Brain NAD Is Associated With ATP Energy Production and Membrane Phospholipid Turnover in Humans

Bernard Cuenoud*, Ozlem Ipek, Maya Shevlyakova, Maurice Beaumont, Stephen C. Cunnane, Rolf Gruetter, Lijing Xin

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

16 Citations (Scopus)


The brain requires a large amount of energy, mostly derived from the metabolism of glucose, which decreases substantially with age and neurological diseases. While mounting evidence in model organisms illustrates the central role of brain nicotinamide adenine dinucleotide (NAD) for maintaining energy homeostasis, similar data are sparse in humans. This study explores the correlations between brain NAD, energy production and membrane phospholipid metabolism by 31-phosphorous magnetic resonance spectroscopy (31P-MRS) across 50 healthy participants including a young (mean age 27.1-year-old) and middle-aged (mean age 56.4-year-old) group. The analysis revealed that brain NAD level and NAD+/NADH redox ratio were positively associated with ATP level and the rate of energy production, respectively. Moreover, a metabolic network linking NAD with membrane phospholipid metabolism, energy production, and aging was identified. An inverted trend between age and NAD level was detected. These results pave the way for the use of 31P-MRS as a powerful non-invasive tool to support the development of new therapeutic interventions targeting NAD associated phospho-metabolic pathways in brain aging and neurological diseases.

Original languageEnglish
Article number609517
JournalFrontiers in Aging Neuroscience
Publication statusPublished - 16 Dec 2020


  • P-MRS
  • ATP metabolism
  • ATP synthase
  • brain energy
  • creatine kinase
  • membrane phospholipid metabolism
  • NAD
  • redox ratio


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