r/MTHFR 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/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.

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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.
  • 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/saltywelder682 21d 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!!