Omega-3 supplementation and non-alcoholic fatty liver disease: A systematic review and meta-analysis

Abstract

Non-alcoholic fatty liver disease (NAFLD) is a frequent accompaniment of obesity and insulin resistance. With the prevalence approaching 85% in obese populations, new therapeutic approaches to manage NAFLD are warranted. A systematic search of the literature was conducted for studies pertaining to the effect of omega-3 polyunsaturated fatty acid (PUFA) supplementation on NAFLD in humans. Primary outcome measures were liver fat and liver function tests: alanine aminotransferase (ALT) and aspartate aminotransferase [1]. Data were pooled and meta-analyses conducted using a random effects model. Nine eligible studies, involving 355 individuals given either omega-3 PUFA or control treatment were included. Beneficial changes in liver fat favoured PUFA treatment (effect size=-0.97, 95% CI: -0.58 to -1.35, p<0.001). A benefit of PUFA vs. control was also observed for AST (effect size=-0.97, 95% CI: -0.13 to -1.82, p=0.02). There was a trend towards favouring PUFA treatment on ALT but this was not significant (effect size=-0.56, 95% CI: -1.16 to 0.03, p=0.06). Sub-analyses of only randomised control trials (RCTs) showed a significant benefit for PUFA vs. control on liver fat (effect size=-0.96, 95% CI: -0.43 to -1.48, p<0.001), but not for ALT (p=0.74) or AST (p=0.28). There was significant heterogeneity between studies. The pooled data suggest that omega-3 PUFA supplementation may decrease liver fat, however, the optimal dose is currently not known. Well designed RCTs which quantify the magnitude of effect of omega-3 PUFA supplementation on liver fat are needed.

EASL–EASD–EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease

“…Preliminary data from small or uncontrolled studies suggested that n-3 polyunsaturated fatty acids (PUFA) might reduce liver fat [136], but two trials testing PUFA on histological outcomes were negative [102,104]. Available data on pentoxifylline and orlistat are limited or inconclusive [86,91,97].…”

Supplementation With 2:1 Ratio of N-6:n-3 Polyunsaturated Fatty Acid Improves Liver Steatosis and Serum Cytokine Levels in Young Obese Balinese Women: A Randomized Clinical Trial

“…Lionetti et al described that EPA effectively minimized saturated fat-induced insulin resistance in mice and decreased leptin alleviated LS and improved secondary outcomes, such as BMI, TG and alanine transaminase levels, and homeostasis model assessment of insulin resistance values in both groups when compared to the control group [25]. A systematic review and meta-analysis of five randomized controlled trials (nine studies) in which n-3 LC-PUFA supplementation was provided for 8 weeks to 12 months to 355 adults with NAFLD demonstrated that n-3 LC-PUFA was beneficial in reducing liver fat (p<0.001) and aspartate aminotransferase (p=0.02) but not alanine aminotransferase activity [26]. Another study reported that a reduction in the n-6:n-3 PUFA ratio (3:1) in the diet resulted in decreased plasma TG levels in mRNA expression in vivo and in vitro.…”

Pharmacologic Management of Non-Alcoholic Fatty Liver Disease

“…Other studies have provided collaborative observations [53]. A meta-analysis of 9 trials and 355 patients found that there were beneficial changes in hepatic steatosis but less convincing evidence of improvement in aminotransaminases with PUFA therapy [55]. Two recent randomised controlled trials which provided histological outcome measures did not demonstrate improved liver histology, but in fact suggested worsening of insulin resistance with PUFA therapy in one trial [56,57].…”