The acute effect of different NAD+ precursors included in the combined metabolic activators
Journal article, 2023
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.
Systems medicine
NAD precursors +
Cysteine
Metabolomics
Carnitine
Serine
Author
Xiangyu Li
Bash Biotech Inc.
Southern Marine Science and Engineering Guangdong Laboratory (Guangzhou)
Royal Institute of Technology (KTH)
Hong Yang
Royal Institute of Technology (KTH)
Han Jin
Royal Institute of Technology (KTH)
Hasan Turkez
Atatürk University
Gurkan Ozturk
Istanbul Medipol Universitesi
Hamdi Levent Doganay
Bahcesehir University
VM Medicalpark Pendik Hospital Orthopedics and Traumatology
C. Zhang
Royal Institute of Technology (KTH)
Jens B Nielsen
BioInnovation Institute
Chalmers, Life Sciences, Systems and Synthetic Biology
Mathias Uhlen
Royal Institute of Technology (KTH)
Jan Borén
University of Gothenburg
Adil Mardinoglu
King's College London
Royal Institute of Technology (KTH)
Free Radical Biology and Medicine
0891-5849 (ISSN) 18734596 (eISSN)
Vol. 205 77-89Subject Categories
Biochemistry and Molecular Biology
Public Health, Global Health, Social Medicine and Epidemiology
DOI
10.1016/j.freeradbiomed.2023.05.032
PubMed
37271226