Review article: omega‐3 fatty acids – a promising novel therapy for non‐alcoholic fatty liver disease

Abstract

Aliment Pharmacol Ther 31, 679–692 Summary Background Non‐alcoholic fatty liver disease affects 10–35% of the adult population worldwide; there is no consensus on its treatment. Omega‐3 fatty acids have proven benefits for hyperlipidaemia and cardiovascular disease, and have recently been suggested as a treatment for non‐alcoholic fatty liver disease. Aims To review the evidence base for omega‐3 fatty acids in non‐alcoholic fatty liver disease and critically appraise the literature relating to human trials. Methods A Medline and PubMed search was performed to identify relevant literature using search terms ‘omega‐3’, ‘N‐3 PUFA’, ‘eicosapentaenoic acid’, ‘docosahexaenoic acid’, ‘non‐alcoholic fatty liver disease’ and ‘NAFLD’. Results Omega‐3 fatty acids are important regulators of hepatic gene transcription. Animal studies demonstrate that they reduce hepatic steatosis, improve insulin sensitivity and reduce markers of inflammation. Clinical trials in human subjects generally confirm these findings, but have significant design inadequacies. Conclusions Omega‐3 fatty acids are a promising treatment for non‐alcoholic fatty liver disease which require to be tested in randomized placebo‐controlled trials.

Mechanisms Linking Nonalcoholic Fatty Liver Disease with Coronary Artery Disease

“…Vitamin E (400 IU/day) and omega-3 may be recommended [138,139]; however, vitamin E is not approved yet and high dosage may increase all cause mortality [140]. Ursodeoxycholic acid has no benefit for NASH patients as compared to placebo [141].…”

Non-alcoholic fatty liver disease and cardiovascular risk: metabolic aspects and novel treatments

“…For example, n-3 PUFAs (i) reduce hepatic fatty acid content through decreasing hepatic de novo lipogenesis by activation of peroxisome proliferatoractivated receptor alpha (PPAR-a); (ii) downregulate SREBP-1c, which is the key transcriptional factor of de novo lipogenesis; (iii) improve IR [66]; (iv) diminish inflammation by reducing activation of NF-jB; and (v) lower plasma TG and ALT [67]. A therapeutic dose of 2-3 g of n-3 PUFAs decreases plasma levels of TG by 30%, and although there is a theoretical benefit for the use of n-3 PUFAs in NAFLD, and there is some evidence of benefit in treating atherosclerosis [68], more evidence is required to test the effects of n-3 PUFA treatment in NAFLD.…”

Plasma Free Myristic Acid Proportion Is a Predictor of Nonalcoholic Steatohepatitis

“…Hepatocyte apoptosis and injury were independent of dietary PUFA content in animal models [10]. Animal studies do demonstrate that omega-3 PUFAs reduce hepatic steatosis, improve insulin sensitivity, and reduce markers of inflammation [11].…”