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Mujdat Zeybel, MD, NIHR Nottingham Biomedical Research Centre This study demonstrated CMCS supplementation significantly decreased liver fat, improved liver function, and decreased liver inflammation in NAFLD patients, suggesting CMCS may be an effective therapeutic strategy for NAFLD, No drugs have been approved to treat NAFLD, and effective treatment options with long-term safety are urgently required. The combined metabolic cofactor supplementation (CMCS) regimen developed by the Nottingham group and used in this trial consists of: 1g nicotinamide riboside (NR), which raises mitochondrial NAD+ levels, and boosts fat metabolism 3.73g L-carnitine tartrate, which promotes transport of fat into the mitochondria 12.35g L-serine, which increases glutathione synthesis 2.55g N acetyl-L-cysteine (NAC), which also promotes glutathione production and reduces oxidative stress A total of 31 patients with MRI-confirmed non-alcoholic steatosis were randomized to either placebo (N=11) or the CMCS combination (N= 20)

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Among these, three studies lacked mechanistic analyses, and three involved treatments other than acupuncture

These effects might be facilitated via AMPK/Sirtuin 1 (SIRT1), autophagy, and the Toll-like receptor-4 (TLR-4)/NF-B/NLRP3 signal transduction cascade [264]

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