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Grant Abstract

Grant Number: 1R01AG042411-01A1
PI Name: Houston
Project Title: Trial of vitamin D supplementation and neuromuscular functioin in older adults

Abstract: DESCRIPTION (provided by applicant): The scientific community disagrees on the amount of vitamin D required for optimal health. In 2011, the Institute of Medicine (IOM) concluded that while scientific evidence supports a role of vitamin D for bone health, compelling evidence was lacking for non-bone health outcomes such as neuromuscular function due to the paucity of randomized trials. The IOM committee also concluded that 25-hydroxyvitamin D (25[OH]D) concentrations e20 ng/mL (50 nmol/L) were sufficient for bone and overall health. This conclusion has sparked controversy as a large volume of observational research has found that 25(OH)D concentrations e30 ng/mL (75 nmol/L) are beneficial for non-bone health outcomes. The resolution of this controversy is important since almost 20 million older adults (or one-half of the older U.S. adult population) have 25(OH)D concentrations between 20 and 30 ng/mL. There is growing evidence that vitamin D's effect on reducing falls is mediated by improvements in neuromuscular function. Observational studies show associations between 25(OH)D concentrations and muscle strength and physical performance measures associated with fall risk (e.g., gait, balance). Results from previous vitamin D supplementation trials on changes in muscle strength and physical performance have been equivocal, however. Moreover, the underlying mechanisms for vitamin D's effect on neuromuscular function are lacking. We propose to: 1) determine whether increasing 25(OH)D concentrations to e30 ng/mL will improve neuromuscular function in older adults with initial 25(OH)D concentrations of 20-<30 ng/mL~ and 2) examine potential underlying mechanisms by which vitamin D supplementation may enhance muscle physiology and performance. To achieve these goals we will conduct a 12-month, double-blind randomized placebo controlled trial in 200 older (70-89 yrs) men and women with 25(OH)D concentrations of 20-<30 ng/mL to determine the effect of vitamin D3 supplementation on 1) change in neuromuscular functions that are established risk-factors for falls in older adults (Aim 1)~ and 2) changes in the underlying physiological mechanisms over 4 months in a subset of 40 randomly selected participants (Aim 2). Participants will be randomized to 2000 IU/d vitamin D3 plus 600 mg/d calcium or placebo plus calcium. Lower extremity muscle power and strength, physical performance, and postural sway will be assessed at baseline, 4 months and 12 months and falls assessed monthly (Aim 1). Muscle biopsies of the vastus lateralis will be taken at baseline and 4 months to assess muscle fiber type, contractility, and denervation, and number and differentiation stage of satellite cell (Aim 2). Determining whether increasing 25(OH)D concentrations to e30 ng/mL will improve neuromuscular deficits that are risk factors for falls and the associated underlying physiological mechanisms linking vitamin D and neuromuscular function will provide important data to inform vitamin D supplementation recommendations for neuromuscular-related outcomes in older adults. PUBLIC HEALTH RELEVANCE: Low 25-hydroxyvitamin D (25[OH]D) concentrations are common even in community-dwelling older adults. Remediating low 25(OH)D concentrations can be done through simple and inexpensive means with vitamin D supplementation. Thus, determining whether increasing 25(OH)D concentrations to e30 ng/mL provides additional benefit for neuromuscular functions related to fall risk in older adults and a better understanding of the relationship between vitamin D and the underlying neuromuscular mechanisms is of significant public health importance.

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