Journal Article

25-Hydroxyvitamin D 3 promotes slow-twitch fiber type transition in skeletal muscle

Whang, Kwang-Youn, Kim, Jun-Mo, Park, Min Young, Seok, Min-Ki, Kim, Do-Young

2026

Overview

Vitamin D supports musculoskeletal health, including bone mineral density and skeletal muscle function. Vitamin D₃ (VitD3, cholecalciferol) is an inactive form which requires two enzymatic hydroxylation steps, from VitD₃ to 25-hydroxyvitamin D₃ (25OHD₃, calcifediol) in liver and then to active form 1,25-dihydroxyvitamin D3 (1,25(OH)2D3, calcitriol) in kidney. Vitamin D status is determined by circulating 25OHD levels. Compared with VitD3, calcifediol bypasses the hepatic 25-hydroxylation step and is more hydrophilic, resulting in higher bioavailability and less sequestration in adipose tissue. Previous studies have linked both VitD₃ and 25OHD₃ to muscle mass, strength or atrophy markers, but their effects on skeletal muscle fiber-type composition remains unclear. We hypothesize that dietary 25OHD₃ versus VitD₃ differentially modulates skeletal muscle fiber composition during postnatal growth. Three-week-old male rats were fed a VitD₃–deficient diet for 4 weeks and then assigned for 4 weeks to diets that were deficient or replete with VitD₃ or 25OHD₃. Relative to VitD₃ repletion, 25OHD₃ repletion increased the proportion of slow-twitch type I fibers and decreased fast type IIb fibers in the bicep femoris, without altering muscle mass. This shift was accompanied by higher mitochondrial DNA copy number. Transcriptomic profiling indicated enrichment of extracellular signal-regulated kinase (ERK) and calcium signaling pathways, including genes in vascular endothelial growth factor receptor-2 (VEGFR2) and nitric oxide synthase (NOS) pathways and inositol 1,4,5-trisphosphate kinase (IP3K). These data suggest that, following early-life vitamin D deficiency, dietary 25OHD₃ preferentially promotes slow-oxidative fiber transition compared with VitD₃, and is associated with transcriptional enrichment of ERK- and calcium-dependent signaling.

• Subject: Animals / Calcifediol - metabolism / Calcifediol - pharmacology / Cholecalciferol / Male / Muscle Fibers, Slow-Twitch - drug effects / Muscle Fibers, Slow-Twitch - metabolism / Muscle, Skeletal - drug effects / Muscle, Skeletal - metabolism / Rats / Vitamin D Deficiency - metabolism