The acute effect of different NAD plus precursors included in the combined metabolic activators
Li, Xiangyu, Yang, Hong, Jin, Han, Turkez, Hasan, Ozturk, Gurkan, Doganay, Hamdi Levent, Zhang, Cheng, Nielsen, Jens, Uhlen, Mathias, Boren, Jan, Mardinoglu, Adil
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.
- Journal
- FREE RADICAL BIOLOGY AND MEDICINE
- Year
- 2023
- Volume
- 205
- Pages
- 77-89
- ISSN
- 0891-5849
- eISSN
- 1873-4596
- DOI
- 10.1016/j.freeradbiomed.2023.05.032
- WoS UID
- WOS:001053802900001