Pentieva · The Journal of nutrition 2004 · randomized double-blind crossover trial · n=13

The short-term bioavailabilities of [6S]-5-methyltetrahydrofolate and folic acid are equivalent in men.

Cited 70 times in the scientific literature.

Level 2 - randomized trial

Individual randomized crossover trial

PubMed 14988450 · doi:10.1093/jn/134.3.580 · record verified 2026-08-26

What was done

In a double-blind, randomized crossover trial, 13 men presaturated with folic acid received three single oral treatments in random order at 1-week intervals: placebo capsule, 500 µg folic acid (FA) capsule, and 500 µg [6S]-5-methyltetrahydrofolate ([6S]-5-MTHF) capsule. Total plasma folate concentrations were measured before and at multiple time points up to 10 hours after each treatment (10 samples per treatment).

What was found

Plasma folate concentrations increased significantly from 0.5 to 5 hours after both active treatments compared to baseline. Maximum plasma folate response did not differ significantly between treatments (mean ± SEM: 33.4 ± 3.9 nmol/L for FA vs. 31.8 ± 3.9 nmol/L for [6S]-5-MTHF, P = 0.7) and peaked between 0.5 and 3 hours postprandially. The area under the plasma folate response curve was significantly greater after both folate treatments compared with placebo, with no difference between the two active treatments.

Why it matters

Single-dose [6S]-5-MTHF shows short-term bioavailability equivalent to synthetic folic acid. This provides support for [6S]-5-MTHF as an alternative supplement that may avoid the potential disadvantage of masking vitamin B-12 deficiency anemia.

Limits

The study sample was small (n = 13) and limited exclusively to men who were pre-saturated with folic acid. The trial assessed only acute pharmacokinetic response over 10 hours after a single dose and did not assess long-term supplementation outcomes, tissue status, or efficacy in women or folate-deficient individuals.

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