Science Criticism

Melatonin: How Strong Is the Evidence for Morpheus-in-a-Bottle?

While my body embraces rest, my mind, despite its organic roots, plows on ahead. It foregoes running and projects itself at stressful speeds, branching out and accelerating, carrying my heart beat with it. The pillow is only slowly warming up. The time is 1:30 AM.

I have learned to protect myself against insomnia but, once in a while, the temptation to forego what is funnily referred to as “sleep hygiene” is too difficult to overcome. That’s nothing: a friend of mine works nights and switches to something approaching a day schedule every weekend. But don’t worry, there’s a pill for that.

Despite being a hormone, melatonin is readily available over the counter in both Canada and the United States. It is classified as a dietary supplement, although it cannot be found in the food items we eat nor is it supplementing morbidly low melatonin levels in our bodies. It is claimed that melatonin can reduce the sleep onset latency—the time it takes to fall asleep—and increase sleep efficiency—the amount of bedtime actually spent sleeping. It is being promoted as a safe cure for jet lag and shift work and supposedly works wonders against basic insomnia. Is there any evidence for these claims?

When investigating assertions of the sort, two important questions need to be asked: can it work and does it work? The first question is mechanistic: does our current understanding of science provide us with a hypothetical mechanism by which this substance could produce the effect that is claimed? In the case of melatonin, the answer is yes. Melatonin is not just a pill; it’s a hormone that is naturally produced by the body and is linked to the onset of sleep in diurnal animal species. Indeed, melatonin levels in the blood of human beings increases ten-fold at night compared to daytime levels, so there is a reason to believe that exogenous melatonin—that is, melatonin of external origin—could potentially fix a melatonin-related sleep disorder. If your iron levels are low, take an iron supplement; likewise, if you have difficulty falling asleep, one may wonder if you are suffering from a melatonin deficiency. The use of exogenous melatonin passes the first skeptical test. That is not to say that insomnia is caused by low levels of melatonin, but one can think up a theoretical framework within which over-the-counter melatonin pills could work.

The second question to ask is “does it work?” and this is where the claim flounders. The studies that have looked at the effect of administering exogenous melatonin to treat a variety of sleep disorders have varied in quality, used differing amounts of the hormone, and produced mixed results. Reviews have been conducted which have taken into consideration the strength of these studies to evaluate the state of our knowledge regarding melatonin “supplements”. Even looking at the best studies, the evidence for sleep improvement is weak.

A review published by the Agency for Healthcare Research and Quality in the United States in 2004 found a reduction in the time it takes to fall asleep and an increase in sleep efficiency, neither of which were deemed “clinically significant”1. Indeed, a year later, a review published in Sleep Medicine Research looking at 17 studies (for a total of 284 subjects) showed a reduction of sleep onset latency by 2.5 to 5.4 minutes (95% confidence interval)2. Similarly, the increased sleep efficiency—bedtime spent sleeping divided by total bedtime—was a mere 0.2 to 4.2%. The increased total sleep duration across all these studies was between 2.9 and 22.8 minutes. We are a far cry from an insomnia panacea.

Interestingly enough, the Cochrane Collaboration, well known for its objectivity and the quality of its systematic reviews, concluded that “melatonin is remarkably effective in preventing or reducing jet lag”, becoming more effective the greater the number of time zones one travels through3. Meanwhile, a 2006 review showed no evidence for melatonin influencing sleep onset latency in people with secondary sleep disorders (in which the insomnia is due to a mental or physical problem) or in individuals experiencing sleep restriction (such as shift workers)4. A very recent review looking at 19 studies (a total of 1683 participants) showed that, in people with primary insomnia, the time to fall asleep was reduced by 4.37 to 9.75 minutes with exogenous melatonin, an effect the authors characterized as “significant”, although I fail to see how falling asleep up to 10 minutes faster represents a victory5. Statistical significance (with a p value below 0.05) is clearly acknowledged as the first hurdle to overcome in scientific publishing, so much so that clinical significance and common sense can get thrown out the window.

For what it is worth, the use of exogenous melatonin does seem to be relatively safe, in the short term at least. In very high doses, it could create a hangover and may even desensitize melatonin receptors, thus leading to more insomnia. The Cochrane review suggests that exogenous melatonin’s effect on people suffering from epilepsy and its potential interaction with warfarin, a clot formation inhibitor, should be investigated. Other than that, melatonin seems safe. Its impact on sleep in people suffering from insomnia or shift work does however seem to be minimal at best. Many studies have shown no effect at all; when there is improvement, it is incredibly mild.

Given the present data, I fail to see how melatonin could be of use to people suffering from insomnia or shift work. It may be easily available but, if it doesn’t work, it’s wasted money.

 

(Feature picture by RobArthur2908)

 

1. Buscemi N, Vandermeer B, Pandya R, Hooton N, Tjosvold L, Hartling L, Baker G, Vohra S, Klassen T. 2004. Melatonin for treatment of sleep disorders. Evid Rep Technol Assess (Summ) (108):1-7. Text available here.

2. Brzezinski A1, Vangel MG, Wurtman RJ, Norrie G, Zhdanova I, Ben-Shushan A, Ford I. 2005. Effects of exogenous melatonin on sleep: a meta-analysis. Sleep Med Rev 9(1):41-50. Text available here.

3. Herxheimer A, Petrie KJ. 2002. Melatonin for the prevention and treatment of jet lag. Cochrane Database of Systematic Reviews, Issue 2. Art. No.: CD001520. DOI: 10.1002/14651858.CD001520.

4. Buscemi N1, Vandermeer B, Hooton N, Pandya R, Tjosvold L, Hartling L, Vohra S, Klassen TP, Baker G. 2006. Efficacy and safety of exogenous melatonin for secondary sleep disorders and sleep disorders accompanying sleep restriction: meta-analysis. BMJ 18;332(7538):385-93. Text available here.

5. Ferracioli-Oda E1, Qawasmi A, Bloch MH. 2013. Meta-analysis: melatonin for the treatment of primary sleep disorders. PLoS One 17;8(5):e63773. Text available here.

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