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Sleep Disorders Editorial Low Doses of Melatonin Promote Sleep Onset and Maintenance in Older People—An Update Richard J Wurtman, MD Massachusetts Institute of Technology, Cambridge, Massachusetts, US Abstract Plasma melatonin levels in young adults are about 10-fold higher during the night than during daylight hours, and these high levels promote both the onset of sleep at bedtime and the speedy resumption of sleep after premature nocturnal awakenings. With aging, melatonin’s nocturnal secretion from the pineal gland declines, as do plasma melatonin levels, total sleep time, and sleep efficiency. A very small dose (0.3 mg) of melatonin is usually sufficient to restore nighttime plasma melatonin levels to those characteristic of young people, and to accelerate the resumption of sleep after premature awakenings. The much larger doses that are marketed can produce side effects that are not observed when the melatonin in the plasma derives solely from its secretion by the pineal. Very high doses may also desensitize melatonin’s receptors in the brain, subsequently diminishing melatonin’s efficacy in promoting sleep. This article updates an earlier summary (Richard J Wurtman, Use of melatonin to promote sleep in older people, US Neurology, 2012;8(1):10–1) of melatonin’s utility in promoting sleep among older people. Keywords Melatonin, sleep, insomnia, desensitization, melatonin receptors, FDA Disclosure: Richard J Wurtman, MD, has been a short-term consultant to several companies that required advice as to the correct melatonin dose to put in their products: Dreamerz, Healthy Directions, and Nature’s Bounty, but no longer has formal relations with any of them. Similarly, Massachusetts Institute of Technology (MIT) formerly owned US patents on his discoveries relating melatonin dose to sleep; however, these patents have all expired. All of his melatonin research has been fully and exclusively supported by the US National Institutes of Health. No funding was received for the publication of this article. Received: September 2, 2014 Accepted: September 18, 2014 Citation: US Neurology, 2014;10(2):117–9 Correspondence: Richard J Wurtman, MD, Massachusetts Institute of Technology, 77 Mass Ave, 46-5009, Cambridge, MA 02139 US. E: dick@mit.edu Many older people purchase the hormone melatonin and consume it orally, each evening, to promote the onset of sleep at bedtime and, particularly, the resumption of sleep after premature nocturnal awakenings. This need for exogenous melatonin to supplement that secreted from the aging pineal arises from the gland’s progressive, age- related calcification, which decreases the number of active pineal cells, causing parallel reductions in melatonin’s synthesis and secretion. 1–3 In younger people, plasma melatonin levels generally are about 8-10 pcg/ml during the daytime hours when little melatonin is secreted, quickly rise to 100–200 pcg/ml with the onset of darkness, and remain at around that level until daybreak. With aging, plasma melatonin levels may be slightly lower during the daylight hours, however, nighttime levels are markedly reduced, usually rising only to 20–50 pcg/ml. 4 A single bedtime dose of 0.2–0.5 mg of melatonin will restore nighttime levels to those of younger people for several hours; 4,5 however, this dosage is not stocked in most pharmacies, so patients usually have little choice but to take the much higher doses (e.g. 3–10  mg) that are available. As discussed below, the very high doses may actually exacerbate insomnia in some people, by desensitizing the melatonin receptors on the brain neurons that mediate the hormone’s sleep-promoting effects. Moreover such doses may © TO U CH MED ICA L MEDIA 201 4 also produce side effects (hypothermia, 4 hyperprolactinemia, 6 morning grogginess 5 ), which rarely, if ever, occur with endogenous melatonin secretion. Even with access to low melatonin dosages, it is still difficult, using melatonin supplements, for older people to reproduce the normal ‘square-wave’ pattern of plasma melatonin levels observed in younger people, i.e. the sudden, 10-fold-or-greater rise around 9–11  PM and the similar fall around daybreak. Doses that are high enough to produce satisfactory elevations in nocturnal plasma levels throughout the night usually cause plasma levels initially to peak well beyond their normal range, thus risking desensitization of the melatonin receptors. Some possible strategies for obviating this problem were described previously (Richard J Wurtman, Use of melatonin to promote sleep in older people, US Neurology, 2012;8(1):10–1) and additional ones are discussed below. Regulatory Considerations in the Availability of Oral Melatonin Although large numbers of older Americans purchase the hormone melatonin and take it nightly to promote and sustain sleep, the US Food and Drug Administration (FDA) does not require that consumers be provided with guidelines concerning its proper dosage, nor information 117