Cocoa Shows Limited Benefit for Reducing Macular Degeneration Risk

A recent prespecified ancillary study examining the results of the Cocoa Supplement and Multivitamins Outcomes Study (COSMOS) trial revealed brief beneficial effects of cocoa flavanol treatment for age-related macular degeneration (AMD). However, the overall results indicated no significant benefit.

“Additional analyses conducted because of evidence of nonproportional hazards could not rule out a possible benefit of supplementation during the first 2 years of treatment, with little additional benefit for longer treatment,” wrote William G. Christen, ScD, OD, PhD, division of preventive medicine, Brigham and Women’s Hospital and Harvard Medical School, and colleagues. “Further research is warranted to clarify whether long-term cocoa extract supplementation may reduce AMD events.”1

Investigators examined the data collected during the COSMOS trial, a double-blind, placebo-controlled, 2 x 2 factorial randomized clinical trial conducted from 2015-2020. The COSMOS trial tested the effectiveness of a cocoa extract supplement and a multivitamin supplement in preventing cancer and cardiovascular disease (CVD) in adults.1

According to previous trials, the ingestion of cocoa flavanols results in the dilation of several blood vessels throughout the body. Research has indicated that cocoa causes an alteration in the brachial artery diameter up to 3% flow-mediated dilation.2 From this example, investigators believed that flavanols would have a similarly dilative effect on blood vessels in the eye, thereby avoiding a common trigger of AMD.

The COSMOS trial examined 21,442 US randomized participants – of these, 12,666 were female ≥65 years of age, and 8776 were male ≥60 years of age. Participants were screened for myocardial infarction, stroke, and recently diagnosed cancer within the past 2 years. They were asked to complete a placebo run-in over the course of ≥ 2 months. During this period, participants took ≥75% of the study pills, which included 2 capsules per day of 500 mg of cocoa flavanols – namely 80 mg epicatechin – and the multivitamin Centrum Silver. The study was broken up into 4 main arms, which are as follows:

• Active cocoa extract and active multivitamin
• Active cocoa extract and multivitamin placebo
• Cocoa extract placebo and active multivitamin
• Both placebos1

Follow-up questionnaires were distributed following randomization, monitoring adherence to the trial’s schedule and signs of major illnesses – including AMD.

Christen and colleagues’ study makes use of the data collected by the COSMOS trial to determine the incidence of AMD among its participants and thereby ascertain the supplement’s effectiveness in preventing the disease. During a median period of 3.6 years of treatment and follow-up, 344 participants had indicated an AMD event – of these, 316 were cases of incident AMD and 28 were of AMD progression.

A total of 159 cases came from the cocoa extract subgroup and 185 from the placebo group (hazard ratio [HR], 0.87; 95% CI, 0.71-1.08; P = .21). Excluding the first year of follow-up, the HR for AMD incidence was modestly attenuated, lowering to 235 events (HR, 0.91; 95% CI, 0.71-1.18).1

While the overall conclusion was that the cocoa extract offered no benefits towards prevention of AMD, an additional post hoc analysis stratified by time based on inspection of cumulative incidence curves indicated a potential modest treatment effect for AMD incidence in the first 2 years of follow-up (213 events; HR, 0.77, 95% CI, 0.59-1.01) but showed little to no benefit after 2 years (131 events; HR, 1.06; 95% CI, 0.76-1.50).1

Notably, investigators indicated that this study’s findings are at odds with studies conducted in the past.

“Our finding of no additional benefit beyond 2 years of treatment appears at odds with prior studies, which show that with regular consumption, the acute effects of flavanols translate into long-term benefits in flow-mediated dilation,” noted Christen and colleagues. “The reasons for this apparent discrepancy are unclear.”1

References

1. Christen WG, Rist PM, Moorthy MV, et al. Cocoa flavanol supplementation and risk of age-related macular degeneration. JAMA Ophthalmology. Published online March 27, 2025. doi:10.1001/jamaophthalmol.2025.0353

2. Monahan KD, Feehan RP, Kunselman AR, Preston AG, Miller DL, Lott ME. Dose-dependent increases in flow-mediated dilation following acute cocoa ingestion in healthy older adults. Journal of Applied Physiology. 2011;111(6):1568-1574. doi:10.1152/japplphysiol.00865.2011