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Thromb Haemost
DOI: 10.1055/a-2806-3554
Original Article: Stroke, Systemic or Venous Thromboembolism

Effects of Cocoa Extract and Multivitamin Supplementation on Venous Thromboembolism in the COSMOS Trial

Authors

  • Sarah Jaehwa Park 

    1   Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, United States
    2   Osher Center for Integrative Health, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, United States

  • JoAnn E. Manson

    1   Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, United States
    3   Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, United States

  • Eunjung Kim

    1   Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, United States

  • Robert J. Glynn

    1   Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, United States
    4   Department of Biostatistics, Harvard T. H. Chan School of Public Health, Boston, Massachusetts, United States

  • Pamela M. Rist

    1   Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, United States
    3   Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, United States

  • Matthew A. Allison

    5   Department of Family Medicine, University of California, San Diego, California, United States

  • Howard D. Sesso

    1   Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, United States
    2   Osher Center for Integrative Health, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, United States
    3   Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, United States

Funding Information This publication was supported in part by the National Center for Complementary and Integrative Health of the National Institutes of Health (NIH), Bethesda, MD with training grant 5T32AT000051 (SJP). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. The COcoa Supplement and Multivitamin Outcomes Study (COSMOS) is supported by an investigator-initiated grant from Mars Edge (JEM, HDS), a segment of Mars dedicated to nutrition research and products, which included infrastructure support and the donation of study pills and packaging. Pfizer Consumer Healthcare (now Haleon) provided support through the partial provision of study pills and packaging (JEM, HDS). COSMOS is also supported in part by NIH grants AG050657, AG071611, EY025623, and HL157665. The WHI program is funded by the National Heart, Lung, and Blood Institute, National Institutes of Health, US Department of Health and Human Services through 75N92021D00001, 75N92021D00002, 75N92021D00003, 75N92021D00004, 75N92021D00005.
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Graphical Abstract

Abstract

Background

Epidemiological and experimental studies suggest cocoa flavanols and multivitamin-multimineral (MVM) supplements may confer arterial vascular benefits. However, their effects on clinical venous thromboembolic events have been infrequently examined.

Objective

To evaluate whether cocoa extract (CE) or MVM supplementation reduces the risk of venous thromboembolism (VTE) among older adults.

Methods

We conducted an ancillary study analysis of the COcoa Supplement and Multivitamin Outcomes Study (COSMOS), a completed randomized, double-blind, placebo-controlled, 2-by-2 factorial trial of CE and MVM supplementation for the prevention of cardiovascular disease and cancer among 21,442 older US adults. Our primary outcome was self-reported incident VTE, defined as the first reported deep vein thrombosis (DVT) or pulmonary embolism (PE) event after randomization; secondary outcomes were the individual components.

Results

Over a median follow-up of 3.5 years, 379 participants reported an incident VTE event (including 277 DVT and 165 PE). In intention-to-treat analyses, neither CE (HR: 0.88; 95% CI: 0.72, 1.08) nor MVM (HR: 0.89; 95% CI: 0.73, 1.09) significantly reduced VTE risk, with similar findings for DVT and PE. Exploratory latency and per-protocol analyses suggested potential patterns of benefit that merit further evaluation.

Conclusion

In this large trial of older adults, neither CE nor MVM supplementation significantly reduced the risk of VTE or its component parts in intention-to-treat analyses. Additional research may help clarify whether these supplements influence VTE risk in other contexts or populations.

Keywords

cocoa extract - multivitamin - venous thromboembolism - deep vein thrombosis - pulmonary embolism

Data Availability Statement

The dataset(s) will be de-identified prior to release for sharing. We will make the data and associated documentation available to users only under a data-sharing agreement. Details on the availability of the study data to other investigators will be on our study Web site at https://cosmostrial.org/.


Contributors' Statement

H.D.S. had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis; S.J.P. and H.D.S. conceptualized and designed the study; E.K. performed statistical analysis; S.J.P., J.E.M., E.K., R.J.G., P.M.R., M.A.A., and H.D.S. acquired, analyzed, or interpreted the data; S.J.P. drafted the manuscript; S.J.P., J.E.M., E.K., R.J.G., P.M.R., M.A.A., and H.D.S. provided critical edits to the manuscript. All the authors read and approved the final manuscript.


Supplementary Material



Publication History

Received: 26 June 2025

Accepted after revision: 04 February 2026

Accepted Manuscript online:
06 February 2026

Article published online:
16 February 2026

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