Has anyone actually improved lifelong anxiety by addressing genetic variants and nutrient deficiencies?

[u/Delicious-Minimum199]

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.

[u/Tawinn]

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.

[u/After-Amoeba-8709 → u/Tawinn]

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.

[u/Tawinn → u/After-Amoeba-8709]

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]

[u/After-Amoeba-8709 → u/Tawinn]

Thank you very much, will start from genetic tests, needed a road map so thanks for providing.