Vitamin B9 and Increased Folate Level

Research synthesisModerate evidenceLarge effect3 studies · 2 beneficial · 1 neutral · 0 harmful

Across 3 studies, 2 reported beneficial large-sized effects of vitamin B9 supplementation on increasing folate levels, while 1 study on rice fortification showed a small neutral effect. The most-studied dose was 1 mg/day (from a single RCT in healthy women), and effects were typically observed at 12 weeks. Evidence comes primarily from a meta-analysis in patients with phenylketonuria and an RCT in healthy adults.

Effective dose range: 1 mg/day (observed in one study)
Studied populations: healthy adults and individuals with phenylketonuria

Caveats: Evidence base is small (only 3 studies) — conclusions should be considered preliminary. One study assessed rice fortification (combined micronutrients), not direct supplementation, and showed a small non-significant effect. The beneficial RCT used l-5-methyltetrahydrofolate, which may not be representative of all vitamin B9 forms. Median study duration was 84 days, suggesting effects may require at least 12 weeks.

Generated Jun 15, 2026

Doses used in studies

mg/day: 1 (median 1, IQR 1–1) — 1 study

Time to effect

Median: 2.8 months · IQR 2.8 months–2.8 months · Range 2.8 months–2.8 months — Reported in 1 of 3 studies

3 of 3 papersPopulation:

Vitamin Status in Patients with Phenylketonuria: A Systematic Review and Meta-Analysis.
- 2024-05-07
- Meta-Analysis · n = 770
- International journal of molecular sciences 25(10)
- - Kamila Bokayeva
  - Małgorzata Jamka
  - Dariusz Walkowiak
  - Monika Duś-Żuchowska
  - Karl-Heinz Herzig
  - Jarosław Walkowiak
- PubMed: 38791104
- DOI: 10.3390/ijms25105065
12 Insights on
- Increased Folate Level
- High evidence
- Rigorous Journal
- Clinical
PKU patients demonstrated significantly higher folate levels (random-effects model, SMD: 1.378, 95% CI: 0.436, 2.320, p = 0.004)
Effect
Beneficial
Effect size
Large
Significant
Yes
Fortification of rice with vitamins and minerals for addressing micronutrient malnutrition.
- 2019-10-25
- Meta-Analysis · n = 8,245
- The Cochrane database of systematic reviews 2019(10)
- - Juan Pablo Peña-Rosas
  - Prasanna Mithra
  - Bhaskaran Unnikrishnan
  - Nithin Kumar
  - Luz Maria De-Regil
  - N Sreekumaran Nair
  - Maria N Garcia-Casal
  - Juan Antonio Solon
- PubMed: 31684687
- DOI: 10.1002/14651858.cd009902.pub2
8 Insights on
- Increased Folate Level
- High evidence
- Mixed
One study reported that fortification of rice (with folic acid as one of the micronutrients) may improve serum or plasma folate (nmol/L) (MD 4.30, 95% CI 2.00 to 6.60; 215 participants; low-certainty evidence)
Effect
Neutral
Effect size
Small
Significant
No
Dose
as part of combined micronutrient fortification
l-5-Methyltetrahydrofolate Supplementation Increases Blood Folate Concentrations to a Greater Extent than Folic Acid Supplementation in Malaysian Women.
- 2018-06
- RCT · n = 142
- The Journal of nutrition 148(6)
- - Amanda M Henderson
  - Rika E Aleliunas
  - Su Peng Loh
  - Geok Lin Khor
  - Sarah Harvey-Leeson
  - Melissa B Glier
  - David D Kitts
  - Tim J Green
  - Angela M Devlin
- PubMed: 29878267
- DOI: 10.1093/jn/nxy057
15 Insights on
- Increased Folate Level
- High evidence
- Large Human Trial
- Adults
The l-5-MTHF group had higher (P < 0.001) plasma folate [median (25th, 75th percentiles): 52.0 nmol/L (42.7, 73.1 nmol/L)] ... compared with ... placebo group at 12 wk.
Effect
Beneficial
Effect size
Large
Significant
Yes
Dose
1.13 mg/day

Vitamin B9 and Increased Folate Level

Vitamin Status in Patients with Phenylketonuria: A Systematic Review and Meta-Analysis.

Fortification of rice with vitamins and minerals for addressing micronutrient malnutrition.

l-5-Methyltetrahydrofolate Supplementation Increases Blood Folate Concentrations to a Greater Extent than Folic Acid Supplementation in Malaysian Women.