An unexplained decrease in muscle strength occurs with increasing age. Persons over seventy years old average about 50 percent of the strength of those less than 35 years old. As strength declines with increasing age, mobility, functional capacity and independence are lost, and the risk of injury as a result of falling increases. Decreased muscle strength is also a well-documented symptom of vitamin D deficiency and particularly of 1,25 D deficiency. The myopathy associated with 1,25 D deficiency, like that seen with aging, is characterized by proximal muscle atrophy and a selective loss of type II muscle fibers. Administration of 1,25 D to patients with 1,25 D deficiency restores muscle strength. Serum concentration of 1,25 D decreases with increasing age. Serum 1,25 D levels in persons over 70 years old average about 55 percent of those in persons in their mid thirties. In uncontrolled studies, administration of 1,25 D to elderly subjects has improved muscle strength. In a pilot study, we showed a 27.5 percent increase in muscle strength in healthy elderly men after one month of oral treatment with 1,25 D, and a 35 percent improvement in those over 70 years old. In the pilot study the percent increase in strength was strongly correlated with the percent increase in serum 1,25 D level (correlation coefficient = .9). Based on these observations and biochemical evidence linking 1,25 D to muscle function, we hypothesize that the weakness associated with aging is, in part, due to inadequate serum concentrations of 1,25 D in the elderly. To test this hypothesis, we proposed to perform a randomized, controlled, double-blinded trial of the effects of oral treatment with 1,25 D in 100 persons over 70 years old using the isokinetic dynamometer as a precise measure of strength. Our study will have a 90 percent power to show a 20 percent difference between the treated and placebo groups. A positive study will establish a metabolic etiology for the weakness presently considered a """"""""normal"""""""" part of the aging process and open a new area for biochemical research in aging. If effective, treatment with vitamin D may make it possible to improve mobility, reduce functional dependence and decrease the risk of falling in the elderly.

National Institute of Health (NIH)
National Institute on Aging (NIA)
Research Project (R01)
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Epidemiology and Disease Control Subcommittee 3 (EDC)
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University of California San Francisco
Schools of Medicine
San Francisco
United States
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Grady, D; Halloran, B; Cummings, S et al. (1991) 1,25-Dihydroxyvitamin D3 and muscle strength in the elderly: a randomized controlled trial. J Clin Endocrinol Metab 73:1111-7