The acute effect of different NAD+ precursors included in the combined metabolic activators

Li X., Yang H., Jin H., TÜRKEZ H., ÖZTÜRK G., Doganay H. L., ...More

Free Radical Biology and Medicine, vol.205, pp.77-89, 2023 (SCI-Expanded) identifier identifier

  • Publication Type: Article / Article
  • Volume: 205
  • Publication Date: 2023
  • Doi Number: 10.1016/j.freeradbiomed.2023.05.032
  • Journal Name: Free Radical Biology and Medicine
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, BIOSIS, CAB Abstracts, Chemical Abstracts Core, EMBASE, MEDLINE, Veterinary Science Database
  • Page Numbers: pp.77-89
  • Keywords: Carnitine, Cysteine, Metabolomics, NAD+ precursors, Serine, Systems medicine
  • Istanbul Medipol University Affiliated: Yes


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.