Large-scale randomized trial found signs of preventive cardiovascular effects for cocoa flavanols, including a 27 percent reduction in the secondary endpoint of cardiovascular death. There was a 10 percent reduction in total cardiovascular events, the trial’s primary outcome, that was not statistically significant.
In papers published in The American Journal of Clinical Nutrition, a team led by Howard Sesso, ScD, MPH, and JoAnn Manson, MD, DrPH, both of the Division of Preventive Medicine at Brigham and Women’s Hospital, unpacks the main outcomes of the COcoa Supplement and Multivitamin Outcomes Study (COSMOS), a randomized, placebo-controlled trial that tested a cocoa flavanol supplement and a multivitamin in the prevention of cardiovascular disease and cancer.
While neither supplement significantly reduced the primary outcome of total cardiovascular events, people randomized to receive the cocoa flavanol supplement had a 27 percent lower rate of cardiovascular death, a pre-specified secondary endpoint.
“When we look at the totality of evidence for both the primary and secondary cardiovascular endpoints in COSMOS, we see promising signals that a cocoa flavanol supplement may reduce important cardiovascular events, including death from cardiovascular disease,” said Sesso. “These findings merit further investigation to better understand the effects of cocoa flavanols on cardiovascular health."
“Previous studies have suggested health benefits of flavanols — compounds in several plant-based foods including cocoa, tea, grapes, and berries,” said Manson. “COSMOS was not a chocolate trial — rather, it’s a rigorous trial of a cocoa extract supplement that contains levels of cocoa flavanols that a person could never realistically consume from chocolate without adding excessive calories, fat, and sugar to their diet.”
Smaller, short-term trials have found cardiovascular benefits for cocoa flavanols on blood pressure and blood vessel dilation. COSMOS offered the first opportunity to study if a cocoa flavanol supplement might also lead to longer-term reductions in clinical cardiovascular events. Investigators also looked for reductions in risk of cancer. In addition, the trial was designed to test a common multivitamin in the prevention of cancer and cardiovascular disease.
The primary cardiovascular outcome for the cocoa flavanol intervention was a composite of total cardiovascular events, including heart attacks, stroke, coronary revascularization, cardiovascular death, carotid artery disease, peripheral artery surgery, and unstable angina. More than 21,000 participants were randomized to take daily capsules that contained 500 mg cocoa flavanols (donated by Mars Edge), a multivitamin tablet (donated by GSK Consumer Healthcare), neither or both.
The study found that cocoa flavanols reduced total cardiovascular events by 10 percent, but this was not statistically significant. However, several secondary analyses provided broader support for a potential benefit of cocoa flavanols on cardiovascular events. First, those receiving the cocoa flavanol supplement had a significant 27 percent reduction in death from cardiovascular disease.
Second, when the study team took adherence to study pills into account (by looking at those taking their study pills regularly), the team saw a stronger, 15 percent reduction in total cardiovascular events and a 39 percent reduction in death from cardiovascular disease.
Third, a composite endpoint of major cardiovascular events (heart attacks, strokes, and cardiovascular deaths), although not a trial focus, was also significantly reduced. The authors note in their report that their promising results on cocoa flavanols and cardiovascular events warrant cautious interpretation and underscore the need for additional research.