Why vitamin C and corticosteroids are inadequate and how essential fatty acids (EFAs) can augment recovery from sepsis.

The failed regimens for sepsis include but are not limited to steroids, antibiotic coverage for gram-negatives, and activated protein C. Reports of dramatic successes with vitamin C, its low cost and virtual absence of side effects in sepsis are encouraging despite some negative reports. I propose that this discrepancy in the results could be attributed to the altered status of essential fatty acid (EFA) metabolism in sepsis. Patients with sepsis have reduced plasma phospholipid concentrations of gamma-linolenic acid (GLA, 18:3 ω-6), dihomo-GLA (20:3 ω-6), arachidonic acid (AA, 20:4 ω-6), alpha-linolenic acid (ALA, 8:3 ω-3), and eicosapentaenoic acid (EPA, 20:5 ω-3) that are generated from dietary essential fatty acids {EFAs: cis-linoleic acid (LA) and α-linolenic acid (ALA)}. EFAs form the precursors to both pro-inflammatory and anti-inflammatory eicosanoids. Lipoxin A4 (LXA4), an anti-inflammatory eicosanoid derived from AA, enhances blood and peritoneal neutrophil phagocytic action, improves survival and promotes a more complete resolution of inflammation in sepsis. Prostaglandin E1 (PGE1), derived from DGLA, has actions like LXA4 and augments LXA4 generation. Vitamin C enhances the formation of PGE1 that may account for its beneficial action in sepsis and other conditions. EFAs metabolism is interfered with by corticosteroids and pro-inflammatory interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). EFAs need several co-factors including but not limited to vitamins B1, B6, and B12 for their optimum metabolism. Hence, it is proposed that co-administration of EFAs along with vitamins C, B1, B6, and B12 with or without corticosteroids may be of significant benefit in sepsis and septic shock.