Compelling epidemiological data suggests that low Vitamin C levels are associated with obesity and obesity-related disease such as type 2 diabetes and cardiovascular disease; however numerous supplementation studies have failed to demonstrate benefits. The basis for this disparity is unknown, but failure to identify Vitamin C-deficient subjects (approximately 10-20% in Western populations), and the heterogeneity in Vitamin C metabolism between individuals, may significantly contribute. We previously reported that human adipocytes supplemented with Vitamin C in vitro, exhibited a dose-dependent increase in secretion of the most metabolically active (high molecular weight - HMW) form of the anti-diabetic, cardioprotective hormone adiponectin but not total adiponectin1.
We have now extended these observations in a pre-clinical model of Vitamin C deficiency, the Gulo-/- mouse. Like humans, the key gene in the biosynthetic pathway of Vitamin C (L-gulonolactone oxidase) is defective in Gulo-/- mice making them dependent on dietary intake. We found Gulo-/- mice supplemented with low Vitamin C (330 mg/ml - a ‘maintenance dose’ to prevent scurvy but not render mice replete) had lower levels of HMW adiponectin than WT littermates, and supplementation with high Vitamin C (3300 mg/ml) for 3 weeks significantly increased HMW adiponectin 2-fold. Circulating levels of HMW adiponectin returned to baseline 1 week after a reversal to low Vitamin C supplementation. In contrast, total adiponectin was not different between WT and Gulo-/- mice, nor was it affected by Vitamin C supplementation.
These results fully recapitulate our in vitro findings1 as well as clinical trials which have found no correlation between Vitamin C and total adiponectin, and provide a foundation for further preclinical investigation into the impact of Vitamin C on adiponectin and cardiometabolic parameters. We anticipate these results will provide the basis for rational investigations in humans.