Combined effect of n-3 fatty acids and phytosterol esters on alleviating hepatic steatosis in non-alcoholic fatty liver disease subjects: a double-blind placebo-controlled clinical trial

Abstract

The aim of this study was to investigate the combined effect of n-3 fatty acids (EPA and DHA, at an EPA:DHA ratio of 150:500) and phytosterol esters (PS) on non-alcoholic fatty liver disease (NAFLD) patients. We conducted a randomised, double-blind, placebo-controlled trial. Ninety-six NAFLD subjects were randomly assigned to the following groups: the PS group (receiving 3·3 g/d PS); the FO group (receiving 450 mg EPA + 1500 mg DHA/d); the PS + FO combination group (receiving 3·3 g/d PS and 450 mg EPA + 1500 mg DHA/d) and the PO group (a placebo group). The baseline clinical characteristics of the four groups were similar. The primary outcome was liver:spleen attenuation ratio (L:S ratio). The percentage increase in liver–spleen attenuation (≤1) in the PS + FO group was 36 % (P = 0·083), higher than those in the other three groups (PS group, 11 %, P = 0·519; FO group, 18 %, P = 0·071; PO group, 15 %, P = 0·436). Compared with baseline, transforming growth factor-β (TGF-β) was significantly decreased in the three study groups at the end of the trial (PS, P = 0·000; FO, P = 0·002; PS + FO, P = 0·001) and TNF-α was significantly decreased in the FO group (P = 0·036), PS + FO group (P = 0·005) and PO group (P = 0·032) at the end of the intervention. Notably, TGF-β was reduced significantly more in the PS + FO group than in the PO group (P = 0·032). The TAG and total cholesterol levels of the PS + FO group were reduced by 11·57 and 9·55 %, respectively. In conclusion, co-supplementation of PS and EPA + DHA could increase the effectiveness of treatment for hepatic steatosis.

Effects of Omega-3 Polyunsaturated Fatty Acid Supplementation on Non-Alcoholic Fatty Liver: A Systematic Review and Meta-Analysis

“…In the wake of inspecting the full text, 22 RCTs with 1366 participants were included. The characteristics of the included RCTs studies [ 3 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 ] are listed in Table 2 .…”

“…However, the treatment dose and duration could not be described in the study. Compared to the previous research, our systematic review included seven more RCTs and provides the most updated research evidence [ 43 , 44 , 46 , 48 , 50 , 55 , 57 ].…”

Functional Foods for the Management of Non-Alcoholic Fatty Liver Disease

“…Intragastric administration of phytosterol esters for 12 weeks to HFD fed rats reduced liver size, lipid content and improved intestinal flora [78]. In combination with EPA and DHA, phytosterol esters significantly reduced the levels of TGs, cholesterol, LDL cholesterol and decreased the pro-inflammatory cytokines in NAFLD subjects [79]. β-sitosterol supplementation for 12 weeks mitigated high-fructose diet-induced macrovesicular steatosis and progression of steatohepatitis [80].…”

The Role of Phytosterols in Nonalcoholic Fatty Liver Disease

“…A more recent study, based on the favorable results of phytosterol supplementation on lipid metabolism and the evolution of NAFLD, evaluated in a randomized, double-blind, placebo-controlled trial the effects of the administrations of PS (3.3 g/d, equal to 2.5 g phytosterol in the free form/d) plus n-3 PUFA (450 mg EPA + 1500 mg DHA) [ 50 ]. Anthropometric evaluations (body mass index, Waist circumference, Hip circumference), blood samples (Serum TC, TAG, HDL-cholesterol, LDL-cholesterol, glucose, liver and kidney function markers, TNF-α, TGF-β), and CT-scanning (for quantify the liver:spleen attenuation ratio) were performed at the beginning and end of the study.…”

“…The findings were encouraging, showing the synergism of the mechanisms of action of PS + DHA + EPA in daily administration, more effective compared to separate or placebo administration, in reducing serum TAG, TC, and LDL-Cholesterol, decreasing the level of pro-inflammatory cytokines and improving liver damage. However, the authors emphasize the need for a large population trial with NAFLD subjects and simultaneous administration of phytosterol and n-3 Long-chain PUFA (especially EPA and DHA) [ 50 ].…”