Call for funds to review melatonin

UK scientists claim that funding should be provided to back proper testing of the supplement melatonin, used to relieve jet lag symptoms, so that it can be widely used by the public.

Researchers from the Cochrane Collaboration, which reviews medical treatments, say that there are no purity standards for the supplement, or enough clinical evidence to support its safety, despite the fact that it is very popular in many countries.

Writing in this week's British Medical Journal​, Andrew Herxheimer, emeritus fellow of the UK Cochrane Centre: "It seems that many people and organisations, including governments and armed forces, would benefit from the use of melatonin to reduce jet lag. If use of the drug is in the public interest then public funds should be used to get it properly tested and licensed."​

Melatonin (N-acetyl-5-methoxytryptamine) is a hormone that is produced by the pineal gland in the brain. It is currently available in the US, and some other countries such as Thailand, and Singapore, as a 'dietary supplement' but the available products vary in purity, according to Herxheimer. In Europe, Australia, and many other countries, melatonin is regulated as a medicine and requires a licence, but no licensed preparation is marketed; only the internet offers a grey or black market.

A recent Cochrane review found 10 randomised controlled trials comparing melatonin with placebo in long distance travellers, eight of which found a clear reduction in jet lag when melatonin had been taken, notes Herxheimer in his report. However, the trials used different methods to assess jet lag or its components, observations were made at different times, and most results are reported as group means without data for individual participants, so that they are difficult to combine.

For the two studies reporting individual results, however, for a total of 46 people as many as one in two people using melatonin may benefit. And there are other notable variations in the efficacy of the supplement, said Herxheimer.

Also adverse effects have been reported rarely but have not been looked for systematically. Reports of adverse events, possibly related to use of melatonin, imply that two categories of people should avoid it until more is known: anyone taking warfarin or another oral anticoagulant, and people with epilepsy.

Herxheimer pointed out that no pharmaceutical company wants to pay for the toxicological studies and the data required to obtain a product licence because it cannot have exclusivity. "A finance initiative is urgently needed to solve the problem and might best begin with a cost benefit assessment," he concluded.

In the US, the Committee on the Framework for Evaluating the Safety of Dietary Supplements (charged with assessing ingredients for dietary supplements for the Food and Drug Administration) recently published prototype monographs for three supplements including melatonin, and is asking for comment and contributions to its information.