People who use melatonin supplements have an 89% higher risk of developing heart failure, according to a new study of over 130,000 adults [1].
And there were two other equally grim findings covered below.
This is major news, and it has been making headlines [2],
especially because melatonin use has been rising sharply — including the use of very high doses over 5 mg/day [3].
But the problem is, up to this point, there has not been great data about long-term safety.
This new study looked at patient outcomes over five years. So it promises to finally help fill in that knowledge gap about long-term use. And, at first glance, it looks like melatonin is a disaster for heart health.
This article dives into the details of the study and examines what the evidence actually shows.
Table of Contents
The Study
The researchers looked at a health dataset provided by the TriNetX Global Research Network. They reviewed five years of electronic health records, focusing on adults with chronic insomnia. They then identified all those with melatonin recorded in their records who had used it for at least a year [4].
"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." [4]
The researchers also assembled a comparison group by finding others in the same database who had insomnia but whose health records didn't show melatonin use [4].
Looking at these two groups, the study compared a set of health outcomes.
Here is what the data showed:
-
Heart Failure:
- 3,021 melatonin users (4.6%) developed heart failure
- Compared to 1,797 controls (2.7%)
- This corresponds to a hazard ratio (HR) of 1.89 (95% CI 1.78–2.00)
- Absolute risk difference: 1.9% (p < 0.001) [1]
-
Heart Failure–Related Hospitalizations:
- 12,411 melatonin users (19.0%) were hospitalized for HF
- Compared to 4,309 controls (6.6%)
- HR: 3.44 (95% CI 3.32–3.56) [1]
-
All-Cause Mortality:
-
5,118 melatonin users (7.8%) died during the study
-
Compared to 2,820 controls (4.3%)
- HR: 2.09 (95% CI 1.99–2.18) [1]
-
5,118 melatonin users (7.8%) died during the study
These numbers look alarming for melatonin.
Problems with the Research
Looking below the surface reveals significant problems with the study's methodology.
1. Who's Actually Taking Melatonin?
What the researchers were trying to do is separate long-term melatonin users from those who didn't use it. That is foundational for answering their central question — is long-term melatonin safe?
Here is how they formed the groups:
- The melatonin group: those whose records showed ≥1 melatonin prescription and ≥365 exposure-days [1]
- The non-melatonin group: those with no melatonin exposure listed in their medical records
"The exposed cohort required ≥ 1 melatonin prescription and ≥ 365 exposure-days; controls had no melatonin exposure." [1]
Now here is the key issue: the TriNetX Global Research Network includes data from many countries [5].
In some countries (like the UK), melatonin requires a prescription. But in others (like the US), it doesn't.
By requiring a prescription in the records, the study would miss all U.S. patients using melatonin over the counter. These patients would end up in the non-melatonin group, even though they were taking melatonin [4].
That is a major confounder. If the non-melatonin group was actually taking melatonin, the comparison between the two groups becomes unreliable.
2. Observational ≠ Causal
The second major issue is that this is an observational study, not a randomized controlled trial. So it only tells us about associations, not causation.
There are many examples of misleading correlations:
- Ice cream sales and shark attacks both rise in summer [6]
- Autism diagnoses track closely with the rise in organic food sales [7]
These things correlate, but they are not causally connected.
3. Is It the Insomnia, Not the Melatonin?
Setting aside the two problems above and assuming the association between heart failure and melatonin is real — what might explain it?
One plausible explanation: people with more severe insomnia may be more likely to seek a prescription for melatonin.
And there is strong evidence that insomnia itself increases the risk of heart problems.
A 2024 meta-analysis showed a possible causal association between insomnia and cardiovascular disease (CVD) [8].
This makes physiological sense — sleep loss drives inflammation, and inflammation plays a key role in heart disease [9].
So the association observed may reflect the underlying insomnia, rather than any effect of melatonin itself.
4. What Does RCT Evidence Show?
To really understand causation, randomized controlled trials (RCTs) are needed — where one group receives melatonin and the other gets a placebo.
There is meaningful RCT data available.
A 2025 meta-analysis looked at 4 RCTs in people who already had heart failure. Here is what it found [10]:
- Improved New York Heart Association (NYHA) functional class
- Improved quality of life
- Improved blood vessel health (flow-mediated dilation)
- Trend toward improved heart pumping (ejection fraction), though this was not statistically significant
These findings are consistent with an earlier review in 2022, which found that melatonin had cardioprotective effects in both animal and human studies [11].
"Therefore, melatonin has been shown to have cardioprotective activity in multiple animal and human studies." [11]
So while the observational data appeared alarming, the controlled trial data suggests melatonin might actually benefit people with heart failure.
Practical Notes About Melatonin
Here is what the evidence shows about real-world melatonin use — including some valid cautions.
Melatonin is a hormone produced by the brain in response to darkness. It helps regulate the 24-hour circadian rhythm — the body's sleep-wake cycle.
Melatonin Can Help Sleep
A meta-analysis of 14 studies showed that melatonin can reduce the time it takes to fall asleep [12].
Another review of 23 randomized controlled trials found that melatonin significantly improves sleep quality [13].
The Real Problem: Dosage
A key concern is that many melatonin supplements contain very high doses — over 5 mg/day.
Here is how that compares to the body's natural production:
- The brain produces 10–80 micrograms (μg) of melatonin at night [14]
- Only 15% of a supplement dose is absorbed [15]
So taking 5 mg (that is 5,000 μg) with 15% absorption delivers 750 μg — roughly 10× more than the body naturally produces.
Based on the evidence, a dose of no more than 1 mg per night appears more appropriate for most adults. The research supports using doses that more closely mirror the body's natural melatonin production range.
The studies supporting melatonin's sleep benefits often use doses of just 0.3 mg (300 μg). At 15% bioavailability, this brings absorbed melatonin within the range of what the brain produces naturally — far lower than most over-the-counter products.
From the MicroVitamin range
Sleep by Dr Brad uses a 300 mcg melatonin micro-dose — the dose used in clinical research that most closely mirrors the body's natural overnight production — alongside magnesium bisglycinate and glycine. Sleep by Dr Brad.
Timing also matters: melatonin works best when taken about 2 hours before bed. That allows it time to shift the circadian rhythm and support natural sleep onset.
Final Thoughts
Melatonin is a popular supplement widely associated with sleep support. The headline finding from this new study has generated significant concern — but a closer look at the methodology reveals why caution is warranted before drawing conclusions.
Here is the bottom line:
- The study showed a strong association, but serious methodological flaws limit its reliability — including a prescription-only ascertainment bias that misclassified many melatonin users in the US
- RCT evidence suggests melatonin may actually benefit heart health in people with existing heart failure
- Melatonin can help with sleep — but dosage and timing are key
- The insomnia itself — not the melatonin — may be driving the cardiovascular risk signal observed in the observational data
- Better long-term RCTs are still needed before firm conclusions about melatonin's long-term safety can be drawn
Reference List
1. https://eppro02.ativ.me/web/planner.php?id=AHA25
3. https://pmc.ncbi.nlm.nih.gov/articles/PMC8808329/
5. https://trinetx.com/data-sets-analytics/
6. https://www.fpfairfax.com/blog/breaking-news-eating-ice-cream-causes-shark-attacks
7. https://nerd.wwnorton.com/nerd/274511/r/goto/cfi/48!/4?demo=
8. https://jcsm.aasm.org/doi/10.5664/jcsm.11326
9. https://link.springer.com/article/10.1007/s11818-025-00495-6
10. https://pmc.ncbi.nlm.nih.gov/articles/PMC11873767/
11. https://pmc.ncbi.nlm.nih.gov/articles/PMC9251346/
12. https://www.sciencedirect.com/science/article/abs/pii/S0022395619309872?via%3Dihub
13. https://pubmed.ncbi.nlm.nih.gov/33417003/
