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1546-170X3232026MarNature medicineNat MedEffects of daily multivitamin-multimineral and cocoa extract supplementation on epigenetic aging clocks in the COSMOS randomized clinical trial.101210221012-102210.1038/s41591-026-04239-3Large-scale randomized trials have found that multivitamin-multimineral (MVM) supplements and cocoa flavanols may benefit several age-related chronic conditions among older adults, but it remains unclear whether these two supplements directly slow the biological aging process. This prespecified ancillary study evaluated the 2-year effect of a daily MVM (Centrum Silver) and cocoa extract (500 mg cocoa flavanols per day, including 80 mg (-)-epicatechin) on five DNA methylation measures of biological aging (PCHannum, PCHorvath, PCPhenoAge, PCGrimAge and DunedinPACE) among 958 participants (482 women and 476 men) in the COcoa Supplement and Multivitamin Outcomes Study (COSMOS). Compared with placebo, daily MVM supplementation modestly reduced the rate of increase of second-generation epigenetic clocks, with a between-group difference in yearly change of -0.113 years (95% confidence interval (CI) -0.205 to -0.020; P = 0.017) for PCGrimAge and -0.214 years (-0.410 to -0.019; P = 0.032) for PCPhenoAge. MVM had a stronger effect on PCGrimAge among those with accelerated biological aging at baseline (-0.236 [-0.380 to -0.091]) compared with those with normal or decelerated biological aging (-0.013 [-0.130 to 0.104]; P = 0.018 for interaction). Cocoa extract did not have an effect on the five epigenetic clocks tested. Although the statistically significant but small effects of daily MVM supplementation on slowing biological aging are encouraging, additional studies are needed to determine the clinical relevance of daily MVM supplementation on epigenetic clocks and whether such effects can help explain the beneficial effects of MVM supplementation on aging-related chronic conditions.© 2026. The Author(s), under exclusive licence to Springer Nature America, Inc.LiSidongS0000-0002-4798-8920Institute of Public Health Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.HamayaRikutaRDivision of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.ZhuHaidongH0000-0002-8384-0464Georgia Prevention Institute, Medical College of Georgia, Augusta University, Augusta, GA, USA.ChenBrian HBH0000-0001-9065-3301California Pacific Medical Center Research Institute, San Francisco, CA, USA.PereiraAlexandre CAC0000-0002-7782-5540Division of Aging, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.IveyKerry LKLDivision of Aging, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.RistPamela MPM0000-0003-3543-045XDivision of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.MansonJoAnn EJE0000-0002-9426-7595Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.Mary Horrigan Connors Center for Women's Health Research, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.DongYanbinYGeorgia Prevention Institute, Medical College of Georgia, Augusta University, Augusta, GA, USA.SessoHoward DHD0000-0002-9698-9954Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA. hsesso@bwh.harvard.edu.Division of Aging, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA. hsesso@bwh.harvard.edu.Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA. hsesso@bwh.harvard.edu.engHL157665U.S. Department of Health & Human Services | National Institutes of Health (NIH)AG050657, AG071611, and EY025623U.S. Department of Health & Human Services | National Institutes of Health (NIH)NAMassachusetts Life Sciences Center (MLSC)Journal ArticleRandomized Controlled Trial20260309
United StatesNat Med95020151078-89560Vitamins0Plant Extracts0MineralsIMHumansDietary SupplementsAgingdrug effectsgeneticsCacaochemistryEpigenesis, Geneticdrug effectsFemaleVitaminsadministration & dosagepharmacologyPlant Extractsadministration & dosagepharmacologyDNA Methylationdrug effectsAgedMaleMineralsadministration & dosagepharmacologyMiddle AgedCompeting interests: J.E.M. and H.D.S. 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. H.D.S. additionally received investigator-initiated grants from FOXO Technologies, Massachusetts Life Sciences Center, 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. P.M.R. has received in-kind support (specifically donations of study pills and packaging) from Mars Edge to be used in an NIH-funded, investigator-initiated trial (U01 AT012611 ). B.H.C. was formerly an employee of FOXO Technologies, who provided in-kind donations to generate and preprocess the DNA methylation data. S.L. received the EPI Early Career Travel Grant sponsored by the Council on Epidemiology and Prevention’s Early Career Committee, American Heart Association. The other authors declare no competing interests.2025311202612220263216302026310702026310026ppublish4180334110.1038/s41591-026-04239-310.1038/s41591-026-04239-3Wu, Z., Zhang, W., Qu, J. & Liu, G. H. 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