Epidemiology suggests adequate VitaminC levels are required for more than just the prevention of scurvy however numerous supplementation studies have failed to demonstrate any compelling benefits.  The underlying reasons for these disparate scenarios remain obscure but may be due, at least in part, to a lack of pre-screening to identify subjects with low VitaminC levels (estimated at 10-20% in Western populations), the relative low-dose VitaminC supplementation used in many studies, and the heterogeneity in VitaminC metabolism across individuals.  We previously reported that human adipocytes supplemented with VitaminC 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.    

In the current study we have extended these observations in a mouse model of VitaminC deficiency, the Gulo^-/- mouse.  Like humans, the gene encoding the last step in the biosynthetic pathway of VitaminC (L-gulonolactone oxidase) is defective in the Gulo^-/- mouse making them dependent on dietary intake/supplementation.  We hypothesised that the circulating levels of HMW adiponectin would be sensitive to VitaminC supplementation.  Consistent with this we found Gulo^-/- mice supplemented with low dose VitaminC (330 mg/ml  - a ‘maintenance dose’ required to prevent scurvy but not sufficient to make the mice replete) had lower levels of HMW adiponectin than WT littermates and that supplementation with high dose VitaminC (3300 mg/ml) for 3 weeks increased HMW adiponectin 2-fold (n=10, p<0.001).  Circulating levels of HMW adiponectin returned to baseline 1 week after a reversal to low dose VitaminC supplementation.  In contrast, total adiponectin was not different between WT and Gulo^-/- mice, nor was it affected by VitaminC status in Gulo^-/- mice. 

These results fully recapitulate our in vitro findings¹ as well as clinical trials which have found no correlation between VitaminC and total adiponectin.  These observations provide a foundation for detailed studies investigating the impact of modulating VitaminC levels on adiponectin and cardiometabolic parameters in a pre-clinical model of diet-induced obesity.  We anticipate these results will provide the basis for rational investigations in humans.