# Hydroxocobalamin (B12)
URL: https://genohealth.app/supplements/hydroxocobalamin
Type: Supplement
Evidence: Moderate evidence
Last reviewed: 2025-06-30

## Intro
Hydroxocobalamin is the precursor form of vitamin B12 that the body converts to active methyl- and adenosyl-cobalamin as needed. Because the methylation step happens on-demand, it's a gentler option for people who feel overstimulated by methylcobalamin — particularly slow-COMT carriers.

## Summary
A non-methylated form of vitamin B12 that's well tolerated by people who get jittery, anxious or wired from methylcobalamin.

## Key facts
- Best form: Hydroxocobalamin (oral or sublingual)
- Typical dose: 1000 mcg/day oral
- Take with: Folate, B6
- Time of day: Morning

## Who tends to benefit
- Slow-COMT carriers who don't tolerate methylcobalamin
- People with low B12 (vegan/vegetarian diets, age 60+, PPI users)
- Pernicious anemia and intrinsic-factor issues — under clinician care
- MTHFR carriers seeking a balanced methyl-donor stack

## How it compares to other B12 forms
- Methylcobalamin — already methylated; faster active uptake but can overstimulate sensitive users
- Adenosylcobalamin — supports mitochondrial energy; often paired with hydroxo for full coverage
- Cyanocobalamin — cheap and stable but contains a cyanide group most people can clear; avoid in smokers and kidney disease

## Dosing notes
- 1000 mcg/day oral or sublingual is appropriate for maintenance
- Injections (typically 1 mg every 1-3 months) are used for diagnosed deficiency under clinician guidance
- Re-test serum B12 + MMA (methylmalonic acid) after 8-12 weeks

## Related (knowledge graph)

### Biomarkers
- Homocysteine (/biomarkers/homocysteine): B12 repletion supports the remethylation arm of the methylation cycle and lowers homocysteine when B12 is low. [Moderate evidence]

### Genes
- COMT (/genes/comt): Slow-COMT carriers often tolerate hydroxocobalamin better than methylcobalamin. [Moderate evidence]

## FAQ
**Q: Is hydroxocobalamin as effective as methylcobalamin?**
A: Yes for restoring B12 status. The body converts hydroxocobalamin to the active forms as needed, which is what makes it gentler for sensitive users.

**Q: Should I take hydroxocobalamin if I have MTHFR?**
A: Possibly — especially if you also have a slow-COMT genotype or felt over-activated on methylcobalamin. Many MTHFR carriers do well on a stack of folinic acid + hydroxocobalamin.

## Citations
- Thakkar & Billa, Eur J Clin Nutr 2015 (PMID 25117994): Hydroxocobalamin has a longer half-life and is the preferred form for parenteral B12 replacement.

Disclaimer: Informational only — not medical advice.