Nicotinamide riboside

Nicotinamide riboside
Names
Other names
1-(β-D-Ribofuranosyl)nicotinamide; N-Ribosylnicotinamide
Identifiers
1341-23-7
ChEBI CHEBI:15927
PubChem 439924
Properties
C11H15N2O5+
Molar mass 255.25 g/mol
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
Infobox references

Nicotinamide riboside (NR) is a pyridine-nucleoside form of vitamin B3 that functions as a precursor to nicotinamide adenine dinucleotide or NAD+.[1][2] NR has been a recent focus of life extension research after David Sinclair published a study in 2013 showing NAD+ levels decrease with age in mice.[3][4][5]

Discovery

Bacterial NAD precursor

NR was first described as a growth factor, termed Factor V, for Haemophilus influenza, a bacterium that lives in and depends on blood. Factor V, purified from blood was shown to exist in three forms: NAD+, NMN and NR. NR was the compound that led to the most rapid growth of this bacterium.[6] Notably, H. influenza cannot grow on nicotinic acid, nicotinamide, tryptophan or aspartic acid, which were the previously known precursors of NAD+.[7]

Eukaryotic NAD precursor vitamin

In 2000, yeast Sir2 was shown to be an NAD+-dependent protein lysine deacetylase,[8] which led several groups to probe yeast NAD+ metabolism for genes and enzymes that might regulate lifespan. Biosynthesis of NAD+ in yeast was thought to flow exclusively through NAMN.[9][10][11][12][13]

Surprisingly, when NAD+ synthase (glutamine-hydrolysing) was deleted from yeast cells, NR permitted yeast cells to grow. Thus, these investigators proceeded to clone yeast and human nicotinamide riboside kinases and demonstrate the conversion of NR to NMN by these enzymes in vitro and in vivo. They also demonstrated that NR is a natural product, the so-called hidden vitamin found in cow's milk.[14][15]

Potential applications in human health

High dose nicotinic acid is used as an agent that elevates high-density lipoprotein cholesterol, lowers low-density lipoprotein cholesterol and lower free fatty acids through a mechanism that is not completely understood. It was suggested that nicotinamide riboside might possess such an activity by elevating NAD in the cells responsible for reverse cholesterol transport.[7] An experiment with mice on high fat diet appears to support the potential of treatment or prevention of dyslipidemia with nicotinamide riboside.[16]

The discovery that the Wallerian degeneration slow gene encodes a protein fusion with NMN adenylyltransferase 1 indicated that increased NAD+ precursor supplementation might oppose neurodegenerative processes.[7] NR blocks degeneration of surgically severed dorsal root ganglion neurons ex vivo[17] and protects against noise-induced hearing loss in living mice.[18][19]

Increased muscular regeneration in mice has been observed after treatment with nicotinamide riboside, leading to speculation that it might improve regeneration of organs such as the liver, kidney, and heart.[20]

Commercialization

ChromaDex acquired intellectual property on uses and synthesis of NR from Dartmouth College, Cornell University, and Washington University and began distributing NR as Niagen in 2013.[21] ChromaDex completed a clinical study on nicotinamide riboside in 2015, demonstrating that it can increase the co-enzyme NAD+,[22] and began a clinical trial in March 2016 to examine the benefits if taken daily for eight consecutive weeks.[23]

See also

References

  1. ↑ Bogan, K.L., Brenner, C. (2008). "Nicotinic acid, nicotinamide, and nicotinamide riboside: a molecular evaluation of NAD+ precursor vitamins in human nutrition". Annu. Rev. Nutr. 28: 115–130. doi:10.1146/annurev.nutr.28.061807.155443.
  2. ↑ Chi Y, Sauve AA (November 2013). "Nicotinamide riboside, a trace nutrient in foods, is a vitamin B3 with effects on energy metabolism and neuroprotection". Curr Opin Clin Nutr Metab Care 16 (6): 657–61. doi:10.1097/MCO.0b013e32836510c0. PMID 24071780.
  3. ↑ Sinclair, David A. (19 December 2013). "Declining NAD+ Induces a Pseudohypoxic State Disrupting Nuclear-Mitochondrial Communication during Aging". Cell 155 (7): 1624–1638. doi:10.1016/j.cell.2013.11.037. PMID 24360282. Retrieved 14 April 2015.
  4. ↑ Bellman, Gary. "New Elixir of Youth? Researchers Develop a Drug That Can Reverse Aging in Animal Models". Male Anti-Aging Institute. Retrieved 14 April 2015.
  5. ↑ Cameron, David (19 December 2013). "A New—and Reversible—Cause of Aging". Harvard Medical School. Retrieved 14 April 2015.
  6. ↑ Gingrich, W (1944). "Codehydrogenase I and other pyridinium compounds as V factor for Haemophilus influenzae and Haemophilus parainfluenzae". J. Bacteriol. 47: 535–550.
  7. 1 2 3 Belenky, P. et. al. (2007). "NAD+ Metabolism in Health and Disease". Trends in Biochemical Sciences. 32: 12–19. doi:10.1016/j.tibs.2006.11.006. PMID 17161604.
  8. ↑ Imai, S.; et al. (2000). "Transcriptional silencing and longevity protein Sir2 is an NAD-dependent histone deacetylase". Nature 403 (6771): 795–800.
  9. ↑ Panozzo, C.; et al. (2002). "Aerobic and anaerobic NAD+ metabolism in Saccharomyces cerevisiae". FEBS Lett. 517: 97–102. doi:10.1016/s0014-5793(02)02585-1.
  10. ↑ Sandmeier; et al. (2002). "Telomeric and rDNA silencing in Saccharomyces cerevisiae are dependent on a nuclear NAD Salvage Pathway". Genetics 160: 877–889.
  11. ↑ Bitterman; et al. (2002). "Inhibition of silencing and accelerated aging by nicotinamide, a putative negative regulator of yeast Sir2 and human SIRT1". J. Biol. Chem 277: 45099–45107. doi:10.1074/jbc.m205670200.
  12. ↑ Anderson; et al. (2003). "Nicotinamide and PNC1 govern lifespan extension by calorie restriction in Saccharomyces cerevisiae". Nature 423: 181–185. doi:10.1038/nature01578. PMID 12736687.
  13. ↑ Gallo; et al. (2004). "Nicotinamide clearance by pnc1 directly regulates sir2-mediated silencing and longevity". Mol. Cel. Biol. 24: 1301–1312. doi:10.1128/mcb.24.3.1301-1312.2004.
  14. ↑ Bieganowki, P. and Brenner, C. (2004). "Discoveries of Nicotinamide Riboside as a Nutrient and Conserved NRK Genes Establish a Preiss-Handler Independent Route to NAD+ in Fungi and Humans". Cell 117: 495–502. doi:10.1016/s0092-8674(04)00416-7.
  15. ↑ Hautkooper, R.H.; et al. (2012). "Sirtuins as regulators of metabolism and healthspan". Nat. Rev. Mol. Cell. Bill. 13: 225–238. doi:10.1038/nrm3293.
  16. ↑ Canto, C. et. al. (2012). "The NAD+ Precursor Nicotinamide Riboside Enhances Oxidative Metabolism and Protects against High-Fat Diet-Induced Obesity". Cell Metabolism 15: 838–847. doi:10.1016/j.cmet.2012.04.022.
  17. ↑ Sasaki, Y. et. al. (2006). "Stimulation of nicotinamide adenine dinucleotide biosynthetic pathways delays axonal degeneration after axotomy". J. Neurosci. 26: 8484–8491. doi:10.1523/jneurosci.2320-06.2006.
  18. ↑ Brown, K.D. et. al. (2014). "Activation of SIRT3 by the NAD⁺ precursor nicotinamide riboside protects from noise-induced hearing loss". Cell Metab. 20: 1059–1068. doi:10.1016/j.cmet.2014.11.003.
  19. ↑ Brenner, C. (2014). "Boosting NAD to Spare Hearing". Cell Metab. 20: 926–927. doi:10.1016/j.cmet.2014.11.015.
  20. ↑ Vitamin stops the aging process of organs, Science Daily, April 28, 2016
  21. ↑ "ChromaDex Introduces Niagen". Retrieved 2014-04-23.
  22. ↑ Inc., ChromaDex,. "Results from First Human Clinical Study Demonstrate ChromaDex's NIAGEN(R) Nicotinamide Riboside Effectively Increases the Co-enzyme NAD+ and is Safe". GlobeNewswire News Room. Retrieved 2016-03-22.
  23. ↑ Inc., ChromaDex,. "ChromaDex Initiates Second Human Clinical Study on NIAGEN® -The World’s First and Only Commercially Available Form of Nicotinamide Riboside (NR)". GlobeNewswire News Room. Retrieved 2016-03-22.

Further reading

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