WHAT IS KNOWN AND OBJECTIVE: The increased central sympathetic activity typically associated with chronic heart failure (CHF) is probably mediated by formation of reactive oxygen species (ROS) in the brain. Our objective was to undertake a trial to test our hypothesis that administration of the well-known antioxidant and ROS scavenger ascorbic acid, would reverse or reduce the sympathetic overactivity in CHF patients. METHODS: In a prospective, randomized, placebo-controlled, double-blind, cross-over trial, 11 CHF patients were treated with ascorbic acid 2 g/day or placebo for 3 days. At the end of each treatment period, sympathetic nervous system activity was measured by microneurography for direct muscle sympathetic nerve activity (MSNA) recording, analysis of heart rate variability (HRV) and measurement of plasma norepinephrine concentrations. RESULTS: During ascorbic acid administration, plasma vitamin C levels were higher than during placebo (74.9 +/- 6.0 mumol/L vs. 54.8 +/- 4.6 mumol/L, P = 0.03). Ascorbic acid had no effect on sympathetic activity: MSNA (ascorbic acid: 66.8 +/- 3.3 vs. placebo 66.9 +/- 3.2 bursts/100 beats, P = 0.98). In addition, HRV and plasma norepinephrine levels did not differ. WHAT IS NEW AND CONCLUSION: Short-term administration of the antioxidant ascorbic acid in CHF patients does not reverse the increased sympathetic activity as measured by microneurography, HRV and plasma norepinephrine levels. The use of higher oral dosages seems not feasible due to accompanying side effects.