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 D₃ 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/m², 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 D₃ 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.