Cocoa Flavanol Supplement Shows Promise for Reducing Risk of Cardiovascular Disease

Dietary sources of flavanols. Credit: MARS

• 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

The first large-scale trial to test the long-term effects of a cocoa flavanol supplement to prevent cardiovascular disease offers promising signals that cocoa flavanols could have protective cardiovascular effects. 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.”

COSMOS Trial study pills pack. Credit: MARS

“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.

A daily multivitamin had no significant effect on total or individual cardiovascular events. There were no safety concerns for either cocoa flavanols or a multivitamin.

COSMOS concluded after about 3.6 years, which was likely too short to detect whether the supplements could have affected cancer risk. Although a daily multivitamin improved levels of several nutritional biomarkers, it had no significant effect on total invasive cancer, the primary outcome for the multivitamin analyses. Cocoa flavanols also had no significant effect on total invasive cancer. The authors note that continuing to follow COSMOS participants may help to clarify any longer-term effects on cancer and death. The investigators and collaborators are also leveraging COSMOS to study cognitive decline, falls, eye disease, and other aging-related outcomes that may be influenced by the supplements.

“Although our study suggests intriguing signals for cardiovascular protection with cocoa flavanols, any health benefits due to taking these supplements will need confirmation in a future trial,” said Manson. Adds Sesso: “Our message for consumers is to eat a healthy, balanced diet, rich in natural food sources of flavanols, and to stay tuned as we further evaluate other important health outcomes in COSMOS.”

References:

“Effect of Cocoa Flavanol Supplementation for Prevention of Cardiovascular Disease Events: The COSMOS Randomized Clinical Trial” by Howard D Sesso, JoAnn E Manson, Aaron K Aragaki, Pamela M Rist, Lisa G Johnson, Georgina Friedenberg, Trisha Copeland, Allison Clar, Samia Mora, M Vinayaga Moorthy, Ara Sarkissian, William R Carrick and Garnet L Anderson for the COSMOS Research Group, 16 March 2022, The American Journal of Clinical Nutrition.
DOI: 10.1093/ajcn/nqac055

“Multivitamins in the Prevention of Cancer and Cardiovascular Disease: The COSMOS Randomized Clinical Trial” by Howard D Sesso, Pamela M Rist, Aaron K Aragaki, Susanne Rautiainen, Lisa G Johnson, Georgina Friedenberg, Trisha Copeland, Allison Clar, Samia Mora, M Vinayaga Moorthy, Ara Sarkissian, Jean Wactawski-Wende, Lesley F Tinker, William R Carrick, Garnet L Anderson and JoAnn E Manson for the COSMOS Research Group, 16 March 2022, The American Journal of Clinical Nutrition.
DOI: 10.1093/ajcn/nqac056

Funding: The Cocoa Supplement and Multivitamin Outcomes Study (COSMOS) is supported by an investigator-initiated grant from Mars Edge, a segment of Mars dedicated to nutrition research and products, which included infrastructure support and the donation of cocoa extract-containing study pills and packaging. Pfizer Consumer Healthcare (now part of GSK Consumer Healthcare) provided support through the partial provision of study pills (Centrum Silver) and packaging. COSMOS is also supported in part by grants AG050657, AG071611, EY025623, and HL157665 from the National Institutes of Health, Bethesda, MD. The Women’s Health Initiative (WHI) program is funded by the National Heart, Lung, and Blood Institute, National Institutes of Health, U.S. Department of Health and Human Services through contracts 75N92021D00001, 75N92021D00002, 75N92021D00003, 75N92021D00004, 75N92021D00005. Neither company had a role in the trial design or conduct, data collection (other than blinded assays supported by Mars Edge and completed independently), data analysis, or manuscript preparation or review.

Disclosures: Sesso and Manson reported receiving investigator-initiated grants from Mars Edge, a segment of Mars Incorporated dedicated to nutrition research and products, for infrastructure support and donation of COSMOS study pills and packaging, and Pfizer Consumer Healthcare (now part of GSK Consumer Healthcare) for donation of COSMOS study pills and packaging during the conduct of the study. Dr. Sesso additionally reported receiving investigator-initiated grants from Pure Encapsulations and Pfizer Inc., and honoraria and/or travel for lectures from the Council for Responsible Nutrition, BASF, NIH, and American Society of Nutrition during the conduct of the study.