A Randomized Study on the Effect of Vitamin D3 Supplementation on Skeletal Muscle Morphology and Vitamin D Receptor Concentration in Older Women

Context: Studies examining whether vitamin D supplementation increases muscle mass or muscle-specific vitamin D receptor (VDR) concentration are lacking. Objective: Our objective was to determine whether vitamin D-3 4000 IU/d alters muscle fiber cross-sectional area (FCSA) and intramyonuclear VDR concentration over 4 months. Design and Setting: This was a randomized, double-blind, placebo-controlled study in a single center. Participants: Participants were 21 mobility-limited women (aged >= 65 years) with serum 25-hydroxyvitamin D (25OHD) levels of 22.5 to 60 nmol/L. Main Outcome Measures: Baseline and 4-month FCSA and intramyonuclear VDR were measured from vastus lateralis muscle cross-sections probed for muscle fiber type (I/IIa/IIx) and VDR using immunofluorescence. Results: At baseline, mean (+/- SD) age was 78 +/- 5 years; body mass index was 27 +/- 5 kg/m(2), 25OHD was 46.3 +/- 9.5 nmol/L, and a short physical performance battery score was 7.95 +/- 1.57 out of 12. At 4 months, 25OHD level was 52.5 +/- 17.1 (placebo) vs 80.0 +/- 11.5 nmol/L (vitamin D [ VD]; P < .01), and change in 25OHD level was strongly associated with percent change in intramyonuclear VDR concentration-independent of group (r = 0.87, P < .001). By treatment group, percent change in intramyonuclear VDR concentration was 7.8% +/- 18.2% (placebo) vs 29.7% +/- 11.7% (VD; P = .03) with a more pronounced group difference in type II vs I fibers. Percent change in total (type I/II) FCSA was -7.4% +/- 18.9% (placebo) vs 10.6% +/- 20.0% (VD; P = .048). Conclusion: Vitamin D-3 supplementation increased intramyonuclear VDR concentration by 30% and increased muscle fiber size by 10% in older, mobility-limited, vitamin D-insufficient women. Further work is needed to determine whether the observed effect of vitamin D on fiber size is mediated by the VDR and to identify which signaling pathways are involved.