Melatonin

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• Drug interactions

Melatonin is a natural hormone that regulates the human biological clock.

Where is it found?

Melatonin is produced by the pineal gland, located within the brain. Levels of melatonin in the body fluctuate with the cycles of night and day. The highest melatonin levels are found at night. Melatonin is present in foods only in trace amounts.

Health Concerns

Melatonin has been used in connection with the following conditions (refer to the individual health concern for complete information):

Rating	Health Concerns
	Angelman's syndrome (sleep disturbances only) Cluster headaches Colon cancer Depression Insomnia Irritable bowel syndrome (for abdominal pain only) Jet lag Macular degeneration Schizophrenia (for sleep disturbances only) Sunburn Tardive dyskinesia Tinnitus (insomnia-associated)
	Age-related cognitive decline Breast cancer Epilepsy Fibromyalgia Glaucoma Lung cancer Migraine headaches Myoclonus Prostate cancer Sarcoidosis
Reliable and relatively consistent scientific data showing a substantial health benefit. Contradictory, insufficient, or preliminary studies suggesting a health benefit or minimal health benefit. An herb is primarily supported by traditional use, or the herb or supplement has little scientific support and/or minimal health benefit.

Deficiency Symptoms

Who is likely to be deficient?

Although elderly people often have difficulty sleeping¹ and melatonin supplements have been shown to improve sleep in the elderly,² melatonin secretion does not appear to decline in healthy older adults to a significant degree, despite many preliminary reports to the contrary.³ Most of these preliminary studies failed to verify that older subjects were healthy and not using drugs that suppress melatonin secretion (e.g., aspirin, ibuprofen, beta-blockers). Routine replacement of melatonin in elderly persons is, therefore, not recommended.

Adults with insomnia have been shown to have lower melatonin levels.⁴ Frequent travelers and shift workers are also likely to benefit from melatonin for the resynchronization of their sleep schedules,⁵ though a melatonin "deficiency" as such does not exist for these people. Patients with heart disease have been reported to have low melatonin levels, but whether this abnormality increases the risk of heart disease or whether heart disease leads to the low melatonin level is not yet known.⁶ People with schizophrenia were found to have low melatonin output and experienced significantly improved sleep following melatonin replacement supplementation.⁷

Dosage

How much is usually taken?

Normally, the body secretes melatonin for several hours per night-an effect best duplicated with time-release supplements. Studies using timed-release melatonin for insomnia have reported good results.⁸ Many doctors suggest 1-3 mg of melatonin taken one to two hours before bedtime. Studies with people suffering from sarcoidosis or cancer have used very high amounts of melatonin-typically 20 mg per night. Such levels should never be taken without the supervision of a doctor. Melatonin should not be taken during the day.

Side Effects

Are there any side effects or interactions?

Melatonin is associated with few side effects. However, morning grogginess, undesired drowsiness, sleepwalking, and disorientation have been reported. Researchers have hypothesized that certain people should not use melatonin supplements, including pregnant or breast-feeding women, people with depression or schizophrenia, and those with autoimmune disease, including lupus, at least until more is known.^{9, 10}

In one study, administration of 3 mg per day of melatonin for three months resulted in a marked decline in sperm counts and a decline in sperm quality in two of eight healthy young men.¹¹ In one of these two men, sperm count and quality became normal after melatonin was discontinued. Although this was a small study, it raises the possibility that long-term use of melatonin could lead to infertility.

In a group of children suffering from neurological disorders, 1-5 mg of melatonin per night led to an increase in the rate of seizures despite the fact that sleep improved.¹² Until more is known, children with neurological conditions should take melatonin only under medical supervision.

Many other side effects have been attributed to melatonin supplementation, including inhibition of sex drive, severe headaches, abdominal cramps, and formation of rudimentary breasts in men.^{13, 14} However, these associations have not been supported by solid evidence.^{15, 16, 17, 18} Since none of these claims have been well documented or independently confirmed, these problems may not have been due to melatonin.

Though most research reports that melatonin improves the quality of sleep, at least one trial has found that four of fifteen men given melatonin had their sleep patterns disturbed by supplemental melatonin.¹⁹

One case of painful gynecomastia (enlarged breasts) has been reported involving a 56-year-old man who had been suffering from amyotrophic lateral sclerosis (Lou Gehrig's disease), and was taking 1-2 mg melatonin per day for one and a half years.²⁰ As the signs and symptoms disappeared after melatonin was discontinued, the authors of the report suspected that melatonin caused this side effect.

According to a preliminary report, blood levels of melatonin may be elevated in women with fibromyalgia.²¹ Data in this report did not indicate toxicity from melatonin, nor did the report suggest that melatonin causes or exacerbates the symptoms of fibromyalgia. It did suggest there is no current rationale for melatonin supplementation in people with fibromyalgia.

One-time oral administration of 1 mg of melatonin to post-menopausal women reduced glucose tolerance and insulin sensitivity when tested 45 minutes after administration.²² This finding suggests that people with diabetes should use melatonin with caution and only under the supervision of a doctor.

Are there any drug interactions?

Certain medicines may interact with melatonin. Refer to drug interactions for a list of those medicines.

References

1. Haimov I, Laudon M, Zisapel N, et al. Sleep disorders and melatonin rhythms in elderly people. BMJ 1994;309:167.
2. Singer C, McArthur A, Hughes R, et al. Melatonin and sleep in the elderly. J Am Geriatr Soc 1996;44:51 [abstr #A1].
3. Zeitzer JM, Daniels JE, Duffy JF, et al. Do plasma melatonin concentrations decline with age? Am J Med 1999;107:432-6.
4. Attenburrow MEJ, Dowling BA, Sharpley AL, Cowen PJ. Case-control study of evening melatonin concentration in primary insomnia. BMJ 1996;312:1263-4.
5. Folkard S, Arendt J, Clark M. Can melatonin improve shift workers' tolerance of the night shift? Some preliminary findings. Chronobiol Int 1993;10:315-20.
6. Sakotnik A, Liebmann PM, Stoschitzky K. Decreased melatonin synthesis in patients with coronary artery disease. Eur Heart J 1999;20:1314-7.
7. Shamir E, Laudon M, Barak Y, et al. Melatonin improves sleep quality of patients with chronic schizophrenia. J Clin Psychiatry 2000;61:373-7.
8. Garfinkel D, Laudon M, Nof D, Zisapel N. Improvement of sleep quality in elderly people by controlled-release melatonin. Lancet 1995;346:541-4.
9. Weaver DR. Reproductive safety of melatonin: a "wonder drug" to wonder about. J Biol Rhythms 1997;12:682-9.
10. Arendt J. Safety of melatonin in long-term use(?) J Biol Rhythms 1997;12:673-81.
11. Luboshitzky R, Shen-Orr Z, Nave R, Lavi S, Lavie P. Melatonin administration alters semen quality in healthy men. J Androl 2002;23:572-8.
12. Sheldon SH. Pro-convulsant effects or oral melatonin in neurologically disabled children. Lancet 1998;351:1254.
13. Shannon M. Alternative medicines toxicology: a review of selected agents. Clin Toxicol 1999;37:709-13.
14. Guardiola-Lemaître B. Toxicology of melatonin. J Biol Rhythms 1997;12:697-706.
15. Lamberg L. Melatonin potentially useful but safety, efficacy remain uncertain. JAMA 1996;276:1011-4.
16. Force RW, Hansen L, Badell M. Psychotic episode after melatonin. Ann Pharmacother 1997;31:1408 [letter].
17. Porterfield LM. Can melatonin cause severe headaches? RN 1996;59:75.
18. Bornman MS, Schulenburg GW, Reif S, et al. Seminal plasma melatonin and semen parameters. S Afr Med J 1992;81:485-6.
19. Middleton B. Melatonin and fragmented sleep patterns. Lancet 1996;348:551-2 [letter].
20. De Bleeker JL, Verstraete AG, Schelfhout VJ. Melatonin and painful gynecomastia. Neurology 1999;53:435-6 [letter].
21. Korszun A, Sackett-Lundeen L, Papadopoulos E, et al. Melatonin levels in women with fibromyalgia and chronic fatigue syndrome. J Rheumatol 1999;26:2675-80.
22. Cagnacci A, Arangino S, Renzi A, et al. Influence of melatonin administration on glucose tolerance and insulin sensitivity of postmenopausal women. Clin Endocrinol 2001;54:339-46.

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Last Review: 01-21-2009

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The information presented in Aisle7 is for informational purposes only. It is based on scientific studies (human, animal, or in vitro), clinical experience, or traditional usage as cited in each article. The results reported may not necessarily occur in all individuals. For many of the conditions discussed, treatment with prescription or over the counter medication is also available. Consult your doctor, practitioner, and/or pharmacist for any health problem and before using any supplements or before making any changes in prescribed medications. Information expires February 2010.

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