A number of really bright people are still unsure of what to make about the vitamin C, steroids and thiamine newsflash that’s taken Twitter by storm yesterday. At Sinai here we’re the curious types, so we chatted with our pharmacist who similarly didn’t know what to make of the headlines given the lack of a randomized controlled trial. What follows is some of the ground work that’s been done on animal studies and on the molecular level for vitamin C–just to catch us all up to speed while the news / evidence develops. The EMCrit and PulmCrit posts are certainly deeper dives into the purported vitamin C deficiency abnormalities of sepsis–though, normal is often a philosophical debate. Who knows what the bottom line is at this point given the limited evidence, but the following should be informative background knowledge.

 

Most of this is from the Wilson 2009 paper that predates the recent Marik sepsis media storm:

 

Endothelial health

  • Vitamin C modulates endothelial signaling.
  • Improves microvascular function, capillary blood flow and microvascular permeability barrier.
  • In vitro, vitamin C attenuates the lipopolysaccharide (LPS)-mediated increased endothelial permeability (Dimmler 1995).

 

Capillary blood flow

  • Improves the maldistribution of blood flow
    • The maldistribution initially seen in sepsis is characterized by decreased density of the perfused capillaries with a corresponding increase in the proportion of non-perfused capillaries
    • There is decreased availability of nitric oxide (NO) in endothelial cells / platelets. NO appears to keep microvessels patent.
      • There is decreased NO available inside septic endothelial cells and platelets. This may be secondary to reactive oxygen species.
      • Bolus injection of vitamin C immediately after septic insult improves the capillary blood flow in cecal ligation and puncture rat skeletal muscle.

 

 

Vit C and endogenous vasoactive compounds

  • Vit C may increase vasomotor responsiveness by increasing endogenous synthesis of norepinephrine and vasopressin.
  • Glucocorticoids and vit C may act synergistically inducing SVCT to increase vit C uptake intracellularly and restore glucocorticoid receptor function.

 

 

References

Wilson JX. Mechanism of action of vitamin C in sepsis: ascorbate modulates redox signaling in endothelium. Biofactors. 2009;35(1):5-13.

Wilson JX. Evaluation of vitamin C for adjuvant sepsis therapy. Antioxid Redox Signal 2013;19:2129.