The optimal dose of omega-3 supplementation for non-alcoholic fatty liver disease
Authors: Yan Li, Dongfeng Chen
Journal: Journal of Hepatology (2012)

Omega-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 AccessReply to: "The optimal dose of omega-3 supplementation for non-alcoholic fatty liver disease"Journal of HepatologyVol. 57Issue 2PreviewWe 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]. 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. Full-Text PDF Open Access Non-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]Cohen J.C. Horton J.D. Hobbs H.H. Human fatty liver disease: old questions and new insights.Science. 2011; 332: 1519-1523Crossref PubMed Scopus (1667) Google Scholar]. It was previously reported that various therapeutic regimens can be adopted for NAFLD [[2]Lam B. Younossi Z.M. Treatment options for non-alcoholic fatty liver disease.Therap Adv Gastroenterol. 2010; 3: 121-137Crossref PubMed Scopus (95) Google Scholar], 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. Therefore, new therapeutic approaches to managing NAFLD are urgently needed. We read with interest the study by Parker et al. [[3]Parker H.M. Johnson N.A. Burdon C.A. Cohn J.S. Connor 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]. This is the first meta-analysis to investigate the effect of omega-3 polyunsaturated fatty acid (PUFA) on liver fat in humans. The authors found that omega-3 PUFA could decrease liver fat and that benefits were seen with a consumption of >0.83 g/day. The results are instructive for the therapeutic regimen of NAFLD; however, we have some concerns over the optimal dose mentioned in the article. Given the complications of NAFLD, especially cardiovascular disease (CVD), the optimal dose of omega-3 PUFA should be much higher than 0.83 g/day. Targher et al. revealed a strong association between NAFLD and CVD risk by reviewing accumulating clinical evidence [[4]Targher G. Day C.P. Bonora E. Risk of cardiovascular disease in patients with nonalcoholic fatty liver disease.N Engl J Med. 2010; 363: 1341-1350Crossref PubMed Scopus (1513) Google Scholar]. Previous evidence suggests that CVD dictates the outcome in patients with NAFLD more frequently and to a greater extent than does the progression of liver disease, and CVD is the most important cause of death in NAFLD patients [[5]Targher G. Marra F. Marchesini G. Increased risk of cardiovascular disease in non-alcoholic fatty liver disease: causal effect or epiphenomenon?.Diabetologia. 2008; 51: 1947-1953Crossref PubMed Scopus (326) Google Scholar]. On the other hand, many investigators have demonstrated that omega-3 PUFA could prevent CVD [[6]Kris-Etherton P.M. Harris W.S. Appel L.J. Fish consumption, fish oil, omega-3 fatty acids, and cardiovascular disease.Circulation. 2002; 106: 2747-2757Crossref PubMed Scopus (2971) Google Scholar]. In a large-scale intervention trial of secondary prevention after myocardial infarction, GISSI-Prevenzione investigators identified a substantial reduction in all-cause and cardiovascular mortality with 1 g per day of n-3 PUFA supplementation [[7]GISSI-Prevenzione Investigators (Gruppo Italiano perlo Studio della Sopravvivenza nell'Infarto miocardico) Dietary supplementation with n-3 polyunsaturated fatty acids and vitamin E after myocardial infarction: results of the GISSI-Prevenzione trial.Lancet. 1999; 354: 447-455Abstract Full Text Full Text PDF PubMed Scopus (3796) Google Scholar]. In addition, McKenney et al. recommend n-3 PUFA supplementation at a dose of 2–4 g per day to patients with high triglyceride concentrations [[8]McKenney J.M. Sica D. Role of prescription omega-3 fatty acids in the treatment of hypertriglyceridemia.Pharmacotherapy. 2007; 27: 715-728Crossref PubMed Scopus (112) Google Scholar]. At present, Saravanan et al. found that omega-3 PUFA could act as beneficial pleiotropic agents to prevent CVD, by conducting a review of numerous clinical trials [[9]Saravanan P. Davidson N.C. Schmidt E.B. Calder P.C. Cardiovascular effects of marine omega-3 fatty acids.Lancet. 2010; 376: 540-550Abstract Full Text Full Text PDF PubMed Scopus (435) Google Scholar]. As fish is rich in omega-3 PUFA, the American Heart Association recommends at least two fish meals per week to healthy people, and a supplemental therapy with 1 g of omega-3 PUFA per day to those with myocardial infarction [[6]Kris-Etherton P.M. Harris W.S. Appel L.J. Fish consumption, fish oil, omega-3 fatty acids, and cardiovascular disease.Circulation. 2002; 106: 2747-2757Crossref PubMed Scopus (2971) Google Scholar]. Omega-3 PUFA may treat NAFLD and CVD simultaneously, killing two birds with one stone [[10]Masterton G.S. Plevris J.N. Hayes P.C. Review article: omega-3 fatty acids-a promising novel therapy for non-alcoholic fatty liver disease.Aliment Pharmacol Ther. 2010; 31: 679-692Crossref PubMed Scopus (0) Google Scholar]. In this review, the average dose of omega-3 PUFA was 4 g/day (range: 0.8–13.7 g/day), and the authors found no reports of adverse effects of omega-3 PUFA supplementation in the studies reviewed. We should be cautious about this conclusion, because side effects of omega-3 PUFA supplementation do exist (Table 1).Table 1Risk of side effects from ingestion of omega-3 PUFA [6]Kris-Etherton P.M. Harris W.S. Appel L.J. Fish consumption, fish oil, omega-3 fatty acids, and cardiovascular disease.Circulation. 2002; 106: 2747-2757Crossref PubMed Scopus (2971) Google Scholar.LDL-C, low density lipoprotein–cholesterol.aUsually only in patients with impaired glucose tolerance and diabetes.bUsually only in patients with hypertriglyceridemia. Open table in a new tab LDL-C, low density lipoprotein–cholesterol. aUsually only in patients with impaired glucose tolerance and diabetes. bUsually only in patients with hypertriglyceridemia. We agree to adopt therapeutic regimen for NAFLD. However, we sincerely hope that the researchers take the CVD risk and the side effects of omega-3 PUFA in NAFLD into account when they determine the optimal dose of omega-3 PUFA. Because omega-3 PUFA could treat NAFLD and CVD, it is promising to consider that the optimal dose of omega-3 PUFA could be applied for NAFLD associated risk of CVD. Of course, the hypothesis needs to be validated by well-designed randomized controlled trials. The authors declared that they do not have anything to disclose regarding conflict of interest with respect to this letter.