title: High-dose vitamin C supplementation increases skeletal muscle vitamin C concentration and SVCT2 transporter expression but does not alter redox status in healthy males.
abstract: 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 of accumulation of VC in skeletal muscle and plasma during high-dose VC supplementation in healthy individuals. Concurrently we investigated the 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, crossover trial involving supplementation with ascorbic acid (2×500 mg/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) to 3.9±0.4 mg/100 g wet weight (ww) versus placebo 3.1±0.3 to 2.9±0.2 mg/100 g ww, p=0.001). Plasma VC increased after 1 day, which was maintained at 42 days (VC 61.0±6.1 to 111.5±10.4 µmol/L versus placebo 60.7±5.3 to 59.2±4.8 µmol/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.
authors.affiliation: Centre for Physical Activity and Nutrition Research, School of Exercise and Nutrition Sciences, Deakin University, Burwood, VIC 3125, Australia.
authors.forename: Shaun A
authors.initials: SA
authors.lastname: Mason
authors.affiliation: Centre for Physical Activity and Nutrition Research, School of Exercise and Nutrition Sciences, Deakin University, Burwood, VIC 3125, Australia.
authors.forename: Raquel
authors.initials: R
authors.lastname: Baptista
authors.affiliation: Centre for Physical Activity and Nutrition Research, School of Exercise and Nutrition Sciences, Deakin University, Burwood, VIC 3125, Australia.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Della Gatta
authors.affiliation: Centre for Physical Activity and Nutrition Research, School of Exercise and Nutrition Sciences, Deakin University, Burwood, VIC 3125, Australia.
authors.forename: Adel
authors.initials: A
authors.lastname: Yousif
authors.affiliation: Centre for Physical Activity and Nutrition Research, School of Exercise and Nutrition Sciences, Deakin University, Burwood, VIC 3125, Australia.
authors.forename: Aaron P
authors.initials: AP
authors.lastname: Russell
authors.affiliation: Centre for Physical Activity and Nutrition Research, School of Exercise and Nutrition Sciences, Deakin University, Burwood, VIC 3125, Australia. Electronic address: glenn.wadley@deakin.edu.au.
authors.forename: Glenn D
authors.initials: GD
authors.lastname: Wadley
mesh_terms: D000293:Adolescent; D000328:Adult; D001205:Ascorbic Acid / Q000008:administration & dosage* / Q000493:pharmacokinetics; D018592:Cross-Over Studies; D004311:Double-Blind Method; D015870:Gene Expression; D064368:Healthy Volunteers; D006801:Humans; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism*; D010084:Oxidation-Reduction; D060347:Sodium-Coupled Vitamin C Transporters / Q000235:genetics / Q000378:metabolism*; D055815:Young Adult
chemical_list: C555163:SLC23A2 protein, human; D060347:Sodium-Coupled Vitamin C Transporters; D001205:Ascorbic Acid
keywords: Antioxidant; Free radicals; Reactive oxygen species; Skeletal muscle; Sodium-dependent vitamin C transporter 2; Vitamin C