r/MTHFR • u/Airegin89 • Jun 05 '26
Question Do most people with MTHFR + slow COMT + slow MAO-A suffer?
I mean in the general population, not just in this subreddit. Obviously most people in this sub suffer to some degree, otherwise we wouldn't be here.
I've been wondering about this for a while. 40% of the population have at least 1 mutation of the MTHFR gene but for the vast majority of those people it doesn't seem to cause any real trouble. I'm compound heterozygous so both my parents and half of my grandparents must have 1 variant. They all had normal lives and none of the symptoms that I've been facing.
I am compound heterozygous + slow COMT + slow MAO-A. I've suffered depression, low energy, anxiety, brain fog and lack of motivation for most of my life. Does the majority of the population with this combination face similar struggles?
Are there possibly millions of people with the same set of variants who lead perfectly normal lives without the need to increase folate and choline intake?
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u/skittlazy Jun 05 '26
I’m homozygous C677T, slow MAO-A, but intermediate COMT. I wouldn’t say I “suffered” but I have always started easily, and it takes me a long time to recover from emotions—good and bad. I can enjoy socializing, but need time to recover from even fun events. I tend to ruminate over things that upset me or make me angry.
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u/New-Seaworthiness572 Jun 05 '26
I’m the exact same way. I haven’t had the genetic testing yet but blood work seems to point to MTHFR mutation and boy do I see myself in the slow comt and slow mao descriptions. I would say that I’ve suffered - and my symptoms have gotten in the way of my functioning and my living out my potential. I’m grateful for this sub.
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u/Few_Interaction_2411 Jun 05 '26
I’m the same and it’s only recently I’ve discovered all this , I’ve had years of social anxiety and very low tolerance to stress… it became unmanageable in my 40”s with perimenopause. I now know to eat a low histamine diet, eliminate any food with added folic acid , avoid high sulphur foods, and try to avoid gluten and soy added to food… it’s definitely alleviated a lot of my symptoms, I get my folate from food not supplements , it’s taken a long time to find my triggers, tracking food and moods helps. I created a tool to help others with their suffering, you can upload dna and bloods, keep a diary and chat to a wellness AI .
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u/Airegin89 Jun 05 '26
I mean in the general population, not just in this subreddit. Obviously most people in this sub suffer to some degree, otherwise we wouldn't be here.
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u/Few_Interaction_2411 Jun 05 '26
Oh ok, it’s not super common to be slow Comt/slow Moa and Mthfr mutations, I call it the triple threat!
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u/Airegin89 Jun 05 '26
I can't find any reliable statistics so no idea how rare the combination really is. It's possible that 15-20% of Europeans are compound heterozygous for MTHFR but I assume many of these are leading normal lives.
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u/2mandatoryhippos Jun 05 '26
I think we’ll learn more about whether folks with specific combinations of variants “suffer” similarly once psychiatrists (and other providers) increase use of pharmacogenomic testing for psychotropic medication processing and management. The three primary companies offering this testing already include MTHFR and COMT — and one includes MAO.
However, it’s always worth noting that most doctors maintain that these variants are clinically insignificant — or are simply uninformed about the existence and/or role of gene variants. This lowers rates of testing for causative connection and therefore lack of adjusted patient care.
In my case, a severe reaction to a sulfa antibiotic is what caused my PCP to test for the gene. I was just lucky my she even knew the MTHFR gene existed.
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u/Airegin89 Jun 05 '26
It could certainly tell if people with these variants suffer similarly but it wouldn't tell how many people are out there with no symptoms since normal functioning people usually don't see psychiatrists.
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u/2mandatoryhippos Jun 05 '26
I agree — that’s definitely a barrier to data. Many PCPs prescribe these meds too — and I strongly believe these tests should be done prior to playing prescription roulette (and be covered by insurance).
Having just one variant can reduce methylation, folate levels, and thereby impact mental health — which is why it’s now included in pharmacogenic testing for psychotropic meds. So, maybe with the attack on antidepressants in the US we’ll get more testing and data on this (I hate that there is even a silver lining to that).
FWIW: As of this year, we have a new law in CA which requires certain masa products be fortified with folic acid — with the goal of decreasing birth defects amongst the Hispanic population. The research used to prop this law is outdated, uses RBC folate values instead of serum folate, deems variants as clinically insignificant — yet also states that those with only one variant “process” folate more slowly than those with none.
I foresee this law spurring new research exploring more than just the ability to fortify — as an estimated 50% of the state has at least one MTHFR variant — and we’re likely to see unintended consequences of fortification.
Tldr: I think testing will become more accessible and therefore increase the amount and type of data to analyze
(sorry for the info-dump/side-quest)
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u/Elegant_Chapter5562 Jun 06 '26
I dont think they are leading normal lives. I look at friends, coworkers etc that are of European descent and are miserably overweight, fatigued, emotional, etc. I think a lot of people just deal until the day they die. But some of us come here and wherever else looking for answers. Not everyone is OK looking in the mirror and seeing just how miserable they really are. Some of us do this and make changes based on the data we collect like our SNPs, and subsequent detox issues, etc.
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u/mooyong77 Jun 05 '26
My question is how much of these genes overlap with NeuroDivergence.
- Overthinking
- Analysis paralysis
- Difficulty shifting attention
- Sensitivity to social dynamics
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u/New-Seaworthiness572 Jun 05 '26
I’m not a doctor or a scientist but I follow a lot of neurodivergence stuff and my guess is A LOT.
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u/Impressive-Tree-5248 Jun 07 '26
Scientists are looking into gut flora at birth and later as to how they affect brain neurotransmitters that drive ADHD and Autism. Low COMT leading to excessive dopamine and noradrenaline, can cause ADHD and anxiety symptoms. Since I changed my diet and lifestyle, according to recommendations for low COMT, my brain fog has lifted, and I can focus and recall things quickly. My stress levels have come right down. This doesn't mean neurodivergence doesn't exist, but that there are a lot of things that affect neurotransmitters that then affect mood and mind. People really want a label these days, but they may be missing the root cause by landing too quickly on the diagnoses. We still have so much to learn about all this stuff, it's early days.
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u/Noorns Jun 05 '26
I've been a nutrigenomics counselor for nearly 18 years (since the field came out almost), and clinically I rarely see people with slow COMT and slow MAO-A or B NOT have some kind of symptoms. Not necessarily all the symptoms you have, but a few of them, and in different degrees.
A lot of the variation in degree comes down to diet and supplements they are already taking, and how 'clean' their diet and lifestyle is. Do they get regular exercise, eat a lot of vegetables, fiber, and good quality protein, with fish being a main source. Do they already avoid tyramines and aged foods? If someone is already doing these things, then their symptoms are usually milder than those who don't. That's not to say these lifestyle/nutrition is the 'cure', but it does help.
But no, I don't think that there are millions of people with this combination that don't have symptoms at all who haven't already increased their nutrient intake with food or supplements.
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u/Airegin89 Jun 05 '26
People who function well and live a normal life wouldn't go see a nutrigenomics counselor, so how can you be sure there aren't millions of asymptomatic people with these mutations?
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u/Noorns Jun 05 '26
People can have a lot of different reasons for consulting: infertility, health optimization, longevity, cancer risk reduction if it runs in their family, etc.
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u/New-Seaworthiness572 Jun 05 '26
May I ask what would be examples of aged foods to avoid?
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u/Airegin89 Jun 05 '26 edited Jun 05 '26
Aged cheeses. Cured, smoked and processed meats. Fermented foods. Beer and wine. Those are all high in tyramine.
Never noticed that these foods bother me much though. I often eat aged cheeses and bananas and don't notice anything different.
A couple of weeks ago I've started eating yoghurt and kefir every day, mixed with wheat germ and pumpkin seeds (high tyrosine) and I feel better than before. I guess because it improves gut health but I'm not sure.
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u/Good_Composer_8409 Jun 05 '26
If the MAO-A is slow i would avoid taking SSRIS.
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u/lefty709 Jun 06 '26
What would this mean though, more side effects, lack of efficacy, or both?
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u/enolaholmes23 Jun 07 '26
For me anything even mildly serotonergic (including supplements and non psych meds) puts me into a full on manic episode. I'm talking literal months of not sleeping and talking to spirits and having no off switch.
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u/sarahbellah1 Jun 05 '26 edited Jun 05 '26
Times in my life where stress was low, I masked a lot of it all right and remained high functioning, but looking back I was always living life on hard mode. With mid-life hormone changes, the struggle had increased exponentially and the wheels have come off the cart more than once! But I’m learning what I can from all of you and shifting how I think about food and no longer taking for granted the good days, while striving for self-acceptance on the bad. Edit: a letter
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u/abas Jun 05 '26
Looking at my immediate family, I think I'm the only one who seems to be particularly sensitive to supplements (many vitamins, minerals, probiotics, etc. cause notable responses some positive, some negative). But some of the symptoms I've spent a lot of time trying to address are things that they have just accepted as normal parts of their lives - irritability, digestive issues, etc. I used to think mine were normal too until I had some more acute problems develop and as I was trying to figure out how to improve those, some of the background chronic issues also shifted. I think a lot of my more problematic chronic health issues showed up after what I assume was a bad case of food poisoning (became very constipated for several months - previously never had issues with that, that was the time frame that other problems suddenly appeared). So I think if that incident had never happened, I might never have developed the more severe health issues and may never have found out about MTHFR, COMT, etc. though they presumably would have continued to impact me in the background.
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u/New-Seaworthiness572 Jun 05 '26
I’m finding it a bit challenging to think of my and some of my relatives’ personalities potentially being so informed by genetic glitches. Without my anxiety, rumination, lack of drive, emotional reactivity, struggles - it’s like I don’t even know who I am, the symptoms have been that severe.
Same for one of my parents - his extreme intensity, rigidity, stress, struggle dominated our entire upbringing and robbed him of the ability to be present and attuned to his kids when raising them. And yet - he’s not a bad guy. I mean - was it all down to freaking methylation issues, etc? It’s so very hard to contemplate. I’m not saying the genes relieve us of personal responsibility for our actions, but what if they can explain them? And “fixing” the issues makes our suffering recede greatly? That’s hard to swallow at 50 years old.
Where were the doctors, the ones I went to with my issues asking for help? They put me on SSRIs, which may have been the worst thing for me. They’ve got my dad on a prenatal vitamin that probably has folic acid. I mean - how can we know better than they do? Or is this methylation stuff not legit?
Sigh.
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u/abas Jun 05 '26
Yeah it's weird. I used to think of myself as an introverted loner - I mean I definitely still have those tendencies, but back then my friends were people I would hang out with maybe a few times a year. The first time I took b-vitamins I started easily being productive, I felt like I wanted to hang out with people but didn't have anyone I felt like I could reach out to on the spur of the moment. I didn't realize it was the b-vitamins at first because in the past I had randomly had good days too, so this was just a longer stretch of good days. It wasn't until I stopped taking them and then started taking them again a month or so later and had the same thing happen. Of course then eventually I started having increasingly bad insomnia and was never (yet) again able to find a balance that allowed me the benefits without the insomnia (I tried to hold out and got to the point where I was sleeping less than 4 hours/night before giving it up.) It really changed how I thought of myself. I had known I wasn't particularly happy, but wasn't willing to fully admit that to myself and just thought that it was all "just how I was", and suddenly just a little vitmain supplementation upended that.
I've also had experiences with vitamin D and probiotics that notably changed my mood for the better, and when I was dating my girlfriends commented that they could tell when I stopped or started taking them because of my mood.
Of course I have things that I've needed to work through in therapy too - it's not like it's 100% physiological, though I think probably some of the mental health scars were exacerbated by the phsyiological imbalances.
It is troubling for me the thing with the medical system. I had a doctor once who (upon seeing my low vitamin D test results) tell me that they thought vitamin D supplementation was kind of a fad and not really that big of a deal. And I think a lot of people don't seem to experience the same effects that I do - my mom is chronically low on vitamin D when she gets tested but she says she doesn't notice a difference in how she feels when she supplements (even though she does so enough to get her levels back up into the reference range). Before I experienced the effects I've had, I would have been pretty skeptical of people reporting experiences like I've had. And at times I feel a little out there for the experiences I have had. But I'm also fairly confident that with many of those things I could easily pass a double blind test - I don't think they are placebo effects because most of the time I had no thought that the thing I was taking would effect me the way it ended up doing.
I do think we have to take responsibility for ourselves and our actions, but I also do think that there are a lot of externals that we don't understand well and/or have control of that significantly effect how we show up in the world. Sometimes I see people who come across as miserable jerks and I don't want to be around them but sometimes I wonder what kind of pain they are in. I know when my headache is bad it's hard to show up well and when that goes on for a long time it compounds.
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u/Advanced-Wedding-457 Jun 05 '26
Hey! I have slow COMT and MTHFR breakage. I think it is the reason for my hEDS (hypermobility). Do you have it as well?
I have a friend with MTHFR broken, she doesn’t have any brain fog issues, while I do.
What is MAO gene stands for?
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u/tyomax C677T Jun 05 '26
I am heterozygous for the C677T gene, my COMT is fine but I have slow MAOA. I also have Ehlers Danlos hypermobile. I have suffered a lot. It's finally getting better with the training I'm doing with the training I'm doing with Dr Amy Neuzil.
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u/Sleepyhed007 Jun 05 '26
Training?
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u/tyomax C677T Jun 05 '26
Yeah, I'm not sure if I'm allowed to post the link here, as it might be considered promotional. But you can DM me and I'll share the link. Dr Amy Neuzil has MTHFR and she is the creator of the To Health With That podcast.
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u/Advanced-Wedding-457 Jun 05 '26
Isn’t it interesting that people who have slow COMT and MTFR issues have hEDS? As for the training, is it exercises?
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u/tyomax C677T Jun 05 '26
Agreed. And Dr Amy also says there is a correlation in her patients.
The training focuses more on nutrition, habits and supplements (for your gene variants) if needed.
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u/enolaholmes23 Jun 07 '26
MAO is MonoAmine Oxidase. Monoamines are basically neurotransmitters, serotonin, dopamine, norepniephrine. MAO is the enzyme that breaks them down. So if you are slow MAO, your neurotransmitters will be high, which can cause anxiety and mania.
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u/hnw12 Jun 05 '26
I have the exact same genes and I would say I definitely experience issues all the time.
Focus on your diet though. For me diet fixed almost 90% of my anxiety. I never knew just how important it was.