Nicotinamide riboside

Nicotinamide riboside[p] (NR) is a pyridine-nucleoside form of vitamin B3 that functions as a precursor to nicotinamide adenine dinucleotide or NAD+.[1][2]

In 2016 the FDA granted generally recognized as safe (GRAS) status for nicotinamide riboside as a food ingredient in enhanced water products, protein shakes, nutrition bars, gum and chews at no more than 0.027% of NR by weight.[3] The NOAEL and LOAEL in rodents are 300 and 1,000 mg/kg/day respectively.[3]:2–3

While the molecular weight of nicotinamide riboside is 255.25 g/mol,[4] that of its chloride salt is 290.70 g/mol.[3]:7 As such, 100 mg of nicotinamide riboside chloride provides 88 mg of nicotinamide riboside.

Nicotinamide riboside (NR) was first described in 1944 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.[5] Notably, H. influenza cannot grow on nicotinic acid, nicotinamide, tryptophan or aspartic acid, which were the previously known precursors of NAD+.[6]

In 2000, yeast Sir2 was shown to be an NAD+-dependent protein lysine deacetylase,[7] 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 (nicotinic acid mononucleotide).[8][9][10][11][12]

When NAD+ synthase (glutamine-hydrolysing) was deleted from yeast cells, NR permitted yeast cells to grow. Thus, these Dartmouth College investigators proceeded to clone yeast and human nicotinamide riboside kinases and demonstrate the conversion of NR to NMN by nicotinamide riboside kinases in vitro and in vivo. They also demonstrated that NR is a natural product, a little-noticed vitamin found in cow’s milk.[13][14]

 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. ^ Jump up to: a b c “Spherix/Chromadex GRAS submission” (PDF). March 8, 2016. Archived (PDF) from the original on March 4, 2017. See FDA GRAS index page: “GRAS Notice (GRN) No. 635”. Archived from the original on 2017-02-11.
  4. ^ “Nicotinamide Riboside”.
  5. ^ Gingrich, W (1944). “Codehydrogenase I and other pyridinium compounds as V factor for Haemophilus influenzae and Haemophilus parainfluenzae”. J. Bacteriol. 47: 535–550.
  6. ^ 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.
  7. ^ Imai, S.; et al. (2000). “Transcriptional silencing and longevity protein Sir2 is an NAD-dependent histone deacetylase”. Nature. 403 (6771): 795–800.
  8. ^ 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.
  9. ^ Sandmeier; et al. (2002). “Telomeric and rDNA silencing in Saccharomyces cerevisiae are dependent on a nuclear NAD Salvage Pathway”. Genetics. 160: 877–889.
  10. ^ 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. PMID 12297502.
  11. ^ Anderson; et al. (2003). “Nicotinamide and PNC1 govern lifespan extension by calorie restriction in Saccharomyces cerevisiae”. Nature. 423: 181–185. doi:10.1038/nature01578. PMC 4802858. PMID 12736687.
  12. ^ Gallo; et al. (2004). “Nicotinamide clearance by pnc1 directly regulates sir2-mediated silencing and longevity”. Mol. Cell. Biol. 24: 1301–1312. doi:10.1128/mcb.24.3.1301-1312.2004.
  13. ^ Bieganowki, P. & 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. PMID 15137942.
  14. ^ Hautkooper, R.H.; et al. (2012). “Sirtuins as regulators of metabolism and healthspan”. Nat. Rev. Mol. Cell Biol. 13: 225–238. doi:10.1038/nrm3293. PMC 4872805.
  15. ^ “Nicotinamide Medical Definition”. merriam-webster.com. June 2018. Retrieved 2018-07-29.
  16. ^ “Riboside Medical Definition”. merriam-webster.com. June 2018. Retrieved 2018-07-29.

 

 

Nicotinamide mononucleotide (“NMN” and “β-NMN“) is a nucleotide derived from ribose and nicotinamide.[1] Like nicotinamide riboside, NMN is a derivative of niacin, and humans have enzymes that can use NMN to generate nicotinamide adenine dinucleotide (NADH).[1]

Because NADH is a cofactor for processes inside mitochondria, for sirtuins, and for PARP, NMN has been studied in animal models as a potential neuroprotective and anti-aging agent.[2][3] Dietary supplement companies have aggressively marketedNMN products claiming those benefits,[4][5] though there is no clinical study on humans published yet.[5]

  1. ^ Jump up to: a b Bogan, KL; Brenner, C (2008). “Nicotinic acid, nicotinamide, and nicotinamide riboside: a molecular evaluation of NAD+ precursor vitamins in human nutrition”. Annual Review of Nutrition. 28: 115–30. doi:10.1146/annurev.nutr.28.061807.155443. PMID 18429699.
  2. ^ Brazill, JM; Li, C; Zhu, Y; Zhai, RG (June 2017). “NMNAT: It’s an NAD+ synthase… It’s a chaperone… It’s a neuroprotector”. Current Opinion in Genetics & Development. 44: 156–162. doi:10.1016/j.gde.2017.03.014. PMC 5515290. PMID 28445802.
  3. ^ “Long-Term Administration of Nicotinamide Mononucleotide Mitigates Age-Associated Physiological Decline in Mice”. Cell Metabolism. 13 December 2016.
  4. ^ Stipp, David (March 11, 2015). “Beyond Resveratrol: The Anti-Aging NAD Fad”. Scientific American Blog Network.
  5. ^ Jump up to: a b Bigley, Sharon, A dietary supplement makes old mice youthful. But will it work in people?, STAT, March 22, 2018 (paywalled)

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