Vitamin B₁₂ treatment for delayed sleep phase syndrome: A multi‐center double‐blind study

Abstract

The active form of vitamin B12 (methylcobalamin) has been reported to be effective on sleep‐wake rhythm disorders. Previous studies, however, were performed under open trial, and the effect of vitamin B12 has not been properly evaluated. The aim of this double‐blind study was to investigate the efficacy of methylcobalamin on delayed sleep phase syndrome (DSPS). Methylcobalamin (3 mg/day) or placebo was administered for 4 weeks. The subjects were 50 patients with DSPS aged 13–55 years (26.8 ± 1.3), 27 of whom received the active drug while 23 received the placebo. No significant differences were observed between the 2 groups in subjective evaluations of mood or drowsiness during the daytime or in night sleep by sleep‐log evaluation. These results indicate that 3 mg methylcobalamin administered over 4 weeks is not an effective treatment for DSPS.

Therapeutics for Circadian Rhythm Sleep Disorders

“…Similar success has been reported in several individual cases [24]. However, administration of 1 mg methylcobalamin 3 times per day after each meal for 4 weeks alone did not show improvements compared to placebo, which suggests that its effects may be dependent on its interaction with light [25]. Therefore, there is insufficient evidence to support vitamin B12 as a treatment for DSPD [10].…”

“…There is very limited evidence that methylcobalamin (vitamin B12) when combined with bright light in the morning may be effective for the treatment of DSPD [22-25]. Findings that vitamin B12 injected intravenously (0.5 mg/day) at 12:30 pm for 11 days, followed by oral administration (2 mg 3 times per day) for 7 days increased the phase shift induced with a single morning exposure to bright light led to further examination of its effectiveness in treating CRSDs [22].…”

Clinical Practice Guideline for the Treatment of Intrinsic Circadian Rhythm Sleep-Wake Disorders: Advanced Sleep-Wake Phase Disorder (ASWPD), Delayed Sleep-Wake Phase Disorder (DSWPD), Non-24-Hour Sleep-Wake Rhythm Disorder (N24SWD), and Irregular Sleep-Wake Rhythm Disorder (ISWRD). An Update for 2015

“…In a multicenter study 97 that contained predominantly adult DSWPD patients (n = 50, mean age 26.8 ± 1.3 years), participants received 3 mg total daily dose of vitamin B12 (three times daily divided dosing) versus placebo (double-blinded) for a period of 4 weeks. No clinically significant differences were observed with respect to subjectively assessed TST and SOT (see Table 2 and Appendix, Table S5).…”

Daily expression of clock genes in whole blood cells in healthy subjects and a patient with circadian rhythm sleep disorder

“…Usually, these patients receive various therapies, including light treatment (7,18,19,33,46), physical exercise treatment (24), and administration of vitamin B 12 (25,27,28) and melatonin (21,29,41) to adjust the circadian rhythm. Presently, it is considered that the markers of circadian rhythm for these patients are the profiles of plasma melatonin, cortisol, and retinal temperature.…”