title: Effect of systemic high dose vitamin C therapy on forearm blood flow reactivity during endotoxemia in healthy human subjects.
abstract: OBJECTIVE
  Acute inflammation induced by administration of Escherichia coli lipopolysaccharide endotoxin (LPS) reduces plasma concentrations of vitamin C and impairs vascular endothelium-derived nitric oxide (NO) bioactivity. We tested the hypothesis that systemically administered high dose vitamin C restores the endogenous anti-oxidant potential and improves NO-dependent vasodilatation in the forearm vasculature.
  
  
  METHODS
  36 male subjects were enrolled in this balanced, placebo controlled cross-over study. Forearm blood flow (FBF) reactivity to acetylcholine (ACh) and glyceryl-trinitrate (GTN), a sensitive test for endothelial function, was assessed at baseline and 4h after LPS-administration (20 IU/kg i.v). The effect of two different doses of intravenous vitamin C (Vitamin C-Injektopas®), 320 mg/kg and 480 mg/kg over 2h, or placebo on forearm vascular function was studied after LPS.
  
  
  RESULTS
  LPS caused transient flu-like symptoms, decreased plasma vitamin C concentrations and reduced the ACh-dependent increase in FBF by up to 76%. Vitamin C at a mean plasma concentration of 3.2 or 4.9 mmol/L restored the response to ACh compared to baseline.
  
  
  CONCLUSIONS
  High dose systemic vitamin C recovers LPS-induced endothelium-dependent vasodilation in the forearm resistance vasculature. This provides a rationale for a further clinical study of the systemic vitamin C effect under inflammatory conditions.
authors: Department of Clinical Pharmacology, Medical University of Vienna, Austria.
authors: S
authors: S
authors: Aschauer
authors: Department of Clinical Pharmacology, Medical University of Vienna, Austria.
authors: G
authors: G
authors: Gouya
authors: Department of Clinical Pharmacology, Medical University of Vienna, Austria.
authors: U
authors: U
authors: Klickovic
authors: Department of Clinical Pharmacology, Medical University of Vienna, Austria.
authors: A
authors: A
authors: Storka
authors: Department of Clinical Pharmacology, Medical University of Vienna, Austria.
authors: S
authors: S
authors: Weisshaar
authors: Pascoe Pharmazeutische Präparate GmbH, Giessen, Germany.
authors: C
authors: C
authors: Vollbracht
authors: Pascoe Pharmazeutische Präparate GmbH, Giessen, Germany.
authors: B
authors: B
authors: Krick
authors: Pascoe Pharmazeutische Präparate GmbH, Giessen, Germany.
authors: G
authors: G
authors: Weiss
authors: Department of Clinical Pharmacology, Medical University of Vienna, Austria. Electronic address: michael.wolzt@meduniwien.ac.at.
authors: M
authors: M
authors: Wolzt
mesh_terms: D000328:Adult; D001205:Ascorbic Acid / Q000627:therapeutic use*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D019446:Endotoxemia / Q000188:drug therapy* / Q000503:physiopathology; D005542:Forearm / Q000098:blood supply*; D064368:Healthy Volunteers; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D012039:Regional Blood Flow / Q000187:drug effects
chemical_list: D008070:Lipopolysaccharides; D001205:Ascorbic Acid
keywords: Endothelial dysfunction; Endotoxemia; Forearm blood flow; Inflammation; Vitamin C