Results from clinical trials assessing the therapeutic effects of omega-3 polyunsaturated fatty acids (PUFAs) against NAFLD have been inconsistent so far, leading the researchers to perform a meta-analysis of RCTs testing PUFAs' impact on NAFLD.
They searched databases such as PubMed, Cochrane Library, Springer Link and the Chinese Scientific and Technological Journal for RCTs on oral omega-3 PUFA supplementation in NAFLD patients and selected 19 studies involving a total of 1,424 patients.
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Fat-fighting fatty acids
They then reported significant benefits of omega-3 for liver fat, alanine aminotransferase (ALT, an enzyme found mainly in the liver and kidneys), aspartate aminotransferase (AST, an enzyme found mostly in the liver and heart), gamma-glutamyl transferase (GGT, a liver enzyme traditionally used to determine liver health and alcohol consumption), triglycerides, insulin resistance, and glucose.
Seven of the studies reported that omega-3 supplementation resulted in decreased liver fat, with the meta-analysis showing that the treatment groups were more likely to experience this improvement than the placebo groups.
Eight of the studies showed that that omega-3 intake helped to improve insulin resistance and glucose, both novel findings in this systematic review.
These effects may have been the result of omega-3 PUFAs' ability to lower triglyceride levels, blood pressure, and glucose.
Despite these positive effects, heterogeneity was an issue among several RCTs, possibly because of differences in treatment dose and duration, as well as the subjects' ethnicity and age, though a meta-regression analysis found no significant links between these factors.
Other possible sources of heterogeneity included clinician skill, different measurement techniques, and inconsistent definition of disease criteria.
Additionally, though omega-3 PUFAs are can be obtained easily via diet, dietary intakes of omega-3 were not uniform across the studies, a factor that may have — along with the aforementioned factors — affected the interpretation of the results.
Strong evidence still needs further support
The large sample size allowed for a more accurate assessment of the link between omega-3 PUFAs and NAFLD, and most of the reviewed studies were of high methodologic quality and had a low risk of bias in key domains.
The studies were also prospective, eliminating the influence of recall bias, and most of them saw high compliance rates.
The researchers concluded: "The present analysis provides an updated systematic review and meta-analysis involving only RCTs on omega-3 PUFAs and NAFLD. The results suggest that omega-3 PUFA supplementation can improve liver fat, ALT, AST, GGT, triglycerides, insulin resistance, and glucose in patients with NAFLD.
"So omega-3 PUFA supplementation may improve metabolic and cardiovascular risk factors, and surrogate makers for liver disease progression. However, further studies are warranted to confirm whether omega-3 PUFA supplementation improves hard outcomes, including mortality, progression to cirrhosis, or histologic inflammations.
"In addition, it is too early to validate these findings on liver fat, ALT, AST, GGT, and triglycerides, given the heterogeneity among the studies. More large-scale, well-designed RCTs are needed to confirm the effect of omega-3 PUFA supplementation on these parameters.
"Future studies also need to confirm the dose-dependent effects, and assess the long-term durability and safety of omega-3 PUFA supplementation."
"Omega-3 polyunsaturated fatty acid supplementation and non-alcoholic fatty liver disease: A meta-analysis of randomized controlled trials"
Authors: Jian-Hui Yan, et al.