Notes from an episode of The POTSCAST/Mast Cell Matters:
(this link includes a transcript of the interview down the page)
This episode features Dr Plotnikoff, a highly respected doctor and researcher in the areas of chronic pain and related conditions. For more on Dr Plotnikoff or to follow him go here:
Minnesota Personalized Medicine
on Instagram
He and colleagues are well-known for their foundational contribution to understanding the contribution of vitamin D deficiency to chronic pain conditions. His work on this subject includes:
Prevalence of severe hypovitaminosis D in patients with persistent, nonspecific musculoskeletal pain
"All patients with persistent, nonspecific musculoskeletal pain are at high risk for the consequences of unrecognized and untreated severe hypovitaminosis D. This risk extends to those considered at low risk for vitamin D deficiency: non-elderly, non-housebound, or non-immigrant persons of either sex. Non-immigrant women of childbearing age with such pain appear to be at greatest risk for misdiagnosis or delayed diagnosis. Because osteomalacia is a known cause of persistent, nonspecific musculoskeletal pain, screening all outpatients with such pain for hypovitaminosis D should be standard practice in clinical care."
Vitamin D Deficiency as a Contributor to Multiple Forms of Chronic Pain: In Response
In this follow-up comment, Dr Plotnikoff references the work of others that has identified various unusual pain syndromes involving symptoms such as excessive pain in the skin that is sensitive to bright lights and even light pressure, and that resolves with vitamin D normalization, as well as patients wth bone pain that was resolved with vitamin D supplementation. He encourages readers to further research vitamin D deficiency on Pubmed as there are many new discoveries in this area.
The interview begins with Dr Plotnikoff discussing research findings that he learned about at the most recent Dysautonomia International conference, including a a presentation by Dr. Chip Norris at Medical University of South Carolina (and his lab, which includes many researchers who have hEDS themselves) that found that in a cohort of patients with hEDS, the average number of comorbidities was 25. The most common was pain, the second most common was Dysautonomia, and the third was GI concerns. Dr Dempsey asks if this may be because so many people with hEDS also have MCAS. He also references research by this lab that hasn't been published yet that took a deep look at the genetics involved in hEDS and what they found was surprising- unlike other forms of EDS that have a clear genetic basis in collagen and connective tissue genes, hEDS instead has to do with genes involved in auto-inflammatory states and pathways.
This shifts the focus onto the category of auto-inflammatory syndromes. Dr Dempsey remarks that she and Dr Afrin have found that "a fair number" of their MCAS patients have been found on genetic testing (in vitae or whole genome sequencing) to have auto-inflammatory conditions including NOD2 as well as other, more rare mutations, and that at this point it is unclear whether these genetic factors are drivers of MCAS, predictors of it, or something else.
A new category of auto-inflammatory disease associated with NOD2 gene mutations
Discussion now jumps to a presentation by Tae Chung from Johns Hopkins concerning the genetics involved in Long COVID. He found multiple pathways that were abnormal, including TCN2. Dr Dempsey then relates these findings to a study by Brigham and Women's Long COVID and Chronic Fatigue Syndrome Clinic that also looked at proteomics (the study of proteins) and found 3 that were exceptionally elevated including one protein involved in B12 transport. When considering B12 levels you would also want to know the methylmalonic acid and homocysteine levels. B12 is important for the central nervous system so a problem with a transporter could have significant effects and could explain why many patients seem to require high doses of B12 delivered intramuscularly.
Discussion jumps again to an article in Nature about CoQ10 deficiency. Researchers studied a child with a genetic cause of CoQ10 deficiency and were able to identify which step in which process was not functioning properly. They were then able to treat the child with a synthetic form of whatever the next step in the pathway is and the child regained the ability to walk.
Discussion now jumps to talk of an approach to treating gastroparesis, slow motility, nausea and vomiting, that is used in Japan were they give IV thiamin and pantothenic acid. Thiamin deficiency is sometimes called Beriberi and in America is thought to be essentially non-existent outside of severe cases of alcoholism and malnutrition. The symptoms include Anorexia, nausea, abdominal pain, vomiting, early satiety, low motility, constipation, and eventually parasthesias. There is recent evidence now of a "gastrc Beriberi" from a case study published by Harvard recently. (Thiamine deficiency can be mistaken for MS). Dr Dempsey notes that she has seen low levels of thiamine and riboflavin in many of her patients. She also notes that gluten-free diets are low in thiamine. Baking anything over around 250 degrees causes the thiamine to break down. Baking soda also breaks it down. Washing rice washes it out. It is also destroyed by UV light so clear packaging allows it to break down.
Most importantly, mycotoxins break down thiamine (in particular fumonisins - 30 species of fumonisins are potent thiamin breakers as well as at least one mycotoxin from penicillin). Thiamine contains a fragile methyl bridge so is easily broken down. These mycotoxins can come from molds that grow directly on the grain or are involved in its storage, but can also come from mold in a living environment. There are also organisms in the microbiome that destroy thiamine including bacillus subtilis, candida, H. pylori, and Staph aureus. Some medications destroy thiamine including omeprazole, antibiotics, metformin and diuretics (which can flush thiamine out of the body). Multivitamins tend to contain the forms thiamin hydrochloride or thiamin mononitrate which have very low levels of absorption (around 3% to 5%). The RDA of thiamine for people on feeding tubes or TPN is much higher. Magnesium is necessary to activate thiamine.
Blood tests are not a good measure of the body's thiamine levels because less than 1% of the body's thiamine is in the blood. the rest is on cells, especially red blood cells. "people with Wernicke's encephalopathy have demonstrated normal thiamin levels". Other markers that can indicate low thiamine levels include high pyruvate, "high phytanic acid to pristanic acid ratios or high branch chain fatty acids or high branch chain amino acids. The sister keto acids, isovaleric, et cetera are all decent measures." "And there are 11 different places where thiamin acts in the body, three of them directly related to the Krebs cycle, and including upstream from GABA, the calming neurotransmitter."
Vitamin B1 deficiency in patients with postural tachycardia syndrome (POTS) This paper by Svetlana Blitshteyn found evidence of thiamine deficiency in POTS patients, although didn't take into account the limitations of blood testing. Thiamine is necessary for the body to make acetyl-CoA, which in turn is necessary to make acetylcholine, which is the neurotransmitter of the autonomic nervous system. Thiamine also augments the function of acetylcholine and helps to support acetylcholine levels.
Best ways to supplement thiamine? Thiamin hydrochloride and thiamin mononitrate are both not well absorbed so should not be relied upon. Myers Cocktail, an IV boost of nutrition contains a good dose of thiamine as well as the magnesium needed for it to be used. Allium vegetables are some of the best food sources (onions, garlic, leeks). Allimax is a garlic based supplement that has been helpful for some.
Allithiamin which is a type of thiamin commercially available that can be combined with lipoic acid as Lipothiamin.
Benfotiamine is a fat-soluble form of thiamine that is well absorbed. It has shown some benefit in Alzheimer's patients in several small, randomized trials. Dosing is either 300mg once or twice a day.
Riboflavin (B2) is a mast cell stabilizer and it helps migraines. Dr Plotnikoff discusses the potential nutritional deficiencies that they and other doctors are seeing in some patients on plant-based diets. They specifically mention riboflavin, vitamin B12, and long chain Omega-3 fatty acids. The following paper was published by them to discuss these specific concerns:
Nutritional Assessment of the Symptomatic Patient on a Plant-Based Diet: Seven Key Questions
Additional commentary about nutrition on a gluten-free plant-based diet "gluten-free plant-based diet has no methionine in it, as does Orgain plant-based kind of protein drinks or Kate Farms 1.4 or multiple other plant-based protein, you know, kind of shake type supplements. No methionine. No methionine means no methylation. No methylation means things related to, you know, neurotransmitter production, mood, memory, energy, sleep, estrogen clearance, histamine clearance all depends upon this."
