TY - JOUR
T1 - Longitudinal metabolomics analysis reveals the acute effect of cysteine and NAC included in the combined metabolic activators
AU - Yang, Hong
AU - Li, Xiangyu
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
N1 - Publisher Copyright:
© 2023
PY - 2023/8/1
Y1 - 2023/8/1
N2 - Growing evidence suggests that the depletion of plasma NAD+ and glutathione (GSH) may play an important role in the development of metabolic disorders. The administration of Combined Metabolic Activators (CMA), consisting of GSH and NAD+ precursors, has been explored as a promising therapeutic strategy to target multiple altered pathways associated with the pathogenesis of the diseases. Although studies have examined the therapeutic effect of CMA that contains N-acetyl-L-cysteine (NAC) as a metabolic activator, a system-wide comparison of the metabolic response to the administration of CMA with NAC and cysteine remains lacking. In this placebo-controlled study, we studied the acute effect of the CMA administration with different metabolic activators, including NAC or cysteine with/without nicotinamide or flush free niacin, and performed longitudinal untargeted-metabolomics profiling of plasma obtained from 70 well-characterized healthy volunteers. The time-series metabolomics data revealed the metabolic pathways affected after the administration of CMAs showed high similarity between CMA containing nicotinamide and NAC or cysteine as metabolic activators. Our analysis also showed that CMA with cysteine is well-tolerated and safe in healthy individuals throughout the study. Last, our study systematically provided insights into a complex and dynamics landscape involved in amino acid, lipid and nicotinamide metabolism, reflecting the metabolic responses to CMA administration containing different metabolic activators.
AB - Growing evidence suggests that the depletion of plasma NAD+ and glutathione (GSH) may play an important role in the development of metabolic disorders. The administration of Combined Metabolic Activators (CMA), consisting of GSH and NAD+ precursors, has been explored as a promising therapeutic strategy to target multiple altered pathways associated with the pathogenesis of the diseases. Although studies have examined the therapeutic effect of CMA that contains N-acetyl-L-cysteine (NAC) as a metabolic activator, a system-wide comparison of the metabolic response to the administration of CMA with NAC and cysteine remains lacking. In this placebo-controlled study, we studied the acute effect of the CMA administration with different metabolic activators, including NAC or cysteine with/without nicotinamide or flush free niacin, and performed longitudinal untargeted-metabolomics profiling of plasma obtained from 70 well-characterized healthy volunteers. The time-series metabolomics data revealed the metabolic pathways affected after the administration of CMAs showed high similarity between CMA containing nicotinamide and NAC or cysteine as metabolic activators. Our analysis also showed that CMA with cysteine is well-tolerated and safe in healthy individuals throughout the study. Last, our study systematically provided insights into a complex and dynamics landscape involved in amino acid, lipid and nicotinamide metabolism, reflecting the metabolic responses to CMA administration containing different metabolic activators.
KW - Combined metabolic activators
KW - Cysteine
KW - Metabolomics
KW - N-Acetyl-L-cysteine
KW - Niacin
KW - Nicotinamide
UR - http://www.scopus.com/inward/record.url?scp=85160423966&partnerID=8YFLogxK
U2 - 10.1016/j.freeradbiomed.2023.05.013
DO - 10.1016/j.freeradbiomed.2023.05.013
M3 - Article
C2 - 37245532
AN - SCOPUS:85160423966
SN - 0891-5849
VL - 204
SP - 347
EP - 358
JO - Free Radical Biology and Medicine
JF - Free Radical Biology and Medicine
ER -