Shocking Study Links MELATONIN to 89% Heart Failure Spike

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 we’ll look at in a moment.

This is major news, and it’s 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, we haven’t had 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.

So let’s dive into the details of this study and see if we should stop taking melatonin immediately.

Table of Contents

• The study
• Problems with the research
• Practical notes about melatonin
• Final Thoughts
• Reference List

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. Then they 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]

They 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, they compared a set of health outcomes.

Here’s what they found:

• 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]

These numbers look terrible for melatonin.

Problems with the Research

But we need to look below the surface, because there are some huge problems with the study’s methodology.

1. Who’s Actually Taking Melatonin?

What the researchers are trying to do is separate long-term melatonin users from those who didn’t use it. That’s foundational for answering their central question — is long-term melatonin safe?

But here’s 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’s 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.

So 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’s a huge confounder. If the non-melatonin group was actually taking melatonin, how can we trust the comparison?

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 tons of 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 aren’t causally connected.

3. Is It the Insomnia, Not the Melatonin?

If we ignore the two problems above and assume the association between heart failure and melatonin is real, what might explain it?

Here’s a possibility: people with more severe insomnia may be more likely to get a prescription for melatonin.

And there’s 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].

That makes sense — sleep loss drives inflammation, and inflammation plays a key role in heart disease [9].

So maybe it’s not the melatonin causing the problem — it’s the underlying insomnia.

4. What About RCT Evidence?

To really know what’s going on, we’d need randomized controlled trials — where one group gets melatonin and the other gets a placebo.

We do have some of that data.

A 2025 meta-analysis looked at 4 RCTs in people who already had heart failure. Here’s 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), but it wasn’t 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 even though the observational data looked scary, the controlled trial data suggests melatonin might actually help people with heart failure.

Practical Notes About Melatonin

Let’s talk about real-world use of melatonin — including some valid cautions.

Melatonin is a hormone produced by the brain in response to darkness. It helps regulate our 24-hour circadian rhythm — our 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

Here’s the issue: many melatonin supplements contain very high doses — over 5 mg/day.

But here’s 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 if you take 5 mg (that’s 5,000 μg) and absorb 15%, that’s 750 μg — 10x more than your body naturally makes

That’s why personally, I wouldn’t take more than 1 mg per night.

I do take melatonin regularly as part of a sleep supplement, but it includes just 0.3 mg (or 300 μg). Given bioavailability, that dose closely mimics the natural production range — and it’s far lower than most over-the-counter products.

But just because I take a supplement, that certainly doesn’t mean you also need to.

And timing matters: melatonin works best when taken about 2 hours before bed. That allows it time to shift your circadian rhythm and support natural sleep onset.

Final Thoughts

Melatonin is a popular supplement, and most people associate it with sleep. But based on how this new study has been reported, there’s been a wave of concern.

Here’s the bottom line:

• The study showed a strong association, but serious methodological issues limit its reliability
• RCT data suggests melatonin might actually benefit heart health
• Melatonin can help with sleep — but dosage and timing are key
• We still need better long-term trials before drawing firm conclusions about safety

Reference List

1. https://eppro02.ativ.me/web/planner.php?id=AHA25

2. https://www.foxnews.com/health/new-health-warning-issued-over-popular-sleep-aid-millions-take-nightly

3. https://pmc.ncbi.nlm.nih.gov/articles/PMC8808329/

4. https://newsroom.heart.org/news/long-term-use-of-melatonin-supplements-to-support-sleep-may-have-negative-health-effects

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/

14. https://pmc.ncbi.nlm.nih.gov/articles/PMC4138917

15. https://pubmed.ncbi.nlm.nih.gov/10883420/