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Li X, Yang H, Jin H, Turkez H, Ozturk G, Doganay HL, Zhang C, Nielsen J, Uhlén M, Borén J, Mardinoglu A
Free Radic. Biol. Med. 205 (-) 77-89 [2023-08-20; online 2023-06-02]
NAD+ and glutathione precursors are currently used as metabolic modulators for improving the metabolic conditions associated with various human diseases, including non-alcoholic fatty liver disease, neurodegenerative diseases, mitochondrial myopathy, and age-induced diabetes. Here, we performed a one-day double blinded, placebo-controlled human clinical study to assess the safety and acute effects of six different Combined Metabolic Activators (CMAs) with 1 g of different NAD+ precursors based on global metabolomics analysis. Our integrative analysis showed that the NAD+ salvage pathway is the main source for boosting the NAD+ levels with the administration of CMAs without NAD+ precursors. We observed that incorporation of nicotinamide (Nam) in the CMAs can boost the NAD+ products, followed by niacin (NA), nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN), but not flush free niacin (FFN). In addition, the NA administration led to a flushing reaction, accompanied by decreased phospholipids and increased bilirubin and bilirubin derivatives, which could be potentially risky. In conclusion, this study provided a plasma metabolomic landscape of different CMA formulations, and proposed that CMAs with Nam, NMN as well as NR can be administered for boosting NAD+ levels to improve altered metabolic conditions.
Bioinformatics Support for Computational Resources [Service]
PubMed 37271226
DOI 10.1016/j.freeradbiomed.2023.05.032
Crossref 10.1016/j.freeradbiomed.2023.05.032
pii: S0891-5849(23)00473-2