Rationale for mega-dose vitamin C treatment in sepsis
Intravenous administration of a mega-dose of sodium ascorbate (150 g/~40 kg 7-h) in established ovine hyperdynamic sepsis, induced by infusion of live Escherichia. coli , caused a remarkable improvement in the clinical state from malaise, lethargy and somnolence to an alert, responsive, mobile state (Lankadeva et al., 2021). MAP was restored to pre-septic levels with reduced noradrenaline requirements, which decreased to zero in 4 of 5 cases. Mega-dose vitamin C increased arterial blood oxygen levels, indicative of improvements in lung function, restored body temperature from febrile to normal levels and reduced arterial blood lactate indicating improved metabolic function. The treatment also reversed renal medullary hypoperfusion and hypoxia, accompanied by a reversal in septic AKI, as shown by dramatic increases in urine flow and creatinine clearance leading to a normalisation of plasma creatinine levels.
The re-distribution of intra-renal perfusion in ovine septic AKI (Calzavacca, Evans, Bailey, Bellomo & May, 2015) is accompanied by reduced gene expression of renal medullary endothelial nitric oxide synthase (eNOS) (Langenberg, Bagshaw, May & Bellomo, 2008). The reversal of renal medullary microcirculatory dysfunction by vitamin C may result from its ability to increase eNOS activity and thus nitric oxide bioavailability (Ladurner et al., 2012). Furthermore, the antioxidant effects of vitamin C are likely to reduce mitochondrial dysfunction and cellular injury.