Omega-3 Fatty acids therapy in children with nonalcoholic Fatty liver disease: a randomized controlled trial.

OBJECTIVE: To evaluate the efficacy and safety of omega-3 fatty acid supplementation in children with nonalcoholic fatty liver disease (NAFLD). STUDY DESIGN: Overweight/obese children with NAFLD (n = 76; median age, 13 years; IQR, 11.1-15.2 years) were eligible to participate in the study. The diagnosis of NAFLD was based on elevated alanine aminotransferase (ALT) to ≥ 30% of the upper limit of normal (ULN) and liver hyperechogenicity on ultrasound. Patients were randomized to receive omega-3 fatty acids (docosahexaenoic acid and eicosapentaenoic acid, 450-1300 mg/day) or placebo (omega-6 sunflower oil). The primary outcome was the number of patients who demonstrated decreased ALT activity by ≥ 0.3 times the ULN. Secondary outcomes included alterations in liver function tests, liver hyperechogenicity, insulin resistance, and other metabolic markers after 6 months of intervention. RESULTS: Out of 76 enrolled patients, 64 completed the trial and were analyzed. After 6 months, we found no significant differences between the omega-3 and placebo groups in the number of patients with decreased ALT by ≥ 0.3 times the ULN (24 vs 23) or in median (IQR) ALT activity (48.5 [31-62] U/L vs 39 [27-55] U/L), liver hyperechogenicity, insulin resistance, or serum lipid levels. However, patients in the omega-3 group had lower levels of aspartate aminotransferase (28 [25-36] U/L vs 39 [27-55] U/L; P = .04) and gamma-glutamyl transpeptidase (26 [17.5-36.5] U/L vs 35 [22-52] U/L; P = .04), and significantly higher levels of adiponectin. CONCLUSION: Omega-3 fatty acid supplementation did not increase the number of patients with decreased ALT levels and it did not affect liver steatosis on ultrasound, but it improved aspartate aminotransferase and gamma-glutamyl transpeptidase levels in children with NAFLD compared with placebo. TRIAL REGISTRATION: Registered with ClinicalTrials.gov: NCT01547910.

Omega-3 fatty acids for treatment of non-alcoholic fatty liver disease: design and rationale of randomized controlled trial.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a liver manifestation of metabolic syndrome since obesity and insulin resistance are the main pathogenic contributors for both conditions. NAFLD carries increased risk of atherosclerosis and cardiovascular diseases. There is an urgent need to find effective and safe therapy for children and adults with NAFLD. Data from research and clinical studies suggest that omega-3 fatty acids may be beneficial in metabolic syndrome-related conditions and can reduce the risk of cardiovascular disease. METHODS/DESIGN: We are conducting a randomized, multicenter, double-blind, placebo-controlled trial of treatment with omega-3 fatty acids in children with NAFLD. Patients are randomized to receive either omega-3 fatty acids containing docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) or placebo for 24 weeks. The dose of omega-3 (DHA+ EPA) ranges from 450 to 1300 mg daily. Low calorie diet and increased physical activity are advised and monitored using validated questionnaires. The primary outcome of the trial is the number of patients who decreased ALT activity by ≥ 0,3 of upper limit of normal. The main secondary outcomes are improvement in the laboratory liver tests, liver steatosis on ultrasound, markers of insulin resistance and difference in fat/lean body mass composition after 6 months of intervention. DISCUSSION: Potential efficacy of omega-3 fatty acids in the treatment of NAFLD will provide needed rationale for use of this safe diet supplement together with weight reduction therapy in the growing population of children with NAFLD. TRIAL REGISTRATION: NCT01547910.