Melatonin for Jet Lag and Sleep Disorders
Walsh, Nancy, Clinical Psychiatry News
Mechanisms of Action
Melatonin was first described nearly 50 years ago from bovine pineal tissue. Experiments on tadpoles showed that it was a powerful skin-lightening agent that inhibited melanin dispersal in melanocytes (Best Pract. Res. Clin. Endocrinol. Metab. 17:273-85, 2003). It turned out to be ineffective in human epidermis.
This neurohormone is secreted by the pineal gland in all mammals, with secretion increased in darkness and decreased in light.
Signals from the retina reach the anterior hypothalamus via the optic nerve, and the retinal axons terminate in the suprachiasmatic nuclei, which function as a biological clock or circadian pacemaker (J. Biol. Rhythms 12:489-97, 1997).
Its precursor is the amino acid L-tryptophan, which is transported across cell membranes and converted to serotonin. In its regulatory capacity, melatonin controls cortical secretion, sleep patterns, and core body temperature. It decreases sleep latency, improves sleep efficiency, and can increase sleep propensity by slightly lowering body temperature.
In cell culture and animal models, melatonin also has been shown to exert antioxidant, immune stimulating, and antiproliferative effects.
A recent Cochrane Review identified 10 placebo-controlled trials of melatonin for jet lag. In nine of the studies, melatonin improved symptoms of jet lag caused by flights crossing five or more time zones when taken close to the target bedtime at the destination. Daily doses in the studies ranged from 0.5 mg/day to 5 mg/day, with greater efficacy seen at higher doses. A slow-release 2-mg formulation was not as effective, suggesting that a short-lived peak is more beneficial.
The reviewers concluded that "melatonin is remarkably effective in preventing or reducing jet lag, and occasional short-term use appears to be safe" (Cochrane Database Syst. Rev. 2:CD001520, 2002).
The reviewers noted that melatonin can be particularly beneficial for people who have had jet lag in the past and who are flying in an easterly direction. Timing of the dose is important, because if taken early in the day it can cause sleepiness and a delay in adaptation to the local time.
Finally, they recommended that pharmaceutical-grade quality control be adopted, and that further studies into pharmacology and toxicology be done.
Melatonin levels decline with age, a fact that has spurred interest in its exogenous administration for age-associated sleep and cognitive disorders. In a double-blind, placebo-controlled pilot study, 26 healthy elderly adults were randomized to receive 1 mg melatonin or placebo each night for 4 weeks. They completed a sleep questionnaire and were given a series of tests of cognitive function at baseline and after 4 weeks.
Those given melatonin reported improved sleep latency and morning "restedness," and had higher scores on the California Verbal Learning Test (Am. …