Fatty acid and non-alcoholic fatty liver disease: Meta-analyses of case-control and randomized controlled trials.
Blood and/or liver fatty acid contents of healthy subjects and non-alcoholic fatty liver disease (NAFLD) patients have shown inconsistent associations. In addition, the results of randomized controlled trials (RCTs) in relation to the effects of n-3 polyunsaturated fatty acid (PUFA) supplementation on alanine aminotransferase (ALT), aspartate aminotransferase (AST), liver fat, triglyceride (TAG) and fasting glucose levels are inconsistent. The present study aimed to investigate the differences of fatty acid content in the blood and/or liver tissue between healthy subjects and NAFLD patients, and to quantify the benefits of n-3 PUFA therapy in NAFLD patients.



A systematic literature search was performed up to November 2016 using PubMed and Scopus databases. The differences of fatty acid content between cases and controls were calculated as weighted mean differences (WMD) by using a random-effects model. The intervention effects of RCTs were calculated as WMD for net changes in ALT, AST, liver fat, TAG and fasting glucose levels, respectively. Meta-regression with restricted maximum likelihood estimation was used to evaluate a potential linear relationship between confounding factors and effect sizes. Generalized least square was performed for dose-response analysis.



Ten eligible case-control studies and 11 RCTs were included. The pooled estimates of case-control studies showed that blood and/or liver docosahexaenoic acid (DHA) content was significantly higher in the controls compared with cases. The pooled estimates of RCTs showed that n-3 PUFA supplementation significantly reduced the ALT (-7.53 U/L; 95% CI: -9.98, -5.08 U/L), ASL (-7.10 U/L, 95% CI: -11.67, -2.52 U/L) and TAG (-36.16 mg/dL, 95% CI: -49.15, -23.18 mg/dL) concentrations, and marginally reduced the liver fat content (-5.11%, 95% CI: -10.24, 0.02%, P = 0.051), but not fasting glucose. Dose-response analysis of RCTs showed that 1 g per day increment of eicosapentaenoic acid (EPA)+DHA was associated with a 3.14 U/L, 2.43 U/L, 2.74% and 9.97 mg/dL reduction in ALT (95% CI: -5.25, -1.02 U/L), AST (95% CI: -3.90, -0.90 U/L), liver fat (95% CI: -4.32, -1.16%) and TAG (95% CI: -14.47, -5.48 mg/dL) levels, respectively.



The present meta-analysis provides substantial evidence that n-3 PUFA supplementation, especially DHA, has a favorable effect in treatment of NAFLD.
Department of Food Science and Nutrition, Zhejiang University, Hangzhou, China.
Xiao-Fei
XF
Guo
Institute of Nutrition and Health, Qingdao University, Qingdao, China.
Bo
B
Yang
Department of Food Science and Nutrition, Zhejiang University, Hangzhou, China.
Jun
J
Tang
Department of Food Science and Nutrition, Zhejiang University, Hangzhou, China; Institute of Nutrition and Health, Qingdao University, Qingdao, China. Electronic address: duoli@zju.edu.cn.
Duo
D
Li
D000328:Adult; D000368:Aged; D000410:Alanine Transaminase / Q000097:blood; D016022:Case-Control Studies; D004281:Docosahexaenoic Acids; D004305:Dose-Response Relationship, Drug; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008099:Liver / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease / Q000188:drug therapy / Q000378:metabolism; D016032:Randomized Controlled Trials as Topic
D015525:Fatty Acids, Omega-3; D004281:Docosahexaenoic Acids; D000410:Alanine Transaminase
Dose-response analysis; Meta-analysis; Non-alcoholic fatty liver disease; Randomized controlled trial; n-3 polyunsaturated fatty acids