Fish Oil Supplements Lower Serum Lipids and Glucose in Correlation with a Reduction in Plasma Fibroblast Growth Factor 21 and Prostaglandin E2 in Nonalcoholic Fatty Liver Disease Associated with Hyperlipidemia: A Randomized Clinical Trial

PLoS ONE

Jul 2015

DOI: 10.1371/journal.pone.0133496

Citations:93

Influential Citations:8

Interventional (Human) Studies

Enhanced Details

Methods

Double-blind, randomized, placebo-controlled trial in adults with NAFLD associated with hyperlipidemia. 80 participants randomized to fish oil or corn oil for 3 months; 70 completed (36 fish oil, 34 corn oil). Ultrasound-diagnosed NAFLD; BMI 20–30; no excessive alcohol consumption.

Intervention

Fish oil capsules: 4 g/day (two 1000 mg capsules, each containing 182 mg EPA and 129 mg DHA) for 3 months; taken as two capsules twice daily. Corn oil capsules: 4 g/day (two capsules twice daily) for 3 months; no EPA or DHA.

Results

Fish oil (4 g/day for 3 months) significantly improved lipid and glucose metabolism, liver enzymes and NAFLD biomarkers compared with corn oil. After adjustment, fasting TC decreased by 0.49 ± 0.43 mmol/L, TG by 0.58 ± 0.89 mmol/L, ApoB by 0.28 ± 0.33 g/L and glucose by 0.76 ± 0.56 mmol/L (P<0.05). ALT and GGT decreased (median changes 9.0 and 7.0 IU/L, respectively; P<0.05). Adiponectin rose by 1.29 ± 0.62 μg/mL; TNF-α, LT-B4, FGF21, CK18-M30 and PGE2 declined (P<0.001). Corn oil increased creatinine by 7.7 ± 8.9 μmol/L (P=0.008). Reductions in TC, TG, ApoB and glucose correlated with reductions in FGF21 and PGE2, suggesting metabolic improvements are linked to NAFLD biomarker decreases. Authors conclude fish oil supplementation can benefit metabolic abnormalities associated with NAFLD and hyperlipidemia and may aid NAFLD management.

Limitations

Ultrasound-based NAFLD diagnosis without biopsy or MRI; no measurement of liver fat content; hepatitis B/C infection not serologically tested (only history); short duration; small sample with dropout; single-center; per-protocol analysis may bias results.

Abstract

Fish oil has been used effectively in the treatment of cardiovascular disease via triglyceride reduction and inflammation modulation. This study aimed to assess the effects of fish oil on patients with nonalcoholic fatty liver disease (NAFLD) associated with hyperlipidemia. Eighty participants with NAFLD associated with hyperlipidemia were randomly assigned to consume fish oil (n=40, 4 g/d) or corn oil capsules (n=40, 4 g/d) for 3 months in a double-blind, randomized clinical trial. Blood levels of lipids, glucose and insulin, liver enzymes, kidney parameters and cytokines at baseline and the end of the study were measured. Seventy people finished the trial. Plasma concentrations of eicosapentaenoic acid and docosahexaenoic acid significantly increased in the fish oil group after intervention. After adjustment for age, gender and BMI, fish oil significantly decreased fasting serum concentrations of total cholesterol, triglyceride, apolipoprotein B and glucose (by (mean±SD) 0.49±0.43 mmol/L, 0.58±0.89 mmol/L, 0.28±0.33 g/L and 0.76±0.56 mmol/L, respectively, P<0.05), as well as alanine aminotransferase and γ-glutamyl transpeptidase levels (by (median (interquartile)) 9.0(0.5, 21.5) and 7.0(2.2, 20.0) IU/L, respectively, P<0.05), significantly increased serum adiponectin levels (by 1.29±0.62 μg/mL, P<0.001), and reduced serum levels of tumor necrosis factor α, leukotrienes B4, fibroblast growth factor 21 (FGF21), cytokeratin 18 fragment M30 and prostaglandin E2 (by 1.70±1.18 pg/mL, 0.59±0.28 ng/mL, 121±31 pg/mL, 83±60 IU/L and 10.9±2.3 pg/mL, respectively, P<0.001). Corn oil had no effect except for increasing serum creatinine concentrations by 7.7±8.9 μmol/L (P=0.008). The effects of fish oil on lipids, glucose and γ-glutamyl transpeptidase were positively correlated with the reductions of serum FGF21 and prostaglandin E2 concentrations after adjustment for age, gender and BMI (r = 0.275 to 0.360 and 0.261 to 0.375, respectively, P<0.05). In conclusion, our findings suggest that fish oil can benefit metabolic abnormalities associated with NAFLD treatment. Trial Registration ChiCTR-TRC-12002380 show less