View source for Niacin

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<!--T:1-->
{{Short description|Organic compound and a form of vitamin B3}}
{{Pathnav|Dietary supplement|Vitamin|frame=1}}
{{Chembox
| Watchedfields = changed
| verifiedrevid = 408767536
| ImageFileL1 = Niacin_structure.svg
| ImageFileL1_Ref = {{chemboximage|correct|??}}
| ImageNameL1 = Kekulé, skeletal formula of niacin
| ImageFileR1 = Niacin-3D-balls.png     
| ImageFileR1_Ref = {{chemboximage|correct|??}}
| ImageNameR1 = Ball and stick model of niacin
| PIN = Pyridine-3-carboxylic acid
| pronounce = {{IPAc-en|ˈ|n|aɪ|ə|s|ɪ|n}}
| OtherNames = {{ubl
 | Nicotinic acid ([[International nonproprietary name|INN]])
 | 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

<!--T:2-->
| 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
}}
|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             = 
| width             = 
| alt               = 
| caption           = 
| USAN              = 
| INN_EMA           = Nicotinic acid

<!--T:3-->
<!-- Clinical data -->
| pronounce         = 
| tradename         = Niacor, Niaspan, others
| Drugs.com         = {{drugs.com|monograph|niacin}}
| MedlinePlus       = a682518
| licence_CA        = <!-- Health Canada may use generic or brand name (generic name preferred) -->
| licence_EU        = yes
| DailyMedID        = Niacin
| licence_US        = <!-- FDA may use generic or brand name (generic name preferred) -->
| pregnancy_AU      = 
| pregnancy_AU_comment = Exempt
| pregnancy_category= 
| dependency_liability = 
| addiction_liability = 
| routes_of_administration = Intramuscular, by mouth
| class             = 
| ATCvet            = 
| ATC_supplemental  =

<!--T:4-->
<!-- 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 -->

<!--T:5-->
<!-- Pharmacokinetic data -->
| bioavailability   = 
| protein_bound     = 
| metabolism        = 
| metabolites       = 
| onset             = 
| elimination_half-life = 
| duration_of_action = 
| excretion         =

<!--T:6-->
<!-- Identifiers -->
| CAS_number_Ref    = 
| CAS_number        = 
| CAS_supplemental  = 
| PubChem           = 
| PubChemSubstance  = 
| IUPHAR_ligand     = 
| DrugBank_Ref      = 
| DrugBank          = 
| ChemSpiderID_Ref  = 
| ChemSpiderID      = 
| UNII_Ref          = 
| UNII              = 
| KEGG_Ref          = 
| KEGG              = 
| KEGG2_Ref         = 
| KEGG2             = 
| ChEBI_Ref         = 
| ChEBI             = 
| ChEMBL_Ref        = 
| ChEMBL            = 
| NIAID_ChemDB      = 
| PDB_ligand        = NIO
| synonyms          =

<!--T:7-->
<!-- Chemical and physical data -->
| IUPAC_name        = 
| chemical_formula  = 
| molecular_weight  = 
| SMILES            = 
| Jmol              = 
| StdInChI          = 
| StdInChI_comment  = 
| StdInChIKey       = 
| density           = 
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| melting_point     = 
| melting_high      = 
| melting_notes     = 
| boiling_point     = 
| boiling_notes     = 
| solubility        = 
| sol_units         = 
| specific_rotation = 
}}

<!--T:8-->
[[File:Vitamin B3 (Niacine) space filling model.jpg|thumb|Space-filling model of niacin]]

<!--T:9-->
'''Niacin''', also known as '''nicotinic acid''', is an [[organic compound]] and a [[vitamer]] of [[vitamin]]{{spaces}}[[vitamin B3|B<sub>3</sub>]], an [[essential nutrient|essential human nutrient]]. It is produced by plants and animals from the amino acid [[tryptophan]]. Niacin is obtained in the diet from a variety of [[whole food|whole]] and [[processed foods]], with highest contents in [[fortified food|fortified]] [[packaged food]]s, meat, poultry, red fish such as [[tuna]] and [[salmon]], lesser amounts in nuts, legumes and seeds. Niacin as a [[dietary supplement]] is used to treat [[pellagra]], a disease caused by niacin deficiency. Signs and symptoms of pellagra include skin and mouth lesions, anemia, headaches, and tiredness. Many countries mandate its addition to wheat flour or other [[food grains]], thereby reducing the risk of pellagra.

<!--T:10-->
The amide derivative [[nicotinamide]] (niacinamide) is a component of the coenzymes [[nicotinamide adenine dinucleotide]] (NAD) and [[nicotinamide adenine dinucleotide phosphate]] (NADP<sup>+</sup>). Although niacin and [[nicotinamide]] are identical in their vitamin activity, nicotinamide does not have the same pharmacological, [[hypolipidemic agent|lipid-modifying]] effects or side effects as niacin, i.e., when niacin takes on the ''-amide'' group, it does not reduce cholesterol nor cause [[flushing (physiology)|flushing]]. Nicotinamide is recommended as a treatment for niacin deficiency because it can be administered in remedial amounts without causing the flushing, considered an adverse effect.

<!--T:11-->
Niacin is also a prescription medication. 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 niacin. 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. Despite the proven lipid changes, niacin has not been found useful for decreasing the risk of [[cardiovascular disease]] in those already on a [[statin]]. A 2010 review had concluded that niacin was effective as a mono-therapy, but a 2017 review incorporating twice as many trials concluded that prescription niacin, while affecting lipid levels, did not reduce all-cause mortality, cardiovascular mortality, myocardial infarctions, nor fatal or non-fatal strokes. Prescription niacin was shown to cause hepatotoxicity and increase risk of [[type 2 diabetes]]. Niacin prescriptions in the U.S. had peaked in 2009, at 9.4{{nbsp}}million, declining to 800{{nbsp}}thousand by 2020.

<!--T:12-->
Niacin has the [[chemical formula|formula]] {{chem|C|6|H|5|NO|2}} and belongs to the group of the [[pyridinecarboxylic acids]]. As the [[precursor (chemistry)|precursor]] for [[nicotinamide adenine dinucleotide]] and [[nicotinamide adenine dinucleotide phosphate]], niacin is involved in DNA repair.
{{TOC limit}}

==Definition== <!--T:13-->
Niacin is both a vitamin, i.e., an essential nutrient, marketed as a dietary supplement, and in the US, a prescription medicine. As a vitamin, 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. 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. Niacin but also [[nicotinamide]] (niacinamide) are used for prevention and treatment of [[pellagra]], a disease caused by lack of the vitamin. When niacin is used as a medicine to treat [[hyperlipidemia|elevated cholesterol and triglycerides]], daily doses range from 500 to 3,000&nbsp;mg/day. High-dose nicotinamide does not have this medicinal effect.

==Vitamin deficiency== <!--T:14-->
{{Main|Pellagra}}
[[File:Pellagra2.jpg|thumb|A man with [[pellagra]], which is caused by a chronic lack of vitamin B<sub>3</sub> in the diet]]

<!--T:15-->
Severe deficiency of niacin in the diet causes the disease [[pellagra]], characterized by [[diarrhea]], sun-sensitive [[dermatitis]] involving hyperpigmentation and thickening of the skin (see image), inflammation of the mouth and tongue, delirium, dementia, and if left untreated, death. Common psychiatric symptoms include irritability, poor concentration, anxiety, fatigue, loss of memory, restlessness, apathy, and depression. The biochemical mechanism(s) for the observed deficiency-caused neurodegeneration are not well understood, but may rest on: A) the requirement for [[nicotinamide adenine dinucleotide]] (NAD+) to suppress the creation of neurotoxic tryptophan metabolites, B) inhibition of mitochondrial ATP generation, resulting in cell damage; C), activation of the [[poly (ADP-ribose) polymerase]] (PARP) pathway, as PARP is a nuclear enzyme involved in DNA repair, but in the absence of NAD+ can lead to cell death; D) reduced synthesis of neuro-protective [[brain-derived neurotrophic factor]] or its receptor [[tropomyosin receptor kinase B]]; or E) changes to genome expression directly due to the niacin deficiency.

<!--T:16-->
Niacin deficiency is rarely seen in developed countries, and it is more typically associated with poverty, malnutrition or malnutrition secondary to chronic [[alcoholism]]. It also tends to occur in less developed areas where people eat [[maize]] (corn) as a staple food, as maize is the only grain low in digestible niacin. A cooking technique called [[nixtamalization]] i.e., pretreating with alkali ingredients, increases the bioavailability of niacin during maize meal/flour production. For this reason, people who consume corn as tortillas or [[hominy]] are at less risk of niacin deficiency.

<!--T:17-->
For treating deficiency, the World Health Organization (WHO) recommends administering niacinamide i.e., nicotinamide, instead of niacin, to avoid the flushing side effect commonly caused by the latter. Guidelines suggest using 300&nbsp;mg/day for three to four weeks. Dementia and dermatitis show improvement within a week. Because deficiencies of other B-vitamins may be present, the WHO recommends a multi-vitamin in addition to the niacinamide.

<!--T:18-->
[[Hartnup disease]] is a [[hereditary]] nutritional disorder resulting in niacin deficiency. It is named after an English family with a genetic disorder that resulted in a failure to absorb the essential amino acid [[tryptophan]], tryptophan being a precursor for niacin synthesis. The symptoms are similar to pellagra, including red, scaly rash and sensitivity to sunlight. Oral niacin or niacinamide is given as a treatment for this condition in doses ranging from 50 to 100&nbsp;mg twice a day, with a good prognosis if identified and treated early. Niacin synthesis is also deficient in [[carcinoid syndrome]], because of metabolic diversion of its [[precursor (chemistry)|precursor]] [[tryptophan]] to form [[serotonin]].

===Measuring vitamin status=== <!--T:19-->
Plasma concentrations of niacin and niacin metabolites are not useful markers of niacin status. Urinary excretion of the methylated metabolite N1-methyl-nicotinamide is considered reliable and sensitive. The measurement requires a 24-hour urine collection. For adults, a value of less than 5.8 μmol/day represent deficient niacin status and 5.8 to 17.5 μmol/day represents low. According to the World Health Organization, an alternative mean of expressing urinary N1-methyl-nicotinamide is as mg/g creatinine in a 24-hour urine collection, with deficient defined as <0.5, low 0.5-1.59, acceptable 1.6-4.29, and high >4.3 Niacin deficiency occurs before the signs and symptoms of pellagra appear. Erythrocyte [[nicotinamide adenine dinucleotide]] (NAD) concentrations potentially provide another sensitive indicator of niacin depletion, although definitions of deficient, low and adequate have not been established. Lastly, plasma [[tryptophan]] decreases on a low niacin diet because tryptophan converts to niacin. However, low tryptophan could also be caused by a diet low in this essential [[amino acid]], so it is not specific to confirming vitamin status.

==Dietary recommendations== <!--T:20-->

<!--T:21-->
{| class="wikitable" style="float: right; margin-left: 2em;"
|+ Dietary recommendations
|
{| class="wikitable mw-collapsible mw-collapsed" style="font-size: 80%; text-align: center; width:406px"
|-
|+ style="background: blue; color: white; font-size: 110%; text-align: center;" | Australia and New Zealand
|-
! scope="col" style="width:8em" | Age group
! scope="col" style="width:8em" | RDI for niacin (mg NE/day)
! scope="col" style="width:8em" | Upper level of intake
|-
| Infants 0–6 months || 2&nbsp;mg/d preformed niacin* || rowspan="2"| ND
|-
| Infants 7–12 months || 4&nbsp;mg/d NE*
|-
| 1–3 || 6 || 10
|-
| 4–8 || 8 || 15
|-
| 9–13 || 12 || 20
|-
| 14–18 || – || 30
|-
| 19+ || – || 35
|-
| Females 14+ || 14 || rowspan=2 | –
|-
| Males 14+ || 16
|-
| Pregnant females 14–50 || 18 || –
|-
| Pregnant females 14–18 || – || 30
|-
| Pregnant females 19–50 || – || 35
|-
| Lactating females 14–50 || 17 || –
|-
| Lactating females 14–18 || – || 30
|-
| Lactating females 19–50 || – || 35
|-
| colspan="3" style="text-align: center;" | * Adequate Intake for infants
|-
|}
{| class="wikitable mw-collapsible mw-collapsed" style="font-size: 80%; text-align: center; width:406px"
|-
|+ style="background: blue; color: white; font-size: 110%; text-align: center;" | Canada
|-
! scope="col" style="width:8em" | Age group (years)
! scope="col" style="width:8em" | RDA of niacin (mg NE/d)
! scope="col" style="width:8em" | Tolerable upper intake level
|-
| 0–6 months || 2&nbsp;mg/d preformed niacin* || rowspan=2| ND
|-
| 7–12 months || 4&nbsp;mg/d NE*
|-
| 1–3 || 6 || 10
|-
| 4–8 || 8 || 15
|-
| 9–13 || 12 || 20
|-
| Females 14–18 || 14 || rowspan=2| 30
|-
| Males 14–18 || 16
|-
| Females 19+ || 14 || rowspan=2| 35
|-
| Males 19+ || 16
|-
| Pregnant females <18 || 18 || 30
|-
| Pregnant females 18–50 || 18 || 35
|-
| Lactating females <18 || 17 || 30
|-
| Lactating females 18–50 || 17 || 35
|-
|}
{| class="wikitable mw-collapsible mw-collapsed" style="font-size: 80%; text-align: center; width:406px"
|-
|+ style="background: blue; color: white; font-size: 110%; text-align: center;" | European Food Safety Authority
|-
! scope="col" width=8em | Gender
! colspan=2 width=16em | Adequate Intake (mg NE/MJ)
|-
| Females || colspan=2 width="8em"| 1.3
|-
| Males || colspan=2 width="8em"| 1.6
|-
! scope="col" style="width:8em" | Age (years)
! scope="col" style="width:8em" | Tolerable upper limit of Nicotinic acid (mg/day)
! scope="col" style="width:8em" | Tolerable upper limit of Nicotinamide (mg/day)
|-
| 1–3 || 2 || 150
|-
| 4–6 || 3 || 220
|-
| 7–10 || 4 || 350
|-
| 11–14 || 6 || 500
|-
| 15–17 || 8 || 700
|-
|}
{| class="wikitable mw-collapsible mw-collapsed" style="font-size: 80%; text-align: center; width:406px"
|-
|+ style="background: blue; color: white; font-size: 110%; text-align: center;" | United States
|-
! scope="col" style="width:8em" | Age group
! scope="col" style="width:8em" | RDA for niacin (mg NE/day)
! scope="col" style="width:8em" | Tolerable upper intake level
|-
| Infants 0–6 months || 2* || rowspan="2"| ND**
|-
| Infants 6–12 months || 4*
|-
| 1–3 || 6 || 10
|-
| 4–8 || 8 || 15
|-
| 9–13 || 12 || 20
|-
| Females 14–18 || 14 || 30
|-
| Males 14–18 || 16 || 30
|-
| Females 19+ || 14 || 35
|-
| Males 19+ || 16 || 35
|-
| Pregnant females 14–18 || 18 || 30
|-
| Pregnant females 19–50 || 18 || 35
|-
| Lactating females 14–18 || 17 || 30
|-
| Lactating females 19–50 || 17 || 35
|-
| colspan="3" style="text-align: center;" | * Adequate intake for infants, as an RDA has yet to be established<br />** Not possible to establish; source of intake should be formula and food only
|-
|}
|}
The U.S. Institute of Medicine (renamed [[National Academy of Medicine]] in 2015) updated Estimated Average Requirements (EARs) and Recommended Dietary Allowances (RDAs) for niacin in 1998, also [[Tolerable upper intake levels]] (ULs). In lieu of an RDA, Adequate Intakes (AIs) are identified for populations for which there is not sufficient evidence to identify a dietary intake level that is sufficient to meet the nutrient requirements of most people. (see table).

<!--T:22-->
The [[European Food Safety Authority]] (EFSA) refers to the collective set of information as Dietary Reference Values (DRV), with Population Reference Intake (PRI) instead of RDA, and Average Requirement instead of EAR. For the EU, AIs and ULs have the same definition as in the US, except that units are milligrams per megajoule (MJ) of energy consumed rather than mg/day. For women (including those pregnant or lactating), men and children the PRI is 1.6&nbsp;mg per megajoule. As the conversion is 1 MJ = 239 kcal, an adult consuming 2390 kilocalories should be consuming 16&nbsp;mg niacin. This is comparable to US RDAs (14&nbsp;mg/day for adult women, 16&nbsp;mg/day for adult men).

<!--T:23-->
ULs are established by identifying amounts of vitamins and minerals that cause adverse effects, and then selecting as an upper limit amounts that are the "maximum daily intake unlikely to cause adverse health effects." Regulatory agencies from different countries do not always agree. For the US, 30 or 35&nbsp;mg for teenagers and adults, less for children. The EFSA UL for adults is set at 10&nbsp;mg/day - about one-third of the US value. For all of the government ULs, the term applies to niacin as a supplement consumed as one dose, and is intended as a limit to avoid the skin flush reaction. This explains why for EFSA, the recommended daily intake can be higher than the UL.

<!--T:24-->
Both the DRI and DRV describe amounts needed as niacin equivalents (NE), calculated as 1&nbsp;mg NE = 1&nbsp;mg niacin or 60&nbsp;mg of the essential amino acid tryptophan. This is because the amino acid is utilized to synthesize the vitamin.

<!--T:25-->
For U.S. food and dietary supplement labeling purposes the amount in a serving is expressed as a percent of [[Daily Value]] (%DV). For niacin labeling purposes 100% of the Daily Value is 16&nbsp;mg. Prior to 27 May 2016 it was 20&nbsp;mg, revised to bring it into agreement with the RDA.
Compliance with the updated labeling regulations was required by 1 January 2020 for manufacturers with [[US$]]10&nbsp;million or more in annual food sales, and by 1 January 2021 for manufacturers with lower volume food sales. A table of the old and new adult daily values is provided at [[Reference Daily Intake]].

==Sources== <!--T:26-->
Niacin is found in a variety of [[whole food|whole]] and [[processed foods]], including [[fortified food|fortified]] [[packaged food]]s, [[meat]] from various animal sources, [[seafoods]], and [[spices]]. In general, animal-sourced foods provide about 5–10&nbsp;mg niacin per serving, although dairy foods and eggs have little. Some plant-sourced foods such as nuts, legumes and grains provide about 2–5&nbsp;mg niacin per serving, although in some grain products this naturally present niacin is largely bound to polysaccharides and glycopeptides, making it only about 30% bioavailable. Fortified food ingredients such as wheat flour have niacin added, which is bioavailable. Among whole food sources with the highest niacin content per 100 grams:

<!--T:27-->
<div style="float:left; padding: 1em;">
{|class="wikitable"
|-
!Source
!Amount<br /> (mg / 100g)
|-
|[[Nutritional yeast]]<br />Serving = 2 Tbsp (16 g) contains 56&nbsp;mg || 350
|-
|[[Tuna]], yellowfin || 22.1
|-
|[[Peanut]]s || 14.3
|-
|[[Peanut butter]] || 13.1
|-
|[[Bacon]] || 10.4
|-
|[[Tuna]], light, canned || 10.1
|-
|[[Salmon]] || 10.0
|-
|[[Turkey (bird)|Turkey]] depending on what part, how cooked || 7-12
|-
|[[Chicken as food|Chicken]] depending on what part, how cooked || 7-12
|}
</div>
<div style="float:left; padding: 1em;">
{|class="wikitable"
|-
!Source
!Amount<br /> (mg / 100g)
|-
|[[Beef]] depending on what part, how cooked || 4-8
|-
|[[Pork]] depending on what part, how cooked || 4-8
|-
|[[Sunflower seeds]] || 7.0
|-
|[[Tuna]], white, canned || 5.8
|-
|[[Almond]]s || 3.6
|-
|[[Mushroom]]s, white || 3.6
|-
|[[Cod as food|Cod fish]] || 2.5
|-
|[[Brown rice|Rice, brown]] || 2.5
|-
|[[Hot dog]]s || 2.0
|}
</div>
<div style="float:left; padding: 1em;">
{|class="wikitable"
 |-
!Source
!Amount<br /> (mg / 100g)
|-
|[[Avocado]] || 1.7
|-
|[[Potato]], baked, with skin || 1.4
|-
|[[Maize|Corn]] (maize) || 1.0
|-
|[[White rice|Rice, white]] || 0.5
|-
|[[Kale]] || 0.4
|-
|[[Egg as food|Eggs]] || 0.1
|-
|[[Milk]] || 0.1
|-
|[[Cheese]] || 0.1
|-
|[[Tofu]] || 0.1
|}
</div>{{Clear}}

<!--T:28-->
[[Vegetarianism|Vegetarian]] and [[Veganism|vegan]] diets can provide adequate amounts if products such as nutritional yeast, peanuts, peanut butter, tahini, brown rice, mushrooms, avocado and sunflower seeds are included. Fortified foods and dietary supplements can also be consumed to ensure adequate intake.

===Food preparation=== <!--T:29-->
Niacin naturally found in food is susceptible to destruction from high heat cooking, especially in the presence of acidic foods and sauces. It is soluble in water, and so may also be lost from foods boiled in water.

===Food fortification=== <!--T:30-->
Countries fortify foods with nutrients to address known deficiencies. As of 2020, 54 countries required food fortification of wheat flour with niacin or niacinamide; 14 also mandate fortification of maize flour, and 6 mandate fortification of rice. From country to country, niacin fortification ranges from 1.3 to 6.0&nbsp;mg/100 g.

===As a dietary supplement=== <!--T:31-->
In the United States, niacin 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 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 niacin for prescription niacin because of potentially serious side effects, which means that niacin should only be used under the supervision of a health care professional, and because manufacture of dietary supplement niacin is not as well-regulated by the FDA as prescription niacin. More than 30&nbsp;mg niacin 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.

==As lipid-modifying medication== <!--T:32-->
In the United States, prescription niacin, in immediate-release and slow-release forms, is used to treat primary [[hyperlipidemia]] and [[hypertriglyceridemia]]. 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). Prescriptions in the US peaked in 2009, at 9.4{{nbsp}}million and had declined to 800{{nbsp}}thousand by 2020.

<!--T:33-->
Systematic reviews found no effect of prescription niacin on all-cause mortality, cardiovascular mortality, myocardial infarctions, nor fatal or non-fatal strokes despite raising [[high-density lipoprotein|HDL]] cholesterol. Reported side effects include an increased risk of new-onset type 2 diabetes.

===Mechanisms=== <!--T:34-->
Niacin 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). The lipid-therapeutic effects of niacin 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]]. 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. 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. Niacin also directly inhibits the action of [[diacylglycerol O-acyltransferase 2]] (DGAT2) a key enzyme for triglyceride synthesis.

<!--T:35-->
The mechanism behind niacin increasing HDL-C is not totally understood, but seems to occur in various ways. Niacin increases [[apolipoprotein A1]] levels by inhibiting the breakdown of this protein, which is a component of HDL-C. It also inhibits HDL-C hepatic uptake by suppressing production of the [[cholesterol ester transfer protein]] (CETP) gene. 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.

===Combined with statins=== <!--T:36-->
Extended release niacin was combined with [[lovastatin]] (Advicor), and with [[simvastatin]] (Simcor), as prescription drug combinations. The combination niacin/lovastatin was approved by the U.S. [[Food and Drug Administration]] (FDA) in 2001. The combination niacin/simvastatin was approved by the FDA in 2008. Subsequently, large outcome trials using these niacin and statin therapies were unable to demonstrate incremental benefit of niacin beyond statin therapy alone. 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.

===Contraindications=== <!--T:37-->
Prescription immediate release (Niacor) and extended release (Niaspan) niacin 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. Both products are contraindicated for people with existing [[peptic ulcer disease]], or other bleeding problems because niacin lowers platelet count and interferes with blood clotting. 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 niacin 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 niacin has not been tested or approved for use in children under 16 years.

===Adverse effects=== <!--T:38-->
The most common adverse effects of medicinal niacin ({{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. These can be minimized by initiating therapy at low dosages, increasing dosage gradually, and avoiding administration on an empty stomach.

<!--T:39-->
The acute adverse effects of high-dose niacin 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]]. With long-term use, the adverse effects of high-dose niacin therapy (750&nbsp;mg per day) also include [[liver failure]] (associated with fatigue, nausea, and [[loss of appetite]]), [[hepatitis]], and [[acute liver failure]]; these hepatotoxic effects of niacin occur more often when extended-release [[dosage form]]s are used. The long-term use of niacin 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.

====Flushing==== <!--T:40-->
[[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 due to elevation in prostaglandin GD<sub>2</sub> ([[PGD2]]) and [[serotonin]]. Flushing was often thought to involve histamine, but histamine has been shown not to be involved in the reaction. Flushing is sometimes accompanied by a prickly or [[itching]] sensation, in particular, in areas covered by clothing.

<!--T:41-->
Prevention of flushing requires altering or blocking the prostaglandin-mediated pathway. [[Aspirin]] taken half an hour before the niacin prevents flushing, as does [[ibuprofen]]. Taking niacin with meals also helps reduce this side effect. Acquired tolerance will also help reduce flushing; after several weeks of a consistent dose, most people no longer experience flushing. Slow- or "sustained"-release forms of niacin have been developed to lessen these side effects.

====Liver damage==== <!--T:42-->
Niacin 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. 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.

====Diabetes==== <!--T:43-->
The high doses of niacin used to treat [[hyperlipidemia]] have been shown to elevate [[blood sugar|fasting blood glucose]] in people with type 2 [[diabetes mellitus|diabetes]]. Long-term niacin therapy was also associated with an increase in the risk of new-onset type 2 diabetes.

====Other adverse effects==== <!--T:44-->
High doses of niacin 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. Niaspan, the slow-release product, has been associated with a reduction in platelet content and a modest increase in prothrombin time.

==Pharmacology== <!--T:45-->

===Pharmacodynamics=== <!--T:46-->
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.

<!--T:47-->
Niacin [[Enzyme inhibitor|inhibits]] [[cytochrome P450]] enzymes [[CYP2E1]], [[CYP2D6]] and [[CYP3A4]]. 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. 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.
{{See also|Niacin#Liver_damage}}

===Pharmacokinetics=== <!--T:48-->
Both niacin and niacinamide are rapidly absorbed from the stomach and small intestine. 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. 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 niacin or nicotinuric acid, its primary metabolite. The plasma elimination half-life of niacin ranges from 20 to 45 minutes.

<!--T:49-->
Niacin and nicotinamide are both converted into the [[coenzyme]] NAD. 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. In the liver, niacinamide is converted to storage [[nicotinamide adenine dinucleotide]] (NAD). As needed, liver NAD is hydrolyzed to niacinamide and niacin for transport to tissues, there reconverted to NAD to serve as an enzyme cofactor. Excess niacin is methylated in the liver to N<sup>1</sup>-methylnicotinamide (NMN) and excreted in urine as such or as the oxidized metabolite [[N1-Methyl-2-pyridone-5-carboxamide|N<sup>1</sup>-methyl-2-pyridone-5-carboxamide]] (2-pyridone). Decreased urinary content of these metabolites is a measure of niacin deficiency.
[[Image:Tryptophan metabolism.svg|thumb|300px|Niacin, [[serotonin]] (5-hydroxytryptamine), and [[melatonin]] [[biosynthesis]] from [[tryptophan]]]]

==Production== <!--T:50-->
===Biosynthesis===
In addition to absorbing niacin from diet, niacin 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. 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. 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.

===Industrial synthesis=== <!--T:51-->
Nicotinic acid was first synthesized in 1867 by oxidative degradation of [[nicotine]] with [[potassium chromate]] and [[sulfuric acid]] — this is the origin of the name. Niacin 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 converted to niacin. 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 niacin. 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.

<!--T:52-->
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.

===Climate Impact=== <!--T:53-->
The production of niacin creates [[nitrous oxide]] as a by-product, which is a potent greenhouse gas. In 2018, it was discovered that a niacin factory in [[Visp]], Switzerland, was responsible for around one percent of the country's greenhouse gas emissions. Eventually, catalytic scrubbing technology that avoids most of the emissions was installed in 2021.

==Chemistry== <!--T:54-->
This colorless, water-soluble solid is a derivative of [[pyridine]], with a [[carboxyl group]] (COOH) at the 3-position. Other forms of vitamin B<sub>3</sub> include the corresponding [[amide]] [[nicotinamide]] (niacinamide), where the carboxyl group has been replaced by a [[carboxamide]] group ({{chem|CONH|2}}).

==Preparations== <!--T:55-->
Niacin is incorporated into multi-vitamin and sold as a single-ingredient dietary supplement. The latter can be immediate or slow release.

<!--T:56-->
[[Nicotinamide]] (niacinamide) is used to treat niacin deficiency because it does not cause the flushing adverse reaction seen with niacin. Nicotinamide may be toxic to the liver at doses exceeding 3{{nbsp}}g/day for adults.

<!--T:57-->
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 niacin, 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.

<!--T:58-->
Prescription niacin 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. 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. The study resulted in the withdrawal of Tredaptive from the international market.

<!--T:59-->
[[File:Inositol nicotinate.png|thumb|[[Inositol]] hexanicotinate]]
One form of dietary supplement sold in the US is inositol hexanicotinate (IHN), also called [[inositol nicotinate]]. This is [[inositol]] that has been [[ester]]ified with niacin on all six of inositol's alcohol groups. IHN is usually sold as "flush-free" or "no-flush" niacin in units of 250, 500, or 1000&nbsp;mg/tablets or capsules. In the US, it is sold as an over-the-counter formulation, and often is marketed and labeled as niacin, thus misleading consumers into thinking they are getting an active form of the medication. While this form of niacin does not cause the flushing associated with the immediate-release products, there is not enough evidence to recommend IHN to treat hyperlipidemia.

==History== <!--T:60-->
{{Further|Vitamin#History}}

<!--T:61-->
Niacin as a chemical compound was first described by chemist [[Hugo Weidel]] in 1873 in his studies of [[nicotine]], 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. Over time, eight chemically distinct, water-soluble B vitamins were isolated and numbered, with niacin as vitamin B<sub>3</sub>.

<!--T:62-->
{{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. In northern Italy it was named "pellagra" from the [[Lombard language]] (''agra'' = [[holly]]-like or [[Serous fluid|serum]]-like; ''pell'' = skin). In time, the disease was more closely linked specifically to corn. 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.

<!--T:63-->
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." It was also referred to as "vitamin PP", "vitamin P-P" and "PP-factor", all derived from the term "pellagra-preventive factor". In the late 1930s, studies by [[Tom Douglas Spies]], Marion Blankenhorn, and Clark Cooper confirmed that niacin cured pellagra in humans. The prevalence of the disease was greatly reduced as a result.
Nicotinic acid was initially synthesized by oxidizing [[nicotine]] with [[potassium chromate]] and [[sulfuric acid]]. 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}}''.

<!--T:64-->
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 alkali-treated cornmeal to make tortilla was not at risk for niacin deficiency.

<!--T:65-->
In 1955, Altschul and colleagues described large amounts of niacin as having a lipid-lowering property. As such, niacin is the oldest known [[Lipid-lowering agent|lipid-lowering drug]]. [[Lovastatin]], the first '[[statin]]' drug, was first marketed in 1987.

==Research== <!--T:66-->

<!--T:67-->
In [[animal model]]s and ''[[in vitro]]'', niacin produces marked anti-inflammatory effects in a variety of tissues&nbsp;– including the brain, gastrointestinal tract, skin, and [[Inflammation#Vascular component|vascular tissue]]&nbsp;– through the activation of [[hydroxycarboxylic acid receptor 2]] (HCA2), also known as niacin receptor 1 (NIACR1). Unlike niacin, nicotinamide does not activate NIACR1; however, both niacin and nicotinamide activate the [[G protein-coupled estrogen receptor]] (GPER) ''in vitro''.

== External links == <!--T:68-->
* {{cite web | url = https://druginfo.nlm.nih.gov/drugportal/name/niacin | publisher = U.S. National Library of Medicine | work = Drug Information Portal | title = Niacin }}

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