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Omega-3 Fatty Acids Improve Nonalcoholic Fatty Liver Disease

10/24/2018 11:26:45 AM
Non-alcoholic fatty liver disease (NAFLD), defined as hepatic steatosis resulting from no secondary cause, ranges from simple steatosis to nonalcoholic steatohepatitis (NASH) with the potential to progress to cirrhosis or hepatocellular carcinoma. Medical management of NAFLD relies on diet, exercise, and weight loss, with no approved pharmacologic interventions. Omega-3 polyunsaturated fatty acids have been extensively investigated to supplement dietary interventions for NAFLD.
Omega-3 fatty acids modulate hepatic gene expression, resulting in increased hepatic fatty acid beta-oxidation and reduced hepatic lipogenesis. Omega 3s are also metabolized to eicosanoids that modulate inflammation. Observational studies show that patients with NAFLD have reduced hepatic levels of the omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), potentially because of reduced activity of an enzyme required for their synthesis (delta-5 desaturase). Because of this, it is mechanistically feasible that patients with NAFLD have a higher need and might benefit from omega-3 fatty acid supplementation.  
A 2018 meta-analysis was published in Nutrition Reviews to update the pooled evidence from clinical trials of omega-3 supplementation in patients with NAFLD. The analysis included 24 randomized or nonrandomized controlled trials of patients with NAFLD—17 studies with adults and 7 with children. Sources of EPA + DHA for the interventions were described as algae oil, fish oil, seal oil, EPA + DHA ethyl ester, enriched olive oil, or an omega-3 oil that also contained alpha-linolenic acid, with dosages ranging from less than 1 gram per day to more than 3 grams per day. Duration of interventions ranged from 2 to 24 months.   
Results of all available pooled data showed that omega-3 fatty acids significantly reduced serum liver enzymes ALT and GGT but not AST. Liver fat content and steatosis score (assessed by MRI or ultrasound) were both significantly improved with omega-3 supplementation. The pooled reduction by 5.2% in liver fat content and the pooled reduction by 0.7 in steatosis score were considered clinically meaningful. The improvements in steatosis score remained significant not only in the pooled analysis but also in analyses stratified by age, study length, and study quality.
Pooled data also showed that omega-3 supplementation was associated with significant improvements in total cholesterol, LDL-cholesterol, HDL-cholesterol, and triglycerides. Supplementation was associated with reduced body mass index (BMI) but not changes in body weight, waist circumference, or blood pressure. No effects were seen on fasting glucose, fasting insulin, or adiponectin. HOMA-IR improved significantly only in pediatric studies.
Based on 4 studies of patients with NASH, the meta-analysis found no influence of omega-3 supplementation on liver histology parameters, including fibrosis score, hepatocellular ballooning score, and lobular inflammation score.  
These results suggest that omega-3 fatty acid supplementation improves liver fat content, steatosis score, and cardiometabolic risk factors in adult and pediatric patients with NAFLD. The authors conclude that the effective daily intake appears to be 250 mg of DHA in children and approximately 3.0 grams of EPA + DHA in adults.
Musa-Veloso K, Venditti C, Lee HY et al. Systematic review and meta-analysis of controlled intervention studies on the effectiveness of long-chain omega-3 fatty acids in patients with nonalcoholic fatty liver disease. Nutr Rev. 2018; 76: 581-602.

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