View source for Nicotinic acid

{{Short description|Organic compound and a form of vitamin B3}}
{{Redirect|Niacin|the vitamin group|Vitamin B3|other uses|Niacin (disambiguation)}}
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{{Use dmy dates|date=August 2025}}
{{cs1 config|name-list-style=vanc|display-authors=6}}
{{Chembox
| Watchedfields = changed
| verifiedrevid = 408767536
| ImageFileL1 = Niacin_structure.svg
| ImageFileL1_Ref = {{chemboximage|correct|??}}
| ImageClassL1 = skin-invert
| ImageNameL1 = Kekulé, skeletal formula of nicotinic acid
| ImageFileR1 = Niacin-3D-balls.png  
| ImageClassR1 = bg-transparent    
| ImageFileR1_Ref = {{chemboximage|correct|??}}
| ImageNameR1 = Ball and stick model of nicotinic acid
| PIN = Pyridine-3-carboxylic acid<ref name=iupac2013>{{cite book | title = Nomenclature of Organic Chemistry: IUPAC Recommendations and Preferred Names 2013 (Blue Book) | publisher = [[Royal Society of Chemistry]] | date = 2014 | location = Cambridge | pages = 648–1047 | doi = 10.1039/9781849733069-00648 | isbn = 978-0-85404-182-4| chapter = Chapter P-6. Applications to Specific Classes of Compounds }}</ref>
| pronounce = {{IPAc-en|ˈ|n|aɪ|ə|s|ɪ|n}}
| OtherNames = {{ubl
 | Niacin ([[United States Adopted Name|USAN]] {{abbr|US|United States}})<ref name="Martindale37">{{Cite book |vauthors = Sweetman SC |url= https://archive.org/details/martindalecomple0000unse_37ed/page/2116/mode/2up?q=niacin <!-- ?q=niacin 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>
 | Bionic
 | Vitamin B<sub>3</sub>
 | Vitamin PP
 }}
|Section1={{Chembox Identifiers
| CASNo = 59-67-6
| CASNo_Ref = {{cascite|correct|CAS}}
| PubChem = 938
| ChemSpiderID = 913
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| UNII = 2679MF687A
| UNII_Ref = {{fdacite|correct|FDA}}
| EINECS = 200-441-0
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank = DB00627
| KEGG = D00049
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG1_Ref = {{keggcite|correct|kegg}}
| KEGG1 = C00253
| MeSHName = Niacin
| ChEBI_Ref = {{ebicite|correct|EBI}}
| ChEBI = 15940
| ChEMBL = 573
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| IUPHAR_ligand = 1588
| RTECS = QT0525000

| Beilstein = 109591
| Gmelin = 3340
| 3DMet = B00073
| SMILES = OC(=O)c1cccnc1
| StdInChI = 1S/C6H5NO2/c8-6(9)5-2-1-3-7-4-5/h1-4H,(H,8,9)
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| InChI = 1/C6H5NO2/c8-6(9)5-2-1-3-7-4-5/h1-4H,(H,8,9)
| StdInChIKey = PVNIIMVLHYAWGP-UHFFFAOYSA-N
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| InChIKey = PVNIIMVLHYAWGP-UHFFFAOYAA
}}
|Section2={{Chembox Properties
| C=6 | H=5 | N=1 | O=2
| Appearance = White, translucent crystals
| MeltingPtK = 510
| Density = 1.473 g cm<sup>−3</sup>
| Solubility = 18 g L<sup>−1</sup>
| LogP = 0.219
| pKa = 2.0, 4.85
| IsoelectricPt = 4.75
| RefractIndex = 1.4936
| Dipole = 0.1271305813 D{{citation needed|date=February 2023}}
}}
|Section5={{Chembox Thermochemistry
| DeltaHf = −344.9 kJ mol<sup>−1</sup>
| DeltaHc = −2.73083 MJ mol<sup>−1</sup>
}}
|Section6={{Chembox Pharmacology
| ATCCode_prefix = C04
| ATCCode_suffix = AC01
| ATC_Supplemental = {{ATC|C10|BA01}} {{ATC|C10|AD02}} {{ATC|C10|AD52}}
| Licence_EU=yes
| INN_EMA=Nicotinic acid
| AdminRoutes = Intramuscular, by mouth
| HalfLife = 20–45 min
}}
|Section7={{Chembox Hazards
| GHSPictograms = {{GHS07}}
| GHSSignalWord = Warning
| HPhrases = {{H-phrases|319}}
| PPhrases = {{P-phrases|264|280|305+351+338|337+313|501}}
| NFPA-H = 1
| NFPA-F = 1
| NFPA-R = 0
| FlashPtC = 193
| AutoignitionPtC = 365
}}
}}
{{Infobox drug
| container_only = yes
| drug_name         = 
| INN               = Nicotinic acid
| type              = <!-- empty -->
| image             = 
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| caption           = 
| USAN              = 
| INN_EMA           = Nicotinic acid

<!-- Clinical data -->
| pronounce         = 
| tradename         = Niacor, Niaspan, others
| Drugs.com         = {{drugs.com|monograph|niacin}}
| MedlinePlus       = a682518
| DailyMedID        = Niacin
| pregnancy_AU      = 
| pregnancy_AU_comment = Exempt<ref name="Drugs.com pregnancy">{{cite web | title=Niacin Use During Pregnancy | website=Drugs.com | date=29 July 2019 | url=https://www.drugs.com/pregnancy/niacin.html | access-date=4 May 2020 | archive-date=5 August 2020 | archive-url=https://web.archive.org/web/20200805024846/https://www.drugs.com/pregnancy/niacin.html | url-status=live }}</ref>
| pregnancy_category= 
| routes_of_administration = [[Intramuscular]], [[by mouth]]
| class             = 

<!-- Legal status -->
| legal_AU = <!-- S2, S3, S4, S5, S6, S7, S8, S9 or Unscheduled-->
| legal_AU_comment = 
| legal_BR =  <!-- OTC, A1, A2, A3, B1, B2, C1, C2, C3, C4, C5, D1, D2, E, F-->
| legal_BR_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 = /&nbsp;Rx-only
| legal_UN = <!-- N I, II, III, IV / P I, II, III, IV-->
| legal_UN_comment = 
| legal_status      = <!-- For countries not listed above -->

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| ChEBI_Ref         = 
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| ChEMBL_Ref        = 
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| NIAID_ChemDB      = 
| PDB_ligand        = NIO
| synonyms          =

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}}

[[File:Vitamin B3 (Niacine) space filling model.jpg|thumb|class=bg-transparent|Space-filling model of nicotinic acid]]

'''Nicotinic acid''',{{Efn|[[International nonproprietary name]]}} or '''niacin''',{{Efn|Common name in the United States ([[United States Adopted Name|USAN]])}} is an [[organic compound]] and a [[vitamer]] of{{spaces}}[[vitamin B3|vitamin B<sub>3</sub>]], an [[essential nutrient|essential human nutrient]].<ref name="NIH Fact Sheet">{{cite web |title=Niacin Fact Sheet for Health Professionals |publisher=Office of Dietary Supplements, US National Institutes of Health |date=18 November 2022 |url=https://ods.od.nih.gov/factsheets/Niacin-HealthProfessional/ |access-date=12 December 2024}}</ref><ref name="lpi">{{cite web |title=Niacin |url=https://lpi.oregonstate.edu/mic/vitamins/niacin |publisher=Micronutrient Information Center, Linus Pauling Institute, Oregon State University, Corvallis, OR |access-date=16 September 2019 |date=8 October 2018 |archive-date=12 September 2019 |archive-url=https://web.archive.org/web/20190912214545/https://lpi.oregonstate.edu/mic/vitamins/niacin |url-status=live }}</ref> It is produced by plants and animals from the amino acid [[tryptophan]].<ref name="DRItext">{{cite book |last1= Institute of Medicine |title= Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline |chapter= Niacin |publisher= The National Academies Press |year= 1998 |location= Washington, DC |pages= 123–149 |chapter-url= https://www.nap.edu/read/6015/chapter/8 |access-date= 29 August 2018 |isbn= 978-0-309-06554-2 |archive-date= 1 September 2018 |archive-url= https://web.archive.org/web/20180901175650/https://www.nap.edu/read/6015/chapter/8 |url-status= live }}</ref>

Nicotinic acid is also a prescription medication.<ref name=Drugs/> Amounts far in excess of the recommended dietary intake for vitamin functions will lower blood [[triglyceride]]s and [[low-density lipoprotein|low density lipoprotein cholesterol]] (LDL-C), and raise blood [[high density lipoprotein|high density lipoprotein cholesterol]] (HDL-C, often referred to as "good" cholesterol). There are two forms: immediate-release and sustained-release nicotinic acid. Initial prescription amounts are 500&nbsp;mg/day, increased over time until a therapeutic effect is achieved. Immediate-release doses can be as high as 3,000&nbsp;mg/day; sustained-release as high as 2,000&nbsp;mg/day.<ref name=Drugs>{{cite web |url=https://www.drugs.com/niacin.html |title=Niacin |date=16 March 2019 |website=Drugs.com |access-date=27 April 2020 |archive-date=9 June 2020 |archive-url=https://web.archive.org/web/20200609134807/https://www.drugs.com/niacin.html |url-status=live }}</ref> Despite the proven lipid changes, nicotinic acid has not been found useful for decreasing the risk of [[cardiovascular disease]] in those already prescribed a [[statin]] drug.<ref name=Kee2014/> A 2010 review had concluded that nicotinic acid was effective as a mono-therapy,<ref>{{cite journal | vauthors = Bruckert E, Labreuche J, Amarenco P | title = Meta-analysis of the effect of nicotinic acid alone or in combination on cardiovascular events and atherosclerosis | journal = Atherosclerosis | volume = 210 | issue = 2 | pages = 353–61 | date = June 2010 | pmid = 20079494 | doi = 10.1016/j.atherosclerosis.2009.12.023 }}</ref> but a 2017 review incorporating twice as many trials concluded that prescription nicotinic acid, while affecting lipid levels, did not reduce all-cause mortality, cardiovascular mortality, myocardial infarctions, nor fatal or non-fatal strokes.<ref name=Schand2017 /> Prescription nicotinic acid was shown to cause hepatotoxicity<ref name=LiverTox2014 /> and increase risk of [[type 2 diabetes]].<ref name=Ong2014 /><ref name=Goldie2016 /> Nicotinic acid prescriptions in the United States had peaked in 2009 at 9.4{{nbsp}}million,<ref name="ClinCalc Niacin" /> declining to 800{{nbsp}}thousand by 2020.<ref name="ClinCalc Niacin">{{cite web | title = Niacin - Drug Usage Statistics | website = ClinCalc | url = https://clincalc.com/DrugStats/Drugs/Niacin | access-date = 7 October 2022 | archive-date = 8 July 2020 | archive-url = https://web.archive.org/web/20200708061719/https://clincalc.com/DrugStats/Drugs/Niacin | url-status = deviated }}</ref> In 2023, it was the 288th most commonly prescribed medication in the US, with more than 500,000 prescriptions.<ref name="Top 300 of 2023">{{cite web | title=The Top 300 of 2023 | url=https://clincalc.com/DrugStats/Top300Drugs.aspx | website=ClinCalc | access-date=17 August 2025 | archive-date=17 August 2025 | archive-url=https://web.archive.org/web/20250817043812/https://clincalc.com/DrugStats/Top300Drugs.aspx | url-status=live }}</ref><ref name="Niacin Drug Usage Statistics">{{cite web | title = Niacin Drug Usage Statistics, United States, 2014 - 2023 | website = ClinCalc | url = https://clincalc.com/DrugStats/Drugs/Niacin | access-date = 17 August 2025 }}</ref>

Nicotinic acid has the [[chemical formula|formula]] {{chem|C|6|H|5|NO|2}} and belongs to the group of the [[pyridinecarboxylic acids]].<ref name=lpi/> As the [[precursor (chemistry)|precursor]] for [[nicotinamide adenine dinucleotide]] and [[nicotinamide adenine dinucleotide phosphate]], it is involved in DNA repair.<ref name="pmid26828517">{{cite journal | vauthors = Kennedy DO | title = B Vitamins and the Brain: Mechanisms, Dose and Efficacy—A Review | journal = Nutrients | volume = 8 | issue = 2 | page = 68 | date = January 2016 | pmid = 26828517 | pmc = 4772032 | doi = 10.3390/nu8020068 | doi-access = free | title-link = doi }}</ref>

Extra-terrestrial nicotinic acid 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 | article-number = 2008 | date = April 2022 | pmid = 35473908 | pmc = 9042847 | doi = 10.1038/s41467-022-29612-x | bibcode = 2022NatCo..13.2008O }}</ref> and in sample-returns from the asteroids [[162173 Ryugu]]<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=21 March 2023 |title=Uracil in the carbonaceous asteroid (162173) Ryugu |journal=Nature Communications |language=en |volume=14 |issue=1 |article-number=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> and [[101955 Bennu]].<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 | bibcode = 2025NatAs...9..199G }}</ref>

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==Definition==
The term "niacin" was originally coined from "nicotinic acid vitamin", with the goal of distancing the nutrient B3 from the drug [[nicotine]] in [[tobacco]]. As a result, it originally referred to the nutritional entity of [[vitamin B3|vitamin B<sub>3</sub>]].<ref name=JAMA1942a/> However, in [[American English]], the term has also come to mean "nicotinic acid" in the context of high-dose use as a prescription medicine.<ref name=Niaspan /> In other varieties of English, the medicine is only ever called "nicotinic acid".<ref>{{cite web |title=Substances related to nicotinic acid - referral {{!}} European Medicines Agency (EMA) |url=https://www.ema.europa.eu/en/medicines/human/referrals/substances-related-nicotinic-acid |website=www.ema.europa.eu |language=en |date=13 March 2014}}</ref> The term "nicotinic acid" unambiguously refers to the substance and the prescription medicine containing it, which treats [[hyperlipidemia|elevated cholesterol and triglycerides]]. When used as a drug, daily doses range from 500 to 3,000&nbsp;mg/day.<ref name=DailyMed /><ref name=Niaspan /> High-dose nicotinamide does not have this medicinal effect.<ref name=PKIN2020Niacin />

Vitamin B<sub>3</sub> has several [[vitamer]]s that can act in place of each other, including nicotinic acid and nicotinamide. It is precursor of the coenzymes [[nicotinamide adenine dinucleotide]] (NAD) and [[nicotinamide adenine dinucleotide phosphate]] (NADP). These compounds are coenzymes for many dehydrogenases, participating in many hydrogen transfer processes. NAD is important in [[catabolism]] of fat, carbohydrate, protein, and alcohol, as well as cell signaling and DNA repair, and NADP mostly in [[anabolism]] reactions such as fatty acid and cholesterol synthesis.<ref name=PKIN2020Niacin/> Vitamin intake recommendations made by several countries are that intakes of 14–18&nbsp;mg/day are sufficient to meet the needs of healthy adults.<ref name="DRItext" /><ref name="EFSAtext">{{cite web| title = Overview on Dietary Reference Values for the EU population as derived by the EFSA Panel on Dietetic Products, Nutrition and Allergies| year = 2017| url = https://www.efsa.europa.eu/sites/default/files/assets/DRV_Summary_tables_jan_17.pdf| access-date = 31 August 2017| archive-date = 28 August 2017| archive-url = https://web.archive.org/web/20170828082247/https://www.efsa.europa.eu/sites/default/files/assets/DRV_Summary_tables_jan_17.pdf| url-status = live}}</ref>
<ref name=AusNZ>{{cite web|url = http://www.nhmrc.gov.au/_files_nhmrc/file/publications/synopses/n35.pdf|title = Nutrient reference values for Australia and New Zealand|access-date = 19 June 2018|date = 9 September 2005|work = National Health and Medical Research Council|archive-url = https://web.archive.org/web/20170121003340/https://www.nhmrc.gov.au/_files_nhmrc/file/publications/synopses/n35.pdf|archive-date = 21 January 2017}}</ref> Nicotinic acid and [[nicotinamide]] are both used for prevention and treatment of [[pellagra]], a disease caused by lack of the vitamin.<ref name=Hegyi2004>{{cite journal | vauthors = Hegyi J, Schwartz RA, Hegyi V | title = Pellagra: dermatitis, dementia, and diarrhea | journal = International Journal of Dermatology | volume = 43 | issue = 1 | pages = 1–5 | date = January 2004 | pmid = 14693013 | doi = 10.1111/j.1365-4632.2004.01959.x | s2cid = 33877664 | doi-access = free }}</ref><ref name=PKIN2020Niacin>{{cite book |vauthors=Penberthy WT, Kirkland JB |title = Present Knowledge in Nutrition | edition = Eleventh |chapter = Niacin | veditors = Marriott BP, Birt DF, Stallings VA, Yates AA |publisher = Academic Press (Elsevier) |year=2020 |location = London, United Kingdom |pages = 209–24 |isbn=978-0-323-66162-1}}</ref>

==As a dietary supplement==
In the United States, nicotinic acid is sold as a non-prescription dietary supplement with a range of 100 to 1000&nbsp;mg per serving. These products often have a Structure/Function health claim<ref name=SFclaim>{{cite web |url=https://www.fda.gov/food/food-labeling-nutrition/structurefunction-claims |title=Structure/Function Claims |date=December 2017 |website=U.S. Food & Drug Administration |access-date=30 June 2020 |archive-date=10 June 2020 |archive-url=https://web.archive.org/web/20200610032745/https://www.fda.gov/food/food-labeling-nutrition/structurefunction-claims }}</ref> allowed by the US Food & Drug Administration (FDA). An example would be "Supports a healthy blood lipid profile." The American Heart Association strongly advises against the substitution of dietary supplement nicotinic acid for prescription nicotinic acid because of potentially serious side effects, which means that nicotinic acid should only be used under the supervision of a health care professional, and because manufacture of dietary supplement nicotinic acid is not as well-regulated by the FDA as prescription nicotinic acid.<ref name=AHA>{{cite web |url=https://www.heart.org/en/health-topics/cholesterol/prevention-and-treatment-of-high-cholesterol-hyperlipidemia/cholesterol-medications |title=Cholesterol Medications |date=10 November 2018 |website=American Heart Association |access-date=8 May 2020 |archive-date=5 April 2020 |archive-url=https://web.archive.org/web/20200405090134/https://www.heart.org/en/health-topics/cholesterol/prevention-and-treatment-of-high-cholesterol-hyperlipidemia/cholesterol-medications |url-status=live }}</ref> More than 30&nbsp;mg nicotinic acid consumed as a dietary supplement can cause skin flushing. Face, arms and chest skin turns a reddish color because of vasodilation of small subcutaneous blood vessels, accompanied by sensations of heat, tingling and itching. These signs and symptoms are typically transient, lasting minutes to hours; they are considered unpleasant rather than toxic.<ref name="NIH Fact Sheet" />

==As lipid-modifying medication==
Prescription nicotinic acid, commonly labeled as niacin in the United States, is available in immediate-release and slow-release formulations. It is used to treat primary [[hyperlipidemia]] and [[hypertriglyceridemia]].<ref name=DailyMed /><ref name=Niaspan /> It is used either as a monotherapy or in combination with other lipid-modifying drugs. Dosages start at 500&nbsp;mg/day and are often gradually increased to as high as 3000&nbsp;mg/day for immediate release or 2000&nbsp;mg/day for slow release (also referred to as sustained release) to achieve the targeted lipid changes (lower LDL-C and triglycerides, and higher HDL-C).<ref name=DailyMed>{{cite web |url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=ce739d68-d89c-437c-90fb-3c0c45140f22 |title=NIACOR-niacin tablet |date=March 2020 |website=DAILYMED, US National Library of Medicine |access-date=9 May 2020 |archive-date=9 August 2020 |archive-url=https://web.archive.org/web/20200809105743/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=ce739d68-d89c-437c-90fb-3c0c45140f22 |url-status=live }}</ref><ref name=Niaspan>{{cite web |url=http://www.rxabbott.com/pdf/niaspan.pdf |archive-url=https://ghostarchive.org/archive/20221009/http://www.rxabbott.com/pdf/niaspan.pdf |archive-date=9 October 2022 |url-status=live |title=Niaspan Patient Package and Product Information (PPPI) |date= December 2018 |access-date=9 May 2020}}</ref> Prescriptions in the US peaked in 2009, at 9.4{{nbsp}}million<ref name="ClinCalc Niacin" /> and had declined to 800{{nbsp}}thousand by 2020.<ref name="ClinCalc Niacin" /> In 2023, it was the 288th most commonly prescribed medication in the United States, with more than 500,000 prescriptions.<ref name="Top 300 of 2023" /><ref name="Niacin Drug Usage Statistics" />

Systematic reviews found no effect of prescription nicotinic acid on all-cause mortality, cardiovascular mortality, myocardial infarctions, nor fatal or non-fatal strokes despite raising [[high-density lipoprotein|HDL]] cholesterol in patients already taking statins.<ref name=Kee2014>{{cite journal | vauthors = Keene D, Price C, Shun-Shin MJ, Francis DP | title = Effect on cardiovascular risk of high density lipoprotein targeted drug treatments niacin, fibrates, and CETP inhibitors: meta-analysis of randomised controlled trials including 117,411 patients | journal = BMJ | volume = 349 | article-number = g4379 | date = July 2014 | pmid = 25038074 | pmc = 4103514 | doi = 10.1136/bmj.g4379 }}</ref><ref name=Mani2015>{{cite journal |vauthors=Mani P, Rohatgi A |title=Niacin Therapy, HDL Cholesterol, and Cardiovascular Disease: Is the HDL Hypothesis Defunct? |journal=Curr Atheroscler Rep |volume=17 |issue=8 |article-number=43 |date=August 2015 |pmid=26048725 |pmc=4829575 |doi=10.1007/s11883-015-0521-x }}</ref> Reported side effects include an increased risk of new-onset type 2 diabetes.<ref name=Schand2017>{{cite journal | vauthors = Schandelmaier S, Briel M, Saccilotto R, Olu KK, Arpagaus A, Hemkens LG, Nordmann AJ | title = Niacin for primary and secondary prevention of cardiovascular events | journal = The Cochrane Database of Systematic Reviews | volume = 2017 | article-number = CD009744 | date = June 2017 | issue = 6 | pmid = 28616955 | doi = 10.1002/14651858.CD009744.pub2 | pmc = 6481694 }}</ref><ref name=Ong2014 /><ref name=Goldie2016 /><ref>{{cite journal | vauthors = Garg A, Sharma A, Krishnamoorthy P, Garg J, Virmani D, Sharma T, Stefanini G, Kostis JB, Mukherjee D, Sikorskaya E | title = Role of Niacin in Current Clinical Practice: A Systematic Review | journal = The American Journal of Medicine | volume = 130 | issue = 2 | pages = 173–187 | date = February 2017 | pmid = 27793642 | doi = 10.1016/j.amjmed.2016.07.038 | doi-access = free }}</ref>

===Mechanisms===
Nicotinic acid reduces synthesis of low-density lipoprotein cholesterol (LDL-C), very low-density lipoprotein cholesterol (VLDL-C), [[lipoprotein(a)]] and [[triglycerides]], and increases [[high-density lipoprotein]] cholesterol (HDL-C).<ref name="Villines, T. C. 2012 p 14">{{cite journal | vauthors = Villines TC, Kim AS, Gore RS, Taylor AJ | s2cid = 27925461 | title = Niacin: the evidence, clinical use, and future directions | journal = Current Atherosclerosis Reports | volume = 14 | issue = 1 | pages = 49–59 | date = February 2012 | pmid = 22037771 | doi = 10.1007/s11883-011-0212-1 }}</ref> The lipid-therapeutic effects of nicotinic acid are partly mediated through the activation of [[G protein-coupled receptor]]s, including [[hydroxycarboxylic acid receptor 2]] (HCA<sub>2</sub>)and [[hydroxycarboxylic acid receptor 3]] (HCA<sub>3</sub>), which are highly expressed in [[adipose tissue|body fat]].<ref>{{cite journal | vauthors = Soga T, Kamohara M, Takasaki J, Matsumoto S, Saito T, Ohishi T, Hiyama H, Matsuo A, Matsushime H, Furuichi K |title = Molecular identification of nicotinic acid receptor | journal = Biochemical and Biophysical Research Communications | volume = 303 | issue = 1 | pages = 364–9 | date = March 2003 | pmid = 12646212 | doi = 10.1016/S0006-291X(03)00342-5 |bibcode = 2003BBRC..303..364S }}</ref><ref>{{cite journal | vauthors = Wise A, Foord SM, Fraser NJ, Barnes AA, Elshourbagy N, Eilert M, Ignar DM, Murdock PR, Steplewski K, Green A, Brown AJ, Dowell SJ, Szekeres PG, Hassall DG, Marshall FH, Wilson S, Pike NB | title = Molecular identification of high and low affinity receptors for nicotinic acid | journal = The Journal of Biological Chemistry | volume = 278 | issue = 11 | pages = 9869–74 | date = March 2003 | pmid = 12522134 | doi = 10.1074/jbc.M210695200 | doi-access = free }}</ref> HCA<sub>2</sub> and HCA<sub>3</sub> inhibit [[cyclic adenosine monophosphate]] (cAMP) production and thus suppress the release of free [[fatty acids]] (FFAs) from body fat, reducing their availability to the liver to synthesize the blood-circulating lipids in question.<ref name="Gille, A. 2008">{{cite journal | vauthors = Gille A, Bodor ET, Ahmed K, Offermanns S | title = Nicotinic acid: pharmacological effects and mechanisms of action | journal = Annual Review of Pharmacology and Toxicology | volume = 48 | issue = 1 | pages = 79–106 | year = 2008 | pmid = 17705685 | doi = 10.1146/annurev.pharmtox.48.113006.094746 }}</ref><ref>{{cite journal | vauthors = Wanders D, Judd RL | title = Future of GPR109A agonists in the treatment of dyslipidaemia | journal = Diabetes, Obesity & Metabolism | volume = 13 | issue = 8 | pages = 685–91 | date = August 2011 | pmid = 21418500 | doi = 10.1111/j.1463-1326.2011.01400.x | s2cid = 205536280 }}</ref><ref name=Costet2010>{{cite journal |vauthors=Costet P |title=Molecular pathways and agents for lowering LDL-cholesterol in addition to statins |journal=Pharmacol Ther |volume=126 |issue=3 |pages=263–78 |date=June 2010 |pmid=20227438 |doi=10.1016/j.pharmthera.2010.02.006 }}</ref> A decrease in free fatty acids also suppresses liver expression of [[apolipoprotein C3]] and [[PPARGC1B|PPARg coactivator-1b]], thus increasing VLDL-C turnover and reducing its production.<ref>{{cite journal | vauthors = Hernandez C, Molusky M, Li Y, Li S, Lin JD | title = Regulation of hepatic ApoC3 expression by PGC-1β mediates hypolipidemic effect of nicotinic acid | journal = Cell Metabolism | volume = 12 | issue = 4 | pages = 411–9 | date = October 2010 | pmid = 20889132 | pmc = 2950832 | doi = 10.1016/j.cmet.2010.09.001 }}</ref> Nicotinic acid also directly inhibits the action of [[diacylglycerol O-acyltransferase 2]] (DGAT2) a key enzyme for triglyceride synthesis.<ref name=Costet2010/>

The mechanism behind nicotinic acid increasing HDL-C is not totally understood, but seems to occur in various ways. Nicotinic acid increases [[apolipoprotein A1]] levels by inhibiting the breakdown of this protein, which is a component of HDL particles.<ref>{{cite journal |vauthors=Malik S, Kashyap ML |s2cid=27918392 |title=Niacin, lipids, and heart disease |journal=Curr Cardiol Rep |volume=5 |issue=6 |pages=470–6 |date=November 2003 |pmid=14558989 |doi=10.1007/s11886-003-0109-x }}</ref><ref>{{cite journal | vauthors = Creider JC, Hegele RA, Joy TR | s2cid = 22526314 | title = Niacin: another look at an underutilized lipid-lowering medication | journal = Nature Reviews. Endocrinology | volume = 8 | issue = 9 | pages = 517–28 | date = September 2012 | pmid = 22349076 | doi = 10.1038/nrendo.2012.22 }}</ref> It also inhibits HDL-C hepatic uptake by suppressing production of the [[cholesterol ester transfer protein]] (CETP) gene.<ref name="Villines, T. C. 2012 p 14"/> It stimulates the [[ABCA1|ABCA1 transporter]] in monocytes and macrophages and [[Downregulation and upregulation|upregulates]] [[peroxisome proliferator-activated receptor gamma]], resulting in reverse cholesterol transport.<ref>{{cite journal | vauthors = Rubic T, Trottmann M, Lorenz RL | title = Stimulation of CD36 and the key effector of reverse cholesterol transport ATP-binding cassette A1 in monocytoid cells by niacin | journal = Biochemical Pharmacology | volume = 67 | issue = 3 | pages = 411–9 | date = February 2004 | pmid = 15037193 | doi = 10.1016/j.bcp.2003.09.014 }}</ref>

===Combined with statins===
Extended release nicotinic acid was combined with [[lovastatin]] (Advicor), and with [[simvastatin]] (Simcor), as prescription drug combinations. The combination niacin/lovastatin was approved by the US [[Food and Drug Administration]] (FDA) in 2001.<ref name=Advicor>{{cite web |url=https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/21-249_Advicor.cfm |title=Drug Approval Package: Advicor (Niacin Extended-Release & Lovastatin) NDA #21-249 |date=13 September 2002 |website=U.S. [[Food and Drug Administration]] (FDA) |access-date=17 May 2020 |archive-date=4 August 2020 |archive-url=https://web.archive.org/web/20200804174117/https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/21-249_Advicor.cfm |url-status=live }}</ref> The combination niacin/simvastatin was approved by the FDA in 2008.<ref>{{cite web | title=Drug Approval Package: Simcor (Niacin/Simvastatin) NDA #022078 | website=U.S. [[Food and Drug Administration]] (FDA) | date=31 July 2008 | url=https://www.accessdata.fda.gov/drugsatfda_docs/nda/2008/022078s000TOC.cfm | access-date=14 November 2022 | archive-date=14 November 2022 | archive-url=https://web.archive.org/web/20221114011457/https://www.accessdata.fda.gov/drugsatfda_docs/nda/2008/022078s000TOC.cfm | url-status=live }}</ref><ref name=Simcor>{{Cite press release |url=https://www.drugs.com/newdrugs/abbott-receives-fda-approval-simcor-niaspan-simvastatin-novel-combination-medicine-comprehensive-846.html | work = Drugs.com | title = Abbott Receives FDA Approval for Simcor (Niaspan / simvastatin), a Novel Combination Medicine for Comprehensive Cholesterol Management |access-date=15 March 2008 |archive-date=5 August 2020 |archive-url=https://web.archive.org/web/20200805074725/https://www.drugs.com/newdrugs/abbott-receives-fda-approval-simcor-niaspan-simvastatin-novel-combination-medicine-comprehensive-846.html |url-status=live }}</ref> Subsequently, large outcome trials using these nicotinic acid and statin therapies were unable to demonstrate incremental benefit of nicotinic acid beyond statin therapy alone.<ref>{{cite journal |vauthors=Toth PP, Murthy AM, Sidhu MS, Boden WE |title=Is HPS2-THRIVE the death knell for niacin? |journal=J Clin Lipidol |volume=9 |issue=3 |pages=343–50 |date=2015 |pmid=26073392 |doi=10.1016/j.jacl.2015.01.008 }}</ref> The FDA withdrew approval of both drugs in 2016. The reason given: "Based on the collective evidence from several large cardiovascular outcome trials, the Agency has concluded that the totality of the scientific evidence no longer supports the conclusion that a drug-induced reduction in triglyceride levels and/or increase in HDL-cholesterol levels in statin-treated patients results in a reduction in the risk of cardiovascular events." The drug company discontinued the drugs.<ref name=FDAWithdrawal>{{cite web |url=https://www.federalregister.gov/documents/2016/04/18/2016-08894/abbvie-inc-withdrawal-of-approval-of-new-drug-applications-for-advicor-and-simcor |title=AbbVie Inc.; Withdrawal of Approval of New Drug Applications for Advicor and Simcor |date=18 April 2016 |website=U.S. Federal Register |access-date=17 May 2020 |archive-date=5 August 2020 |archive-url=https://web.archive.org/web/20200805003411/https://www.federalregister.gov/documents/2016/04/18/2016-08894/abbvie-inc-withdrawal-of-approval-of-new-drug-applications-for-advicor-and-simcor |url-status=live }}</ref>

===Contraindications===
Prescription immediate release (Niacor) and extended release (Niaspan) nicotinic acid are [[contraindicated]] for people with either active or a history of [[liver disease]] because both, but especially Niaspan, have been associated with instances of serious, on occasion fatal, liver failure.<ref name=Niaspan /><ref name="ReferenceB"/> Both products are contraindicated for people with existing [[peptic ulcer disease]], or other bleeding problems because nicotinic acid lowers platelet count and interferes with blood clotting.<ref name=DailyMed /><ref name=Niaspan /><ref name="ReferenceB"/> Both products are also contraindicated for women who are pregnant or expecting to become pregnant because safety during pregnancy has not been evaluated in human trials. These products are contraindicated for women who are lactating because it is known that nicotinic acid is excreted into human milk, but the amount and potential for adverse effects in the nursing infant are not known. Women are advised to either not nurse their child or discontinue the drug. High-dose nicotinic acid has not been tested or approved for use in children under 16 years.<ref name=DailyMed /><ref name=Niaspan /><ref name="ReferenceB">{{cite web | title=Niaspan- niacin tablet, film coated, extended release | website=DailyMed | date=20 August 2013 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=0dd18020-c211-423d-b3d8-a926ae626e14 | access-date=14 November 2022 | archive-date=14 November 2022 | archive-url=https://web.archive.org/web/20221114011459/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=0dd18020-c211-423d-b3d8-a926ae626e14 | url-status=live }}</ref>

===Adverse effects===
The most common adverse effects of medicinal nicotinic acid ({{nowrap|500–3000&nbsp;mg}}) are flushing (e.g., warmth, redness, itching or tingling) of the face, neck and chest, headache, abdominal pain, diarrhea, [[dyspepsia]], nausea, vomiting, [[rhinitis]], [[pruritus]] and rash.<ref name=lpi/><ref name="NIH Fact Sheet" /><ref name="ReferenceB"/> These can be minimized by initiating therapy at low dosages, increasing dosage gradually, and avoiding administration on an empty stomach.<ref name="ReferenceB"/>

The acute adverse effects of high-dose nicotinic acid therapy ({{nowrap|1–3&nbsp;grams per day}}) &ndash; which is commonly used in the treatment of [[hyperlipidemia]]s &ndash; can further include [[hypotension]], fatigue, [[glucose intolerance]] and [[insulin resistance]], heartburn, blurred or impaired vision, and [[macular edema]].<ref name=lpi/><ref name="NIH Fact Sheet" /> With long-term use, the adverse effects of high-dose nicotinic acid therapy (750&nbsp;mg per day) also include [[liver failure]] (associated with fatigue, nausea, and [[loss of appetite]]), [[hepatitis]], and [[acute liver failure]];<ref name=lpi/><ref name="NIH Fact Sheet" /> these hepatotoxic effects of nicotinic acid occur more often when extended-release [[dosage form]]s are used.<ref name=lpi/><ref name="NIH Fact Sheet" /> The long-term use of nicotinic acid at greater than or equal to 2&nbsp;grams per day also significantly increases the [[risk ratio|risk]] of [[cerebral hemorrhage]], [[ischemic stroke]], [[gastrointestinal ulcer]]ation and [[gastrointestinal bleeding|bleeding]], [[diabetes]], [[dyspepsia]], and diarrhea.<ref name="NIH Fact Sheet"/>

====Flushing====
[[Flushing (physiology)|Flushing]] &ndash; a short-term [[vasodilation|dilatation]] of skin [[arteriole]]s, causing reddish skin color &ndash; usually lasts for about 15 to 30 minutes, although sometimes can persist for weeks. Typically, the face is affected, but the reaction can extend to neck and upper chest. The cause is blood vessel dilation<ref name=lpi/><ref name="NIH Fact Sheet" /> due to elevation in prostaglandin GD<sub>2</sub> ([[PGD2]]) and [[serotonin]].<ref name="ReferenceA"/><ref>{{cite journal | vauthors = Benyó Z, Gille A, Kero J, Csiky M, Suchánková MC, Nüsing RM, Moers A, Pfeffer K, Offermanns S | title = GPR109A (PUMA-G/HM74A) mediates nicotinic acid-induced flushing | journal = The Journal of Clinical Investigation | volume = 115 | issue = 12 | pages = 3634–40 | date = December 2005 | pmid = 16322797 | pmc = 1297235 | doi = 10.1172/JCI23626 }}</ref><ref>{{cite journal | vauthors = Benyó Z, Gille A, Bennett CL, Clausen BE, Offermanns S | s2cid = 30199951 | title = Nicotinic acid-induced flushing is mediated by activation of epidermal langerhans cells | journal = Molecular Pharmacology | volume = 70 | issue = 6 | pages = 1844–9 | date = December 2006 | pmid = 17008386 | doi = 10.1124/mol.106.030833 }}</ref><ref>{{cite journal | vauthors = Maciejewski-Lenoir D, Richman JG, Hakak Y, Gaidarov I, Behan DP, Connolly DT | title = Langerhans cells release prostaglandin D2 in response to nicotinic acid | journal = The Journal of Investigative Dermatology | volume = 126 | issue = 12 | pages = 2637–46 | date = December 2006 | pmid = 17008871 | doi = 10.1038/sj.jid.5700586 | doi-access = free }}</ref> Flushing was often thought to involve histamine, but histamine has been shown not to be involved in the reaction.<ref name="ReferenceA">{{cite journal | vauthors = Papaliodis D, Boucher W, Kempuraj D, Michaelian M, Wolfberg A, House M, Theoharides TC | s2cid = 5609632 | title = Niacin-induced "flush" involves release of prostaglandin D2 from mast cells and serotonin from platelets: evidence from human cells in vitro and an animal model | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 327 | issue = 3 | pages = 665–72 | date = December 2008 | pmid = 18784348 | doi = 10.1124/jpet.108.141333 }}</ref> Flushing is sometimes accompanied by a prickly or [[itching]] sensation, in particular, in areas covered by clothing.<ref name="NIH Fact Sheet" />

Prevention of flushing requires altering or blocking the prostaglandin-mediated pathway.<ref name="NIH Fact Sheet" /><ref name="kamanna">{{cite journal | vauthors = Kamanna VS, Kashyap ML | title = Mechanism of action of niacin | journal = The American Journal of Cardiology | volume = 101 | issue = 8A | pages = 20B–26B | date = April 2008 | pmid = 18375237 | doi = 10.1016/j.amjcard.2008.02.029 }}</ref> [[Aspirin]] taken half an hour before the nicotinic acid prevents flushing, as does [[ibuprofen]]. Taking nicotinic acid with meals also helps reduce this side effect.<ref name="NIH Fact Sheet" /> Acquired tolerance will also help reduce flushing; after several weeks of a consistent dose, most people no longer experience flushing.<ref name="NIH Fact Sheet" /> Slow- or "sustained"-release forms of nicotinic acid have been developed to lessen these side effects.<ref name=autogenerated1>{{cite book |author=Katzung, Bertram G. |title=Basic and clinical pharmacology |publisher=McGraw-Hill Medical Publishing Division |location=New York |year=2006 |isbn=978-0-07-145153-6 }}</ref><ref>{{cite journal | title = Options for therapeutic intervention: How effective are the different agents? | journal = European Heart Journal Supplements | volume = 8 | pages = F47–F53 | doi = 10.1093/eurheartj/sul041 | vauthors = Barter P | date = October 2006 | issue = F| doi-access = free }}</ref> Nicotinamide and [[inositol nicotinate]] can be used as no-flush forms of vitamin B<sub>3</sub>, however the efficacy of the latter is dubious.<ref>{{Cite web |title=Niacin: The facts on flushing |url=http://www.dpic.org/article/professional/niacin-facts-flushing |access-date=19 March 2025 |website=www.dpic.org}}</ref>

====Liver damage====
Nicotinic acid in medicinal doses can cause modest elevations in serum [[transaminase]] and unconjugated [[bilirubin]], both biomarkers of liver injury. The increases usually resolve even when drug intake is continued.<ref name=LiverTox2014>{{cite book |title = IN: LiverTox: Clinical and Research Information on Drug-Induced Liver Injury (Internet) |chapter = Niacin |publisher=National Institute of Diabetes and Digestive and Kidney Diseases |pmid=31643504 |date=February 2014 |location = Bethesda, MD }}</ref><ref name="bil1" /><ref name="bil2" /> However, less commonly, the sustained release form of the drug can lead to serious [[hepatotoxicity]], with onset in days to weeks. Early symptoms of serious liver damage include nausea, vomiting and abdominal pain, followed by [[jaundice]] and [[Itch|pruritus]]. The mechanism is thought to be a direct toxicity of elevated serum niacin. Lowering dose or switching to the immediate release form can resolve symptoms. In rare instances the injury is severe, and progresses to liver failure.<ref name=LiverTox2014 />

====Diabetes====
The high doses of nicotinic acid used to treat [[hyperlipidemia]] have been shown to elevate [[blood sugar|fasting blood glucose]] in people with type 2 [[diabetes mellitus|diabetes]].<ref name=Ong2014>{{cite journal |vauthors=Ong KL, Barter PJ, Waters DD |title=Cardiovascular drugs that increase the risk of new-onset diabetes |journal=Am. Heart J. |volume=167 |issue=4 |pages=421–8 |date=April 2014 |pmid=24655688 |doi=10.1016/j.ahj.2013.12.025 |s2cid=205306912 |url=http://www.escholarship.org/uc/item/6gd606b1 |access-date=27 June 2020 |archive-date=28 June 2020 |archive-url=https://web.archive.org/web/20200628180527/https://escholarship.org/uc/item/6gd606b1 |url-status=live |hdl=1959.4/unsworks_43825 |hdl-access=free }}</ref> Long-term nicotinic acid therapy was also associated with an increase in the risk of new-onset type 2 diabetes.<ref name=Ong2014 /><ref name=Goldie2016>{{cite journal | vauthors = Goldie C, Taylor AJ, Nguyen P, McCoy C, Zhao XQ, Preiss D | title = Niacin therapy and the risk of new-onset diabetes: a meta-analysis of randomised controlled trials | journal = Heart | volume = 102 | issue = 3 | pages = 198–203 | date = February 2016 | pmid = 26370223 | pmc = 4752613 | doi = 10.1136/heartjnl-2015-308055 }}</ref>

====Other adverse effects====
High doses of nicotinic acid can also cause niacin [[maculopathy]], a thickening of the [[macula]] and [[retina]], which leads to blurred vision and blindness. This maculopathy is reversible after niacin intake ceases.<ref>{{cite journal |vauthors=Domanico D, Verboschi F, Altimari S, Zompatori L, Vingolo EM |title=Ocular Effects of Niacin: A Review of the Literature |journal=Med Hypothesis Discov Innov Ophthalmol |volume=4 |issue=2 |pages=64–71 |date=2015 |pmid=26060832 |pmc=4458328 }}</ref> Niaspan, the slow-release product, has been associated with a reduction in platelet content and a modest increase in prothrombin time.<ref name=Niaspan />

==Pharmacology==

===Pharmacodynamics===
Activating HCA<sub>2</sub> has effects other than lowering serum cholesterol and triglyceride concentrations: antioxidative, anti-inflammatory, antithrombotic, improved [[endothelium|endothelial]] function and [[atheroma|plaque]] stability, all of which counter development and progression of atherosclerosis.<ref name=Zeman2015>{{cite journal |vauthors=Zeman M, Vecka M, Perlík F, Hromádka R, Staňková B, Tvrzická E, Žák A |title=Niacin in the Treatment of Hyperlipidemias in Light of New Clinical Trials: Has Niacin Lost its Place? |journal=Med. Sci. Monit. |volume=21 |pages=2156–62 |date=July 2015 |pmid=26210594 |pmc=4523006 |doi=10.12659/MSM.893619 }}</ref><ref>{{cite journal | vauthors = Wu BJ, Yan L, Charlton F, Witting P, Barter PJ, Rye KA | title = Evidence that niacin inhibits acute vascular inflammation and improves endothelial dysfunction independent of changes in plasma lipids | journal = Arteriosclerosis, Thrombosis, and Vascular Biology | volume = 30 | issue = 5 | pages = 968–75 | date = May 2010 | pmid = 20167660 | doi = 10.1161/ATVBAHA.109.201129 | doi-access = free }}</ref>

Nicotinic acid [[Enzyme inhibitor|inhibits]] [[cytochrome P450]] enzymes [[CYP2E1]], [[CYP2D6]] and [[CYP3A4]].<ref name = "Gaudineau_2004">{{cite journal | vauthors = Gaudineau C, Auclair K | title = Inhibition of human P450 enzymes by nicotinic acid and nicotinamide | journal = Biochemical and Biophysical Research Communications | volume = 317 | issue = 3 | pages = 950–6 | date = May 2004 | pmid = 15081432 | doi = 10.1016/j.bbrc.2004.03.137 | bibcode = 2004BBRC..317..950G }}</ref> Niacin produces a rise in serum [[Bilirubin#Indirect (unconjugated)|unconjugated bilirubin]] in normal individuals and in those with [[Gilbert's Syndrome]]. However, in the Gilbert's Syndrome, the rise in bilirubin is higher and clearance is delayed longer than in normal people.<ref>{{cite book |title=Nathan and Oski's Hematology of Infancy and Childhood |pages=118–119 |isbn=978-1-4160-3430-8| vauthors = Orkin SH, Nathan DG |date=January 2009 |publisher=Elsevier Health Sciences }}</ref> One test used to aid in diagnosing Gilbert's Syndrome involves intravenous administration of nicotinic acid (niacin) in a dose of 50&nbsp;mg over a period of 30 seconds.<ref name="bil1">{{cite journal | vauthors = Dickey W, McAleer JJ, Callender ME | title = The Nicotinic Acid Provocation Test and Unconjugated Hyperbilirubinaemia | journal = The Ulster Medical Journal | volume = 60 | issue = 1 | pages = 49–52 | date = April 1991 | pmid = 1853497 | pmc = 2448612 }}</ref><ref name="bil2">{{cite journal | vauthors = Röllinghoff W, Paumgartner G, Preisig R | title = Nicotinic Acid Test in the Diagnosis of Gilbert's Syndrome: Correlation With Bilirubin Clearance | journal = Gut | volume = 22 | issue = 8 | pages = 663–668 | date = August 1981 | pmid = 7286783 | pmc = 1420060 | doi = 10.1136/gut.22.8.663 }}</ref>
{{See also|Niacin#Liver_damage}}

===Pharmacokinetics===
Both nicotinic acid and nicotinamide are rapidly absorbed from the stomach and small intestine.<ref>{{cite journal | vauthors = Said HM | title = Intestinal absorption of water-soluble vitamins in health and disease | journal = The Biochemical Journal | volume = 437 | issue = 3 | pages = 357–372 | date = August 2011 | pmid = 21749321 | pmc = 4049159 | doi = 10.1042/BJ20110326 }}</ref> Absorption is facilitated by sodium-dependent diffusion, and at higher intakes, via passive diffusion. Unlike some other vitamins, the percent absorbed does not decrease with increasing dose, so that even at amounts of 3-4 grams, absorption is nearly complete.<ref name=PKIN2020Niacin /> With a one gram dose, peak plasma concentrations of 15 to 30 μg/mL are reached within 30 to 60 minutes. Approximately 88% of an oral pharmacologic dose is eliminated by the kidneys as unchanged nicotinic acid or nicotinuric acid, its primary metabolite. The plasma elimination half-life of nicotinic acid ranges from 20 to 45 minutes.<ref name=DailyMed />

Nicotinic acid and nicotinamide are both converted into the [[coenzyme]] NAD.<ref name="isbn1-57259-153-6">{{cite book | vauthors = Cox M, Lehninger AL, Nelson DR | title = Lehninger principles of biochemistry | publisher = Worth Publishers | location = New York | year = 2000 | isbn = 978-1-57259-153-0 | url-access = registration | url = https://archive.org/details/lehningerprincip01lehn }}</ref> NAD converts to NADP by phosphorylation in the presence of the enzyme [[NAD+ kinase]].  High energy requirements (brain) or high turnover rate (gut, skin) organs are usually the most susceptible to their deficiency.<ref>{{cite journal | vauthors = Ishii N, Nishihara Y | title = Pellagra among chronic alcoholics: clinical and pathological study of 20 necropsy cases | journal = Journal of Neurology, Neurosurgery, and Psychiatry | volume = 44 | issue = 3 | pages = 209–15 | date = March 1981 | pmid = 7229643 | pmc = 490893 | doi = 10.1136/jnnp.44.3.209 }}</ref> In the liver, nicotinamide is converted to storage [[nicotinamide adenine dinucleotide]] (NAD). As needed, liver NAD is hydrolyzed to nicotinamide and nicotinic acid for transport to tissues, there reconverted to NAD to serve as an enzyme cofactor.<ref name=PKIN2020Niacin /> Excess nicotinic acid is methylated in the liver to N<sup>1</sup>-methylnicotinamide (NMN) and excreted in urine as such or as the oxidized metabolites [[N1-Methyl-2-pyridone-5-carboxamide|N<sup>1</sup>-methyl-2-pyridone-5-carboxamide]] and [[N1-Methyl-4-pyridone-3-carboxamide]] (2PY and 4PY). Decreased urinary content of these metabolites is a measure of niacin deficiency.<ref name=PKIN2020Niacin />

==Production==
===Biosynthesis===
[[Image:Tryptophan metabolism.svg|thumb|300px|class=skin-invert-image|Nicotinic acid, [[serotonin]] (5-hydroxytryptamine), and [[melatonin]] [[biosynthesis]] from [[tryptophan]]]]
In addition to absorbing niacin from diet, nicotinic acid can be synthesized from the [[Essential amino acid|essential]] [[amino acid]] [[tryptophan]], a five-step process with the penultimate compound being [[quinolinic acid]] (see figure). Some bacteria and plants utilize [[aspartic acid]] in a pathway that also goes to quinolinic acid.<ref>{{cite journal |vauthors=Foster JW, Moat AG |title= Nicotinamide adenine dinucleotide biosynthesis and pyridine nucleotide cycle metabolism in microbial systems |journal= Microbiol. Rev. |volume= 44 |issue= 1 |pages= 83–105 |date= 1 March 1980 |doi= 10.1128/MMBR.44.1.83-105.1980 |pmid= 6997723 |pmc= 373235}}</ref> For humans, the efficiency of conversion is estimated as requiring 60{{nbsp}}[[gram#SI multiples|mg]] of tryptophan to make 1{{nbsp}}mg of niacin. [[Riboflavin]], [[Vitamin B6|vitamin B<sub>6</sub>]] and [[iron]] are required for the process.<ref name=PKIN2020Niacin /> Pellagra is a consequence of a corn-dominant diet because the niacin in corn is poorly bioavailable and corn proteins are low in tryptophan compared to wheat and rice proteins.<ref name=Carpenter1983>{{cite book |doi=10.1007/978-3-0348-6540-1_12 |chapter=The Relationship of Pellagra to Corn and the Low Availability of Niacin in Cereals |title=Nutritional Adequacy, Nutrient Availability and Needs |series=Experientia Supplementum |year=1983 | vauthors = Carpenter KJ |volume=44 |pages=197–222 |pmid=6357846 |isbn=978-3-0348-6542-5 }}</ref>

===Industrial synthesis===
Nicotinic acid was first synthesized in 1867 by oxidative degradation of [[nicotine]] with [[potassium chromate]] and [[sulfuric acid]]<ref name=Ullmann2015/> — this is the origin of the name.<ref name=JAMA1942a>{{cite journal|title=Niacin and Nicotinic Acid|date=7 March 1942|volume=118|issue=10|doi=10.1001/jama.1942.02830100053014|journal=Journal of the American Medical Association|page=823}}</ref> Nicotinic acid is prepared by hydrolysis of [[nicotinonitrile]], which, as described above, is generated by oxidation of 3-picoline. Oxidation can be effected by air, but [[ammoxidation]] is more efficient. In the latter process, nicotinonitrile is produced by ammoxidation of [[3-methylpyridine]]. [[Nitrile hydratase]] is then used to catalyze nicotinonitrile to nicotinamide, which can be sold directly or converted to nicotinic acid.<ref>{{Ullmann|vauthors=Abe N, Ichimura H, Kataoka T, Morishita S, Shimizu S, Shoji T, Watanabe N |year=2007 |doi=10.1002/14356007.a22_399|title=Pyridine and Pyridine Derivatives|isbn=978-3527306732}}</ref> Alternatively, ammonia, acetic acid and paraldehyde are used to make [[5-Ethyl-2-methyl-pyridine|5-ethyl-2-methyl-pyridine]], which is then oxidized to nicotinic acid.<ref name=LONZA>{{cite journal | vauthors = Eschenmooser W |title=100 Years of Progress with LONZA |journal=CHIMIA |date=June 1997 |volume=51 |issue=6 |pages=259–69 |doi=10.2533/chimia.1997.259 |s2cid=100485418 |doi-access=free }}</ref> New "greener" catalysts are being tested using manganese-substituted aluminophosphates that use acetyl peroxyborate as non-corrosive oxidant, avoiding producing nitrogen oxides as do traditional ammoxidations.<ref>{{cite journal| author = Sarah Everts| title = Clean Catalysis: Environmentally friendly synthesis of niacin generates less inorganic waste| journal = Chemical & Engineering News| year = 2008| issn = 0009-2347}}</ref>

The demand for commercial production includes for animal feed and for food fortification meant for human consumption. According to ''[[Ullmann's Encyclopedia of Industrial Chemistry]]'', worldwide 31,000 tons of nicotinamide were sold in 2014.<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>

===Climate impact===
The production of nicotinic acid creates [[nitrous oxide]] as a by-product, which is a potent greenhouse gas. In 2018, it was discovered that a nicotinic acid factory in [[Visp]], Switzerland, was responsible for around one percent of the country's greenhouse gas emissions.<ref>{{cite web | vauthors = Lenz C | title = The climate disgrace of Visp | newspaper = European Press Prize | year = 2021 | url = https://www.europeanpressprize.com/article/the-climate-disgrace-of-visp/ | access-date = 8 September 2023 | archive-date = 8 September 2023 | archive-url = https://web.archive.org/web/20230908132352/https://www.europeanpressprize.com/article/the-climate-disgrace-of-visp/ | url-status = live }}</ref><ref>{{Cite book | vauthors = Laudert D, Hohmann HP |title=Comprehensive Biotechnology |chapter=Application of Enzymes and Microbes for the Industrial Production of Vitamins and Vitamin-Like Compounds  |date=2011 |publisher=Elsevier |isbn=978-0-444-64047-5 |page=620 |language=en |doi=10.1016/b978-0-444-64046-8.00188-9 |quote=[[Lonza Group|Lonza AG]] of Switzerland produces nicotinic acid in their Swiss production site in Visp, whereas the manufacturing site for the amide is in China, Guangdong Province.}}</ref> Eventually, catalytic scrubbing technology that eliminates most of the emissions was installed in 2021.<ref>{{cite journal | vauthors = Davidson EA, Winiwarter W |title=Urgent abatement of industrial sources of nitrous oxide |journal=Nature Climate Change |date=July 2023 |volume=13 |issue=7 |pages=599–601 |doi=10.1038/s41558-023-01723-3|bibcode=2023NatCC..13..599D }}</ref>

==Chemistry==
This colorless, water-soluble solid is a derivative of [[pyridine]], with a [[carboxyl group]] (COOH) at the 3-position.<ref name=PKIN2020Niacin/> Other forms of vitamin B<sub>3</sub> include the corresponding [[amide]] [[nicotinamide]], where the carboxyl group has been replaced by a [[carboxamide]] group ({{chem|CONH|2}}).<ref name=PKIN2020Niacin/>

==Preparations==
Prescription products can be immediate release (Niacor, 500&nbsp;mg tablets) or [[extended release]] (Niaspan, 500 and 1000&nbsp;mg tablets). Niaspan has a film coating that delays release of the nicotinic acid, resulting in an absorption over a period of 8–12 hours. This reduces [[vasodilation]] and [[flushing (physiology)|flushing]] side effects, but increases the risk of [[hepatotoxicity]] compared to the immediate release drug.<ref>{{cite journal | vauthors = Bassan M | title = A case for immediate-release niacin | journal = Heart & Lung | volume = 41 | issue = 1 | pages = 95–8 | year = 2012 | pmid = 21414665 | doi = 10.1016/j.hrtlng.2010.07.019 }}</ref><ref>{{cite journal | vauthors = Reiche I, Westphal S, Martens-Lobenhoffer J, Tröger U, Luley C, Bode-Böger SM | title = Pharmacokinetics and dose recommendations of Niaspan in chronic kidney disease and dialysis patients | journal = Nephrology, Dialysis, Transplantation | volume = 26 | issue = 1 | pages = 276–82 | date = January 2011 | pmid = 20562093 | doi = 10.1093/ndt/gfq344 | doi-access = free }}</ref>

Prescription nicotinic acid preparations in combination with statin drugs (discontinued) are described above. A combination of niacin and [[laropiprant]] had been approved for use in Europe and marketed as Tredaptive. Laropiprant is a [[prostaglandin D2]] binding drug shown to reduce niacin-induced vasodilation and flushing side effects.<ref name="Villines, T. C. 2012 p 14"/><ref>{{cite journal | vauthors = Lai E, De Lepeleire I, Crumley TM, Liu F, Wenning LA, Michiels N, Vets E, O'Neill G, Wagner JA, Gottesdiener K | title = Suppression of niacin-induced vasodilation with an antagonist to prostaglandin D2 receptor subtype 1 | journal = Clinical Pharmacology and Therapeutics | volume = 81 | issue = 6 | pages = 849–57 | date = June 2007 | pmid = 17392721 | doi = 10.1038/sj.clpt.6100180 | s2cid = 2126240 }}</ref><ref>{{cite journal | vauthors = Paolini JF, Bays HE, Ballantyne CM, Davidson M, Pasternak R, Maccubbin D, Norquist JM, Lai E, Waters MG, Kuznetsova O, Sisk CM, Mitchel YB | title = Extended-release niacin/laropiprant: reducing niacin-induced flushing to better realize the benefit of niacin in improving cardiovascular risk factors | journal = Cardiology Clinics | volume = 26 | issue = 4 | pages = 547–60 | date = November 2008 | pmid = 19031552 | doi = 10.1016/j.ccl.2008.06.007 }}</ref> A clinical trial showed no additional efficacy of Tredaptive in lowering cholesterol when used together with other statin drugs, but did show an increase in other side effects.<ref>{{cite journal |vauthors=Landray MJ, Haynes R, Hopewell JC, Parish S, Aung T, Tomson J, Wallendszus K, Craig M, Jiang L, Collins R, Armitage J |title=Effects of extended-release niacin with laropiprant in high-risk patients |journal=N. Engl. J. Med. |volume=371 |issue=3 |pages=203–12 |date=July 2014 |pmid=25014686 |doi=10.1056/NEJMoa1300955 |s2cid=23548060 |doi-access=free }}</ref> The study resulted in the withdrawal of Tredaptive from the international market.<ref>{{Cite web|url=http://www.medscape.com/viewarticle/777519|title=Niacin/Laropiprant Products to Be Suspended Worldwide|vauthors=Nainggolan L|date=11 January 2013|website=Medscape|access-date=20 February 2017|archive-date=26 April 2015|archive-url=https://web.archive.org/web/20150426032404/http://www.medscape.com/viewarticle/777519|url-status=live}}</ref><ref>{{cite news | url=https://www.reuters.com/article/us-merck-cholesteroldrug-withdrawal-idUSBRE90A0MB20130111?feedType=RSS&feedName=healthNews | work=Reuters | title=Merck begins overseas recall of HDL cholesterol drug | date=11 January 2013 | access-date=6 July 2021 | archive-date=21 April 2023 | archive-url=https://web.archive.org/web/20230421215022/https://www.reuters.com/article/us-merck-cholesteroldrug-withdrawal-idUSBRE90A0MB20130111?feedType=RSS&feedName=healthNews | url-status=live }}</ref>

==History==
{{Further|Vitamin#History}}

Niacin as a chemical compound was first described by chemist [[Hugo Weidel]] in 1873 in his studies of [[nicotine]],<ref>{{cite journal | vauthors = Weidel H | title = Zur Kenntniss des Nicotins | journal = [[Justus Liebigs Annalen der Chemie und Pharmacie]] | year = 1873 | volume = 165 | pages = 330–49 | doi = 10.1002/jlac.18731650212 | issue = 2 | url = https://zenodo.org/record/1427317 | access-date = 3 July 2019 | archive-date = 4 August 2020 | archive-url = https://web.archive.org/web/20200804134952/https://zenodo.org/record/1427317 | url-status = live }}</ref> but that predated by many years the concept of food components other than protein, fat and carbohydrates that were essential for life. Vitamin nomenclature was initially alphabetical, with [[Elmer McCollum]] calling these fat-soluble A and water-soluble B.<ref name=Combs2007 /> Over time, eight chemically distinct, water-soluble B vitamins were isolated and numbered, with niacin as vitamin B<sub>3</sub>.<ref name=Combs2007>{{Cite book|url=https://books.google.com/books?id=1CMHiWum0Y4C&pg=PA16|title=The Vitamins: Fundamental Aspects in Nutrition and Health|edition=3rd|vauthors=Combs GF|date=2007|pages=7–33|publisher=Elsevier, Boston, MA|isbn=978-0-080-56130-1|access-date=30 June 2020|archive-date=13 January 2023|archive-url=https://web.archive.org/web/20230113023205/https://books.google.com/books?id=1CMHiWum0Y4C&pg=PA16|url-status=live}}</ref>

{{Further|Pellagra#History}}
Corn (maize) became a staple food in the southeast United States and in parts of Europe. A disease that was characterized by dermatitis of sunlight-exposed skin was described in Spain in 1735 by [[Gaspar Casal]]. He attributed the cause to poor diet.<ref>{{cite book | vauthors = Casal G |chapter=The natural and medical history of the principality of the Asturias |title=Classic Descriptions of Disease | veditors = Major RH |edition=3rd  |location=Springfield |publisher=Charles C Thomas  |year=1945 |pages=607–12}}</ref> In northern Italy it was named "pellagra" from the [[Lombard language]] (''agra'' = [[holly]]-like or [[Serous fluid|serum]]-like; ''pell'' = skin).<ref>F. Cherubini, ''Vocabolario Milanese-Italiano'', Imp. Regia Stamperia, 1840-43, vol. I, III.</ref><ref>{{cite web| title = Definition of Pellagra| work = MedicineNet.com| url = http://www.medterms.com/script/main/art.asp?articlekey=4821|access-date=18 June 2007|url-status = live|archive-url = https://web.archive.org/web/20070930155704/http://www.medterms.com/script/main/art.asp?articlekey=4821| archive-date = 30 September 2007}}</ref> In time, the disease was more closely linked specifically to corn.<ref>Cesare Lombroso, ''Studi clinici ed esperimentali sulla natura, causa e terapia delle pellagra'' (Bologna: Fava e Garagnani, 1869)</ref> In the US, [[Joseph Goldberger]] was assigned to study pellagra by the Surgeon General of the United States. His studies confirmed a corn-based diet as the culprit, but he did not identify the root cause.<ref>{{cite journal |vauthors=Evans BK, Feinstein AR | s2cid = 13226008 | title = Joseph Goldberger: an unsung hero of American clinical epidemiology | journal = Ann Intern Med | date=September 1994| volume = 121 | issue = 5 | pages = 372–75 | pmid = 8042827 | doi=10.7326/0003-4819-121-5-199409010-00010}}</ref><ref name=Kraut>{{Cite web|url=https://history.nih.gov/pages/viewpage.action?pageId=8883184|title=Dr. Joseph Goldberger and the War on Pellagra {{!}} Ashes on the Potomac|vauthors=Kraut A|website=history.nih.gov|access-date=20 February 2017|archive-date=9 May 2020|archive-url=https://web.archive.org/web/20200509172705/https://history.nih.gov/pages/viewpage.action?pageId=8883184}}</ref>

Nicotinic acid was extracted from liver by biochemist [[Conrad Elvehjem]] in 1937. He later identified the active ingredient, referring to it as "pellagra-preventing factor" and the "anti-blacktongue factor."<ref name=Elvehjem>{{cite journal |vauthors=Elvehjem CA, Madden RJ, Strongandd FM, Woolley DW |year=1938 |title=The isolation and identification of the anti-blacktongue factor J |journal = J. Biol. Chem. |volume=123 |pages=137–49 |url=http://www.jbc.org/content/123/1/137.full.pdf |archive-url=https://ghostarchive.org/archive/20221009/http://www.jbc.org/content/123/1/137.full.pdf |archive-date=9 October 2022 |url-status=live |issue=1|doi=10.1016/S0021-9258(18)74164-1 |doi-access=free }}</ref> It was also referred to as "vitamin PP", "vitamin P-P" and "PP-factor", all derived from the term "pellagra-preventive factor".<ref name="Pellagra And Its Prevention">{{cite report|vauthors=((World Health Organization)) | title=Pellagra And Its Prevention And Control In Major Emergencies|publisher=[[World Health Organization]] (WHO) | year=2000 | hdl=10665/66704 | hdl-access=free | id=WHO/NHD/00.10}}</ref> In the late 1930s, studies by [[Tom Douglas Spies]], Marion Blankenhorn, and Clark Cooper confirmed that nicotinic acid cured pellagra in humans.<ref>{{cite journal | vauthors = Spies TD, Cooper C, Blankenhorn MA | title = The use of nicotinic acid in the treatment of pellagra |journal=Journal of the American Medical Association |date=26 February 1938 |volume=110 |issue=9 |pages=622–627 |doi=10.1001/jama.1938.02790090004002 |issn=0002-9955}}</ref> The prevalence of the disease was greatly reduced as a result.<ref>{{cite book | vauthors = Sachs RH | url = https://books.google.com/books?id=WOPfM-0hz1AC&dq=%22pellagra%3A+Drs.+Tom+Douglas%22&pg=PA630 | title = White Rose History | archive-url = https://web.archive.org/web/20230421215022/https://books.google.com/books?id=WOPfM-0hz1AC&dq=%22pellagra:+Drs.+Tom+Douglas%22&pg=PA630 | archive-date=21 April 2023 | volume = I | date = 2003 | page = Appendix D, p. 2 | publisher=Exclamation! Publishers | isbn = 978-0-9710541-9-6 | quote = Men of the Year, outstanding in comprehensive science were three medical researchers who discovered that nicotinic acid was a cure for human pellagra: Drs. Tom Douglas Spies of Cincinnati General Hospital, Marion Arthur Blankenhorn of the University of Cincinnati, Clark Niel Cooper of Waterloo, Iowa. }}</ref> Nicotinic acid was initially synthesized by oxidizing [[nicotine]] with [[potassium chromate]] and [[sulfuric acid]].<ref name=JAMA1942a/> Hence, in 1942, when flour [[food fortification|enrichment]] with nicotinic acid began, a headline in the popular press said "Tobacco in Your Bread." In response, the Council on Foods and Nutrition of the [[American Medical Association]] approved of the [[Food and Nutrition Board]]'s new names ''niacin'' and ''niacin amide'' for use primarily by non-scientists. It was thought appropriate to choose a name to dissociate nicotinic acid from nicotine, to avoid the perception that vitamins or niacin-rich food contains nicotine, or that cigarettes contain vitamins. The resulting name ''niacin'' was derived from ''{{strong|ni}}cotinic {{strong|ac}}id'' + ''vitam{{strong|in}}''.<ref>{{cite journal | vauthors = ((Council on Foods and Nutrition)) |title=Niacin and Niacin Amide| date=7 March 1942|volume=118|issue=10|doi=10.1001/jama.1942.02830100049011|journal=Journal of the American Medical Association|page=819}}</ref><ref name=JAMA1942a/>

Carpenter found in 1951, that niacin in corn is biologically unavailable, and can be released only in very alkaline [[Lime (material)|lime]] water of [[pH]] 11. This explains why a Latin-American culture that used [[Nixtamalization|alkali-treated cornmeal]] to make tortilla was not at risk for niacin deficiency.<ref>{{cite journal | vauthors = Laguna J, Carpenter KJ | title = Raw versus processed corn in niacin-deficient diets | journal = The Journal of Nutrition | volume = 45 | issue = 1 | pages = 21–8 | date = September 1951 | pmid = 14880960 | doi = 10.1093/jn/45.1.21 | doi-access = free }}</ref> The modern explanation is that alkali treatment enhances the bioavailability of [[tryptophan]], not directly for any form of the vitamin.<ref name=fao92>{{cite book |title=Maize in human nutrition |date=1992 |publisher=Food and Agriculture Organization of the United Nations |location=Rome |isbn=978-92-5-103013-4|url=https://www.fao.org/3/T0395E/T0395E00.htm}} &ndash; Section 5.2 "Lime-treated maize (part II)", Section 8 "Improvement of maize diets"</ref>{{rp|at=§5.2}}

In 1955, Altschul and colleagues described large amounts of nicotinic acid as having a lipid-lowering property.<ref>{{cite journal | vauthors = Altschul R, Hoffer A, Stephen JD | title = Influence of nicotinic acid on serum cholesterol in man | journal = Archives of Biochemistry and Biophysics | volume = 54 | issue = 2 | pages = 558–9 | date = February 1955 | pmid = 14350806 | doi = 10.1016/0003-9861(55)90070-9 }}</ref> As such, niacin is the oldest known [[Lipid-lowering agent|lipid-lowering drug]].<ref>{{cite journal |vauthors=Romani M, Hofer DC, Katsyuba E, Auwerx J |title=Niacin: an old lipid drug in a new NAD+ dress |journal=J. Lipid Res. |volume=60 |issue=4 |pages=741–6 |date=April 2019 |pmid=30782960 |pmc=6446705 |doi=10.1194/jlr.S092007  |doi-access=free }}</ref> [[Lovastatin]], the first '[[statin]]' drug, was first marketed in 1987.<ref name=Simons>{{cite journal | vauthors = Simons J | title = The $10 billion pill | journal = Fortune | volume = 147 | issue = 1 | pages = 58–62, 66, 68 | date = January 2003 | pmid = 12602122 | url = https://money.cnn.com/magazines/fortune/fortune_archive/2003/01/20/335643/index.htm }}</ref>

==Extra-terrestrial occurrence==
Extra-terrestrial nicotinic acid has been found in carbonaceous chondrite meteorites and in sample-returns from the asteroids 162173 Ryugu and 101955 Bennu.

{| class="wikitable"
|+ Vitamin B3 vitamers from extra-terrestrial sources
|-
! Asteroid !! Nicotinic acid !! Nicotinamide
|-
| 101955 Bennu<ref name="Glavin2025" /> || 0.43 nmol/g || not reported
|-
| 162173 Ryugu || 0.40 nmol/g,<ref name="Glavin2025" /> 99ppb<ref name="Oba2023" /> || not detected<ref name="Oba2023" />
|-
! Meteorite !! Nicotinic acid !! Nicotinamide
|-
| [[Orgueil (meteorite)|Orgueil]]<ref name="Oba2023" /> || 715ppb || 214ppb
|-
| [[Murray meteorite|Murray]]<ref name="Oba2022" /> || 626ppb || 65ppb
|-
| [[Murchison meteorite|Murchison]] || 2.4 nmol/g,<ref name="Glavin2025" /> 190ppb<ref name="Oba2022" /> || 16ppb<ref name="Oba2022" />
|-
| [[Tagish Lake (meteorite)|Tagish Lake]]<ref name="Oba2022" /> || 108ppb || 5ppb
|}

==Notes==
{{notelist}}{{clear}}

== References ==
{{Reflist}}

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