Rational for vitamin C therapy in sepsis
Vitamin C, ascorbic acid, is an essential vitamin in humans that must be obtained in the diet; it cannot be synthesised because of mutations in the gene for gluconolactone oxidase, the final biosynthetic enzyme in its synthesis. Vitamin C is essential for collagen synthesis, accounting for the symptoms of scurvy caused by its deficiency. Vitamin C also has numerous pleiotropic effects that would be predicted to be of benefit in sepsis, including as an anti-oxidant, anti-inflammatory, anticoagulant, immune-modulator and stimulant of noradrenaline and vasopressin synthesis (Holford et al., 2020). Furthermore, septic patients have abnormally low plasma vitamin C levels, likely due to increased metabolic turnover (de Grooth et al., 2018) and downregulation of cellular sodium-dependent vitamin C transporters (SVCTs) (Subramanian, Sabui, Moradi, Marchant & Said, 2018), which is compounded by the inability of humans to synthesise vitamin C. Importantly, intravenous administration is required to produce high plasma levels of vitamin C as there is a limit on the intestinal absorption (Padayatty et al., 2004). These observations provided the impetus for clinical trials examining the effects of intravenous vitamin C in sepsis.