Vitamin C in sepsis

Subcell Biochem. 2012;56:67-83. doi: 10.1007/978-94-007-2199-9_5.


Bacterial bloodstream infection causes septic syndromes that range from systemic inflammatory response syndrome (SIRS) and encephalopathy to severe sepsis and septic shock. Microvascular dysfunction, comprising impaired capillary blood flow and arteriolar responsiveness, precedes multiple organ failure. Vitamin C (ascorbate) levels are low in critically ill patients. The impact of ascorbate administered orally is moderate because of its limited bioavailability. However, intravenous injection of ascorbate raises plasma and tissue concentrations of the vitamin and may decrease morbidity. In animal models of polymicrobial sepsis, intravenous ascorbate injection restores microvascular function and increases survival. The protection of capillary blood flow and arteriolar responsiveness by ascorbate may be mediated by inhibition of oxidative stress, modulation of intracellular signaling pathways, and maintenance of homeostatic levels of nitric oxide. Ascorbate scavenges reactive oxygen species (ROS) and also inhibits the NADPH oxidase that synthesizes superoxide in microvascular endothelial cells. The resulting changes in redox-sensitive signaling pathways may diminish endothelial expression of inducible nitric oxide synthase (iNOS), tissue factor and adhesion molecules. Ascorbate also regulates nitric oxide concentration by releasing nitric oxide from adducts and by acting through tetrahydrobiopterin (BH4) to stimulate endothelial nitric oxide synthase (eNOS). Therefore, it may be possible to improve microvascular function in sepsis by using intravenous vitamin C as an adjunct therapy.

Publication types

  • Review

MeSH terms

  • Animals
  • Ascorbic Acid / blood
  • Ascorbic Acid / metabolism
  • Ascorbic Acid / therapeutic use*
  • Ascorbic Acid Deficiency / blood
  • Ascorbic Acid Deficiency / drug therapy*
  • Ascorbic Acid Deficiency / etiology*
  • Brain Diseases / etiology
  • Brain Diseases / physiopathology
  • Humans
  • Hypotension / physiopathology
  • Regional Blood Flow / drug effects
  • Sepsis / blood
  • Sepsis / complications
  • Sepsis / drug therapy*


  • Ascorbic Acid