Effects of Dietary Nitrate and Vitamin C supplementation on Blood pressure and Vascular Health in Humans.

Abstract

Endothelial dysfunction (ED) and elevated blood pressure are key risk factors for cardiovascular disease, characterized by reduced nitric oxide (NO) bioavailability. Co-administration of vitamin C and inorganic nitrate (NO3¯) may reduce oxidative stress, boost the conversion of nitrite (NO₂⁻) into NO and elicit positive vascular effects. Systematic review and meta-analysis of 20 randomized controlled trials (890 participants) demonstrated that vitamin C supplementation significantly reduced systolic blood pressure, with greater effects in populations with type 2 diabetes (-4.6 mmHg) and essential hypertension (-3.2 mmHg). Cross-sectional analysis of the InChianti cohort (920 older participants) showed initial inverse correlations between dietary NO3¯ and blood pressure, and vitamin C with systolic blood pressure only, all becoming non-significant after adjustment for confounding factors. No significant interaction was observed between NO3¯ and vitamin C on blood pressure. Analysis of vascular biomarkers revealed that dietary NO3¯ intake maintained significant negative associations with reduced C-reactive protein (CRP) and symmetric dimethylarginine (SDMA) levels even after adjustment for confounders. Vitamin C intake was positively associated with increased homoarginine levels. The only significant interaction effect between dietary NO−3 and vitamin C was observed for L-arginine concentrations. In the experimental study on young healthy participants, combined supplementation of dietary NO3¯ (6 mmol) and vitamin C (1000 mg) for three days significantly reduced home systolic blood pressure, while no significant changes were observed with NO3¯ alone. The subsequent randomized crossover trial in overweight/obese middle-aged adults showed no significant changes in blood pressure across interventions but demonstrated that co-supplementation significantly improved flow-mediated dilation (FMD) and increased NO₂⁻ bioavailability compared to NO3¯ supplementation alone. In conclusion, age, adiposity and metabolic status appear to influence the blood pressure and vascular responses to dietary NO3¯ and vitamin C co-supplementation. While blood pressure responses varied across studies, consistent enhancement of NO₂⁻ bioavailability and improved endothelial function with combined supplementation suggests potential therapeutic applications. These findings highlight the importance of considering individual anthropometric and physiological factors in designing nutritional interventions for cardiovascular health.