Many older Americans purchase the hormone melatonin and take it orally, nightly, to promote sleep onset and to help them fall back asleep after the frequent nocturnal awakenings associated with ageing. This need for exogenous melatonin reflects the fact that the progressive calcification of the human pineal diminishes the organ’s ability to secrete its hormone, so that instead of plasma melatonin levels rising normally by 10-fold or more around bedtime the rise may be only by twofold, or even less. The quantity of melatonin that most ageing people need to restore nocturnal plasma melatonin levels to what they are in youth – and, concurrently, to promote sleep – is tiny, only about 0.2–0.5 mg. However, this dosage is generally unavailable, so patients may take doses 10-fold greater, or more, producing side-effects (e.g., hypothermia; hypoprolactinaemia; morning grogginess) and ultimately desensitising melatonin receptors in the brain. The reasons why low-dose melatonin is generally unavailable are described and a strategy is proposed for enabling patients to consume the correct dosage even when preparations containing that dosage cannot be obtained.
Melatonin, calcified pineal, ageing, sleep, nocturnal awakenings, sleep latency, melatonin receptors, gamma-aminobutyric acid (GABA) receptors, hypothermia, hyperprolactinaemia
Richard J Wurtman is a member of staff at the Massachusetts Institute of Technology (MIT). MIT holds patents on the use of melatonin to promote and sustain sleep. Dr Wurtman receives royalties from these patents, all of which are donated back to the MIT. All of the research in Dr Wurtman’s laboratory described in this article has been supported exclusively by the US National Institutes of Health.
May 08, 2012
May 22, 2012
Richard J Wurtman, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, 77 Mass Ave, Bldg 46-5009, Cambridge, MA 02139, US. E: email@example.com
Although very 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 about its generally minor side-effects, both of which are obligatory for hypnotic drugs.
This reflects the fact that, from a regulatory standpoint, exogenous melatonin is classified not as a drug but as a ‘dietary supplement’ – even though it remains to be proved that any food actually contains more than trace amounts of real melatonin, or that consumption of any food actually elevates plasma melatonin levels. By virtue of the Dietary Supplement Health and Education Act of 1994, dietary supplements are regulated as though they are foods (which do not require prior FDA approval), rather than as drugs, so long as their marketers make only ‘structure or function claims’ relating to their effects on normal people, and do not promote them for treating disease states. Supplements are not subject to the safety and efficacy testing requirements imposed on drugs, and the FDA may take action against their sale only after they have been shown to be unsafe (which, fortunately, has not been the case for melatonin).
Very recently, an official regulatory body – the European Food Safety Authority (EFSA) – has evaluated the available evidence that melatonin can reduce the time it takes for normal sleepers and patients with insomnia to fall asleep.1 It concluded that the evidence from all three of the statistically valid published meta-analyses2,3,4 affirms “a cause and effect relationship… between the consumption of melatonin and [a] reduction of sleep onset latency…”, and that “. 1 mg of melatonin should be consumed close to bedtime…”1 Such recommendations usually win approval by the European Commission and its member states, a process that generally requires about six months. This recommendation should also help American physicians in dealing with patients’ questions about melatonin’s safety, and deciding which of the doses currently marketed is best for them. However, as described below, most Americans have little or no access to the low, maximally effective melatonin dosesrecommended in the EFSA report and the meta-analyses (not more than 1 mg) because, absent FDA regulation, most stores stock melatonin only in doses as much as ten- to thirty-times greater.
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