Improving the Vitamin D Status of Vitamin D Deficient Adults Is Associated With Improved Mitochondrial Oxidative Function in Skeletal Muscle

Abstract

Objective: Suboptimal mitochondrial function has been implicated in several disorders in which fatigue is a prominent feature. Vitamin D deficiency is a well-recognized cause of fatigue and myopathy. The aim of this study was to examine the effects of cholecalciferol therapy on skeletal mitochondrial oxidative function in symptomatic, vitamin D-deficient individuals.Design: This longitudinal study assessed mitochondrial oxidative phosphorylation in the gastrosoleus compartment using phosphorus-31 magnetic resonance spectroscopy measurements of phosphocreatine recovery kinetics in 12 symptomatic, severely vitamin D-deficient subjects before and after treatment with cholecalciferol. All subjects had serum assays before and after cholecalciferol therapy to document serum 25-hydroxyvitamin D (25OHD) and bone profiles. Fifteen healthy controls also underwent 31 P-magnetic resonance spectroscopy and serum 25OHD assessment. Results:The phosphocreatine recovery half-time ( 1/2 PCr) was significantly reduced after cholecalciferol therapy in the subjects indicating an improvement in maximal oxidative phosphorylation (34.44 Ϯ 8.18 sec to 27.84 Ϯ 9.54 sec, P Ͻ .001). This was associated with an improvement in mean serum 25OHD levels (8.8 Ϯ 4.2 nmol/L to 113.8 Ϯ 51.5 nmol/L, P Ͻ .001). There was no difference in phosphate metabolites at rest. A linear regression model showed that decreasing serum 25OHD levels was associated with increasing 1/2 PCr (r ϭ Ϫ0.41, P ϭ .009). All patients reported an improvement in fatigue after cholecalciferol therapy. Conclusions:Cholecalciferol therapy augments muscle mitochondrial maximal oxidative phosphorylation after exercise in symptomatic, vitamin D-deficient individuals. This finding suggests that changes in mitochondrial oxidative phosphorylation in skeletal muscle could at least be partly responsible for the fatigue experienced by these patients.

1α,25-Dihydroxyvitamin D3 Regulates Mitochondrial Oxygen Consumption and Dynamics in Human Skeletal Muscle Cells

“…The differentially expressed mRNAs encode proteins that play significant roles in multiple biochemical pathways involved in muscle contraction and relaxation; extracellular matrix-cell receptor interactions; actin cytoskeleton remodeling; and JAK-STAT, insulin-like (17) 0.014 Reactome p53 pathway (16) 0.014 Panther Interferon-signaling (11) 0.017 Panther Muscle contraction (9) 0.022 Reactome Terpenoid backbone biosynthesis (6) 0.028 KEGG Cell adhesion molecules (24) 0.048 KEGG (27), which showed that treatment of vitamin D-deficient humans with cholecalciferol improves muscle phosphocreatine recovery after exercise, suggesting an effect of 1␣,25(OH) 2 D 3 on the formation of high energy phosphorylated intermediates and mitochondrial function. The increase in the numbers of mitochondria could also account for the increase in cellular OCR.…”

“…Many reports suggest that the vitamin D receptor (VDR) is expressed in skeletal muscle (20 -24), and VDR deletion in mice results in alterations in muscle function and strength (25,26). Treatment of vitamin D-deficient humans with cholecalciferol improves muscle phosphocreatine recovery after exercise (27), suggesting that vitamin D 3 or its metabolites alter skeletal muscle oxidative capacity.…”

Vitamin D, a modulator of musculoskeletal health in chronic kidney disease

“…They involve the rapid regulation of membrane calcium channels, suggesting a role for vitamin D in the calcium‐mediated muscle functions, such as muscle contraction and mitochondrial function, which leads to an adequate insulin signalling and muscle substrate metabolism 42. All these findings may clarify the relationship between low vitamin D status and muscle weakness,37, 43 intramuscular fat deposition,44 and resistance to insulin,45 which is related to cardiovascular risk and increased skeletal muscle breakdown 46.…”

Do Professional Soccer Players have a Vitamin D Status Supporting Optimal Performance in Winter time?

“…Very recently the beneficial effect of vitamin D on oxidative phosphorylation was shown, giving a clue for the possible mechanism of vitamin D associated fatigue and muscle weakness [13].…”