Melatonin
What is it? Overview Usage Side Effects and Warnings
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Melatonin Side Effects and Warnings

Safety Issues

A safety study found that melatonin at a dose of 10 mg daily produced no toxic effects when given to 40 healthy males for a period of 28 days. 1 However, this does not prove that melatonin is safe when taken on a regular basis over the long term. Keep in mind that melatonin is not truly a food supplement but a hormone. As we know from other hormones used in medicine, such as estrogen and cortisone, harmful effects can take years to appear. Hormones are powerful substances that have many subtle effects in the body, and we're far from understanding them fully. While in one small study, use of melatonin over an 8-day period by healthy men did not affect natural release of melatonin or levels of pituitary or sex hormones, 2 another study found effects on testosterone and estrogen metabolism in men and possible impairment of sperm function. 3 Also, a small study in women found possible effects on the important female hormone called LH (luteinizing hormone). 4 Melatonin appears to cause drowsiness and decreased mental attention for about 2 to 6 hours after using it and may also impair balance. 5 For this reason, you should not drive or operate machinery for several hours after taking melatonin. In a study of healthy middle-aged and older adults, however, an extended release version of melatonin, which is said to more closely mimic natural fluctuations of the hormone in the body, did not impair mental ability or driving skills 1 to 4 hours later compared to placebo. 6 In either case, melatonin does not appear to have any "hangover" effects the following day. 7 Based on theoretical ideas of how melatonin works, some authorities specifically recommend against using it in people with depression, schizophrenia, autoimmune diseases, and other serious illnesses. One study in postmenopausal women found evidence that melatonin might impair insulin action and glucose tolerance, suggesting that people with diabetes should not use it. 8 However, another study found melatonin safe and effective for people with diabetes. 9 Because of these contradictions, we suggest that individuals with diabetes seek physician supervision before using melatonin.

Two exceedingly preliminary studies reported by one research group has led to publicized concerns that use of the supplement melatonin might increase night-time asthma. 10 However, one double-blind study of melatonin in people with asthma found evidence of improved sleep without worsening of symptoms. 11 Again, at the current state of knowledge, caution must be advised for people with night-time asthma who wish to try melatonin.

There is some evidence that melatonin may interfere with the ability of blood to clot normally, at least in healthy volunteers, 12 though the clinical significance of this finding is at yet unknown.

Maximum safe dosages for young children, pregnant or nursing women, or those with serious liver or kidney disease have not been established.

References

  1. de Lourdes M, Seabra V, Bignotto M, et al. Randomized, double-blind clinical trial, controlled with placebo, of the toxicology of chronic melatonin treatment. J Pineal Res. 2000;29:193-200.
  2. Rajaratnam SM, Dijk DJ, Middleton B, et al. Melatonin phase-shifts human circadian rhythms with no evidence of changes in the duration of endogenous melatonin secretion or the 24-hour production of reproductive hormones. J Clin Endocrinol Metab. 2003;88:430-39.
  3. Luboshitzky R, Shen-Orr Z, Nave R, Lavi S, Lavie P. Melatonin administration alters semen quality in healthy men. J Androl. 23(4):572-8.
  4. Kripke DF M D, Kline LE D O, Shadan FF M D Ph D, et al. Melatonin effects on luteinizing hormone in postmenopausal women: A pilot clinical trial NCT00288262. BMC Womens Health. 2006 May 16 [Epub ahead of print].
  5. Graw P, Werth E, Kräuchi K, Gutzwiller F, Cajochen C, Wirz-Justice A. Early morning melatonin administration impairs psychomotor vigilance. Behav Brain Res. 121(1-2):167-72.
  6. Otmani S, Demazières A, Staner C, Jacob N, Nir T, Zisapel N, Staner L. Effects of prolonged-release melatonin, zolpidem, and their combination on psychomotor functions, memory recall, and driving skills in healthy middle aged and elderly volunteers. Hum Psychopharmacol. 23(8):693-705.
  7. Paul MA, Brown G, Buguet A, Gray G, Pigeau RA, Weinberg H, Radomski M. Melatonin and zopiclone as pharmacologic aids to facilitate crew rest. Aviat Space Environ Med. 72(11):974-84.
  8. Cagnacci A, Arangino S, Renzi A, et al. Influence of melatonin administration on glucose tolerance and insulin sensitivity of postmenopausal women. Clin Endocrinol (Oxford). 2001;54:339-346.
  9. Garfinkel D, Wainstein J, Halabe A, et al. Beneficial effect of controlled release melatonin on sleep quality and hemoglobin A1C in type 2 diabetic patients. Presented at: World Congress of Gerontology; July 1-6, 2001; Vancouver, Canada.
  10. Sutherland ER, Ellison MC, Kraft M, Martin RJ. Elevated serum melatonin is associated with the nocturnal worsening of asthma. J Allergy Clin Immunol. 112(3):513-7.
  11. Campos FL, da Silva-Júnior FP, de Bruin VM, de Bruin PF. Melatonin improves sleep in asthma: a randomized, double-blind, placebo-controlled study. Am J Respir Crit Care Med. 170(9):947-51.
  12. Wirtz PH, Spillmann M, Bärtschi C, Ehlert U, von Känel R. Oral melatonin reduces blood coagulation activity: a placebo-controlled study in healthy young men. J Pineal Res. 44(2):127-33.
 
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