We have previously found that combined metabolic cofactor supplementation (CMCS) promotes the oxidation of fat, attenuates the resulting oxidative stress, activates mitochondria and eventually removes excess fat from the liver. Here, we tested the safety and efficacy of CMCS in Nonalcoholic fatty liver disease (NAFLD) patients in a placebo-controlled 10-week study. We found that CMCS significantly decreased hepatic steatosis and levels of aspartate aminotransferase, alanine aminotransferase, uric acid, and creatinine whereas found no differences on these variables in the placebo group after adjustment for weight loss. By integrating clinical data with plasma metabolomics and inflammatory proteomics as well as oral and gut metagenomics data, we revealed the underlying molecular mechanisms associated with the reduced hepatic fat and inflammation in NAFLD patients and identified the key players involved in the host-microbiome interactions. In conclusion, we observed that CMCS could develop a pharmacological treatment strategy in NAFLD patients.
Keywords: Nonalcoholic fatty liver disease, CMCS, Metabolomics, Proteomics, gut and oral metagenomics, Systems Medicine
Zeybel, Mujdat and Altay, Ozlem and Arif, Muhammad and Li, Xiangyu and Yang, Hong and Fredolini, Claudia and Akyildiz, Murat and Saglam, Burcin and Gonenli, Mehmet Gokhan and Ural, Dilek and Kim, Woonghee and Schwenk, Jochen M. and Zhang, Cheng and Shoaie, Saeed and Nielsen, Jens and Uhlen, Mathias and Boren, Jan and Mardinoglu, Adil, Combined Metabolic Cofactor Supplementation Reduces Liver Fat in Nonalcoholic Fatty Liver Disease. Available at SSRN: https://ssrn.com/abstract=3778301 or http://dx.doi.org/10.2139/ssrn.3778301
This version of the paper has not been formally peer reviewed.
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