*Updated 20 March 2014*
MTHFR gene mutations are complicated and certainly just the tip of the iceberg. With each day that passes I think most of us realize that for as much as we know about genetics and health, we really know very little. There are so many pathways in the body and so many more biochemical processes at play than just methylation. I know that every day I learn something new, something that makes me question whether I am on the right health path, whether there is something I’m overlooking and who the doctors are out there that truly get how all of it works and how to heal us. I will write more about this in the future but for now I hope that awareness of today’s topic will bring forward another piece of the puzzle for some of you.
Fermented foods are one of the hot health trends at the moment among natural food authors and some health practitioners. But did you know that some people cannot tolerate them? In fact, fermented foods make some people very ill. This is because of the high histamines they release. For many of the people who cannot tolerate them, conditions called mast cell activation disorder/disease (MCAD) and mastocytosis also cause a number of other symptoms. Mast cells are part of our immune system and within them are granules that contain inflammation-causing chemicals. We generally need these for healing wounds, forming new blood vessels, remodeling tissues and to defend against pathogens. Their role in the allergic response is the way most of us are familiar with them as histamine is one of the chemicals found in mast cells.
As Jess of The Patient Celiac explains:
Mast cells are innate immune cells that play a role in defending the body against bacteria, viruses, and parasites, but are best known for their participation in the allergic response. When mast cells degranulate, or burst open, histamine and other chemicals are released, leading to symptoms which we associate with allergies, including having a runny nose, wheezing, hives, etc. Most of us are familiar with the antihistamine drugs that are used to treat allergic symptoms, such as Claritin, Allegra, and [Zyrtec]. Although these medications do not prevent mast cells from releasing histamine, they prevent symptoms by blocking histamine receptors.
With MCAD, genetically altered mast cells are overabundant, building up in the skin, gastrointestinal tract, reproductive organs or other places where they can cause trouble. Certain triggers then cause them to degranulate excessively and release their chemicals, leading to an array of symptoms that often overlap with other chronic conditions. These symptoms range in severity and include:
- Flushing, itching, rash, hives
- Heart palpitations or irregularities, low blood pressure
- Lightheadedness, shortness of breath, fatigue, weakness, dizziness
- Headache, chest pain, joint pain
- Nausea, loss of appetite, weight loss or gain
- Fainting, cognitive problems, brain fog
- Swelling of the liver (jaundice), spleen or lymph nodes
- Gastrointestinal symptoms: diarrhea, stomach pain, vomiting, bloating
- Wheezing, blurred vision, anxiety, sunlight sensitivity
- Urinary frequency or pain
- Bone pain
While once thought rare, these disorders are actually on the rise. Symptoms can occur in virtually every organ and tissue yet MCAD is difficult to determine and diagnose. Here you’ll find a list of tests you can ask your doctor for, including serum histamine and serum tryptase as a starting point. As avoidance of triggers is a major part of treatment, one may troubleshoot whether mast cells are at play based on those as well. Common triggers include insect stings, high histamine or histamine-releasing food and beverages, exercise, perfumes, chemicals, gas fumes, exercise, extreme temperatures, certain medications, stress and pollen.
So where does MTHFR come into the picture? Check out this theory, originally from MTHFRHEDS.com:
MTHFR polymorphism may be a predisposing factor to mast cell disease. 5-MTHF regulates biosynthesis of BH4. The A1298 mutation in the MTHFR enzyme [affects] the conversion of BH2 to BH4. Less amounts of BH4 inhibits NO formation resulting in increased mast cell degranulation. Inadequate BH4 formation also puts a strain on the conversion of tryptophan to serotonin and tyrosine to dopamine, leading to low levels of the neurotransmitters: dopamine, norepinephrine, serotonin and melatonin.
Low blood serotonin levels help define a sub-group of patients with mastocytosis that are more likely to present with neurological and gastrointestinal complaints. Human mast cells can express and be activated through multiple serotonin receptors, and synthesize and release serotonin. Low blood serotonin levels in such patients may be the result of low BH4 levels due to 5-MTHF deficiency, the result of long-term malabsorption from chronic inflammation of the gastrointestinal tract or both, as is the case with me.
BH4 is a critical factor in cellular activities such as cell proliferation, cell cycle regulation and differentiation. Could BH4 deficiency secondary to MTHFR polymorphism be one of the fundamental mechanisms that underlie mast cell proliferation?
Another consideration is the fact that methylation clears excess histamine from the bloodstream. So undermethylators may be more sensitive to histamines. There is a large body of research linking MCAD, mastocytosis and histamine intolerance to a variety of chronic conditions, including autism, irritable bowel syndrome (IBS), atopic dermatitis, migraines, asthma, arthritis and eczema. So this becomes another piece of the puzzle for those looking to treat or cure these illnesses.
This brings me back to high histamine foods and their avoidance. A frequently asked question in MTHFR circles is: what is the best diet for people with MTHFR? The answer is that it’s impossible to answer that question. Each person with MTHFR also has unique aspects of his or her biochemistry that make his or her case different from everyone else with MTHFR. There can be no MTHFR protocol or diet. There are some things that everyone can agree on, like folic acid being detrimental, but then all the other factors of a person’s health and physiology come into play and that makes it difficult to address one gene mutation unilaterally. So far this blog has focused on MTHFR exclusively but over the course of this year I plan to bring in more information about other crucial gene mutations and health conditions that will hopefully assist people in assessing their own situations a bit better. MTHFR is just one part of the overall picture.
I have compound heterozygous MTHFR, for example, and have never noticed a reaction to fermented and other high histamine foods. That doesn’t mean that I don’t have any problems with mast cells, but my histamine levels aren’t high and I don’t have severe reactions at this time. That can change with age. But those people who do notice either a reaction or a significant symptom from the list may want to consider this disorder and troubleshoot with their doctors. Mast cells can store the histamine from these foods and release it later on, over time damaging nerves. In this instance, mast cells and MTHFR are connected and those people should avoid fermented foods and a high histamine diet. Fermented foods also raise glutamate (also found in processed food) acting as a neuro-excitotoxin and spelling trouble, especially for those with migraines, epilepsy, bipolar and related disorders. Certain probiotics may also aggravate MCAD so this is something else to be aware of when working on your gut issues.
As an important side note, mast cells play a big role in allergies, so if this is a problem for you or a loved one, check out this article from AllergicChild.com.
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