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Principal Investigator: MERYL Susan LEBOFF
Organization: BRIGHAM AND WOMEN'S HOSPITAL
Fiscal Year: 2024
Award: $670,395
Funding agency: National Institute on Aging
ABSTRACT
Falls and decreased physical function increase markedly with age and result in injury, hospitalization, and
death. Safe, cost-effective primary prevention strategies are needed to reduce these adverse outcomes in the
aging U.S. population. Basic, preclinical, and clinical studies suggest that flavanols, a class of nutrients present
in high concentrations in cocoa, have favorable effects on muscle and physical performance. Flavanols
decrease oxidative stress and improve biomarkers of mitochondrial biogenesis and muscle growth. Emerging
studies show potential benefits of supplemental cocoa flavanols on physical performance, including grip
strength and walking speed in older adults. However, there are no large, long-term randomized controlled trials
(RCTs) of the effects of supplemental flavanols on falls, muscle performance, and/or fall-related injuries. In an
ancillary study to the COcoa Supplement and Multivitamins Outcomes Study (COSMOS), which is testing the
effects of supplemental cocoa flavanols and/or multivitamin for the prevention of cardiovascular disease and
cancer, we propose the first large, placebo-controlled, prospective study to determine whether supplemental
flavanols reduce falls and improve musculoskeletal health in women aged ≥ 65 and men aged ≥ 60. In the
proposed study, we will determine effects of a cocoa flavanol supplement [600 mg/d flavanols, including 80 mg
(-)- epicatechins] and/or multivitamin on the following clinically meaningful outcomes: falls in the overall
COSMOS cohort (n=21,444) and physical performance in a clinic sub-cohort (n=603). We will test the following
hypotheses: Aim 1: In the overall COSMOS cohort, cocoa flavanol supplementation will reduce risk of: (a)
injurious fall(s) resulting in a visit to a healthcare provider or hospital with medical record review and (b) two or
more falls per year and (c) injurious fall(s) (not resulting in healthcare utilization) as assessed by annual
questionnaires. Aim 2: In the clinic sub-cohort, cocoa flavanol supplementation will benefit physical
performance measures at 2-year post randomization, as assessed by grip strength, walking speed, and Short
Physical Performance Battery (a composite of standing balance, walking speed, and chair stands). Aim 3: In
the overall COSMOS cohort, cocoa flavanol supplementation reduces incident fractures as assessed by
annual questionnaires. We will explore whether effects of cocoa flavanols on fracture outcomes are mediated
through falls and/or bone density changes. In exploratory aims we will also assess effects of multivitamins on
these same outcomes. RCTs testing effects of multivitamins on falls and musculoskeletal outcomes are
lacking. This ancillary study maximizes cost-efficiency to fill gaps in knowledge regarding effects of flavanols
for the primary prevention of falls. We expect the proposed, rigorous translational study will elucidate whether
supplemental flavanols improve musculoskeletal health and prevent falls and declining physical performance in
the increasing number of older adults in the U.S. with potential for clinical and public health benefits.
Terms: <21+ years old><65 and older><65 or older><65 years of age and older><65 years of age or more><65 years of age or older><65+ years><65+ years old><> 65 years><Active Follow-up><Adult><Adult Human><Age><Aged 65 and Over><Aging><Ancillary Study><Attention><BMI><BMI percentile><BMI z-score><Beverages><Biogenesis><Biological Markers><Blood Sample><Blood specimen><Body Composition><Body mass index><Bone Density><Bone Mineral Density><Boston><CVD prevention><Cancers><Cardiovascular Diseases><Center for Translational Science Activities><Cessation of life><Clinic><Clinical><Clinical Research><Clinical Sciences><Clinical Study><Cocoa><Cocoa Powder><Cohort Studies><Concurrent Studies><Cost efficiency><Data><Death><Double-Blind Method><Double-Blind Study><Double-Blinded><Double-Masked Method><Double-Masked Study><Elderly><Equilibrium><Ethnic Origin><Ethnicity><Exercise><Fall prevention><Flavanol><Forearm Fracture><Fracture><Generalized Growth><Grip strength><Growth><Hand Strength><Health><Health Benefit><Health Care Providers><Health Care Utilization><Health Personnel><Healthcare Providers><Healthcare worker><Hip Fractures><Hospital Admission><Hospitalization><Hospitals><Hydrogen Oxide><Injury><Intervention><Intervention Strategies><Knowledge><Leanness><Literature><Location><Malignant Neoplasms><Malignant Tumor><Measurement><Measures><Mediating><Medical><Medical Records><Mitochondria><Modification><Multivitamin><Muscle><Muscle Tissue><Muscle function><Musculoskeletal><NIH><National Institutes of Health><Nutrient><Origin of Life><Outcome><Outcome Study><Oxidative Stress><Participant><Performance><Peripheral arterial disease><Phenotype><Physical Function><Physical Performance><Physical assessment><Physicians><Placebo Control><Placebos><Population><Preventative strategy><Prevention strategy><Preventive strategy><Primary Prevention><Prospective Studies><Public Health><Questionnaires><Quetelet index><Race><Races><Randomized><Randomized, Controlled Trials><Recovery><Recurrence><Recurrent><Reporting><Research Resources><Resources><Risk><Risk Reduction><Sham Treatment><Source><Spinal Fractures><Supplementation><Testing><Thinness><Tissue Growth><United States National Institutes of Health><Visit><Water><Woman><Women's trial><above age 65><active followup><adjudication><adjudicative process and procedure><adult youth><adulthood><advanced age><adverse consequence><adverse outcome><after age 65><age 65 and greater><age 65 and older><age 65 or older><age > 65><age associated decline><age dependent decline><age of 65 years onward><age related decline><aged><aged 65 and greater><aged 65+><aged ≥65><ages><balance><balance function><bio-markers><biologic marker><biomarker><bone><bone fracture><cancer risk><cardiac disease prevention><cardiovascular disease prevention><cardiovascular disorder><cardiovascular disorder prevention><cohort><cost><cost effective><cost efficient><decline with age><design><designing><epicatechin><fall injury><fall related injury><falls><female trial><follow up><follow-up><followed up><followup><geriatric><health care personnel><health care service use><health care service utilization><health care worker><health provider><health workforce><healthcare personnel><healthcare service use><healthcare service utilization><healthcare utilization><human old age (65+)><improved><injuries><injurious falls><interventional strategy><malignancy><medical personnel><men><meter><mitochondrial><muscle strength><muscular><neoplasm/cancer><old age><older adult><older adulthood><older men><older women><ontogeny><over 65 years><peripheral artery disease><placebo controlled><pre-clinical study><preclinical study><preventing falls><primary outcome><racial><racial background><racial origin><randomisation><randomization><randomized control trial><randomly assigned><reduce risk><reduce risks><reduce that risk><reduce the risk><reduce these risks><reduces risk><reduces the risk><reducing risk><reducing the risk><risk-reducing><senior citizen><sex related variation><sex variable><sex variation><sex-related variable><sham therapy><spine fracture><translational research center><translational sciences center><translational study><treatment provider><trial among women><trial in females><trial in women><varies by sex><vertebral fracture><walking pace><walking speed><wrist fracture><young adult><young adulthood><≥65 years>