Supplementation with omega-3 fatty acids (docosahexaenoic acid [DHA] + eicosapentaenoic acid [EPA]) has previously shown to improve multiple parameters associated with NAFLD: omega-3s improve insulin sensitivity, lower plasma triglyceride concentrations and have the potential to decrease liver fat.
To further understand the mechanisms by which omega-3 supplementation influences NAFLD, researchers in the United Kingdom conducted a proof-of-concept pilot study.
The study aimed to evaluate whether increased erythrocyte DHA enrichment was associated with changes in hepatic de-novo lipogenesis, postprandial fatty acid partitioning and insulin sensitivity in patients with NAFLD.
A small sub-sample of patients (n=16) from the WELCOME trial were included in the study.
Patients were randomised to EPA + DHA (4g/d) or placebo for 15–18 months. At the end of the study period, seven participants demonstrated changes in erythrocyte DHA enrichment of >2% (eight in EPA + DHA group and one in placebo group), and nine participants demonstrated changes in erythrocyte DHA enrichment of <2% (all in placebo group).
Erythrocyte DHA enrichment >2% was associated with a non-significant (26%) decrease in hepatic fat content but significant decreases in hepatic de novo lipogenesis and serum VLDL-triglyceride concentrations (both fasting and postprandial).
The absolute concentration of fatty acids derived from hepatic de novo lipogenesis to VLDL-triglycerides was significantly lower in the DHA >2% group.
The DHA >2% group demonstrated significant improvements in hepatic fatty acid oxidation and hepatic insulin sensitivity, with evidence that intrahepatic metabolism was being moved toward ketogenic pathways during the postprandial period.
The results of this study suggest that tissue enrichment with DHA may be one mechanism to explain the clinical effects of omega-3 supplementation in patients with NAFLD.
In short, patients with NAFLD who achieve higher tissue enrichment of DHA (achieved by taking 4g/d DHA +EPA in this study) experience lower hepatic lipogenesis, higher hepatic fat oxidation, and better hepatic insulin sensitivity than those with lower DHA enrichment.
