The acute effect of different NAD+ precursors included in the combined metabolic activators.
- 2023-08
- Free radical biology & medicine 205
- Xiangyu Li
- Hong Yang
- Han Jin
- Hasan Turkez
- Gurkan Ozturk
- Hamdi Levent Doganay
- Cheng Zhang
- Jens Nielsen
- Mathias Uhlén
- Jan Borén
- Adil Mardinoglu
- PubMed: 37271226
- DOI: 10.1016/j.freeradbiomed.2023.05.032
Study Design
- Type
- Clinical Trial
- Methods
- One-day double-blinded, placebo-controlled human clinical study with six different Combined Metabolic Activators (CMAs) containing 1 g of NAD+ precursors; global metabolomics analysis.
- Blinding
- Double-blind
- Duration
- 1 day
- Funding
- Unclear
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.