I have looked at supplementary S5 which does compare Ionising Radiation alone with Ionising Radiation and Melatonin. This does seem to substantiate the conclusion in “discussion”, but I don’t really have the time to spend on going through the paper in any detail.
It could be that melatonin reduces the oxidising effect of the IR so that the cell doesn’t think it has as much damage.
New claims about melatonin (not just high-dose) and heart failure:
That’s interesting. I would like to see melatonin users compared to users of other sleeping drugs. I feel like here they compared melatonin users to non-users among people with chronic insomnia: surely those getting melatonin prescribed (even more so in the US where it’s OTC) must have had way more severe insomnia.
I was taking 2mg of melatonin for years now and it for the last few days I increased the dose to 5mg and wasn’t expecting much. I was wrong! My sleep is much better, I wake up less.
I still have in case I woke up in the night to pee or something a spray in my bed, 1mg per pschitt.
This study presents correlation and does not prove causation.
Those with significant insomnia may have other underlying problems which lead to CHF et.
I have taken OTC melatonin for 10+ years at 5mg qhs, and now 120mg qhs x 8 months, and I remain healthy.
I do not take melatonin for insomnia, rather for its other potential benefits.
Melatonin-article-Shallenberger_Townsend_2019.pdf
Experts say new research findings suggesting that long-term use of melatonin could be associated with increased risk of heart failure need further investigation.
But the study, which has not yet been peer reviewed, has drawn mixed reactions from sleep medicine experts and cardiologists, who are urging the public not to panic and are calling for more research into using melatonin for long periods.
The preliminary results, which appear to contradict existing research suggesting that melatonin might have health benefits for people with heart failure, are from a research abstract that is expected to be presented at the American Heart Association’s Scientific Sessions, a conference for cardiovascular science and medicine. Several experts who reviewed the study also noted limitations that make it challenging to determine whether and how long-term melatonin use could influence heart failure, which is when your heart isn’t pumping as well as it should.
“The findings are certainly provocative and warrant attention, especially given the widespread perception of melatonin as a benign, ‘natural’ sleep aid,” said Muhammad Rishi, an associate professor of clinical medicine and spokesperson for the American Academy of Sleep Medicine, who was not involved in the study. “However, the study is observational and based on electronic health record data, which limits its ability to establish causality.”
Limitations
The study’s authors noted several limitations, including that the group of people who did not have an official record of melatonin use could have included individuals who purchased supplements over the counter.
“The most problematic part” of the study, said David Neubauer, a sleep expert at Johns Hopkins University who was not involved in the research, “is we don’t know whether or not those people in the control group were taking melatonin.”
Only using prescriptions to identify melatonin users means it’s possible that people who take over-the-counter melatonin supplements were classified as nonusers, Rishi said. This could result in findings that inflated risk, he said.
The health record data also did not capture details about whether patients with insomnia who were prescribed melatonin reported changes in their sleep, Oen-Hsiao said.
“If they had such bad insomnia that they needed prescription-dose melatonin, were they actually getting the benefit of the melatonin for sleep?” she said. “And if the answer is no, then you cannot have a correlation that melatonin causes heart failure.”
It’s more likely, she said, that the insomnia could be contributing to declining heart health and leading to heart failure. She added that the study did not appear to distinguish what type of heart failure patients were diagnosed with.
Read the full article: New study links melatonin and heart failure, but experts say don’t panic yet (WaPo)
I just learned that melatonin can worsen symptoms of Sick Sinus Syndrome and other arrhythmias. It may cause bradycardia and too low blood pressure.
I would be interested in reading any references to this.
I have Sick Sinus Syndrome (SSS) and noticed that my heart rate became slower than normal for me and I also started having very frequent pauses, which are typical for SSS. I asked Chart GPT if Melatonin may worsen the symptoms of SSS and was given an unequivocal answer. Melatonin does worsen SSS, causes slow heart rate and may exacerbate other arrhythmia’s. My cardiologist/electrophysiologist was not concerned that I was taking Melatonin. I since decreased the dose from 50 mg to 1.5 IR/XR from Life Extension. I only hope it will help.
Important to mention, that I have a genotype, rs12506228(AA). The A allele was associated with reduced MTNR1A gene expression and fewer melatonin receptors in the brain. I can’t say I understand this well, but there is supposedly an increased risk of dementia after age of 85. I was unable to learn about any strategies preventing this type of dementia associated with fewer melatonin receptors and decided that taking a high dose of melatonin made sense. I may had decided completely incorrectly- don’t know.
This is my response from chatGPT
Thank you very much for this detailed review of the information about cardiac arrythmias and the role of melatonin.
My observation was correct: in predisposed individuals melatonin may cause bradycardia and worsening of Sick Sinus Syndrome, which happened to me. Abnormal MT-1 receptors may also be a predisposing factor.
It is very unfortunate because I do believe in antioxidant and other great qualities of melatonin.
I’ve recently read about this link between melatonin and increased risk of heart failure. I’ve been taking small doses of melatonin for a few years, but this is something that I am trying to reduce. Certainly the massive does of melatonin some here are taking are concerning.
Not concerning to me.
When you make a statement like that, please include the source.
The source was cite above by @RapAdmin , but in case you missed it, here it is again:
The study cited has many critics. Name me any drug or supplement, and I can find a negative statistical association without causation.
“The research behind these headlines, which has not yet been peer-reviewed, is early and does not prove that the supplement causes heart problems.”
The most problematic part” of the study, said David Neubauer, a sleep expert at Johns Hopkins University who was not involved in the research, “is we don’t know whether or not those people in the control group were taking melatonin.”
“While the association we found raises safety concerns about the widely used supplement, our study cannot prove a direct cause-and-effect relationship.”
“This preliminary data (Nnadi et al.) must be interpreted with extreme caution. It is not proof of causation and is heavily confounded by the underlying insomnia.”
"A substantial body of preclinical and human trial data supports a cardioprotective role for melatonin, particularly in acute cardiovascular events. Its potent antioxidant, anti-inflammatory, and mitochondria-protecting properties have been validated in human meta-analyses. These studies demonstrate that melatonin administration can attenuate heart dysfunction, significantly improve left ventricular ejection fraction (LVEF), and reduce myocardial damage (measured by troponin) in patients following acute cardiac events. Furthermore, meta-analyses of randomized controlled trials (RCTs) confirm a modest but statistically significant blood pressure-lowering effect.
In summary, preclinical studies clearly suggest the cardiovascular health benefit of both endogenous and supplementary melatonin. Melatonin is an important safe molecule with a wide range of physiological functions in animals and humans, with a strong therapeutic potential in CVDs.
The core thesis of this medical discourse features an updated paradigm shift in sleep science, transitioning from a historical focus on sleep duration to a multidimensional prioritization of circadian regularity, prophylactic sleep banking, and targeted neurochemical interventions. Dr. Matthew Walker establishes that while sleep quantity remains a critical determinant of all-cause mortality, the Sleep Regularity Index (SRI) serves as a more powerful statistical predictor of longevity and cardiometabolic health. Large-scale prospective data demonstrate that high night-to-night variability in sleep onset and wake times drives systemic pathology, whereas maintaining a narrow 30-minute consistency window reduces all-cause mortality by 49%.
From a biotechnological and therapeutic perspective, this analysis deconstructs long-standing consumer health myths and introduces novel pharmacological mechanisms for neurodegenerative prophylaxis. Traditional over-the-counter interventions—such as standard oral magnesium salts (oxide, citrate) and supra-physiological melatonin megadoses (10–20 mg)—are exposed as pharmacologically inefficient. Most magnesium variants fail to navigate the blood-brain barrier, while high-dose melatonin induces profound next-day hormonal fog and receptor desynchronization without providing superior sleep-generation kinetics.
Conversely, the discovery of genetic short sleepers (harboring mutations in the DEC2 and ADRB1 loci) proves that human sleep architecture can be compressed into highly efficient, dense windows that protect cognitive and physiological baselines. This evolutionary efficiency underpins the deployment of Web 3.0 sleeping medications: Dual Orexin Receptor Antagonists (DORAs), such as suvorexant, lemborexant, and daridorexant. Unlike classical GABAA receptor agonists (e.g., zolpidem) that sedate the cerebral cortex and suppress the brain’s internal clearance mechanisms, DORAs selectively downregulate the wakefulness drive within the brainstem. Recent human randomized controlled trials validate that DORA-induced sleep preserves naturalistic slow-wave sleep architecture, directly facilitating the glymphatic system’s convective clearance of neurotoxic proteins, including beta-amyloid and hyperphosphorylated tau. Consequently, these compounds represent a validated therapeutic class for mitigating the long-term cascade of Alzheimer’s disease pathology.
| Claim from Video | Speaker’s Evidence | Scientific Reality (Current Data) | Evidence Grade | Verdict |
|---|---|---|---|---|
Sleep regularity is a stronger statistical predictor of all-cause mortality than total sleep quantity [00:45:21]. |
Large-scale statistical head-to-head analysis from the UK Biobank dataset. | Device-measured actigraphy in 88,975 UK Biobank participants confirmed that a high Sleep Regularity Index (SRI) is non-linearly and robustly associated with up to a 49% reduction in all-cause mortality, independent of sleep duration. Cribb et al., 2023 | Level C (Cohort) | Strong Support |
Standard forms of magnesium (oxide, citrate) are useless for sleep because they fail to cross the blood-brain barrier [01:05:53]. |
A comprehensive literature deep-dive conducted by the speaker. | While peripheral bioavailability is poor and centrally mediated sleep generation is unaltered, these forms reduce somatic hyperarousal via smooth muscle relaxation and NMDA receptor regulation. They also correct explicit systemic deficiencies. Didwal, 2026 | Level C | Plausible (With Peripheral Caveats) |
New DORA drugs enhance glymphatic clearance and actively reduce Alzheimer’s beta-amyloid and tau protein levels in human CSF [01:59:52]. |
Lumbar spinal puncture human biomarker studies tracking siphoned CSF fluid. | A double-blind RCT demonstrated that 20 mg of the DORA suvorexant acutely decreased amyloid-beta by 10–20% and hyperphosphorylated tau-181 by 10–15% in human central nervous system fluid. Lucey et al., 2023 | Level B (RCT) | Strong Support |
Exogenous melatonin provides little benefit beyond a placebo for standard sleep issues, altering sleep onset by just 3.4 minutes [00:22:38]. |
Pooled bucket data from comprehensive pharmacological meta-analyses. | Systematic reviews confirm that for non-circadian primary insomnia, the effect size of standard melatonin on sleep onset latency and sleep efficiency is minimal, closely tracking placebo values. Hardeland, 2013 | Level A (Meta-analysis) | Strong Support |
Ambient lighting below 30 lux for 90 minutes before bed expands REM sleep architecture by 18% without drugs [00:54:07]. |
Specific environmental light manipulation laboratory studies. | Broad consensus supports that dimming light and eliminating short-wavelength blue light shifts human melatonin onset profiles, preventing the suppression of nocturnal REM cycles and maximizing structural sleep architecture. Esteban-Zubero et al., 2024 | Level B (RCT) | Strong Support |
When dieting under sleep restriction, 70% of mass lost is derived from lean muscle tissue, not adipose tissue [01:52:33]. |
Controlled human metabolic and dietary sleep deprivation studies. | Randomized crossover metabolic ward studies show that sleep-restricted dieters lose significantly less fat mass and lose up to 60–70% more fat-free lean mass due to altered respiratory quotients and elevated cortisol. Life Extension Sleep Loss Data | Level B (RCT) | Strong Support |
I’m going with Matthew Walker on this. Around 22 minutes he speaks firmly against the use of megadoses of melatonin (10-20mg and more). We are all free to disagree or not.
I am not going to bother listening to the video. I would spend some time reading any written arguments, but I have heard Matthew Walker on this before.
Looking at my records I started averaging over 1g of Melatonin a night in July 2024. I continue doing weekly blood draws. I see reasons to continue and no reason to stop. This may not apply to anyone else, but I make my own decisions.
Highlights