# Anxiety
URL: https://genohealth.app/symptoms/anxiety
Type: Symptom
Evidence: Moderate evidence
Last reviewed: 2025-06-30

## Intro
Anxiety has many causes — psychological, hormonal, gut-related, nutritional. A specific genetic pattern worth knowing: slow-COMT carriers clear dopamine and norepinephrine more slowly under stress, and they can be paradoxically over-activated by common 'methylation support' supplements.

## Summary
Some people are genetically wired to clear stress chemistry more slowly — and methylated supplements can make it worse before they make it better.

## Key facts
- Key gene: COMT (rs4680)
- Often helps: Magnesium glycinate, L-theanine
- Often worsens (in slow-COMT): Methylfolate, methyl-B12

## Genetic context
COMT rs4680 Met/Met (often called 'slow COMT') reduces enzyme activity to about 25% of the fast variant. These individuals tend to be more attentive at baseline but more easily overwhelmed under stress, and they accumulate catecholamines longer when activated.

## Supplements worth considering
- Magnesium glycinate 200-400 mg evening
- L-theanine 100-200 mg as needed
- Glycine 1-3 g at bedtime if anxiety affects sleep
- Adequate B6 (P-5-P) to support GABA synthesis

## What to be cautious with (slow-COMT)
- L-methylfolate at higher doses — switch to folinic acid if you feel wired or irritable
- Methylcobalamin — hydroxocobalamin is often better tolerated
- Caffeine — slow-COMT carriers often metabolize and feel it for longer
- Tyrosine, DLPA on top of stimulants

## When to seek care
Anxiety that interferes with daily function, sleep or relationships deserves professional support. Genetic factors describe susceptibility; effective treatment usually combines therapy, lifestyle and (sometimes) medication.

## Related (knowledge graph)

### Genes
- COMT (/genes/comt): Slow-COMT (Met/Met) clears stress chemistry more slowly; some carriers report higher anxiety under stress. [Moderate evidence]

### Supplements
- Magnesium Glycinate (/supplements/magnesium-glycinate): Magnesium glycinate has trial evidence for reducing subjective anxiety. [Moderate evidence]

## FAQ
**Q: Why does methylfolate make me anxious?**
A: Slow-COMT carriers build up dopamine/norepinephrine more readily and methyl donors can amplify that. Folinic acid usually delivers the same downstream support more gently.

**Q: What's the best supplement for COMT-related anxiety?**
A: Magnesium glycinate, L-theanine and adequate B6 are reasonable starting points. Most slow-COMT users also do better with non-methylated B12 (hydroxocobalamin).

## Citations
- Stein et al., Neuropsychopharmacology 2005 (PMID 15470376): COMT Met/Met associated with higher anxiety phenotypes under stress.

Disclaimer: Informational only — not medical advice.