Limited evidence for a beneficial effect of vitamin C supplementation on biomarkers of cardiovascular diseases: an umbrella review of systematic reviews and meta-analyses

Vitamin C is an essential nutrient with important antioxidant properties. Higher vitamin C intake appears to be associated with positive effects on cardiovascular risk factors in cohort studies, whereas large randomized controlled clinical trials did not confirm the benefits of supplemental vitamin C on cardiovascular disease (CVD) outcomes. In this overview of systematic reviews and meta-analyses, an “umbrella review,” we investigated the effects of vitamin C supplementation on biomarkers of cardiovascular risk, that is, arterial stiffness, blood pressure, endothelial function, glycemic control, and lipid profile. In addition, we assessed the strength of the evidence and the methodological qualities of available studies. Two independent investigators searched 4 databases (Medline, Embase, Scopus, and The Cochrane Library databases) from inception until February 2018. After full text examination, 10 systematic reviews and meta-analyses were included in the umbrella review which included 6409 participants. Three systematic reviews investigated the effects of vitamin C on endothelial function with contrasting results (2 reviews reported a significant effect, and all 3 showed a high heterogeneity [I2> 50%]); 1 systematic review reported significant improvement for each of the following risk factors: blood pressure, and blood concentrations of glucose, low-density lipoprotein cholesterol, and triglycerides. There were no overall effects of vitamin C on arterial stiffness and blood concentration of insulin, total cholesterol, and high-density lipoprotein cholesterol, but subgroup analyses revealed some evidence for significant improvements in subpopulations with higher body mass index, higher plasma concentrations of glucose or cholesterol, and low plasma concentration of vitamin C. Results from this umbrella review emphasize the weakness of the current evidence base about effects of vitamin C supplementation on markers of CVD risk. There is limited evidence that some population subgroups (older people, the obese, those with lower vitamin C status at baseline, and those at higher CVD risk) may be more responsive to vitamin C supplementation and offer opportunities for tailored nutritional interventions to improve cardiometabolic health. Future studies should implement a selective recruitment strategy that is informed by evidence-based literature synthesis.