Research synthesisHigh evidenceMixed effect size6 studies · 5 beneficial · 1 neutral · 0 harmful
Across 6 studies, 5 reported beneficial effects on reducing homocysteine levels, with effect sizes ranging from small to large (mixed). The median study duration was 84 days (12 weeks), indicating effects typically observed at that timeframe. Most studies used doses of 400 μg to 1 mg per day in diverse adult populations, including healthy adults, patients with coronary heart disease, and those with type 2 diabetes.
- Effective dose range: 400 μg to 1 mg per day
Caveats: Some studies used combined B-vitamin supplementation, making it difficult to isolate the effect of vitamin B9 alone. One trial in children with sickle cell disease found no significant effect, suggesting the benefit may not generalize to all populations. Both folic acid and l-5-MTHF forms were effective, but differences between forms remain underexplored.
Generated Jun 12, 2026