Melatonin

The following is an extract from The Life Extension Foundation® (www.lef.org) website

In the Jan. 16, 1997, issue of The New England Journal of Medicine (NEJM), there is a 10 page review article on melatonin . . . the most extensive overview about melatonin that has ever been published in a conventional medical journal.

The NEJM article extols the many virtues of melatonin, including its powerful antioxidant effects, its potential benefit in preventing and treating cancer, its immune enhancement properties, its potential to slow aging, and its ability to promote better sleep and to avoid jet lag.

"There is now evidence," notes the NEJM, "that melatonin may have a role in the biologic regulation of circadian rhythms, sleep, mood, and perhaps reproduction, tumor growth and aging. . . ."

Here are verbatim excerpts from the NEJM article:

Effects on Cancer

"There is evidence from experimental studies that melatonin influences the growth of spontaneous and induced tumors in animals. Pinealectomy enhances tumor growth, and the administration of melatonin reverses this effect or inhibits tumorigenesis caused by carcinogens.

Free Radical Scanvenging

"Both in vitro studies and in vivo studies have shown that melatonin is a potent scavenger of the highly toxic hydroxyl radical and other oxygen-centered radicals, suggesting that it has actions not mediated by receptors. In one study, melatonin seemed to be more effective than other known antioxidants (e.g., mannitol, glutathione, and vitamin E) in protecting against oxidative damage.

Therefore, melatonin may provide protection against diseases that cause degenerative or proliferative changes by shielding macromolecules, particularly DNA, from such injuries. However, these antioxidant effects require concentrations of melatonin that are much higher than peak nighttime serum concentrations. Thus, the antioxidant effects of melatonin in humans probably occur only at pharmacologic concentrations."

(Editor's Note: The NEJM defines pharmacological doses of melatonin as 1-5 mg a night.)

Immune Function

"Melatonin may exert certain biologic effects (such as the inhibition of tumor growth and counteraction of stress-induced immunodepression) by augmenting the immune response. Studies in mice have shown that melatonin stimulates the production of interleukin-4 in bone marrow T-helper cells and of granulocyte-macrophage colony-stimulating factor in stromal cells, as well as protecting bone marrow cells from apoptosis induced by cytotoxic compounds. The purported effect of melatonin on the immune system is supported by the finding of high-affinity (Kd, 0.27 nM) melatonin receptors in human T lymphocytes (CD4 cells) but not in B lymphocytes."

Impact on Sleep

". . . Ingestion of melatonin affects sleep propensity (the speed of falling asleep), as well as the duration and quality of sleep, and has hypnotic effects. In young adults, oral administration of 5 mg of melatonin caused a significant increase in sleep propensity and the duration of rapid-eye-movement (REM) sleep. In other studies, sleep propensity was increased in normal subjects given much lower doses of melatonin (0.1, 0.3, or 1 mg), either in the daytime or in the evening, and sleepiness in the morning was not increased. The time to the maximal hypnotic effect varies linearly from about three hours at noon to one hour at 9 p.m. The administration of melatonin for three weeks in the form of sustained-release tablets (1 mg or 2 mg per day) may improve the quality and duration of sleep in elderly persons with insomnia.

"These results indicate that increasing serum melatonin concentrations (to normal nighttime values or pharmacologic values) can trigger the onset of sleep, regardless of the prevailing endogenous circadian rhythm. The hypnotic effect of melatonin may thus be independent of its synchronizing influence on the circadian rhythm and may be mediated by a lowering of the core body temperature. This possibility is supported by the observations that the circadian cycle of body temperature is linked to the 24-hour cycle of subjective sleepiness and inversely related to serum melatonin concentrations and that pharmacologic doses of melatonin can induce a decrease in body temperature. However, physiologic, sleep-promoting doses of melatonin do not have any effect on body temperature. Alternatively, melatonin may modify brain levels of monoamine neurotransmitters, thereby initiating a cascade of events culminating in the activation of sleep mechanisms... .

A Role in Aging

"The decrease in nighttime serum melatonin concentrations that occurs with aging, together with its multiple biologic effects, has led several investigators to suggest that melatonin has a role in aging and age-related diseases. Studies in rats and mice suggest that diminished melatonin secretion may be associated with an acceleration of the aging process. Melatonin may provide protection against aging through attenuation of the effects of cell damage induced by free radicals or through immuno-enhancement. However, the age-related reduction in nighttime melatonin secretion could well be a consequence of the aging process rather than its cause, and there are no data supporting an anti aging effect of melatonin in humans."

Please Note ...

For more detailed information on Melatonin, please access the Life Extension Foundation web-site http://www.lef.org/