Editing Nicotinamide

{{Short description|Dietary supplement and medication}}
{{Use dmy dates|date=March 2023}}
{{cs1 config|name-list-style=vanc|display-authors=6}}
{{Infobox drug
| image              = Nicotinamid.svg
| image_class        = skin-invert-image
| width              = 
| alt                = 
| image2             = Nicotinamide-from-xtal-2011-Mercury-3D-sf.png
| image_class2       = bg-transparent
| width2             = 
| alt2               = 
| caption            =

<!-- Clinical data -->
| pronounce          = {{IPAc-en|ˌ|n|aɪ|ə|ˈ|s|ɪ|n|ə|m|aɪ|d}}, {{IPAc-en|ˌ|n|ɪ|k|ə|ˈ|t|ɪ|n|ə|m|aɪ|d}}
| tradename          = 
| Drugs.com          = {{Drugs.com|cdi|niacinamide}}
| MedlinePlus        = 
| DailyMedID         = Niacinamide
| pregnancy_AU       = <!-- A/B1/B2/B3/C/D/X -->
| pregnancy_AU_comment = 
| pregnancy_category = 
| routes_of_administration = [[Oral administration|oral]], [[Topical administration|topical]]
| class              = 
| ATC_prefix         = A11
| ATC_suffix         = HA01
| ATC_supplemental   =

| legal_AU           = <!-- S2, S3, S4, S5, S6, S7, S8, S9 or Unscheduled-->
| legal_AU_comment   = 
| legal_CA           = <!-- OTC, Rx-only, Schedule I, II, III, IV, V, VI, VII, VIII -->
| legal_CA_comment   = 
| legal_DE           = <!-- Anlage I, II, III or Unscheduled-->
| legal_DE_comment   = 
| legal_NZ           = <!-- Class A, B, C -->
| legal_NZ_comment   = 
| legal_UK           = <!-- GSL, P, POM, CD, CD Lic, CD POM, CD No Reg POM, CD (Benz) POM, CD (Anab) POM or CD Inv POM / Class A, B, C -->
| legal_UK_comment   = 
| legal_US           = OTC
| legal_US_comment   = 
| legal_UN           = <!-- N I, II, III, IV / P I, II, III, IV-->
| legal_UN_comment   = 
| legal_status       = <!--For countries not listed above-->

<!-- Pharmacokinetic data -->
| bioavailability    = 
| protein_bound      = 
| metabolism         = 
| metabolites        = 
| onset              = 
| elimination_half-life = 
| duration_of_action = 
| excretion          =

<!-- Identifiers -->
| CAS_number         = 98-92-0
| CAS_supplemental   = {{cascite|correct|CAS}}
| PubChem            = 936
| IUPHAR_ligand      = 
| DrugBank           = DB02701
| ChemSpiderID       = 911
| UNII               = 25X51I8RD4
| KEGG               = D00036
| ChEBI              = 17154
| ChEMBL             = 1140
| NIAID_ChemDB       = 
| synonyms           = NAM, 3-pyridinecarboxamide<br />niacinamide ([[United States Adopted Name|USAN]] {{abbr|US|United States}})<br />nicotinic acid amide<br />vitamin PP<br />nicotinic amide<br />vitamin B<sub>3</sub>

<!-- Chemical and physical data -->
| IUPAC_name         = pyridine-3-carboxamide
| C                  = 6
| H                  = 6
| N                  = 2
| O                  = 1
| SMILES             = c1cc(cnc1)C(=O)N
| StdInChI           = 1S/C6H6N2O/c7-6(9)5-2-1-3-8-4-5/h1-4H,(H2,7,9)
| StdInChIKey        = DFPAKSUCGFBDDF-UHFFFAOYSA-N
| density            = 1.40 g/cm<sup>3</sup>
| density_notes      = <ref name=GESTIS>{{GESTIS|ZVG=40300}}</ref>
| melting_point      = 129.5
| melting_high       = 
| melting_notes      = 
| boiling_point      = 334
| boiling_notes      = 
| solubility         = 
| specific_rotation  = 
}}

<!-- Definition and medical uses -->
'''Nicotinamide''' ([[International nonproprietary name|INN]], [[British Approved Name|BAN]] {{abbr|UK|United Kingdom}}<ref name="Martindale37">{{Cite book | vauthors = Sweetman SC |url= https://archive.org/details/martindalecomple0000unse_37ed/page/2116/mode/2up?q=nicotinamide <!-- don't remove ?q=nicotinamide tag, it is required to unlock the page without login --> |title=Martindale: the complete drug reference |date=2011 |publisher=Pharmaceutical press |isbn=978-0-85369-933-0 |edition=37 |location=London |page=2117 |language=en |oclc=1256529676}}</ref>) or '''niacinamide''' ([[United States Adopted Name|USAN]] {{abbr|US|United States}}) is a form of [[vitamin B3|vitamin B<sub>3</sub>]] found in food and used as a [[dietary supplement]] and medication.<ref>{{cite book| vauthors = Bender DA |title = Nutritional Biochemistry of the Vitamins|year = 2003|publisher = [[Cambridge University Press]]|isbn = 978-1-139-43773-8|page = 203|url = https://books.google.com/books?id=umylV1Jbm4EC&pg=PA203|url-status = live|archive-url = https://web.archive.org/web/20161230000447/https://books.google.ca/books?id=umylV1Jbm4EC&pg=PA203|archive-date = 30 December 2016}}</ref><ref name = WHO2008 /><ref name = BNF69>{{cite book|title = British National Formulary: BNF 69|year = 2015|publisher = [[British Medical Association]]|isbn = 978-0-85711-156-2|page = 822|edition = 69th}}</ref> As a supplement, it is used [[oral administration|orally]] (swallowed by mouth) to prevent and treat [[pellagra]] (niacin deficiency).<ref name=WHO2008/> While [[nicotinic acid]] (niacin) may be used for this purpose, nicotinamide has the benefit of not causing [[Flushing (physiology)|skin flushing]].<ref name=WHO2008>{{cite book | title = WHO Model Formulary 2008 | year = 2009 | isbn = 978-92-4-154765-9 | vauthors = ((World Health Organization)) | veditors = Stuart MC, Kouimtzi M, Hill SR | hdl = 10665/44053 | author-link = World Health Organization | publisher = World Health Organization | hdl-access=free |pages = 496, 500 }}</ref> As a cream, it is used to treat [[acne]], and has been observed in clinical studies to improve the appearance of aging skin by reducing [[hyperpigmentation]] and redness.<ref name=BNF69/><ref>{{cite journal | vauthors = Bissett DL, Oblong JE, Berge CA | title = Niacinamide: A B vitamin that improves aging facial skin appearance | journal = Dermatologic Surgery | volume = 31 | issue = 7 Pt 2 | pages = 860–5; discussion 865 | date = July 2005 | pmid = 16029679 | doi = 10.1111/j.1524-4725.2005.31732 }}</ref> It is a [[Water-soluble vitamins|water-soluble vitamin]].

<!-- Side effects and mechanism -->
Side effects are minimal.<ref name=Kn2000/><ref name=Mac2012>{{cite journal | vauthors = MacKay D, Hathcock J, Guarneri E | title = Niacin: chemical forms, bioavailability, and health effects | journal = Nutrition Reviews | volume = 70 | issue = 6 | pages = 357–66 | date = June 2012 | pmid = 22646128 | doi = 10.1111/j.1753-4887.2012.00479.x | doi-access = free }}</ref> At high doses, [[liver problems]] may occur.<ref name=Kn2000/> Normal amounts are safe for use during [[pregnancy]].<ref name=Preg2016>{{cite web|title = Niacinamide Use During Pregnancy|website = [[Drugs.com]]|url = https://www.drugs.com/pregnancy/niacinamide.html|access-date = 29 December 2016|url-status = live|archive-url = https://web.archive.org/web/20161230002412/https://www.drugs.com/pregnancy/niacinamide.html|archive-date = 30 December 2016}}</ref> Nicotinamide is in the [[vitamin B]] family of medications, specifically the [[vitamin B3 complex|vitamin B<sub>3</sub> complex]].<ref name=CDI2016>{{cite web|title = Niacinamide: Indications, Side Effects, Warnings|website = [[Drugs.com]]|url = https://www.drugs.com/cdi/niacinamide.html|date = 6 June 2017|access-date = 30 June 2017|url-status = live|archive-url = https://web.archive.org/web/20170805061933/https://www.drugs.com/cdi/niacinamide.html|archive-date = 5 August 2017}}</ref><ref name=Healthy-Skin>{{cite book| vauthors = Krutmann J, Humbert P |title = Nutrition for Healthy Skin: Strategies for Clinical and Cosmetic Practice|year = 2010|publisher = [[Springer Science & Business Media]]|isbn = 978-3-642-12264-4|page = 153|url = https://books.google.com/books?id=rUNZHmpBu2sC&pg=PA153|url-status = live|archive-url = https://web.archive.org/web/20170410213829/https://books.google.ca/books?id=rUNZHmpBu2sC&pg=PA153|archive-date = 10 April 2017}}</ref> It is an [[amide]] of nicotinic acid.<ref name=Kn2000>{{cite journal | vauthors = Knip M, Douek IF, Moore WP, Gillmor HA, McLean AE, Bingley PJ, Gale EA | s2cid = 24763480 | title = Safety of high-dose nicotinamide: a review | journal = Diabetologia | volume = 43 | issue = 11 | pages = 1337–45 | date = November 2000 | pmid = 11126400 | doi = 10.1007/s001250051536 | url = https://link.springer.com/content/pdf/10.1007%2Fs001250051536.pdf | doi-access = free | title-link = doi | access-date = 20 April 2018 | archive-date = 22 September 2017 | archive-url = https://web.archive.org/web/20170922055550/https://link.springer.com/content/pdf/10.1007%2Fs001250051536.pdf | url-status = live }}</ref> Foods that contain nicotinamide include [[yeast]], [[meat]], milk, and [[green vegetables]].<ref>{{cite book| vauthors = Burtis CA, Ashwood ER, Bruns DE |title = Tietz Textbook of Clinical Chemistry and Molecular Diagnostics|year = 2012|publisher = [[Elsevier Health Sciences]]|isbn = 978-1-4557-5942-2|page = 934|edition = 5th|url = https://books.google.com/books?id=BBLRUI4aHhkC&pg=PA934|url-status = live|archive-url = https://web.archive.org/web/20161230230446/https://books.google.ca/books?id=BBLRUI4aHhkC&pg=PA934|archive-date = 30 December 2016}}</ref>

<!-- History and culture -->
Nicotinamide was discovered between 1935 and 1937.<ref>{{cite book| vauthors = Sneader W |title = Drug Discovery: A History|year = 2005|publisher = [[John Wiley & Sons]]|isbn = 978-0-470-01552-0|page = 231|url = https://books.google.com/books?id=jglFsz5EJR8C&pg=PA231|url-status = live|archive-url = https://web.archive.org/web/20161230002103/https://books.google.ca/books?id=jglFsz5EJR8C&pg=PA231|archive-date = 30 December 2016}}</ref><ref name=Ullmann2015/> It is on the [[WHO Model List of Essential Medicines|World Health Organization's List of Essential Medicines]].<ref name="WHO21st">{{cite book | vauthors = ((World Health Organization)) | title = World Health Organization model list of essential medicines: 21st list 2019 | year = 2019 | hdl = 10665/325771 | author-link = World Health Organization | publisher = World Health Organization | location = Geneva | id = WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO | hdl-access=free }}</ref><ref name="WHO22nd">{{cite book | vauthors = ((World Health Organization)) | title = World Health Organization model list of essential medicines: 22nd list (2021) | year = 2021 | hdl = 10665/345533 | author-link = World Health Organization | publisher = World Health Organization | location = Geneva | id = WHO/MHP/HPS/EML/2021.02 | hdl-access=free }}</ref> Nicotinamide is available as a [[generic medication]] and [[over the counter]].<ref name=CDI2016/> Commercially, nicotinamide is made from either [[Niacin (substance)|nicotinic acid]] (niacin) or [[nicotinonitrile]].<ref name = Ullmann2015/><ref name = Synthesis2015 /> In some countries, [[food grains|grains]] have nicotinamide added to them.<ref name=Ullmann2015>{{cite encyclopedia|encyclopedia = [[Ullmann's Encyclopedia of Industrial Chemistry]]|year = 2015|publisher = [[Wiley-VCH]]|location = Weinheim|isbn = 978-3-527-30385-4|edition = 6th|title = Vitamins, 11. Niacin (Nicotinic Acid, Nicotinamide|pages = 1–9| vauthors = Blum R |doi = 10.1002/14356007.o27_o14.pub2|chapter = Vitamins, 11. Niacin (Nicotinic Acid, Nicotinamide)}}</ref>

Extra-terrestrial nicotinamide has been found in [[carbonaceous chondrite]] meteorites.<ref name="Oba2022">{{cite journal | vauthors = Oba Y, Takano Y, Furukawa Y, Koga T, Glavin DP, Dworkin JP, Naraoka H | title = Identifying the wide diversity of extraterrestrial purine and pyrimidine nucleobases in carbonaceous meteorites | journal = Nature Communications | volume = 13 | issue = 1 | pages = 2008 | date = April 2022 | pmid = 35473908 | pmc = 9042847 | doi = 10.1038/s41467-022-29612-x }}</ref>

== Medical uses ==

=== Niacin deficiency ===
Nicotinamide is the preferred treatment for [[pellagra]], caused by niacin deficiency.<ref name="WHO2008" />

=== Acne ===
Nicotinamide [[Cream (pharmaceutical)|cream]] is used as a treatment for [[acne]].<ref name="BNF69" /> It has anti-inflammatory actions, which may benefit people with inflammatory skin conditions.<ref>{{cite journal | vauthors = Niren NM | title = Pharmacologic doses of nicotinamide in the treatment of inflammatory skin conditions: a review | journal = Cutis | volume = 77 | issue = 1 Suppl | pages = 11–6 | date = January 2006 | pmid = 16871774 }}</ref>

Nicotinamide increases the biosynthesis of [[ceramide]]s in human [[keratinocyte]]s in vitro and improves the epidermal permeability barrier in vivo.<ref>{{cite journal | vauthors = Tanno O, Ota Y, Kitamura N, Katsube T, Inoue S | title = Nicotinamide increases biosynthesis of ceramides as well as other stratum corneum lipids to improve the epidermal permeability barrier | journal = The British Journal of Dermatology | volume = 143 | issue = 3 | pages = 524–31 | date = September 2000 | pmid = 10971324 | doi = 10.1111/j.1365-2133.2000.03705.x | s2cid = 21874670 }}</ref> The application of 2% topical nicotinamide for 2 and 4 weeks has been found to be effective in lowering the [[Sebaceous gland|sebum]] excretion rate.<ref>{{cite journal | vauthors = Draelos ZD, Matsubara A, Smiles K | s2cid = 36713665 | title = The effect of 2% niacinamide on facial sebum production | journal = Journal of Cosmetic and Laser Therapy | volume = 8 | issue = 2 | pages = 96–101 | date = June 2006 | pmid = 16766489 | doi = 10.1080/14764170600717704 }}</ref> Nicotinamide has been shown to prevent ''[[Cutibacterium acnes]]''-induced activation of [[TLR2|toll-like receptor 2]], which ultimately results in the down-regulation of pro-inflammatory [[Interleukin 8|interleukin-8]] production.<ref>{{cite journal | vauthors = 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 | title = Activation of toll-like receptor 2 in acne triggers inflammatory cytokine responses | journal = Journal of Immunology | volume = 169 | issue = 3 | pages = 1535–41 | date = August 2002 | pmid = 12133981 | pmc = 4636337 | doi = 10.4049/jimmunol.169.3.1535 }}</ref>

=== Skin cancer ===
Nicotinamide at doses of 500 to 1000{{nbsp}}mg a day decreases the risk of [[skin cancer]]s, other than [[melanoma]], in those at high risk.<ref>{{cite journal | vauthors = Snaidr VA, Damian DL, Halliday GM | title = Nicotinamide for photoprotection and skin cancer chemoprevention: A review of efficacy and safety | journal = Experimental Dermatology | volume = 28 | issue = Suppl 1 | pages = 15–22 | date = February 2019 | pmid = 30698874 | doi = 10.1111/exd.13819 | doi-access = free | title-link = doi }}</ref>

== Side effects ==
Nicotinamide has minimal side effects.<ref name=Kn2000/><ref name=Mac2012 /> At very high doses above 3g/ day acute [[liver toxicity]] has been documented in at least one case.<ref name=Kn2000/> Normal doses are safe during [[pregnancy]].<ref name=Preg2016 />

== Chemistry ==
The structure of nicotinamide consists of a [[pyridine]] ring to which a [[primary amide]] group is attached in the [[arene substitution pattern|''meta'']] position. It is an [[amide]] of [[nicotinic acid]].<ref name=Kn2000/> As an [[aromatic compound]], it undergoes [[electrophilic aromatic substitution|electrophilic substitution]] reactions and transformations of its two [[functional group]]s. Examples of these reactions reported in ''[[Organic Syntheses]]'' include the preparation of [[2-chloronicotinonitrile]] by a two-step process via the [[N-oxide|''N''-oxide]],<ref>{{OrgSynth|title = Nicotinamide-1-oxide|year = 1957|volume = 37|pages = 63|doi = 10.15227/orgsyn.037.0063| vauthors = Taylor EC, Crovetti AJ |collvol = 4|collvolpages = 704|prep = CV4P0704}}</ref><ref>{{OrgSynth|title = 2-Chloronicitinonitrile|year = 1957|volume = 37|pages = 12|doi = 10.15227/orgsyn.037.0012| vauthors = Taylor EC, Crovetti AJ |collvol = 4|collvolpages = 166|prep = CV4P0166}}</ref>

:[[File:Nicotinamide to 2-chloronicotinonitrile.png|500px|class=skin-invert-image]]

from [[nicotinonitrile]] by reaction with [[phosphorus pentoxide]],<ref>{{OrgSynth|title = Nicotinonitrile|year = 1953|volume = 33|pages = 52|doi = 10.15227/orgsyn.033.0052| vauthors = Teague PC, Short WA |collvol = 4|collvolpages = 706|prep = CV4P0706}}</ref> and from [[3-aminopyridine]] by reaction with a solution of [[sodium hypobromite]], prepared ''in situ'' from [[bromine]] and [[sodium hydroxide]].<ref>{{OrgSynth|title = 3-Aminopyridine|year = 1950|volume = 30|pages = 3|doi = 10.15227/orgsyn.030.0003| vauthors = Allen CF, Wolf CN |collvol = 4|collvolpages = 45|prep = CV4P0045}}</ref>
[[File:Nicotinamide highlighted in NAD+.svg|thumb|right|class=skin-invert-image|NAD<sup>+</sup>, the oxidized form of [[nicotinamide adenine dinucleotide|NADH]], contains the nicotinamide [[moiety (chemistry)|moiety]] (highlighted in red)]]

===Industrial production===
The hydrolysis of [[nicotinonitrile]] is catalysed by the enzyme [[nitrile hydratase]] from ''[[Rhodococcus rhodochrous]]'' J1,<ref>{{cite journal | vauthors = Nagasawa T, Mathew CD, Mauger J, Yamada H | title = Nitrile Hydratase-Catalyzed Production of Nicotinamide from 3-Cyanopyridine in Rhodococcus rhodochrous J1 | journal = Applied and Environmental Microbiology | volume = 54 | issue = 7 | pages = 1766–1769 | date = July 1988 | pmid = 16347686 | pmc = 202743 | doi = 10.1128/AEM.54.7.1766-1769.1988 | bibcode = 1988ApEnM..54.1766N }}</ref><ref>{{cite book|title = White Biotechnology| veditors = Ulber R, Sell D |chapter = Building Blocks|volume = 105|series = Advances in Biochemical Engineering / Biotechnology|isbn = 978-3-540-45695-7|doi = 10.1007/10_033|pmid = 17408083|pages = 133–173|chapter-url = https://books.google.com/books?id=_tXoG93OWHgC&pg=PA141|publisher = [[Springer Science & Business Media]]|year = 2007|url-status = live|archive-url = https://web.archive.org/web/20171105201921/https://books.google.com.au/books?id=_tXoG93OWHgC&pg=PA141|archive-date = 5 November 2017 | vauthors = Hilterhaus L, Liese A |s2cid = 34552222}}</ref><ref name=Synthesis2015>{{cite book|title = Biocatalysis in Organic Synthesis 1|series = Science of Synthesis|publisher = [[Georg Thieme Verlag]]|year = 2015|chapter = Enzymatic Synthesis of Amides| vauthors = Schmidberger JW, Hepworth LJ, Green AP, Flitsch SL |pages = 329–372|isbn = 978-3-13-176611-3| veditors  = Faber K, Fessner WD, Turner NJ |chapter-url = https://books.google.com/books?id=8h_wBgAAQBAJ&pg=PA362|url-status = live|archive-url = https://web.archive.org/web/20171105201921/https://books.google.com.au/books?id=8h_wBgAAQBAJ&pg=PA362|archive-date = 5 November 2017}}</ref> producing 3500 tons per annum of nicotinamide for use in animal feed.<ref>{{cite book|title = Biocatalysis in Organic Synthesis 1|series = Science of Synthesis|publisher = [[Georg Thieme Verlag]]|year = 2015|chapter = Hydrolysis of Nitriles to Amides|vauthors = Asano Y |pages = 255–276|isbn = 978-3-13-176611-3| veditors = Faber K, Fessner WD, Turner NJ |chapter-url = https://books.google.com/books?id=8h_wBgAAQBAJ&pg=PA256|url-status = live|archive-url = https://web.archive.org/web/20171105201921/https://books.google.com.au/books?id=8h_wBgAAQBAJ&pg=PA256|archive-date = 5 November 2017}}</ref> The enzyme allows for a more selective synthesis as further hydrolysis of the amide to [[nicotinic acid]] is avoided.<ref>{{cite journal|title = Biocatalysis| vauthors = Petersen M, Kiener A |doi = 10.1039/A809538H|journal = [[Green Chem.]]|year = 1999|volume = 1|issue = 2|pages = 99–106}}</ref><ref>{{cite book|title = Biocatalysis in Organic Synthesis 1|series = Science of Synthesis|publisher = [[Georg Thieme Verlag]]|year = 2015|chapter = Historical Perspectives: Paving the Way for the Future | vauthors = Servi S, Tessaro D, Hollmann F |pages = 1–39|isbn = 978-3-13-176611-3 | veditors = Faber NJ, Fessner WD, Turner K |chapter-url = https://books.google.com/books?id=8h_wBgAAQBAJ&pg=PA7|url-status = live|archive-url = https://web.archive.org/web/20171105201921/https://books.google.com.au/books?id=8h_wBgAAQBAJ&pg=PA7|archive-date = 5 November 2017}}</ref> 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.<ref name=Ullmann2015/>

=== Biochemistry ===
[[File:NAD+ Oxidation and Reduction.png|thumb|upright=1.3|class=skin-invert-image|The active Nicotinamide group on the molecule NAD<sup>+</sup> undergoes oxidation in many metabolic pathways.]]
Nicotinamide, as a part of the cofactor [[nicotinamide adenine dinucleotide]] (NADH / NAD<sup>+</sup>) is crucial to life. In cells, nicotinamide is incorporated into NAD<sup>+</sup> and [[nicotinamide adenine dinucleotide phosphate]] (NADP<sup>+</sup>). NAD<sup>+</sup> and NADP<sup>+</sup> are [[Cofactor (biochemistry)|cofactor]]s in a wide variety of enzymatic [[redox|oxidation-reduction]] reactions, most notably [[glycolysis]], the [[citric acid cycle]], and the [[electron transport chain]].<ref name="Belenky">{{cite journal | vauthors = Belenky P, Bogan KL, Brenner C | title = NAD+ metabolism in health and disease | journal = Trends in Biochemical Sciences | volume = 32 | issue = 1 | pages = 12–9 | date = January 2007 | pmid = 17161604 | doi = 10.1016/j.tibs.2006.11.006 | url = http://www.dartmouth.edu/~brenner/belenky07a.pdf | archive-url = https://web.archive.org/web/20070927170330/http://www.dartmouth.edu/~brenner/belenky07a.pdf | url-status = live | archive-date = 27 September 2007 }}</ref> 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<sup>+</sup>. This method of creation of NAD<sup>+</sup> is called a [[Salvage Pathway|salvage pathway]]. However, the human body can produce NAD<sup>+</sup> from the amino acid [[tryptophan]] and niacin without our ingestion of nicotinamide.<ref>{{cite journal | vauthors = Williams AC, Cartwright LS, Ramsden DB | title = Parkinson's disease: the first common neurological disease due to auto-intoxication? | journal = QJM | volume = 98 | issue = 3 | pages = 215–26 | date = March 2005 | pmid = 15728403 | doi = 10.1093/qjmed/hci027 | doi-access = free | title-link = doi }}</ref>

NAD<sup>+</sup> acts as an electron carrier that mediates the interconversion of energy between nutrients and the cell's energy currency, [[adenosine triphosphate]] (ATP). In oxidation-reduction reactions, the active part of the cofactor is the nicotinamide. In NAD<sup>+</sup>, 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<sup>+</sup> 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]].<ref name="Oxidative Phosphorylation">{{cite web|url = http://www.chemistry.wustl.edu/~edudev/LabTutorials/Cytochromes/cytochromes.html|title = Energy for the Body: Oxidative Phosphorylation|website = www.chemistry.wustl.edu|date = 5 September 2008|access-date = 14 March 2017| vauthors = Casiday R, Herman C, Frey R |publisher = Department of Chemistry, [[Washington University in St. Louis]]|url-status = live|archive-url = https://web.archive.org/web/20161122122250/http://www.chemistry.wustl.edu/~edudev/LabTutorials/Cytochromes/cytochromes.html|archive-date = 22 November 2016}}</ref>

When one mole of NADH is oxidized, 158.2{{nbsp}}kJ of energy will be released.<ref name="Oxidative Phosphorylation"/>

=== Biological role ===
Nicotinamide occurs as a component of a variety of biological systems, including within the [[vitamin B]] family and specifically the [[vitamin B3 complex|vitamin B<sub>3</sub> complex]].<ref name="CDI2016" /><ref name="Healthy-Skin" /> It is also a critically important part of the structures of [[nicotinamide adenine dinucleotide|NADH and NAD<sup>+</sup>]], where the ''N''-substituted aromatic ring in the oxidised NAD<sup>+</sup> form undergoes reduction with hydride attack to form NADH.<ref name="Belenky" /> The [[Nicotinamide adenine dinucleotide phosphate|NADPH/NADP<sup>+</sup>]] structures have the same ring, and are involved in similar biochemical reactions.

Nicotinamide can be methylated in the liver to biologically active [[1-Methylnicotinamide]] when there are sufficient methyl donors.

== Food sources ==
Nicotinamide occurs in trace amounts mainly in meat, fish, nuts, and mushrooms, as well as to a lesser extent in some vegetables.<ref>{{cite journal | vauthors = Rolfe HM | s2cid = 28160151 | title = A review of nicotinamide: treatment of skin diseases and potential side effects | journal = Journal of Cosmetic Dermatology | volume = 13 | issue = 4 | pages = 324–8 | date = December 2014 | pmid = 25399625 | doi = 10.1111/jocd.12119 }}</ref> It is commonly added to cereals and other foods. Many multivitamins contain 20–30{{nbsp}}mg of vitamin B<sub>3</sub> and it is also available in higher doses.<ref>{{cite web|url = http://www.dermnetnz.org/topics/nicotinamide/|title = Nicotinamide|website = DermNet New Zealand (www.dermnetnz.org)|publisher = DermNet New Zealand Trust|access-date = 30 June 2017| vauthors = Ranaweera A |year = 2017|url-status = live|archive-url = https://web.archive.org/web/20170325025401/http://www.dermnetnz.org/topics/nicotinamide/|archive-date = 25 March 2017}}</ref>

== Compendial status ==
* [[British Pharmacopoeia]]<ref name=ib29>{{cite book|author = British Pharmacopoeia Commission Secretariat|title = Index, BP 2009|year = 2009|url = http://www.pharmacopoeia.co.uk/pdf/2009_index.pdf|access-date = 4 February 2010|url-status = dead|archive-date = 22 July 2011|archive-url = https://web.archive.org/web/20110722134527/http://www.pharmacopoeia.co.uk/pdf/2009_index.pdf}}</ref>
* [[Japanese Pharmacopoeia]]<ref name=jp15>{{cite book|title = Japanese Pharmacopoeia|edition = 15th|year = 2006|url-status = dead|url = http://jpdb.nihs.go.jp/jp15e/JP15.pdf|access-date = 4 February 2010|archive-date = 22 July 2011|archive-url = https://web.archive.org/web/20110722105441/http://jpdb.nihs.go.jp/jp15e/JP15.pdf}}</ref>

== Research ==
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.<ref>{{cite journal | vauthors = Minocha R, Damian DL, Halliday GM | title = Melanoma and nonmelanoma skin cancer chemoprevention: A{{nbsp}}role for nicotinamide? | journal = Photodermatology, Photoimmunology & Photomedicine | volume = 34 | issue = 1 | pages = 5–12 | date = January 2018 | pmid = 28681504 | doi = 10.1111/phpp.12328 | doi-access = free | title-link = doi }}</ref>

Nicotinamide has been investigated for many additional disorders, including treatment of [[bullous pemphigoid]] and nonmelanoma skin cancers.<ref name = "Chen_2014">{{cite journal | vauthors = Chen AC, Damian DL | title = Nicotinamide and the skin | journal = The Australasian Journal of Dermatology | volume = 55 | issue = 3 | pages = 169–75 | date = August 2014 | pmid = 24635573 | doi = 10.1111/ajd.12163 | s2cid = 45745255 }}</ref>

Nicotinamide may be beneficial in treating psoriasis.<ref>{{cite journal | vauthors = Namazi MR | title = Nicotinamide: a potential addition to the anti-psoriatic weaponry | journal = FASEB Journal | volume = 17 | issue = 11 | pages = 1377–9 | date = August 2003 | pmid = 12890690 | doi = 10.1096/fj.03-0002hyp | doi-access = free | s2cid = 39752891 }}</ref>

There is tentative evidence for a potential role of nicotinamide in treating acne, rosacea, autoimmune blistering disorders, ageing skin, and atopic dermatitis.<ref name = "Chen_2014"/> Nicotinamide also inhibits poly(ADP-ribose) [[polymerase]]s ([[PARP1|PARP-1]]), enzymes involved in the rejoining of DNA strand breaks induced by radiation or chemotherapy.<ref>{{cite web|url = http://www.cancer.gov/drugdictionary/?CdrID=42044|title = Definition of niacinamide|work = NCI Drug Dictionary|publisher = [[National Cancer Institute]]|access-date = 30 June 2017|url-status = live|archive-url = https://web.archive.org/web/20150428051605/http://www.cancer.gov/drugdictionary?cdrid=42044|archive-date = 28 April 2015|date = 2 February 2011}}</ref> ARCON (accelerated radiotherapy plus carbogen inhalation and nicotinamide) has been studied in cancer.<ref name="Kaanders2002">{{cite journal | vauthors = Kaanders JH, Bussink J, van der Kogel AJ | title = ARCON: a novel biology-based approach in radiotherapy | journal = The Lancet. Oncology | volume = 3 | issue = 12 | pages = 728–37 | date = December 2002 | pmid = 12473514 | doi = 10.1016/s1470-2045(02)00929-4 }}</ref>

Research has suggested nicotinamide may play a role in the treatment of [[HIV]].<ref>{{cite news | vauthors=Mandavilli A | title=Patient Is Reported Free of H.I.V., but Scientists Urge Caution | website=The New York Times | date=7 July 2020 | url=https://www.nytimes.com/2020/07/07/health/hiv-remission-brazil.html | access-date=22 September 2020 | archive-date=23 September 2020 | archive-url=https://web.archive.org/web/20200923005235/https://www.nytimes.com/2020/07/07/health/hiv-remission-brazil.html | url-status=live }}</ref>

==Extra-terrestrial occurrence==
Extra-terrestrial nicotinamide has been found in carbonaceous chondrite meteorites. 

{| class="wikitable"
|+ Vitamin B3 vitamers from extra-terrestrial sources
|-
! Meteorite !! Nicotinic acid !! Nicotinamide
|-
| [[Orgueil (meteorite)|Orgueil]]<ref name="Oba2023">{{Cite journal | vauthors = Oba Y, Koga T, Takano Y, Ogawa NO, Ohkouchi N, Sasaki K, Sato H, Glavin DP, Dworkin JP, Naraoka H, Tachibana S, Yurimoto H, Nakamura T, Noguchi T, Okazaki R |date=2023-03-21 |title=Uracil in the carbonaceous asteroid (162173) Ryugu |journal=Nature Communications |language=en |volume=14 |issue=1 |pages=1292 |doi=10.1038/s41467-023-36904-3 |pmid=36944653 |bibcode=2023NatCo..14.1292O |s2cid=257641373 |issn=2041-1723|doi-access=free |pmc=10030641 }}</ref> || 715ppb || 214ppb
|-
| [[Murray meteorite|Murray]]<ref name="Oba2022"></ref> || 626ppb || 65ppb
|-
| [[Murchison meteorite|Murchison]] || 2.4 nmol/g<ref name=",<ref name="Glavin2025">{{cite journal | vauthors = Glavin DP, Dworkin JP, Alexander CM, Aponte JC, Baczynski AA, Barnes JJ, Bechtel HA, Berger EL, Burton AS, Caselli P, Chung AH, Clemett SJ, Cody GD, Dominguez G, Elsila JE, Farnsworth KK, Foustoukos DI, Freeman KH, Furukawa Y, Gainsforth Z, Graham HV, Grassi T, Giuliano BM, Hamilton VE, Haenecour P, Heck PR, Hofmann AE, House CH, Huang Y, Kaplan HH, Keller LP, Kim B, Koga T, Liss M, McLain HL, Marcus MA, Matney M, McCoy TJ, McIntosh OM, Mojarro A, Naraoka H, Nguyen AN, Nuevo M, Nuth JA, Oba Y, Parker ET, Peretyazhko TS, Sandford SA, Santos E, Schmitt-Kopplin P, Seguin F, Simkus DN, Shahid A, Takano Y, Thomas-Keprta KL, Tripathi H, Weiss G, Zheng Y, Lunning NG, Righter K, Connolly HC, Lauretta DS | title = Abundant ammonia and nitrogen-rich soluble organic matter in samples from asteroid (101955) Bennu | journal = Nature Astronomy | volume = 9 | issue = 2 | pages = 199–210 | date = 2025 | pmid = 39990238 | pmc = 11842271 | doi = 10.1038/s41550-024-02472-9 }}</ref> 190ppb<ref name="Oba2022"></ref> || 16ppb<ref name="Oba2022"></ref>
|-
| [[Tagish Lake (meteorite)|Tagish Lake]]<ref name="Oba2022"></ref> || 108ppb || 5ppb
|}

== References ==
{{Reflist}}

{{Vitamins}}
{{Estrogen receptor modulators}}
{{GABAAR PAMs}}
{{HDAC inhibitors}}
{{Portal bar|Medicine}}
{{Authority control}}

[[Category:Nicotinamides| ]]
[[Category:B vitamins]]
[[Category:CYP2D6 inhibitors]]
[[Category:CYP3A4 inhibitors]]
[[Category:GABAA receptor positive allosteric modulators]]
[[Category:GPER agonists]]
[[Category:World Health Organization essential medicines]]
[[Category:Wikipedia medicine articles ready to translate]]
[[Category:Skin whitening]]