High dose vitamin C supplementation increases skeletal muscle vitamin C concentration and SVCT2 transporter expression but does not alter redox status in healthy males.

Antioxidant vitamin C (VC) supplementation is of potential clinical benefit to individuals with skeletal muscle oxidative stress. However there is a paucity of data reporting on the bioavailability of high dose oral VC in human skeletal muscle. We aimed to establish the time-course accumulation of VC in skeletal muscle and plasma during high dose VC supplementation in healthy individuals. Concurrently we investigated effects of VC supplementation on expression levels of the key skeletal muscle VC transporter, sodium-dependent vitamin C transporter 2 (SVCT2) and intramuscular redox and mitochondrial measures. Eight healthy males completed a randomized placebo-controlled, cross-over trial involving supplementation with ascorbic acid (2×500mg/day) over 42 days. Participants underwent muscle and blood sampling on days 0, 1, 7 and 42 during each treatment. VC supplementation significantly increased skeletal muscle VC concentration after 7 days, which was maintained at 42 days (VC: 3.0±0.2 [mean±SEM] mg/100gwet weight [ww] to 3.9±0.4mg/100g ww versus placebo: 3.1±0.3mg/100g ww to 2.9±0.2mg/100g ww, p=0.001). Plasma VC increased after 1 day, which was maintained at 42 days (VC: 61.0±6.1μmol/l to 111.5±10.4μmol/l versus placebo: 60.7±5.3μmol/l to 59.2±4.8μmol/l, p<0.001). VC supplementation significantly increased skeletal muscle SVCT2 protein expression (main treatment effect p=0.006) but did not alter skeletal muscle redox measures or citrate synthase activity. A main finding of our study was that 7 days of high dose VC supplementation was required to significantly increase skeletal muscle vitamin C concentration in healthy males. Our findings implicate regular high dose vitamin C supplementation as a means to safely increase skeletal muscle vitamin C concentration without impairing intramuscular ascorbic acid transport, antioxidant concentrations or citrate synthase activity.