Li, XiangyuYang, HongJin, HanTürkez, HasanÖztürk, GürkanDoğanay, Hamdi LeventZhang, ChengNielsen, JensUhlen, MathiasBoren, JanMardinoğlu, Adil2023-09-112023-09-112023Li, X., Yang, H., Jin, H., Türkez, H., Öztürk, G., Doğanay, H. L. ... Mardinoğlu, A. (2023). The acute effect of different NAD plus precursors included in the combined metabolic activators. Free Radical Biology and Medicine, 205, 77-89. https://dx.doi.org/10.1016/j.freeradbiomed.2023.05.0320891-58491873-4596https://dx.doi.org/10.1016/j.freeradbiomed.2023.05.032https://hdl.handle.net/20.500.12511/11401NAD+ 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.eninfo:eu-repo/semantics/closedAccessNAD+ PrecursorsSerineCysteineCarnitineMetabolomicsSystems MedicineArticle205778910.1016/j.freeradbiomed.2023.05.032Q10010538029000012-s2.0-8516127699137271226Q1