All subjects were required to maintain their usual level of physical activity and their habitual diet during the 4-month study to limit the impact of physical activity and dietary variation on skeletal muscle. According to the 2011 Institute of Medicine report, 4000 IU daily is the safe upper limit for supplementation ( 16).Īmbulatory, community-dwelling, postmenopausal women 65 years of age and over were recruited from direct mailings and advertisements. The vitamin D 3 4000 IU daily dose was chosen as a high yet safe dose of supplementation to minimize risk of underdosing (proof-of-principle study). A 4-month duration was selected to evaluate changes in muscle tissue and simultaneously have a steady state in 25OHD level after the change in intake ( 15). The study obtained a fasting blood draw, a 24-hour urine collection, muscle performance measures, and a muscle biopsy of the vastus lateralis at baseline and 4 months. Subjects were randomized to take an oral vitamin D 3 capsule 4000 IU daily or matching placebo for 4 months. Department of Agriculture Human Nutrition Research Center on Aging at Tufts University. This was a randomized, double-blind, placebo-controlled study conducted at the Metabolic Research Unit at the Jean Mayer U.S. Subjects and Methods Study design and subjects The study also aimed to examine the effects of vitamin D on the proportion of type I and/or II muscle fibers and urine nitrogen (UNi) excretion (a marker of muscle breakdown) and to confirm previously reported effects of vitamin D 3 on muscle strength and physical function. We conducted a pilot study to test the hypothesis that oral vitamin D 3 4000 IU daily compared with placebo alters total and/or subtype muscle fiber cross-sectional area (FCSA) and intramyonuclear VDR concentration over a 4-month period in mobility-limited women aged 65 years and over with moderately low baseline vitamin D status. Yet, clinical studies examining effects of parent vitamin D compounds on human muscle fibers and concentration of VDR in muscle, particularly in older adults, are lacking.
These studies have also demonstrated that concentration of the intramyonuclear VDR increases after both 1,25-dihydroxyvitamin D and 25-hydroxyvitamin D (25OHD) administration.
Administration of vitamin D, as 1,25-dihydroxyvitamin D, stimulated key pathways of muscle growth and differentiation in C2C12 myoblasts ( 10, 12, 14) and acted directly on these cells via a nuclear vitamin D receptor (VDR) ( 10, 11).
Experiments in vitro have examined potential mechanisms by which vitamin D acts on skeletal muscle cells ( 10– 13). Several intervention studies have reported that vitamin D supplementation increases appendicular muscle strength and improves physical function particularly in older women with low vitamin D status ( 6– 9). Low vitamin D status has been associated with reduced muscle mass, strength, and performance in older adults ( 1– 5).
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