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.

2025-08-29
Age and ageing 54(9)
- Sidong Li
- Rikuta Hamaya
- Haidong Zhu
- Allison Clar
- Pamela M Rist
- Ying Huang
- JoAnn E Manson
- Howard D Sesso
- Yanbin Dong

PubMed: 40966617
DOI: 10.1093/ageing/afaf269

Study Design

Type: Randomized Controlled Trial (RCT)
Sample size: n = 598
Population: women aged ≥65 years and men aged ≥60 years
Methods: Randomised, double-blind, placebo-controlled, 2×2 factorial trial of cocoa extract supplement (containing 500 mg cocoa flavanols/day, including 80 mg (-)-epicatechin); ancillary study measured five serum inflammaging biomarkers in a random sample of 598 participants
Blinding: Double-blind
Duration: 2 years
Funding: Unclear

Large Human Trial

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.