Plain language summary
Cocoa is made from the bean of the cacao tree and has a long history of potential health benefits based upon its flavanol and procyanidin content. Cocoa extract also contains methylxanthines [alkaloids] such as theobromine and caffeine, which may enhance the vascular and central nervous system effects of cocoa flavanols. The aim of this study was to evaluate the flavanol-rich cocoa extract containing all potential bioactive components of the cocoa bean on clinical cardiovascular outcomes. This study is a randomised, double-blind, placebo-controlled, 2 × 2 factorial trial testing a cocoa extract supplement and a multivitamin supplement (COSMOS). This study focuses on the cocoa extract component of the trial. A total of 21,442 participants underwent randomisation to one of the four groups. Results show that after a median of 3.6 years of treatment there was no statistically significant effect on the primary outcome of total cardiovascular events. However, cocoa flavanol supplementation significantly reduced cardiovascular disease death by 27%, whereas other individual cardiovascular outcomes had no significant reductions in risk. Authors conclude that longer-term follow-up of the trial cohort and ongoing ancillary mechanistic studies in COSMOS may further elucidate the relation between cocoa extract supplementation and clinical cardiovascular events.
Abstract
BACKGROUND Cocoa extract is a source of flavanols that favorably influence vascular risk factors in small and short-term trials, yet effects on clinical cardiovascular events are untested. OBJECTIVES We examined whether cocoa extract supplementation decreases total cardiovascular disease (CVD) among older adults. METHODS We conducted a randomized, double-blind, placebo-controlled, 2-by-2 factorial trial of cocoa extract supplementation and multivitamins for prevention of CVD and cancer among 21,442 US adults (12,666 women aged ≥65 y and 8776 men aged ≥60 y), free of major CVD and recently diagnosed cancer. The intervention phase was June 2015 through December 2020. This article reports on the cocoa extract intervention. Participants were randomly assigned to a cocoa extract supplement [500 mg flavanols/d, including 80 mg (-)-epicatechin] or placebo. The primary outcome was a composite of confirmed incident total cardiovascular events, including myocardial infarction (MI), stroke, coronary revascularization, cardiovascular death, carotid artery disease, peripheral artery surgery, and unstable angina. RESULTS During a median follow-up of 3.6 y, 410 participants taking cocoa extract and 456 taking placebo had confirmed total cardiovascular events (HR: 0.90; 95% CI: 0.78, 1.02; P = 0.11). For secondary endpoints, HRs were 0.73 (95% CI: 0.54, 0.98) for CVD death, 0.87 (95% CI: 0.66, 1.16) for MI, 0.91 (95% CI: 0.70, 1.17) for stroke, 0.95 (95% CI: 0.77, 1.17) for coronary revascularization, neutral for other individual cardiovascular endpoints, and 0.89 (95% CI: 0.77, 1.03) for all-cause mortality. Per-protocol analyses censoring follow-up at nonadherence supported a lower risk of total cardiovascular events (HR: 0.85; 95% CI: 0.72, 0.99). There were no safety concerns. CONCLUSIONS Cocoa extract supplementation did not significantly reduce total cardiovascular events among older adults but reduced CVD death by 27%. Potential reductions in total cardiovascular events were supported in per-protocol analyses. Additional research is warranted to clarify whether cocoa extract may reduce clinical cardiovascular events. This trial is registered at www.clinicaltrials.gov as NCT02422745.
Methodological quality
Jadad score
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5
Allocation concealment
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Yes
