title: High dose ascorbic acid does not reverse central sympathetic overactivity in chronic heart failure.
abstract: 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 μmol/L vs. 54·8 ± 4·6 μmol/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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Internal Medicine Department of Cardiology Department of Pharmacology Toxicology, University Medical Center Nijmegen, Nijmegen, The Netherlands.
authors.forename: M E
authors.initials: ME
authors.lastname: Gomes
authors.forename: S
authors.initials: S
authors.lastname: El Messaoudi
authors.forename: J W M
authors.initials: JW
authors.lastname: Lenders
authors.forename: L
authors.initials: L
authors.lastname: Bellersen
authors.forename: F W A
authors.initials: FW
authors.lastname: Verheugt
authors.forename: P
authors.initials: P
authors.lastname: Smits
authors.forename: C J
authors.initials: CJ
authors.lastname: Tack
mesh_terms: D000368:Aged; D001205:Ascorbic Acid / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D001794:Blood Pressure / Q000502:physiology; D002908:Chronic Disease; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D016166:Free Radical Scavengers / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D006333:Heart Failure / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D006339:Heart Rate / Q000502:physiology; D006801:Humans; D008297:Male; D008839:Microelectrodes / Q000706:statistics & numerical data; D008875:Middle Aged; D009132:Muscles / Q000294:innervation / Q000503:physiopathology; D009638:Norepinephrine / Q000097:blood; D010919:Placebos; D011446:Prospective Studies; D017382:Reactive Oxygen Species / Q000378:metabolism; D018401:Sample Size; D013564:Sympathetic Nervous System / Q000502:physiology / Q000503:physiopathology*
chemical_list: D016166:Free Radical Scavengers; D010919:Placebos; D017382:Reactive Oxygen Species; D001205:Ascorbic Acid; D009638:Norepinephrine