Supplements to deal with COMT mutation

I have a dobbel mutation on COMT (+/+) with AA Allelle, what to take of supplement to deal with this?

I struggle with chronic pain due to a ehler danlos and all the fun that comes with this (nervepain, dysmenorrea, cramps, stiffness, fatigue, muscle pain, dislocations of joints, burning sendations, migraine). Althoug this is a chronic condition I had so many years with better function. And Due to pain and constantly new crisis in my body I`ve been in constant stress last 1,5 years. After reading about my COMT mutation I also understand why I am stuch in this cirkle of pain and feeling of having increadibly little stresstolerance, fatigue and depression. I do not brake down the nevrotransmitters causing the fight flight responce easily. I need to get my methylation process back on track. I have already imoroved a little after taking 2000 ug doses of B12 (it was on 220) and iron supplementation (ferritin was as low as 19). I read I need magnesium, B9 and folate as well. Are there other things to do?

A friend takes RNA treatment for her MAO A mutation (Amy Yasko protocol). What can I expect from similar treatment for COMT?

(Other medications and supplements: plaquenil, omega 3, marvelon, coq10, brintellix, probiotics)

It sounds like you’re dealing with a lot and you have my sympathies.

I’m certainly not qualified to advise on medicine nor genetics, but it’s my opinion that it’s easy to over-focus on or even worry about individual gene variants. I wouldn’t recommend basing diagnosis or treatment solely upon variant reports.
For one thing, there are so very many gene-gene interactions and “we” are only at the very beginning of understanding these and their effects on health conditions… having identified only perhaps a tiny fraction of all that is relevant; and some counteract the expression of others while some others amplify them. Also, of course, as the body, with all its marvelous interrelated processes is so amazingly complex, health conditions are often a function of quite a few different genes and their interactions - as well as of “environmental” factors including diet, lifestyle, and others.

That said, if we use what we can apply what we do know about our genotypes and the researched linkages between our SNPs and possible disease conditions alongside diagnostic lab tests, this can indeed help us to look for and address deficiencies and get healthier.

Though I had a bout with a rare cancer some 12 years ago, my main focus has been on preventing or reducing my risk of deep vein thrombosis (DVT), which for me caused two incidents of pulmonary embolism…which can be fatal. Besides variants in clotting-cascade genes (FI-F13), there are a number of other relevant genes, including some involved in methylation cycle or other metabolic pathways (e.g. folate pathway defect), which can also be risk factors.

For example, COMT V157M (rs4680) has an effect on serum homocysteine (Hcy), which for me was high, and is associated with VT risk.

In fact, I am homozygous for 3 COMT gene SNPs: COMT H62H rs4633 (TT); COMT V158M rs4680 (AA); and COMT rs165599(AA).

I don’t have any of the symptoms that you have. That goes to my point that diagnosing or treating for one gene SNP may not be the best idea. Too many other variables!

A few relevant bits about these from published research:

COMT V158M rs4680 (AA) = “Worrier” as compared to “Warrior”. This implies “… lower COMT enzymatic activity, therefore higher dopamine levels; lower pain threshold, enhanced vulnerability to stress, yet also more efficient at processing information under most conditions…” . That summary does seem to match your symptoms.

COMT H62H rs4633 is similar in effect to rs4680. (also associated with VT risk, and schizophrenia and bipolar disorder - one of my brothers succumbed to the latter).
COMT rs165599: assoc. as part of a 3-SNP haplotype (that includes rs4633 ) with incr. risk of schizophrenia and bipolar disorder .
[…No, I don’t have SCZ nor bipolar :blush: ]

Through a specific B-vitamin supplementation protocol (B12 as hydroxycobalamin / adenosylcobalamin, 2000mcg, in sublingual form; B6 as P-5-P; folate (5-methyltetrahydrofolic acid, 800mcg); and TMG (betaine), I have lowered my serum Hcy to reference range, which, while not a proven guarantee against future DVTs, might lower my risk. This supplement regime was based on the combination of symptom(s), lab tests, genotypes; with my doctor’s assistance & approval.

If you haven’t done this, having Vitamin B levels (and other metabolic-related factors)tested is worth doing… possibly as a guide for assuring proper levels of these. In any case, I’m a firm believer in using lab tests to confirm or rule out various systemic-level conditions that might persist if unaddressed.

Keep in mind that sometimes malabsorption is the problem, not necessarily just a lack of correct intake. In some cases for example, the stomach isn’t able to provide substances needed for absorption; or other enzyme defects are involved in metabolic pathways.
So it’s not only a matter of getting “enough” of a certain vitamin, but equally important is getting the right forms of the vitamin/nutrient for you. (Metabolic cycles are complex and depending on our genotypes, we absorb/process/use various nutrients differently. The detoxification pathways are also closely linked.

I do recommend finding if at all possible a doctor who practices “functional medicine” - someone knowledgeable about fundamental issues and systems, including the above. They aren’t always easy to find, but some are willing to do phone consultations if travel isn’t possible. Actually, I consult with different doctors, including my functional med. MD, and also insurance-network-included hematologist and a regular GP, both of whom are covered by my insurance network who’s willing to order diagnostic tests that might otherwise be questioned or challenged by the insurance provider.

I also have Yasko’s methylation report (and others) but found i still had a lot of questions that suggest further testing / discussion. But having compiled a lot of genomic information related to my condition(s), I can share all of that with my doctors - further enabling them to assist me.
(In addition to variant reports generated by and/or , I have created an elaborate database (an Excel spreadsheet, actually), showing my processed gene SNPS, my genotype / phenotype, and in various columns, associations with various conditions of concern (e.g. clotting, cancers, autoimmune, metabolic conditions, etc.); which allows me then to filter my genomic info to look at just those SNPs related to certain conditions, like thromophilia. I often will add links to PubMed articles related to these.

Good luck in any case! You’re on the right path and keep at it. And I hope you’ll steadily feel better.

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Hi, thank you for your answer.

The lab test came out fine, however my B12 (221) and ferritin (19) were in the lowest range.I eat enough B12 though my daily diet, but It can be low due to celiac disease. The doctor did not do anything, but I startet eating more liver and taking this huge doses of B12 and my fatigue improved after doing this for two weeks. My doctor told me it was only placebo.

The lab results showed also I had enough folate (22), low levels of homocysteine (7), T4 and TSH was also ok.The doctor did not test any other B vitamins.

My COMT genes with mutations are COMT V158; (AA ++), COMT H62H (TT ++). COMT [rs165599] (AG -/+) and COMT [rs9332377] (CT +/-).


I also have MTHFR A1298C GT (+/-). VDR Taq +/- and SHMT1 +/- with more.


COMT gives clinical meaning for me, due to stress tolerance, pain and limited of brakedown of neurotransmittors (and yeah, also the extreme ability to consentrate for hours on weird topics. Maybe thats why we end up in the SNPs…). There is nothing else in my lab reports to adress than this borderline B12. I am considering following your protocol to help with my stress tolerance and fatigue. I have also read that SAMe could help, but is seams scary to lower the dopamine levels in the brain.

The reason why I try adress my pain through the metylation pathway is also the fact that through the last 6 years, I had over 400 days on antbiotics and multiple cures on prednisolon. This affects the gut flora, and also affects my immun system. I will try to get to the functional medicine institute in Norway. But we dont have a Medical Professional with such competance in my area.

If you listen to Jesse Yu on YouTube, for perhaps 3 times, (From a Cancer Survivor: Top 3 Things that everyone can do every day to stay Healthy) you will begin to understand how small tweaks as you discuss are compared to a method where you reset your health. The Gerson therapy was established over tens of thousands of tweaks where some things worked and others did not. To start today with the few clues we get from crowdsourcing snp differences in our toxic environments will probably produce several decades of frustration and, at best, marginally improved health. Genetic mutations have been around from the beginning of time but epidemic poor health (autism in the US is 1 in 36; attention deficit 1 in 8; asthma 1 in 10; allergies 1 in 4; diabetes 1 in 4; obesity 1 in 3; major depression 1 in 2; cancer 1 in 2; dementia 1 in 1) happened in the last decade and a half. What a curative therapy does is take detox very seriously and eliminate food that is toxic. Three things Jesse says everyone should do is: 1. go easy on the salt, 2. detox, and 3. give yourself the best nutrition.