nicotinic acid amide
|AHFS/Drugs.com||Consumer Drug Information|
|by mouth, topical|
|CompTox Dashboard (EPA)|
|Chemical and physical data|
|Molar mass||122.127 g·mol−1|
|3D model (JSmol)|
|Density||1.40 g/cm3 g/cm3|
|Melting point||129.5 °C (265.1 °F)|
|Boiling point||334 °C (633 °F)|
Nicotinamide (NAM), also known as niacinamide, is a form of vitamin B3 found in food and used as a dietary supplement and medication. 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. As a cream, it is used to treat acne.
Side effects are minimal. At high doses liver problems may occur. Normal amounts are safe for use during pregnancy. Nicotinamide is in the vitamin B family of medications, specifically the vitamin B3 complex. It is an amide of nicotinic acid. Foods that contain nicotinamide include yeast, meat, milk, and green vegetables.
Nicotinamide was discovered between 1935 and 1937. It is on the World Health Organization's List of Essential Medicines, the most effective and safe medicines needed in a health system. Nicotinamide is available as a generic medication and over the counter. In the United Kingdom a 60 g tube costs the NHS about £7.10. Commercially, nicotinamide is made from either nicotinic acid or nicotinonitrile. In a number of countries grains have nicotinamide added to them.
Nicotinamide increases the biosynthesis of ceramides in human keratinocytes in vitro and improves the epidermal permeability barrier in vivo. The application of 2% topical nicotinamide for 2 and 4 weeks has been found to be effective in lowering the sebum excretion rate. Nicotinamide has been shown to prevent Cutibacterium acnes-induced activation of toll-like receptor 2, which ultimately results in the down-regulation of pro-inflammatory interleukin-8 production.
The structure of nicotinamide consists of a pyridine ring to which a primary amide group is attached in the meta position. It is an amide of nicotinic acid. As an aromatic compound, it undergoes electrophilic substitution reactions and transformations of its two functional groups. Examples of these reactions reported in Organic Syntheses include the preparation of 2-chloronicotinonitrile by a two-step process via the N-oxide,
The hydrolysis of nicotinonitrile is catalysed by the enzyme nitrile hydratase from Rhodococcus rhodochrous J1, producing 3500 tons per annum of nicotinamide for use in animal feed. The enzyme allows for a more selective synthesis as further hydrolysis of the amide to nicotinic acid is avoided. Nicotinamide can also be made from nicotinic acid. According to Ullmann's Encyclopedia of Industrial Chemistry, worldwide 31,000 tons of nicotinamide were sold in 2014.
Nicotinamide, as a part of the coenzyme nicotinamide adenine dinucleotide (NADH / NAD+) is crucial to life. In cells, nicotinamide is incorporated into NAD+ and nicotinamide adenine dinucleotide phosphate (NADP+). NAD+ and NADP+ are coenzymes in a wide variety of enzymatic oxidation-reduction reactions, most notably glycolysis, the citric acid cycle, and the electron transport chain. 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.
NAD+ acts as an electron carrier that helps with the interconversion of energy between nutrients and the cell's energy currency, adenosine triphosphate (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.
When one mole of NADH is oxidized, 158.2 kJ of energy will be released.
Nicotinamide occurs as a component of a variety of biological systems, including within the vitamin B family and specifically the vitamin B3 complex. It is also a critically important part of the structures of NADH and NAD+, where the N-substituted aromatic ring in the oxidised NAD+ form undergoes reduction with hydride attack to form NADH. The NADPH/NADP+ structures have the same ring, and are involved in similar biochemical reactions.
Nicotinamide occurs in trace amounts mainly in meat, fish, nuts, and mushrooms, as well as to a lesser extent in some vegetables. It is commonly added to cereals and other foods. Many multivitamins contain 20–30 mg of vitamin B3 and it is also available in higher doses.
A 2015 trial found nicotinamide to reduce the rate of new nonmelanoma skin cancers and actinic keratoses in a group of people at high risk for the conditions.
Niacinamide may be beneficial in treating psoriasis.
There is tentative evidence for a potential role of nicotinamide in treating acne, rosacea, autoimmune blistering disorders, ageing skin, and atopic dermatitis. Niacinamide also inhibits poly(ADP-ribose) polymerases (PARP-1), enzymes involved in the rejoining of DNA strand breaks induced by radiation or chemotherapy. ARCON (accelerated radiotherapy plus carbogen inhalation and nicotinamide) has been studied in cancer.
- "Niacinamide Use During Pregnancy". Drugs.com. Archived from the original on December 30, 2016. Retrieved December 29, 2016.
- Record in the GESTIS Substance Database of the Institute for Occupational Safety and Health
- Bender DA (2003). Nutritional Biochemistry of the Vitamins. Cambridge University Press. p. 203. ISBN 978-1-139-43773-8. Archived from the original on 2016-12-30.
- WHO Model Formulary 2008 (PDF). World Health Organization. 2009. pp. 496, 500. ISBN 978-924-154765-9. Archived (PDF) from the original on December 13, 2016. Retrieved December 8, 2016.
- British National Formulary: BNF 69 (69th ed.). British Medical Association. 2015. p. 822. ISBN 978-0-85711-156-2.
- Knip M, Douek IF, Moore WP, Gillmor HA, McLean AE, Bingley PJ, Gale EA (November 2000). "Safety of high-dose nicotinamide: a review" (PDF). Diabetologia. 43 (11): 1337–45. doi:10.1007/s001250051536. PMID 11126400.
- 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.
- "Niacinamide: Indications, Side Effects, Warnings". Drugs.com. June 6, 2017. Archived from the original on August 5, 2017. Retrieved June 30, 2017.
- Krutmann J, Humbert P (2010). Nutrition for Healthy Skin: Strategies for Clinical and Cosmetic Practice. Springer Science & Business Media. p. 153. ISBN 9783642122644. Archived from the original on 2017-04-10.
- 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. Archived from the original on 2016-12-30.
- Sneader W (2005). Drug Discovery: A History. John Wiley & Sons. p. 231. ISBN 978-0-470-01552-0. Archived from the original on 2016-12-30.
- Blum, René (2015). "Vitamins, 11. Niacin (Nicotinic Acid, Nicotinamide)". Vitamins, 11. Niacin (Nicotinic Acid, Nicotinamide. Ullmann's Encyclopedia of Industrial Chemistry (6th ed.). Weinheim: Wiley-VCH. pp. 1–9. doi:10.1002/14356007.o27_o14.pub2. ISBN 978-3-527-30385-4.
- "WHO Model List of Essential Medicines (19th List)" (PDF). WHO Model List of Essential Medicines. World Health Organization. 2015. Archived (PDF) from the original on December 13, 2016. Retrieved December 8, 2016.
- Schmidberger JW, Hepworth LJ, Green AP, Flitsch SL (2015). "Enzymatic Synthesis of Amides". In Faber K, Fessner W, Turner NJ (eds.). Biocatalysis in Organic Synthesis 1. Science of Synthesis. Georg Thieme Verlag. pp. 329–372. Archived from the original on 2017-11-05.
- 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.
- 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.
- 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.
- Kim J, Ochoa MT, Krutzik SR, Takeuchi O, Uematsu S, Legaspi AJ, et al. (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. PMC 4636337. PMID 12133981.
- Snaidr VA, Damian DL, Halliday GM (February 2019). "Nicotinamide for photoprotection and skin cancer chemoprevention: A review of efficacy and safety". Experimental Dermatology. 28 Suppl 1: 15–22. doi:10.1111/exd.13819. PMID 30698874.
- Taylor EC, Crovetti AJ (1957). "Nicotinamide-1-oxide". Organic Syntheses. 37: 63. doi:10.15227/orgsyn.037.0063.; Collective Volume, 4, p. 704
- Taylor EC, Crovetti AJ (1957). "2-Chloronicitinonitrile". Organic Syntheses. 37: 12. doi:10.15227/orgsyn.037.0012.; Collective Volume, 4, p. 166
- Teague PC, Short WA (1953). "Nicotinonitrile". Organic Syntheses. 33: 52. doi:10.15227/orgsyn.033.0052.; Collective Volume, 4, p. 706
- Allen CF, Wolf CN (1950). "3-Aminopyridine". Organic Syntheses. 30: 3. doi:10.15227/orgsyn.030.0003.; Collective Volume, 4, p. 45
- Nagasawa T, Mathew CD, Mauger J, Yamada H (July 1988). "Nitrile Hydratase-Catalyzed Production of Nicotinamide from 3-Cyanopyridine in Rhodococcus rhodochrous J1". Applied and Environmental Microbiology. 54 (7): 1766–9. PMID 16347686. Archived from the original on 2017-11-05.
- Hilterhaus L, Liese A (2007). "Building Blocks". In Ulber R, Sell D (eds.). White Biotechnology. Advances in Biochemical Engineering/Biotechnology. Advances in Biochemical Engineering / Biotechnology. 105. Springer Science & Business Media. pp. 133–173. doi:10.1007/10_033. ISBN 9783540456957. PMID 17408083. Archived from the original on 2017-11-05.
- Asano Y (2015). "Hydrolysis of Nitriles to Amides". In Faber K, Fessner W, Turner NJ (eds.). Biocatalysis in Organic Synthesis 1. Science of Synthesis. Georg Thieme Verlag. pp. 255–276. Archived from the original on 2017-11-05.
- Petersen M, Kiener A (1999). "Biocatalysis". Green Chem. 1 (2): 99–106. doi:10.1039/A809538H.
- Servi S, Tessaro D, Hollmann F (2015). "Historical Perspectives: Paving the Way for the Future". In Faber K, Fessner W, Turner NJ (eds.). Biocatalysis in Organic Synthesis 1. Science of Synthesis. Georg Thieme Verlag. pp. 1–39. Archived from the original on 2017-11-05.
- 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. Archived (PDF) from the original on 2007-09-27.
- Williams AC, Cartwright LS, Ramsden DB (March 2005). "Parkinson's disease: the first common neurological disease due to auto-intoxication?". QJM. 98 (3): 215–26. doi:10.1093/qjmed/hci027. PMID 15728403.
- Casiday R, Herman C, Frey R (September 5, 2008). "Energy for the Body: Oxidative Phosphorylation". www.chemistry.wustl.edu. Department of Chemistry, Washington University in St. Louis. Archived from the original on November 22, 2016. Retrieved March 14, 2017.
- 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.
- Ranaweera, Anoma (2017). "Nicotinamide". DermNet New Zealand (www.dermnetnz.org). DermNet New Zealand Trust. Archived from the original on March 25, 2017. Retrieved June 30, 2017.
- British Pharmacopoeia Commission Secretariat (2009). Index, BP 2009 (PDF). Archived from the original (PDF) on July 22, 2011. Retrieved February 4, 2010.
- Japanese Pharmacopoeia (PDF) (15th ed.). 2006. Archived from the original (PDF) on July 22, 2011. Retrieved February 4, 2010.
- Minocha R, Damian DL, Halliday GM (January 2018). "Melanoma and nonmelanoma skin cancer chemoprevention: A role for nicotinamide?". Photodermatology, Photoimmunology & Photomedicine. 34 (1): 5–12. doi:10.1111/phpp.12328. PMID 28681504.
- 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.
- Namazi MR (August 2003). "Nicotinamide: a potential addition to the anti-psoriatic weaponry". FASEB Journal. 17 (11): 1377–9. doi:10.1096/fj.03-0002hyp. PMID 12890690.
- "Definition of niacinamide". NCI Drug Dictionary. National Cancer Institute. 2011-02-02. Archived from the original on April 28, 2015. Retrieved June 30, 2017.
- Kaanders JH, Bussink J, van der Kogel AJ (December 2002). "ARCON: a novel biology-based approach in radiotherapy". The Lancet. Oncology. 3 (12): 728–37. doi:10.1016/s1470-2045(02)00929-4. PMID 12473514.