Pinitol consumption improves liver health status by reducing oxidative stress and fatty acid accumulation in subjects with non-alcoholic fatty liver disease: A randomized, double-blind, placebo-controlled trial

Non-alcoholic fatty liver disease (NAFLD) is the most prevalent cause of chronic hepatic injury in the world. One of the most important therapeutic strategies for this disease is modulating oxidative stress. This study hypothesized that supplementation of pinitol might exert hepatic protective effects, by modulating oxidative stress in subjects with NAFLD. A randomized, double-blind controlled trial was conducted in 90 subjects with ultrasonography-proven NAFLD, who were randomly assigned to the placebo, low-dose (300 mg/d), or high-dose (500 mg/d) of pinitol for 12 weeks. The outcome measures were liver fat content, liver enzymes, fasting and postprandial lipids, and oxidative stress levels. To understand the underlying mechanism, plasma metabolomic analysis based on a gas chromatography/time-of-flight mass spectrometry and urinary pinitol analysis were also performed. The pinitol group showed significantly lower levels in liver fat content, plasma liver enzymes, fasting/postprandial urinary malondialdehyde levels, and postprandial triglycerides concentrations, but significantly higher in glutathione peroxidase level compared with the placebo group. The metabolomic analysis identified 27 differential metabolites involved in glycine/serine/threonine metabolism, alanine/aspartate/glutamate metabolism, D-glutamine/D-glutamate metabolism, and fatty acid synthesis, implicating the role of pinitol in glutathione-related lipid and energy metabolism. These results suggest that pinitol may exert modulatory effects upon energy and metabolic pathways by reducing oxidative stress and fatty acid accumulation, which can lead to hepatoprotective benefits in NAFLD subjects.