Nicotinic acid

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Nicotinic acid
Kekule, skeletal formula of nicotinic acid Niacin structure.svg
Kekulé, skeletal formula of nicotinic acid
Ball and stick model of nicotinic acid Niacin-3D-balls.png
Ball and stick model of nicotinic acid
Names
Pronunciation /ˈnaɪəsɪn/
Preferred IUPAC name
Pyridine-3-carboxylic acid [1]
Other names
  • Niacin (USAN US) [2]
  • Bionic
  • Vitamin B3
  • Vitamin PP
Identifiers
3D model (JSmol)
109591
ChEBI
ChEMBL
ChemSpider
DrugBank
ECHA InfoCard 100.000.401 OOjs UI icon edit-ltr-progressive.svg
EC Number
  • 200-441-0
3340
KEGG
MeSH Niacin
PubChem CID
RTECS number
  • QT0525000
UNII
  • InChI=1S/C6H5NO2/c8-6(9)5-2-1-3-7-4-5/h1-4H,(H,8,9) Yes check.svgY
    Key: PVNIIMVLHYAWGP-UHFFFAOYSA-N Yes check.svgY
  • InChI=1/C6H5NO2/c8-6(9)5-2-1-3-7-4-5/h1-4H,(H,8,9)
    Key: PVNIIMVLHYAWGP-UHFFFAOYAA
  • OC(=O)c1cccnc1
Properties
C6H5NO2
Molar mass 123.111 g·mol−1
AppearanceWhite, 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[ citation needed ]
Thermochemistry
−344.9 kJ mol−1
−2.73083 MJ mol−1
Pharmacology
C04AC01 ( WHO ) C10BA01 ( WHO ) C10AD02 ( WHO ) C10AD52 ( WHO )
License data
Intramuscular, by mouth
Pharmacokinetics:
20–45 min
Hazards
GHS labelling:
GHS-pictogram-exclam.svg
Warning
H319
P264, P280, P305+P351+P338, P337+P313, P501
NFPA 704 (fire diamond)
NFPA 704.svgHealth 1: Exposure would cause irritation but only minor residual injury. E.g. turpentineFlammability 1: Must be pre-heated before ignition can occur. Flash point over 93 °C (200 °F). E.g. canola oilInstability 0: Normally stable, even under fire exposure conditions, and is not reactive with water. E.g. liquid nitrogenSpecial hazards (white): no code
1
1
0
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 check.svgY  verify  (what is  Yes check.svgYX mark.svgN ?)
Nicotinic acid
INN: Nicotinic acid
Clinical data
Trade names Niacor, Niaspan, others
AHFS/Drugs.com Monograph
MedlinePlus a682518
License data
Pregnancy
category
Routes of
administration 		Intramuscular, by mouth
Legal status
Legal status
  • US: OTC / Rx-only
Identifiers
PDB ligand
CompTox Dashboard (EPA)
ECHA InfoCard 100.000.401 OOjs UI icon edit-ltr-progressive.svg
Space-filling model of nicotinic acid Vitamin B3 (Niacine) space filling model.jpg
Space-filling model of nicotinic acid

Nicotinic acid, [a] or niacin, [b] is an organic compound and a vitamer of  vitamin B3, an essential human nutrient. [4] [5] It is produced by plants and animals from the amino acid tryptophan. [6] Niacin is obtained in the diet from a variety of whole and processed foods, with highest contents in fortified packaged foods, meat, poultry, red fish such as tuna and salmon, lesser amounts in nuts, legumes and seeds. [5] [4] 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. [7] Many countries mandate its addition to wheat flour or other food grains, thereby reducing the risk of pellagra. [5] [8]

The amide derivative nicotinamide is a component of the coenzymes nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP+). Although nicotinic acid and nicotinamide are identical in their vitamin activity, nicotinamide does not have the same pharmacological, lipid-modifying effects or side effects as nicotinic acid, i.e., when nicotinic acid takes on the -amide group, it does not reduce cholesterol nor cause flushing. [9] [10] 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. [11]

Nicotinic acid is also a prescription medication. [12] Amounts far in excess of the recommended dietary intake for vitamin functions will lower blood triglycerides and low density lipoprotein cholesterol (LDL-C), and raise blood 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 mg/day, increased over time until a therapeutic effect is achieved. Immediate-release doses can be as high as 3,000 mg/day; sustained-release as high as 2,000 mg/day. [12] Despite the proven lipid changes, nicotinic acid has not been found useful for decreasing the risk of cardiovascular disease in those already on a statin. [13] A 2010 review had concluded that nicotinic acid was effective as a mono-therapy, [14] 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. [15] Prescription nicotinic acid was shown to cause hepatotoxicity [16] and increase risk of type 2 diabetes. [17] [18] nicotinic acid prescriptions in the U.S. had peaked in 2009 at 9.4 million, declining to 800 thousand by 2020. [19]

Nicotinic acid has the formula C
6H
5NO
2 and belongs to the group of the pyridinecarboxylic acids. [5] As the precursor for nicotinamide adenine dinucleotide and nicotinamide adenine dinucleotide phosphate, it is involved in DNA repair. [20]

Definition

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. [21] Vitamin intake recommendations made by several countries are that intakes of 14–18 mg/day are sufficient to meet the needs of healthy adults. [6] [22] [23] Nicotinic acid but also nicotinamide are used for prevention and treatment of pellagra, a disease caused by lack of the vitamin. [7] [21] When nicotinic acid is used as a medicine to treat elevated cholesterol and triglycerides, daily doses range from 500 to 3,000 mg/day. [24] [25] High-dose nicotinamide does not have this medicinal effect. [21]

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 mg per serving. These products often have a Structure/Function health claim [26] 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. [27] More than 30 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. [4]

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. [24] [25] It is used either as a monotherapy or in combination with other lipid-modifying drugs. Dosages start at 500 mg/day and are often gradually increased to as high as 3000 mg/day for immediate release or 2000 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). [24] [25] Prescriptions in the US peaked in 2009, at 9.4 million[ citation needed ] and had declined to 800 thousand by 2020. [19]

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 HDL cholesterol in patients already taking statins. [13] [28] Reported side effects include an increased risk of new-onset type 2 diabetes. [15] [17] [18] [29]

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). [30] The lipid-therapeutic effects of nicotinic acid are partly mediated through the activation of G protein-coupled receptors, including hydroxycarboxylic acid receptor 2 (HCA2)and hydroxycarboxylic acid receptor 3 (HCA3), which are highly expressed in body fat. [31] [32] HCA2 and HCA3 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. [33] [34] [35] A decrease in free fatty acids also suppresses liver expression of apolipoprotein C3 and PPARg coactivator-1b, thus increasing VLDL-C turnover and reducing its production. [36] Nicotinic acid also directly inhibits the action of diacylglycerol O-acyltransferase 2 (DGAT2) a key enzyme for triglyceride synthesis. [35]

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-C. [37] [38] It also inhibits HDL-C hepatic uptake by suppressing production of the cholesterol ester transfer protein (CETP) gene. [30] It stimulates the ABCA1 transporter in monocytes and macrophages and upregulates peroxisome proliferator-activated receptor gamma, resulting in reverse cholesterol transport. [39]

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 U.S. Food and Drug Administration (FDA) in 2001. [40] The combination niacin/simvastatin was approved by the FDA in 2008. [41] [42] Subsequently, large outcome trials using these nicotinic acid and statin therapies were unable to demonstrate incremental benefit of nicotinic acid beyond statin therapy alone. [43] 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. [44]

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. [25] [45] 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. [24] [25] [45] 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. [24] [25] [45]

Adverse effects

The most common adverse effects of medicinal nicotinic acid (500–3000 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. [5] [4] [45] These can be minimized by initiating therapy at low dosages, increasing dosage gradually, and avoiding administration on an empty stomach. [45]

The acute adverse effects of high-dose nicotinic acid therapy (1–3 grams per day) – which is commonly used in the treatment of hyperlipidemias – can further include hypotension, fatigue, glucose intolerance and insulin resistance, heartburn, blurred or impaired vision, and macular edema. [5] [4] With long-term use, the adverse effects of high-dose nicotinic acid therapy (750 mg per day) also include liver failure (associated with fatigue, nausea, and loss of appetite), hepatitis, and acute liver failure; [5] [4] these hepatotoxic effects of nicotinic acid occur more often when extended-release dosage forms are used. [5] [4] The long-term use of nicotinic acid at greater than or equal to 2 grams per day also significantly increases the risk of cerebral hemorrhage, ischemic stroke, gastrointestinal ulceration and bleeding, diabetes, dyspepsia, and diarrhea. [4]

Flushing

Flushing – a short-term dilatation of skin arterioles, causing reddish skin color – 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 [5] [4] due to elevation in prostaglandin GD2 (PGD2) and serotonin. [46] [47] [48] [49] Flushing was often thought to involve histamine, but histamine has been shown not to be involved in the reaction. [46] Flushing is sometimes accompanied by a prickly or itching sensation, in particular, in areas covered by clothing. [4]

Prevention of flushing requires altering or blocking the prostaglandin-mediated pathway. [4] [50] 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. [4] Acquired tolerance will also help reduce flushing; after several weeks of a consistent dose, most people no longer experience flushing. [4] Slow- or "sustained"-release forms of nicotinic acid have been developed to lessen these side effects. [51] [52]

Liver damage

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. [16] [53] [54] 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 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. [16]

Diabetes

The high doses of nicotinic acid used to treat hyperlipidemia have been shown to elevate fasting blood glucose in people with type 2 diabetes. [17] Long-term nicotinic acid therapy was also associated with an increase in the risk of new-onset type 2 diabetes. [17] [18]

Other adverse effects

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. [55] Niaspan, the slow-release product, has been associated with a reduction in platelet content and a modest increase in prothrombin time. [25]

Pharmacology

Pharmacodynamics

Activating HCA2 has effects other than lowering serum cholesterol and triglyceride concentrations: antioxidative, anti-inflammatory, antithrombotic, improved endothelial function and plaque stability, all of which counter development and progression of atherosclerosis. [56] [57]

Niacin inhibits cytochrome P450 enzymes CYP2E1, CYP2D6 and CYP3A4. [58] Niacin produces a rise in serum 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. [59] One test used to aid in diagnosing Gilbert's Syndrome involves intravenous administration of nicotinic acid (niacin) in a dose of 50 mg over a period of 30 seconds. [53] [54]

Pharmacokinetics

Both nicotinic acid and nicotinamide are rapidly absorbed from the stomach and small intestine. [60] 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. [21] 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. [24]

Nicotinic acid and nicotinamide are both converted into the coenzyme NAD. [61] 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. [62] 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. [21] Excess nicotinic acid is methylated in the liver to N1-methylnicotinamide (NMN) and excreted in urine as such or as the oxidized metabolites N1-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. [21]

Production

Biosynthesis

Nicotinic acid, serotonin (5-hydroxytryptamine), and melatonin biosynthesis from tryptophan Tryptophan metabolism.svg
Nicotinic acid, serotonin (5-hydroxytryptamine), and melatonin biosynthesis from tryptophan

In addition to absorbing niacin from diet, niacin can be synthesized from the 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. [63] For humans, the efficiency of conversion is estimated as requiring 60  mg of tryptophan to make 1 mg of niacin. Riboflavin, vitamin B6 and iron are required for the process. [21] 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. [64]

Industrial synthesis

Nicotinic acid was first synthesized in 1867 by oxidative degradation of nicotine with potassium chromate and sulfuric acid [65] — this is the origin of the name. [66] 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. [67] Alternatively, ammonia, acetic acid and paraldehyde are used to make 5-ethyl-2-methyl-pyridine, which is then oxidized to niacin. [68] 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. [69]

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. [65]

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. [70] [71] Eventually, catalytic scrubbing technology that eliminates most of the emissions was installed in 2021. [72]

Chemistry

This colorless, water-soluble solid is a derivative of pyridine, with a carboxyl group (COOH) at the 3-position. [21] Other forms of vitamin B3 include the corresponding amide nicotinamide, where the carboxyl group has been replaced by a carboxamide group (CONH
2). [21]

Preparations

Inositol hexanicotinate Inositol nicotinate.png
Inositol hexanicotinate

Niacin is incorporated into multi-vitamin and sold as a single-ingredient dietary supplement. The latter can be immediate or slow release. [73]

Nicotinamide 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 g/day for adults. [74]

Prescription products can be immediate release (Niacor, 500 mg tablets) or extended release (Niaspan, 500 and 1000 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 side effects, but increases the risk of hepatotoxicity compared to the immediate release drug. [75] [76]

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. [30] [77] [78] 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. [79] The study resulted in the withdrawal of Tredaptive from the international market. [80] [81]

One form of dietary supplement sold in the US is inositol hexanicotinate (IHN), also called inositol nicotinate. This is inositol that has been esterified with niacin on all six of inositol's alcohol groups. [82] IHN is usually sold as "flush-free" or "no-flush" niacin in units of 250, 500, or 1000 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. [83]

History

Niacin as a chemical compound was first described by chemist Hugo Weidel in 1873 in his studies of nicotine, [84] 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. [85] Over time, eight chemically distinct, water-soluble B vitamins were isolated and numbered, with niacin as vitamin B3. [85]

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. [86] In northern Italy it was named "pellagra" from the Lombard language (agra = holly-like or serum-like; pell = skin). [87] [88] In time, the disease was more closely linked specifically to corn. [89] 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. [90] [91]

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." [92] It was also referred to as "vitamin PP", "vitamin P-P" and "PP-factor", all derived from the term "pellagra-preventive factor". [11] 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. [93]

Nicotinic acid was initially synthesized by oxidizing nicotine with potassium chromate and sulfuric acid. [66] Hence, in 1942, when flour 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 nicotinic acid + vitamin. [94] [66]

Carpenter found in 1951, that niacin in corn is biologically unavailable, and can be released only in very alkaline 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. [95]

In 1955, Altschul and colleagues described large amounts of niacin as having a lipid-lowering property. [96] As such, niacin is the oldest known lipid-lowering drug. [97] Lovastatin, the first 'statin' drug, was first marketed in 1987. [98]

Research

In animal models and in vitro , nicotinic acid produces marked anti-inflammatory effects in a variety of tissues – including the brain, gastrointestinal tract, skin, and vascular tissue  – through the activation of hydroxycarboxylic acid receptor 2 (HCA2), also known as niacin receptor 1 (NIACR1). [99] [100] [101] [102] Unlike nicotinic acid, nicotinamide does not activate NIACR1; however, both nicotinic acid and nicotinamide activate the G protein-coupled estrogen receptor (GPER) in vitro. [103]

In 2024, it was reported that metabolites of niacin promote vascular inflammation and contribute to the risk of developing atherosclerosis. [104]

Notes

  1. ↑ International nonproprietary name
  2. ↑ Common name in the United States (USAN)

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<span class="mw-page-title-main">Ezetimibe</span> Medication used to treat high cholesterol

Ezetimibe, sold under the brand name Zetia among others, is a medication used to treat high blood cholesterol and certain other lipid abnormalities. Generally it is used together with dietary changes and a statin. Alone, it is less preferred than a statin. It is taken by mouth. It is also available in the fixed-dose combinations ezetimibe/simvastatin, ezetimibe/atorvastatin, ezetimibe/rosuvastatin, and ezetimibe/bempedoic acid.

Megavitamin therapy is the use of large doses of vitamins, often many times greater than the recommended dietary allowance (RDA) in the attempt to prevent or treat diseases. Megavitamin therapy is typically used in alternative medicine by practitioners who call their approach orthomolecular medicine. Vitamins are useful in preventing and treating illnesses specifically associated with dietary vitamin shortfalls, but the conclusions of medical research are that the broad claims of disease treatment by advocates of megavitamin therapy are unsubstantiated by the available evidence. It is generally accepted that doses of any vitamin greatly in excess of nutritional requirements will result either in toxicity or in the excess simply being metabolised; thus evidence in favour of vitamin supplementation supports only doses in the normal range. Critics have described some aspects of orthomolecular medicine as food faddism or even quackery. Research on nutrient supplementation in general suggests that some nutritional supplements might be beneficial, and that others might be harmful; several specific nutritional therapies are associated with an increased likelihood of the condition they are meant to prevent.

<span class="mw-page-title-main">Fenofibrate</span> Drug of the fibrate class, mainly used to reduce cholesterol levels

Fenofibrate, is an oral medication of the fibrate class used to treat abnormal blood lipid levels. It is less commonly used compared to statins because it treats a different type of cholesterol abnormality to statins. While statins have strong evidence for reducing heart disease and death, there is evidence to suggest that fenofibrate also reduces the risk of heart disease and death. However, this seems only to apply to specific populations of people with elevated triglyceride levels and reduced high-density lipoprotein (HDL) cholesterol. Its use is recommended together with dietary changes.

<span class="mw-page-title-main">Red yeast rice</span> Type of bright reddish purple fermented rice

Red yeast rice or red rice koji is a bright reddish purple fermented rice, which acquires its color from being cultivated with the mold Monascus purpureus. Red yeast rice is what is referred to as a kōji in Japanese, meaning "grain or bean overgrown with a mold culture", a food preparation tradition going back to ca. 300 BC.

<span class="mw-page-title-main">Picamilon</span> Chemical compound

Picamilon is a drug formed by a synthetic combination of niacin and γ-aminobutyric acid (GABA). It was developed in the Soviet Union in 1969 and further studied in both Russia and Japan as a prodrug of GABA.

<span class="mw-page-title-main">Acipimox</span> Chemical compound

Acipimox is a niacin derivative used as a lipid-lowering agent. It reduces triglyceride levels and increases HDL cholesterol. It may have less marked adverse effects than niacin, although it is unclear whether the recommended dose is as effective as standard doses of niacin.

A vitamer is any of the related forms in which some vitamin occurs. Each vitamer of a particular vitamin is a compound that performs the functions of that vitamin and prevents the symptoms of deficiency of the vitamin.

<span class="mw-page-title-main">Laropiprant</span> Chemical compound

Laropiprant (INN) was a drug used in combination with nicotinic acid to reduce blood cholesterol that is no longer sold, due to increases in side-effects with no cardiovascular benefit. Laropiprant itself has no cholesterol lowering effect, but it reduces facial flushes induced by nicotinic acid.

<span class="mw-page-title-main">Nicotinamide riboside</span> Chemical compound

Nicotinamide riboside (NR, SR647) is a pyridine-nucleoside and a form of vitamin B3. It functions as a precursor to nicotinamide adenine dinucleotide, or NAD+, through a two-step and a three-step pathway.

Vitamin B<sub>3</sub> Class of chemically related vitamers

Vitamin B3, colloquially referred to as niacin, is a vitamin family that includes three forms, or vitamers: nicotinic acid (niacin), nicotinamide (niacinamide), and nicotinamide riboside. All three forms of vitamin B3 are converted within the body to nicotinamide adenine dinucleotide (NAD). NAD is required for human life and people are unable to make it within their bodies without either vitamin B3 or tryptophan. Nicotinamide riboside was identified as a form of vitamin B3 in 2004.

References

  1. ↑ "Chapter P-6. Applications to Specific Classes of Compounds". Nomenclature of Organic Chemistry : IUPAC Recommendations and Preferred Names 2013 (Blue Book). Cambridge: Royal Society of Chemistry. 2014. pp. 648–1047. doi:10.1039/9781849733069-00648. ISBN   978-0-85404-182-4.
  2. ↑ Sweetman SC (2011). Martindale: the complete drug reference. Martindale (37 ed.). London: Pharmaceutical press. p. 2117. ISBN   978-0-85369-933-0. OCLC   1256529676.
  3. ↑ "Niacin Use During Pregnancy". Drugs.com. 29 July 2019. Archived from the original on 5 August 2020. Retrieved 4 May 2020.
  4. 1 2 3 4 5 6 7 8 9 10 11 12 13 "Niacin Fact Sheet for Health Professionals". Office of Dietary Supplements, US National Institutes of Health. 18 November 2022. Retrieved 12 December 2024.
  5. 1 2 3 4 5 6 7 8 9 "Niacin". Micronutrient Information Center, Linus Pauling Institute, Oregon State University, Corvallis, OR. 8 October 2018. Archived from the original on 12 September 2019. Retrieved 16 September 2019.
  6. 1 2 Institute of Medicine (1998). "Niacin". Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline. Washington, DC: The National Academies Press. pp. 123–149. ISBN   978-0-309-06554-2. Archived from the original on 1 September 2018. Retrieved 29 August 2018.
  7. 1 2 Hegyi J, Schwartz RA, Hegyi V (January 2004). "Pellagra: dermatitis, dementia, and diarrhea". International Journal of Dermatology. 43 (1): 1–5. doi: 10.1111/j.1365-4632.2004.01959.x . PMID   14693013. S2CID   33877664.
  8. ↑ "Why fortify?". Food Fortification Initiative. 2017. Archived from the original on 4 April 2017. Retrieved 4 April 2017.
  9. ↑ Jaconello P (October 1992). "Niacin versus niacinamide". CMAJ. 147 (7): 990. PMC   1336277 . PMID   1393911.
  10. ↑ Kirkland JB (May 2012). "Niacin requirements for genomic stability". Mutation Research. 733 (1–2): 14–20. Bibcode:2012MRFMM.733...14K. doi:10.1016/j.mrfmmm.2011.11.008. PMID   22138132. Archived from the original on 4 August 2020. Retrieved 3 July 2019.
  11. 1 2 World Health Organization (2000). Pellagra And Its Prevention And Control In Major Emergencies (Report). World Health Organization (WHO). hdl: 10665/66704 . WHO/NHD/00.10.
  12. 1 2 "Niacin". Drugs.com. 16 March 2019. Archived from the original on 9 June 2020. Retrieved 27 April 2020.
  13. 1 2 Keene D, Price C, Shun-Shin MJ, Francis DP (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. 349: g4379. doi:10.1136/bmj.g4379. PMC   4103514 . PMID   25038074.
  14. ↑ Bruckert E, Labreuche J, Amarenco P (June 2010). "Meta-analysis of the effect of nicotinic acid alone or in combination on cardiovascular events and atherosclerosis". Atherosclerosis. 210 (2): 353–61. doi:10.1016/j.atherosclerosis.2009.12.023. PMID   20079494.
  15. 1 2 Schandelmaier S, Briel M, Saccilotto R, Olu KK, Arpagaus A, Hemkens LG, et al. (June 2017). "Niacin for primary and secondary prevention of cardiovascular events". The Cochrane Database of Systematic Reviews. 2017 (6): CD009744. doi:10.1002/14651858.CD009744.pub2. PMC   6481694 . PMID   28616955.
  16. 1 2 3 "Niacin". IN: LiverTox: Clinical and Research Information on Drug-Induced Liver Injury (Internet). Bethesda, MD: National Institute of Diabetes and Digestive and Kidney Diseases. February 2014. PMID   31643504.
  17. 1 2 3 4 Ong KL, Barter PJ, Waters DD (April 2014). "Cardiovascular drugs that increase the risk of new-onset diabetes". Am. Heart J. 167 (4): 421–8. doi:10.1016/j.ahj.2013.12.025. hdl: 1959.4/unsworks_43825 . PMID   24655688. S2CID   205306912. Archived from the original on 28 June 2020. Retrieved 27 June 2020.
  18. 1 2 3 Goldie C, Taylor AJ, Nguyen P, McCoy C, Zhao XQ, Preiss D (February 2016). "Niacin therapy and the risk of new-onset diabetes: a meta-analysis of randomised controlled trials". Heart. 102 (3): 198–203. doi:10.1136/heartjnl-2015-308055. PMC   4752613 . PMID   26370223.
  19. 1 2 "Niacin - Drug Usage Statistics". ClinCalc. Archived from the original on 8 July 2020. Retrieved 7 October 2022.
  20. ↑ Kennedy DO (January 2016). "B Vitamins and the Brain: Mechanisms, Dose and Efficacy—A Review". Nutrients. 8 (2): 68. doi: 10.3390/nu8020068 . PMC   4772032 . PMID   26828517.
  21. 1 2 3 4 5 6 7 8 9 Penberthy WT, Kirkland JB (2020). "Niacin". In BP Marriott, DF Birt, VA Stallings, AA Yates (eds.). Present Knowledge in Nutrition, Eleventh Edition. London, United Kingdom: Academic Press (Elsevier). pp. 209–24. ISBN   978-0-323-66162-1.
  22. ↑ "Overview on Dietary Reference Values for the EU population as derived by the EFSA Panel on Dietetic Products, Nutrition and Allergies" (PDF). 2017. Archived (PDF) from the original on 28 August 2017. Retrieved 31 August 2017.
  23. ↑ "Nutrient reference values for Australia and New Zealand" (PDF). National Health and Medical Research Council. 9 September 2005. Archived from the original (PDF) on 21 January 2017. Retrieved 19 June 2018.
  24. 1 2 3 4 5 6 "NIACOR-niacin tablet". DAILYMED, US National Library of Medicine. March 2020. Archived from the original on 9 August 2020. Retrieved 9 May 2020.
  25. 1 2 3 4 5 6 7 "Niaspan Patient Package and Product Information (PPPI)" (PDF). December 2018. Archived (PDF) from the original on 9 October 2022. Retrieved 9 May 2020.
  26. ↑ "Structure/Function Claims". U.S. Food & Drug Administration. December 2017. Archived from the original on 10 June 2020. Retrieved 30 June 2020.
  27. ↑ "Cholesterol Medications". American Heart Association. 10 November 2018. Archived from the original on 5 April 2020. Retrieved 8 May 2020.
  28. ↑ Mani P, Rohatgi A (August 2015). "Niacin Therapy, HDL Cholesterol, and Cardiovascular Disease: Is the HDL Hypothesis Defunct?". Curr Atheroscler Rep. 17 (8): 43. doi:10.1007/s11883-015-0521-x. PMC   4829575 . PMID   26048725.
  29. ↑ Garg A, Sharma A, Krishnamoorthy P, Garg J, Virmani D, Sharma T, et al. (February 2017). "Role of Niacin in Current Clinical Practice: A Systematic Review". The American Journal of Medicine. 130 (2): 173–187. doi: 10.1016/j.amjmed.2016.07.038 . PMID   27793642.
  30. 1 2 3 Villines TC, Kim AS, Gore RS, Taylor AJ (February 2012). "Niacin: the evidence, clinical use, and future directions". Current Atherosclerosis Reports. 14 (1): 49–59. doi:10.1007/s11883-011-0212-1. PMID   22037771. S2CID   27925461.
  31. ↑ Soga T, Kamohara M, Takasaki J, Matsumoto S, Saito T, Ohishi T, et al. (March 2003). "Molecular identification of nicotinic acid receptor". Biochemical and Biophysical Research Communications. 303 (1): 364–9. doi:10.1016/S0006-291X(03)00342-5. PMID   12646212.
  32. ↑ Wise A, Foord SM, Fraser NJ, Barnes AA, Elshourbagy N, Eilert M, et al. (March 2003). "Molecular identification of high and low affinity receptors for nicotinic acid". The Journal of Biological Chemistry. 278 (11): 9869–74. doi: 10.1074/jbc.M210695200 . PMID   12522134.
  33. ↑ Gille A, Bodor ET, Ahmed K, Offermanns S (2008). "Nicotinic acid: pharmacological effects and mechanisms of action". Annual Review of Pharmacology and Toxicology. 48 (1): 79–106. doi:10.1146/annurev.pharmtox.48.113006.094746. PMID   17705685.
  34. ↑ Wanders D, Judd RL (August 2011). "Future of GPR109A agonists in the treatment of dyslipidaemia". Diabetes, Obesity & Metabolism. 13 (8): 685–91. doi:10.1111/j.1463-1326.2011.01400.x. PMID   21418500. S2CID   205536280.
  35. 1 2 Costet P (June 2010). "Molecular pathways and agents for lowering LDL-cholesterol in addition to statins". Pharmacol Ther. 126 (3): 263–78. doi:10.1016/j.pharmthera.2010.02.006. PMID   20227438.
  36. ↑ Hernandez C, Molusky M, Li Y, Li S, Lin JD (October 2010). "Regulation of hepatic ApoC3 expression by PGC-1β mediates hypolipidemic effect of nicotinic acid". Cell Metabolism. 12 (4): 411–9. doi:10.1016/j.cmet.2010.09.001. PMC   2950832 . PMID   20889132.
  37. ↑ Malik S, Kashyap ML (November 2003). "Niacin, lipids, and heart disease". Curr Cardiol Rep. 5 (6): 470–6. doi:10.1007/s11886-003-0109-x. PMID   14558989. S2CID   27918392.
  38. ↑ Creider JC, Hegele RA, Joy TR (September 2012). "Niacin: another look at an underutilized lipid-lowering medication". Nature Reviews. Endocrinology. 8 (9): 517–28. doi:10.1038/nrendo.2012.22. PMID   22349076. S2CID   22526314.
  39. ↑ Rubic T, Trottmann M, Lorenz RL (February 2004). "Stimulation of CD36 and the key effector of reverse cholesterol transport ATP-binding cassette A1 in monocytoid cells by niacin". Biochemical Pharmacology. 67 (3): 411–9. doi:10.1016/j.bcp.2003.09.014. PMID   15037193.
  40. ↑ "Drug Approval Package: Advicor (Niacin Extended-Release & Lovastatin) NDA #21-249". U.S. Food and Drug Administration (FDA). 13 September 2002. Archived from the original on 4 August 2020. Retrieved 17 May 2020.
  41. ↑ "Drug Approval Package: Simcor (Niacin/Simvastatin) NDA #022078". U.S. Food and Drug Administration (FDA). 31 July 2008. Archived from the original on 14 November 2022. Retrieved 14 November 2022.
  42. ↑ "Abbott Receives FDA Approval for Simcor (Niaspan / simvastatin), a Novel Combination Medicine for Comprehensive Cholesterol Management". Drugs.com (Press release). Archived from the original on 5 August 2020. Retrieved 15 March 2008.
  43. ↑ Toth PP, Murthy AM, Sidhu MS, Boden WE (2015). "Is HPS2-THRIVE the death knell for niacin?". J Clin Lipidol. 9 (3): 343–50. doi:10.1016/j.jacl.2015.01.008. PMID   26073392.
  44. ↑ "AbbVie Inc.; Withdrawal of Approval of New Drug Applications for Advicor and Simcor". U.S. Federal Register. 18 April 2016. Archived from the original on 5 August 2020. Retrieved 17 May 2020.
  45. 1 2 3 4 5 "Niaspan- niacin tablet, film coated, extended release". DailyMed. 20 August 2013. Archived from the original on 14 November 2022. Retrieved 14 November 2022.
  46. 1 2 Papaliodis D, Boucher W, Kempuraj D, Michaelian M, Wolfberg A, House M, et al. (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". The Journal of Pharmacology and Experimental Therapeutics. 327 (3): 665–72. doi:10.1124/jpet.108.141333. PMID   18784348. S2CID   5609632.
  47. ↑ Benyó Z, Gille A, Kero J, Csiky M, Suchánková MC, Nüsing RM, et al. (December 2005). "GPR109A (PUMA-G/HM74A) mediates nicotinic acid-induced flushing". The Journal of Clinical Investigation. 115 (12): 3634–40. doi:10.1172/JCI23626. PMC   1297235 . PMID   16322797.
  48. ↑ Benyó Z, Gille A, Bennett CL, Clausen BE, Offermanns S (December 2006). "Nicotinic acid-induced flushing is mediated by activation of epidermal langerhans cells". Molecular Pharmacology. 70 (6): 1844–9. doi:10.1124/mol.106.030833. PMID   17008386. S2CID   30199951.
  49. ↑ Maciejewski-Lenoir D, Richman JG, Hakak Y, Gaidarov I, Behan DP, Connolly DT (December 2006). "Langerhans cells release prostaglandin D2 in response to nicotinic acid". The Journal of Investigative Dermatology. 126 (12): 2637–46. doi: 10.1038/sj.jid.5700586 . PMID   17008871.
  50. ↑ Kamanna VS, Kashyap ML (April 2008). "Mechanism of action of niacin". The American Journal of Cardiology. 101 (8A): 20B –26B. doi:10.1016/j.amjcard.2008.02.029. PMID   18375237.
  51. ↑ Katzung, Bertram G. (2006). Basic and clinical pharmacology. New York: McGraw-Hill Medical Publishing Division. ISBN   978-0-07-145153-6.
  52. ↑ Barter P (October 2006). "Options for therapeutic intervention: How effective are the different agents?". European Heart Journal Supplements. 8 (F): F47 –F53. doi: 10.1093/eurheartj/sul041 .
  53. 1 2 Dickey W, McAleer JJ, Callender ME (April 1991). "The Nicotinic Acid Provocation Test and Unconjugated Hyperbilirubinaemia". The Ulster Medical Journal. 60 (1): 49–52. PMC   2448612 . PMID   1853497.
  54. 1 2 Röllinghoff W, Paumgartner G, Preisig R (August 1981). "Nicotinic Acid Test in the Diagnosis of Gilbert's Syndrome: Correlation With Bilirubin Clearance". Gut. 22 (8): 663–668. doi:10.1136/gut.22.8.663. PMC   1420060 . PMID   7286783.
  55. ↑ Domanico D, Verboschi F, Altimari S, Zompatori L, Vingolo EM (2015). "Ocular Effects of Niacin: A Review of the Literature". Med Hypothesis Discov Innov Ophthalmol. 4 (2): 64–71. PMC   4458328 . PMID   26060832.
  56. ↑ Zeman M, Vecka M, Perlík F, Hromádka R, Staňková B, Tvrzická E, et al. (July 2015). "Niacin in the Treatment of Hyperlipidemias in Light of New Clinical Trials: Has Niacin Lost its Place?". Med. Sci. Monit. 21: 2156–62. doi:10.12659/MSM.893619. PMC   4523006 . PMID   26210594.
  57. ↑ Wu BJ, Yan L, Charlton F, Witting P, Barter PJ, Rye KA (May 2010). "Evidence that niacin inhibits acute vascular inflammation and improves endothelial dysfunction independent of changes in plasma lipids". Arteriosclerosis, Thrombosis, and Vascular Biology. 30 (5): 968–75. doi: 10.1161/ATVBAHA.109.201129 . PMID   20167660.
  58. ↑ Gaudineau C, Auclair K (May 2004). "Inhibition of human P450 enzymes by nicotinic acid and nicotinamide". Biochemical and Biophysical Research Communications. 317 (3): 950–6. doi:10.1016/j.bbrc.2004.03.137. PMID   15081432.
  59. ↑ Orkin SH, Nathan DG (January 2009). Nathan and Oski's Hematology of Infancy and Childhood. Elsevier Health Sciences. pp. 118–119. ISBN   9781416034308.
  60. ↑ Said HM (August 2011). "Intestinal absorption of water-soluble vitamins in health and disease". The Biochemical Journal. 437 (3): 357–372. doi:10.1042/BJ20110326. PMC   4049159 . PMID   21749321.
  61. ↑ Cox M, Lehninger AL, Nelson DR (2000). Lehninger principles of biochemistry . New York: Worth Publishers. ISBN   978-1-57259-153-0.
  62. ↑ Ishii N, Nishihara Y (March 1981). "Pellagra among chronic alcoholics: clinical and pathological study of 20 necropsy cases". Journal of Neurology, Neurosurgery, and Psychiatry. 44 (3): 209–15. doi:10.1136/jnnp.44.3.209. PMC   490893 . PMID   7229643.
  63. ↑ Foster JW, Moat AG (1 March 1980). "Nicotinamide adenine dinucleotide biosynthesis and pyridine nucleotide cycle metabolism in microbial systems". Microbiol. Rev. 44 (1): 83–105. doi:10.1128/MMBR.44.1.83-105.1980. PMC   373235 . PMID   6997723.
  64. ↑ Carpenter KJ (1983). "The Relationship of Pellagra to Corn and the Low Availability of Niacin in Cereals". Nutritional Adequacy, Nutrient Availability and Needs. Experientia Supplementum. Vol. 44. pp. 197–222. doi:10.1007/978-3-0348-6540-1_12. ISBN   978-3-0348-6542-5. PMID   6357846.
  65. 1 2 Blum R (2015). "Vitamins, 11. Niacin (Nicotinic Acid, Nicotinamide)". Vitamins, 11. Niacin (Nicotinic Acid, Nicotinamide. Ullmann's Encyclopedia of Industrial Chemistry (6th ed.). Weinheim: Wiley-VCH. pp. 1–9. doi:10.1002/14356007.o27_o14.pub2. ISBN   978-3-527-30385-4.
  66. 1 2 3 "Niacin and Nicotinic Acid". Journal of the American Medical Association. 118 (10): 823. 7 March 1942. doi:10.1001/jama.1942.02830100053014.
  67. ↑ Abe N, Ichimura H, Kataoka T, Morishita S, Shimizu S, Shoji T, et al. (2007). "Pyridine and Pyridine Derivatives". Ullmann's Encyclopedia of Industrial Chemistry . Weinheim: Wiley-VCH. doi:10.1002/14356007.a22_399. ISBN   978-3527306732.
  68. ↑ Eschenmooser W (June 1997). "100 Years of Progress with LONZA". CHIMIA. 51 (6): 259–69. doi: 10.2533/chimia.1997.259 . S2CID   100485418.
  69. ↑ Sarah Everts (2008). "Clean Catalysis: Environmentally friendly synthesis of niacin generates less inorganic waste". Chemical & Engineering News. ISSN   0009-2347.
  70. ↑ Lenz C (2021). "The climate disgrace of Visp". European Press Prize. Archived from the original on 8 September 2023. Retrieved 8 September 2023.
  71. ↑ Laudert D, Hohmann HP (2011). Application of Enzymes and Microbes for the Industrial Production of Vitamins and Vitamin-Like Compounds. Elsevier. p. 620. doi:10.1016/b978-0-444-64046-8.00188-9. ISBN   978-0-444-64047-5. 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.
  72. ↑ Davidson EA, Winiwarter W (July 2023). "Urgent abatement of industrial sources of nitrous oxide". Nature Climate Change. 13 (7): 599–601. Bibcode:2023NatCC..13..599D. doi:10.1038/s41558-023-01723-3.
  73. ↑ Dunatchik AP, Ito MK, Dujovne CA (1 March 2012). "A systematic review on evidence of the effectiveness and safety of a wax-matrix niacin formulation". Journal of Clinical Lipidology. 6 (2): 121–31. doi:10.1016/j.jacl.2011.07.003. PMID   22385545.
  74. ↑ Knip M, Douek IF, Moore WP, Gillmor HA, McLean AE, Bingley PJ, et al. (November 2000). "Safety of high-dose nicotinamide: a review". Diabetologia. 43 (11): 1337–45. doi: 10.1007/s001250051536 . PMID   11126400.
  75. ↑ Bassan M (2012). "A case for immediate-release niacin". Heart & Lung. 41 (1): 95–8. doi:10.1016/j.hrtlng.2010.07.019. PMID   21414665.
  76. ↑ Reiche I, Westphal S, Martens-Lobenhoffer J, Tröger U, Luley C, Bode-Böger SM (January 2011). "Pharmacokinetics and dose recommendations of Niaspan in chronic kidney disease and dialysis patients". Nephrology, Dialysis, Transplantation. 26 (1): 276–82. doi: 10.1093/ndt/gfq344 . PMID   20562093.
  77. ↑ Lai E, De Lepeleire I, Crumley TM, Liu F, Wenning LA, Michiels N, et al. (June 2007). "Suppression of niacin-induced vasodilation with an antagonist to prostaglandin D2 receptor subtype 1". Clinical Pharmacology and Therapeutics. 81 (6): 849–57. doi:10.1038/sj.clpt.6100180. PMID   17392721. S2CID   2126240.
  78. ↑ Paolini JF, Bays HE, Ballantyne CM, Davidson M, Pasternak R, Maccubbin D, et al. (November 2008). "Extended-release niacin/laropiprant: reducing niacin-induced flushing to better realize the benefit of niacin in improving cardiovascular risk factors". Cardiology Clinics. 26 (4): 547–60. doi:10.1016/j.ccl.2008.06.007. PMID   19031552.
  79. ↑ Landray MJ, Haynes R, Hopewell JC, Parish S, Aung T, Tomson J, et al. (July 2014). "Effects of extended-release niacin with laropiprant in high-risk patients". N. Engl. J. Med. 371 (3): 203–12. doi: 10.1056/NEJMoa1300955 . PMID   25014686. S2CID   23548060.
  80. ↑ Nainggolan L (11 January 2013). "Niacin/Laropiprant Products to Be Suspended Worldwide". Medscape. Archived from the original on 26 April 2015. Retrieved 20 February 2017.
  81. ↑ "Merck begins overseas recall of HDL cholesterol drug". Reuters. 11 January 2013. Archived from the original on 21 April 2023. Retrieved 6 July 2021.
  82. ↑ Aguilar F, Charrondiere UR, Dusemund B, Galtier PM, Gilbert J, Gott DM, et al. (January 2009). "Inositol hexanicotinate (inositol hexaniacinate) as a source of niacin (vitamin B3) added for nutritional purposes in food supplements". The EFSA Journal. 949: 1–20. Archived from the original on 5 March 2017. Retrieved 4 March 2017.
  83. ↑ Taheri (15 January 2003). "No-Flush Niacin for the Treatment of Hyperlipidemia". Medscape . Archived from the original on 5 December 2008. Retrieved 31 March 2008.
  84. ↑ Weidel H (1873). "Zur Kenntniss des Nicotins". Justus Liebigs Annalen der Chemie und Pharmacie . 165 (2): 330–49. doi:10.1002/jlac.18731650212. Archived from the original on 4 August 2020. Retrieved 3 July 2019.
  85. 1 2 Combs GF (2007). The Vitamins: Fundamental Aspects in Nutrition and Health (3rd ed.). Elsevier, Boston, MA. pp. 7–33. ISBN   978-0-080-56130-1. Archived from the original on 13 January 2023. Retrieved 30 June 2020.
  86. ↑ Casal G (1945). "The natural and medical history of the principality of the Asturias". In Major RH (ed.). Classic Descriptions of Disease (3rd ed.). Springfield: Charles C Thomas. pp. 607–12.
  87. ↑ F. Cherubini, Vocabolario Milanese-Italiano, Imp. Regia Stamperia, 1840-43, vol. I, III.
  88. ↑ "Definition of Pellagra". MedicineNet.com. Archived from the original on 30 September 2007. Retrieved 18 June 2007.
  89. ↑ Cesare Lombroso, Studi clinici ed esperimentali sulla natura, causa e terapia delle pellagra (Bologna: Fava e Garagnani, 1869)
  90. ↑ Evans BK, Feinstein AR (September 1994). "Joseph Goldberger: an unsung hero of American clinical epidemiology". Ann Intern Med. 121 (5): 372–75. doi:10.7326/0003-4819-121-5-199409010-00010. PMID   8042827. S2CID   13226008.
  91. ↑ Kraut A. "Dr. Joseph Goldberger and the War on Pellagra | Ashes on the Potomac". history.nih.gov. Archived from the original on 9 May 2020. Retrieved 20 February 2017.
  92. ↑ Elvehjem CA, Madden RJ, Strongandd FM, Woolley DW (1938). "The isolation and identification of the anti-blacktongue factor J" (PDF). J. Biol. Chem. 123 (1): 137–49. doi: 10.1016/S0021-9258(18)74164-1 . Archived (PDF) from the original on 9 October 2022.
  93. ↑ Ruth Hanna Sachs, White Rose History. Archived 21 April 2023 at the Wayback Machine Volume I. 2003. Appendix D, p. 2 ISBN   978-0-9710541-9-6 "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."
  94. ↑ "Niacin and Niacin Amide". Journal of the American Medical Association. 118 (10): 819. 7 March 1942. doi:10.1001/jama.1942.02830100049011.
  95. ↑ Laguna J, Carpenter KJ (September 1951). "Raw versus processed corn in niacin-deficient diets". The Journal of Nutrition. 45 (1): 21–8. doi: 10.1093/jn/45.1.21 . PMID   14880960.
  96. ↑ Altschul R, Hoffer A, Stephen JD (February 1955). "Influence of nicotinic acid on serum cholesterol in man". Archives of Biochemistry and Biophysics. 54 (2): 558–9. doi:10.1016/0003-9861(55)90070-9. PMID   14350806.
  97. ↑ Romani M, Hofer DC, Katsyuba E, Auwerx J (April 2019). "Niacin: an old lipid drug in a new NAD+ dress". J. Lipid Res. 60 (4): 741–6. doi: 10.1194/jlr.S092007 . PMC   6446705 . PMID   30782960.
  98. ↑ Simons J (January 2003). "The $10 billion pill". Fortune. 147 (1): 58–62, 66, 68. PMID   12602122.
  99. ↑ Offermanns S, Schwaninger M (April 2015). "Nutritional or pharmacological activation of HCA(2) ameliorates neuroinflammation". Trends in Molecular Medicine. 21 (4): 245–55. doi:10.1016/j.molmed.2015.02.002. PMID   25766751.
  100. ↑ Chai JT, Digby JE, Choudhury RP (May 2013). "GPR109A and vascular inflammation". Current Atherosclerosis Reports. 15 (5): 325. doi:10.1007/s11883-013-0325-9. PMC   3631117 . PMID   23526298.
  101. ↑ Graff EC, Fang H, Wanders D, Judd RL (February 2016). "Anti-inflammatory effects of the hydroxycarboxylic acid receptor 2". Metabolism. 65 (2): 102–13. doi:10.1016/j.metabol.2015.10.001. PMID   26773933.
  102. ↑ Wakade C, Chong R (December 2014). "A novel treatment target for Parkinson's disease". Journal of the Neurological Sciences. 347 (1–2): 34–8. doi:10.1016/j.jns.2014.10.024. PMID   25455298. S2CID   29760853.
  103. ↑ 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". Cellular Signalling. 26 (7): 1466–75. doi:10.1016/j.cellsig.2014.03.011. PMID   24662263.
  104. ↑ Mole B (26 February 2024). "Surprising link found between niacin and risk of heart attack and stroke". Ars Technica. Retrieved 24 May 2024.
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