# Homocysteine
URL: https://genohealth.app/biomarkers/homocysteine
Units: µmol/L
Functional optimal: < 8 µmol/L (functional optimal)
Clinical reference: < 15 µmol/L (standard reference)
Evidence: Moderate evidence
Last reviewed: 2025-06-30

## Summary
Homocysteine is an amino acid that accumulates when methylation pathways are inefficient. Elevated levels flag B-vitamin deficiency, MTHFR variants, and cardiovascular and cognitive risk.

## What it is
Homocysteine is an intermediate amino acid in methionine metabolism. It is normally recycled back to methionine (requiring folate and B12) or converted to cysteine (requiring B6). Levels rise when these pathways are bottlenecked.

## Why it matters
Elevated homocysteine is a marker of impaired methylation. It is associated with increased cardiovascular disease, cognitive decline, and pregnancy complications. Whether lowering it directly reduces these risks is more debated than the association itself.

## Causes of high
- MTHFR C677T (especially TT homozygous) — reduced enzyme activity
- B12, folate, or B6 deficiency
- Hypothyroidism, renal insufficiency
- Heavy alcohol intake, smoking
- Some medications (methotrexate, certain anticonvulsants, metformin long-term)
- Older age

## Causes of low
- Very low or normal levels are generally favorable
- Pregnancy (transiently lower)

## Lifestyle
- Reduce or quit smoking and heavy alcohol
- Address thyroid and kidney function if abnormal

## Nutrition
- Folate-rich foods (leafy greens, legumes, liver) — for MTHFR carriers prefer L-methylfolate over folic acid
- B12 from animal foods or methylcobalamin/hydroxocobalamin supplement
- B6 from poultry, fish, bananas, potatoes
- Limit ultra-processed food and excessive alcohol

## Testing notes
Fasting blood draw preferred. Re-test 8-12 weeks after starting B-vitamin therapy.

## Related (knowledge graph)

### Biomarkers
- 25(OH)D (/biomarkers/25-oh-vitamin-d): B-vitamin and vitamin D status are often assessed together in fatigue and cognitive work-ups. [Emerging evidence]

### Genes
- MTHFR (/genes/mthfr): MTHFR C677T TT reduces enzyme activity by ~65%, raising homocysteine when folate intake is low. [Strong evidence]

### Supplements
- L-Methylfolate (/supplements/methylfolate): Active folate plus B12 reliably lowers homocysteine in deficiency or MTHFR-related elevations. [Strong evidence]
- Hydroxo-B12 (/supplements/hydroxocobalamin): B12 repletion supports the remethylation arm of the methylation cycle and lowers homocysteine when B12 is low. [Moderate evidence]

### Symptoms
- Brain Fog (/symptoms/brain-fog): Elevated homocysteine is linked to slower cognition; B-vitamin correction helps when levels are high. [Moderate evidence]

### Pathways
- Methylation (/pathways/methylation-cycle): Homocysteine accumulates when methylation cycle activity is impaired. [Strong evidence]

## FAQ
**Q: What is a good homocysteine level?**
A: Standard labs flag levels above 15 µmol/L, but many functional and integrative clinicians target under 8 µmol/L based on observational data linking lower levels to better cardiovascular and cognitive outcomes.

**Q: Does MTHFR always cause high homocysteine?**
A: No. MTHFR variants reduce enzyme efficiency but only translate to elevated homocysteine when B-vitamin intake (especially folate and B12) is insufficient. Many MTHFR carriers have normal homocysteine on an adequate diet.

**Q: How do I lower high homocysteine?**
A: The standard approach is B-vitamin support: L-methylfolate (rather than folic acid), B12 (methyl- or hydroxocobalamin), and B6. Treating contributing factors (thyroid, kidney function, alcohol use) matters too. Re-test 8-12 weeks after changes.

## Citations
- Frosst et al., Nat Genet 1995 — MTHFR C677T (PMID 7647779): MTHFR C677T TT homozygotes have ~30% residual enzyme activity and tend to higher homocysteine when folate is low.
- Smith & Refsum, Annu Rev Nutr 2016 (PMID 27431367): Homocysteine-lowering with B-vitamins slows brain atrophy in adults with mild cognitive impairment, particularly when baseline B12 is adequate.

Disclaimer: Informational only — not medical advice.