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melatonin, tryptophan is hydroxylated to 5-hydroxytryptophan (5-HTP), which in turn is
decarboxylated to 5-hydroxytryptamine (serotonin). Serotonin is converted to the
melatonin precursor and metabolite Nacetylserotonin by the enzyme N-acetyl
transferase. N-acetylserotonin is methylated via the enzyme hydroxyindole-o-
methyltransferase to produce melatonin. Approximately 90 percent of melatonin is cleared
in a single passage through the liver. A small proportion of non-metabolized melatonin is
also excreted in the urine. Commercially available melatonin may be isolated from the
pineal glands of beef cattle or chemically synthesized. However, there is no standard
preparation, making studies very difficult to compare.
- THE AGENCY FOR HEALTHCARE RESEARCH AND QUALITY (AHRQ, part of the U.S.
Department of Health and Human Services) determined in 2004 that: “Evidence suggests
that melatonin is not effective in treating most primary sleep disorders with short-term
use, although there is some evidence to suggest that melatonin is effective in treating
delayed sleep phase syndrome with short-term use. Evidence suggests that melatonin is
not effective in treating most secondary sleep disorders with short-term use. No evidence
suggests that melatonin is effective in alleviating the sleep disturbance aspect of jet lag
and shift-work disorder. Evidence suggests that melatonin is safe with short-term use.”
The AHRQ suggested that the apparent effectiveness of melatonin in alleviating jet lag may
not involve alleviation of the sleep disturbance, but rather, alleviation of the daytime
fatigue associated with jet lag.
- EFFICACY: JET LAG AND SLEEP DISORDERS: Dissenting from the AHRQ, all five sources that
mention melatonin except the federal government (Brown et al., Mischoulon and
Rosenbaum (through Zhdanova, I.V. and Friedman, L.), the Natural Standard, Berkeley
Wellness, the Mayo Clinic and Weil) find melatonin to be effective for jet lag and shift
work adjustment, and all except the federal government and Berkeley Wellness
recommend it for sleep latency (delay in falling asleep), at least in older people. Other
uses of melatonin remain controversial, particularly in cognition maintenance and
