Narrative review associates melatonin use with delayed age-related macular degeneration in Americans over 40

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Frontiers in Medicine Published April 15, 2026 Medically reviewed April 25, 2026 Study authors: Russel J. Reiter, Ramaswamy Sharma, Janusz Blasiak, Sergio Rosales-Corral, Doris Loh DOI ↗ By Dr. Lars van Dijk, PhD · Surgical, Procedural & Diagnostic

Key Takeaway

Note that melatonin use is associated with delayed AMD, but causality and clinical certainty remain unproven in this narrative review.

This narrative review focuses on the potential relationship between melatonin use and the progression of age-related macular degeneration (AMD) in the American population over 40 years of age. Unlike primary trials, this source does not report specific sample sizes, intervention details, or adverse event rates. The authors synthesize existing literature to evaluate whether melatonin might play a role in AMD management or prevention.

The primary finding presented is that melatonin use in humans is associated with delayed AMD. The review notes this association but explicitly avoids reporting effect sizes, absolute numbers, or confidence intervals. Consequently, the strength of this association is difficult to quantify based on the provided data.

The authors acknowledge significant limitations inherent to this narrative approach. Key details such as the study phase, setting, and specific outcomes are not reported. Furthermore, the review does not provide data on tolerability, discontinuations, or serious adverse events. These gaps prevent a comprehensive assessment of the risk-benefit profile of melatonin for AMD patients.

Given the observational nature of the evidence and the lack of statistical rigor, the practice relevance is uncertain. Clinicians should interpret these findings as suggestive rather than definitive. The review cautions against inferring specific clinical trial data or causality where only an association is reported. Further high-quality research is needed to clarify the role of melatonin in AMD.

Study Details

Study typeSystematic review

EvidenceLevel 1

PublishedApr 2026

View Original Abstract ↓

Approximately 1.5 million Americans over the age of 40 suffer from vision-threatening age-related macular degeneration (AMD), a number expected to rise with aging demographics. AMD exists in two defined forms: dry (non-exudative) which accounts for up to 90% of cases, and wet (exudative). Dry AMD is characterized by the slow buildup of drusen under the retina, eventually leading to geographical atrophy. Wet AMD involves vascular endothelial growth factor (VEGF)-induced blood vessel formation from the choriocapillaris into the subretinal space, a process referred to as neovascularization. These newly formed blood vessels leak fluid into the subretinal space leading to atrophy of the retinal pigment epithelium (RPE) and associated photoreceptors. Despite clinical distinctions, dry and wet AMD share overlapping pathophysiological features, marked by degeneration of the RPE and the overlying photoreceptors. A major feature of the RPE and photoreceptors are their high metabolically activity and their large numbers of mitochondria, which generate reactive oxygen species (ROS) during ATP production. ROS-induced oxidative stress damages lipids, proteins and DNA, resulting in cellular degradation which contributes to AMD. Because of the elevated oxidative stress levels, antioxidants which neutralize ROS are often recommended as a treatment for AMD. A major objective of this review is to examine the role of melatonin, a powerful and multifunctional antioxidant, in altering the trajectory of AMD progression. Melatonin is synthesized in the RPE and photoreceptors of young individuals but its expression declines with age. As shown in an epidemiological report, its loss contributes to age-related degeneration of the RPE and photoreceptors. Moreover, melatonin inhibits VEGF, suggesting that it would be useful as a treatment for wet AMD. This review explores melatonin-mediated protective mechanisms in the retina, a likely mechanistic basis for the already published findings showing that melatonin use by humans is associated with delayed AMD, and potential clinical applications.