Interaction of low dose of fish oil and glucocorticoids on insulin sensitivity and lipolysis in healthy humans: A randomized controlled study

Scope This study examined the interaction of fish oil (FO) with dexamethasone on glucose and lipid metabolisms in healthy subjects. Methods and results The study included two consecutive parts. Part A (randomized) in 16 subjects studied the effects of dexamethasone (2 days, 2 mg/day) versus placebo (lactose), part B (two parallel subgroups of eight) studied the interaction of FO (3 wk, 840 mg/day of EPA + DHA) with dexamethasone. Insulin sensitivity of lipolysis (d5‐glycerol infusion + microdialysis), endogenous glucose production, and muscle glucose uptake were assessed by a three‐step hot insulin clamp and substrate oxidation by indirect calorimetry. Dexamethasone induced liver and peripheral insulin resistance, an increase in fat oxidation, and a decrease in suppression of plasma nonesterified fatty acids (NEFAs). FO amplified the effects of dexamethasone by increasing liver and muscle insulin resistance, by reducing suppression of plasma NEFAs and fat oxidation and by increasing adipose tissue (AT) lipolysis. Conclusion FO, given at a moderate dose in healthy subjects prior to a very short‐term (2 days) low dose of a synthetic glucocorticoid, worsened its deleterious effects on insulin sensitivity. The enhancing effect of FO on fat oxidation and AT lipolysis might be a protective effect toward an increase in fat mass.