The COSMOS randomized clinical trial has found that daily supplementation with cocoa extract, a source of flavanols, did not significantly affect the overall occurrence or progression of age-related macular degeneration (AMD) in older adults over a median treatment period of 3.6 years.
Researchers from Brigham and Women's Hospital and Harvard Medical School conducted this large-scale study as an ancillary segment of the COSMOS trial (NCT03205202) to investigate whether cocoa flavanols could reduce AMD incidence or progression, given the potential vascular basis for the disease.
Potential Link Between AMD and Cardiovascular Disease
The research team, led by William G. Christen, ScD, noted that while AMD's pathophysiology remains unclear, consistent observations of decreased choroidal circulation in affected eyes support a vascular basis for the disease. This has led some investigators to hypothesize that AMD and cardiovascular disease (CVD) may share common underlying mechanisms and risk factors.
"Epidemiologic studies have shown that the risk of AMD is higher in those with CVD compared to those without and in those with CVD risk factors, such as elevated blood pressure, dyslipidemia, higher body mass index, and smoking," the researchers explained.
Nutrition has been thought to contribute to both AMD and CVD. The potential cardiovascular benefits of moderate consumption of cocoa products, particularly cocoa flavanols found in the cocoa bean, has become an area of growing interest in recent years.
Study Design and Methods
The trial included 21,442 US adults aged 60 years and older (12,666 women, mean age 72.1 years). Participants received either a cocoa extract supplement (500 mg/day cocoa flavanols, including 80 mg (-)-epicatechin, a bioactive component in dark chocolate) or a placebo. The intervention phase ran from June 2015 through December 2020.
The primary endpoint 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.
Key Findings
During the median treatment period of 3.6 years, 344 participants (1.6%) experienced a confirmed AMD event:
- 316 had incident AMD
- 28 progressed to advanced AMD
Of these events, 159 cases (1.5%) occurred in the cocoa extract group and 185 cases (1.7%) in the placebo group, yielding a hazard ratio (HR) of 0.87 (95% confidence interval [CI], 0.71-1.08; P=0.21).
Interestingly, separate Cox models fitted due to evidence of nonproportional hazards (P=0.048) 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 visually significant AMD and advanced AMD.
Implications for Future Research
While the overall results did not show significant benefits of cocoa extract supplementation over the entire study period, the researchers noted that they could not rule out a possible benefit during the first 2 years of treatment.
"Further research is warranted to clarify whether long-term cocoa extract supplementation may reduce AMD events," the study authors concluded. This suggests that additional studies with longer follow-up periods or different dosing regimens might be needed to fully understand the potential role of cocoa flavanols in AMD prevention or management.
The findings contribute important data to the ongoing exploration of nutritional approaches to managing AMD, a leading cause of vision loss in older adults worldwide.
