Reply to: “The optimal dose of omega-3 supplementation for non-alcoholic fatty liver disease”
Authors: Helen M. Parker, Nathan A. Johnson, Jacob George
Journal: Journal of Hepatology (2012)

The optimal dose of omega-3 supplementation for non-alcoholic fatty liver diseaseJournal of HepatologyVol. 57Issue 2PreviewNon-alcoholic fatty liver disease (NAFLD) is a burgeoning health problem that affects one-third of adults and an increasing number of children in developed countries [1]. It was previously reported that various therapeutic regimens can be adopted for NAFLD [2], including weight loss agents, bariatric surgery, insulin-sensitizing agents, lipid-lowering agents, antioxidants, and other novel compounds. However, there is no consensus on its treatment. Both lifestyle therapy and pharmacotherapy have limitations due to poor compliance and side effects. Full-Text PDF Open AccessOmega-3 supplementation and non-alcoholic fatty liver disease: A systematic review and meta-analysisJournal of HepatologyVol. 56Issue 4PreviewNon-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]. Full-Text PDF Open Access We read with interest the letter by Drs. Li and Chen regarding our systematic review and meta-analysis of omega-3 supplementation in non-alcoholic fatty liver disease (NAFLD) [[1]Parker H.M. Johnson N.A. Burdon K.A. Cohn J.S. OConnor H.T. George J. Omega-3 supplementation and non-alcoholic fatty liver disease: a systematic review and meta-analysis.J Hepatol. 2012; 56: 944-951Abstract Full Text Full Text PDF PubMed Scopus (421) Google Scholar]. We showed that, when compared with a control therapy, dietary omega-3 supplementation led to beneficial changes in liver fat in adults. On the basis of the pooled results of studies, which employed omega-3 supplementation of 0.83–13.7 g per day, we observed a statistically significant benefit on liver fat, which persisted even when only randomized controlled trials were examined. Due to the strong association between NAFLD and cardiovascular disease (CVD), the importance of CVD to mortality in patients with NAFLD, and the benefit of omega-3 supplementation in CVD risk reduction, Li and Chen suggest that the optimal dose of omega-3 should be higher than 0.83 g per day. We point out that pooling of data by meta-analysis is a useful tool for objectively evaluating the consensus of a therapy such as omega-3 supplementation (vs. a suitable control). However, the heterogeneity and relative paucity of data entail that these results should not be used to inform clinical recommendations on issues such as optimal dosage in NAFLD. Using the data from trials in cardiovascular disease of omega-3 supplementation to recommend a particular omega-3 dose for NAFLD would be an inference, not supported by the NAFLD data we have presented. As stated in our manuscript, more data from randomized controlled trials are required for this. While our meta-analysis substantiates the efficacy of omega-3 supplementation for modifying liver fat per se, the choice of dose in an individual with NAFLD will depend on an assessment by the clinician of whether in fact he/she has cardiac or other co-morbidities. We found no reports of adverse events for omega-3 supplementation in the relatively limited pool (nine) of studies, which met the criteria for inclusion in our review. However, we wholeheartedly agree that these should not be used to reflect the consensus of all intervention trials involving omega-3 supplementation. As Drs. Li and Chen have correctly highlighted, side-effects of omega-3 supplementation have been reported in previous studies, which did not have liver fat and serum aminotransferases as inclusion criteria [[2]Kris-Etherton P.M. Harris W.S. Appel L.J. Nutrition Committee of the American Heart AssociationFish consumption, fish oil, omega-3 fatty acids, and cardiovascular disease [Erratum appears in Circulation 2003;107:512].Circulation. 2002; 106: 2747-2757Crossref PubMed Scopus (2971) Google Scholar]. Our study provides an important first step in establishing an hepatic benefit of omega-3 therapy in adults, but caution should be taken when interpreting the clinical implications of the meta-analysis. Our findings should serve as a stimulus for future research examining issues such as dose-responsiveness, safety and patient tolerance with omega-3 therapy. The authors declared that they do not have anything to disclose regarding funding or conflict of interest with respect to this manuscript.