Marine omega-3 fatty acid supplementation in non-alcoholic fatty liver disease: Plasma proteomics in the randomized WELCOME trial

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. ; © 2018 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND. Received 19 April 2018, Accepted 31 July 2018, Available online 17 August 2018. WELCOME = Wessex Evaluation of fatty Liver and Cardiovascular markers in NAFLD (non-alcoholic fatty liver disease) with OMacor thErapy. We thank Roger Allsopp and Derek Coates for establishing the mass spectrometry facility at the University of Southampton. SDG is partly supported by the Visiting Professor Program of King Saud University. ES, PCC and CDB are ...