PSA that melatonin use was way out of control before this study was even published.
Sleep aid melatonin is shipped in pills containing ridiculous amounts of the stuff—I’ve seen 10, 12, and 20mg myself, Amazon has a 40mg fast dissolve and 60mg gummies.
This spikes your blood amount with 100x-1000x of your natural cycle of melatonin. Why? Because melatonin is not, repeat not, the signaling molecule that makes you sleepy. It responds to light levels and triggers the cascade of other molecules that make you sleepy, several hours after it peaks. So that's why the 100x overdose—you are trying to kick those secondary mechanisms into overdrive, “hey everyone it is black as the abyss of hell I guess we gotta sleep!!”, because Americans taking melatonin want to pop one just before bed and have it knock them out.
And it does that for like 2 or 3 days before your body starts down-regulating all of its sensitivities to those melatonin byproducts. Nerve cells like to be tickled, not zapped, when you shock them like this they react angrily.
You want to use melatonin to reinforce circadian rhythm and fight jet lag, you do it with amounts in the ~100 micrograms range, slow release if you can find it, and you take that at sunset and let it reinforce your normal cycle. If you're looking for an acute sleep aid, take a walk, get fresh air, drink water, and if those don't help pop a Benadryl/Unisom (it's the same drug either way). If you have doctor’s orders of course follow those, but if you're just trying to self-medicate that’s how you do it.
Absolutely unsurprising that punching your sleep apparatus in the gut once every day for five years increases some sort of stress on your heart.
In grad school I got to attend a talk by one of the researchers who was involved in the discovery of melatonin as a sleep aid for humans. He said that his team had hoped for it to become a prescription medicine dosed at 500 mcg, because anything higher gave paradoxical effects and actually made sleep worse. But it ended up being classified as a supplement in the US rather than a drug, so they had no way to control the dosage on the market.
The other useful thing I learned is that melatonin isn't primarily involved in falling asleep, its main function as a hormone is in staying asleep. I've started taking it sporadically if I wake up in the middle of the night, to make sure I get back to a deep sleep and stay there, and it seems to be super effective for this.
I suspect each brand tries to put more to out-compete with other brands.
People look at multivitamins and think “more is better”. Unfortunately they are stuffed with ingredients that can’t be absorbed well together, but do result in higher sales…
> He said that his team had hoped for it to become a prescription medicine dosed at 500 mcg, because anything higher gave paradoxical effects and actually made sleep worse.
Tangentially, I'm reminded of this interview around ~31m.
TL;DR they found something that promoted deeper sleep, but people didnt necessary feel "well rested", and so it was shelved for something that subjectively improved sleep but actually reduced the quality of sleep.
There was a collection of studies about a decade ago that seemed to determine the optimal use of Melatonin was about 350 micrograms taken about 1 hour before bed. The ideal was also slow release which was the best you could do to match the bodies process currently. The doses you can buy are far too high even the 1.5mg ones.
Just so you know, some doctors recommend being careful with melatonin for kids since it’s a hormone and there’s not a ton of research on long-term effects. They say it might disrupt sexual development during adolescence. Kids produce more melatonin naturally and it is though that a reduction in melatonin production during adolescence is actually what triggers pubertal development. Might be worth looking into a bit more before making it something regular.
> you take that at sunset and let it reinforce your normal cycle
Yes, the way Michael Grandner explains it in this podcast[0], melatonin is an ancient molecule that signals, "it is dark." If you give it to nocturnal species, it wakes them up!
Are you sure about this? Everything I can find says Benadryl is diphenhydramine, and Unisom is doxylamine. (Both linked to increased dementia risk, for what it's worth.)
Yes, I would use first generation antihistamines like those sparingly as they are anticholergenic. It's more of a long term concern rather than for occasional use.
For the low dose melatonin, Life Extension brand sells patented MicroActive formula of fast release/slow release melatonin in a 1.5mg dosage and a 6 hour time released 300mcg version. It's a quality brand and those are the dosage ranges I would recommend sticking around.
I have seen the insanely high 30mg+ amounts being sold and that's ridiculous. If you need that much, there's other factors going on. I would look into reducing caffeine intake, doing proper sleep hygiene (google it), and talk to a doctor/get a referral to a sleep specialist if it's an ongoing thing.
But, also look into l-theanine, glycine/magnesium glycinate, valerian root extract, passionflower, lemon balm and things of that sort for occasional sleeplessness or trouble falling asleep. (Visit examine.com & ergo-log.com and search for these ingredients on there to see all the references, how they work, and for more info.)
Natural isn't necessarily better, but I would recommend those any day over Z drugs, antihistamines and a lot of other rx sleep drugs. Make sure you're buying a quality brand though.
Finally, please don't give melatonin to children...
I’ll never understand the desire of people to take pills for everything. There are always side effects. If you have a medically diagnosed acute or chronic condition and there’s not another option that’s one thing. But if you can eat better, be more active, lose excess weight, etc that’s what you should try to do.
They're both first generation antihistamines and work as agonists on the H1 receptor, causing sedation. There's no reason to choose one over the other for a first time user, but they can cause rapid tolerance. So, I'm guessing the only reason they offer both is if you'd become tolerant to one of them and can no longer fall asleep on it.
I know someone with a condition (I don't recall the name of it) but it actually calls for these massive doses of melatonin (up to 100 mg). The vast majority of people wanting to use it should start LOW- as in 0.25-0.5 mg.
Sleep experts say it is not possible to draw conclusions about melatonin from this study's findings — it did not prove cause and effect. A more likely explanation of the results is that insomnia itself could be to blame. In that case, melatonin would be an “innocent bystander”.
I have wondered if the first generation antihistamine dementia studies might have the same problem. People popping antihistamines for sleep probably have insomnia, which is already known to cause dementia.
I'd been taking 3mg slow release melatonin daily for years up until a few months ago. To be honest, I'm not sure it has any significant effect.
Regular exercise and a consistent sleep routine (cardio, weight lifting, going to bed early, and waking up early) has been more effective for me.
According to my fitbit, my average sleep duration is 6hr 30min over the last 2 years, down from 7hr30. When I wake up, there's no going back.
The biggest contributor to my reduction in sleep is my job, which in the last few years added stack ranking and by-annual performance reviews which requires daily book keeping of my "company impact".
I also got an echo-cardiogram last week (unrelated) and it came back in top shape (have a calcium score test coming up). Not saying melatonin isn't a risk for cardio health, but as a male in his early 30s with a family history of heart disease, nothing seems to indicate an increase in damage in my case.
This is a trash study and the title implying that this is an AHA statement is misleading. It was a data dredge associational study with minimal controlling for other covariates / risk factors for heart failure. The implication that melatonin has a causal relationship with CHF based on this alone is a pretty big jump.
There's a thing going on in Australia with Melatonin. It's not OTC, it's a prescription thing. BUT doctors typically just tell people to buy online from America because it's much cheaper. So the TGA(Therapeutic Goods Administration) did some testing of what you can get online from America:
and are now recommending not to buy online because the doses are completely unregulated. They even reached out to companies like iHerb and asked them not to sell to Australians.
So, whatever dose you think you're taking, assume it's a bit of a guesstimate...
This study is garbage and I suspect it exists to help justify making melatonin a controlled substance so phrama can push their prescription sleep aides.
This is an abstract that hasn’t been peer-reviewed… based on prescription data for an over-the-counter medication. This will be horribly inaccurate because it will miss all the folks who just buy the medication on their own and never have it documented.
These TriNetX studies are usually garbage because they’re entirely dependent on how accurate/up-to-date the medical record is.
Yes, this should have been a pure dose-response study among people with any history of filled melatonin scripts.
The comparison between the US and UK probably leads to two issues - US users use way too much melatonin and swamp heart disease signal, while UK patients prescribed melatonin probably have significant sleep derangement (consider how much effort it takes to get prescribed something for sleep - you need to schedule an appointment, convince your doctor, go to the pharmacy, etc)
I was scrolling around to see if I can find someone else that thought the same.
In my usage of melatonin, it's only when I'm super stressed and can't seem to calm down enough to sleep.
Reading the comments here: why does every society on this planet produce a group of people that just try to medicate every little inconvenience away without regard for their bodies? It is horrifying. I suppose it is for emotional comfort?
I tried to make the title a little less hyperbolic than the article starts out, as it's not a published study and it's basically a huge meta analysis that has no other information on age range, dosage, other health problems, etc. But the implications are worth considering.
It's very plausible that anxiety causes heart disease, anxiety causes insomnia, and insomnia leads people to use melatonin. Same with diphenhydramine, overactive inflammatory response causes allergies, allergic people take allergy meds, and too much inflammation contributes to dementia.
Association studies too easily get interpreted as X causes Y. Maybe that's true, but not necessarily.
I mentioned this study to my wife and she immediately shot back “it’s a garbage study that doesn’t control for anything in particular sleep apnea which is correlated with elevated risk of heart attacks.”
It's just important to remember that melatonin, like most all dietary supplements sold in the U.S. is severly under studied. Melatonin is allowed to be sold because it exists in nature, not because it has been proven safe. This is essentially true of anything sold as a dietary supplement.
Having said that, it doesn't necessarily make it dangerous. But, like myself and others have said in this post, please do take your dosage into consideration, as well as whether you're using it on a daily basis, as there are other things that could be preventing you from falling asleep/staying asleep that may be better addressed by a doctor, such as sleep apnea, as you mentioned.
i tried to deal with sleeplessness by using multiple 5mg melatonin pills per night and it did nothing and made me fell gross. then my doctor said to cut 3 mg pills in half, and 1.5 mg worked far better than over-dosing myself! but he didn't tell me it was bad for me, but only i was taking TOO much of it.
This study is just another case of confusing correlation with causation, wrapped in a scary headline to grab attention.
The problem here is that they compared people who were already sick enough to need long-term melatonin prescriptions with those who weren’t. That’s not testing melatonin’s effects, it’s just showing that people with serious health problems (like chronic insomnia, depression, or anxiety) tend to have worse outcomes. And surprise, those same conditions are already known to increase heart risks.
Here’s the kicker: in the US, melatonin is over-the-counter. So their "non-melatonin" group probably included plenty of people using it anyway (they just didn’t have a prescription on record).
No info on doses, no explanation of how it might actually cause heart issues, and it’s not even peer-reviewed, it's just a conference abstract. Even the AHA expert they quoted sounds pretty skeptical (but of course, the press release still makes it sound like melatonin is the villain).
Honestly, if you wanted to design a study that would produce misleading results, you’d do exactly this: use observational data, ignore selection bias, and skip adjusting for how severe people’s conditions were. The real takeaway is that people with chronic insomnia have worse health. Groundbreaking stuff (not), applause.
PSA that melatonin use was way out of control before this study was even published.
Sleep aid melatonin is shipped in pills containing ridiculous amounts of the stuff—I’ve seen 10, 12, and 20mg myself, Amazon has a 40mg fast dissolve and 60mg gummies.
This spikes your blood amount with 100x-1000x of your natural cycle of melatonin. Why? Because melatonin is not, repeat not, the signaling molecule that makes you sleepy. It responds to light levels and triggers the cascade of other molecules that make you sleepy, several hours after it peaks. So that's why the 100x overdose—you are trying to kick those secondary mechanisms into overdrive, “hey everyone it is black as the abyss of hell I guess we gotta sleep!!”, because Americans taking melatonin want to pop one just before bed and have it knock them out.
And it does that for like 2 or 3 days before your body starts down-regulating all of its sensitivities to those melatonin byproducts. Nerve cells like to be tickled, not zapped, when you shock them like this they react angrily.
You want to use melatonin to reinforce circadian rhythm and fight jet lag, you do it with amounts in the ~100 micrograms range, slow release if you can find it, and you take that at sunset and let it reinforce your normal cycle. If you're looking for an acute sleep aid, take a walk, get fresh air, drink water, and if those don't help pop a Benadryl/Unisom (it's the same drug either way). If you have doctor’s orders of course follow those, but if you're just trying to self-medicate that’s how you do it.
Absolutely unsurprising that punching your sleep apparatus in the gut once every day for five years increases some sort of stress on your heart.
In grad school I got to attend a talk by one of the researchers who was involved in the discovery of melatonin as a sleep aid for humans. He said that his team had hoped for it to become a prescription medicine dosed at 500 mcg, because anything higher gave paradoxical effects and actually made sleep worse. But it ended up being classified as a supplement in the US rather than a drug, so they had no way to control the dosage on the market.
The other useful thing I learned is that melatonin isn't primarily involved in falling asleep, its main function as a hormone is in staying asleep. I've started taking it sporadically if I wake up in the middle of the night, to make sure I get back to a deep sleep and stay there, and it seems to be super effective for this.
I suspect each brand tries to put more to out-compete with other brands.
People look at multivitamins and think “more is better”. Unfortunately they are stuffed with ingredients that can’t be absorbed well together, but do result in higher sales…
My wife diagnosed a patient with acute vitamin E toxicity. They were taking a “more is better” daily dose.
Don’t do that.
> He said that his team had hoped for it to become a prescription medicine dosed at 500 mcg, because anything higher gave paradoxical effects and actually made sleep worse.
Tangentially, I'm reminded of this interview around ~31m.
TL;DR they found something that promoted deeper sleep, but people didnt necessary feel "well rested", and so it was shelved for something that subjectively improved sleep but actually reduced the quality of sleep.
https://youtu.be/UWhk2LMDwCc?t=31m
There was a collection of studies about a decade ago that seemed to determine the optimal use of Melatonin was about 350 micrograms taken about 1 hour before bed. The ideal was also slow release which was the best you could do to match the bodies process currently. The doses you can buy are far too high even the 1.5mg ones.
I buy 300mcg for me and my kids, it’s a fantastic sleep aid. Thanks to Scott Alexander talking about it.
Are you sure that your kids need to be medicated like this during development?
Just so you know, some doctors recommend being careful with melatonin for kids since it’s a hormone and there’s not a ton of research on long-term effects. They say it might disrupt sexual development during adolescence. Kids produce more melatonin naturally and it is though that a reduction in melatonin production during adolescence is actually what triggers pubertal development. Might be worth looking into a bit more before making it something regular.
> you take that at sunset and let it reinforce your normal cycle
Yes, the way Michael Grandner explains it in this podcast[0], melatonin is an ancient molecule that signals, "it is dark." If you give it to nocturnal species, it wakes them up!
[0] https://www.youtube.com/watch?v=AQF_eopP1ys
>Benadryl/Unisom (it's the same drug either way)
Are you sure about this? Everything I can find says Benadryl is diphenhydramine, and Unisom is doxylamine. (Both linked to increased dementia risk, for what it's worth.)
Yes, I would use first generation antihistamines like those sparingly as they are anticholergenic. It's more of a long term concern rather than for occasional use.
For the low dose melatonin, Life Extension brand sells patented MicroActive formula of fast release/slow release melatonin in a 1.5mg dosage and a 6 hour time released 300mcg version. It's a quality brand and those are the dosage ranges I would recommend sticking around.
I have seen the insanely high 30mg+ amounts being sold and that's ridiculous. If you need that much, there's other factors going on. I would look into reducing caffeine intake, doing proper sleep hygiene (google it), and talk to a doctor/get a referral to a sleep specialist if it's an ongoing thing.
But, also look into l-theanine, glycine/magnesium glycinate, valerian root extract, passionflower, lemon balm and things of that sort for occasional sleeplessness or trouble falling asleep. (Visit examine.com & ergo-log.com and search for these ingredients on there to see all the references, how they work, and for more info.)
Natural isn't necessarily better, but I would recommend those any day over Z drugs, antihistamines and a lot of other rx sleep drugs. Make sure you're buying a quality brand though.
Finally, please don't give melatonin to children...
Parents give kids more melatonin than ever, with unknown long-term effects https://arstechnica.com/health/2025/04/melatonin-for-kids-sa...
I’ll never understand the desire of people to take pills for everything. There are always side effects. If you have a medically diagnosed acute or chronic condition and there’s not another option that’s one thing. But if you can eat better, be more active, lose excess weight, etc that’s what you should try to do.
There are two kinds of Unisom: diphenhydramine and doxylamine succinate.
They're both first generation antihistamines and work as agonists on the H1 receptor, causing sedation. There's no reason to choose one over the other for a first time user, but they can cause rapid tolerance. So, I'm guessing the only reason they offer both is if you'd become tolerant to one of them and can no longer fall asleep on it.
https://en.wikipedia.org/wiki/H1_antagonist#First-generation...
Can you point to a source about the body down-regulating melatonin?
I also thought this was the case, but everything I've seen suggests that taking melatonin does not alter the natural production of melatonin.
You are correct about everything else though.
It doesn't. There's some minor evidence, but it's very quickly reversed.
I know someone with a condition (I don't recall the name of it) but it actually calls for these massive doses of melatonin (up to 100 mg). The vast majority of people wanting to use it should start LOW- as in 0.25-0.5 mg.
https://slatestarcodex.com/2018/07/10/melatonin-much-more-th...
Sleep experts say it is not possible to draw conclusions about melatonin from this study's findings — it did not prove cause and effect. A more likely explanation of the results is that insomnia itself could be to blame. In that case, melatonin would be an “innocent bystander”.
Source: https://www.nytimes.com/2025/11/05/well/melatonin-heart-heal...
I have wondered if the first generation antihistamine dementia studies might have the same problem. People popping antihistamines for sleep probably have insomnia, which is already known to cause dementia.
I'd been taking 3mg slow release melatonin daily for years up until a few months ago. To be honest, I'm not sure it has any significant effect.
Regular exercise and a consistent sleep routine (cardio, weight lifting, going to bed early, and waking up early) has been more effective for me.
According to my fitbit, my average sleep duration is 6hr 30min over the last 2 years, down from 7hr30. When I wake up, there's no going back.
The biggest contributor to my reduction in sleep is my job, which in the last few years added stack ranking and by-annual performance reviews which requires daily book keeping of my "company impact".
I also got an echo-cardiogram last week (unrelated) and it came back in top shape (have a calcium score test coming up). Not saying melatonin isn't a risk for cardio health, but as a male in his early 30s with a family history of heart disease, nothing seems to indicate an increase in damage in my case.
This is a trash study and the title implying that this is an AHA statement is misleading. It was a data dredge associational study with minimal controlling for other covariates / risk factors for heart failure. The implication that melatonin has a causal relationship with CHF based on this alone is a pretty big jump.
I came in here to say the same thing. The study is a total joke. I expected it to get ripped apart in this discussion thread.
There's a thing going on in Australia with Melatonin. It's not OTC, it's a prescription thing. BUT doctors typically just tell people to buy online from America because it's much cheaper. So the TGA(Therapeutic Goods Administration) did some testing of what you can get online from America:
https://www.abc.net.au/news/2025-09-29/tga-safety-concerns-o...
and are now recommending not to buy online because the doses are completely unregulated. They even reached out to companies like iHerb and asked them not to sell to Australians.
So, whatever dose you think you're taking, assume it's a bit of a guesstimate...
This study is garbage and I suspect it exists to help justify making melatonin a controlled substance so phrama can push their prescription sleep aides.
This is an abstract that hasn’t been peer-reviewed… based on prescription data for an over-the-counter medication. This will be horribly inaccurate because it will miss all the folks who just buy the medication on their own and never have it documented.
These TriNetX studies are usually garbage because they’re entirely dependent on how accurate/up-to-date the medical record is.
Yes, this should have been a pure dose-response study among people with any history of filled melatonin scripts.
The comparison between the US and UK probably leads to two issues - US users use way too much melatonin and swamp heart disease signal, while UK patients prescribed melatonin probably have significant sleep derangement (consider how much effort it takes to get prescribed something for sleep - you need to schedule an appointment, convince your doctor, go to the pharmacy, etc)
I’d guess it’s just correlated with poor sleepers.
I was scrolling around to see if I can find someone else that thought the same. In my usage of melatonin, it's only when I'm super stressed and can't seem to calm down enough to sleep.
Reading the comments here: why does every society on this planet produce a group of people that just try to medicate every little inconvenience away without regard for their bodies? It is horrifying. I suppose it is for emotional comfort?
I tried to make the title a little less hyperbolic than the article starts out, as it's not a published study and it's basically a huge meta analysis that has no other information on age range, dosage, other health problems, etc. But the implications are worth considering.
Think Melatonin is Safe? Well this study is terrible and demonstrates nothing.
It's very plausible that anxiety causes heart disease, anxiety causes insomnia, and insomnia leads people to use melatonin. Same with diphenhydramine, overactive inflammatory response causes allergies, allergic people take allergy meds, and too much inflammation contributes to dementia.
Association studies too easily get interpreted as X causes Y. Maybe that's true, but not necessarily.
But all anticholineric drugs seem to cause dementia in susceptible persons, not just anti-allergy ones.
insomnia is also highly correlated with heart attack risk so there's that
https://newsroom.heart.org/news/long-term-use-of-melatonin-s...
I mentioned this study to my wife and she immediately shot back “it’s a garbage study that doesn’t control for anything in particular sleep apnea which is correlated with elevated risk of heart attacks.”
It's just important to remember that melatonin, like most all dietary supplements sold in the U.S. is severly under studied. Melatonin is allowed to be sold because it exists in nature, not because it has been proven safe. This is essentially true of anything sold as a dietary supplement.
Having said that, it doesn't necessarily make it dangerous. But, like myself and others have said in this post, please do take your dosage into consideration, as well as whether you're using it on a daily basis, as there are other things that could be preventing you from falling asleep/staying asleep that may be better addressed by a doctor, such as sleep apnea, as you mentioned.
Controlling for things is bad practice in general because most variables are not good controls. (https://en.wikipedia.org/wiki/Collider_(statistics))
You should instead design the study so it doesn't need massaging afterwards.
i tried to deal with sleeplessness by using multiple 5mg melatonin pills per night and it did nothing and made me fell gross. then my doctor said to cut 3 mg pills in half, and 1.5 mg worked far better than over-dosing myself! but he didn't tell me it was bad for me, but only i was taking TOO much of it.
"may be linked" indicates low certainity
probably written by a statin exec. There is no reason to trust anything anymore.
This study is just another case of confusing correlation with causation, wrapped in a scary headline to grab attention.
The problem here is that they compared people who were already sick enough to need long-term melatonin prescriptions with those who weren’t. That’s not testing melatonin’s effects, it’s just showing that people with serious health problems (like chronic insomnia, depression, or anxiety) tend to have worse outcomes. And surprise, those same conditions are already known to increase heart risks.
Here’s the kicker: in the US, melatonin is over-the-counter. So their "non-melatonin" group probably included plenty of people using it anyway (they just didn’t have a prescription on record).
No info on doses, no explanation of how it might actually cause heart issues, and it’s not even peer-reviewed, it's just a conference abstract. Even the AHA expert they quoted sounds pretty skeptical (but of course, the press release still makes it sound like melatonin is the villain).
Honestly, if you wanted to design a study that would produce misleading results, you’d do exactly this: use observational data, ignore selection bias, and skip adjusting for how severe people’s conditions were. The real takeaway is that people with chronic insomnia have worse health. Groundbreaking stuff (not), applause.
This whole thing is akin to the "I'm just asking questions" crowd.