Entrainment of free-running circadian rhythms by melatonin in blind people.
Level 2 - randomized trial
Placebo-controlled crossover clinical trial
PubMed 11027741 · doi:10.1056/NEJM200010123431503
What was done
Seven totally blind individuals with free-running circadian rhythms participated in a crossover trial comparing 10 mg of daily melatonin against placebo, taken one hour before preferred bedtime for three to nine weeks per phase. Circadian phase was tracked using endogenous melatonin production timing, and sleep parameters were recorded with polysomnography. Three subjects also underwent a stepwise dose-reduction protocol down to 0.5 mg daily over three months.
What was found
Baseline circadian cycles averaged 24.5 hours (range, 24.2 to 24.9) and were unaffected by placebo. During melatonin administration, rhythms entrained to a 24.0-hour cycle in 6 of 7 participants (P<0.001). Post-entrainment, time awake after sleep onset decreased significantly (P=0.05) and sleep efficiency showed a non-significant trend toward improvement (P=0.06). Entrainment persisted at 0.5 mg daily in all 3 subjects tested during dose tapering.
Why it matters
It demonstrates that exogenous melatonin can act as an effective non-photic time cue to synchronize free-running endogenous clocks to the 24-hour day in people without light perception.
Limits
The sample size is very small (n=7 total, n=3 for dose de-escalation). The abstract does not report whether crossover allocation was randomized or double-blinded, sleep efficiency gains did not reach conventional statistical significance (P=0.06), and long-term clinical outcomes like daytime alertness were not quantified.
Cited by
- supports Administering a 0.3 to 0.5 mg dose of melatonin in the evening entrains the circadian clock in blind individuals with non-24-hour circadian rhythm disorder.