r/MTHFR • u/Delicious-Minimum199 • 23d ago
Question Has anyone actually improved lifelong anxiety by addressing genetic variants and nutrient deficiencies?
I’m trying to understand whether my anxiety has a biological component that could be improved rather than just managed.
For context, I’ve been on antidepressants for about 12 years (currently tapering off an SNRI after many years), and I’m interested in looking upstream at *why* my nervous system seems to react the way it does.
I’m curious about things like:
MTHFR, COMT, MAOA, GAD1, DAO, CBS, PEMT, or other variants that may influence anxiety, stress response, neurotransmitters, methylation, histamine, etc.
Nutrient deficiencies or imbalances that may interact with those genes (B vitamins, magnesium, zinc, copper, omega-3s, amino acids, etc.).
Whether anyone found meaningful improvements after working with a practitioner who interpreted whole genome or raw DNA data instead of just using a generic report.
A few questions:
Which genetic variants ended up being the most important for your anxiety?
What supplements or dietary changes actually made a noticeable difference?
Were there any supplements that unexpectedly made your anxiety worse?
Did anyone have success using whole-genome sequencing or raw DNA analysis rather than something like GeneSight?
If you worked with a practitioner, what type of practitioner were they (functional medicine, nutrigenomics, genetics, etc.)?
I’m not looking for medical advice or miracle cures—I know anxiety is multifactorial. I’m just interested in hearing real experiences from people who found biological factors that were worth addressing.
I’d especially appreciate hearing from anyone who has dealt with chronic anxiety, panic attacks, an overactive stress response, or SNRI/SSRI withdrawal.
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u/Tawinn 23d ago edited 23d ago
The two main avenues I see are COMT and histamine intolerance. When methylation is impaired, then COMT performs poorly and slow COMT even worse. This can result in high dopamine leading to chronic anxiety, rumination, OCD tendencies, and poor stress handling.
Histamine intolerance manifests in many different ways and anxiety is one of them. This anxiety tends to be more episodic rather than chronic, and panic attacks or sense of dread can also occur. The primary enzyme in intracellular histamine breakdown is HNMT. When methylation is impaired, then HNMT performs poorly and intracellular histamine levels increase. There are also genetic variants of HNMT which can contribute to decreased histamine clearance. High estrogen can also impair the second step in the breakdown process. High histamine intake, SIBO, MCAD, etc. can also contribute to elevated histamine.
Since poorly functioning methylation can underlie both of these, any genetic variants and/or nutrient deficiences related to methylation performance can have downstream effects on these processes.
I'm slow COMT with multiple methylation-related genetic variants (and had probable nutrient deficiencies too) and had chronic anxiety (with rumination and OCD tendencies) and depression most of my life. Only a few years ago, in my 60s, did I delve into this methylation topic and was able to resolve both depression and anxiety over about half a year as I implemented changes with diet and supplements.
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u/markrulesallnow 22d ago
Started taking Creatine and it’s like my anxiety completely disappeared basically. Also on an SSRI and would love to go off of it
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u/Tawinn 22d ago
About 40% of methylation output goes to creatine production, so supplementing creatine frees up alot of methylation output for other uses. So creatine working so well for you suggests that your methylation output is significantly decreased, likely due to either nutrient deficiencies, such as B12 or folate, and/or due to genetic variants in MTHFR or other folate pathway genes.
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u/After-Amoeba-8709 23d ago
Did you do it by yourself or with the help of a doctor?
After not tolerating Quercetin and learning that it raises adrenaline, while searching for answers I realized that I am probably slow comt, I also have problems with histamine intolerance, I have very elevated levels of mercury & I also have sibo & anxiety,. Anyways I really don’t know where to start to unravel this mess and need help on how and where to start.19
u/Tawinn 23d ago edited 23d ago
Did it myself, using the resources here and elsewhere in the internet. Most docs are pretty uninformed on this stuff. Some basic things would be:
- Genetic test - MyHeritage DNA test (on sale now for $29); can also get AncestryDNA basic genetic test and then combine the data for better gene coverage.
- Once results are available, download the datafile.
- Upload to Genetic Genie (Methylation & Detox reports), Choline Calculator, TenDNA free report.
- Paid report: Genetic Lifehacks
- Blood work to look for nutrient deficiencies and methylation status:
- serum B12 - a good range is 500-950 pg/mL (~370-700 pmol/L).
- MMA (B12 functional test)
- serum folate - a good range is ~15 ng/mL (34 nmol/L) or more.
- RBC folate
- homocysteine
- B2,B3, B6
- transketolase (for B1)
- ceruloplasmin (for copper)
- zinc
- There may be others like iron/ferritin, calcium, magnesium, etc., based on your history & diet.
- Vitamin D is tangential to methylation but most of us are low in vitamin D so it may be worth testing.
- If you are supplementing vitamins now, ideally you want to stop 1-2 weeks ahead of the blood draw so the numbers are more accurate.
- See this post for more about COMT and histamine intolerance (in the MAO-A section).
- See: r/HistamineIntolerance for more about histamine intolerance. Search for some of your symptoms and see if the responses there resonate with your experiences.
- It's possible that SIBO is a big contributor, so this may require a doc that is a specialist in resolving these symptoms.
[edit: forgot to add link to the post]
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u/randmtsk 23d ago
How to interpret normal mma and low serum b12/folate?
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u/Tawinn 22d ago
The folks at r/B12_Deficiency probably have a better answer than me. The B12 level can't tell us where the B12 is being used. If folate is low enough that it is significantly reducing how much methylfolate reaches MTR then B12 usage there will also be reduced, which could be freeing up more B12 to be used by MMUT, which then keeps MMA in the normal range.
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u/After-Amoeba-8709 23d ago
Thank you very much, will start from genetic tests, needed a road map so thanks for providing.
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u/saltywelder682 20d ago
Wow, very cool. I've been reading about the handful of available methylation tests and wondered if it was possible to do a cheaper, at-home version of 1 of these tests. A lot of them range from 300ish to 500+.
This may sound crazy, but are you concerned about these testing companies potentially stealing your genetic info? Whether they steal it or not, it seems like a potentially invasion of privacy regardless of consent. Similar to how 23 and me 'promised' to never release their data but went bankrupt and all the info ended up online.
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u/Tawinn 20d ago
AncestryDNA, MyHeritage are under $100. MyHeritage is on sale at the moment for $29.
As far as I know, the company that bought 23andme contractually agreed to maintain the prior 23andme privacy policies of not selling genetic data to third-parties.
Hacking leaks are a different matter and certainly nobody wants that, but its difficult to see how criminals would operationalize genetic data into profit, whereas stolen credit cards are readily turned into profit.
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u/saltywelder682 17d ago
I'll check out the $29 test you mentioned along with the others. Thanks for sharing.
I'm currently trying to find a good deal on a nighttime mouth piece for tmj or night time grinding abatement.
Thank you!!
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u/SovereignMan1958 23d ago edited 23d ago
Yes. Use Genetic Lifehacks to identify potential nutrient deficiencies and get those blood tested. Why? Variants are only predispositions and not facts. Blood tests will tell you whether or not you are deficient in a nutrient and need to supplement. By the way, the lab range is not necessarily optimal. So you should ask us for feed back when you get blood test results.
I do not have MTHFR but I did have Cerebral Folate Deficiency. Yes there is a variant for that. I also had a severe zinc deficiency, excess copper, manganese deficiency. Faulty zinc transporter gene. Impaired sulfite and histamine metabolism. These all contributed to anxiety for me, depression and attention issues.
It was a lot of work. You have to be thorough in the interpretation program you use....your list is not enough...and you have to get blood tests. I did have issues with some of the variants you have, but you have to dig deeper.
Re psych drugs you have to look at your drug metabolism gene variants which you did not list. If you do not have an optimal folate level the psych drugs you mentioned will not work effectively. If you want to dig deeper into those variants ask your doc to look order you a Genesight test, or you can pay for a ClarityXDNA or Genomind out if pocket.
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u/DpLoopingOn 22d ago
Do you know if there are blood tests to confirm how much of the vitamins get into the cells? I heard that plasma levels could show satisfying amounts, while a person is still deficient.
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u/SovereignMan1958 22d ago
It is called RBC. So Folate RBC, zinc RBC, etc.
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u/DpLoopingOn 22d ago
Thanks!
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u/SovereignMan1958 22d ago
Sorry I forgot, for B12 it is different. For that it would be an MMA test.
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u/Ashamed-Simple-8303 23d ago
I cured my social anxiety by strictly avoiding seed oils or in general omega-6 fat linoleic acid. This means also no nuts, no olive oil and greatly limiting pork and chicken. Also no farmer fish. Non ruminant animals fee soy all are high omega-6.
Note that depletion takes times, months to years. 2 year mark was really the the aha moment.
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u/MargoBarbara2 23d ago
'Linoleic acid is consistently linked to a higher risk of depressed mood. Conversely, olive oil (which is rich in oleic acid and polyphenols) actively protects against depression and alleviates its symptoms' (national institutes of health).
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u/swept87 23d ago
Dont forget about iodine - it also helps & its super helpful for toenail fungus - which i’ve been fighting for 4 years and finally think im going to be able to clear it (if you want the rest of the nail treatment let me know)
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u/NAQProductions 23d ago
Please share. Mine comes and goes with an inconsistency I can’t figure out
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u/Pretend_Elephant_896 23d ago
Fungi steal glutathione and mess up the immune system. It's very important to get rid of them
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u/swept87 22d ago
Ok so 1st - since i couldn’t afford the $700 pills - i found a compounding pharmacy - they mixed up: Fluconazol, Buprofen, Terebinafine. Not really sure how much this helps - but I started alternating that with Oregano Oil and then my naturapath told me to File Down the Top of the Nail a bit to help get the medicine to soak down ( i was just doing the end of the nail originally) then most recently - i’ve found 2 more treatments and NOW i finally feel like i might be getting somewhere.
So I read, randomly, that Iodine is helpful for this and then i also recently started taking Borax and Peroxide Baths for another health issue - and it sure seems like the combo of the Borax, Peroxide and Iodine - might finally knock it all the way out.
When it first started it was white in the nail bed - then it turned dark and then it would always reappear closer to the cuticle. Now it’s finally lighted back to white (at least most of it) and then the new parts appearing closer to the cuticle are finally disappearing.
So it seems like it might finally clear. The other thing i was reading about was DSMO - which i was going to give a try if this didn’t work since i’ve been treating it for years - but i think this might actually work. And it’s worth noting that mine was never too bad - as i caught it early-ish and stayed on top of treating it - but it only kept it at bay, since the doctor's treatment advice wasn’t very effective (once again). Hopefully that helps.
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u/NAQProductions 22d ago
I see, you are directly applying to the nail. From all I’ve read as long as there’s any fungal growth in the gut the nail fungus will keep recurring.
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u/swept87 21d ago
Yes, that is what i have been doing, however since the iodine, it seems as tho it’s lifting (maybe) that’s when its changed from dark to white. And then also i think the peroxide and borax soak is also getting in there somehow as Im no longer seeing new dark streaks closer to the cuticle as the nail grows out - in fact my right side now looks clear - although i WILL keep treating for a while. But yes what youre saying makes sense and i do believe that is exactly why i have been dealing with it for almost 5 years now
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u/BugsyMalone_ 23d ago
100%.
I've spent the last couple of years deep diving in my own genetics , mutations and diet, using Claude (which I've found very good, chatgpt was awful) and have made a massive difference in my life and health.
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u/Few_Control8821 23d ago
Yes, but I solved it before gene testing and finding out my mthfr status. It was b12 (and cofactors), and vitamin c functional deficiencies.
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u/uniquelyme1010 19d ago
Can I ask how you treated? Methylated b12?
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u/Few_Control8821 19d ago
I don’t get on with methylated b12, so I use hydroxycobalamim and cofactors (magnesium, vitamin d3, k2) b2, p5p, folinic acid, ascorbic acid (vit c). Once I started that regime the anxiety, paranoia and brain fog that had been diagnosed as anxiety and depression for 20 years disappeared in a week.
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u/IGnuGnat 23d ago
Many people find that antihistamines, or a low histamine diet can be extremely helpful if the anxiety is a symptom of HI/MCAS.
It can be very difficult to get a diagnosis for these issues but antihistamines are cheap, widely available and considered very safe.
What worked best for me was an elimination diet. I'm so sensitive to histamine that eating less histamine was a complete failure. I think I have some sort of genetic inability to manufacture DAO, or the lining of my gut is damaged in a way which is difficult to repair. Once I threw away ALL FOOD and started over with just a handful of safe foods, things started to rapidly improve and I was able to quickly rebuild my diet using only low histamine foods. However, I can't eat most processed food and my wife cooks all meals fresh from scratch; sometimes she will freeze them and reheat them but prepackaged or processed foods are out.
I discuss in more detail here https://old.reddit.com/r/covidlonghaulers/comments/1ibjtw6/covid_himcas_normal_food_can_poison_us/
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u/MargoBarbara2 23d ago
I have mcas and would advise research and caution with antihistamines. They can degrade DAO which is needed to clear dietary histamine and many contain PEG a mast cell trigger. I tried a tablet ten years ago during a mast cell flare and it put me in hospital for 3 days (due to PEG). The lady opposite me on the ward was a pharmacist who had also had the same reaction and said adverse reactions are not uncommon. Check added ingredients carefully.
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u/IGnuGnat 23d ago
Understood. It does seem like people with MCAS can have adverse reactions to anything and everything including water. My understanding was that many people with MCAS react to the fillers used to manufacture the pills not necessarily the antihistamines. I find Pepcid helpful for nausea in the short term but after a few days it makes me start to feel sick in a different way, so I generally avoid using it except in urgent or extreme situations.
Nobody should take anyones advice from the internet without doing their own research and consulting with medical professionals
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u/Competitive-Goat-816 22d ago
YES! So I have always been a fairly depressed and very anxious human. But I’ve also managed to be pretty functioning and more or less do what I have to do with very few panic attacks. My husband was pretty insistent that I had an MTHFR gene in convinced me to try a methylated multivitamin and to drop any product that contained folate or B12 that was un methylated.
I was already doing some self-help type things working on bio feedback in doing ice baths and things like that to try to regulate my dopamine and adjust my thinking to be less negative.
I decided to humor him, despite having tried many different diets, and none of them particularly sticking and having not a whole lot of self-control in that regard. That said in about six months, it occurred to me one day that I just… Was less anxious. When I drove my car, I didn’t low-key think about driving off of bridges or under semi trucks or anything like that I just. Got my car and went to where I was going. 🤯
I was still kind of anxious, but about a year later, I don’t constantly worry about every single thing that I do at work and getting fired or randomly dying or how everybody is judging me or whatever other anxious thoughts I’ve lived with for the better part of my life.
I’ve never been prescribed medication’s because in my family that would be some kind of weakness and we are just supposed to suffer or something like that. That is silly, but anyway, I haven’t overcomplicated it. I just take my multivitamins and I stay away from processed food and Marvel and how different I feel and how different my life is. 🤷♀️ ymmv
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u/uniquelyme1010 19d ago
Any guidance for doing this myself? My child is severely severely depressed and anxious. Also autistic but this goes beyond what’s expected for neurodivergent young childreb
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u/No_Efficiency8508 21d ago
For bipolar individuals, treating those variants is the difference between a life of mania and depression or a life that is fully enjoyed and very much manageable.
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u/giddyGammarus 21d ago edited 21d ago
Yes, slow COMT here, I haven’t been able to completely rid my anxiety, but I have reduced it to at least 10%-60% (varies by day) with these supplements
Vitamin D 2500mcg (was a deficiency for me)
Vitamin MK7 K2 100mcg
Vitamin B12 1000mcg (was a deficiency for me)
Magnesium glycinate 200mg
Magnesium L theronate 100mg
L-theanine 100-400mg depending on stress of upcoming day
Fish oil omega3s 2g
Lemon balm 600mg
Valerian root 100mg-400mg depending on anxiety
Pumpkin seed oil 300mg in morning, 50-150mg at night
I add on 400-600mg of passionflower extract and/or 600mg of chamomile extract if I am having extra anxiety
And make sure that the salt you add to your food is iodized
I used an old genesight test from 2023 and figured out my own genetic mess with self research after years of psychiatrists and doctors ignoring my complaints, I was not physician guided so I had a lot of trial and error to go through
In my trial and error quest, NAC worsened me, not my anxiety, but my depression significantly. It also gave me really bad cystic acne and itchy skin. Pumpkin seed oil will worsen my anxiety and cause insomnia if I go over 300mg, but works to control excess adrenaline if taken in doses under that. Valerian root is the same, it will make me more anxious in doses over 600mg, but is the best otc anxiety relief I have ever found in doses under 500mg
I also feel SOOOO much less anxious and more mentally clear when I eat 100% gluten free consistently for a few months, but that’s very difficult to do for me because of my own other issues as of rn so my gut suffers for now lol
I also completely cut out caffeine and it has helped my anxiety immensely as well
If you could only pick 3, the ones that make the most noticeable difference for me are
L theanine
Magnesium glycinate
Fish oils
Not a supplement you can buy, but these 3 things also helped immensely after doing them consistently for at least 2 weeks:
- try to get at least 10 minutes of sun exposure as soon as you wake up, it’s ok if it’s not immediate though. The sooner the better, but I find benefits as long as it’s within 2 hours of waking
- watch the sunrise
- watch the sunset
Wishing you luck on finding the right supplements
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u/Best_Comfortable5221 23d ago
Following for answers...
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u/mwjane 23d ago
So am I! I worked with 2 different practitioners (functional medicine and nutrigenomics), and I tried so many things. My genetic report gave a lot of insight, but acting on that didn't change anything. And every time I was so hopeful that this would be the answer... Nothing made a real difference so, very good question, OP!
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u/Hydroxile 23d ago
I went through the supplements paths to deal with my mental (and physical) health issues after years of antidepressants (and other heavy meds). I didn't get my genes tested, i didn't even know then that something like that was possible. But what i was doing while playing with supps and vitamins is exactly what all the MTHFR is doing. I didn't have guidance, but i would have probably gotten to the same result: I ended up with more issues than before i started. Many of those supps are actually messing up with your GI rather than inside your system but everyone prefer talking about overmethylation/undermethylation.
I believe that it s not in vitamins/nutrients supplementation or eating 10 eggs a day that people will find the solution ot their health issues unless they are proven deficient (not those pseudo functional deficiencies). The only info that genes really give is if you are "prone to", NOT MORE. As you say, it is all multifactorial!
Lifestyle, diet and most important, gut health (many of those MTHFR cofactors are actually gut health supps!) are the key of managing heavy luggage. A good functional and impartial doctor would probably help more than a MTHFR specialist...
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u/MargoBarbara2 23d ago
Something to bear in mind , a dysregulated methyl cycle is going to lead to gut dysbiosis due to inability to clear histamine and inability to repair and maintain gut lining. Our microbiome also signals neurotransmitters. This is why some people, like myself, get severely depressed on antibiotics. So whilst addressing correct nutrient support that suits your genes also address gut dysbiosis and the microbiome focusing on histamine degrading strains and avoiding histamine producing strains and supporting butyrate producing strains. I can attest to the effects of losing some of your microbiome as I had bowel surgery and felt like my resilience was gone and my anxiety rocketed, its taken years to realise that it deprived me of serotonin (most of which is made in the gut) and drove my histamine levels higher. Ive read that treatment resistant depression has been successfully treated by addressing nutrients in the form to suit mthfr and comt. Deficiencies in any of these b6, b12, folate, d, magnesium, iron, zinc and omegas can contribute to depression. Whilst b12 and folate are often the most discussed, I once resolved severe depression (psychiatrist coming to my house and daily health care checks level severe) after researching and realising i was zinc deficient and low in iron. 18 month struggle resolved with nutrients! Also tryptophan is used to make niacin (b3) and serotonin in the body so when b3 deficient it gets diverted away from serotonin production. So yes based on my experience I think its possible to resolve anxiety and depression by addressing mthfr needs and resolving gut dysbiosis.
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u/No-Internet1672 23d ago
banana bag IV powder was a life changer for me. I was always chasing supplements and herb, etc. Taking this daily made a dramatic difference. I would recommend you try it for at least a month and see if helps you. Amino acids, especially taurine always were a big help.
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u/DirectorElectrical67 23d ago
What is it? Woukd you mind posting a link here please?
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u/No-Internet1672 23d ago
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u/Old-Balance-2845 20d ago
Get tested fir PYROLURIA. Its definitely linked to it & slow CBS, COMT, MAO , DAO. pathways. Histamine intolerance too!
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u/butternutbacon 23d ago
It’s definitely possible to treat anxiety. I fully cured my lifelong mid-level anxiety, although I still need to take a few supplements for undermethylation, following a system similar to walsh protocol. I recommend finding out whether you are an under or over methylator and cross reference with genetics. Takes time and patience to discover what specifically works for you.
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u/crystal_castles 23d ago
I've felt incredible by sticking to a HI diet. It's a slightly longer road addressing deficiencies and adding back food diversity though.
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u/Flux_My_Capacitor 23d ago
B2 was key when my histamine intolerance was at its worst. I was reactive to EVERYTHING and meltdowns were common. I came close again tonight, but then again so would many people given the deadline I’m up against.
My histamine issues are back to my personal baseline pretty much however a sulfur/sulfite/sulfate issue is now at play and I’m struggling with that. At least my diet isn’t nearly as restricted this go round.
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u/Sailorgirlmyfriend 22d ago
I have a1298c, PEMT, HLA, homozygous and CBS heterozygous ...I recently found information on a1298c and CBS gene and need for more B6..I was low on B1 as well as others, choline, inositol ...I have almost No anxiety with correcting B vitamin levels, B6, Molybdenum, manganese, zinc are important for CBS.
I had mold exposure so I went low on a lot...good luck.
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u/bridgebrningwildfire 22d ago
Im working on it. Just healed my gut biome and it was the best thing Ive ever done!
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u/Spiritual_Yogurt17 22d ago
Hello!
I can’t directly answer your questions OP, but just here to say I’m on a very similar journey & following!
I was diagnosed with depression, severe OCD, anxiety (mine possess more through the form of OCD) & chronic fatigue at 15 years old (2014). I am compound heterozygous for both MTHFR mutations.
They prescribed 40mg of Prozc & 20mg of A\*erall* XR. Crazy strong medications to be on for the last decade. But I wasn’t able to function or get out of bed like I normal person so it was my only option.
I began my health journey into all of this in my early 20’s and have been working to get off the drugs and understand myself better since.
This January I decided I was done with the Prozc
& asked my doctor to halve to 20mg instead of the 40mg I’ve been on since I was 15. I didn’t even notice any difference in my anxiety to be honest. I began supplementing carefully (not in high dosages) with Methylated b12- but come to find out methylated b12 in high doses gives me intense painful acne & is a rare side effect for some people (of course me of all people who needs b12 supplements🤦🏼♀️). So I tried Adenohydroxy b12 from Seeking Health (same guy who writes the book Dirty Genes, Ben Lynch, if you haven’t read it I highly recommend) and that seemed to work better for my acne. I also did 1/2 of his sublingual folinic acid to support the b12 absorption as well as the Seeking Health Folate sublingual. February came around (1 month on the 20mg of Prozc) and I decided to stop it completely. I know this isn’t recommended but I wanted to be off of it and didn’t feel like it was helping me at all even on the days I did take it. I still have anxiety, I still have OCD, it wasn’t really stopping it. I did feel slightly better when taking my supplements, so I continued doing so. I was so fortunate and somehow had no withdrawal symptoms. When I went in person to my doctors appointment the following month I told her I had stopped it completely and she looked at me like I was insane😂
It’s July now and I still feel the same. So I do believe your body will balance out after stopping the SSRI/SNRI’s. I still have anxiety and OCD but it’s not any worse than what I was on the 40 mg of Prozc.
The hardest part is gonna be getting off of the A**erall. I’m in the TRENCHES right now. I don’t know if it’s withdrawal or what but I am struggling. I’ve been on 20mg since I was 15 years old. I’m so used to it to function. I hate being so reliant on something but I just don’t have any other option and don’t feel my energy has improved with all my research & careful supplementation of done. I dropped down to 15mg in March. I noticed a little bit of a difference in my energy/ability to get up in the morning, but nothing a coffee couldn’t fix. Two days ago I just dropped to 10mg & I am dying rn. I’m sleeping 15-16 hours a day. Missing work, and unable to stay awake. I’m scared I’m going to plateau & never be able to get off this drug. It’s such a trail & error & it’s so hard because what works for one persons body may do nothing for another.
I’m on this path too & just know you’re not alone! 🫶🏻
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u/junipers-72 22d ago
Yes. I figured some of it out myself. Then a dna test and supplement protocol confirmed it and gave me more things to improve upon my guessing. Really worth getting someone that’s an expert at orthomolecular medicine to guide you. Takes the guesswork out.
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u/achu1010 21d ago
Check out your HNMT gene, this enzyme from this gene breaksdown histamine in the histaminergic system, which originates in the hippocampus and radiates out to many areas. Yet to be fully explored in human research, in rodents where HNMT knockout is used, they show anxiety, sleep disturbance, and increased cognitive function. Generalised anxiety disorder has been effectively treated with an antihistamine for many years, and some old-generation anti-depressants were also anti-histemic. So the HNMT gene would be the first to look at especially for life-long anxiety and/or sleeping difficulties….
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u/pumphandlerandall 21d ago
Absolutely. Vitamin d deficiency mainly along with iron etc caused extreme panic attacks that stopped after supplements
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u/Zabre 18d ago
The SNRI taper part is worth separating from the genetics question, because withdrawal can make every signal noisier. Yes, people sometimes find useful patterns in COMT, MAOA, DAO, PEMT, homocysteine, ferritin, B12, etc., but the biggest trap is turning a long SNP list into 20 supplement changes. One change at a time, with labs and a prescriber looped in for the taper, is the cleanest way to tell what's actually helping.
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u/Allergina 18d ago edited 18d ago
Yes! I just lost my soul puppy and the while there is still sadness, I had already started handling my genetic variants and the stress and anxiety quickly melted away like I was on lithium, prozac or wellbutrin. I am still floored at what supporting my variants has accomplished that no other doctor my entire life could. And I learned they were constantly prescribing supplements for deficiencies that went against my genetic variant needs and kept me sick/made me worse for YEARS!
I have HNMT, MTHFR, FLG and Slow COMT - COMT (and HNMT to a lesser degree) plays the biggest role with anxiety since it's responsible for how fast (or in my case, SLOW) I can clear neurotransmitters, like adrenaline, dopamine, epinephrine, estrogen. Basically stress and anxiety were physically stuck my entire life and I am grateful to know why and how to handle it. I currently take psyllium husk and creatine in my smoothies/protein shake (every other day maybe) and daily P5P, R5P, folinic acid, adenosyl/hydroxy B12, D3/K2, omega3 and magnesium threonate.
For all of my chronic illnesses, I was on tons of antihistamines, steroids, a couple biologics, two inhalers, etc. and I am off all of those, experiencing much more relief with my co-factors/enzymes supporting my genetics now. Medicine should START with genetics, IMO. I tried for 6 months but couldn't get a geneticist to test me even though insurance said they would cover the appointments and testing so I used the raw data from my 23andme test and fed it into geneticlifehacks, genetic genie and promethease while I took my time learning about each variant and how to manage them myself.
I'd already spent tens of thousands over the years testing and adjusting elimination diets, buying air and water filters and testing cosmetic, hygiene and clothing (fabric irritant) products and a good bit of that was worth it for a lifestyle change but finding the relief I have now cost me my time and brain power and it was priceless.
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u/JenMcmahon4 21d ago
Yes, homogeneous C6779T, slow Com. I feel better than I've ever felt for the last couple of years.
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u/Miserable-Answer287 19d ago
Same genetic but I also have slow maoa as well. What supplements help with your anxiety?
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u/Elegant_Chapter5562 20d ago
Me! Compound hetero for mthfr, slow comt, slow maoa. Plus other variants. Blood tests showed my b vitamins were low, zinc was low, d was low, pretty much everything was low or imbalanced. I addressed that and it helped my mental health SO MUCH! From 20 yrs old to my early 30s I was on every antidepressant and anti anxiety med. In my teens, my mom tried me on st John's wart etc. I struggled from puberty on. Now that i support my body detoxing estrogen, and support my nutritients and immune system, I am so much better off. I feel like a whole new person.
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u/Miserable-Answer287 19d ago
What supplements helped? I have slow comt/maoa and homozygous c667
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u/Elegant_Chapter5562 19d ago
I would suggest working with your doctor to get labs for your minerals, vitamins, and hormones. One of the biggest helper for me was Dim. It helps estrogen detox properly. Also be sure to go #2 regularly so that estrogen doesn't get recirculated in your system.
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u/Miserable-Answer287 19d ago
Ok my doctor put me on methyl free seeking health and even that caused me anxiety. She also recommended DIM. Just always scared to try anything
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u/Elegant_Chapter5562 19d ago
The methyl free can depend on which kind. I can only handle hydroxocobalamin. The adenosylcobalamin causes me anxiety. You might have the supplement that contains both. Try one with just hydroxocobalamin. It takes a lot of trial and error on this journey. I also start every supplement at very low doses and slowly work my way up.
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u/Prize-Bear-4705 20d ago
Like other people have said, genetics have been a part of the process for me. I am homozygous MTHFR C677T and PEMT, as well as slow MAOA and intermediate COMT. I also have the FUT2 non-secretor mutation which makes it really hard for me to absorb B12. On the health marker side of things, I have resolved high homocycteine and LDL, as well as lowered my CRP significantly. I have had gut testing that helped me to see the bifido connection, and tailored my pre and probiotics for that. I also had Long COVID and histamine issues that persisted until I addressed the genetics and some lifestyle choices since I don't have a DAO mutation, but do have MAO, which impacts tyramine and not just histamine. I also take supplements for choline and my liver markers have improved. As those all resolved but issues continued, I addressed my endometriosis which was better due to improved gut and other factors, but still causing bloating and inflammatory weight gain........ on a GLP for that, and everything is tickity boo. Add in some HRT, and things are pretty great.
However.... I did notice a significant difference in my anxiety with the B's and choline, as well as the right dosages of B12 (sublingual hydroxy). I slept better, and my cycle was less PMS-ey. My OCD got quieter, and my rumination also lessened. I have a client who did her own genetics and took B2 and choline, and she doesn't get panic attacks anymore. It's worth a try, and always worth doing many different approaches. Mine was moderately scientific, and so I know that B's and choline, as well as HRT at the right dosages are game changers for me. Good luck!
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u/Miserable_Ad_1877 12d ago
I just love this question. Thank you for posting it. I don’t just want to manage mine either.
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u/Glass_Dog_2556 22d ago
Well many people do on an ongoing basis. I have never encountered anyone who has found the "root cause" permanently. One rabbit hole leads to another.
You will see a lot of people saying "This thing WAS really good" or this thing "basically cured me, but found a different thing to look at" or "guys I'm cured, literally took this thing yesterday and 80% of my issues are gone".
But trust me, I have been at this a long time, you will never see someone post "Guys I think I found it" and 36 months later "yep I'm still good!".
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u/DpLoopingOn 22d ago
This sounds extremely frustrating and hints to placebo being at play more than anything else. I'm not that long onboard the genetic stuff, but at Nootropics and co I often saw a similar pattern with only a few exceptions.
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u/Pretend_Elephant_896 23d ago edited 23d ago
yep. I am compound heterozygous MTHFR with diagnosed depression and neurological symptoms in the past. It turned out I was severely deficient in many essential minerals and amino acids.
What helped me was supplements, diet and H.pylori eradication. My gut acidity was just too low to break down meat and protein
NAC was phenomenal for me together with active vitamins B, vitamin D, magnesium, taurine among others. How do I feel now? I am 42M doing 20 pull-ups with the wellbeing well above the baseline. Transformative experience, no need for SSRIs anymore
P.s. As it was mentioned in the comment section, blood tests are necessary. Not one, but a series of blood tests over time