gwern comments on Case study: Melatonin - Less Wrong
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I did link to Wikipedia for a reason; see http://en.wikipedia.org/wiki/Melatonin#Availability_and_safety . But besides AngryParsley's link, there's
Given the unanimous results of safety in the short-term, positive results in long-term child use, the exploitation of a regular physiological process, the long track-record of melatonin use, and the lack of evidence for any long-term harm, I think I'd say the onus is on any doomsayers.
(No doubt there's a witty Eliezerism or post on the topics of negative results and burdens of proof, but offhand I can't think of it.)
It took large scale randomized studies to establish the negative health effects of vitamin supplements/antioxidants and HRT both of which appeared safe in the short term, exploited a regular physiological process and had a long track record of use. I'd want to see a large randomized study of the long term effects of melatonin use in adults to establish the long term effects of melatonin use in adults.
The Wikipedia link you give merely concludes that "evidence suggests that melatonin is safe with short-term use, three months or less". From your other links:
The evidence you present for the benefits of melatonin is also weak and the Wikipedia article is fairly circumspect about the benefits of melatonin. The first review you link to states:
and
and
Nowhere have in these links do I see any evidence supporting your key claim that melatonin allows for the benefits of 8 hours of sleep in 7 hours.
I think your post spent too much time discussing the relatively uninteresting topic of the cost of melatonin and not enough on the evidence for safety or efficacy. Based on the discussion and the further research you and others have linked I'm not persuaded enough by the evidence for safety or efficacy to adopt melatonin for long term use, but I may try it out for jet lag or other short term sleep difficulties.
How big a study do you need before you'll judge something as safe? You selected two examples of a class of therapies that "appeared safe in the short term, exploited a regular physiological process and had a long track record of use."
From the wikipedia article on the HRT study:
The reason huge studies were required to find issues with HRT is because HRT so rarely causes issues. The question you should be asking is: If it is known that a drug is safe in the short term, exploits a regular physiological process, and has a long track record of use, what is the chance that it is harmful in the long term (and to what degree)? The two examples you pointed out are not the entire data set. Your behavior is extremely risk-averse compared to other choices you make daily.
I don't think it makes sense to ask that question in isolation. When judging whether some risk is worth taking I'd generally look at both the evidence for the potential risks and for the potential benefits. I focused on the potential risks in my original post but the reason I'm not convinced that taking melatonin on a long term basis is justified is that the evidence for the benefits is also weak. If there was extremely strong evidence for the claimed benefits of taking melatonin over the long term then I might consider the risks of long term side effects worth taking. My position at the moment is that the balance of evidence suggests that the risk/reward proposition is not compelling for long term use of melatonin, though as I have said I may well try it next time I have a transatlantic flight to counter jetlag.
I don't think that's the right question. The right question is whether the evidence for benefits outweighs the evidence for harm. I used to take vitamin supplements because the risk/reward based on the available evidence seemed compelling. In light of more recent large scale studies that show no long term benefits and some evidence of long term harm I no longer take vitamin supplements.
I am not risk-averse in general, in fact I think I probably have a higher than average risk tolerance in general. I probably require a higher risk/reward payoff for any kind of long term use of supplements or drugs than the average North American however.