Infammatory markers response to citrulline supplementation in patients with non-alcoholic fatty liver disease:

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

Zahra Darabi , Mina Darand , Zahra Yari , Mehdi Hedayati , Amirhosein Faghihi3, Shahram Agah







Abstract

Objectives: The aim of this study was to investigate the efects of citrulline (Cit) supplementation on inflammatory markers and liver histopathology in patients with non-alcoholic fatty liver disease (NAFLD). In this clinical trial, ffty 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.




Limitations
One of the limitations of this study was that we did not use different dosages of Cit. We could not use higher dosages of Cit because we did not find enough evidence for their safety in human. Secondly, we could not obtain liver biopsy to estimate hepatic steatosis, and fibrosis. Liver biopsy is gold standard for the evaluation of liver fibrosis during of chronic liver diseases. However transient elastography (FibroScan®) used that provides quantitative, safely evaluation of NAFLD by scaling hepatic steatosis (CAP score) and fibrosis. Tis technique was a reliable, noninvasive way for identification of patients with significant hepatic steatosis and fibrosis. It is readily, replicability and its score has low inter- and intra-observer variability [27, 28]. Thirdly, the clinical significance of reduced inflammatory markers is not clear so additional studies are needed to see if these reductions translate to less liver- or cardiovascular-related endpoints.




Conclusion
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.
 

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