Honma · Experientia 1992 · single-blind placebo-controlled crossover trial · n=9

Effects of vitamin B12 on plasma melatonin rhythm in humans: increased light sensitivity phase-advances the circadian clock?

Cited 57 times in the scientific literature.

Level 3 - non-randomized controlled study

Single-blind controlled crossover trial; randomization is not specified in the abstract.

PubMed 1516676 · doi:10.1007/BF02124286 · record verified 2026-08-29

What was done

Nine healthy subjects completed a subject-blinded crossover trial receiving oral vitamin B12 (methylcobalamin, 3 mg/day) or placebo for 4 weeks. Plasma melatonin levels over 24 hours, nocturnal melatonin levels after bright light exposure (approximately 2500 lx), and sleep timing were measured.

What was found

The 24-hour plasma melatonin rhythm phase-advanced by 1.1 hours during the vitamin B12 trial compared with placebo. The 24-hour mean plasma melatonin concentration and nocturnal melatonin levels during bright light exposure were significantly lower with vitamin B12 than with placebo (exact values not provided in the abstract). Vitamin B12 did not alter sleep timing.

Why it matters

This study provides early preliminary evidence that high-dose methylcobalamin may influence circadian rhythm regulation and enhance human circadian light sensitivity.

Limits

The study is constrained by a very small sample size (n = 9), lack of reported confidence intervals or numerical baseline values, unclear randomization details, and absence of an observed functional shift in sleep timing.

Cited by