Long-term use of melatonin supplements to support sleep may have negative health effects

Mij

Senior Member (Voting Rights)
American Heart Association Scientific Sessions 2025
  • Among adults with insomnia, those whose electronic health records indicated long-term melatonin use (12 months or more) had about a 90% higher chance of incident heart failure over 5 years compared with matched non-users (4.6% vs. 2.7%, respectively).
  • There was a similar result (82% higher) when researchers analyzed people who had at least 2 melatonin prescriptions filled at least 90 days apart. (Melatonin is only available by prescription in the United Kingdom.)
A secondary analysis found:
  • Participants taking melatonin were nearly 3.5 times as likely to be hospitalized for heart failure when compared to those not taking melatonin (19.0% vs. 6.6%, respectively).
  • Participants in the melatonin group were nearly twice as likely to die from any cause than those in the non-melatonin group (7.8% vs. 4.3%, respectively) over the 5-year period.
 
I've tried different doses of melatonin in the past but it doesn't work for me. My understanding is that it has an antioxidant effect?
 
  • The association between melatonin and increased risk of heart failure or death found in this study, which cannot prove a cause-and-effect relationship, raises safety concerns about the use of melatonin, which is widely available, and may warrant more research on melatonin to assess its cardiovascular safety, researchers said.
Does someone have a link to the paper?
 
These are insane numbers - nearly a fifth of melatonin users hospitalized for heart failure in a five-year period?

Would have to see the actual study, but given that they are including patients from the USA, I am confident in saying that the majority of melatonin users would not be identified by this study. Melatonin can be bought anywhere in the US (pharmacies, grocery stores, cosmetics stores, gas stations, they've all have it in one form or another) and the number of patients who report its use, or any supplement use, really, to their GPs is vanishingly small. Even for those who do, it is not infrequently un-recorded - I am a case in point. I have reported using it multiple times and, so far as I am aware, it has never been recorded nor appeared in my chart; during the next visit, it is never in the list of medications that I am asked to confirm.
 
People don't take melatonin without reason. I think the study is finding that people with those reasons (stress, lack of healthy sleep, etc) are more likely to die than people without those factors in their lives.
Yeah, I wonder how much of this correlation is due to poor health > poor sleep > gets melatonin, or poor sleep leading to both poor health and getting melatonin.
 
Yeah, I wonder how much of this correlation is due to poor health > poor sleep > gets melatonin, or poor sleep leading to both poor health and getting melatonin.
Well the study is among people with insomnia, not the general population. Perhaps there is still a bias in that people who get prescribed melatonin are less healthy or have worse insomnia etc.
 
Well the study is among people with insomnia, not the general population. Perhaps there is still a bias in that people who get prescribed melatonin are less healthy or have worse insomnia etc.
Ah, I missed that.
In this study, researchers classified people who had used melatonin long-term (with long-term use defined as a year or more documented in their electronic health records) as part of the “melatonin group.” In contrast, those who never had melatonin recorded anywhere in their medical records were classified as the “non-melatonin group.”
Using a large international database (the TriNetX Global Research Network), the researchers reviewed 5 years of electronic health records for adults with chronic insomnia who had melatonin recorded in their health records and used it for more than a year. They were matched with peers in the database who also had insomnia but never had melatonin recorded in their health records. People were excluded from the analysis if they had previously been diagnosed with heart failure or had been prescribed other sleep medications.
 
Yep, that probably creates a bias towards the melatonin group having worse health issues and/or insomnia
Yeah, it compares people with not bad enough sleep issues to be prescribed anything for their sleep issues, to people that have had bad enough sleep issues to be prescribed melatonin.

Although I think the evidence for using melatonin for insomnia is pretty poor, so there might not be a case for using it at all.
 
Yep, that probably creates a bias towards the melatonin group having worse health issues and/or insomnia
I thought about this too, it may be the case, but I can also think that it may be that the bias is in exactly the opposite direction: For example people with serious health issues that also have insomnia (say MS, Lupus etc) might be seen be a proper specialist that describes serious drugs for their issues but not something more bening like melatonin. I doubt there's many specialists at university hospitals prescribing melatonin.

I think one would really have to have a closer look at the cohorts.

I wasn't aware that it was only available as prescription in the UK, but as @DHagen mentions in the US things are very different, so things are much harder to interpret, for it to become part of your medical records might mean you have some serious health incident or something else happened, which could again shift the bias in one direction.
 
I thought about this too, it may be the case, but I can also think that it may be that the bias is in exactly the opposite direction: For example people with serious health issues that also have insomnia (say MS, Lupus etc) might be seen be a proper specialist that describes serious drugs for their issues but not something more bening like melatonin. I doubt there's many specialists at university hospitals prescribing melatonin.

I think one would really have to have a closer look at the cohorts.

I wasn't aware that it was only available as prescription in the UK, but as @DHagen mentions in the US things are very different, so things are much harder to interpret, for it to become part of your medical records might mean you have some serious health incident or something else happened, which could again shift the bias in one direction.
I think it is by using the UK even more skewed than they are hinting at. I'm really intrigued by what they mean by 'matched pairs' and whether those who were being matched were really looked into for not diagnosed comorbidities and were real matches particularly for things related to heart failure.

It feels like that would theoretically be a fascinating follow-up to look at how many of those who died or had heart failure turned out to have something else and whether it was related to either insomnia (ie meds not working enough) or the melatonin or something else was either underlying both, or whether this is 'something that happens when insomnia gets bad enough/is left too long' or is melatonin. Because it feels there must have been red flags along the way.

And because given the context of how limited who can get melatonin on prescription in the UK it is a much more select group they are potentially looking at and perhaps therefore says as much about how serious insomnia impacts are when left if you have a system that wants to try all the other obvious for too long (and does it check everyone for comorbid like apnea which I think is related to causing heart issues? are there other things?)

From what I remember the 'can prescribe' has really tight guidelines regarding different age groups. Something like it being somewhat allowed to be very liberally prescribed to those who are in the 'old age' bracket,

but working age you have fat chance unless you see a consultant and they can manage the care plan of it, ie I'm not sure even getting it from a GP with barn door sleep issues is possible. And of course that doubly means that those who in the UK of that age to try melatonin there is a stronger chance they've been put on other sleep drugs before?

I think also there is some leeway for kids short term, but they'd surely says kids here if it included those.

And of course UK is absolutely obsessed with putting off anyone whose issues fall into certain categories such as sleep through the years long hoop-jumping of IAPT, mindfulness apps etc and 'go away and try that for 6months' on cycle to have to prove all the obvious don't work. I also get the impression in the UK that melatonin is one of the last/harder to get of any sleeping medication. I think there are only a few biomedical sleep clinics/hospitals in the UK too, with most that bear that name just at best ruling out apnea then putting someone thru hygiene assuming if it aint that then those are the only tools that they have. So it would be a case of being in the part of the country or knowing how to get a referral and able to travel and keep going to and not be discharged from one of those few big centres. Which likely due to all of this are having to focus on certain cases.

So it isn't even just a case of 'need to have good reason' that most prescriptions in other countries would be assumed to be.
 
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