Objective: Suboptimal mitochondrial function has been implicated in several disorders where fatigue is a prominent feature. Vitamin D deficiency is a well-recognised 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 gastro-soleus 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 (1012 weeks later). All subjects had serum assays before and after cholecalciferol therapy to document serum 25OHD and bone profiles. 15 healthy controls also underwent 31P-MRS and serum 25OHD assessment.
Results: The phosphocreatine recovery half-time (τ1/2PCr, τ1/2ADP) was significantly reduced following cholecalciferol therapy in the subjects indicating an improvement in maximal oxidative phosphorylation (P<0.001, P=0.003). This was associated with an improvement in mean serum 25OHD levels (8.8±4.2 to 113.8±51.5 nmol/l, P<0.001). There was no difference in phosphate metabolites at rest. A linear regression model showed that decreasing serum 25OHD levels are associated with increasing τ1/2PCr (r=−0.41, P=0.009). All patients reported an improvement in fatigue following cholecalciferol therapy.
Conclusions: Cholecalciferol therapy augments muscle mitochondrial maximal oxidative phosphorylation following 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. For the first time, we demonstrate a link between vitamin D and the mitochondria in human skeletal muscle.
Declaration of funding
This research was supported by the British Society of Paediatric Endocrinology and Diabetes (BSPED) prize to Dr Akash Sinha (2011).