How do We Create NAD in the Body?

The NAD Biosynthesis Pathways

Biosynthesis is the creation of complex molecules within living organisms or cells. NAD+ can be synthesized from a variety of different dietary sources which naturally contain tryptophan (Trp), nicotinic acid (NA), nicotinamide (NAM), nicotinamide riboside (NR), or NAD+ itself. These nutrients are metabolized in the gut, then synthesized again in the cells.  These dietary sources and another NAD precursor called nicotinamide mononucleotide (NMN) can be consumed as supplements  to further synthesize NAD. Depending on the bioavailability of the precursors, there are three different pathways the body uses to generate NAD – they are the de novo pathway (which uses Trp), the Preiss–Handler pathway (utilizes NA), and the salvage pathway (utilizes NAM, NR & NMN).5

What is NMN?

NMN is an intermediate molecule made in the conversion of both nicotinamide (NAM) and nicotinamide riboside (NR) to NAD.1, 2 It is a type of molecule called a nucleotide, which is very similar to the building blocks of DNA. As an intermediary in NAD metabolism, it is expected that NMN would be found in food, however no natural dietary sources have been identified to date. As a nucleotide, any NMN consumed through the diet or supplementation must be converted prior to entering the cell2-11. In humans, it is hypothesized that NMN is converted to NR in order to enter cells2-11. Once in the cell, the NR is converted back to NMN and subsequently to NAD1, 2, 4, 6, 7, 10-12.

The niacin equivalent of NMN is likely to be 1 to 1, but no controlled studies have reported the conversion of NMN to niacin or NAD in the body.

nmn vs nr nam intracellular

What is Tryptophan?

tryptophan molecular structureTryptophan, commonly associated with turkey, is a naturally occurring amino acid (a building block that make proteins). It is consumed in the diet from protein rich foods, such as eggs, meat, and seeds. Once consumed, tryptophan can be used to make new proteins, serotonin (a molecule that works in the brain), and the hormone melatonin. In addition, it can be converted to NAD through the 7-step, de novo process. Because of its many uses, it is safe to assume that all tryptophan consumed does not go toward creating NAD1. Calculations done to determine “niacin equivalents” have revealed that 60 mg of tryptophan may have the same NAD raising ability as 1 mg of a B3 vitamin (niacin), but these calculations may vary depending on the nutritional state of the consumer13-15

  1. Canto, C., K.J. Menzies, and J. Auwerx, NAD(+) Metabolism and the Control of Energy Homeostasis: A Balancing Act between Mitochondria and the Nucleus. Cell Metab, 2015. 22(1): p. 31-53.
  2. Garrido, A. and N. Djouder, NAD(+) Deficits in Age-Related Diseases and Cancer. Trends Cancer, 2017. 3(8): p. 593-610.
  3. Camacho-Pereira, J., et al., CD38 Dictates Age-Related NAD Decline and Mitochondrial Dysfunction through an SIRT3-Dependent Mechanism. Cell Metab, 2016. 23(6): p. 1127-1139.
  4. Diguet, N., et al., Nicotinamide Riboside Preserves Cardiac Function in a Mouse Model of Dilated Cardiomyopathy. Circulation, 2017.
  5. Fang, E.F., et al., NAD(+) in Aging: Molecular Mechanisms and Translational Implications. Trends Mol Med, 2017. 23(10): p. 899-916.
  6. Ratajczak, J., et al., NRK1 controls nicotinamide mononucleotide and nicotinamide riboside metabolism in mammalian cells. Nat Commun, 2016. 7: p. 13103.
  7. Vaur, P., et al., Nicotinamide riboside, a form of vitamin B3, protects against excitotoxicity-induced axonal degeneration. FASEB J, 2017. 31(12): p. 5440-5452.
  8. Grozio, A., et al., CD73 protein as a source of extracellular precursors for sustained NAD+ biosynthesis in FK866-treated tumor cells. J Biol Chem, 2013. 288(36): p. 25938-49.
  9. Kato, M. and S.J. Lin, Regulation of NAD+ metabolism, signaling and compartmentalization in the yeast Saccharomyces cerevisiae. DNA Repair (Amst), 2014. 23: p. 49-58.
  10. Sociali, G., et al., Antitumor effect of combined NAMPT and CD73 inhibition in an ovarian cancer model. Oncotarget, 2016. 7(3): p. 2968-84.
  11. Yoshino, J., et al., Nicotinamide mononucleotide, a key NAD(+) intermediate, treats the pathophysiology of diet- and age-induced diabetes in mice. Cell Metab, 2011. 14(4): p. 528-36.
  12. Imai, S. and L. Guarente, NAD+ and sirtuins in aging and disease. Trends Cell Biol, 2014. 24(8): p. 464-71.
  13. Canto, C. and J. Auwerx, NAD+ as a signaling molecule modulating metabolism. Cold Spring Harb Symp Quant Biol, 2011. 76: p. 291-8.
  14. Bogan, K.L. and C. Brenner, Nicotinic acid, nicotinamide, and nicotinamide riboside: a molecular evaluation of NAD+ precursor vitamins in human nutrition. Annu Rev Nutr, 2008. 28: p. 115-30.
  15. Canto, C., A.A. Sauve, and P. Bai, Crosstalk between poly(ADP-ribose) polymerase and sirtuin enzymes. Mol Aspects Med, 2013. 34(6): p. 1168-201.

New data suggest NAD plays an even larger role in the anti-aging story than was previously understood.

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