It sounds interesting but I’m a little wary of your one line dismissal of any potential side effects without reference. To the best of my knowledge the function of sleep is still not completely understood and the long term effects of reduced sleep are not known. A suggestion to take any kind of supplement every day for the rest of your life places a fairly high bar on safety. Taking melatonin to overcome jet-lag seems very likely to be safe but I’m more wary of using it on an ongoing daily basis.
Do you have any references to support the claim that there are no long term side effects of daily use?
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 findings of this review suggest that exogenous melatonin is a relatively safe substance when used in the short term, over a period of days or weeks, and is safe at relatively high doses and in various formulations. However, the safety of exogenous melatonin when used in the long-term, over months and years, remains unclear.
There are no published long-term safety data on the use of melatonin for whatever purpose, assuming long term to mean more than 6 months of daily medication. In the light of its physiological role in animals, the potential deleterious effects include inhibition of reproductive function, delayed timing of puberty, and influence (when taken during pregnancy and lactation) on the circadian status of the fetus and neonate and on future development. Its interactions with other medications are virtually unexplored. For most positive effects published, there also exist negative reports.
There is evidence to suggest that melatonin is not effective in treating most primary sleep disorders with short-term use (4 weeks or less); however, additional large-scale RCTs are needed before firm conclusions can be drawn. There is some evidence to suggest that melatonin is effective in treating delayed sleep phase syndrome with short-term use. There is evidence to suggest that melatonin is safe with short-term use (3 months or less).
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:
Melatonin decreased sleep onset latency (SOL) in normal sleepers (weighted mean difference (WMD): −3.9 min; 95- percent CI: −5.3 min., −2.6 min.). The magnitude of this effect appears to be clinically insignificant. There was evidence of possible publication bias in the selection of studies that were analyzed; we found a greater number of studies reporting positive results compared to negative results.
and
Melatonin increased sleep efficiency in normal sleepers (WMD: 2.3 percent; 95-percent CI: 0.7 percent, 3.9 percent), and this effect was dependent on the timing of sleep, such that the effect of melatonin was greater in daytime sleepers (daytime sleep: WMD: 8.0 percent; 95- percent CI: 1.0 percent, 15.0 percent; night-time sleep: WMD: 1.2 percent; 95-percent CI: 0 percent, 2.4 percent). The magnitude of this effect appears to be clinically insignificant. There was considerable evidence of possible publication bias in the selection of studies analyzed; we found a greater number of studies reporting positive results compared to negative results.
and
Generally, these studies were of low-to-moderate quality.
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.
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.
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 risk in current users was increased about 1.2 fold; for every 1000 women using HRT, 2.6 developed ovarian cancer over 5 years, compared with 2.2 in those not taking HRT.
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.
How big a study do you need before you’ll judge something as safe?
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.
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)?
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.
Your behavior is extremely risk-averse compared to other choices you make daily.
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.
Basically, children taking melatonin for several years didn’t develop any problems. Melatonin is also used by blind people quite a bit, since without it their circadian rhythms are longer than 24 hours.
The fact that the study was on children certainly doesn’t help the validity when applied to adults, but I think you’re being overly risk-averse. Melatonin’s mechanism of action is pretty well understood, and it occurs in the body already. The long-term effects would have to be very bad to outweigh the advantages of a regular sleep schedule and an extra hour of wakefulness every day. That’s assuming melatonin works, of course.
Endorphins are chemicals that occur naturally in the body, with a mechanism that is pretty well understood. Yet taking opioids regularly is not good for you.
You cannot assume health-benefits simply because it already occurs in the body.
There may well be benefits, but they must be proved independently of simply understanding the natural mechanism.
It sounds interesting but I’m a little wary of your one line dismissal of any potential side effects without reference. To the best of my knowledge the function of sleep is still not completely understood and the long term effects of reduced sleep are not known. A suggestion to take any kind of supplement every day for the rest of your life places a fairly high bar on safety. Taking melatonin to overcome jet-lag seems very likely to be safe but I’m more wary of using it on an ongoing daily basis.
Do you have any references to support the claim that there are no long term side effects of daily use?
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
http://www.ahrq.gov/Clinic/epcsums/melatsum.htm
http://jbr.sagepub.com/cgi/content/abstract/12/6/673
http://linkinghub.elsevier.com/retrieve/pii/S0387760498000722
http://www.springerlink.com/index/D5U5L315J8X79105.pdf
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.
Here’s the longest-term study I could find: http://www.ncbi.nlm.nih.gov/pubmed/19486273
Basically, children taking melatonin for several years didn’t develop any problems. Melatonin is also used by blind people quite a bit, since without it their circadian rhythms are longer than 24 hours.
I believe it’s not generally considered valid to apply results from medical studies on adults to children. I’m not sure if the reverse applies.
The fact that the study was on children certainly doesn’t help the validity when applied to adults, but I think you’re being overly risk-averse. Melatonin’s mechanism of action is pretty well understood, and it occurs in the body already. The long-term effects would have to be very bad to outweigh the advantages of a regular sleep schedule and an extra hour of wakefulness every day. That’s assuming melatonin works, of course.
Endorphins are chemicals that occur naturally in the body, with a mechanism that is pretty well understood. Yet taking opioids regularly is not good for you.
You cannot assume health-benefits simply because it already occurs in the body.
There may well be benefits, but they must be proved independently of simply understanding the natural mechanism.