Intravenous fish oil blunts the physiological response to endotoxin in healthy subjects

Objective: To assess the effects of intravenous fish oil fat emulsion on the metabolic alterations induced by lipopolysaccharide (LPS) challenge in healthy volunteers. Design: Two groups of eight healthy subjects were randomized to receive either two pharmacological doses of intravenous FO fat emulsion or no treatment. The FO group received twice 0.5 g/kg 10% emulsion (Omegaven) 48 and 24 h before investigation. LPS (2 ng/kg) was injected as a bolus on the investigation day. Systemic parameters, indirect calorimetry, heart rate variability, and platelet membrane phospholipid composition were measured. Results: Basal EPA and DHA content in platelet phospholipids was low (0.28% and 2.54%, respectively) and increased significantly after FO to 1.68% and 3.32%. LPS induced reproducible effects in all subjects. Fever was higher in the FO group than in controls; the difference was significant from t(120) until t(360). FO blunted the neuroendocrine response: the rise in plasma norepinephrine was sevenfold lower at t(120) while the ACTH peak was fourfold lower. Tumor necrosis factor alpha was significantly lower between t(360) and t(180) in the FO group. Conclusions: Two doses of intravenous FO fat emulsion modified the phospholipid composition of platelets in healthy subjects. FO blunted fever and increased the neuroendocrine and the inflammatory responses to LPS.