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.