Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Randomized Controlled Trial
. 2025 Aug 29;54(9):afaf269.
doi: 10.1093/ageing/afaf269.

Effects of 2-year cocoa extract supplementation on inflammaging biomarkers in older US adults: findings from the COcoa Supplement and Multivitamin Outcomes Study randomised clinical trial

Sidong Li  1   2 , Rikuta Hamaya  2   3 , Haidong Zhu  4 , Allison Clar  2 , Pamela M Rist  2   3 , Ying Huang  4 , JoAnn E Manson  2   3 , Howard D Sesso  2   3 , Yanbin Dong  4
Affiliations
Randomized Controlled Trial

Effects of 2-year cocoa extract supplementation on inflammaging biomarkers in older US adults: findings from the COcoa Supplement and Multivitamin Outcomes Study randomised clinical trial

Sidong Li et al. Age Ageing. .

Abstract

Objective: To examine the long-term effect of cocoa flavanols on inflammaging biomarkers in the COcoa Supplement and Multivitamin Outcomes Study (COSMOS).

Methods: COSMOS is a large, randomised, double-blind, placebo-controlled, 2 × 2 factorial trial testing the effects of a cocoa extract supplement (containing 500 mg cocoa flavanols/day, including 80 mg (-)-epicatechin) among women aged ≥65 years and men aged ≥60 years. This ancillary study measured five widely used serum inflammaging biomarkers, including three pro-inflammatory markers (high-sensitivity C-reactive protein [hsCRP], interleukin-6, tumour necrosis factor-α), one anti-inflammatory cytokine (interleukin-10) and one pleotropic cytokine (interferon-γ [IFN-γ]) in a random sample of 598 participants with biospecimens collected at baseline, Year 1, and Year 2.

Results: The mean age was 70.0 ± 5.6 years, and 49.8% were female. Cocoa extract supplementation significantly decreased hsCRP levels compared with placebo, with a between-group difference in yearly percentage change relative to baseline levels of -8.4% (95% CI, -14.1% to -2.3%; nominal P = .008; Holm-adjusted P value = .039). Moreover, cocoa extract increased IFN-γ with a 6.8% (95% CI, 1.5% to 12.2%, nominal P = .011; Holm-adjusted P value = .043) difference in yearly percentage change versus placebo. The effects of cocoa extract on other inflammatory markers were not significant (all adjusted P values >.05).

Conclusion: Cocoa extract supplementation significantly decreased hsCRP, supporting a role in modulating the chronic inflammaging process as a potential mechanism underlying its cardio-protective effects, including a 27% reduction in cardiovascular disease death in the COSMOS trial. The biological effect of increased IFN-γ by cocoa extract warrants further exploration.

Keywords: cocoa extract; hsCRP; inflammaging; older adults; randomised controlled trial.

PubMed Disclaimer

Conflict of interest statement

Drs. Manson and Sesso received 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 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, American Pistachio Growers and Haleon, and honoraria and/or travel for lectures from the Council for Responsible Nutrition, BASF, Haleon and NIH during the conduct of the study. No other authors reported any conflicts of interests for this study.

References

    1. Ortman JM, Velkoff VA, Hogan H. An Aging Nation: The Older Population in the United States. Current Population Reports, P25-1140. U.S. Census Bureau, Washington, DC, 2014. Available at: https://www.census.gov/content/dam/Census/library/publications/2014/demo.... Accessed 17 June 2024.
    1. Franceschi C, Bonafè M, Valensin S et al. Inflamm-aging. An evolutionary perspective on immunosenescence. Ann N Y Acad Sci 2000;908:244–54. 10.1111/j.1749-6632.2000.tb06651.x. - DOI - PubMed
    1. Minciullo PL, Catalano A, Mandraffino G et al. Inflammaging and anti-Inflammaging: the role of cytokines in extreme longevity. Arch Immunol Ther Exp (Warsz) 2016;64:111–26. 10.1007/s00005-015-0377-3. - DOI - PubMed
    1. Calder PC, Bosco N, Bourdet-Sicard R et al. Health relevance of the modification of low grade inflammation in ageing (inflammageing) and the role of nutrition. Ageing Res Rev 2017;40:95–119. 10.1016/j.arr.2017.09.001. - DOI - PubMed
    1. Goya L, Martin MA, Sarria B et al. Effect of cocoa and its flavonoids on biomarkers of inflammation: studies of cell culture, animals and humans. Nutrients. 2016;8:212. 10.3390/nu8040212. - DOI - PMC - PubMed

Publication types

MeSH terms