Effects of 2-year cocoa extract supplementation on inflammaging biomarkers in older US adults
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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% (see).
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. The decrease in hsCRP suggests an explanation for the cardio-protective effects seen with cocoa extract supplement in the larger COSMOS trial, where participants experienced a reduction in cardiovascular disease death.
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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@DavidPS this is interesting. I looked for a cocoa extract and found many, but they don’t tend to list the specific content of the polyphenols. There was one in particular that was mentioned at a dose of 80mg, (so it seemed like the researchers thought it was particularly significant).
I was looking into it because I was curious if simply eating cocoa powder would be an effective means of achieving the same results. I assume not as extracts tend to have more potency, but this may be difficult to replicate. Anyone have any insights.
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@evan-hinkle said in Effects of 2-year cocoa extract supplementation on inflammaging biomarkers in older US adults:
There was one in particular that was mentioned at a dose of 80mg, (so it seemed like the researchers thought it was particularly significant).
I would not put too much credence in 80 mg. The study below shows that 70% cocoa dark chocolate consumption can benefit verbal episodic memory two hours post consumption in healthy young adults relative to a white chocolate control. These findings support the notion that everyday available portions (35 g or 35,000 mg) of dark chocolate can confer benefits to the brain in healthy consumers.
I suspect that the 80mg was used for safety reasons. Perhaps to get the study approved.

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IL-6 isn't an "inflammatory protein". It is a transient signalling molecule of immune involvement..it raises when you go for a walk and eat a carb heavy meal, so is walking and eating inflammatory too?
You can't look at cytokines in isolation..cytokines are not inflammation..they are the response to something like PAMP's e.g PRR's,TLR2/4, Dectin-1, CARD9, DAMP's e.g TLR-9, TNF-a, IL-β, hypoxia e.g chronic HIF-1a signalling , mitochondrial ineffiency e.g reduced PGC-1a, reduced OXPHOS that immune function has decided it doesn't have the energy or resources to resolve, so the threat assessment never reaches the resolution phase e.g IL-10, Tregs, M1-M2, SPM's like it would with food poisoning, wound healing, bacterial infections that induce aggressive acute immune function like c.difficile infections and waterborne illness
Inflammation is the dysregulated response of immune function to a perceived threat that it does not have the facility to, or has not received the gating to resolve, so it just manages the situation. That "management" is the inflammation as it wastes NAD, forces longer windows of aerobic glycolysis, induces more hypoxia. Not cytokines .which means all these studies are particularly nonsense. Furthemore there isn't anything in cacao xanthines or polyphenols or any other polyphenol for that matter that can resolve inflammation. The keyword is resolve..it can transiently inhibit NF-kB through IKK, and it can push Nrf2(this would probably just result in even more redox stress though without resolution), but neither of these things equal resolution..without the signalling cacscade i mentioned earlier, there is no getting out of "inflammaging" or chronic inflammation and because inflammaging is largely driven by hypoxia through things like uncoupling of eNOS, BH4, mitochondrial inefficiency etc this is something you cannot reverse beyond a certain point or age..inflammaging to use the cringe term, is inevitable and you might as well just call it aging.