High Dose Melatonin Therapy

[Aiming]

As I can see, the source of this study is the American Heart Association. If we look back at their previous "studies" and their dietary guidelines, for example, I am very suspicious about any "scientific wisdom" that comes from there.

I‘ve thought the same, especially given what I’ve read at one point about melatonin‘s benefits on heart health. Makes sense from their point of view to discredit a helpful substance.

 

[Gaby]

Sayer Ji did the favor to look into it:

No, Melatonin Doesn’t Cause Heart Failure: What the Media Got Wrong About the AHA’s Preliminary Study

Breaking down the facts behind the headlines — and why the real risk lies in scientific illiteracy, not melatonin.

sayerji.substack.com

A Study Designed to Confuse​

When we dig into the methods, the implausibility becomes obvious.
The study only counted people with a prescription for melatonin—which is common in the U.K. but almost nonexistent in the U.S., where melatonin is sold over the counter. As the authors admit:

“Everyone taking it as an over-the-counter supplement… would have been in the non-melatonin group.”

This means that millions of people who actually use melatonin nightly were classified as non-users, while the so-called “melatonin group” was composed almost entirely of patients sick enough to have their sleep problems documented and treated in medical systems requiring prescriptions.

That’s not a safety signal — it’s a statistical illusion.

Confounding, Not Causation​

Even if the data were reliable, the confounders are overwhelming. Chronic insomnia often travels with anxiety, depression, hypertension, and metabolic dysfunction — each a major risk factor for cardiovascular disease. Matching patients by demographics or comorbidities doesn’t erase the underlying severity bias: those who seek prescriptions tend to be those who are already unwell.

Moreover, the researchers lacked basic data on:

• Sleep quality and circadian rhythm disruption
• Lifestyle factors (diet, alcohol, shift work, screen exposure)
• Supplement dosage and purity
• Psychiatric medications used concurrently

Without these, there’s no meaningful inference about melatonin itself.

Moreover, the study failed to account for several key pharmacological confounders. While the authors excluded patients taking benzodiazepines, they did not control for other pharmaceutical sleep drugs such as zolpidem (Ambien), eszopiclone (Lunesta), or trazodone — all of which carry well-documented cardiometabolic risks. Nor did they adjust for the use of statins, SSRIs, or antihypertensives, which are both common among insomnia patients and known to alter cardiovascular function (learn more about the cardiotoxicity of statin drugs) and sleep architecture. Failing to isolate these variables makes it virtually impossible to determine whether the observed risks stem from melatonin itself or from concurrent drug exposure.

The Biological Reality: Melatonin as a Protector​

For decades, melatonin has been one of the most studied molecules in the realm of oxidative stress and cardiometabolic protection. Peer-reviewed studies have shown that it:

• Reduces blood pressure and improves endothelial function
• Protects mitochondria and heart tissue after ischemic injury
• Mitigates oxidative damage and inflammation across numerous organs

A 2022 meta-analysis in the Journal of Pineal Research found melatonin to be broadly cardioprotective, not cardiotoxic.

This aligns with the GreenMedInfo research database, which has indexed nearly 1,000 studies on melatonin’s diverse physiological benefits across more than 400 health conditions, and documents up to 130 distinct pharmacological actions of the molecule — including antioxidant, anti-inflammatory, neuroprotective, and cardioprotective effects (see the research compendium here).



Within this body of literature, there are dozens of studies specifically identifying melatonin’s cardioprotective roles — from improving myocardial recovery to reducing ischemia-reperfusion injury and modulating autonomic balance (cardiovascular studies here).

To reverse that entire corpus of evidence based on a five-minute abstract summary would be scientifically reckless.

It's actually quite audacious for the AHA to pick up on melatonin, the one supplement that protects the architecture of the sleeping cycle. I've specialized in sleep disorders and have read a few hundred sleep graphs. One of the worst offenders is a heart drug (ticagrelor), it literally gives you severe central sleep apnea. Then comes the zombie drugs - zolpidem, benzos, etc. It's impossible to have a normal sleeping cycle with those. An abnormal sleeping cycle on a vulnerable person translates into serious health problems. More info on the latter here: The Polyvagal Theory - Stephen W. Porges)