Summary: A large clinical trial found that cocoa flavanol supplements can lower age-related inflammation, potentially explaining their heart-protective effects. Researchers analyzed blood samples and discovered a consistent reduction in hsCRP, a biomarker tied to cardiovascular risk, among participants taking cocoa extract.
Other inflammatory markers stayed relatively stable, though some shifts, like an increase in immune-related interferon-γ, raised new questions. These findings highlight cocoa flavanols as a promising tool for modulating inflammation while reinforcing the importance of plant-based foods in healthy aging.
Key Facts
- hsCRP Reduction: Cocoa extract lowered this key inflammatory marker by 8.4% yearly.
- Heart Protection: Results support prior evidence of reduced cardiovascular mortality in the COSMOS trial.
- Dietary Insight: Flavanol-rich foods like cocoa, berries, and tea may support healthy aging.
Source: Mass General
Could cocoa extract supplements rich in cocoa flavanols reduce inflammation and, in turn, prevent age-related chronic diseases?
In a new study from the COcoa Supplement and Multivitamin Outcomes Study (COSMOS), investigators from Mass General Brigham and their colleagues looked at changes in five age-related markers of inflammation among participants who received daily cocoa supplements over several years.
They found that hsCRP—an inflammatory marker that can signal increased risk of cardiovascular disease—decreased in participants taking the cocoa extract supplement, suggesting its anti-inflammatory potential may help explain its heart-protective effects.
Their results are published in Age and Ageing.
Nutritional interventions have become an increasingly attractive solution for slowing inflammatory aging, so called “inflammaging.” Cocoa extract has been shown in previous, smaller studies to reduce inflammatory biomarkers, thanks to flavanols—small, bioactive compounds found not only in the cocoa bean but also berries, grapes, tea, and other plant-based foods.
To bridge the gap between these studies and humans, researchers launched the large-scale COSMOS trial, which examines the effects of cocoa extract on cardiovascular disease, and whether inflammaging may explain those effects.
“Our interest in cocoa extract and inflammaging started on the basis of cocoa-related reductions in cardiovascular disease,” said corresponding author Howard Sesso, ScD, MPH, associate director of the Division of Preventive Medicine and associate epidemiologist at Brigham and Women’s Hospital, a founding member of the Mass General Brigham healthcare system.
“We also appreciate the important overlap between healthy aging and cardiovascular health, where aging-related inflammation can harden arteries and lead to cardiovascular disease. Because of that, we wanted to see whether multi-year cocoa extract supplementation versus a placebo could modulate inflammaging—and the data suggests it does.”
Between 2014 and 2020, Brigham and Women’s Hospital led the COSMOS trial, a large-scale, randomized, double-blind, placebo-controlled clinical trial with 21,442 participants over 60 years old, finding that cocoa extract supplementation decreased cardiovascular disease mortality by 27%.
In this new study, researchers collected and analyzed blood samples of 598 COSMOS participants to measure several inflammaging biomarkers: three pro-inflammatory proteins (hsCRP, IL-6, and TNF-α), one anti-inflammatory protein (IL-10), and one immune-mediating protein (IFN-γ). Comparing changes in these biomarkers measured at baseline, 1, and 2 years follow-up, hsCRP levels decreased by 8.4% each year compared with placebo, while the other biomarkers remained relatively consistent or increased modestly.
“Interestingly, we also observed an increase in interferon-γ, an immune-related cytokine, which opens new questions for future research,” said senior author Yanbin Dong, MD/PhD, Director of the Georgia Prevention Institute (GPI) and cardiologist/population geneticist at the Medical College of Georgia/Augusta University.
“While cocoa extract is not a replacement for a healthy lifestyle, these results are encouraging and highlight its potential role in modulatingi nflammation as we age.
The decrease in hsCRP may help explain the cardio-protective effects seen with cocoa extract supplement in the larger COSMOS trial, where participants experienced a reduction in cardiovascular disease death.
Researchers said that changes in the other inflammaging markers, including a small reduction in IL-6 observed in female but not male participants, warrant additional study.
The team will continue to evaluate the COSMOS trial to determine whether the cocoa – and multivitamin – regimens can curb more severe inflammaging, as well as other important aging-related health outcomes.
“This study calls for more attention to the advantage of plant-based foods for cardiovascular health, including cocoa products rich in flavanols,” added Sesso. “It reinforces the importance of a diverse, colorful, plant-based diet—especially in the context of inflammation.”
Authorship: In addition to Sesso, Mass General Brigham authors include Sidong Li, Rikuta Hamaya, Allison Clar, Pamela M. Rist, and JoAnn E. Manson. In addition to Dong, Augusta University authors include Haidong Zhu and Ying Huang.
Disclosures: 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 (now Haleon) for donation of COSMOS study pills and packaging during the conduct of the study.
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
Funding: This work is supported by the National Institutes of Health (HL157665).
The COcoa Supplement and Multivitamin Outcomes Study (COSMOS) is supported by an investigator-initiated grant from Mars Edge, 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.
COSMOS is also supported in part by the National Institutes of Health (AG050657, AG071611, and EY025623). Neither company had a role in the trial design or conduct, data collection, data analysis, or manuscript preparation or review.
About this supplementation and inflammation research news
Author: Alexandra Pantano
Source: Mass General
Contact: Alexandra Pantano – Mass General
Image: The image is credited to Neuroscience News
Original Research: Open access.
“Effects of Two-year Cocoa Extract Supplementation on Inflammaging Biomarkers in Older US Adults: Findings from the COSMOS Randomized Clinical Trial” by Howard Sesso et al. Age and Ageing
Abstract
Effects of Two-year Cocoa Extract Supplementation on Inflammaging Biomarkers in Older US Adults: Findings from the COSMOS Randomized Clinical 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.
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