A Summary of the article on “Effect of cocoa flavanol supplementation for the prevention of cardiovascular disease events: the COcoa Supplement and Multivitamin Outcomes Study (COSMOS) randomized clinical trial”
Background
The COcoa Supplement and Multivitamin Outcomes Study (COSMOS) was a significant randomised, double-blind, placebo-controlled, 2-by-2 factorial clinical trial investigating the long-term effects of cocoa extract supplementation on cardiovascular disease (CVD) events and cancer prevention in older adults. It was conducted by Sesso et al. (2022) and published in The American Journal of Clinical Nutrition in June 2022. Previous smaller, short-term trials had indicated that cocoa flavanols favourably influenced vascular risk factors, but their effects on clinical cardiovascular events remained untested.
Methods
The trial involved 21,442 US adults, comprising 12,666 women aged 65 years or older and 8,776 men aged 60 years or older, all free of major CVD and recently diagnosed cancer. Participants were randomly assigned to receive either a cocoa extract supplement (providing 500 mg flavanols/day, including 80 mg (–)-epicatechin) or a placebo. The intervention phase ran from June 2015 through December 2020, with a median follow-up of 3.6 years. Funding for COSMOS included grants from Mars Edge (which also supplied study pills) and Pfizer Consumer Healthcare, along with support from the National Institutes of Health. Compliance was high, confirmed by a more than three-fold increase in urinary flavanol metabolites (gVLM) in the active cocoa extract group compared to placebo.
Results
The primary outcome was a composite of confirmed incident total cardiovascular events, which included myocardial infarction (MI), stroke, coronary revascularisation, cardiovascular death, carotid artery disease, peripheral artery surgery, and unstable angina. This expanded definition was adopted due to lower-than-projected CVD event rates, partly influenced by increasing use of preventive treatments and the COVID-19 pandemic.
The study found that cocoa extract supplementation did not significantly reduce the primary outcome of total cardiovascular events in older adults (Hazard Ratio [HR]: 0.90; 95% Confidence Interval [CI]: 0.78, 1.02; P = 0.11). However, a significant reduction was observed for one of the secondary endpoints: CVD death, which decreased by 27% (HR: 0.73; 95% CI: 0.54, 0.98). No significant reductions were seen for MI, stroke, or revascularisations individually. In per-protocol analyses, which censored follow-up for non-adherence, there was support for a lower risk of total cardiovascular events (HR: 0.85; 95% CI: 0.72, 0.99). Additionally, a non-prespecified composite outcome of major cardiovascular events (MI, stroke, and CVD death) showed a significant 16% reduction (HR: 0.84; 95% CI: 0.71, 0.99).
Regarding cancer, the trial found no significant effect of cocoa extract supplementation on total invasive cancer or site-specific cancers. There were generally no safety concerns, although participants taking cocoa extract were 6% more likely to report nausea. Conversely, they experienced significant reductions in self-reported flu-like symptoms and headaches, including a 15% reduction in migraine.
Conclusions
The authors acknowledged several limitations, including the broad nature of the primary composite CVD endpoint, the inability to discern the effects of individual components within the cocoa extract, and potential generalisability limitations due to recruitment methods. They also cautioned that findings from secondary and exploratory analyses should be interpreted carefully due to the lack of adjustment for multiple testing.
In conclusion, while cocoa extract supplementation did not significantly reduce the overall primary outcome of total cardiovascular events, the trial did reveal a statistically significant 27% reduction in CVD death and potential benefits for total cardiovascular events in per-protocol analyses. Further research and longer-term follow-up are warranted to clarify these findings and their potential public health implications.
References
Sesso, H. D., Manson, J. E., Aragaki, A. K., Rist, P. M., Johnson, L. G., Friedenberg, G., Copeland, T., Clar, A., Mora, S., Moorthy, M. V., Sarkissian, A., Carrick, W. R., & Anderson, G. L. (2022). Effect of cocoa flavanol supplementation for the prevention of cardiovascular disease events: The COcoa Supplement and Multivitamin Outcomes Study (COSMOS) randomized clinical trial. The American Journal of Clinical Nutrition, 115(6), 1490–1500. https://doi.org/10.1093/ajcn/nqac055
This post is based on Open Access research and is for informational purposes only.
