Is Sepsis an Essential Fatty Acids Deficiency State?

Sepsis is associated with significant morbidity and mortality in critical care units, for which there is no effective therapy at present. The failure of corticosteroids and cytokine-targeted therapies suggests that an out-of-the-box approach is needed to understand their pathobiology and develop effective therapy. Essential fatty acids (EFAs) and their metabolites have both pro- and anti-inflammatory actions, regulate the production and actions of cytokines, and modulate immune response. Patients with sepsis have significantly lower concentrations of gamma-linolenic acid (GLA), dihomo-GLA (DGLA), arachidonic acid (AA) of the n-6 series, and alpha-linolenic acid (ALA) and eicosapentaenoic acid (EPA) of the n-3 series that are derived from EFAs in their plasma phospholipid fraction. Corticosteroids inhibit the metabolism of EFAs to their long-chain metabolites in addition to suppressing the formation of eicosanoids from DGLA, AA, EPA, and DHA. Interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) inhibit the activities of desaturases and thus decrease the formation of GLA and AA from LA and EPA and DHA from ALA. Thus, corticosteroids and cytokines interfere with EFA metabolism, which may explain their ineffectiveness in sepsis. It is suggested that sepsis is an EFAs deficiency state that leads to dysregulated inflammation and immune response and failure of resolution of inflammation and wound healing. It is proposed that restoring EFAs and their metabolism to normal can prevent and manage sepsis and other similar inflammatory disorders/diseases.

Das UN. Is Sepsis an Essential Fatty Acids Deficiency State? Indian J Crit Care Med 2025;29(10):802-806.