Summary Background & aims Non-alcoholic fatty liver disease (NAFLD) is a liver condition characterised by liver fat accumulation and often considered to be the liver manifestation of metabolic syndrome. The aim of this study was to examine in patients with NAFLD the system-wide effects of treatment with docosahexaenoic acid + eicosapentaenoic acid (DHA + EPA) versus placebo on the plasma proteome. Methods Plasma from patients that participated in a 15–18 months randomised, double-blind placebo-controlled trial testing the effects of 4 g DHA + EPA daily was analysed using depletion-free quantitative proteomics. Results Bioinformatics interpretation of the proteomic analysis showed that DHA + EPA treatment affected pathways involving blood coagulation, immune/inflammatory response and cholesterol metabolism (p < 0.05). Two key proteins of cardiovascular risk, prothrombin and apolipoprotein B-100, were shown to decrease as a result of DHA + EPA supplementation [Prothrombin: Males DHA + EPA Mean iTRAQ log2ratio (SD) = −0.13 (0.20) p = 0.05, Females DHA + EPA Mean iTRAQ log2ratio (SD) = −0.48 (0.35) p = 0.03; Apo B-100: Males DHA + EPA Mean iTRAQ log2ratio (SD) = −0.24 (0.16) p = 0.01, Females DHA + EPA Mean iTRAQ log2ratio (SD) = −0.15 (0.05) p = 0.02]. Conclusions Plasma proteomics applied in a randomised, placebo-controlled trial showed that high dose DHA + EPA treatment in patients with NAFLD affects multiple pathways involved in chronic non-communicable diseases.
