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Niacin

From Wikipedia, the free encyclopedia
  (Redirected from Vitamin B3)
 
This article is about the nutrient. For the neo-fusion band, see Niacin (band). For niacins, see Nicotinic acids.
Niacin
Kekulé, skeletal formula of niacin
Ball and stick model of niacin
Names
Preferred IUPAC name
Pyridine-3-carboxylic acid[1]
Other names
Nicotinic acid (INN)
Bionic
Vitamin B3
Identifiers
59-67-6 Yes
3D model (Jmol) Interactive image
3DMet B00073
109591
ChEBI CHEBI:15940 Yes
ChEMBL ChEMBL573 Yes
ChemSpider 913 Yes
DrugBank DB00627 Yes
ECHA InfoCard 100.000.401
EC Number 200-441-0
3340
1588
KEGG D00049 Yes
MeSH Niacin
PubChem 938
RTECS number QT0525000
UNII 2679MF687A Yes
Properties
C
6
NH
5
O
2
Molar mass 123.1094 g mol−1
Appearance White, translucent crystals
Density 1.473 g cm−3
Melting point 237 °C; 458 °F; 510 K
18 g L−1
log P 0.219
Acidity (pKa) 2.0,4.85
Isoelectric point 4.75
1.4936
0.1271305813 D
Thermochemistry
−344.9 kJ mol−1
−2.73083 MJ mol−1
Pharmacology
C04AC01 (WHOC10AD02 (WHO)
Intramuscular, Oral
Pharmacokinetics:
20–45 min
Hazards
Irritant Xi
R-phrases R36/37/38
S-phrases S26S36
NFPA 704
Flammability code 1: Must be pre-heated before ignition can occur. Flash point over 93 °C (200 °F). E.g., canola oil Health code 1: Exposure would cause irritation but only minor residual injury. E.g., turpentine Reactivity code 0: Normally stable, even under fire exposure conditions, and is not reactive with water. E.g., liquid nitrogen Special hazards (white): no code NFPA 704 four-colored diamond
Flash point 193 °C (379 °F; 466 K)
365 °C (689 °F; 638 K)
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
Yes verify (what is Yes ?)
Infobox references
   

Niacin, also known as vitamin B3 and nicotinic acid, is an organic compound with the formula C
6
H
5
NO
2
and, depending on the definition used, one of the 20 to 80 essential human nutrientsPharmaceutical and supplemental niacin are primarily used to treat hypercholesterolemia (high cholesterol) and pellagra (niacin deficiency). Insufficient niacin in the diet can cause nausea, skin and mouth lesions, anemia, headaches, and tiredness. The lack of niacin may also be observed in pandemic deficiency disease, which is caused by a lack of five crucial vitamins (niacin, vitamin Cthiaminvitamin D, and vitamin A) and is usually found in areas of widespread poverty and malnutrition. Niacin has not been found to be useful in decreasing the risk of cardiovascular disease in those already on a statin[2] but appears to be effective in those not taking a statin.[3]

This colorless, water-soluble solid is a derivative of pyridine, with a carboxyl group (COOH) at the 3-position. Other forms of vitamin B3 include the corresponding amide and nicotinamide ("niacinamide"), where the carboxyl group has been replaced by a carboxamide group (CONH
2
), as well as more complex amides and a variety of esters. Nicotinic acid and niacinamide are convertible to each other with steady world demand rising from 8,500 tonnes per year in the 1980s to 40,000 in recent years.[4]

Niacin cannot be directly converted to nicotinamide, but both compounds are precursors of the coenzymesnicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP) in vivo.[5] NAD converts to NADP by phosphorylation in the presence of the enzyme NAD+ kinase. NADP and NAD are coenzymes for many dehydrogenases, participating in many hydrogen transfer processes.[6] 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.[6] High energy requirements (brain) or high turnover rate (gut, skin) organs are usually the most susceptible to their deficiency.[7] Although the two are identical in their vitamin activity, nicotinamide does not have the same pharmacological effects (lipid modifying effects) as niacin. Nicotinamide does not reduce cholesterol or cause flushing.[8] As the precursor for NAD and NADP, niacin is also involved in DNA repair.[9][10]

Dietary reference intake

The Food and Nutrition Board of the U.S. Institute of Medicine updated Estimated Average Requirements (EARs) and Recommended Dietary Allowances (RDAs) for niacin in 1998. The current EARs for niacin for women and men ages 14 and up are 11 mg/day and 12 mg/day, respectively; the RDAs are 14 and 16 mg/day, respectively. RDAs are higher than EARs so as to identify amounts that will cover people with higher than average requirements. RDA for pregnancy equals 18 mg/day. RDA for lactation equals 17 mg/day. For infants up to 12 months the Adequate Intake (AI) is 2–4 mg/day. and for children ages 1–13 years the RDA increases with age from 6 to 12 mg/day. As for safety, the Food and Nutrition Board also sets Tolerable Upper Intake Levels (known as ULs) for vitamins and minerals when evidence is sufficient. In the case of niacin the UL is set at 35 mg/day.[11] The European Food Safety Authority reviewed the same safety question and set its UL at 10 mg/day.[12] Safety issues are presented at length in the Side Effects section. Collectively the EARs, RDAs, AIs and ULs are referred to as Dietary Reference Intakes.

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 was 20 mg, but as of May 2016 it has been revised to 16 mg. A table of the pre-change adult Daily Values is provided at Reference Daily Intake. Food and supplement companies have until July 28, 2018, to comply with the change.

Deficiency

Main article: Pellagra
 
A man with pellagra, which is caused by a chronic lack of vitamin B3in the diet

Between 1906 and 1940 more than 3 million Americans were affected by pellagra with more than 100,000 deaths. Dr. Joseph Goldberger was assigned to study pellagra by the Surgeon General of the United States and produced good results. In the late 1930s, studies by Dr. Tom Spies, Marion Blankenhorn, and Clark Cooper established that niacin cured pellagra in humans. The disease was greatly reduced as a result.

At present, niacin deficiency is sometimes seen in developed countries, and it is usually apparent in conditions of poverty, malnutrition, and chronic alcoholism.[13] It also tends to occur in areas where people eat maize (corn) as a staple food, since it is the only grain low in digestible niacin. A cooking technique called nixtamalization increases the bioavailability of niacin during maize meal/flour production.

Mild niacin deficiency has been shown to slow metabolism, causing decreased tolerance to cold.

Severe deficiency of niacin in the diet causes the disease pellagra, which is characterized by diarrhea, dermatitis, and dementia, as well as Casal's necklace lesions on the lower neck, hyperpigmentation, thickening of the skin, inflammation of the mouth and tongue, digestive disturbances, amnesia, delirium, and eventually death, if left untreated.[14] Common psychiatric symptoms of niacin deficiency include irritability, poor concentration, anxiety, fatigue, restlessness, apathy, and depression.[14] Studies have indicated that, in patients with alcoholic pellagra, niacin deficiency may be an important factor influencing both the onset and severity of this condition. Patients with alcoholism typically experience increased intestinal permeability, leading to negative health outcomes.

Hartnup disease is a hereditary nutritional disorder resulting in niacin deficiency.[14] This condition was first identified in the 1950s by the Hartnup family in London. It is due to a deficit in the intestines and kidneys, making it difficult for the body to break down and absorb dietary tryptophan. The resulting condition is similar to pellagra, including symptoms of red, scaly rash, and sensitivity to sunlight. Oral niacin is given as a treatment for this condition in doses ranging from 40–200 mg, with a good prognosis if identified and treated early.[14] Niacin synthesis is also deficient in carcinoid syndrome, because of metabolic diversion of its precursor tryptophan to form serotonin.

Medical uses

Abnormal lipids

Niacin is sometimes used in addition to other lipid-lowering medication.[15]

A 2014 review of niacin did not find that it affected either cardiovascular disease or risk of death in those already taking a statin, in spite of raising HDLcholesterol.[2] Niacin alone appears to reduce the rate of cardiovascular events, but not the rate of coronary or cardiovascular deaths.[16][17]

Treatment of deficiency

Niacin and niacinamide are used for prevention and treatment of pellagra.[18]

Contraindications

Niacin is contraindicated with active liver disease, persistent elevated serum transaminases, active peptic ulcer disease, or arterial bleeding.[19]

Side effects

The most common adverse effects are flushing (e.g., warmth, redness, itching and/or tingling), headache, pain, 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.[19] High doses of niacin often temporarily reduce blood pressure as a result of acute vasodilation.[20] In the longer term, high-dose niacin use may persistently lower blood pressure in individuals with hypertension, but more research is needed to determine the extent of this effect.[20]

Facial flushing

Flushing usually lasts for about 15 to 30 minutes, though it can sometimes last up to two hours. It is sometimes accompanied by a prickly or itchingsensation, in particular, in areas covered by clothing. Flushing can be blocked by taking 300 mg of aspirin half an hour before taking niacin, by taking one tablet of ibuprofen per day or by co-administering the prostaglandin receptor antagonist laropiprant. 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 patients no longer experience flushing.[21]Reduction of flushing focuses on altering or blocking the prostaglandin mediated pathway.[22] Slow- or "sustained"-release forms of niacin have been developed to lessen these side effects.[23][24] One study showed the incidence of flushing was significantly lower with a sustained-release formulation,[25]though doses above 2 g per day have been associated with liver damage, in particular, with slow-release formulations.[26]

Prostaglandin (PGD2) is the primary cause of the flushing reaction, with serotonin appearing to have a secondary role in this reaction.[27] The effect is mediated by prostaglandin E2 and D2 due to GPR109A activation of epidermal Langerhans cells and keratinocytes.[28][29] Langerhans cells use cyclooxygenase type 1 (COX-1) for PGE2 production and are more responsible for acute flushing, while keratinocytes are COX-2 dependent and are in active continued vasodilation.[30][31] Flushing was often thought to involve histamine, but histamine has been shown not to be involved in the reaction.[27]

Gastrointestinal and hepatic

Gastrointestinal complaints, such as indigestion, nausea and liver failure, have also been reported. Hepatotoxicity is possibly related to metabolism via amidation resulting in NAD production.[32] The time-release form has a lower therapeutic index for lowering serum lipids relative to this form of toxicity.[33]

Metabolic

Although high doses of niacin may elevate blood sugar, thereby worsening diabetes mellitus,[26] recent studies show the actual effect on blood sugar to be only 5–10%. Patients with diabetes who continued to take anti-diabetes drugs containing niacin did not experience major blood glucose changes. Thus, overall, niacin continues to be recommended as a drug for preventing cardiovascular disease in patients with diabetes.

Hyperuricemia is another side effect of taking high-dose niacin and may exacerbate gout.[34]

Other

Side effects of heart arrhythmias have also been reported.[26][page needed] Increased PT and decreased platelet count have been reported; therefore, these should be monitored closely in patients who are also taking anticoagulants.[19]

Particularly the time-release variety, at extremely high doses, can cause acute toxic reactions.[35] Extremely 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.[36]

In pregnancy

Niacin in doses used to lower cholesterol levels has been associated with birth defects in laboratory animals, with possible consequences for infant development in pregnant women.[26]

Pharmacology

Pharmacodynamics

Niacin's therapeutic effects are partly mediated through the activation of G protein-coupled receptors, including niacin receptor 1 (NIACR1) and niacin receptor 2 (NIACR2) which are highly expressed in adipose tissuespleenimmune cells and keratinocytes but not in other expected organs such as liverkidneyheart or intestine.[37][38] NIACR1 and NIACR2 inhibit cyclic adenosine monophosphate (cAMP) production and thus fat breakdown in adipose tissue and free fatty acids available for liver to produce triglycerides and very-low-density lipoproteins (VLDL) and consequently low-density lipoprotein(LDL) or "bad" cholesterol.[32][39] Decrease in free fatty acids also suppress hepatic expression of apolipoprotein C3 (APOC3) and PPARg coactivator-1b(PGC-1b) thus increase VLDL turn over and reduce its production.[40] It also inhibits diacylglycerol acyltransferase-2 (important hepatic TG synthesis).

The mechanism behind increasing HDL is not totally understood but it seems to be done in various ways. Niacin increases apolipoprotein A1 levels due to anti catabolic effects resulting in higher reverse cholesterol transport. It also inhibits HDL hepatic uptake, down-regulating production of the cholesterol ester transfer protein (CETP) gene.[41] Finally, it stimulates the ABCA1 transporter in monocytes and macrophages and up-regulates peroxisome proliferator-activated receptor γ results in reverse cholesterol transport.[42]

It reduces secondary outcomes associated with atherosclerosis, such as low density lipoprotein cholesterol (LDL), very low-density lipoprotein cholesterol (VLDL-C), and triglycerides (TG), but increases high density lipoprotein cholesterol (HDL).[41] Despite the importance of other cardiovascular risk factors, high HDL was associated with fewer cardiovascular events independent of LDL reduction.[43][44] Other effects include anti-thrombotic and vascular inflammation, improving endothelial function, and plaque stability.[45] Adipokines are the adipocytes’ produced mediators. Some adipokines such as tumor necrosis factor (TNF)-a, interleukins and chemokines, have pro-inflammatory effect and some others such as adiponectin have anti-inflammatory effect that regulates inflammatory process, decrease vascular progression and atherosclerosis.[46]

Niacin also appears to upregulate brain-derived neurotrophic factor (BDNF) and tropomyosin receptor kinase B (TrkB) expression.[47]

Research has been able to show the function of niacin in the pathway lipid metabolism. It is seen that this vitamin can decrease the synthesis of apoB-containing lipoproteins such as VLDL, LDL, IDL and Lipoprotein (a) via several mechanisms: (1) Directly inhibiting the action of DGAT2, a key enzyme for triglyceride synthesis; (2) It has the ability to bind to the receptor HCAR2 thereby decreasing lipolysis and FFA flux to the liver for triglyceride synthesis;[11] and (3) increased apoB catabolism. On the other hand, HDL cholesterol levels are increased by niacin through direct and indirect pathways. (4) Niacin decreases CETP mass and activity, and this synergistic effect with the decrease in triglyceride levels, can indirectly raise HDL cholesterol levels. The study has also been able to show direct effects on the beta chain of ATP synthase (5) and on production (6) and hepatic uptake (7) of apoA-I also increase HDL cholesterol levels. Thus by affecting the pathway reducing lipid levels help in reducing CVD.[48]

Pharmacokinetics

 
Niacin, serotonin (5-hydroxytryptamine), and melatonin biosynthesis from tryptophan

Biosynthesis

The liver can synthesize niacin from the essential amino acid tryptophan, requiring 60 mg of tryptophan to make one mg of niacin.[49] Riboflavinvitamin B6 and iron are required in some of the reactions involved in the conversion of tryptophan to NAD.

Physical and chemical properties

Laboratory synthesis

Several thousand tons of niacin are manufactured each year, starting from 3-methylpyridine.

Preparations

Many preparations of niacin are available over-the-counter as dietary supplements. Non-prescription extended release niacin, such as Endur-acin, which uses a wax matrix to delay release is available as well.[50][51]

Over-the counter plain niacin has FDA regulatory approval.[52] Some “no flush” types, such as inositol hexanicotinate contain convertible niacin compounds, but have little clinical efficacy in reducing cholesterol levels.[53][54] “Slow release” varieties have higher hepatotoxic activity, hence some types of prescription niacin are not recommended due to potential harm.[55]

Nicotinic acid

Extended release

A prescription extended release niacin, Niaspan, has a film coating that delays release of the niacin, resulting in an absorption over a period of 8–12 hours. The extended release formulations generally reduce vasodilation and flushing side effects, but increase the risk of hepatotoxicity compared to the immediate release forms.[56][57][58]

A formulation of laropiprant (Merck & Co., Inc.) and niacin had previously been approved for use in Europe and marketed as Tredaptive. Laropiprant is a prostaglandin D2 binding drug shown to reduce vasodilatation and flushing up to 73%.[41][59][60][61] The HPS2-THRIVE study,[62] a study sponsored by Merck, 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 complete withdrawal of Tredaptive from the international market.[63][64]

Inositol hexanicotinate

One form of dietary supplement is inositol hexanicotinate (IHN), which is inositol that has been esterified 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 mg/tablets or capsules. 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 the active form of the medication. While this form of niacin does not cause the flushing associated with the immediate-release products, the evidence that it has lipid-modifying functions is disputed. As the clinical trials date from the early 1960s (Dorner, Welsh) or the late 1970s (Ziliotto, Kruse, Agusti), it is difficult to assess them by today's standards.[65] One of the last of those studies affirmed the superiority of inositol and xantinol esters of nicotinic acid for reducing serum free fatty acid,[66] but other studies conducted during the same period found no benefit.[67] Studies explain that this is primarily because "flush-free" preparations do not contain any free nicotinic acid. A more recent placebo-controlled trial was small (n=11/group), but results after three months at 1500 mg/day showed no trend for improvements in total cholesterol, LDL-C, HDL-C or triglycerides.[68] Thus, so far there is not enough evidence to recommend IHN to treat dyslipidemia.

Nicotinamide[edit]

Nicotinamide may be obtained from the diet where it is present primarily as NAD+ and NADP+. These are hydrolysed in the intestine and the resulting nicotinamide is absorbed either as such, or following its hydrolysis to nicotinic acid. Nicotinamide is present in nature in only small amounts. In unprepared foods, niacin is present mainly in the form of the cellular pyridine nucleotides NAD and NADP. Enzymatic hydrolysis of the co-enzymes can occur during the course of food preparation. Boiling releases most of the total niacin present in sweet corn as nicotinamide (up to 55 mg/kg).[69]

Nicotinamide may be toxic to the liver at doses exceeding 3 g/day for adults.[70]

Food sources

Niacin is found in a variety of foods, including liver, chicken, beef, fish, cereal, peanuts, and legumes, and is also synthesized from tryptophan, an essential amino acid found in most forms of protein.

Animal products:

Fruits and vegetables:

Seeds:

Fungi:

Other:

History

Niacin was first described by chemist Hugo Weidel in 1873 in his studies of nicotine.[74] The original preparation remains useful: The oxidation of nicotineusing nitric acid.[75] For the first time, niacin was extracted by Casimir Funk, but he thought that it was thiamine and due to the discovered amine group he coined the term "vitamine". Niacin was extracted from livers by biochemist Conrad Elvehjem in 1937, who later identified the active ingredient, then referred to as the "pellagra-preventing factor" and the "anti-blacktongue factor."[76] Soon after, in studies conducted in Alabama and Cincinnati, Dr. Tom Spies found that nicotinic acid cured the sufferers of pellagra.[77]

Niacin is referred to as vitamin B3 because it was the third of the B vitamins to be discovered. It has historically been referred to as "vitamin PP", "vitamin P-P" and "PP-factor", that are derived from the term "pellagra-preventive factor".[78] When the biological significance of nicotinic acid was realized, it was thought appropriate to choose a name to dissociate it from nicotine, to avoid the perception that vitamins or niacin-rich food contains nicotine, or that cigarettes contain vitamins.[79] The resulting name 'niacin' was derived from nicotinic acid + vitamin.[78][80]

Carpenter found in 1951 that niacin in corn is biologically unavailable, and can be released only in very alkaline lime water of pH 11.[81]

In 1955, Altschul and colleagues described niacin as having a lipid lowering property.[82] Niacin is the oldest lipid lowering drug.

On April 22, 2014, Pennsylvania State University researchers working with NASA at the Goddard Astrobiology Analytical Laboratory reported[83] of finding niacin within eight CM-2 type carbonaceous chondrite meteorites. The meteorite’s vitamin B3 levels ranged from 30–600 parts per billion, the study reports. Related molecules discovered in the meteorites include pyridine carboxylic acids and pyridine dicarboxylic acids.

Research

In animal models and in vitro, niacin produces marked anti-inflammatory effects in a variety of tissues – including the brain, gastrointestinal tract, skin, and vascular tissue – through the activation of NIACR1.[84][85][86][87] Niacin has been shown to attenuate neuroinflammation and may have efficacy in treating neuroimmune disorders such as multiple sclerosis and Parkinson's disease.[84][87] Unlike niacin, nicotinamide does not activate NIACR1, however both niacin and nicotinamide activate the G protein-coupled estrogen receptor (GPER) in vitro.[88]

References

  1. Jump up^  Nomenclature of Organic Chemistry : IUPAC Recommendations and Preferred Names 2013 (Blue Book). Cambridge: The Royal Society of Chemistry. 2014. pp. 747, 750. doi:10.1039/9781849733069-FP001ISBN 978-0-85404-182-4.
  2. Jump up to:a b Keene, D; Price, C; Shun-Shin, MJ; Francis, DP (18 July 2014). "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."BMJ (Clinical research ed.)349: g4379. doi:10.1136/bmj.g4379PMC 4103514Freely accessiblePMID 25038074.
  3. Jump up^  Bruckert, Eric; Labreuche, Julien; Amarenco, Pierre (June 2010). "Meta-analysis of the effect of nicotinic acid alone or in combination on cardiovascular events and atherosclerosis"Atherosclerosis210 (2): 353–361. doi:10.1016/j.atherosclerosis.2009.12.023PMID 20079494. Retrieved 13 December 2014.
  4. Jump up^  Cantarella L, Gallifuoco A, Malandra A, Martínková L, Spera A, Cantarella M (2011). "High-yield continuous production of nicotinic acid via nitrile hydratase-amidase cascade reactions using cascade CSMRs". Enzyme and Microbial Technology48 (4–5): 345–50. doi:10.1016/j.enzmictec.2010.12.010PMID 22112948.
  5. Jump up^  Cox, Michael; Lehninger, Albert L; Nelson, David R. (2000). Lehninger principles of biochemistry. New York: Worth Publishers. ISBN 1-57259-153-6.
  6. Jump up to:a b Wan P, Moat S, Anstey A (2011). "Pellagra: A review with emphasis on photosensitivity". The British journal of dermatology164 (6): 1188–200. doi:10.1111/j.1365-2133.2010.10163.xPMID 21128910.
  7. Jump up^  Ishii N, Nishihara Y (1981). "Pellagra among chronic alcoholics: Clinical and pathological study of 20 necropsy cases"Journal of neurology, neurosurgery, and psychiatry44 (3): 209–15. doi:10.1136/jnnp.44.3.209PMC 490893Freely accessiblePMID 7229643.
  8. Jump up^  Jaconello P (October 1992). "Niacin versus niacinamide"CMAJ147 (7): 990. PMC 1336277Freely accessiblePMID 1393911.
  9. Jump up^  Kennedy DO (January 2016). "B Vitamins and the Brain: Mechanisms, Dose and Efficacy-A Review"Nutrients8 (2). doi:10.3390/nu8020068PMC 4772032Freely accessiblePMID 26828517.
  10. Jump up^  Kirkland JB (May 2012). "Niacin requirements for genomic stability". Mutat. Res733 (1-2): 14–20. doi:10.1016/j.mrfmmm.2011.11.008PMID 22138132.
  11. Jump up^  Niacin. IN: Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline. National Academy Press. 1998, PP.123-149.
  12. Jump up^  Tolerable Upper Intake Levels For Vitamins And Minerals (PDF), European Food Safety Authority, 2006
  13. Jump up^  Pitsavas S, Andreou C, Bascialla F, Bozikas VP, Karavatos A (2004). "Pellagra encephalopathy following B-complex vitamin treatment without niacin"Int J Psychiatry Med34 (1): 91–5. doi:10.2190/29XV-1GG1-U17K-RGJHPMID 15242145.
  14. Jump up to:a b c d Prakash R, Gandotra S, Singh LK, Das B, Lakra A (2008). "Rapid resolution of delusional parasitosis in pellagra with niacin augmentation therapy"General Hospital Psychiatry30 (6): 581–4. doi:10.1016/j.genhosppsych.2008.04.011PMID 19061687.
  15. Jump up^  Niacin tablet label Updated March 14, 2013. Page accessed Feb 11, 2016
  16. Jump up^  Bruckert E, Labreuche J, Amarenco P (2010). "Meta-analysis of the effect of nicotinic acid alone or in combination on cardiovascular events and atherosclerosis". Atherosclerosis210 (2): 353–61. doi:10.1016/j.atherosclerosis.2009.12.023PMID 20079494.
  17. Jump up^  Duggal JK, Singh M, Attri N, Singh PP, Ahmed N, Pahwa S, Molnar J, Singh S, Khosla S, Arora R (2010). "Effect of niacin therapy on cardiovascular outcomes in patients with coronary artery disease". Journal of cardiovascular pharmacology and therapeutics15 (2): 158–66. doi:10.1177/1074248410361337PMID 20208032.
  18. Jump up^  "Niacin and niacinamide (Vitamin B3)". MedlinePlus, US National Library of Medicine, National Institutes of Health. 2016. Retrieved 12 October 2016.
  19. Jump up to:a b c Kos Pharmaceuticals Inc. Niaspan® (niacin extended-release) tablets prescribing information. Cranbury, NJ; 2005 Oct.
  20. Jump up to:a b Bays HE, Rader DJ (2009). "Does nicotinic acid (niacin) lower blood pressure?"Int. J. Clin. Pract63 (1): 151–9. doi:10.1111/j.1742-1241.2008.01934.xPMC 2705821Freely accessiblePMID 19054161.
  21. Jump up^  "Guidelines for Niacin Therapy For the Treatment of Elevated Lipoprotein a (Lpa)" (PDF)Rush Hemophilia & Thrombophilia Center. 27 July 2005 [15 August 2002]. Retrieved 20 November 2009facial flushing is a common side effect of niacin therapy that usually subsides after several weeks of consistent niacin use
  22. Jump up^  Kamanna VS, Kashyap ML (2008). "Mechanism of action of niacin". The American journal of cardiology101 (8A): 20B–26B. doi:10.1016/j.amjcard.2008.02.029PMID 18375237.
  23. Jump up^  Katzung, Bertram G. (2006). Basic and clinical pharmacology. New York: McGraw-Hill Medical Publishing Division. ISBN 0-07-145153-6.
  24. Jump up^  Barter, P (2006). "Options for therapeutic intervention: How effective are the different agents?". European Heart Journal Supplements8 (F): F47–F53. doi:10.1093/eurheartj/sul041.
  25. Jump up^  Chapman MJ, Assmann G, Fruchart JC, Shepherd J, Sirtori C (2004). "Raising high-density lipoprotein cholesterol with reduction of cardiovascular risk: the role of nicotinic acid—a position paper developed by the European Consensus Panel on HDL-C". Curr Med Res Opin20 (8): 1253–68. doi:10.1185/030079904125004402PMID 15324528.
  26. Jump up to:a b c d Brunton, Laurence L.; Lazo, John S.; Parker, Keith, eds. (2005). Goodman & Gilman's The Pharmacological Basis of Therapeutics (11th ed.). New York: McGraw-Hill. ISBN 0-07-142280-3.
  27. Jump up to:a b Papaliodis D, Boucher W, Kempuraj D, Michaelian M, Wolfberg A, House M, Theoharides TC (December 2008). "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"J Pharmacol Exp Ther327 (3): 665–72. doi:10.1124/jpet.108.141333PMID 18784348.
  28. Jump up^  Benyó Z, Gille A, Kero J, Csiky M, Suchánková MC, Nüsing RM, Moers A, Pfeffer K, Offermanns S (2005). "GPR109A (PUMA-G/HM74A) mediates nicotinic acid-induced flushing"The Journal of Clinical Investigation115(12): 3634–40. doi:10.1172/JCI23626PMC 1297235Freely accessiblePMID 16322797.
  29. Jump up^  Benyó Z, Gille A, Bennett CL, Clausen BE, Offermanns S (2006). "Nicotinic acid-induced flushing is mediated by activation of epidermal langerhans cells". Molecular Pharmacology70 (6): 1844–9. doi:10.1124/mol.106.030833PMID 17008386.
  30. Jump up^  Hanson J, Gille A, Zwykiel S, Lukasova M, Clausen BE, Ahmed K, Tunaru S, Wirth A, Offermanns S (2010). "Nicotinic acid- and monomethyl fumarate-induced flushing involves GPR109A expressed by keratinocytes and COX-2-dependent prostanoid formation in mice"The Journal of Clinical Investigation120 (8): 2910–9. doi:10.1172/JCI42273PMC 2912194Freely accessiblePMID 20664170.
  31. Jump up^  Maciejewski-Lenoir D, Richman JG, Hakak Y, Gaidarov I, Behan DP, Connolly DT (2006). "Langerhans cells release prostaglandin D2 in response to nicotinic acid". The Journal of Investigative Dermatology126 (12): 2637–46. doi:10.1038/sj.jid.5700586PMID 17008871.
  32. Jump up to:a b Gille A, Bodor ET, Ahmed K, Offermanns S (2008). "Nicotinic acid: Pharmacological effects and mechanisms of action". Annual Review of Pharmacology and Toxicology48 (1): 79–106. doi:10.1146/annurev.pharmtox.48.113006.094746PMID 17705685.
  33. Jump up^  Rader JI, Calvert RJ, Hathcock JN (January 1992). "Hepatic toxicity of unmodified and time-release preparations of niacin". The American Journal of Medicine92 (1): 77–81. doi:10.1016/0002-9343(92)90018-7PMID 1731514.
  34. Jump up^  Capuzzi DM, Morgan JM, Brusco OA, Intenzo CM (2000). "Niacin dosing: relationship to benefits and adverse effects". Curr Atheroscler Rep2 (1): 64–71. doi:10.1007/s11883-000-0096-yPMID 11122726.
  35. Jump up^  Mittal MK, Florin T, Perrone J, Delgado JH, Osterhoudt KC (2007). "Toxicity from the use of niacin to beat urine drug screening". Ann Emerg Med50 (5): 587–90. doi:10.1016/j.annemergmed.2007.01.014PMID 17418450.
  36. Jump up^  Gass JD (2003). "Nicotinic acid maculopathy". Retina (Philadelphia, Pa.)23 (6 Suppl): 500–10. PMID 15035390.
  37. Jump up^  Soga T, Kamohara M, Takasaki J, Matsumoto S, Saito T, Ohishi T, Hiyama H, Matsuo A, Matsushime H, Furuichi K (2003). "Molecular identification of nicotinic acid receptor". Biochemical and Biophysical Research Communications303 (1): 364–9. doi:10.1016/S0006-291X(03)00342-5PMID 12646212.
  38. Jump up^  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 (2003). "Molecular identification of high and low affinity receptors for nicotinic acid". The Journal of Biological Chemistry278 (11): 9869–74. doi:10.1074/jbc.M210695200PMID 12522134.
  39. Jump up^  Wanders D, Judd RL (2011). "Future of GPR109A agonists in the treatment of dyslipidaemia". Diabetes, obesity & metabolism13 (8): 685–91. doi:10.1111/j.1463-1326.2011.01400.xPMID 21418500.
  40. Jump up^  Hernandez C, Molusky M, Li Y, Li S, Lin JD (2010). "Regulation of hepatic ApoC3 expression by PGC-1β mediates hypolipidemic effect of nicotinic acid"Cell Metabolism12 (4): 411–9. doi:10.1016/j.cmet.2010.09.001PMC 2950832Freely accessiblePMID 20889132.
  41. Jump up to:a b c Villines TC, Kim AS, Gore RS, Taylor AJ (2012). "Niacin: The evidence, clinical use, and future directions". Current atherosclerosis reports14 (1): 49–59. doi:10.1007/s11883-011-0212-1PMID 22037771.
  42. Jump up^  Rubic T, Trottmann M, Lorenz RL (2004). "Stimulation of CD36 and the key effector of reverse cholesterol transport ATP-binding cassette A1 in monocytoid cells by niacin". Biochemical Pharmacology67 (3): 411–9. doi:10.1016/j.bcp.2003.09.014PMID 15037193.
  43. Jump up^  Barter P, Gotto AM, LaRosa JC, Maroni J, Szarek M, Grundy SM, Kastelein JJ, Bittner V, Fruchart JC (2007). "HDL cholesterol, very low levels of LDL cholesterol, and cardiovascular events". The New England Journal of Medicine357 (13): 1301–10. doi:10.1056/NEJMoa064278PMID 17898099.
  44. Jump up^  Jafri H, Alsheikh-Ali AA, Karas RH (2010). "Meta-analysis: Statin therapy does not alter the association between low levels of high-density lipoprotein cholesterol and increased cardiovascular risk". Annals of Internal Medicine153 (12): 800–8. doi:10.7326/0003-4819-153-12-201012210-00006PMID 21173414.
  45. Jump up^  Wu BJ, Yan L, Charlton F, Witting P, Barter PJ, Rye KA (2010). "Evidence that niacin inhibits acute vascular inflammation and improves endothelial dysfunction independent of changes in plasma lipids". Arteriosclerosis, thrombosis, and vascular biology30 (5): 968–75. doi:10.1161/ATVBAHA.109.201129PMID 20167660.
  46. Jump up^  Gustafson B (2010). "Adipose tissue, inflammation and atherosclerosis". Journal of atherosclerosis and thrombosis17 (4): 332–41. doi:10.5551/jat.3939PMID 20124732.
  47. Jump up^  Fu L, Doreswamy V, Prakash R (2014). "The biochemical pathways of central nervous system neural degeneration in niacin deficiency"Neural Regen Res9 (16): 1509–1513. doi:10.4103/1673-5374.139475PMC 4192966Freely accessiblePMID 25317166Recent evidences suggest that niacin administration may up-regulate the expression of BDNF-TrkB. ... At present, we can safely raise the possibility that niacin-mediated neural growth by the BDNF-TrkB pathway could be at least partially mediated by enhanced HDL-C levels.
  48. Jump up^  Creider, JC; Hegele, RA; Joy, TR (September 2012). "Niacin: another look at an underutilized lipid-lowering medication.". Nature reviews. Endocrinology8 (9): 517–28. doi:10.1038/nrendo.2012.22PMID 22349076.
  49. Jump up^  Jacobson, EL (2007). "Niacin"Linus Pauling Institute. Retrieved 31 March 2008.
  50. Jump up^  Endur-Acin Oral : Uses, Side Effects, Interactions, Pictures, Warnings & Dosing – WebMD
  51. Jump up^  L-arginine, niacin, phytosterols, pantethine, calcium, vitamin c, b complex, cholesterol control without diet, 8 week cholesterol cure, linus pauling
  52. Jump up^  http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm?fuseaction=Search.SearchAction&SearchType=BasicSearch&SearchTerm=NIACIN
  53. Jump up^  Study Finds Extended Release Niacin, but not IHN, Effective in Lowering Cholesterol Levels
  54. Jump up^  Norris RB (2006). ""Flush-free niacin": Dietary supplement may be "benefit-free"". Preventive cardiology9 (1): 64–5. doi:10.1111/j.1520-037X.2006.04736.xPMID 16407706.
  55. Jump up^  "A case for immediate-release niacin". Heart Lung41: 95–8. 2012. doi:10.1016/j.hrtlng.2010.07.019PMID 21414665.
  56. Jump up^  Pharmacokinetics and dose recommendations of Niaspan® in chronic kidney disease and dialysis patients
  57. Jump up^  Niaspan (Niacin) Drug Information: Description, User Reviews, Drug Side Effects, Interactions – Prescribing Information at RxList
  58. Jump up^  About NIASPAN® (niacin extended-release)
  59. Jump up^  Lai E, De Lepeleire I, Crumley TM, Liu F, Wenning LA, Michiels N, Vets E, O'Neill G, Wagner JA, Gottesdiener K (2007). "Suppression of niacin-induced vasodilation with an antagonist to prostaglandin D2 receptor subtype 1". Clinical pharmacology and therapeutics81 (6): 849–57. doi:10.1038/sj.clpt.6100180PMID 17392721.
  60. Jump up^  Paolini JF, Bays HE, Ballantyne CM, Davidson M, Pasternak R, Maccubbin D, Norquist JM, Lai E, Waters MG, Kuznetsova O, Sisk CM, Mitchel YB (November 2008). "Extended-release niacin/laropiprant: reducing niacin-induced flushing to better realize the benefit of niacin in improving cardiovascular risk factors". Cardiol Clin26 (4): 547–60. doi:10.1016/j.ccl.2008.06.007PMID 19031552.
  61. Jump up^  Kamanna VS, Vo A, Kashyap ML (2008). "Nicotinic acid: Recent developments". Current Opinion in Cardiology23 (4): 393–8. doi:10.1097/HCO.0b013e3283021c82PMID 18520725..
  62. Jump up^  Treatment of HDL to Reduce the Incidence of Vascular Events HPS2-THRIVE – Full Text View – ClinicalTrials.gov
  63. Jump up^  Medscape: Medscape Access
  64. Jump up^  "Merck begins overseas recall of HDL cholesterol drug"Reuters. 11 January 2013.
  65. Jump up^  Taheri, R (15 January 2003). "No-Flush Niacin for the Treatment of Hyperlipidemia"Medscape. Retrieved 31 March 2008.
  66. Jump up^  Kruse W, Kruse W, Raetzer H, Heuck CC, Oster P, Schellenberg B, Schlierf G (1979). "Nocturnal inhibition of lipolysis in man by nicotinic acid and derivatives". European Journal of Clinical Pharmacology16 (1): 11–15. doi:10.1007/BF00644960PMID 499296.
  67. Jump up^  Meyers CD, Carr MC, Park S, Brunzell JD (2003). "Varying cost and free nicotinic acid content in over-the-counter niacin preparations for dyslipidemia" (PDF)Annals of Internal Medicine139 (12): 996–1002. doi:10.7326/0003-4819-139-12-200312160-00009PMID 14678919.
  68. Jump up^  Benjó AM, Maranhão RC, Coimbra SR, Andrade AC, Favarato D, Molina MS, Brandizzi LI, da Luz PL (2006). "Accumulation of chylomicron remnants and impaired vascular reactivity occur in subjects with isolated low HDL cholesterol: effects of niacin treatment". Atherosclerosis187 (1): 116–122. doi:10.1016/j.atherosclerosis.2005.08.025PMID 16458316.
  69. Jump up^  F. Aguilar; U.R. Charrondiere; B. Dusemund; P. Galtier; J. Gilbert; D.M. Gott; S. Grilli; R. Guertler; G.E.N. Kass; J. Koenig; C. Lambré; J-C. Larsen; J-C. Leblanc; A. Mortensen; D. Parent-Massin; I. Pratt; I.M.C.M. Rietjens; I. Stankovic; P. Tobback; T. Verguieva; R.A. Woutersen (2009). "Inositol hexanicotinate (inositol hexaniacinate) as a source of niacin (vitamin B3) added for nutritional purposes in food supplements" (PDF)The EFSA Journal949: 1–20.
  70. Jump up^  Knip M, Douek IF, Moore WP, Gillmor HA, McLean AE, Bingley PJ, Gale EA (2000). "Safety of high-dose nicotinamide: a review". Diabetologia43 (11): 1337–45. doi:10.1007/s001250051536PMID 11126400.
  71. Jump up^  Diet & Fitness today. "Niacin in beer".
  72. Jump up^  "Vegemite – Nutritional information". Retrieved 6 November 2013.
  73. Jump up^  "Marmite – Nutritional information". Retrieved 19 November 2014.
  74. Jump up^  Weidel, H (1873). "Zur Kenntniss des Nicotins". Justus Liebigs Annalen der Chemie und Pharmacie165 (2): 330–349. doi:10.1002/jlac.18731650212.
  75. Jump up^  Samuel M. McElvain (1941). "Nicotinic Acid" (PDF)Org. Synth.Coll. Vol.1, p. 385
  76. Jump up^  Elvehjem CA, Madden RJ, Strongandd FM, Woolley DW (1938). "The isolation and identification of the anti-blacktongue factor J" (PDF)J. Biol. Chem123 (1): 137–149.
  77. Jump up^  Dr. Joseph Goldberger and the war on Pellagra – Office of NIH History
  78. Jump up to:a b "Pellagra And Its Prevention And Control In Major Emergencies"(PDF)World Health Organization. World Health Organization. Retrieved 17 April 2015.
  79. Jump up^  "Niacin and Nicotinic Acid"Journal of the American Medical Association. American Medical Association. 118 (10): 823. March 7, 1942. doi:10.1001/jama.1942.02830100053014. Retrieved May 7, 2016.
  80. Jump up^  "Niacin and Niacin Amide"Journal of the American Medical Association. American Medical Association. 118 (10): 819. March 7, 1942. doi:10.1001/jama.1942.02830100049011. Retrieved May 7, 2016.
  81. Jump up^  Laguna J, Carpenter KJ (September 1951). "Raw versus processed corn in niacin-deficient diets"J. Nutr45 (1): 21–8. PMID 14880960.
  82. Jump up^  Altschul R, Hoffer A, Stephen JD (1955). "Influence of nicotinic acid on serum cholesterol in man". Archives of Biochemistry and Biophysics54 (2): 558–9. doi:10.1016/0003-9861(55)90070-9PMID 14350806.
  83. Jump up^  Vitamins B3 found in Meteorites http://canadajournal.net/science/vitamins-b3-found-meteorites-study-6534-2014/
  84. Jump up to:a b Offermanns S, Schwaninger M (2015). "Nutritional or pharmacological activation of HCA(2) ameliorates neuroinflammation". Trends Mol Med21(4): 245–255. doi:10.1016/j.molmed.2015.02.002PMID 25766751Neuroinflammatory cells express HCA2, a receptor for the endogenous neuroprotective ketone body β-hydroxybutyrate (BHB) as well as for the drugs dimethyl fumarate (DMF) and nicotinic acid, which have established efficacy in the treatment of MS and experimental stroke, respectively. This review summarizes the evidence that HCA2 is involved in the therapeutic effects of DMF, nicotinic acid, and ketone bodies in reducing neuroinflammation.
  85. Jump up^  Chai JT, Digby JE, Choudhury RP (May 2013). "GPR109A and vascular inflammation"Curr Atheroscler Rep15 (5): 325. doi:10.1007/s11883-013-0325-9PMC 3631117Freely accessiblePMID 23526298As GPR109A's primary pharmacological ligand in clinical use, niacin has been used for over 50 years in the treatment of cardiovascular disease, mainly due to its favourable effects on plasma lipoproteins.
  86. Jump up^  Graff EC, Fang H, Wanders D, Judd RL (February 2016). "Anti-inflammatory effects of the hydroxycarboxylic acid receptor 2". Metab. Clin. Exp65 (2): 102–113. doi:10.1016/j.metabol.2015.10.001PMID 26773933HCA2 is highly expressed on immune cells, including macrophages, monocytes, neutrophils and dermal dendritic cells, among other cell types. ... Recent studies demonstrate that HCA2 mediates profound anti-inflammatory effects in a variety of tissues.
  87. Jump up to:a b Wakade C, Chong R (December 2014). "A novel treatment target for Parkinson's disease". J. Neurol. Sci347 (1-2): 34–38. doi:10.1016/j.jns.2014.10.024PMID 25455298.
  88. Jump up^  Santolla MF, De Francesco EM, Lappano R, Rosano C, Abonante S, Maggiolini M (July 2014). "Niacin activates the G protein estrogen receptor (GPER)-mediated signalling". Cell. Signal26 (7): 1466–1475. doi:10.1016/j.cellsig.2014.03.011PMID 24662263Nicotinic acid, also known as niacin, is the water soluble vitamin B3 used for decades for the treatment of dyslipidemic diseases. Its action is mainly mediated by the G protein-coupled receptor (GPR) 109A.

External links

Source: https://en.wikipedia.org/wiki/Niacin