Quick Answer
A July 2026 systematic review published in Pharmaceuticals (Q1 journal, no author COI declared) identified 3 prior case reports of cardiac arrhythmias temporally associated with melatonin supplementation at 1 to 10 mg/day, plus presents a new case of second-degree atrioventricular block in a patient taking 10 mg daily. In all cases symptoms improved or resolved after stopping melatonin. Evidence quality is very low (case reports only; causality not established). The authors name a "melatonin paradox": a molecule that is cardioprotective in most research contexts may, in rare susceptible individuals, produce the opposite outcome. Melatonin is a hormone - its effects vary based on individual physiology, metabolism, and genetic predisposition. Reincarn Night Reboot contains no melatonin.
At a Glance
Read this first. This article covers a paper documenting rare adverse events associated with melatonin supplementation. Melatonin has a strong general safety record and well-documented cardioprotective properties in most research. The paper itself states it should not be read as a general statement against melatonin. The publisher of this article (Zandra Life Sciences Pvt. Ltd.) manufactures Reincarn Night Reboot, a melatonin-free product - a direct commercial conflict of interest, disclosed here. Do not stop any supplement or medication without consulting a healthcare professional.
Why Hiya chose this study
Our editor Hiya Aidasani was initially skeptical when she encountered this paper. The premise - that melatonin supplementation could be associated with cardiac arrhythmias - is counterintuitive. Melatonin is widely understood to be cardioprotective. The antioxidant, anti-inflammatory, and mitochondrial protective effects of melatonin are well-documented across multiple systematic reviews.
The evidence base in this paper is extremely thin: the systematic review screened three major databases and found only 2 studies, which together described 3 cases. No meta-analysis was possible. Publication bias is a real concern at this sample size. These limitations are significant and Hiya weighed them seriously.
She chose to include it for two specific reasons. First, the authors declared no conflicts of interest, which matters when the finding challenges a widely used supplement. Second, she evaluated the journal independently and confirmed that Pharmaceuticals carries a Q1 ranking across both JCR and CiteScore, with a credible impact factor. The combination of an unbiased author group and a rigorous publication venue gave the paper enough credibility to warrant coverage - despite the limitations.
Why this paper was selected for the Digest
What the cases showed
Across the 3 cases from the systematic review and the 1 new case, the pattern was consistent: patients developed cardiac arrhythmias during melatonin use, and those arrhythmias improved or resolved when melatonin was stopped. All four patients were male, aged 55 to 72, and all had some prior cardiovascular history. Melatonin doses ranged from 1 mg to 10 mg daily.
| Source | Age | Dose | Finding | After stopping |
|---|---|---|---|---|
| de Vries 2017, Case 1 | 72M | 1 mg/day | 2,000 multiform PVCs/24h | Improvement |
| de Vries 2017, Case 2 | 63M | 1 mg/day | PVCs + non-sustained ventricular tachycardia | Improvement |
| Panattil 2023 | 55M | 10 mg/day (1 yr) | 16-18% PVCs (left ventricular origin) | Burden fell from 10% to <2% over 4 months |
| Sola et al. 2026 (new case) | 63M | 10 mg/day | 1st and 2nd degree atrioventricular block; max 2,200ms pause | Resolution; normal sinus rhythm |
Two of the four cases involved just 1 mg per day of melatonin - a dose that is often described as "low dose" and is within the range commonly sold in pharmacies. Dose alone does not predict risk.
The melatonin paradox
The authors use the phrase "melatonin paradox" and it is the correct framing. Melatonin has antioxidant, anti-inflammatory, and mitochondrial protective effects that are well-documented in animal and clinical models. Multiple reviews support its cardioprotective properties. The mechanisms are biologically credible and the evidence base is substantial.
And yet, in a small number of cases, melatonin supplementation appears to have produced the opposite outcome - triggering cardiac rhythm disturbances rather than protecting against them. The authors propose that this paradox depends on an interplay of factors: dose, timing, formulation, sleep architecture, concomitant drugs, obesity-related signalling, pharmacokinetic variability, and genetic predisposition.
The likely mechanism involves melatonin's direct effect on cardiac tissue via MT1 and MT2 receptors. These G-protein-coupled receptors are expressed in cardiovascular tissue and modulate calcium handling in cardiac cells, including L-type calcium channels and ryanodine receptors. Calcium dysregulation is a known contributor to triggered arrhythmic activity. In susceptible individuals - particularly those with genetic variation in the MTNR1B gene encoding MT2 receptors - this modulation may produce unexpected electrophysiological effects.
Melatonin is a hormone, not a supplement
This distinction matters more than most melatonin users realise. Unlike magnesium, glycine, or L-theanine - nutrients the body can use or excrete with wide tolerability - melatonin is a hormone. It is synthesised and secreted by the pineal gland, acts on specific receptors in the brain, gut, immune system, and cardiovascular tissue, and is tightly regulated by the body's own circadian clock.
Taking exogenous melatonin is therefore not analogous to taking a vitamin. It is introducing a hormone into a system that is designed to produce and regulate that hormone itself. The effects will vary based on an individual's physiology, metabolism, receptor density, genetic predisposition, and overall health. The 25-fold pharmacokinetic variability documented in the literature - meaning a 5 mg tablet can produce blood levels 25 times higher in one person than another at the same dose - reflects this biological reality.
Most over-the-counter melatonin sold in India and globally is dosed at 5 mg or 10 mg per day. Sleep researchers who study melatonin physiology typically consider 0.3 to 0.5 mg to be the physiologically relevant dose for sleep onset. The doses most people actually take can be ten to thirty times higher than this. In the context of a molecule that acts as a hormone with receptor expression in cardiovascular tissue, that dosing gap is relevant.
Our verdict: Noteworthy - limitations clearly acknowledged
The evidence is too limited to draw clinical conclusions. Four case reports, all older males, no causality framework, high publication bias risk. This paper does not establish that melatonin causes arrhythmias. What it does do - published in a Q1 journal by authors with no declared conflicts - is identify a biological signal that warrants properly designed follow-up research. The melatonin paradox framing is intellectually honest and clinically important. We cover it because we believe people should have access to this literature when making decisions about what they put in their bodies.
Why Reincarn Night Reboot contains no melatonin
Reincarn Night Reboot was designed without melatonin before this paper was published. The reasoning has not changed because of it - but this paper illustrates it clearly.
The primary argument is about mechanism: melatonin governs sleep timing, signalling to the body that darkness has arrived. It does not govern sleep depth, sleep architecture, cortisol suppression overnight, or the nervous system's capacity to disengage from the day. Most adults with poor sleep quality are not suffering from a timing problem. They are suffering from a system that cannot complete the recovery process even when sleep occurs.
The secondary argument is about individual variability: because melatonin is a hormone with receptor expression across multiple body systems and up to 25-fold pharmacokinetic variability at standard doses, it is not a consistent or predictable intervention at the population level.
Reincarn Night Reboot's 7 ingredients target the recovery pathways: Glycine for NREM architecture and core body temperature regulation, Magnesium Bisglycinate for GABA synthesis, L-Theanine for alpha wave induction and anxiety-driven arousal reduction, Maizinol UP165 for slow-wave amplification, Tagara Root for GABA-A modulation and sympathetic suppression, KSM-66 Ashwagandha for cortisol recalibration via the HPA axis, and Vitamin B6 (P5P) for neurotransmitter cofactor support. None of these act on the MT1/MT2 receptor pathway implicated in the cases described in this paper.
Reincarn Night Reboot
7 clinically-referenced ingredients. Zero melatonin.
Formulated to support sleep depth and recovery, not just sleep timing. 4,352mg per serving across Glycine, Magnesium Bisglycinate, L-Theanine, Maizinol UP165, Tagara Root, KSM-66 Ashwagandha, and Vitamin B6 (P5P).
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What to hold in mind when reading this paper
Frequently asked questions
Can melatonin cause heart arrhythmia?
A small number of case reports have documented cardiac arrhythmias including premature ventricular contractions and atrioventricular block in patients taking 1 to 10 mg of melatonin daily, with improvement after stopping. Evidence quality is very low and causality is not established. Melatonin has well-documented cardioprotective properties in most research. This appears to be a rare effect in susceptible individuals.
Is melatonin a hormone?
Yes. Melatonin is a hormone produced by the pineal gland, not a nutritional supplement. It acts on MT1 and MT2 receptors across multiple body systems including the cardiovascular system. Its effects depend on individual physiology, genetics, and metabolism - which is why the same dose can produce blood levels up to 25 times higher in one person than another.
Should I stop taking melatonin after reading this?
This is not medical advice. Four case reports do not justify population-level guidance. If you take melatonin and experience unexplained palpitations, mention it to a doctor. If you are considering stopping, discuss it with a healthcare professional first. Do not make supplement decisions based on a single case report series without clinical input.
What doses were involved in these cases?
1 mg per day in two cases, and 10 mg per day in two cases. Importantly, the 1 mg cases demonstrate that low doses are not necessarily safe for all individuals. The large pharmacokinetic variability (up to 25-fold in blood levels at the same dose) means any fixed dose is highly individual in its actual effect.
Why is Reincarn Night Reboot melatonin-free?
Because melatonin addresses sleep timing, not sleep depth. Most adults with poor sleep quality have adequate melatonin production - their problem is not when sleep arrives but how restorative it is once it does. Reincarn Night Reboot's 7 ingredients target the pathways that govern sleep architecture, nervous system recovery, and cortisol suppression overnight. As a hormone with significant individual variability in effects, melatonin is also not a consistent intervention across people.