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

Hong Yang, Adil Mardinoglu, Xiangyu Li, Han Jin, Hasan Turkez, Gurkan Ozturk, Hamdi Levent Doganay, Cheng Zhang, Jens Nielsen, Mathias Uhlén, Jan Borén

Journal: Free radical biology & medicine 2023;205():77-89

PMID: 37271226

Full Text on Elsevier Science View on PubMed

Abstract

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.

Address: Bash Biotech Inc, 600 West Broadway, Suite 700, San Diego, CA, 92101, USA; Science for Life Laboratory, KTH - Royal Institute of Technology, Stockholm, Sweden; Guangzhou Laboratory, Guangzhou, 510005, China. Electronic address: [email protected].; Science for Life Laboratory, KTH - Royal Institute of Technology, Stockholm, Sweden. Electronic address: [email protected].; Science for Life Laboratory, KTH - Royal Institute of Technology, Stockholm, Sweden. Electronic address: [email protected].; Department of Medical Biology, Faculty of Medicine, Atatürk University, Erzurum, Turkey. Electronic address: [email protected].; Research Institute for Health Sciences and Technologies (SABITA), International School of Medicine, Istanbul Medipol University, 34810, Istanbul, Turkey. Electronic address: [email protected].; Gastroenterology and Hepatology Unit, VM Pendik Medicalpark Teaching Hospital, İstanbul, Turkey; Department of Internal Medicine, Bahçeşehir University (BAU), Istanbul, Turkey. Electronic address: [email protected].; Science for Life Laboratory, KTH - Royal Institute of Technology, Stockholm, Sweden. Electronic address: [email protected].; Department of Biology and Biological Engineering, Chalmers University of Technology, Gothenburg, Sweden; BioInnovation Institute, Ole Maaløes Vej 3, DK2200, Copenhagen, Denmark. Electronic address: [email protected].; Science for Life Laboratory, KTH - Royal Institute of Technology, Stockholm, Sweden. Electronic address: [email protected].; Department of Molecular and Clinical Medicine, University of Gothenburg and Sahlgrenska University Hospital, Gothenburg, Sweden. Electronic address: [email protected].; Science for Life Laboratory, KTH - Royal Institute of Technology, Stockholm, Sweden; Centre for Host-Microbiome Interactions, Faculty of Dentistry, Oral & Craniofacial Sciences, King's College London, London, United Kingdom. Electronic address: [email protected].

DOI: 10.1016/j.freeradbiomed.2023.05.032

Link outs

Free resources

Medical:

https://medlineplus.gov/metabolicdisorders.html

Subscription / membership required

Full Text Sources:

MeSH Terms: Humans, Metabolic Diseases, NAD, Neurodegenerative Diseases, Niacin, Niacinamide, Nicotinamide Mononucleotide