Effects of Vitamin D Supplementation on Neural Plasticity, Serum Brain-derived Neurotrophic Factor (BDNF) and Functional Performance in Older Adults: A 10-week Double-Blinded Randomised Controlled Trial

Vitamin D has direct effects on muscle modulated by specific VDRs present in muscle tissue, but VDRs are also located in the brain and CNS, including the primary motor cortex (M1) which is responsible for controlling movement. Thus it is possible that the beneficial effects of Vit D on neuromuscular function may be mediated by changes in neural plasticity (eg. the ability of the brain to adapt and strengthen neural connections). Transcranial magnetic stimulation (TMS) is a non-invasive technique that allows an objective assessment of neurophysiological changes such as corticomotor plasticity and altered synaptic activity, and thus provides direct evidence of changes in the responsiveness of the human corticospinal tract. The aim of this 10- wk double-blinded, placebo controlled trial was to examine the effects of Vit D on: 1) corticomotor excitability and plasticity; 2) serum brain-derived neurotrophic factor (BDNF), a neurotrophin involved in regulating synaptic plasticity and neurogenesis, and 3) muscle strength, power and function. Healthy adults aged 60+ yrs with serum 25OHD ,60 nmol/L were randomized to 2000IU/d Vit D3 (n=13) or a matched placebo group (n=13). Single and paired-pulse TMS applied over the M1 was used to assess changes in motor evoked potentials (MEPs) and short-interval intracortical inhibition (SICI), as a measure of corticomotor excitability and inhibition, respectively, by recording EMG responses to stimulation from the wrist extensors. Muscle strength (leg extension), power (stair climb), function (TUG, four square step test), serum 25OHD and BDNF were assessed. 96% of the participants completed the trial; supplement compliance was similar between the groups (98% Vit D; 89% placebo, P=0.13). Serum 25OHD increased by 34 nmol/L in the Vit D group with no change in the controls (-1.2 nmol/L). After 10-weeks, treatment with Vit D resulted in an increase in muscle strength (8-11%) and a reduction in cortical excitability (MEP amplitude) and intracortical inhibition (all P,0.05). However, these changes were not significantly different from those observed in the controls. There was no effect of Vit D on muscle power, function or serum BDNF. While the lack of significant between group differences may relate to the sample size, the reduction in excitability and inhibition suggests that Vit D may improve the efficacy of neural transmission within the corticospinal pathway, and thereby facilitate motor output and improve muscle performance.