Melatonin Use Tied to Decreased Risk of Age-Related Macular Degeneration

Use of melatonin was associated with a decreased risk of development and progression of age-related macular degeneration (AMD), a retrospective cohort study suggested.

Among propensity-matched patients ages 50 and older, melatonin use was associated with a reduced risk of developing AMD (risk ratio [RR] 0.42, 95% CI 0.28-0.62), reported Rishi P. Singh, MD, of Cole Eye Institute at the Cleveland Clinic, and colleagues in JAMA Ophthalmology.

In addition, for patients with non-exudative AMD, use of melatonin was associated with a reduced risk of progression to exudative AMD (RR 0.44, 95% CI 0.34-0.56).

Results were consistent among subsets of patients ages 60 and older (AMD-naive cohort: RR 0.36, 95% CI 0.25-0.54; non-exudative AMD cohort: RR 0.38, 95% CI 0.30-0.49) and 70 and older (AMD-naive cohort: RR 0.35, 95% CI 0.23-0.53; non-exudative AMD cohort: RR 0.40, 95% CI 0.31-0.51).

Despite these findings, “it would be too early to make a clinical recommendation at this time,” co-author Hejin Jeong, BA, a medical student at Case Western Reserve University School of Medicine in Cleveland, told MedPage Today. “However, if our findings are confirmed in subsequent randomized controlled studies, ophthalmologists may want to suggest a trial of melatonin for at-risk patients, especially given its safety profile and low cost.”

Melatonin is sold as an over-the-counter dietary supplement, and is typically used to improve sleep. A 2022 study found that its use among U.S. adults increased from 0.4% in 1999-2000 to 2.1% in 2017-2018, and the use of doses over 5 mg per day is growing.

Some research has linked the antioxidant properties of melatonin to better eye health, but Jeong said there’s been little research into the therapeutic use of melatonin in the context of AMD. However, one small prospective study in China linked melatonin supplementation to slower progression of macular damage and slower decline in visual acuity in AMD.

“This seemed like a promising finding,” Jeong said, “so I decided to explore this further on a larger and a more diverse population of both AMD-naive individuals and those who already have existing AMD.”

Bobeck Sam Modjtahedi, MD, of Kaiser Permanente in Pasadena, California, told MedPage Today that the research is “thought-provoking.”

“AMD is a multifactorial disease, and there is still a lot we do not know about why patients get AMD and why those with dry AMD progress to the wet form of the disease,” he said. “On a molecular level, melatonin has effects such as combatting oxidative and inflammatory damage, which are thought to play a role in AMD. If melatonin does impact AMD, it could be in any number of ways, since AMD pathogenesis and melatonin’s therapeutic effects overlap in several places.”

Modjtahedi agreed that it’s too early to make clinical recommendations based on the findings. Still, “repurposing a medication like melatonin is attractive because it is already available and would not have to go through all the steps of developing and getting a new medication approved. And it benefits from already being a known entity when it comes to understanding its systemic safety profile.”

Adverse effects from melatonin appear to be rare, although the 2022 study noted that supplements may include much more melatonin than their labels claim. Melatonin supplements are very inexpensive, often selling for pennies per tablet.

For this study, Singh and colleagues used data from TriNetX, a national database of de-identified electronic medical records across the U.S., from December 2023 to March 2024. Patients were queried for instances of melatonin medication codes from November 2008 to November 2023.

Melatonin users were defined as those whose records mentioned the supplements at least four times and at least 3 months apart.

Among the 4,580 patients in the melatonin group, mean age was 68.24, 56.5% were women, 68.4% were white, and 15.7% were Black, while among the 4,580 in the control group, mean age was 68.17, 58.5% were women, 69% were white, and 15.7% were Black. For the subset with non-exudative AMD, mean age was 80, and 61-62% were women.

Jeong noted that “although all of these findings are statistically significant, this was a retrospective study that was based on medical records. We therefore cannot establish a causal relationship between melatonin use and the development and progression of AMD.”

In addition, the researchers couldn’t fully control for confounders, such as variations in socioeconomic circumstances, lifestyle habits, and how often patients visited healthcare facilities, he added. Nor did the data allow them to take melatonin dosages into account.

It’s also possible that participants who took melatonin may have been healthier overall, due to being more health-conscious, Jeong said.