Inflammatory markers response to citrulline supplementation in patients with non-alcoholic fatty liver disease: a randomized, double blind, placebo-controlled, clinical trial.

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Objectives: The aim of this study was to investigate the effects of citrulline (Cit) supplementation on inflammatory markers and liver histopathology in patients with non-alcoholic fatty liver disease (NAFLD). In this clinical trial, fifty NAFLD patients were assigned to receive 2 g/day Cit or placebo for 3 months.Results: At the end of study, serum high sensitive C-reactive protein (hs-CRP) and activity of nuclear factor kappa B (NF-κB) were reduced in Cit group significantly more than placebo group (P-value = 0.02 and < 0.01 respectively). Serum concentrations of tumor necrosis factor-α (TNF-α) was reduced in Cit group significantly more than placebo after adjusting for levels of baseline (P-value < 0.001). Moreover, Cit supplementation decreased serum alanine aminotransferase (ALT) and hepatic steatosis significantly (P = 0.04). Anthropometric measurements and hepatic enzymes did not change significantly in any group (P ≥ 0.05). In conclusion, our results showed that 12 weeks supplementation with 2 g/day Cit improved inflammatory markers in patients with NAFLD. Further studies with longer period of supplementation and different dosages of Cit are needed to be able to conclude. Trial registration IRCT201703194010N18 on 2017-10-13.