Nicotinamide

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Nicotinamide
Nicotinamid.svg
Nicotinamide-from-xtal-2011-Mercury-3D-sf.png
Clinical data
Pronunciation /ˌnɪkəˈtɪnəmaɪd/
AHFS/Drugs.com Consumer Drug Information
Pregnancy
category
  • US: A (No risk in human studies) and C[1]
Routes of
administration		 by mouth, topical
ATC code
Identifiers
Synonyms 3-pyridinecarboxamide
niacinamide
nicotinic acid amide
vitamin PP
nicotinic amide
vitamin B3
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
ECHA InfoCard 100.002.467
Chemical and physical data
Formula C6H6N2O
Molar mass 122.13 g·mol−1
3D model (Jmol)
Density 1.40 g/cm3[2] g/cm3
Melting point 129.5 °C (265.1 °F)
Boiling point 334 °C (633 °F)

Nicotinamide (NAA), also known as niacinamide and vitamin B3, is a vitamin found in food, used as a dietary supplement, and used as a medication.[3][4][5] As a supplement, it is used by mouth to prevent and treat pellagra (niacin deficiency). While nicotinic acid (niacin) may be used for this purpose, nicotinamide has the benefit of not causing skin flushing.[4] As a cream, it is used to treat acne.[5]

Side effects are minimal.[6][7] At high doses liver problems may occur.[6] Normal amounts are safe for use during pregnancy.[1] Nicotinamide is in the vitamin B family of medications.[8] It is an amide of nicotinic acid.[6] Foods that contain nicotinamide include yeast, meat, milk, and green vegetables.[9]

Nicotinamide was discovered between 1935 and 1937.[10][11] It is on the World Health Organization's List of Essential Medicines, the most effective and safe medicines needed in a health system.[12] Nicotinamide is available as a generic medication and over the counter.[8] In the United Kingdom a 60 gm tube costs the NHS about 7.10 pounds.[5] Commercially nicotinamide is made from either nicotinic acid or 3-cyanopyridine. In a number of countries grains have nicotinamide added to them.[11]

Medical uses[edit]

Niacin deficiency[edit]

Nicotinamide is the preferred treatment for niacin deficiency (pellagra).[4] A patient's diagnosis of Pellagra is based on their history, as well as a presence of dermatitis, diarrhea, and dementia.[13] While nicotinic acid (niacin) may be used nicotinamide has the benefit of not causing skin flushing.[4]

Nicotinamide, circled in red, as a part of the overall structure of Nicotinamide Adenine Dinucleotide.

Acne[edit]

Nicotinamide in the form of a cream is used as a treatment for acne.[5]

It has anti-inflammatory actions. These may be of benefit to people with inflammatory skin conditions.[14]

Nicotinamide increases the biosynthesis of ceramides in human keratinocytes in vitro and improves the epidermal permeability barrier in vivo.[15] The application of 2% topical nicotinamide for 2 and 4 weeks has been found to be effective in lowering the sebum excretion rate in study participants.[16] Nictotinamide has been shown to prevent Propionibacterium acnes-induced activation of toll-like receptor (TLR)-2, which ultimately results in the down-regulation of pro-inflammatory IL-8 production.[17]

Side effects[edit]

Side effects are minimal.[6][7] At high doses liver problems may occur.[6] Normal amounts are safe for use during pregnancy.[1] Foods that contain nicotinamide include yeast, meat, milk, and green vegetables.[18]

Nicotinamide lacks the vasodilator, gastrointestinal, hepatic, and hypolipidemic actions of nicotinic acid. As such, nicotinamide has not been shown to produce the flushing, itching, and burning sensations of the skin as is commonly seen when large doses of nicotinic acid are administered orally. High-dose nicotinamide should still, however, be considered as a drug with toxic potential at adult doses in excess of 3 g/day and unsupervised use should be discouraged.[6] Overall, however, it rarely causes side effects, and is considered generally safe as a food additive, and as a component in cosmetics and medication.[19]

Structure[edit]

The structure of nicotinamide consists of an aromatic ring with an amido group attached to the third carbon. One of the atoms in the six membered aromatic ring is nitrogen, a trivalent molecule.[20] Nitrogen is most stable when it is bonded to only three other atoms,[21] however in the molecule nicotinamide adenine dinucleotide (NAD+), nitrogen is bonded to four other atoms, and thus has a positive formal charge.[22] Each carbon molecule in this ring is bound to a hydrogen atom except for the third carbon, which is covalently bonded to an amido group.[23] The amido group adds to the stabilization of the molecule through a form of stability called conjugation. Conjugation stability is added when there are multiple pi (double) bonds in series. It allows for the electron density in a certain part of the molecule to have more freedom, and adds more molecular stability.[24]

The structure of this molecule helps to determine its biological function, as the forming and breaking of an aromatic ring increases and decreases a molecules stability. The systems of the body pick up electrons, and add energy to NAD+ during Glycolysis and the Citric acid cycle, and then they release it in the Electron transport chain, forming Adenosine triphosphate, the primary energy currency of the cell.[25]

Biochemistry[edit]

The active Nicotinamide group on the molecule NAD+ undergoes oxidation in many metabolic pathways.

Nicotinamide, as a part of the coenzyme Nicotinamide adenine dinucleotide(NAD+) is crucial to life. In cells, nicotinamide is incorporated into Nicotinamide adenine dinucleotide (NAD+) and nicotinamide adenine dinucleotide phosphate (NADP+). NAD+ and NADP+ are coenzymes in a wide variety of enzymatic oxidation-reduction reactions the most notable being Glycolysis, the Citric acid cycle, and the Electron transport chain.[26] If humans ingest nicotinamide, it will likely undergo a series of reactions that transform it into NAD+, which can then undergo a transformation to form NADP+. This method of creation of NAD+ is called a salvage pathway. However, the human body can produce NAD+ from the amino acid Tryptophan and Niacin without our ingestion of Nicotinamide.[27]

NAD+ acts as an electron carrier that helps with the interconversion of energy between nutrients and the cell’s energy currency, ATP. In oxidation-reduction reactions, the active part of the coenzyme is the nicotinamide. In NAD+, the nitrogen in the aromatic nicotinamide ring is covalently bonded to adenine dinucleotide. The formal charge on the nitrogen is stabilized by the shared electrons of the other carbon atoms in the aromatic ring. When a hydride atom is added onto NAD+ to form NADH, the molecule loses its aromaticity, and therefore a good amount of stability. This higher energy product later releases its energy with the release of a hydride, and in the case of the Electron Transport Chain, it assists in forming Adenosine triphosphate.[28]

For every one mole of NADH that is oxidized, 158.2 KJ of energy will be released.[29]

Food sources[edit]

Nicotinamide occurs in trace amounts mainly in meat, fish, nuts, and mushrooms, as well as to a lesser extent in some vegetables.[30] It is commonly added to cereals and other foods. If one would want to take it orally, it is present in many multivitamins, and there are around 20-30 mg in each. It is also available as a standalone vitamin, in much higher quantities around 500mg.[31]

Production[edit]

Commercially nicotinamide is made from either nicotinic acid or 3-cyanopyridine. In 2014 31,000 tons of nicotinamide were sold.[11]

Compendial status[edit]

Research[edit]

There is tentative evidence that it may reduce the risk of nonmelanoma skin cancers among people who have had a previous basal cell carcinoma or squamous cell carcinoma.[34] There is also tentative evidence for its effective use to treat bullous pemphigoid.[34] Nicotinamide may aid chemotherapy-and-radiation therapy by acting as a sensitizing agent/cancer-growth-promoter resulting in enhanced blood flow to tumors and thus increased oxygen supply to tumors, thereby reducing tumor hypoxia. Niacinamide also inhibits poly(ADP-ribose) polymerases (PARP-1), enzymes involved in the rejoining of DNA strand breaks induced by radiation or chemotherapy.[35] There is also evidence that niacinamide is beneficial in treating psoriasis.[36]

See also[edit]

References[edit]

  1. ^ a b c "Niacinamide Use During Pregnancy | Drugs.com". www.drugs.com. Retrieved 29 December 2016. 
  2. ^ Record in the GESTIS Substance Database of the Institute for Occupational Safety and Health
  3. ^ Bender DA (2003). Nutritional Biochemistry of the Vitamins. Cambridge University Press. p. 203. ISBN 978-1-139-43773-8. 
  4. ^ a b c d WHO Model Formulary 2008 (PDF). World Health Organization. 2009. pp. 496, 500. ISBN 978-924-154765-9. Retrieved 8 December 2016. 
  5. ^ a b c d British National Formulary: BNF 69 (69th ed.). British Medical Association. 2015. p. 822. ISBN 978-0-85711-156-2. 
  6. ^ a b c d e f Knip M, Douek IF, Moore WP, Gillmor HA, McLean AE, Bingley PJ, Gale EA (November 2000). "Safety of high-dose nicotinamide: a review". Diabetologia. 43 (11): 1337–45. doi:10.1007/s001250051536. PMID 11126400. 
  7. ^ a b MacKay D, Hathcock J, Guarneri E (June 2012). "Niacin: chemical forms, bioavailability, and health effects". Nutrition Reviews. 70 (6): 357–66. doi:10.1111/j.1753-4887.2012.00479.x. PMID 22646128. 
  8. ^ a b "Niacinamide: Indications, Side Effects, Warnings - Drugs.com". www.drugs.com. Retrieved 29 December 2016. 
  9. ^ Burtis CA, Ashwood ER, Bruns DE (2012). Tietz Textbook of Clinical Chemistry and Molecular Diagnostics (5th ed.). Elsevier Health Sciences. p. 934. ISBN 978-1-4557-5942-2. 
  10. ^ Sneader W (2005). Drug Discovery: A History. John Wiley & Sons. p. 231. ISBN 978-0-470-01552-0. 
  11. ^ a b c "Vitamins, 11. Niacin (Nicotinic Acid, Nicotinamide)". Ullmann's encyclopedia of industrial chemistry (6th ed.). Weinheim: Wiley-VCH. 2015. ISBN 978-3-527-30385-4. 
  12. ^ "WHO Model List of Essential Medicines (19th List)" (PDF). World Health Organization. April 2015. Retrieved 8 December 2016. 
  13. ^ Pitche, Palokinam T. (2005-07-01). "[Pellagra]". Sante (Montrouge, France). 15 (3): 205–208. ISSN 1157-5999. PMID 16207585. 
  14. ^ Niren NM (January 2006). "Pharmacologic doses of nicotinamide in the treatment of inflammatory skin conditions: a review". Cutis. 77 (1 Suppl): 11–6. PMID 16871774. 
  15. ^ Tanno O, Ota Y, Kitamura N, Katsube T, Inoue S (September 2000). "Nicotinamide increases biosynthesis of ceramides as well as other stratum corneum lipids to improve the epidermal permeability barrier". The British Journal of Dermatology. 143 (3): 524–31. doi:10.1111/j.1365-2133.2000.03705.x. PMID 10971324. 
  16. ^ Draelos ZD, Matsubara A, Smiles K (June 2006). "The effect of 2% niacinamide on facial sebum production". Journal of Cosmetic and Laser Therapy. 8 (2): 96–101. doi:10.1080/14764170600717704. PMID 16766489. 
  17. ^ Kim J, Ochoa MT, Krutzik SR, Takeuchi O, Uematsu S, Legaspi AJ, Brightbill HD, Holland D, Cunliffe WJ, Akira S, Sieling PA, Godowski PJ, Modlin RL (August 2002). "Activation of toll-like receptor 2 in acne triggers inflammatory cytokine responses". Journal of Immunology. 169 (3): 1535–41. doi:10.4049/jimmunol.169.3.1535. PMID 12133981. 
  18. ^ Burtis CA, Ashwood ER, Bruns DE (2012). Tietz Textbook of Clinical Chemistry and Molecular Diagnostics (5th ed.). Elsevier Health Sciences. p. 934. ISBN 978-1-4557-5942-2. 
  19. ^ "Final report of the safety assessment of niacinamide and niacin". International Journal of Toxicology. 24 Suppl 5: 1–31. 2005. doi:10.1080/10915810500434183. PMID 16596767. 
  20. ^ "Chemistry Tutorial: Aromaticity" (PDF). UCLA Chemistry. Retrieved March 13, 2017. 
  21. ^ "Illustrated Glossary of Organic Chemistry - Trivalent". web.chem.ucla.edu. Retrieved 2017-03-14. 
  22. ^ "Illustrated Glossary of Organic Chemistry - Formal charge". web.chem.ucla.edu. Retrieved 2017-03-14. 
  23. ^ "Structural Biochemistry/Organic Chemistry/Organic Functional Group/Amide - Wikibooks, open books for an open world". en.wikibooks.org. Retrieved 2017-02-21. 
  24. ^ "How to Determine Conjugation" (PDF). UCLA Chemistry. March 13, 2017. 
  25. ^ "Chapter 7- Cellular Respiration" (PDF). Citrus College. March 13, 2017. 
  26. ^ Belenky P, Bogan KL, Brenner C (January 2007). "NAD+ metabolism in health and disease" (PDF). Trends in Biochemical Sciences. 32 (1): 12–9. doi:10.1016/j.tibs.2006.11.006. PMID 17161604. 
  27. ^ Williams, Cartwright, and Ramsden (February 20, 2017). "Parkinson's disease: the first common neurological disease due to auto-intoxication?". QJM. 
  28. ^ "Oxidative Phosphorylation". www.chemistry.wustl.edu. Retrieved 2017-03-14. 
  29. ^ "Oxidative Phosphorylation". www.chemistry.wustl.edu. Retrieved 2017-03-14. 
  30. ^ Rolfe HM (December 2014). "A review of nicotinamide: treatment of skin diseases and potential side effects". Journal of Cosmetic Dermatology. 13 (4): 324–8. doi:10.1111/jocd.12119. PMID 25399625. 
  31. ^ "Nicotinamide | DermNet New Zealand". www.dermnetnz.org. Retrieved 2017-03-24. 
  32. ^ British Pharmacopoeia Commission Secretariat (2009). "Index, BP 2009" (PDF). Retrieved 4 February 2010. 
  33. ^ "Japanese Pharmacopoeia, Fifteenth Edition" (PDF). 2006. Retrieved 4 February 2010. 
  34. ^ a b Chen AC, Damian DL (August 2014). "Nicotinamide and the skin". The Australasian Journal of Dermatology. 55 (3): 169–75. doi:10.1111/ajd.12163. PMID 24635573. 
  35. ^ Definition of niacinamide, National Cancer Institute
  36. ^ Namazi, Mohammad Reza (2003-08-01). "Nicotinamide: a potential addition to the anti-psoriatic weaponry". The FASEB Journal. 17 (11): 1377–1379. doi:10.1096/fj.03-0002hyp. ISSN 0892-6638. PMID 12890690. 

External links[edit]

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