Welcome to the COSMOS Trial!
The COcoa Supplement and Multivitamin Outcomes Study (COSMOS) at Brigham and Women’s Hospital – an affiliate of Harvard Medical School (Boston, MA) – and the Fred Hutchinson Cancer Research Center (Seattle, WA) is a clinical trial that randomized 21,444 men and women across the U.S. The study has investigated whether taking daily supplements of cocoa flavanols (600 mg/day) or a common multivitamin reduces the risk for developing heart disease, stroke, cancer, and other important health outcomes.
Although results from previous studies have been promising, the health benefits of taking these supplements have not yet been proven. The only way to determine whether or not cocoa flavanol and multivitamin supplements help maintain health is by conducting a large-scale trial, such as COSMOS.
We are excited to announce that study pill taking has ended on December 31, 2020. Other important information about the end of this phase of the COSMOS trial can be found in COSMOS Connection Issue 5, which you can access in the COSMOS Connection Newsletters tab.
Why Is COSMOS Important?
The COcoa Supplement and Multivitamin Outcomes Study (COSMOS) is a randomized, double-blind, placebo-controlled trial testing a cocoa extract supplement (containing 600 mg/d flavanols), and a multivitamin supplement in the maintenance of cardiovascular health and cancer risk in a total of 21,444 participants, including 12,680 women aged ≥65 years and more than 8,764 men aged ≥60 years with an average of 4 years of treatment and follow-up. These promising interventions have both already shown favorable results in research studies, and are well-tolerated and safe.
Cocoa is an ancient fermented product that the Aztecs made from the bean of the cacao tree, Theobroma cacao. Cocoa products contain catechins and epicatechins, readily water-soluble flavonoids classified as flavan-3-ols,1 a subclass of flavonoids with vascular health benefits. Experimental and clinical studies testing the consumption of cocoa products and cocoa flavanols have noted potential benefits on platelet activation,2 LDL oxidation,3 lipid profiles,4 endothelium-dependent vasodilation,5 inflammation,6 blood pressure,7 and insulin resistance,8 which may translate into important cardiovascular benefits. COSMOS represents the first large-scale trial in women and men to evaluate the long-term effects of a cocoa extract supplement on cardiovascular health outcomes.
Multivitamins are the most common dietary supplement taken in the U.S., with more than one-third of adults reporting regular multivitamin use.9 While the primary purpose of multivitamins is to reduce vitamin or mineral deficiencies, many U.S. adults still take multivitamin supplements to reduce chronic diseases or promote general health and well-being.10 Our research group previously conducted the Physicians’ Health Study (PHS) II, a randomized trial testing a multivitamin in 14,641 men aged ≥50 years. We found a modest but significant 8% reduction in total cancer,11 and no effect on cardiovascular disease.12 Further, there was suggestive evidence that daily multivitamin use may have greater benefits among men with a prior cancer diagnosis. As yet there are no corresponding randomized trials conducted among women, and the nature of the data in men indicates that these findings should be replicated to determine whether a multivitamin reduces the risk of cancer, particularly among women and those with a history of cancer.
For both interventions, a confirmatory large-scale randomized trial such as the COSMOS in women and men could have major clinical and public health implications.
1. Aron PM, Kennedy JA. Flavan-3-ols: nature, occurrence and biological activity. Mol Nutr Food Res 2008;52:79-104.
2. Rull G, Mohd-Zain ZN, Shiel J, Lundberg MH, Collier DJ, Johnston A, Warner TD, Corder R. Effects of high flavanol dark chocolate on cardiovascular function and platelet aggregation. Vascul Pharmacol 2015.
3. Baba S, Osakabe N, Kato Y, Natsume M, Yasuda A, Kido T, Fukuda K, Muto Y, Kondo K. Continuous intake of polyphenolic compounds containing cocoa powder reduces LDL oxidative susceptibility and has beneficial effects on plasma HDL-cholesterol concentrations in humans. Am J Clin Nutr 2007;85:709-717.
4. Tokede OA, Gaziano JM, Djoussé L. Effects of cocoa products/dark chocolate on serum lipids: a meta-analysis. Eur J Clin Nutr 2011;65:879-886.
5. Heiss C, Sansone R, Karimi H, Krabbe M, Schuler D, Rodriguez-Mateos A, Kraemer T, Cortese-Krott MM, Kuhnle GG, Spencer JP, Schroeter H, Merx MW, Kelm M. Impact of cocoa flavanol intake on age-dependent vascular stiffness in healthy men: a randomized, controlled, double-masked trial. Age (Dordr) 2015;37:9794.
6. Monagas M, Khan N, Andres-Lacueva C, Casas R, Urpi-Sarda M, Llorach R, Lamuela-Raventos RM, Estruch R. Effect of cocoa powder on the modulation of inflammatory biomarkers in patients at high risk of cardiovascular disease. Am J Clin Nutr 2009;90:1144-1150.
7. Ried K, Sullivan TR, Fakler P, Frank OR, Stocks NP. Effect of cocoa on blood pressure. Cochrane Database Syst Rev 2012;8:CD008893.
8. Lin X, Zhang I, Li A, Manson JE, Sesso HD, Wang L, Liu S. Cocoa Flavanol Intake and Biomarkers for Cardiometabolic Health: A systematic review and meta-analysis of randomized controlled trials. J Nutr 2016;146:2325-2333.
9. Gahche J, Bailey R, Burt V, Hughes J, Yetley E, Dwyer J, Picciano MF, McDowell M, Sempos C. Dietary supplement use among U.S. adults has increased since NHANES III (1988-1994). NCHS Data Brief 2011:1-8.
10. Bailey RL, Gahche JJ, Miller PE, Thomas PR, Dwyer JT. Why US adults use dietary supplements. JAMA Intern Med 2013:1-7.
11. Gaziano JM, Sesso HD, Christen WG, Bubes V, Smith JP, MacFadyen J, Schvartz M, Manson JE, Glynn RJ, Buring JE. Multivitamins in the prevention of cancer in men: the Physicians’ Health Study II randomized controlled trial. JAMA 2012;308:1871-1880.
12. Sesso HD, Christen WG, Bubes V, Smith JP, MacFadyen J, Schvartz M, Manson JE, Glynn RJ, Buring JE, Gaziano JM. Multivitamins in the prevention of cardiovascular disease in men: the Physicians’ Health Study II randomized controlled trial. JAMA 2012;308:1751-1760.