominance also shuts down the gall bladder and the pancreas further impairing good digestion. Watching television, reading, texting, checking Facebook etc. while you’re eating will draw you out of your rest and digest state resulting in poor digestion.

Antibiotics are major cause of bad digestion and the more antibiotics you have taken in your life, the more likely you are to have digestive problems. Each time you take an antibiotic the bacteria in your gut change their genes to become resistant to antibiotics. Additionally, the bacteria will behave differently and will actually be out of balance for appoximately 13 months after a single round of antibiotics.

Birth control pills have been linked to Inflammatory Bowel Diseases (IBD) including Crohn’s disease and ulcerative colitis. Birth control pills deplete the body of many vital vitamins and minerals including folic acid, magnesium, and zinc that are important for gut health. The longer you have taken oral contraceptives, the more likely you are to develop gut problems.

Dental infections can cause bad digestion if you are constantly swallowing bad bacteria from the mouth. Proper oral hygeine is vital to improve your digestive health. Sinus infections can also be connected to bad digestion as these bacteria make their way down the back of the throat and are swallowed into the gut.

Antacid medications lower your natural production of stomach acid which will impair digestion. This leads to poorly digested food entering the small intestine which can increase inflammation, cause dysbiosis, and irritate the gall bladder and pancreas. Those who take antacids are at risk for developing many nutrient deficiences as well as infections in the gut. Stomach acid is absolutely vital for a healthy digestive tract so suppressing it can only cause problems in the long run. If you have heartburn the key is to figure out what is causing it rather than just suppressing acid levels.

Are there any conditions that cause bad digestion?

Helicobacter pylori is a bacteria in your stomach that overgrows when someone is under chronic stress resulting in low stomach acid, heartburn and poor digestion. This bacteria causes ulcers and it can wreak havoc on your digestion.

Small intestinal bacterial overgrowth or SIBO, is a condition where too many bacteria are in your upper intestine causing dysbiosis which results in the signs and symptoms of irritable bowel syndrome (IBS). Dysbiosis mainly means that the bacterial colonies in your gut are out of balance. If you have taken a lot of antibiotics throughout your life or have eaten a lot of sugar and refined carbohydrates then you may have SIBO or dysbiosis. Symptoms of SIBO include:

Gas

Bloating

Abdominal pain & discomfort

Abdominal cramps

Fatigue

Weight gain with difficulty losing weight

Feeling like you don’t completely empty your bowel when you have a movement

Alternating constipation and diarrhea

Inconsistently formed stools such as random changes in size, shape and color

Passing mucus

Sometimes feeling hungry shortly after meals

Fatigue after meals

Brain fog

Other conditions that can lower stomach acid and cause bad digestion include:

Hypothyroidism

Hashimoto’s disease

Hyperthyroidism due to Graves' disease

Adrenal stress

Zinc deficiency

B-vitamin deficiency

Intestinal infections such as parasites, yeast, viruses or bacteria

Leaky gut syndrome

Food sensitivities such as gluten and dairy

Gallstones

Celiac disease

If you have any of these conditions above then it’s best to be evaluated thoroughly by a functional medicine practitioner to find the root cause of your digestive system problems.

What can you do to improve digestion?

Chew your food slowly and completely until it is liquefied before swallowing.

Sit in a quiet and comfortable place without distractions such as TV, your cell phone, computer etc.

Do not read anything while eating.

Think about positive thoughts and how grateful you are to have the food.

Do not eat “on the run”. Put time aside each day for healthy and relaxing meals.

Keep your portion sizes about the size of your fist so you’re not eating too much.

Lemon or lime squeezed in warm water can help digestion.

Do not drink ice water with meals. Always ask for water with no ice.

Herbal bitters aka Swedish bitters taken with a little bit of water prior to eating can help digestion. These herbs stimulate HCL and digestive enzyme production.

A tablespoon of apple cider vinegar in a full size glass of water can help with digestion. Vinegar eats away tooth enamel so take it with plenty of water and ideally sip through a straw to bypass your teeth.

Put your fork, spoon, or chopsticks down in between bites.

Ginger tea sipped with your meal or in between meals is an excellent digestive aid.

Breathe deeply into your belly while you are eating.

What about digestive enzymes?

Digestive enzymes can be very helpful and I use them regularly with my patients. These products help to ensure that the food you are eating is properly digested before it leaves the stomach. There are three main varieties of digestive enzymes:

1. Betaine HCL

Betaine HCL helps to maintain and restore healthy hydrochloric acid levels in your stomach. I like the Betaine HCL because it is not derived from animal products so I can use it with my vegetarian and vegan patients. 1 capsule with each meal is a standard dose but more can be taken as long as it doesn’t cause burning, stomach discomfort, or pain. This is best used if low stomach acid is suspected and you want to try a product with a single ingredient. Burping and bloating after meals are good signs that your stomach acid levels are low.

2. Pancreatic enzyme blends

These products contain a blend of enzymes and herbs to support digestion. These supplements usually contain:

Protease to break down proteins.

Lipase to break down fats.

Amylase to break down carbohydrates.

Betaine HCL as described above.

Ox bile to digest fats.

Artichoke leaf and Gentian root which are herbal bitters to stimulate digestion.

Some extra lipase for enhanced fat digestion.

I use this with most patients because it covers every aspect of digestion so nothing gets missed. 1 capsule with each meal is a standard dose but more can be taken with the same caveats as noted above for Betaine HCL.

3. Plant-based enzyme blends

These are ideal for vegetarians and vegans since they are 100% plant-based. These supplements usually contain:

Amylase to digest carbohydrates.

Protease to digest proteins.

Lipase to digest fats.

Lactase and alpha-galactosidase enzymes are added to help support the healthy digestion of milk sugar (lactose) from dairy foods, and complicated starches such as those found in beans, grains, and cruciferous vegetables.

1 capsule per meal is usually sufficient but 2 can be taken with larger meals. Digest Select can actually be combined with Betaine HCL for stronger digestive support.

All of the above products can be taken until the gut is healed and then weaning off of them can be done over a 1-2 weeks period.

A word about probiotics and prebiotics

Probiotic and prebiotic-rich foods contain healthy bacteria and compounds that feed these bacteria which improves digestion. Foods like yogurt, kefir, kimchi and sauerkraut provide healthy bacteria which improve how you digest your food. Including some of these foods with each meal can really improve digestion. However, if you have SIBO, IBS, or intestinal dysbiosis, these types of foods may cause gas, bloating, or other unwanted digestive symptoms. If you do experience side effects from these foods then there is something out of balance in your gut that requires a thorough investigation.

Digestion requires a lot of energy and resources so you must do everything you can to take extra stress off of your body. You will be amazed how much better you feel when you begin to improve your digestion with these simple and effective tips.