{"doi":"10.1093/ageing/afaf269","title":"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","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.","journal":"Age and Ageing","year":2025,"id":531723,"datarank":0.26876392038420827,"base_score":1.791759469228055,"endowment":1.791759469228055,"self_citation_contribution":0.26876392038420827,"citation_network_contribution":0.0,"self_endowment_contribution":0.26876392038420827,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":5,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9501,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":331314,"name":"Rikuta Hamaya","orcid":"0000-0003-1635-1983","position":1,"is_corresponding":false},{"id":292485,"name":"Haidong Zhu","orcid":"0000-0002-8384-0464","position":2,"is_corresponding":false},{"id":844943,"name":"Allison Clar","orcid":null,"position":3,"is_corresponding":false},{"id":302168,"name":"Pamela M. Rist","orcid":"0000-0003-3543-045X","position":4,"is_corresponding":false},{"id":1412535,"name":"Ying Huang","orcid":"0000-0001-8532-9494","position":5,"is_corresponding":false},{"id":11268,"name":"JoAnn E. Manson","orcid":"0000-0002-9426-7595","position":6,"is_corresponding":false},{"id":420934,"name":"Howard D. Sesso","orcid":"0000-0002-9698-9954","position":7,"is_corresponding":false},{"id":292486,"name":"Yanbin Dong","orcid":"0000-0001-7848-7160","position":8,"is_corresponding":false},{"id":1412534,"name":"Sidong Li","orcid":"0000-0002-4798-8920","position":0,"is_corresponding":true}],"reference_count":45,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:51:18.928280Z","pmid":"40966617","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}