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

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

doi:10.1016/j.freeradbiomed.2023.05.032

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

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

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

12 Citations (Scopus)

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.

Original language	English
Pages (from-to)	77-89
Number of pages	13
Journal	Free Radical Biology and Medicine
Volume	205
Early online date	8 Jun 2023
DOIs	https://doi.org/10.1016/j.freeradbiomed.2023.05.032
Publication status	Published - 20 Aug 2023

Keywords

Carnitine
Cysteine
Metabolomics
NAD precursors
Serine
Systems medicine

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1016/j.freeradbiomed.2023.05.032

Cite this

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title = "The acute effect of different NAD+ precursors included in the combined metabolic activators",

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.",

keywords = "Carnitine, Cysteine, Metabolomics, NAD precursors, Serine, Systems medicine",

author = "Xiangyu Li and Hong Yang and Han Jin and Hasan Turkez and Gurkan Ozturk and Doganay, {Hamdi Levent} and Cheng Zhang and Jens Nielsen and Mathias Uhl{\'e}n and Jan Bor{\'e}n and Adil Mardinoglu",

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AU - Li, Xiangyu

AU - Yang, Hong

AU - Jin, Han

AU - Turkez, Hasan

AU - Ozturk, Gurkan

AU - Doganay, Hamdi Levent

AU - Zhang, Cheng

AU - Nielsen, Jens

AU - Uhlén, Mathias

AU - Borén, Jan

AU - Mardinoglu, Adil

PY - 2023/8/20

Y1 - 2023/8/20

N2 - 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.

AB - 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.

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