Moderate evidenceVitamins & minerals

Methylated B-Complex

B-complex using 5-MTHF and methylcobalamin instead of folic acid and cyanocobalamin. The active forms do raise folate status effectively, but the popular claim that MTHFR carriers need them is not supported by outcome trials.

Evidence last reviewed: August 2026

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What the science says

Active folate raises folate status as well as folic acid Moderate evidence
A systematic review and meta-analysis in women of childbearing age found the active form of folate improved folate biochemical parameters comparably to folic acid, with less unmetabolised folic acid in circulation. Comparative trials confirm both forms raise serum and red cell folate.
No proven clinical advantage for MTHFR variants Limited evidence
Direct comparisons show differences in folate species in blood after supplementation, but no randomized trial has shown better health outcomes from methylfolate in people carrying MTHFR C677T. The genotype-based recommendation runs ahead of the evidence.
B vitamins and cognition Limited evidence
A systematic review and meta-analysis of B vitamin supplementation in older adults found no reliable improvement in global cognitive function despite lowered homocysteine. Lowering a marker is not the same as protecting the brain.

Dosage & safety

Studied doseTypical products supply 400–800 µg of (6S)-5-methyltetrahydrofolate and 500–1,000 µg of methylcobalamin, with B6 usually 1.3–25 mg. Pregnancy folate requirements are met by 400–800 µg/day of either form.

SafetyHigh-dose B6 above roughly 50 mg/day taken long term can cause peripheral neuropathy. Folate in any form can mask B12 deficiency anaemia while nerve damage progresses, so check B12 first. Some people report irritability or insomnia with methylated forms; B vitamins also interact with methotrexate, levodopa and some anticonvulsants.

Scientific references

The effectiveness and safety of the active form of folate on biochemical parameters in women of childbearing age: A systematic review and meta-analysis
Xie M, Qing X, Huang H — Medicine (Baltimore), 2025
Serum Concentrations of Folate Forms Following Supplementation of Multimicronutrients with 400 µg or 800 µg Mix of (6S)-5-Methyltetrahydrofolate and Folic Acid (1:1) in Women of Childbearing Age
Obeid R, Rube E, Schön C — Mol Nutr Food Res, 2024
Efficacy of B Vitamin Supplementation on Global Cognitive Function in Older Adults: A Systematic Review and Meta-analysis
Berg J, Grant R, Siervo M — Nutr Rev, 2025

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