Cocoa Flavanol Supplementation and Risk of Age-Related Macular Degeneration: An Ancillary Study of the COSMOS Randomized Clinical Trial.

Abstract

Importance: Abnormalities of choroidal blood flow in the eye are associated with occurrence of age-related macular degeneration (AMD). Cocoa flavanols show beneficial effects on vascular risk factors in small and short-term trials and may help reduce AMD risk.

Objective: To examine whether daily supplementation with cocoa extract, a source of flavanols, prevents the development or progression of AMD.

Design, setting, and participants: This was a prespecified ancillary study of the COSMOS (COcoa Supplement and Multivitamins Outcomes Study) trial, a double-blind, placebo-controlled, 2 × 2 factorial randomized clinical trial of a cocoa extract supplement and a multivitamin supplement in the prevention of cardiovascular disease and cancer among 21 442 US adults, including 12 666 women aged 65 years and older and 8776 men aged 60 years and older. The intervention phase was performed from June 2015 through December 2020; data analysis was completed in August 2024.

Intervention: Cocoa extract supplement (500 mg/day cocoa flavanols, including 80 mg (-)-epicatechin) or placebo.

Main outcomes and measures: The primary end point was a composite of incident cases of AMD plus cases of progression to advanced AMD (geographic atrophy, neovascular membrane, retinal pigment epithelium detachment, or disciform scar) among participants with AMD at baseline, based on self-report confirmed by medical record review.

Results: Mean (SD) participant age was 72.1 (6.6) years, and 12 666 participants (59.1%) were female. During a median (IQR) period of 3.6 (3.2-4.2) years of treatment and follow-up, 344 participants (1.6%) experienced a confirmed AMD event (316 incident AMD, 28 progression to advanced AMD). For the primary composite end point, there were 159 cases (1.5%) in the cocoa extract group and 185 cases (1.7%) in the placebo group (hazard ratio [HR], 0.87; 95% CI, 0.71-1.08; P = .21). Separate Cox models fitted because of evidence of nonproportional hazards (P = .048) indicated a 23% decreased risk in the cocoa extract group during the first 2 years of treatment (HR, 0.77; 95% CI, 0.59-1.01), with no added benefit for treatment beyond 2 years (HR, 1.06; 95% CI, 0.76-1.50). Similar time-dependent findings were observed for the secondary trial outcomes of incident visually significant AMD and advanced AMD.

Conclusions and relevance: In this ancillary study of the COSMOS randomized clinical trial, cocoa extract supplementation for a median period of 3.6 years among older women and men had no effect overall on occurrence of AMD. However, a possible modest treatment effect early in the trial could not be ruled out, which warrants further investigation to clarify whether cocoa extract may help reduce AMD risk.

Trial registration: ClinicalTrials.gov Identifier: NCT03205202.