Impact of Long-Term Supplementation with Fish Oil in Individuals with Non-Alcoholic Fatty Liver Disease: A Double Blind Randomized Placebo Controlled Clinical Trial

Abstract

Non-alcoholic fatty liver disease (NAFLD) is a chronic disease affecting up to 25% of the population worldwide. n-3 long-chain polyunsaturated fatty acids (n-3 PUFA) have been associated with improved clinical parameters of NAFLD. Our purpose was to conduct a pilot study to evaluate the effects of n-3 PUFA supplementation in a randomized, double-blind, placebo-controlled clinical study performed on NAFLD individuals diagnosed by ultrasound. Patients received n-3 PUFA (n = 13) or placebo (n = 11) supplementation for six months. Circulating miR-122 expression (determined by quantitative real time-polymerase chain reaction (qRT-PCR), liver fibrosis (FibroScan®), red blood cells (RBC) fatty acids (gas chromatography), and biochemical tests were performed at baseline and after intervention. After the intervention, in the n-3 PUFA group, docosahexaenoic acid (DHA) and omega index increased significantly in RBC (p = 0.022 and p = 0.012, respectively), in addition to a significant reduction in alkaline phosphatase (ALP) (p = 0.002) and liver fibrosis (p = 0.039). However, there was no change in the expression of circulating miR-122 in both groups. Our results showed that omega-3 PUFA were incorporated in erythrocytes after six months of fish oil supplementary intake, and that n-3 PUFA were effective in reducing ALP and liver fibrosis without altering the expression of circulating miR-122 in individuals with NAFLD.

Vitamin D3 enhances the effects of omega‐3 oils against metabolic dysfunction‐associated fatty liver disease in rat

“…Concomitantly, the hepatic concentrations of adiponectin alongside the antioxidants and anti-inflammatory markers increased significantly, while leptin with the pro-inflammatory and pro-oxidative stress molecules diminished in the VD and OM groups than the PC group. Our results are aligned with many reports that have advocated the potential therapeutic values of VD 3 [26][27][28][48][49][50] and omega-3 oils 17,[21][22][23][24][25] against MAFLD, plausibly by enhancing insulin sensitivity, reducing lipogenesis alongside antioxidative and antiinflammatory actions. Nevertheless, the OM group disclosed lower body weight with enhanced hepatoprotective effects than the VD group.…”

Hepatic Unsaturated Fatty Acids Are Linked to Lower Degree of Fibrosis in Non-alcoholic Fatty Liver Disease

“…Due to the limited conversion rate from α-linolenic acid (18:3n-3) and 20:5n-3, plasma and tissue levels of 22:6n-3 mainly reflect dietary intake of marine sources, such as fatty fish and fish-oil supplements ( 26 ). On the contrary however, human supplementation trials of omega-3 fatty acids in NAFLD fibrosis have been few and findings have been mixed, with durations ranging from 6 to 12 months and with combined doses of both 22:6n-3 and 20:5n-3 ranging from 600 to 3,600 mg/day ( 27 , 28 ). This apparent heterogeneity makes it difficult to draw any firm conclusions regarding the role of 22:6n-3 supplementation in NAFLD fibrosis.…”

The Significance of the Mediterranean Diet in the Management of Non-Alcoholic Fatty Liver Disease: A Systematic Review

“…The most important PUFA for NAFLD is long-chain n-3 fatty acids, which include eicosapentaenoic, EPA, and docosahexaenoic, DHA [15]. These prevent liver adipogenesis by modifying transcription and suppressing peroxisome proliferator-activated receptor α and sterol regulatory element-binding protein-1 genes [16]. The main role of these genes is the regulation of hepatic fatty acid oxidation and synthesis, respectively [16].…”

“…These prevent liver adipogenesis by modifying transcription and suppressing peroxisome proliferator-activated receptor α and sterol regulatory element-binding protein-1 genes [16]. The main role of these genes is the regulation of hepatic fatty acid oxidation and synthesis, respectively [16]. Additionally, n-3 fatty acids suppress the direct uptake of fat into hepatocytes and modulate the expression of particular miRNAs [16,17].…”

“…The main role of these genes is the regulation of hepatic fatty acid oxidation and synthesis, respectively [16]. Additionally, n-3 fatty acids suppress the direct uptake of fat into hepatocytes and modulate the expression of particular miRNAs [16,17]. The wellestablished outcome of PUFA and NAFLD by research is the prevention of hepatic steatosis, resulting in a beneficial role in disease management [18].…”