Date: December 10th, 2018 9:24 PM
Author: Flushed legal warrant hall
What is the right dose of melatonin?
0.3 mg.
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“But my local drugstore sells 10 mg pills! When I asked if they had anything lower, they looked through their stockroom and were eventually able to find 3 mg pills! And you’re saying the correct dose is a third of a milligram?!”
Yes. Most existing melatonin tablets are around ten to thirty times the correct dose.
Many early studies were done on elderly people, who produce less endogenous melatonin than young people and so are considered especially responsive to the drug. Several lines of evidence determined that 0.3 mg was the best dose for this population. Elderly people given doses around 0.3 mg slept better than those given 3 mg or more and had fewer side effects (Zhdanova et al 2001). A meta-analysis of dose-response relationships concurred, finding a plateau effect around 0.3 mg, with doses after that having no more efficacy, but worse side effects (Brzezinski et al, 2005). And doses around 0.3 mg cause blood melatonin spikes most similar in magnitude and duration to the spikes seen in healthy young people with normal sleep (Vural et al, 2014).
Other studies were done on blind people, who are especially sensitive to melatonin since they lack light cues to entrain their circadian rhythms. This is a little bit of a different indication, since it’s being used more as a chronobiotic than a sleeping pill, but the results were very similar: lower doses worked better than higher doses. For example, in Lewy et al 2002, nightly doses of 0.5 mg worked to get a blind subject sleeping normally at night; doses of 20 mg didn’t. They reasonably conclude that the 20 mg is such a high dose that it stays in their body all day, defeating the point of a hormone whose job is to signal nighttime. Other studies on the blind have generally confirmed that doses of around 0.3 to 0.5 mg are optimal.
There have been disappointingly few studies on sighted young people. One such, Attenburrow et al 1996 finds that 1 mg works but 0.3 mg doesn’t, suggesting these people may need slightly higher doses, but this study is a bit of an outlier. Another Zhdanova study on 25 year olds found both to work equally. And Pires et al studying 22-24 year olds found that 0.3 mg worked better than 1.0. I am less interested in judging the 0.3 mg vs. 1.0 mg debate than in pointing out that both numbers are much lower than the 3 – 10 mg doses found in the melatonin tablets sold in drugstores.
UpToDate, the gold standard research database used by doctors, agrees with these low doses. “We suggest the use of low, physiologic doses (0.1 to 0.5 mg) for insomnia or jet lag (Grade 2B). High-dose preparations raise plasma melatonin concentrations to a supraphysiologic level and alter normal day/night melatonin rhythms.” Mayo Clinic makes a similar recommendation: they recommend 0.5 mg. John Hopkins’ experts almost agree: they say “less is more” but end up chickening out and recommending 1 to 3 mg, which is well above what the studies would suggest.
Based on a bunch of studies that either favor the lower dose or show no difference between doses, plus clear evidence that 0.3 mg produces an effect closest to natural melatonin spikes in healthy people, plus UpToDate usually having the best recommendations, I’m in favor of the 0.3 mg number. I think you could make an argument for anything up to 1 mg. Anything beyond that and you’re definitely too high. Excess melatonin isn’t grossly dangerous, but tends to produce tolerance and might mess up your chronobiology in other ways. Based on anecdotal reports and the implausibility of becoming tolerant to a natural hormone at the dose you naturally have it, I would guess sufficiently low doses are safe and effective long term, but this is just a guess, and most guidelines are cautious in saying anything after three months or so.
(http://www.autoadmit.com/thread.php?thread_id=4153279&forum_id=2#37385943)