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…
I've taken it rarely, but not found it to be a panacea on the night I'm having trouble sleeping. That is, if it isn't already early when I take it, I'm positively trashed for the morning after. The next night is when I find that taking one early helps in catching up.
> 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.
It can be difficult to find low dose melatonin unfortunately. Especially in slow release.
Often kids sleep tablets are better. Also kids chewable gummies can be cut in half to get an effective dosage. I've not found a good long release version of those.
> 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 mean it's understudied, but at the very least you have [1], children given high doses daily of melatonin developed delayed sleep/wake cycles when measured by DLMO (the time of day that your endogenous melatonin starts to rise) and that “Nearly all children who temporarily discontinued melatonin experienced a delay in sleep onset time,” both of which strongly suggest downregulation is happening. (Usually endogenous melatonin skews earlier with melatonin supplementation, see [2].)
Similar inefficacies have been seen clinically e.g. in [3] and are (caution, anecdata) widespread on the internet, with "melatonin doesn't work" being a popular search term with tons of articles about it. An honest to goodness test seems to have been done at [4] where they made sleep disturbance symptoms "disappear" by resuming treatment at a lower dosage, but instead of blaming the neurons they are blaming the liver, saying that it got overloaded and couldn't clear melatonin out of the bloodstream anymore in some patients—I just want to include that as a plausible alternative explanation so that you don't take my words as gospel truth or anything. I’m trained as a physicist, not a physician, and there is this meme of people with physics degrees thinking that everybody else’s field is their expertise and like I want to be deliberately self conscious about my limitations here.
From streetlights everywhere, emergency vehicles blasting sirens at all hours, trains blasting horns (miles away but are still audible), its no surprise that Americans are struggling to sleep if this is your environment.
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.
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'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 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.
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...
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.
Readit News
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.
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.
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…
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
Often kids sleep tablets are better. Also kids chewable gummies can be cut in half to get an effective dosage. I've not found a good long release version of those.
Dead Comment
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
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.)
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 effectshttps://arstechnica.com/health/2025/04/melatonin-for-kids-sa...
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.
Similar inefficacies have been seen clinically e.g. in [3] and are (caution, anecdata) widespread on the internet, with "melatonin doesn't work" being a popular search term with tons of articles about it. An honest to goodness test seems to have been done at [4] where they made sleep disturbance symptoms "disappear" by resuming treatment at a lower dosage, but instead of blaming the neurons they are blaming the liver, saying that it got overloaded and couldn't clear melatonin out of the bloodstream anymore in some patients—I just want to include that as a plausible alternative explanation so that you don't take my words as gospel truth or anything. I’m trained as a physicist, not a physician, and there is this meme of people with physics degrees thinking that everybody else’s field is their expertise and like I want to be deliberately self conscious about my limitations here.
[1]: PDF Warning: https://www.herbogeminis.com/revista/IMG/pdf/melatonin-adhd....
[2]: https://academic.oup.com/sleep/article-abstract/33/12/1605/2...
[3]: https://www.psychiatrist.com/jcp/effects-exogenous-melatonin...
[4]: https://pubmed.ncbi.nlm.nih.gov/20576063/
From streetlights everywhere, emergency vehicles blasting sirens at all hours, trains blasting horns (miles away but are still audible), its no surprise that Americans are struggling to sleep if this is your environment.
Melatonin isn't going to fix that.
After 1-3mg, you’re doing yourself a disservice.
At least, for sleep purposes. I cannot comment on its use as an antioxidant.
Source: https://www.nytimes.com/2025/11/05/well/melatonin-heart-heal...
Maybe.
It'd be far more interesting if they could exclude folks who used either as a sleep aid, but I'm not sure how realistically you could find any.
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.
These TriNetX studies are usually garbage because they’re entirely dependent on how accurate/up-to-date the medical record is.
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)
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...