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Learn more: PMC Disclaimer | PMC Copyright Notice JBMR Plus . 2026 Mar 18;10(5):ziag041. doi: 10.1093/jbmrpl/ziag041 Search in PMC Search in PubMed View in NLM Catalog Add to search Effects of cocoa extract supplementation on physical performance measures: results from the randomized controlled COcoa Supplement and Multivitamin Outcomes study Sharon H Chou Sharon H Chou 1 Division of Endocrinology, Diabetes and Hypertension, Brigham and Women’s Hospital, Boston, MA 02115, United States 2 Harvard Medical School, Boston, MA 02115, United States Conceptualization, Investigation, Methodology, Writing - original draft, Writing - review & editing Find articles by Sharon H Chou 1, 2, ✉ , Nancy Cook Nancy Cook 3 Harvard Medical School, Boston, MA 02115, United States 4 Division of Preventive Medicine, Brigham and Women’s Hospital, Boston, MA 02115, United States 5 Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA 02115, United States Conceptualization, Formal analysis, Investigation, Methodology, Writing - review & editing Find articles by Nancy Cook 3, 4, 5 , Eunjung Kim Eunjung Kim 6 Harvard Medical School, Boston, MA 02115, United States 7 Division of Preventive Medicine, Brigham and Women’s Hospital, Boston, MA 02115, United States 8 Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA 02115, United States Formal analysis Find articles by Eunjung Kim 6, 7, 8 , Gregory Kotler Gregory Kotler 9 Harvard Medical School, Boston, MA 02115, United States 10 Division of Preventive Medicine, Brigham and Women’s Hospital, Boston, MA 02115, United States 11 Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA 02115, United States Formal analysis Find articles by Gregory Kotler 9, 10, 11 , David A Ganz David A Ganz 12 Department of Medicine, David Geffen School of Medicine at University of California, Los Angeles, CA 90095, United States 13 Geriatric Research, Education and Clinical Center, Veterans Affairs Greater Los Angeles, CA 90073, United States 14 RAND, Santa Monica, CA 90401, United States Conceptualization, Writing - review & editing Find articles by David A Ganz 12, 13, 14 , Peggy M Cawthon Peggy M Cawthon 15 Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, CA 94115, United States 16 California Pacific Medical Center, Research Institute, San Francisco, CA 94143, United States Conceptualization, Writing - review & editing Find articles by Peggy M Cawthon 15, 16 , Allison Clar Allison Clar 17 Harvard Medical School, Boston, MA 02115, United States 18 Division of Preventive Medicine, Brigham and Women’s Hospital, Boston, MA 02115, United States 19 Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA 02115, United States Project administration, Writing - review & editing Find articles by Allison Clar 17, 18, 19 , Aladdin H Shadyab Aladdin H Shadyab 20 Herbert Wertheim School of Public Health and Human Longevity Science, University of California San Diego, La Jolla, CA 92093, United States 21 Division of Geriatrics, Gerontology, and Palliative Care, Department of Medicine, University of California San Diego, La Jolla, CA 92093, United States Writing - review & editing Find articles by Aladdin H Shadyab 20, 21 , JoAnn E Manson JoAnn E Manson 22 Harvard Medical School, Boston, MA 02115, United States 23 Division of Preventive Medicine, Brigham and Women’s Hospital, Boston, MA 02115, United States 24 Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA 02115, United States Conceptualization, Data curation, Funding acquisition, Investigation, Methodology, Resources, Supervision, Visualization, Writing - review & editing Find articles by JoAnn E Manson 22, 23, 24 , Howard D Sesso Howard D Sesso 25 Harvard Medical School, Boston, MA 02115, United States 26 Division of Preventive Medicine, Brigham and Women’s Hospital, Boston, MA 02115, United States 27 Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA 02115, United States Conceptualization, Data curation, Funding acquisition, Investigation, Methodology, Resources, Supervision, Visualization, Writing - review & editing Find articles by Howard D Sesso 25, 26, 27 , Carolyn J Crandall Carolyn J Crandall 28 Division of General Internal Medicine and Health Services Research, Department of Medicine, David Geffen School of Medicine at University of California, Los Angeles, CA 90024, United States Conceptualization, Funding acquisition, Investigation, Methodology, Supervision, Visualization, Writing - review & editing Find articles by Carolyn J Crandall 28 , Meryl LeBoff Meryl LeBoff 29 Division of Endocrinology, Diabetes and Hypertension, Brigham and Women’s Hospital, Boston, MA 02115, United States 30 Harvard Medical School, Boston, MA 02115, United States Conceptualization, Funding acquisition, Investigation, Methodology, Supervision, Visualization, Writing - review & editing Find articles by Meryl LeBoff 29, 30 Author information Article notes Copyright and License information 1 Division of Endocrinology, Diabetes and Hypertension, Brigham and Women’s Hospital, Boston, MA 02115, United States 2 Harvard Medical School, Boston, MA 02115, United States 3 Harvard Medical School, Boston, MA 02115, United States 4 Division of Preventive Medicine, Brigham and Women’s Hospital, Boston, MA 02115, United States 5 Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA 02115, United States 6 Harvard Medical School, Boston, MA 02115, United States 7 Division of Preventive Medicine, Brigham and Women’s Hospital, Boston, MA 02115, United States 8 Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA 02115, United States 9 Harvard Medical School, Boston, MA 02115, United States 10 Division of Preventive Medicine, Brigham and Women’s Hospital, Boston, MA 02115, United States 11 Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA 02115, United States 12 Department of Medicine, David Geffen School of Medicine at University of California, Los Angeles, CA 90095, United States 13 Geriatric Research, Education and Clinical Center, Veterans Affairs Greater Los Angeles, CA 90073, United States 14 RAND, Santa Monica, CA 90401, United States 15 Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, CA 94115, United States 16 California Pacific Medical Center, Research Institute, San Francisco, CA 94143, United States 17 Harvard Medical School, Boston, MA 02115, United States 18 Division of Preventive Medicine, Brigham and Women’s Hospital, Boston, MA 02115, United States 19 Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA 02115, United States 20 Herbert Wertheim School of Public Health and Human Longevity Science, University of California San Diego, La Jolla, CA 92093, United States 21 Division of Geriatrics, Gerontology, and Palliative Care, Department of Medicine, University of California San Diego, La Jolla, CA 92093, United States 22 Harvard Medical School, Boston, MA 02115, United States 23 Division of Preventive Medicine, Brigham and Women’s Hospital, Boston, MA 02115, United States 24 Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA 02115, United States 25 Harvard Medical School, Boston, MA 02115, United States 26 Division of Preventive Medicine, Brigham and Women’s Hospital, Boston, MA 02115, United States 27 Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA 02115, United States 28 Division of General Internal Medicine and Health Services Research, Department of Medicine, David Geffen School of Medicine at University of California, Los Angeles, CA 90024, United States 29 Division of Endocrinology, Diabetes and Hypertension, Brigham and Women’s Hospital, Boston, MA 02115, United States 30 Harvard Medical School, Boston, MA 02115, United States ✉ Corresponding author: Sharon H. Chou, Division of Endocrinology, Diabetes and Hypertension, Brigham and Women’s Hospital, 221 Longwood Avenue, Boston, MA 02115, United States ( [email protected] ). Roles Sharon H Chou : Conceptualization, Investigation, Methodology, Writing - original draft, Writing - review & editing Nancy Cook : Conceptualization, Formal analysis, Investigation, Methodology, Writing - review & editing Eunjung Kim : Formal analysis Gregory Kotler : Formal analysis David A Ganz : Conceptualization, Writing - review & editing Peggy M Cawthon : Conceptualization, Writing - review & editing Allison Clar : Project administration, Writing - review & editing Aladdin H Shadyab : Writing - review & editing JoAnn E Manson : Conceptualization, Data curation, Funding acquisition, Investigation, Methodology, Resources, Supervision, Visualization, Writing - review & editing Howard D Sesso : Conceptualization, Data curation, Funding acquisition, Investigation, Methodology, Resources, Supervision, Visualization, Writing - review & editing Carolyn J Crandall : Conceptualization, Funding acquisition, Investigation, Methodology, Supervision, Visualization, Writing - review & editing Meryl LeBoff : Conceptualization, Funding acquisition, Investigation, Methodology, Supervision, Visualization, Writing - review & editing Received 2026 Feb 4; Accepted 2026 Mar 7; Collection date 2026 May. © The Author(s) 2026. Published by Oxford University Press on behalf of the American Society for Bone and Mineral Research. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( https://creativecommons.org/licenses/by/4.0/ ), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. PMC Copyright notice PMCID: PMC13089503 PMID: 42004609 Abstract Poor physical performance is associated with a higher risk of falls, fractures, and premature death among older adults. We determined whether supplementation with cocoa extract vs placebo or multivitamin/multimineral (MVM) vs placebo for 2 yr benefited physical performance measures. The COcoa Supplement and Multivitamin Outcomes Study was a double-blinded, placebo-controlled randomized trial of supplemental cocoa extract and/or MVM vs placebo for the primary prevention of cardiovascular disease and cancer in 21 442 US adults. This ancillary study was completed in a New England sub-cohort that underwent physical performance measurements, including grip strength, walking speed, standing balance, repeated chair stands, and timed-up and go (TUG) test, at baseline and 2-yr follow-up. In the clinic sub-cohort ( n = 603) with a mean (±SD) age of 69.7 ± 5.5 yr and 49.3% women, supplemental cocoa extract, compared to cocoa-extract placebo, did not affect 2-yr changes in our primary pre-specified, co-equal outcomes of grip strength, walking speed, and the Short Physical Performance Battery (composite of walking speed, standing balance, and chair stands) or in secondary outcomes of standing balance, chair stands, or TUG tests. No effect modification by baseline characteristics of age, sex, body mass index, or randomization to MVM supplementation was observed. In parallel analyses, MVM, compared to MVM placebo, also did not affect physical performance measures. Supplementation with cocoa extract did not prevent age-related declines in physical performance measures in older ambulatory US men and women. Keywords: cocoa extract, flavanol, multivitamin/multimineral, physical performance, grip strength, walking speed, Short Physical Performance Battery Introduction In the United States, there are more than 3 million emergency department visits per year for falls in adults 65 yr and older, and falls are the leading cause of death due to injury in this age group. 1 In total, medical costs for falls exceed $80 billion/yr in the United States. Physical performance measures predict fall risk. 2 Weak grip strength, slow walking speed, and other measures of poor physical performance have been associated with recurrent falls, hospitalization, and fractures. 3–8 Given the personal and economic burden, safe and effective interventions are needed to prevent falls and maintain good physical function in older adults. Preclinical data suggest that dietary flavanols or (−)-epicatechins, which are enriched in cocoa, may have benefits on muscle function by improving blood flow, decreasing oxidative stress, and stimulating mitochondrial biogenesis. 9–11 In small clinical studies of short duration, ranging from 6 wk to 6 mo, supplements with (−)-epicatechin or cocoa flavanol products have been found to improve grip strength and walking speed. 11–18 However, there are no large, long-term randomized controlled trials (RCTs) investigating the effects of a standardized cocoa flavanol formulation on physical performance measures. Although multivitamin/multimineral (MVM) use is high in athletes and US military personnel, 19 , 20 the sparse studies on the effects of MVM on physical performance have shown no benefit in active adults. 21 , 22 One small trial conducted in older adults (≥70 yr old who were institutionalized) found that a multivitamin beverage did not improve physical performance. 23 Since MVMs are widely used among older adults, 24 a better understanding of the impact of these supplements on age-related declines in physical function is needed. The COcoa Supplement and Multivitamin Outcomes Study (COSMOS) was a randomized, double-blind, placebo-controlled trial that investigated the effects of a cocoa extract supplement and/or an MVM on the primary prevention of cardiovascular disease and invasive cancer in 21 442 US participants. COSMOS featured a hybrid design and also included a clinic sub-cohort of 603 participants from the New England region for detailed, in-person phenotyping for mechanistic studies. 25 The ancillary study COSMOS: Effects on Falls and Physical Performance ( NCT05232669 ) was designed to investigate the effects of cocoa extract supplementation, compared to placebo, on falls (primary aim) and self-reported fractures (tertiary aim) in the overall cohort and on physical performance (secondary aim) in the clinic sub-cohort. 26 We have previously reported that supplemental cocoa extract did not reduce the incidence of self-reported fractures over a median duration of 3.6 yr in the overall COSMOS cohort of 21 442 older adults. 27 We herein report the effects of a cocoa extract supplement, compared to placebo, on 2-yr changes in physical performance measures in the clinic sub-cohort of 603 older ambulatory adults. We also examined the effects of an MVM supplement on physical performance. Materials and methods The parent COSMOS trial randomized participants across the United States to a cocoa extract supplement (2 capsules/d containing a total of 500 mg/d of flavanols, including 80 mg (−)-epicatechin, ~50 mg theobromine, and ~15 mg caffeine [Mars Edge]) and/or an MVM (Centrum Silver; Pfizer Consumer Healthcare, now Haleon) in a 2 × 2 factorial design with respective placebos, using a computer-generated permuted block approach, which has been previously detailed. 25 , 28 , 29 Eligible participants were women aged ≥65 yr and men aged ≥60 yr who had no history of myocardial infarction or stroke in their lifetime and no history of cancer (except non-melanoma skin cancer) in the past 2 yr. Participants who had self-reported taking ≥3/4 of study pills during a 2-mo placebo run-in phase were eligible for randomization. A total of 21 442 participants were randomized into COSMOS from April 2016 to March 2018 and treated for a median of 3.6 yr. For the duration of the trial, participants were asked not to take their own cocoa extract or MVM supplements. Participants self-reported health history, medication and supplement use, dietary patterns, and physical activity levels in questionnaires. This study was performed in a clinical subset of COSMOS participants. Participants were eligible for the clinic sub-cohort if they participated in the parent trial, were generally healthy, and were ambulatory. Eligible participants who lived ≤50 miles of Boston were invited for detailed in-person visits, including physical performance measures, at the Center for Clinical Investigations under the Harvard Catalyst Clinical and Translational Science Center in Boston, MA. A total of 603 participants completed baseline visits, and 535 participants completed 2-yr follow up visits (88.7% retention), which concluded in November 2020. Physical performance measures, using standardized protocols, included gait speed, grip strength, timed up and go (TUG) test, chair stands, and standing balance tests. Gait speed was assessed over 6 m at normal and fast paces, using a rolling start. The walking course was 7 m in length, and participants were timed as they walked between the 0.5 and 6.5 m marks. Grip strength testing of the dominant hand was assessed with a JAMAR Plus+ Digital Hand Dynamometer (Sammons Preston Rolyan, Bolingbrook, IL, USA). 30 , 31 For the TUG test, participants were timed as they stood up from a chair, walked 3 m, turned around, and returned to sit in the chair. For the standing balance tests, participants were asked to hold 3 basic standing positions for 10 s each: feet side-by-side, semi-tandem (toe by mid-foot), and full tandem stand (heel-to-toe), and the total time for all 3 positions was used for analyses. For chair stands, participants were timed as they stood and sat down, with arms folded, on a straight-back chair 5 times. Gait speed, standing balance and chair stands are components of the Short Physical Performance Battery (SPPB), scored from 0 to 12, with 12 indicating the best physical performance. Since gait speed in COSMOS was calculated over 6 m, the SPPB point system for the 3-m walk was converted to speed (ie, 1 point for <0.46 m/s, 2 points for 0.46-0.64 m/s, 3 points for 0.65-0.83 m/s, and 4 points for >0.83 m/s). All performance measures were assessed twice at each visit with the mean score used for statistical analysis, except for balance tests, which were assessed once at each visit. To evaluate compliance with the cocoa extract intervention, participants also provided urine specimens at baseline and 2-yr follow-up for measurement of 5-(3, 4-dihydroxyphenyl)-γ-valerolactone-3 /4-sulphate (gVL3S) and gVL-3 /4-O-glucuronide metabolites (gVLM), biomarkers of flavanol intake, which was analyzed by ultra-performance LC-tandem mass spectrometry. 32 This ancillary study was approved by the Institutional Review Board of Brigham and Women’s Hospital, and all participants provided written informed consent. In this ancillary study COSMOS: Effects on Falls and Physical Performance , the effect of supplemental cocoa extract, compared to placebo, on 2-yr changes in physical performance in the clinic sub-cohort was the secondary aim. Our pre-specified primary outcomes for this aim were changes in grip strength, walking speed and SPPB score. Grip strength adjusted for BMI, which is recognized by the Sarcopenia Definition and Outcomes Consortium, was also pre-specified as a secondary sensitivity analysis. 33 Secondary outcomes included changes in normal walking speed, fast walking speed, standing balance, chair stands, and TUG test. We examined treatment effects in an intention-to-treat fashion. Participants randomized to cocoa extract with and without MVM supplementation were compared to participants randomized to cocoa extract-placebo with and without MVM supplementation. Although the sample size of the clinic sub-cohort was determined by the parent COSMOS trial, we expected to have 80% power to detect differences of 1.03 kg for grip strength, 0.03 m/s for walking speed, and a score of 0.34 for SPPB, assuming an alpha level of 0.05. The estimates of variation over time used in these power calculations were based on changes in physical performance measures observed in the placebo group in the VITamin D and OmegA-3 TriaL, assuming 603 participants at baseline and 10% loss to follow-up. 34 Calculation of post hoc power revealed 80% power to detect differences of 1.32 kg for grip strength, 0.03 m/s for walking speed, and a score of 0.25 for SPPB. Baseline characteristics according to randomized treatment assignment were first compared to verify balance across intervention groups among the clinic sub-cohort. Chi-square tests were used to compare proportions, and tests for trend across ordinal variables were used. T-tests and analysis of variance (or the Wilcoxon rank sum and Kruskal Wallis tests if non-normal) were used to compare continuous variables across intervention groups. The effect of cocoa extract supplementation on 2-yr changes in measures of physical performance was adjusted for age, sex, and randomization to active MVM supplementation. Missing data were assumed to be missing at random. All available participant data were analyzed to help prevent bias due to missing data. Repeated measures analysis with an unstructured variance matrix was used with all physical performance measures as outcomes. A time by treatment interaction was used to test intervention effects. Finally, we explored subgroup effects and effect modification by age, sex, BMI, leisure-time physical activity, history of fall(s) in the year prior to randomization, self-reported general health, randomization to MVM, and baseline urinary gVLM using 3-way time × treatment × subgroup interactions. Parallel analyses were performed for MVM vs placebo. Statistical analyses were performed using SAS 9.4 (SAS Institute, Cary, NC). p values < .05 were considered statistically significant and not adjusted for multiple hypotheses testing. Thus, secondary and subgroup analyses should be interpreted with caution. Results 603 participants completed physical performance measures at baseline, and 535 participants returned for 2-yr follow-up (88.7% retention)( Figure S1 ). Baseline characteristics of the clinic sub-cohort are shown in Table 1 . Mean (±SD) age was 69.7 ± 5.5 yr and 49.3% were women. At baseline, few participants had muscle weakness or low muscle performance, as defined by the European Working Group on Sarcopenia in Older People 2 (EWGSOP2). 35 Overall, 6.5% of men and 8.1% of women had low grip strength (<27 kg in men, <16 kg in women), 2.1% had a low SPPB score ≤ 8, and 1 participant had a TUG time longer than 20 s. No participants took longer than 15 s to complete the repeated chair stands or had gait speeds slower than ≤0.8 m/s. Table 1. Baseline characteristics of the clinic sub-cohort, according to randomized cocoa extract assignment. Variable All Cocoa extract Cocoa extract placebo Sex, no. (%) Men 306 (50.7%) 158 (52.8%) 148 (48.7%) Women 297 (49.3%) 141 (47.2%) 156 (51.3%) Age, years, mean (SD) 69.7 (5.5) 70.0 (5.7) 69.5 (5.2) Race, no. (%) Non-Hispanic White 582 (96.5%) 291 (97.3%) 291 (95.7) African American/Black 6 (1.0%) 3 (1.0%) 3 (1.0%) Hispanic 5 (0.8%) 3 (1.0%) 2 (0.7%) Asian/Pacific Islander 3 (0.5%) 2 (0.7%) 1 (0.3%) Multiracial/other/unknown 7 (1.2%) 0 (0.0%) 7 (2.3%) BMI, kg/m 2 , mean (SD) 28.0 (5.2) 28.3 (5.4) 27.7 (5.0) BMI group, kg/m 2 , no. (%) <18.5 5 (0.8%) 0 (0.0%) 5 (1.6%) 18.5-24.9 178 (29.5%) 86 (28.8%) 92 (30.3%) 25-29.9 240 (39.8%) 120 (40.1%) 120 (39.5%) 30-34.9 116 (19.2%) 54 (18.1%) 62 (20.4%) 35+ 64 (10.6%) 39 (13.0%) 25 (8.2%) History of ≥1 fall in the last year, no. (%) 177 (29.5%) 90 (30.4%) 87 (28.6%) History of fragility fracture, no. (%) 116 (19.2%) 55 (18.4%) 61 (20.1%) Diabetes, no. (%) 66 (11.0%) 42 (14.0%) 24 (7.9%) Leisure-time physical activity and stair climbing, total MET-hours/wk, median [IQR] 20.0 [8.1–36.6] 19.2 [7.6–36.5] 21.2 [9.3–36.6] Smoking, no. (%) Never 323 (54.1%) 165 (55.9%) 158 (52.3%) Past 260 (43.6%) 126 (42.7%) 134 (44.4%) Current 14 (2.3%) 4 (1.4%) 10 (3.3%) Alcohol use, no. (%) Rarely 131 (22.9%) 76 (27.1%) 55 (18.9%) Monthly 33 (5.8%) 20 (7.1%) 13 (4.5%) Weekly 226 (39.6%) 106 (37.9%) 120 (41.2%) Daily 181 (31.7%) 78 (27.9%) 103 (35.4%) General health, no. (%) Excellent 211 (35.6%) 98 (33.4%) 113 (37.7%) Very good 294 (49.6%) 143 (48.8%) 151 (50.3%) Good 79 (13.3%) 49 (16.7%) 30 (10.0%) Fair 9 (1.5%) 3 (1.0%) 6 (2.0%) Baseline use of supplemental cocoa extract, no. (%) 2 (0.3%) 1 (0.3%) 1 (0.3%) Baseline use of MVM, no. (%) 231 (38.4%) 127 (42.5%) 104 (34.3%) Baseline use of supplemental vitamin D, no. (%) 249 (41.7%) 130 (43.6%) 119 (39.8%) Dark chocolate intake, servings/wk, median [IQR] 0.5 [0.0-1.0] 0.5 [0.0-1.0] 0.5 [0.0-1.0] Milk chocolate intake, servings/wk, median [IQR] 0.5 [0.0-0.5] 0.5 [0.0-1.0] 0.5 [0.0-0.5] Baseline urinary gVLM, μmol/L, median [IQR] 2.81 [0.67-9.45] 2.12 [0.59-9.37] 2.91 [0.77-9.72] Randomized to MVM, no. (%) 289 (47.9%) 154 (51.5%) 135 (44.4%) Open in a new tab Abbreviations: MET, metabolic equivalent of task; IQR, interquartile range. Baseline characteristics were well-balanced between the cocoa extract group and the cocoa-extract placebo group in terms of sex, age, race, BMI, leisure-time physical activity, tobacco use, and self-reported general health ( Table 1 ). More participants randomized to cocoa extract had history of diabetes compared to placebo (14% vs 7.9%, respectively). Alcohol intake was more frequent in the placebo group. While there was greater use of MVM prior to the trial in the cocoa extract group, there were only 2 participants in the entire clinic sub-cohort who took cocoa extract supplements prior to the trial and there was no difference in chocolate intake or urinary gVLM, a biomarker of flavanols, at baseline between the groups. There were no significant differences in baseline characteristics between the MVM group and the MVM placebo group ( Table S1 ). Over 2 yr, urinary gVLM increased from mean (±SE) of 9.5 ± 1.0 to 21.1 ± 1.8 μmol/L in the cocoa extract group. As expected, there were no changes in urinary gVLM in the cocoa-extract placebo group (8.7 ± 1.0 to 8.0 ± 1.7 μmol/L, p = .65, treatment effect p < .001). After 2 yr, grip strength was notably weaker in all participants, similarly between the active and placebo cocoa extract groups, with change of −12 kg, p < .001, and − 12 kg, p < .001, respectively in men, and change of −6.7 kg, p < .001, and − 6.2 kg, p < .001, respectively in women ( Table 2 ). Over 95% of the participants used the same hand (right vs left) to assess grip strength at baseline and 2-yr follow-up; only 19 participants used different hands. In exploratory analyses, a greater 2-yr decline in grip strength was observed in men than women (changes of −12 kg and −6.5 kg, respectively). Older participants (≥70 yr old) did not have greater loss in grip strength than younger participants (<70 yr old), with changes of −8.4 kg and − 10 kg, respectively. Table 2. Two-year changes in physical performance measure, according to randomized cocoa extract assignment, adjusted for age, sex, and treatment group. Cocoa extract Cocoa extract placebo Treatment effect Measure N Mean (SE) p -value Mean (SE) p -value Mean (SE) p -value Grip strength, men, kg Baseline 306 37.71 (0.63) 37.84 (0.66) Year 2 272 25.70 (0.60) 26.06 (0.62) 2-yr change −12.01 (0.47) <.001 −11.77 (0.49) <.001 −0.23 (0.68) .74 Grip strength, women, kg Baseline 297 21.99 (0.38) 22.00 (0.36) Year 2 263 15.27 (0.35) 15.76 (0.33) 2-yr change −6.72 (0.33) <.001 −6.24 (0.31) <.001 −0.48 (0.45) .29 SPPB score Baseline 569 11.05 (0.06) 11.19 (0.06) Year 2 509 10.96 (0.07) 10.97 (0.07) 2-yr change −0.09 (0.07) .19 −0.22 (0.06) <.001 0.13 (0.09) .15 Normal walking speed, m/s Baseline 599 1.19 (0.01) 1.20 (0.01) Year 2 529 1.16 (0.01) 1.16 (0.01) 2-yr change −0.03 (0.01) <.001 −0.04 (0.01) <.001 0.01 (0.01) .35 Fast walking speed, m/s Baseline 587 1.66 (0.01) 1.68 (0.01) Year 2 522 1.64 (0.02) 1.65 (0.01) 2-yr change −0.02 (0.01) .045 −0.03 (0.01) .01 0.01 (0.02) .72 Standing balance, s Baseline 595 28.98 (0.16) 29.08 (0.16) Year 2 526 29.43 (0.14) 29.33 (0.13) 2-yr change 0.46 (0.17) .007 0.25 (0.16) .13 0.20 (0.24) .39 Chair stands, s Baseline 573 11.48 (0.15) 11.33 (0.14) Year 2 513 12.03 (0.20) 11.89 (0.20) 2-yr change 0.55 (0.18) .003 0.56 (0.18) .002 −0.01 (0.25) .98 Timed up and go, s Baseline 597 8.36 (0.08) 8.31 (0.08) Year 2 522 7.95 (0.09) 7.86 (0.09) 2-yr change −0.41 (0.08) <.001 −0.45 (0.08) <.001 0.04 (0.11) .75 Open in a new tab Abbreviation: SPPB, Short Physical Performance Battery. There were minimal declines in walking speeds (≤−0.04 m/s) and increased time for the completion of chair stands (<0.8 s) across all treatment groups. Participants were slightly faster in completing the TUG tests, though the change was clinically very small (<−0.5 s). Supplementation with cocoa extract for 2 yr, compared to the cocoa-extract placebo, did not affect physical performance measures in our clinic sub-cohort ( Table 2 ). We found no benefit of supplemental cocoa extract on our primary pre-specified outcomes of grip strength, walking speed, and SPPB or secondary outcomes of standing balance, chair stands, or TUG tests. As a pre-specified sensitivity analysis, we also examined changes in grip strength adjusted for BMI, as acknowledged by the Sarcopenia Definition and Outcomes Consortium, 33 and also did not find any differences in 2-yr changes between the cocoa extract and cocoa-extract placebo groups ( Table S3 ). In subgroup analyses, there was no effect modification for the effect of cocoa extract supplementation on grip strength, normal gait speed, or SPPB, by sex, age (divided at the median), BMI (divided at the median), baseline urinary gVLM (divided at the median), leisure-time physical activity by metabolic equivalent of task (divided at the median), self-reported general health, or randomization to MVM ( Table 3 ). Among participants who had a fall within the year before the start of the study, those who were randomized to cocoa extract had less of a decline in grip strength than those randomized to cocoa-extract placebo, while participants who did not have a fall had a greater decline in grip strength with cocoa extract than with cocoa-extract placebo ( p for interaction <.001). Among the participants who had a prior fall at baseline, 63% were women and 37% were men. In exploratory analyses, men with a prior fall were found to have a greater decline in grip strength with placebo than with cocoa extract supplementation (−13.53 [0.85] kg and −10.28 [1.00] kg, respectively; p -value, treatment effect, .016), while women with a prior fall had similar declines in grip strength in the 2 treatment arms (−6.34 [0.56] kg and −6.48 [0.51] kg, respectively; p -value, treatment effect, .85; p for interaction .016). Since a single fall may be a spurious event and recurrent falls may suggest ongoing functional limitation, subgroup analyses were also performed for participants with 2 or more falls in the prior year at baseline. Participants who had 2 or more falls in the prior year also had a greater decline in grip strength with placebo than cocoa extract, while participants without 2 or more falls had a slightly greater decline in grip strength with cocoa extract than with placebo ( p for interaction .01). Table 3. Effect of cocoa extract supplementation vs placebo on physical performance measures in subgroups. Cocoa extract Cocoa extract placebo p -value, treatment effect P for interaction Subgroup N 2-yr change (SE) p -value N 2-yr change (SE) p -value Grip strength, kg Sex .72 Men 158 −12.01 (0.47) <.001 148 −11.77 (0.49) <.001 0.74 Women 141 −6.72 (0.33) <.001 156 −6.24 (0.31) <.001 0.29 Age .43 <Median (69.2 yr) 143 −10.77 (0.49) <.001 158 −9.76 (0.47) <.001 0.14 ≥Median 156 −8.32 (0.44) <.001 146 −8.09 (0.44) <.001 0.71 BMI .16 <Median (26.5 kg/m 2 ) 143 −9.25 (0.47) <.001 158 −8.07 (0.44) <.001 0.06 ≥Median 156 −9.77 (0.47) <.001 146 −9.91 (0.49) <.001 0.84 Baseline urinary gVLM .58 <Median (2.8 μmol/L) 127 −9.15 (0.50) <.001 112 −8.79 (0.53) <.001 0.62 ≥Median 117 10.35 (0.57) <.001 122 −9.38 (0.55) <.001 0.22 Leisure-time physical activity and stair climbing, total MET .48 <Median (20.0 h/wk) 155 −8.57 (0.45) <.001 144 −8.33 (0.46) <.001 0.70 ≥Median 142 −10.45 (0.49) <.001 158 −9.54 (0.47) <.001 0.18 History of ≥1 fall in the last year <.001 Yes 90 −7.66 (0.57) <.001 87 −9.49 (0.57) <.001 0.02 No 206 −10.34 (0.40) <.001 217 −8.71 (0.39) <.001 0.004 History of ≥2 falls in the last year .01 Yes 31 −8.68 (1.06) <.001 41 −11.13 (0.90) <.001 0.08 No 265 −9.65 (0.35) <.001 263 −8.61 (0.35) <.001 0.04 General health, self-reported .24 Excellent 98 −9.90 (0.58) <.001 113 −8.84 (0.53) <.001 0.18 Very good 143 −9.30 (0.48) <.001 151 −9.50 (0.47) <.001 0.77 Good 49 −9.29 (0.83) <.001 30 −7.03 (1.03) <.001 0.09 Fair 3 −6.60 (3.63) .14 6 −10.16 (2.80) .02 0.48 Randomized to MVM .76 Yes 154 −9.72 (0.47) <.001 135 −9.33 (0.49) <.001 0.60 No 145 −9.33 (0.47) <.001 169 −8.62 (0.44) <.001 0.27 SPPB score Sex .97 Men 158 −0.19 (0.08) .02 148 −0.33 (0.09) <.001 0.23 Women 141 0.04 (0.10) .7 156 −0.11 (0.09) .26 0.30 Age .22 <Median (69.2 yr) 143 −0.14 (0.09) .10 158 −0.16 (0.08) .05 0.86 ≥Median 156 −0.03 (0.10) .77 146 −0.28 (0.10) .005 0.08 BMI .87 <Median (26.5 kg/m 2 ) 143 −0.14 (0.09) .12 158 −0.26 (0.08) .002 0.32 ≥Median 156 −0.03 (0.10) .76 146 −0.18 (0.10) .07 0.29 Baseline urinary gVLM .88 <Median (2.8 μmol/L) 127 0.03 (0.11) .77 112 −0.13 (0.12) .27 0.32 ≥Median 117 −0.13 (0.10) .20 122 −0.31 (0.09) .001 0.18 Leisure-time physical activity and stair climbing, total MET .35 <Median (20.0 h/wk) 155 −0.06 (0.10) .55 144 −0.29 (0.10) .005 0.12 ≥Median 142 −0.12 (0.08) .17 158 −0.17 (0.08) .04 0.66 History of ≥1 fall in the last year .96 Yes 90 −0.19 (0.12) .13 87 −0.33 (0.12) .008 0.41 No 206 −0.04 (0.08) .62 217 −0.17 (0.07) .02 0.21 History of ≥2 falls in the last year .96 Yes 31 −0.28 (0.23) .22 41 −0.42 (0.19) .04 0.64 No 265 −0.06 (0.07) .38 263 −0.19 (0.07) .005 0.18 General health, self-reported .67 Excellent 98 −0.21 (0.10) .04 113 −0.25 (0.09) .009 0.80 Very good 143 −0.01 (0.10) .93 151 −0.18 (0.09) .05 0.20 Good 49 0.10 (0.20) .61 30 −0.23 (0.23) .32 0.28 Fair 3 *** *** 6 *** *** Randomized to MVM .10 Yes 154 −0.05 (0.09) .57 135 −0.34 (0.09) <.001 0.02 No 145 −0.12 (0.10) .22 169 −0.11 (0.09) .20 0.97 Normal walking speed, m/s Sex .62 Men 158 −0.01 (0.01) .62 148 −0.02 (0.01) .09 0.39 Women 141 −0.06 (0.01) <.001 156 −0.07 (0.01) <.001 0.87 Age .57 <Median (69.2 yr) 143 −0.02 (0.01) .06 158 −0.03 (0.01) .02 0.79 ≥Median 156 −0.04 (0.01) <.001 146 −0.06 (0.01) <.001 0.26 BMI .22 <Median (26.5 kg/m 2 ) 143 −0.03 (0.01) .02 158 −0.06 (0.01) <.001 0.15 ≥Median 156 −0.03 (0.01) .002 146 −0.03 (0.01) .008 0.82 Baseline urinary gVLM .52 <Median (2.8 μmol/L) 127 −0.04 (0.01) .003 112 −0.04 (0.01) .006 0.96 ≥Median 117 −0.03 (0.01) .03 122 −0.05 (0.01) <.001 0.40 Leisure-time physical activity and stair climbing, total MET 1.00 <Median (20.0 h/wk) 155 −0.04 (0.01) .004 144 −0.04 (0.01) <.001 0.64 ≥Median 142 −0.03 (0.01) .004 158 −0.04 (0.01) <.001 0.58 History of ≥1 fall in the last year .49 Yes 90 −0.02 (0.02) .21 87 −0.04 (0.02) .009 0.34 No 206 −0.04 (0.01) <.001 217 −0.04 (0.01) <.001 0.74 History of ≥2 falls in the last year .72 Yes 31 −0.04 (0.03) .18 41 −0.03 (0.02) .16 0.92 No 265 −0.03 (0.01) <.001 263 −0.05 (0.01) <.001 0.35 General health, self-reported .01 Excellent 98 −0.01 (0.01) .48 113 −0.07 (0.01) <.001 0.003 Very good 143 −0.05 (0.01) <.001 151 −0.03 (0.01) .005 0.32 Good 49 −0.04 (0.02) .09 30 −0.00 (0.03) .97 0.28 Fair 3 −0.15 (0.07) .13 6 −0.17 (0.07) .10 0.85 Randomized to MVM .45 Yes 154 −0.03 (0.01) .03 135 −0.05 (0.01) <.001 0.27 No 145 −0.04 (0.01) <.001 169 −0.04 (0.01) <.001 0.88 Open in a new tab Abbreviations: MET, metabolic equivalent of task; MVM, multivitamin/multimineral; gVLM, 5-(3,4-dihydroxyphenyl)-γ-valerolactone metabolites ; SPPB, Short Physical Performance Battery. As the COSMOS clinic sub-cohort was generally healthy and included few participants with muscle weakness or low muscle performance, physical performance measures of SPPB and overall balance tests may exhibit ceiling effects in our study population. Thus, we performed sensitivity analyses on individual balance tests of semi-tandem and tandem stand, which is the most difficult position to hold. There were no between group differences with 2-yr changes in semi-tandem stand. Participants randomized to supplemental cocoa extract exhibited improvements in the tandem stand, compared to placebo ( p = .028)( Table S3 ). Supplementation with an MVM, compared to an MVM placebo, also did not affect 2-yr changes in physical performance measures ( Table S2 ), including grip strength adjusted for BMI ( Table S3 ). In sensitivity analyses, there were no between group differences with 2-yr changes in semi-tandem and tandem stands ( Table S3 ). There was also no effect modification by age, sex, prior use of MVM (discontinued during 2-mo placebo run-in phase and intervention period), other baseline characteristics, or randomization to cocoa extract ( Table S4 ). Potential adverse effects of cocoa extract supplementation, including nausea and upset stomach, have been previously reported by the parent COSMOS trial. 30 Discussion Our study in ambulatory older men and women with a mean age of 69.7 yr found that, compared to placebo, cocoa extract supplementation did not affect 2-yr changes in physical performance measures of grip strength, walking speed, or SPPB score. Multivitamin/multimineral supplementation also did not affect 2-yr changes in physical performance measures. Our study population was overall healthy, with a low prevalence of muscle weakness or low muscle performance, as defined by EWGSOP2, 35 at baseline. Thus, the physical performance measures assessed in our study, particularly the SPPB, may have exhibited ceiling effects. In sensitivity analyses, we found that supplemental cocoa extract, compared to placebo, did improve the ability to hold the tandem stand position. We had explored if cocoa extraction supplementation would benefit participants with poorer physical function, using a history of fall(s) in the year prior to randomization as subgroups. In these participants with a prior-year fall, supplemental cocoa extract lessened the decline in grip strength compared to placebo. However, this may be a chance finding as we have no explanation for why participants without a history of fall(s) in the prior year would have worsening grip strength with cocoa extract supplementation. Also, the difference in grip strength decline (Δ1.81 kg) in the participants with a prior-year fall was less than the estimated annual loss of grip strength in the placebo group overall (3.12-5.89 kg, depending on sex). Findings from other RCTs, which were smaller and of shorter duration, indicate that cocoa may benefit high risk individuals. An RCT in older adults ( n = 61, mean ± SD age of 75.9 ± 5.7 yr) found that daily supplementation with a cocoa powder-based beverage with 25 mg of epicatechin for 12 wk improved walking speed, grip strength, and quality of life and decreased frailty, compared to a control beverage without flavonoids. 15 Another 8-wk RCT in 62 men with sarcopenia (mean ± SD age of 68.6 ± 2.9 yr) found that supplemental epicatechin (dosed at 1 mg/kg of body weight) improved times for the TUG test slightly (Δ0.22 s) and the appendicular muscle mass index (Δ0.34 kg/m 2 ) compared to placebo, but not compared to resistance training alone. 14 A phase II clinical trial randomized people with lower extremity peripheral artery disease ( n = 44) to a daily cocoa beverage with 75 mg of epicatechin vs a placebo beverage and found that cocoa improved 5-min walking distance by 42.6 m. 11 Furthermore, on calf muscle biopsies, cocoa improved mitochondrial cytochrome c oxidase activity, capillary density, and calf muscle perfusion and reduced the accumulation of central nuclei, an indicator of myopathy. 11 The authors also found evidence of cocoa activating nuclear factor erythroid 2-related factor 2 (Nfr2), leading to increased antioxidants heme oxygenase-1 (HO-1) and NAD(P)H dehydrogenase [quinone] (NQO1) and protection against skeletal muscle damage. 36 These RCTs had administered supplements with similar or lower doses of epicatechin compared to the 80 mg/d regimen used in our study. Furthermore, we do not suspect that the baseline intake of cocoa in our RCT was higher than in these earlier studies, as baseline use of supplemental cocoa extract in our clinical trial was very low at 0.3%. Chocolate intake was also minimal in our study with 0.5 servings per wk of each dark and milk chocolate, which have some flavanols but at much lower concentrations. The daily cocoa extract supplement administered in COMSOS was highly concentrated with 500 mg of flavanols including 80 mg (−)-epicatechin, which is the equivalent of 90.7 g (3.2 ounces) of dark chocolate or 771.1 g (1.7 pounds) of milk chocolate. The main difference between our study and prior RCTs is our overall healthy study population. The populations of the clinical trials that found benefits in physical performance measures were selected on the basis of peripheral artery disease, 11 , 13 heart failure and diabetes, 16 , 18 and sarcopenia. 14 In subgroup analyses for COSMOS, there may have been a benefit with cocoa extract for grip strength in participants with fall(s) in the last year. Overall, however, we did not find a benefit for cocoa extract vs placebo in older or less active participants in this ambulatory sub-cohort. The few RCTs testing an MVM for physical performance have not found a benefit for daily MVM, even in those at highest risk. 21–23 In a small study in institutionalized participants in their eighth and ninth decades of life ( n = 55), a multivitamin beverage did not improve physical performance as assessed by spiroergometric tests. 23 Grip strength, including when adjusted for BMI, notably declined over 2 yr in all participants, without any difference between treatment groups. While the grip strength assessed at baseline was compatible to other cohorts, the loss of grip strength after 2 yr was more than we expected. 34 , 37 The equipment and protocol, including the verbal script for study staff to instruct participants, to assess grip strength did not change during the study and were comparable across all treatment groups at each time point. There may have been a calibration issue with the equipment between the baseline and 2-yr visits. Despite the larger-than-expected 2-yr reductions in grip strength, we believe our comparisons for both COSMOS interventions are valid. These findings complement our previously reported results that neither supplementation with cocoa extract nor an MVM reduced the incidence of self-reported fractures in the overall COSMOS cohort of 21 442 older adults over a median of 3.6 yr of follow up. 27 Since both the overall COSMOS cohort and the clinic sub-cohort were overall healthy, our results may not apply to older individuals with medical comorbidities and/or sarcopenia. In the overall COSMOS cohort, supplemental cocoa extract and MVM, compared to respective placebos, did not reduce the composite cardiovascular outcome or all-cause mortality, though cocoa extract reduced cardiovascular death by 27%. 28 , 29 Cocoa extract and MVM supplementation, compared to respective placebos, also did not reduce the incidence of invasive cancer overall, though the MVM had a protective effect on lung cancer. 28 , 29 In ancillary studies, MVM supplementation was found to have benefits on cognitive function and memory. 38–40 Strengths of this study include a large sample size, inclusion of women and men, a long study duration, and high adherence. This is the first large, randomized trial of cocoa extract vs placebo over 2 yr on changes in physical performance. Although the sample size of the clinic sub-cohort was determined by the parent COSMOS trial, we had excellent power to determine minimal changes in physical performance measures. Despite no definitive explanation for the greater than expected decline in grip strength, the effect was similar by treatment group, and we do not expect any other bias. Because COSMOS investigated the effects of cocoa extracts in primarily community-dwelling older adults and included few participants with muscle weakness or low muscle performance, the results are not generalizable to institutionalized adults or individuals with poor physical function. Cocoa extract or MVM supplementation for 2 yr did not slow age-related declines in physical performance in generally healthy ambulatory older adults. Supplementary Material Physical_performance_supplementary_clean_ziag041 physical_performance_supplementary_clean_ziag041.docx (64.5KB, docx) Acknowledgments S.H.C., P.M.C., N.C., C.J.C., M.L., J.E.M., and H.D.S. designed research; A.C., J.E.M., and H.D.S. conducted research; E.K., G.K., and N.C. analyzed data; and S.H.C., D.A.G., A.H.S., C.J.C., and M.L. wrote the paper. C.J.C., M.L., J.E.M., and H.D.S. had primary responsibility for final content. All authors read and approved the final manuscript. The content of this publication is solely the responsibility of the authors and does not necessarily represent the official views of the Department of Veterans Affairs or the United States government. We would also like to acknowledge investigators of the Women’s Health Initiative. Program Office: (National Heart, Lung, and Blood Institute, Bethesda, Maryland) Jacques Rossouw, Jared Reis, and Candice Price Clinical Coordinating Center: (Fred Hutchinson Cancer Center, Seattle, WA) Garnet Anderson, Ross Prentice, Andrea LaCroix, and Charles Kooperberg Steering Committee and Academic Centers: (University of Alabama at Birmingham) Gretchen Wells; (Albert Einstein College of Medicine) Yasmin Mossavar-Rahmani; (University at Buffalo) Amy Millen; (University at Buffalo) Jean Wactawski-Wende; (Fred Hutchinson Cancer Center) Marian Neuhouser; (Fred Hutchinson Cancer Center) Holly Harris; (University of Massachusetts) Brian Silver; (University of North Carolina) Nora Franceschini; (Stanford Prevention Research Center) Marcia L. Stefanick; (The Ohio State University) Electra Paskett; (Wake Forest University) Mara Vitolins For a list of all the investigators who have contributed to WHI science, please visit: https://s3-us-west-2.amazonaws.com/www-whi-org/wp-content/uploads/WHI-Investigator-Long-List.pdf Contributor Information Sharon H Chou, Division of Endocrinology, Diabetes and Hypertension, Brigham and Women’s Hospital, Boston, MA 02115, United States; Harvard Medical School, Boston, MA 02115, United States. Nancy Cook, Harvard Medical School, Boston, MA 02115, United States; Division of Preventive Medicine, Brigham and Women’s Hospital, Boston, MA 02115, United States; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA 02115, United States. Eunjung Kim, Harvard Medical School, Boston, MA 02115, United States; Division of Preventive Medicine, Brigham and Women’s Hospital, Boston, MA 02115, United States; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA 02115, United States. Gregory Kotler, Harvard Medical School, Boston, MA 02115, United States; Division of Preventive Medicine, Brigham and Women’s Hospital, Boston, MA 02115, United States; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA 02115, United States. David A Ganz, Department of Medicine, David Geffen School of Medicine at University of California, Los Angeles, CA 90095, United States; Geriatric Research, Education and Clinical Center, Veterans Affairs Greater Los Angeles, CA 90073, United States; RAND, Santa Monica, CA 90401, United States. Peggy M Cawthon, Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, CA 94115, United States; California Pacific Medical Center, Research Institute, San Francisco, CA 94143, United States. Allison Clar, Harvard Medical School, Boston, MA 02115, United States; Division of Preventive Medicine, Brigham and Women’s Hospital, Boston, MA 02115, United States; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA 02115, United States. Aladdin H Shadyab, Herbert Wertheim School of Public Health and Human Longevity Science, University of California San Diego, La Jolla, CA 92093, United States; Division of Geriatrics, Gerontology, and Palliative Care, Department of Medicine, University of California San Diego, La Jolla, CA 92093, United States. JoAnn E Manson, Harvard Medical School, Boston, MA 02115, United States; Division of Preventive Medicine, Brigham and Women’s Hospital, Boston, MA 02115, United States; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA 02115, United States. Howard D Sesso, Harvard Medical School, Boston, MA 02115, United States; Division of Preventive Medicine, Brigham and Women’s Hospital, Boston, MA 02115, United States; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA 02115, United States. Carolyn J Crandall, Division of General Internal Medicine and Health Services Research, Department of Medicine, David Geffen School of Medicine at University of California, Los Angeles, CA 90024, United States. Meryl LeBoff, Division of Endocrinology, Diabetes and Hypertension, Brigham and Women’s Hospital, Boston, MA 02115, United States; Harvard Medical School, Boston, MA 02115, United States. Author contributions Sharon H. Chou (Conceptualization, Investigation, Methodology, Writing—original draft, Writing—review & editing), Nancy Cook (Conceptualization, Formal analysis, Investigation, Methodology, Writing—review & editing), Eunjung Kim (Formal analysis), Gregory Kotler (Formal analysis), David A. Ganz (Conceptualization, Writing—review & editing), Peggy M. Cawthon (Conceptualization, Writing—review & editing), Allison Clar (Project administration, Writing—review & editing), Aladdin H. Shadyab (Writing—review & editing), JoAnn E. Manson (Conceptualization, Data curation, Funding acquisition, Investigation, Methodology, Resources, Supervision, Visualization, Writing—review & editing), Howard D. Sesso (Conceptualization, Data curation, Funding acquisition, Investigation, Methodology, Resources, Supervision, Visualization, Writing—review & editing), Carolyn J. Crandall (Conceptualization, Funding acquisition, Investigation, Methodology, Supervision, Visualization, Writing—review & editing), and Meryl LeBoff (Conceptualization, Funding acquisition, Investigation, Methodology, Supervision, Visualization, Writing—review & editing) Funding The ancillary study COSMOS: Effects on Falls and Physical Performance is supported by grant R01AG071611 from the National Institute on Aging and Grant Numbers 1UL1TR001102 and 1UL1TR002541-01. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources, the National Center for Advancing Translational Science, or the National Institutes of Health. The COcoa Supplement and Multivitamin Outcomes Study (COSMOS) parent trial is supported by grants AG050657, AG071611, EY025623, and HL157665 from the National Institutes of Health, Bethesda, MD and by 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. The Women’s Health Initiative (WHI) program is funded by the National Heart, Lung, and Blood Institute, National Institutes of Health, U.S. Department of Health and Human Services through 75N92021D00001, 75N92021D00002, 75N92021D00003, 75N92021D00004, and 75N92021D00005. Conflicts of interest E.K., G.K., A.C., N.C., S.H.C., A.H.S.: None declared. D.A.G. reports funding from National Institute of Aging, Department of Veterans Affairs. C.J.C. reports grants from the National Institutes of Health during the conduct of this study. H.D.S. reports receiving 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 reports receiving investigator-initiated grants from Pure Encapsulations and Pfizer Inc. and honoraria and/or travel for lectures from the Council for Responsible Nutrition, BASF, NIH, and American Society of Nutrition during the conduct of the study. J.E.M. reports receiving investigator-initiated grants from Mars Edge and support from Pfizer Consumer Healthcare (now Haleon) for donation of COSMOS study pills and packaging during the conduct of the trial. M.L. reports grants from the National Institutes of Health during the conduct of this study and Amgen stock ownership unrelated to this study. 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Am J Clin Nutr. 2023;118(1):273-282. 10.1016/j.ajcnut.2023.05.011 [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] Associated Data This section collects any data citations, data availability statements, or supplementary materials included in this article. Supplementary Materials Physical_performance_supplementary_clean_ziag041 physical_performance_supplementary_clean_ziag041.docx (64.5KB, docx) Data Availability Statement Data described in the manuscript, code book, and analytic code will be made available upon request pending application and approval. 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