A mixture of natural ingredients, namely docosahexaenoic acid (DHA), phosphatidylcholine, silymarin, choline, curcumin and D-α-tocopherol, was studied in subjects with non alcoholic fatty liver disease (NAFLD). Primary end-points were serum levels of hepatic enzymes; other parameters of liver function, metabolic syndrome and inflammation were secondary end-points. The coagulation-fibrinolysis balance was also thoroughly investigated, as NAFLD is associated with haemostatic alterations, which might contribute to the increased cardiovascular risk of this condition. Study design: double-blind, randomized, multicenter, controlled trial on two parallel groups. Subjects with NAFLD (18-80 years, either sex) received the active or control treatment for three months. All assays were performed before and at the end of supplementation, on 113 total subjects. The hepatic enzymes aspartate aminotransferase (AST), alanine aminotransferase and γ-glutamyl transpeptidase decreased after treatment from 23.2% to 3.7%, reaching statistical significance only for AST levels. However, there were no differences between control and active groups. Metabolic and inflammatory variables were unchanged, except for a slight (less than 10%) increase of cholesterol and glucose levels after the active treatment. Coagulation-fibrinolytic parameters were unaffected by either treatment. In conclusion, chronic supplementation with the mixture of dietary compounds was well tolerated and apparently safe in NAFLD subjects. The trial failed to demonstrate any efficacy on relevant physio-pathological markers, but its protocol and results may be useful to design future studies with natural compounds.