A Systems Approach To NAD+ Restoration

Nuchido CEO and Chief Scientist Dr Nichola Conlon recently published a review article in the Journal of Biochemical Pharmacology entitled ‘A systems-approach to NAD+ restoration’. The peer-reviewed article discusses why NAD+ is critical to healthy aging and the best approach to boost NAD+ levels.

Read a summary of the paper below or click here to read the full review paper.


A systems approach to boosting NAD+ levels
  • NAD+ is now known to be a very important molecule for cellular health and to support healthy aging, but NAD+ levels are known to decline with age.
  • Preclinical studies in animals have shown the great benefits of restoring NAD+ levels including:
      • Improved cellular energy levels and supporting mitochondrial health
      • Supporting cognitive function
      • Supporting cardiovascular function
      • Supporting metabolic health
      • Supporting muscle strength
  • Following the positive preclinical studies focus has now shifted to human clinical trials. These trials take a single target approach using precursor compounds such as NR (nicotinamide riboside) and NMN (nicotinamide mononucleotide) – raw materials used by the cell to make NAD+.
  • A wealth of data now shows that this isn’t the best approach to boosting NAD+ levels as the cause of NAD+ decline is more complex than previously thought.
    • Overall, age related NAD+ decline occurs due to multiple issues:
      • Decreased production and recycling of NAD+ by cells
      • Increased consumption and wastage of the limited NAD+ by hyperactivated consumers
      • Leading to a deficit of NAD+ for key cellular processes that depend on it
    • NR and NMN supplementation do not address any of these underlying root causes of NAD+ decline.
    • Evidence suggests that while precursor supplements may cause a temporary increase in cellular NAD+, once this NAD+ is broken down and used by the hyperactivated NAD+ consumers it is effectively wasted because the cell is unable to recycle the breakdown products back into fresh NAD+.
    • This can lead to further issues as the cell has to compensate for this sudden boost in NAD+ breakdown products by methylating the waste products so they can be excreted from the cell. Leaving a shortage of methyl donors available for other vital cellular reactions.
    • Dr Conlon proposes evidence for an alternative and more sustainable strategy to boost NAD+ by using a multi-target approach which addresses the root causes of NAD+ decline.
    • A multitargeted approach involves simultaneously:
      • Providing NAD+ precursors to the cell
      • Inhibiting hyperactivated NAD+ consumers such as CD38
      • Activating key NAD+ salvage and recycling enzymes such as NAMPT
      • Inhibiting NNMT to prevent excessive methylation and promote NAD+ recycling
    • The use of a multi-targeted approach could provide synergistic increases in NAD+ levels by addressing the multiple root causes of NAD+ decline.
    • This could provide greater levels of NAD+ restoration with greater measurable health benefits and reduce potential unwanted effects associated with high doses of NAD+ precursors.


    That is exactly why Dr Conlon and her team spent years studying the best combination of ingredients which target the key areas of the NAD+ production network described. This research led to the development of Nuchido TIME+, a next generation NAD+ supplement which goes beyond just providing cells with precursors ingredients. Using this multi-target approach Nuchido TIME+ has been shown to increase NAD+ levels by 242% in our pilot study.


    To learn more about Nuchido TIME+ and our multi-targeted approach click here.