text:
(Redirected from Nicotinic acid)
This article is about the nutrient. For the neo-fusion band, see Niacin (band).
Pronunciation /ˈnaɪəsɪn/
Preferred IUPAC name
Pyridine-3-carboxylic acid[1]
Nicotinic acid (INN)
Vitamin PP
59-67-6 Y
3D model (JSmol)
3DMet
Beilstein Reference
ChEBI
CHEBI:15940 Y
ChEMBL573 Y
DB00627 Y
ECHA InfoCard 100.000.401
Gmelin Reference
IUPHAR/BPS
D00049 Y
C00253 Y
MeSH Niacin
RTECS number
QT0525000
2679MF687A Y
CompTox Dashboard (EPA)
DTXSID1020932
InChI=1S/C6H5NO2/c8-6(9)5-2-1-3-7-4-5/h1-4H,(H,8,9) Y
Key: PVNIIMVLHYAWGP-UHFFFAOYSA-N Y
InChI=1/C6H5NO2/c8-6(9)5-2-1-3-7-4-5/h1-4H,(H,8,9)
Key: PVNIIMVLHYAWGP-UHFFFAOYAA
OC(=O)c1cccnc1
C6H5NO2
Molar mass 123.111 g·mol−1
Appearance White, translucent crystals
Density 1.473 g cm−3
Melting point 237 °C; 458 °F; 510 K
Solubility in water
18 g L−1
log P 0.219
Acidity (pKa) 2.0, 4.85
Isoelectric point 4.75
Refractive index (nD)
0.1271305813 D
Std enthalpy of
formation (ΔfH⦵298)
−344.9 kJ mol−1
combustion (ΔcH⦵298)
−2.73083 MJ mol−1
C04AC01 (WHO) C10BA01 (WHO) C10AD02 (WHO) C10AD52 (WHO)
License data
EU EMA: by Nicotinic acid
Routes of
Intramuscular, by mouth
Biological half-life
GHS pictograms
GHS Signal word Warning
GHS hazard statements
GHS precautionary statements
P264, P280, P305+351+338, P337+313, P501
NFPA 704 (fire diamond)
Flash point 193 °C (379 °F; 466 K)
Autoignition
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).
Y verify (what is Y N ?)
INN: Nicotinic acid
Niacor, Niaspan, others
AHFS/Drugs.com
US DailyMed: Niacin
AU: Exempt[2]
US: OTC / Rx-only
PDB ligand
NIO (PDBe, RCSB PDB)
ECHA InfoCard
Niacin, also known as nicotinic acid, is an organic compound and a form of vitamin B3, an essential human nutrient.[3] It can be manufactured by plants and animals from the amino acid tryptophan. 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.[3][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.[5] Many countries require its addition to wheat flour or other food grains, thereby reducing the risk of pellagra.[3][6]
The amide derivative nicotinamide (niacinamide) is a component of the coenzymes nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP+). Although niacin and nicotinamide (niacinamide) are identical in their vitamin activity, nicotinamide does not have the same pharmacological, lipid-modifying effects or side effects as niacin, i.e., when niacin takes on the -amide group, it does not reduce cholesterol nor cause flushing.[7][8] 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.[9]
Niacin is also a prescription medication. 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 niacin. 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.[10] Despite the proven lipid changes, niacin has not been found useful for decreasing the risk of cardiovascular disease in those already on a statin.[11] A 2010 review had concluded that niacin was effective as a mono-therapy,[12] but a 2017 review incorporating twice as many trials concluded that prescription niacin, while affecting lipid levels, did not reduce all-cause mortality, cardiovascular mortality, myocardial infarctions, nor fatal or non-fatal strokes.[13] Prescription niacin was shown to cause hepatotoxicity[14] and increase risk of type 2 diabetes.[15][16] Niacin prescriptions in the U.S. had peaked in 2009, at 9.4 million, declining to 1.3 million by 2017.[17]
Niacin has the formula C
2 and belongs to the group of the pyridinecarboxylic acid.[3] As the precursor for nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP), niacin is involved in DNA repair.[18]
2 Vitamin deficiency
2.1 Measuring vitamin status
3 Dietary recommendations
4.1 Food preparation
4.2 Food fortification
4.3 As a dietary supplement
5 As lipid-modifying medication
5.1 Mechanisms
5.2 Combined with statins
5.3 Contraindications
5.4 Adverse effects
5.4.1 Flushing
5.4.2 Liver damage
5.4.3 Diabetes
5.4.4 Other adverse effects
6 Pharmacology
6.1 Pharmacodynamics
6.2 Pharmacokinetics
7.1 Biosynthesis
7.2 Industrial synthesis
9 Preparations
10 History
Definition[edit]
Niacin is both a vitamin, i.e., an essential nutrient, marketed as a dietary supplement, and 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.[19] Vitamin intake recommendations made by several countries are that intakes of 14–18 mg/day are sufficient to meet the needs of healthy adults.[20][21][22] Niacin or nicotinamide (niacinamide) are used for prevention and treatment of pellagra, a disease caused by lack of the vitamin.[5][19] When niacin is used as a medicine to treat elevated cholesterol and triglycerides, daily doses range from 500 to 3,000 mg/day.[23][24] High-dose nicotinamide does not have this medicinal effect.[19]
Vitamin deficiency[edit]
Main article: Pellagra
A man with pellagra, which is caused by a chronic lack of vitamin B3 in the diet
Severe deficiency of niacin in the diet causes the disease pellagra, characterized by diarrhea, sun-sensitive dermatitis involving hyperpigmentation and thickening of the skin (see image), inflammation of the mouth and tongue, delirium, dementia, and if left untreated, death.[5] Common psychiatric symptoms include irritability, poor concentration, anxiety, fatigue, loss of memory, restlessness, apathy, and depression.[19] The biochemical mechanism(s) for the observed deficiency-caused neurodegeneration are not well understood, but may rest on: A) the requirement for nicotinamide adenine dinucleotide (NAD+) to suppress the creation of neurotoxic tryptophan metabolites, B) inhibition of mitochondrial ATP generation, resulting in cell damage; C), activation of the poly (ADP-ribose) polymerase (PARP) pathway, as PARP is a nuclear enzyme involved in DNA repair, but in the absence of NAD+ can lead to cell death; D) reduced synthesis of neuro-protective brain-derived neurotrophic factor or its receptor tropomyosin receptor kinase B; or E) changes to genome expression directly due to the niacin deficiency.[25]
Niacin deficiency is rarely seen in developed countries, and it is more typically associated with poverty, malnutrition or malnutrition secondary to chronic alcoholism.[26] It also tends to occur in less developed areas where people eat maize (corn) as a staple food, as maize is the only grain low in digestible niacin. A cooking technique called nixtamalization i.e., pretreating with alkali ingredients, increases the bioavailability of niacin during maize meal/flour production.[27] For this reason, people who consume corn as tortillas or hominy are at less risk of niacin deficiency.
For treating deficiency, the World Health Organization (WHO) recommends administering niacinamide instead of niacin, to avoid the flushing side effect commonly caused by niacin. Guidelines suggest using 300 mg/day for three to four weeks.[9] Dementia and dermatitis show improvement within a week. Because deficiencies of other B-vitamins may be present, the WHO recommends a multi-vitamin in addition to the niacinamide.[9]
Hartnup disease is a hereditary nutritional disorder resulting in niacin deficiency.[28] It is named after an English family with a genetic disorder that resulted in a failure to absorb the essential amino acid tryptophan, tryptophan being a precursor for niacin synthesis. The symptoms are similar to pellagra, including red, scaly rash and sensitivity to sunlight. Oral niacin or niacinamide is given as a treatment for this condition in doses ranging from 50–100 mg twice a day, with a good prognosis if identified and treated early.[28] Niacin synthesis is also deficient in carcinoid syndrome, because of metabolic diversion of its precursor tryptophan to form serotonin.[3]
Measuring vitamin status[edit]
Plasma concentrations of niacin and niacin metabolites are not useful markers of niacin status.[20] Urinary excretion of the methylated metabolite N1-methyl-nicotinamide is considered reliable and sensitive. The measurement requires a 24-hour urine collection. For adults, a value of less than 5.8 µmol/day represent deficient niacin status and 5.8 to 17.5 µmol/day represents low.[20] According to the World Health Organization, an alternative mean of expressing urinary N1-methyl-nicotinamide is as mg/g creatinine in a 24-hour urine collection, with deficient defined as <0.5, low 0.5-1.59, acceptable 1.6-4.29, and high >4.3[9] Niacin deficiency occurs before the signs and symptoms of pellagra appear.[20] Erythrocyte nicotinamide adenine dinucleotide (NAD) concentrations potentially provide another sensitive indicator of niacin depletion, although definitions of deficient, low and adequate have not been established. Lastly, plasma tryptophan decreases on a low niacin diet because tryptophan converts to niacin. However, low tryptophan could also be caused by a diet low in this essential amino acid, so it is not specific to confirming vitamin status.[20]
Dietary recommendations[edit]
RDI for niacin (mg NE/day)[22]
Upper level of intake[22]
Infants 0–6 months 2 mg/d preformed niacin* ND
Infants 7–12 months 4 mg/d NE*
19+ – 35
Females 14+ 14 –
Males 14+ 16
Pregnant females 14–50 18 –
Pregnant females 14–18 – 30
Lactating females 14–50 17 –
Lactating females 14–18 – 30
* Adequate Intake for infants[20]
Age group (years)
RDA of niacin (mg NE/d)[29]
Tolerable upper intake level[29]
0–6 months 2 mg/d preformed niacin* ND
7–12 months 4 mg/d NE*
Females 14–18 14 30
Males 14–18 16
Females 19+ 14 35
Pregnant females <18 18 30
Pregnant females 18–50 18 35
Lactating females <18 17 30
Lactating females 18–50 17 35
Adequate Intake (mg NE/MJ)[30]
Females 1.3
Males 1.6
Tolerable upper limit of Nicotinic acid (mg/day)[30]
Tolerable upper limit of Nicotinamide (mg/day)[30]
11–14 6 500
RDA for niacin (mg NE/day)
Infants 0–6 months 2* ND**
Infants 6–12 months 4*
Males 14–18 16 30
Males 19+ 16 35
* Adequate intake for infants, as an RDA has yet to be established
** Not possible to establish; source of intake should be formula and food only[20]
The U.S. Institute of Medicine (renamed National Academy of Medicine in 2015) updated Estimated Average Requirements (EARs) and Recommended Dietary Allowances (RDAs) for niacin in 1998, also Tolerable upper intake levels (ULs). In lieu of an RDA, Adequate Intakes (AIs) are identified for populations for which there is not sufficient evidence to identify a dietary intake level that is sufficient to meet the nutrient requirements of most people.[31] (see table).
The European Food Safety Authority (EFSA) refers to the collective set of information as Dietary Reference Values (DRV), with Population Reference Intake (PRI) instead of RDA, and Average Requirement instead of EAR. For the EU, AIs and ULs have the same definition as in the US, except that units are milligrams per megajoule (MJ) of energy consumed rather than mg/day. For women (including those pregnant or lactating), men and children the PRI is 1.6 mg per megajoule. As the conversion is 1 MJ = 239 kcal, an adult consuming 2390 kilocalories should be consuming 16 mg niacin. This is comparable to US RDAs (14 mg/day for adult women, 16 mg/day for adult men).[21]
ULs are established by identifying amounts of vitamins and minerals that cause adverse effects, and then selecting as an upper limit amounts that are the "maximum daily intake unlikely to cause adverse health effects."[31] Regulatory agencies from different countries do not always agree. For the US, 30 or 35 mg for teenagers and adults, less for children.[20] The EFSA UL for adults is set at 10 mg/day - about one-third of the US value. For all of the government ULs, the term applies to niacin as a supplement consumed as one dose, and is intended as a limit to avoid the skin flush reaction. This explains why for EFSA, the recommended daily intake can be higher than the UL.[32]
Both the DRI and DRV describe amounts needed as niacin equivalents (NE), calculated as 1 mg NE = 1 mg niacin or 60 mg of the essential amino acid tryptophan. This is because the amino acid is utilized to synthesize the vitamin.[20][21]
For U.S. food and dietary supplement labeling purposes the amount in a serving is expressed as a percent of Daily Value (%DV). For niacin labeling purposes 100% of the Daily Value is 16 mg. Prior to 27 May 2016 it was 20 mg, revised to bring it into agreement with the RDA.[33][34] Compliance with the updated labeling regulations was required by 1 January 2020 for manufacturers with US$10 million or more in annual food sales, and by 1 January 2021 for manufacturers with lower volume food sales.[35][36] A table of the old and new adult daily values is provided at Reference Daily Intake.
Niacin is found in a variety of whole and processed foods, including fortified packaged foods, meat from various animal sources, seafoods, and spices.[3][37] In general, animal-sourced foods provide about 5–10 mg niacin per serving, although dairy foods and eggs have little. Some plant-sourced foods such as nuts and grains provide about 2–5 mg niacin per serving, although this naturally present niacin is largely bound to polysaccharides and glycopeptides, making it only about 30% bioavailable. Fortified food ingredients such as wheat flour have niacin added, which is bioavailable.[4] Among whole food sources with the highest niacin content per 100 grams:
Source[38]
(mg / 100g)
Nutritional yeast[39] per 2 Tbsp (16 g) 56
Tuna, yellowfin 22.1
Peanuts 14.3
Peanut butter 13.1
Bacon 10.4
Tuna, light, canned 10.1
Salmon 10.0
Turkey depending on what part, how cooked 7-12
Chicken depending on what part, how cooked 7-12
Beef depending on what part, how cooked 4-8
Pork depending on what part, how cooked 4-8
Sunflower seeds 7.0
Tuna, white, canned 5.8
Almonds 3.6
Mushrooms, white 3.6
Cod fish 2.5
Rice, brown 2.5
Hot dogs 2.0
Avocado 1.7
Potato, baked, with skin 1.4
Corn (maize) 1.0
Rice, white 0.5
Kale 0.4
Eggs 0.1
Milk 0.1
Cheese 0.1
Tofu 0.1
Vegetarian and vegan diets can provide adequate amounts if products such as nutritional yeast, peanuts, peanut butter, tahini, brown rice, mushrooms, avocado and sunflower seeds are included. Fortified foods and dietary supplements can also be consumed to ensure adequate intake.[4][40]
Food preparation[edit]
Niacin naturally found in food is susceptible to destruction from high heat cooking, especially in the presence of acidic foods and sauces. It is soluble in water, and so may also be lost from foods boiled in water.[41]
Food fortification[edit]
Countries fortify foods with nutrients to address known deficiencies.[6] As of 2020, 54 countries required food fortification of wheat flour with niacin or niacinamide; 14 also mandate fortification of maize flour, and 6 mandate fortification of rice.[42] From country to country, niacin fortification ranges from 1.3 to 6.0 mg/100 g.[42]
As a dietary supplement[edit]
In the United States, niacin 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[43] allowed by the US Food & Drug Administration (FDA). An example would be "Supports a healthy blood lipid profile." The American Heart Association strongly advises against the substitution of dietary supplement niacin for prescription niacin because of potentially serious side effects, which means that niacin should only be used under the supervision of a health care professional, and because manufacture of dietary supplement niacin is not as well-regulated by the FDA as prescription niacin.[44] More than 30 mg niacin consumed as a dietary supplement can cause skin flushing. Face, arms and chest skin turns a reddish color because of vasodilation of small subcutaneous blood vessels, accompanied by sensations of heat, tingling and itching. These signs and symptoms are typically transient, lasting minutes to hours; they are considered unpleasant rather than toxic.[4]
As lipid-modifying medication[edit]
Prescription niacin, in immediate-release and slow-release forms, is used to treat primary hyperlipidemia and hypertriglyceridemia. It is used either as a monotherapy or in combination with other lipid-modifying drugs. Dosages start at 500 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).[23][24] Prescriptions in the U.S. peaked in 2009, at 9.4 million and had declined to 1.3 million by 2017.[17] Systematic reviews found no effect of prescription niacin on all-cause mortality, cardiovascular mortality, myocardial infarctions, nor fatal or non-fatal strokes despite raising HDL cholesterol.[11][45] Reported side effects include an increased risk of new-onset type 2 diabetes.[13][15][16][46]
Mechanisms[edit]
Niacin reduces synthesis of low-density lipoprotein cholesterol (LDL-C), very low-density lipoprotein cholesterol (VLDL-C), lipoprotein(a) and triglycerides, and increases high-density lipoprotein cholesterol (HDL-C).[47] The lipid-therapeutic effects of niacin 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.[48][49] 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.[50][51][52] 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.[53] Niacin also directly inhibits the action of diacylglycerol O-acyltransferase 2 (DGAT2) a key enzyme for triglyceride synthesis.[52]
The mechanism behind niacin increasing HDL-C is not totally understood, but seems to occur in various ways. Niacin increases apolipoprotein A1 levels by inhibiting the breakdown of this protein, which is a component of HDL-C.[54][55] It also inhibits HDL-C hepatic uptake by suppressing production of the cholesterol ester transfer protein (CETP) gene.[47] It stimulates the ABCA1 transporter in monocytes and macrophages and upregulates peroxisome proliferator-activated receptor gamma, resulting in reverse cholesterol transport.[56]
Combined with statins[edit]
Extended release niacin was combined with the lovastatin trade-named Advicor, and with simvastatin, trade-named Simcor as prescription drug combinations. Advicor was approved by the U.S. Food and Drug Administration (FDA) in 2001.[57] Simcor was approved in 2008.[58] Subsequently, large outcome trials using these niacin and statin therapies were unable to demonstrate incremental benefit of niacin beyond statin therapy alone.[59] 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.[60]
Contraindications[edit]
Prescription immediate release (Niacor) and extended release (Niaspan) niacin are contraindicated for people with either active or a past history of liver disease because both, but especially Niaspan, have been associated with instances of serious, on occasion fatal, liver failure.[24][61] 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.[23][24][61] Both products are also contraindicated for women who are pregnant or expecting to become pregnant because safety during pregnancy has not been evaluated in human trials. These products are contraindicated for women who are lactating because it is known that niacin is excreted into human milk, but the amount and potential for adverse effects in the nursing infant are not known. Women are advised to either not nurse their child or discontinue the drug. High-dose niacin has not been tested or approved for use in children under 16 years.[23][24][61]
Adverse effects[edit]
The most common adverse effects of medicinal niacin (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.[3][4][61] These can be minimized by initiating therapy at low dosages, increasing dosage gradually, and avoiding administration on an empty stomach.[61]
The acute adverse effects of high-dose niacin 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.[3][4] With long-term use, the adverse effects of high-dose niacin therapy (750 mg per day) also include liver failure (associated with fatigue, nausea, and loss of appetite), hepatitis, and acute liver failure;[3][4] these hepatotoxic effects of niacin occur more often when extended-release dosage forms are used.[3][4] The long-term use of niacin 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[edit]
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[3][4] due to elevation in prostaglandin GD2 (PGD2) and serotonin.[62][63][64][65] Flushing was often thought to involve histamine, but histamine has been shown not to be involved in the reaction.[62] 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][66] Aspirin taken half an hour before the niacin prevents flushing, as does ibuprofen. Taking niacin 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 niacin have been developed to lessen these side effects.[67][68]
Liver damage[edit]
Niacin in medicinal doses can cause modest elevations in serum transaminase and unconjugated bilirubin, both biomarkers of liver injury. The increases usually resolves even when drug intake is continued.[14][69][70] 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.[14]
Diabetes[edit]
The high doses of niacin used to treat hyperlipidemia have been shown to elevate fasting blood glucose in people with type 2 diabetes.[15] Long-term niacin therapy was also associated with an increase in the risk of new-onset type 2 diabetes.[15][16]
Other adverse effects[edit]
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.[71] Niaspan, the slow-release product, has been associated with a reduction in platelet content and a modest increase in prothrombin time.[24]
Pharmacology[edit]
Pharmacodynamics[edit]
Niacin and nicotinamide are both converted into the coenzyme NAD.[72] NAD converts to NADP by phosphorylation in the presence of the enzyme NAD+ kinase. NAD and NADP are coenzymes for many dehydrogenases, participating in many hydrogen transfer processes.[73] 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.[73] High energy requirements (brain) or high turnover rate (gut, skin) organs are usually the most susceptible to their deficiency.[74]
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.[75][76]
Niacin inhibits cytochrome P450 enzymes CYP2E1, CYP2D6 and CYP3A4.[77] 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.[78] 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.[69][70]
See also: Niacin § Liver_damage
Pharmacokinetics[edit]
Both niacin and niacinamide are rapidly absorbed from the stomach and small intestine. Absorption is facilitated by sodium-dependent diffusion, and at higher intakes, via passive diffusion. Unlike some other vitamins, the percent absorbed does not decrease with increasing dose, so that even at amounts of 3-4 grams, absorption is nearly complete.[19] With a one gram dose, peak plasma concentrations of 15 to 30 μg/mL are reached within 30 to 60 minutes. Approximately 88% of an oral pharmacologic dose is eliminated by the kidneys as unchanged niacin or nicotinuric acid, its primary metabolite. The plasma elimination half-life of niacin ranges from 20 to 45 minutes.[23]
Niacinamide is the major form in the bloodstream. In the liver, niacinamide is converted to storage nicotinamide adenine dinucleotide (NAD). As needed, liver NAD is hydrolyzed to niacinamide and niacin for transport to tissues, there reconverted to NAD to serve as an enzyme cofactor.[19] Excess niacin is methylated in the liver to N1-methylnicotinamide (NMN) and excreted in urine as such or as the oxidized metabolite N1-methyl-2-pyridone-5-carboxamide (2-pyridone). Decreased urinary content of these metabolites is a measure of niacin deficiency.[19]
Niacin, serotonin (5-hydroxytryptamine), and melatonin biosynthesis from tryptophan
Biosynthesis[edit]
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.[79] 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.[19] 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.[80]
Industrial synthesis[edit]
Nicotinonitrile is produced by ammoxidation of 3-methylpyridine. Nitrile hydratase is then used to catalyze nicotinonitrile to nicotinamide, which can be converted to niacin.[81] Alternatively, ammonia, acetic acid and paraldehyde are used to make 5-ethyl-2-methyl-pyridine, which is then converted directly to niacin.[82]
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.[83]
This colorless, water-soluble solid is a derivative of pyridine, with a carboxyl group (COOH) at the 3-position.[19] Other forms of vitamin B3 include the corresponding amide nicotinamide (niacinamide), where the carboxyl group has been replaced by a carboxamide group (CONH
2).[19]
Preparations[edit]
Niacin is incorporated into multi-vitamin and sold as a single-ingredient dietary supplement. The latter can be immediate or slow release.[84]
Nicotinamide (niacinamide) is used to treat niacin deficiency because it does not cause the flushing adverse reaction seen with niacin. Nicotinamide may be toxic to the liver at doses exceeding 3 g/day for adults.[85]
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.[86][87]
Prescription niacin in combination with statin drugs (discontinued) is 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.[47][88][89] 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.[90] The study resulted in the withdrawal of Tredaptive from the international market.[91][92]
Inositol hexanicotinate
One form of dietary supplement sold in the US is inositol hexanicotinate (IHN), also called inositol nicotinate. This is inositol that has been esterified with niacin on all six of inositol's alcohol groups.[93] 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.[94]
Further information: Vitamin § History
Niacin as a chemical compound was first described by chemist Hugo Weidel in 1873 in his studies of nicotine,[95] 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.[96] Over time, eight chemically distinct, water-soluble B vitamins were isolated and numbered, with niacin as vitamin B3.[96]
Further information: Pellagra § History
Corn (maize) became a staple food in the southeast United States and in parts of Europe. A disease that was characterized by dermatitis of sunlight-exposed skin was described in Spain in 1735 by Gaspar Casal. He attributed the cause to poor diet.[97] In northern Italy it was named "pellagra" from the Lombard language (agra = holly-like or serum-like; pell = skin).[98][99] In time, the disease was more closely linked specifically to corn.[100] 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.[101][102]
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."[103] It was also referred to as "vitamin PP", "vitamin P-P" and "PP-factor", all derived from the term "pellagra-preventive factor".[9] 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.[104]
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.[105] The resulting name niacin was derived from nicotinic acid + vitamin.[9][106] 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.[107]
In 1955, Altschul and colleagues described large amounts of niacin as having a lipid-lowering property.[108] As such, niacin is the oldest known lipid-lowering drug.[109] Lovastatin, the first 'statin' drug, was first marketed in 1987.[110]
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 hydroxycarboxylic acid receptor 2 (HCA2), also known as niacin receptor 1 (NIACR1).[111][112][113][114] Unlike niacin, nicotinamide does not activate NIACR1; however, both niacin and nicotinamide activate the G protein-coupled estrogen receptor (GPER) in vitro.[115]
^ "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.
^ a b "Niacin Use During Pregnancy". Drugs.com. 29 July 2019. Retrieved 4 May 2020.
^ a b c d e f g h i j k "Niacin". Micronutrient Information Center, Linus Pauling Institute, Oregon State University, Corvallis, OR. 8 October 2018. Retrieved 16 September 2019.
^ a b c d e f g h i j k l m n "Niacin Fact Sheet for Health Professionals". Office of Dietary Supplements, US National Institutes of Health. 3 June 2020. Retrieved 29 June 2020. Cite journal requires |journal= (help)
^ a b c 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.
^ a b "Why fortify?". Food Fortification Initiative. 2017. Retrieved 4 April 2017.
^ Jaconello P (October 1992). "Niacin versus niacinamide". CMAJ. 147 (7): 990. PMC 1336277. PMID 1393911.
^ Kirkland JB (May 2012). "Niacin requirements for genomic stability". Mutation Research. 733 (1–2): 14–20. doi:10.1016/j.mrfmmm.2011.11.008. PMID 22138132.
^ a b c d e f World Health Organization (2000). "Pellagra And Its Prevention And Control In Major Emergencies". World Health Organization (WHO). hdl:10665/66704. WHO/NHD/00.10. Cite journal requires |journal= (help)
^ "Niacin". Drugs.com. 16 March 2019. Retrieved 27 April 2020.
^ a b 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.
^ 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.
^ a b Schandelmaier S, Briel M, Saccilotto R, Olu KK, Arpagaus A, Hemkens LG, Nordmann AJ (June 2017). "Niacin for primary and secondary prevention of cardiovascular events". The Cochrane Database of Systematic Reviews. 6: CD009744. doi:10.1002/14651858.CD009744.pub2. PMC 6481694. PMID 28616955.
^ a b c "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.
^ a b c d 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. PMID 24655688.
^ a b c 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.
^ a b "Niacin - Drug Usage Statistics". ClinCalc. Retrieved 11 April 2020.
^ 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.
^ a b c d e f g h i j 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.
^ a b c d e f g h i j 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. Retrieved 29 August 2018.
^ a b c "Overview on Dietary Reference Values for the EU population as derived by the EFSA Panel on Dietetic Products, Nutrition and Allergies" (PDF). 2017.
^ a b c "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.
^ a b c d e "NIACOR-niacin tablet". DAILYMED, US National Library of Medicine. March 2020. Retrieved 9 May 2020.
^ a b c d e f "Niaspan Patient Package and Product Information (PPPI)" (PDF). December 2018. Retrieved 9 May 2020.
^ Fu L, Doreswamy V, Prakash R (August 2014). "The biochemical pathways of central nervous system neural degeneration in niacin deficiency". Neural Regeneration Research. 9 (16): 1509–13. doi:10.4103/1673-5374.139475. PMC 4192966. PMID 25317166.
^ Pitsavas S, Andreou C, Bascialla F, Bozikas VP, Karavatos A (March 2004). "Pellagra encephalopathy following B-complex vitamin treatment without niacin". International Journal of Psychiatry in Medicine. 34 (1): 91–5. doi:10.2190/29XV-1GG1-U17K-RGJH. PMID 15242145. S2CID 29070525. Archived from the original on 10 July 2012. Retrieved 27 November 2009.
^ Bressani R, Gomez-Brenes R, Scrimshaw NS (1961). "Effect of processing on distribution and in vitro availability of niacin of corn (Zea mays)". Food Technol. 15: 450–4.
^ a b LaRosa, CJ (January 2020). "Hartnup Disease". Retrieved 6 July 2020.
^ a b Health Canada (20 July 2005). "Dietary Reference Intakes". Government of Canada. Retrieved 20 June 2018.
^ a b c "Tolerable Upper Intake Levels for Vitamins and Minerals" (PDF). European Food Safety Authority. February 2006. Retrieved 18 June 2018.
^ a b "Nutrient Recommendations: Dietary Reference Intakes (DRI)". National Institutes of Health, Office of Dietary Supplements. Retrieved 30 June 2020.
^ "Tolerable Upper Intake Levels For Vitamins And Minerals" (PDF). European Food Safety Authority. 2006.
^ "Federal Register May 27, 2016 Food Labeling: Revision of the Nutrition and Supplement Facts Labels" (PDF).
^ "Daily Value Reference of the Dietary Supplement Label Database (DSLD)". Dietary Supplement Label Database (DSLD). Retrieved 16 May 2020.
^ "Changes to the Nutrition Facts Label". U.S. Food and Drug Administration (FDA). 27 May 2016. Retrieved 16 May 2020. This article incorporates text from this source, which is in the public domain.
^ "Industry Resources on the Changes to the Nutrition Facts Label". U.S. Food and Drug Administration (FDA). 21 December 2018. Retrieved 16 May 2020. This article incorporates text from this source, which is in the public domain.
^ "Niacin content per 100 grams; select food subset, abridged list by food groups". United States Department of Agriculture, Agricultural Research Service, USDA Branded Food Products Database v.3.6.4.1. 17 January 2017. Retrieved 23 January 2017.
^ a b c "USDA National Nutrient Database for Standard Reference Legacy: Niacin" (PDF). U.S. Department of Agriculture, Agricultural Research Service. 2018. Retrieved 12 May 2020.
^ "Nutritional Yeast Flakes (two tablespoons = 16 grams". NutritionData.Self.com. Retrieved 13 May 2020.
^ "Vitamin B3 (Niacin)". VivaHealth.org. 2000. Retrieved 12 May 2020.
^ "Effects of Cooking on Vitamins (Table)". Beyondveg. Archived from the original on 16 October 2012. Retrieved 30 April 2019.
^ a b "Map: Count of Nutrients In Fortification Standards". Global Fortification Data Exchange. Retrieved 4 July 2020.
^ "Structure/Function Claims". U.S. Food & Drug Administration. December 2017. Retrieved 30 June 2020.
^ "Cholesterol Medications". American Heart Association. 10 November 2018. Retrieved 8 May 2020.
^ 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.
^ Garg A, Sharma A, Krishnamoorthy P, Garg J, Virmani D, Sharma T, Stefanini G, Kostis JB, Mukherjee D, Sikorskaya E (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.
^ a b c 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.
^ Soga T, Kamohara M, Takasaki J, Matsumoto S, 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.
^ Wise A, Foord SM, Fraser NJ, Barnes AA, 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.
^ 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.
^ 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.
^ a b 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.
^ 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.
^ 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.
^ 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.
^ 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.
^ "Advicor (Niacin Extended-Release & Lovastatin) Tablets". U.S. Food and Drug Administration; Drug Approval Package. 13 September 2002. Retrieved 17 May 2020.
^ "Drugs.com, Abbott Receives FDA Approval for Simcor (Niaspan / simvastatin), a Novel Combination Medicine for Comprehensive Cholesterol Management". Retrieved 15 March 2008.
^ 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.
^ "AbbVie Inc.; Withdrawal of Approval of New Drug Applications for ADVICOR and SIMCOR". U.S. Federal Register. 18 April 2016. Retrieved 17 May 2020.
^ a b c d e Niaspan (niacin extended-release) tablets prescribing information. AbbVie Inc., US-NIAS-180036, North Chicago, IL 60064, December 2018
^ 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". The Journal of Pharmacology and Experimental Therapeutics. 327 (3): 665–72. doi:10.1124/jpet.108.141333. PMID 18784348. S2CID 5609632.
^ Benyó Z, Gille A, Kero J, Csiky M, Suchánková MC, Nüsing RM, Moers A, Pfeffer K, Offermanns S (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.
^ 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.
^ 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.
^ 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.
^ Katzung, Bertram G. (2006). Basic and clinical pharmacology. New York: McGraw-Hill Medical Publishing Division. ISBN 978-0-07-145153-6.
^ 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.
^ a b Dickey, W.; McAleer, J. J.; Callender, M. E. (1991). "The Nicotinic Acid Provocation Test and Unconjugated Hyperbilirubinaemia". The Ulster Medical Journal. 60 (1): 49–52. PMC 2448612. PMID 1853497.
^ a b Röllinghoff, W.; Paumgartner, G.; Preisig, R. (1981). "Nicotinic Acid Test in the Diagnosis of Gilbert's Syndrome: Correlation With Bilirubin Clearance". Gut. 22 (8): 663–8. doi:10.1136/gut.22.8.663. PMC 1420060. PMID 7286783.
^ 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.
^ Cox M, Lehninger AL, Nelson DR (2000). Lehninger principles of biochemistry. New York: Worth Publishers. ISBN 978-1-57259-153-0.
^ a b Wan P, Moat S, Anstey A (June 2011). "Pellagra: a review with emphasis on photosensitivity". The British Journal of Dermatology. 164 (6): 1188–200. doi:10.1111/j.1365-2133.2010.10163.x. PMID 21128910. S2CID 205261045.
^ 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.
^ Zeman M, Vecka M, Perlík F, Hromádka R, Staňková B, Tvrzická E, Žák A (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.
^ 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.
^ 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.
^ Orkin, Stuart H.; Nathan, David G. (January 2009). Nathan and Oski's Hematology of Infancy and Childhood. pp. 118–119. ISBN 9781416034308.
^ 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.
^ Carpenter KJ (1983). "The relationship of pellagra to corn and the low availability of niacin in cereals". Experientia Suppl. Experientia Supplementum. 44: 197–222. doi:10.1007/978-3-0348-6540-1_12. ISBN 978-3-0348-6542-5. PMID 6357846.
^ Abe N, Ichimura H, Kataoka T, Morishita S, Shimizu S, Shoji T, Watanabe N (2007). "Pyridine and Pyridine Derivatives". Ullmann's Encyclopedia of Industrial Chemistry. Weinheim: Wiley-VCH. doi:10.1002/14356007.a22_399.
^ Eschenmooser, Walter (June 1997). "100 Years of Progress with LONZA". Chimia. 51 (6): 259-69. Retrieved 8 October 2020.
^ Blum, René (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.
^ 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.
^ Knip M, Douek IF, Moore WP, Gillmor HA, McLean AE, Bingley PJ, Gale EA (November 2000). "Safety of high-dose nicotinamide: a review". Diabetologia. 43 (11): 1337–45. doi:10.1007/s001250051536. PMID 11126400.
^ 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.
^ 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.
^ Lai E, De Lepeleire I, Crumley TM, Liu F, Wenning LA, Michiels N, Vets E, O'Neill G, Wagner JA, Gottesdiener K (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.
^ 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". Cardiology Clinics. 26 (4): 547–60. doi:10.1016/j.ccl.2008.06.007. PMID 19031552.
^ Landray MJ, Haynes R, Hopewell JC, Parish S, Aung T, Tomson J, Wallendszus K, Craig M, Jiang L, Collins R, Armitage J (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.
^ Nainggolan L (11 January 2013). "Niacin/Laropiprant Products to Be Suspended Worldwide". Medscape. Retrieved 20 February 2017.
^ "Merck begins overseas recall of HDL cholesterol drug". Reuters. 11 January 2013.
^ 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.
^ Taheri, R (15 January 2003). "No-Flush Niacin for the Treatment of Hyperlipidemia". Medscape. Retrieved 31 March 2008.
^ Weidel, H (1873). "Zur Kenntniss des Nicotins". Justus Liebigs Annalen der Chemie und Pharmacie. 165 (2): 330–49. doi:10.1002/jlac.18731650212.
^ a b 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.
^ 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.
^ F. Cherubini, Vocabolario Milanese-Italiano, Imp. Regia Stamperia, 1840-43, vol. I, III.
^ "Definition of Pellagra". MedicineNet.com. Archived from the original on 30 September 2007. Retrieved 18 June 2007.
^ Cesare Lombroso, Studi clinici ed esperimentali sulla natura, causa e terapia delle pellagra (Bologna: Fava e Garagnani, 1869)
^ 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. CS1 maint: multiple names: authors list (link)
^ Kraut A. "Dr. Joseph Goldberger and the War on Pellagra | Ashes on the Potomac". history.nih.gov. Retrieved 20 February 2017.
^ 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.
^ Ruth Hanna Sachs, White Rose History. 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."
^ "Niacin and Nicotinic Acid". Journal of the American Medical Association. 118 (10): 823. 7 March 1942. doi:10.1001/jama.1942.02830100053014.
^ "Niacin and Niacin Amide". Journal of the American Medical Association. 118 (10): 819. 7 March 1942. doi:10.1001/jama.1942.02830100049011.
^ 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.
^ 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.
^ 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.
^ Simons J (January 2003). "The $10 billion pill". Fortune. 147 (1): 58–62, 66, 68. PMID 12602122.
^ 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.
^ 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.
^ 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.
^ 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.
^ 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.
"Niacin". Drug Information Portal. U.S. National Library of Medicine.
Vitamins (A11)
α-Carotene
β-Carotene
Retinol#
Tretinoin#
Ergosterol
Ergocalciferol#
7-Dehydrocholesterol
Previtamin D3
Cholecalciferol#
25-hydroxycholecalciferol
Calcitriol (1,25-dihydroxycholecalciferol)
Calcitroic acid
Dihydroergocalciferol
D analogues
Alfacalcidol
Dihydrotachysterol
Tacalcitol
Paricalcitol
Tocofersolan
Phylloquinone (K1)#
Menaquinones (K2)
Menadione (K3)‡
Various (K4)
4-Amino-2-methyl-1-naphthol (K5)‡
2-Methylnaphthalene-1,4-diamine (K6)
4-Amino-3-methyl-1-naphthol (K7)
Thiamine#
B1 analogues
Acefurtiamine
Allithiamine
Fursultiamine
Octotiamine
Prosultiamine
Riboflavin#
Nicotinamide#
Pyridoxine#, Pyridoxal phosphate
Folic acid#
Dihydrofolic acid
Folinic acid
Levomefolic acid
Adenosylcobalamin
Hydroxocobalamin#
Methylcobalamin
Ascorbic acid#
Dehydroascorbic acid
#WHO-EM
‡Withdrawn from market
Clinical trials:
†Phase III
§Never to phase III
Peripheral vasodilators (C04)
Phenylethanolamine derivatives
Isoxsuprine
Buphenine
Bamethan
Alpha blockers
Tolazoline
Selective α1-blockers
Terazosin
Niacin and derivatives
Nicotinyl alcohol
Inositol nicotinate
Ciclonicate
Purine derivatives
Pentifylline
Xantinol nicotinate
Etofylline nicotinate
Ergot alkaloids
Ergoloid
Dihydroergocristine
Other peripheral vasodilators
Cyclandelate
Phenoxybenzamine
Vincamine
Moxisylyte
Bencyclane
Vinburnine
Sulcotidil
Buflomedil
Naftidrofuryl
Butalamine
Visnadine
Cetiedil
Cinepazide
Ifenprodil
Azapetine
Fasudil
Lipid-modifying agents (C10)
Cholesterol absorption inhibitors, NPC1L1
Bile acid sequestrants/resins (LDL)
Colesevelam
Colestilan
Colestipol
Colestyramine
Colextran
Statins (HMG-CoA reductase, LDL)
Cerivastatin‡
Mevastatin
Simvastatin#
Niacin and derivatives (HDL and LDL)
Aluminium nicotinate
Niceritrol
Nicofuranose
MTTP inhibitors (VLDL)
Dirlotapide
Lomitapide
Mitratapide
ATP citrate lyase inhibitors (LDL)
Fibrates (PPAR)
Aluminium clofibrate
Bezafibrate
Ciprofibrate
Clinofibrate
Clofibrate‡
Clofibride
Etofibrate
Pemafibrate
Ronifibrate
Simfibrate
CETP inhibitors (HDL)
Anacetrapib†
Dalcetrapib§
Evacetrapib§
Obicetrapib†
Torcetrapib§
PCSK9 inhibitors (LDL)
Alirocumab
Bococizumab
Evolocumab
Amlodipine/atorvastatin
Bempedoic acid/ezetimibe
Ezetimibe/atorvastatin
Ezetimibe/rosuvastatin
Ezetimibe/simvastatin
Fenofibrate/pravastatin
Fenofibrate/simvastatin
Niacin/laropiprant
Niacin/lovastatin
Niacin/simvastatin
Alipogene tiparvovec
Azacosterol
Azalanstat
Benfluorex‡
Darapladib§
Dextrothyroxine‡
Inclisiran
Lapaquistat§
Magnesium pyridoxal 5-phosphate glutamate
Meglutol
Mipomersen
Probucol
Tiadenol
Triparanol‡
Volanesorsen
Estrogen receptor modulators
Agonists
Steroidal: 2-Hydroxyestradiol
2-Hydroxyestrone
3-Methyl-19-methyleneandrosta-3,5-dien-17β-ol
3α-Androstanediol
3α,5α-Dihydrolevonorgestrel
3β,5α-Dihydrolevonorgestrel
3α-Hydroxytibolone
3β-Hydroxytibolone
3β-Androstanediol
4-Androstenediol
4-Androstenedione
4-Fluoroestradiol
4-Hydroxyestradiol
4-Methoxyestrone
7-Oxo-DHEA
7α-Hydroxy-DHEA
7α-Methylestradiol
7β-Hydroxyepiandrosterone
8,9-Dehydroestradiol
8,9-Dehydroestrone
8β-VE2
10β,17β-Dihydroxyestra-1,4-dien-3-one (DHED)
11β-Chloromethylestradiol
11β-Methoxyestradiol
15α-Hydroxyestradiol
16-Ketoestradiol
16-Ketoestrone
16α-Fluoroestradiol
16α-Hydroxy-DHEA
16α-Hydroxyestrone
16α-Iodoestradiol
16α-LE2
16β-Hydroxyestrone
16β,17α-Epiestriol (16β-hydroxy-17α-estradiol)
17α-Estradiol (alfatradiol)
17α-Dihydroequilenin
17α-Dihydroequilin
17α-Epiestriol (16α-hydroxy-17α-estradiol)
17α-Ethynyl-3α-androstanediol
17α-Ethynyl-3β-androstanediol
17β-Dihydroequilenin
17β-Dihydroequilin
17β-Methyl-17α-dihydroequilenin
Abiraterone acetate
Alestramustine
Almestrone
Anabolic steroids (e.g., testosterone and esters, methyltestosterone, metandienone (methandrostenolone), nandrolone and esters, many others; via estrogenic metabolites)
Atrimustine
Bolandiol
Bolandiol dipropionate
Butolame
Clomestrone
Cloxestradiol
Cloxestradiol acetate
Conjugated estriol
Conjugated estrogens
Cyclodiol
Cyclotriol
DHEA-S
ent-Estradiol
Epiestriol (16β-epiestriol, 16β-hydroxy-17β-estradiol)
Epimestrol
Equilenin
Equilin
ERA-63 (ORG-37663)
Esterified estrogens
Estetrol
Estradiol esters
Lipoidal estradiol
Polyestradiol phosphate
Estramustine phosphate
Estrapronicate
Estrazinol
Estriol
Estriol esters
Polyestriol phosphate
Estrofurate
Estrogenic substances
Estromustine
Estrone
Estrone esters
Estrone methyl ether
Estropipate
Etamestrol (eptamestrol)
Ethinylandrostenediol
Ethandrostate
Ethinylestradiol
Ethinylestradiol 3-benzoate
Ethinylestradiol sulfonate
Ethinylestriol
Ethylestradiol
Etynodiol
Etynodiol diacetate
Hexolame
Hippulin
Hydroxyestrone diacetate
Lynestrenol
Lynestrenol phenylpropionate
Mestranol
Methylestradiol
Moxestrol
Mytatrienediol
Nilestriol
Noretynodrel
Orestrate
Prodiame
Prolame
Promestriene
RU-16117
Quinestradol
Quinestrol
Tibolone
Nonsteroidal: (R,R)-THC
(S,S)-THC
2,8-DHHHC
β-LGND1
β-LGND2 (GTx-878)
Allenestrol
Allenolic acid
Benzestrol
Bifluranol
Bisdehydrodoisynolic acid
Butestrol
Carbestrol
DCW234
Diarylpropionitrile
Dienestrol
Dienestrol diacetate
Diethylstilbestrol esters
Dimestrol (dianisylhexene)
Dimethylstilbestrol
Doisynoestrol (fenocycline)
Doisynolic acid
Efavirenz
ERB-196 (WAY-202196)
Erteberel (SERBA-1, LY-500307)
Estrobin (DBE)
Fenestrel
FERb 033
Fosfestrol (diethylstilbestrol diphosphate)
Furostilbestrol (diethylstilbestrol difuroate)
GTx-758
Hexestrol
Hexestrol esters
ICI-85966 (Stilbostat)
meso-Butestrol
meso-Hexestrol
Mestilbol
Methallenestril
Methestrol
Methestrol dipropionate
Paroxypropione
Pentafluranol
Phenestrol
Prinaberel (ERB-041, WAY-202041)
Propylpyrazoletriol
Quadrosilan
SERBA-2
SKF-82,958
Terfluranol
Triphenylbromoethylene
Triphenylchloroethylene
Triphenyliodoethylene
Triphenylmethylethylene (triphenylpropene)
WAY-204688 (SIM-688)
Unknown/unsorted: ERB-26
ERA-45
ERB-79
Xenoestrogens: Anise-related (e.g., anethole, anol, dianethole, dianol, photoanethole)
Chalconoids (e.g., isoliquiritigenin, phloretin, phlorizin (phloridzin), wedelolactone)
Coumestans (e.g., coumestrol, psoralidin)
Flavonoids (incl. 7,8-DHF, 8-prenylnaringenin, apigenin, baicalein, baicalin, biochanin A, calycosin, catechin, daidzein, daidzin, ECG, EGCG, epicatechin, equol, formononetin, glabrene, glabridin, genistein, genistin, glycitein, kaempferol, liquiritigenin, mirificin, myricetin, naringenin, penduletin, pinocembrin, prunetin, puerarin, quercetin, tectoridin, tectorigenin)
Lignans (e.g., enterodiol, enterolactone, nyasol (cis-hinokiresinol))
Metalloestrogens (e.g., cadmium)
Pesticides (e.g., alternariol, dieldrin, endosulfan, fenarimol, HPTE, methiocarb, methoxychlor, triclocarban, triclosan)
Phytosteroids (e.g., digitoxin (digitalis), diosgenin, guggulsterone)
Phytosterols (e.g., β-sitosterol, campesterol, stigmasterol)
Resorcylic acid lactones (e.g., zearalanone, α-zearalenol, β-zearalenol, zearalenone, zeranol (α-zearalanol), taleranol (teranol, β-zearalanol))
Steroid-like (e.g., deoxymiroestrol, miroestrol)
Stilbenoids (e.g., resveratrol, rhaponticin)
Synthetic xenoestrogens (e.g., alkylphenols, bisphenols (e.g., BPA, BPF, BPS), DDT, parabens, PBBs, PHBA, phthalates, PCBs)
Others (e.g., agnuside, rotundifuran)
(SERMs)
2-Phenylbenzofuran
2-Phenylbenzothiophene
4'-Hydroxynorendoxifen
27-Hydroxycholesterol
Acefluranol
Acolbifene
Afimoxifene
Anordiol
Anordrin
Bazedoxifene
Brilanestrant
Broparestrol
Chlorotrianisene
Clomifenoxide
CN-55945-27
Cyclofenil
Desmethylchlorotrianisene
Droloxifene
Elacestrant
Enclomifene
Etacstil (GW-5638, DPC-974)
Ethamoxytriphetol (MER-25)
Fispemifene
ICI-55548
Idoxifene
Levormeloxifene
LN-1643
LY-117018
Menerba
Miproxifene
Miproxifene phosphate
MRL-37
Nafoxidine
Nitromifene
NNC 45-0095
Ormeloxifene
Ospemifene
Panomifene
Pipendoxifene
Raloxifene
Rimostil (P-081)
Spironolactone
TAS-108 (SR-16234)
Trioxifene
TZE-5323
U-11555A
U-11634
Zindoxifene
Zuclomifene
(R,R)-THC
7β-Hydroxy-DHEA
Chloroindazole
Cytestrol acetate
EM-800 (SCH-57050)
Epitiostanol
Fulvestrant (ICI-182780)
Glyceollins (I, II, III, IV)
ICI-164384
MDL-101906
Mepitiostane
Methylepitiostanol
Methylpiperidinopyrazole
MIBE
Oxabicycloheptene sulfonate
PHTPP
Prochloraz
ZB716
Coregulator-binding modulators: ERX-11
Noncompetitive inhibitors: Trilostane
GPER
Afimoxifene (4-hydroxytamoxifen)
DDT (p,p'-DDT, o',p'-DDE)
Equol
Genistein
GPER-L1
Hydroxytyrosol
Kepone
Oleuropein
PCBs (2,2',5'-PCB-4-OH)
Tectoridin
CCL18
Receptor/signaling modulators
Estrogens and antiestrogens
Androgen receptor modulators
Progesterone receptor modulators
List of estrogens
GABAA receptor positive modulators
Brometone
Chloralodol
Chlorobutanol (cloretone)
Ethanol (alcohol) (alcoholic drink)
Ethchlorvynol
Methylpentynol
Pentanol
Petrichloral
Propanol
tert-Butanol (2M2P)
tert-Pentanol (2M2B)
Tribromoethanol
Trichloroethanol
Triclofos
Trifluoroethanol
(-)-DMBB
Allobarbital
Alphenal
Aprobarbital
Barbexaclone
Barbital
Benzobarbital
Benzylbutylbarbiturate
Brallobarbital
Brophebarbital
Butabarbital/Secbutabarbital
Buthalital
Butobarbital
Butallylonal
Carbubarb
Crotylbarbital
Cyclobarbital
Cyclopentobarbital
Difebarbamate
Enallylpropymal
Ethallobarbital
Eterobarb
Febarbamate
Heptabarb
Heptobarbital
Hexethal
Hexobarbital
Metharbital
Methitural
Methohexital
Methylphenobarbital
Narcobarbital
Nealbarbital
Phenallymal
Phetharbital
Probarbital
Propallylonal
Propylbarbital
Proxibarbital
Reposal
Sigmodal
Spirobarbital
Talbutal
Tetrabamate
Tetrabarbital
Thialbarbital
Thiamylal
Thiobarbital
Thiobutabarbital
Thiotetrabarbital
Valofane
Vinbarbital
Vinylbital
2-Oxoquazepam
3-Hydroxyphenazepam
Adinazolam
Arfendazam
Avizafone
Bentazepam
Bromazepam
Brotizolam
Camazepam
Carburazepam
Ciclotizolam
Cinazepam
Cinolazepam
Clazolam
Climazolam
Clonazolam
Cloniprazepam
Clorazepate
Clotiazepam
Cloxazolam
CP-1414S
Cyprazepam
Delorazepam
Demoxepam
Doxefazepam
Elfazepam
Estazolam
Ethyl carfluzepate
Ethyl dirazepate
Ethyl loflazepate
Etizolam
EVT-201
FG-8205
Fletazepam
Flubromazepam
Fludiazepam
Flunitrazolam
Flutazolam
Flutemazepam
Flutoprazepam
Fosazepam
Gidazepam
Halazepam
Haloxazolam
Iclazepam
Imidazenil
Irazepine
Ketazolam
Lofendazam
Lopirazepam
Loprazolam
Lormetazepam
Meclonazepam
Medazepam
Menitrazepam
Metaclazepam
Mexazolam
Motrazepam
N-Desalkylflurazepam
Nifoxipam
Nimetazepam
Nitrazepam
Nitrazepate
Nitrazolam
Nordazepam
Nortetrazepam
Oxazolam
Phenazepam
Pinazepam
Pivoxazepam
Prazepam
Premazepam
Proflazepam
Pyrazolam
QH-II-66
Quazepam
Reclazepam
Rilmazafone
Ripazepam
Ro48-6791
SH-053-R-CH3-2′F
Sulazepam
Tetrazepam
Tolufazepam
Triflubazam
Triflunordazepam (Ro5-2904)
Tuclazepam
Uldazepam
Zapizolam
Zolazepam
Zomebazam
Carbamates
Carisbamate
Carisoprodol
Clocental
Cyclarbamate
Emylcamate
Ethinamate
Hexapropymate
Lorbamate
Mebutamate
Meprobamate
Nisobamate
Pentabamate
Phenprobamate
Procymate
Styramate
Tybamate
6-Methylapigenin
Ampelopsin (dihydromyricetin)
Baicalein
Baicalin
Hispidulin
Linarin
Rc-OMe
Skullcap constituents (e.g., baicalin)
Wogonin
Metomidate
Propoxate
Kava constituents
10-Methoxyyangonin
11-Hydroxyyangonin
Desmethoxyyangonin
11-Methoxy-12-hydroxydehydrokavain
7,8-Dihydroyangonin
Kavain
5-Hydroxykavain
7,8-Dihydrokavain
5,6,7,8-Tetrahydroyangonin
5,6-Dehydromethysticin
Methysticin
7,8-Dihydromethysticin
Yangonin
Monoureides
Acecarbromal
Apronal (apronalide)
Bromisoval
Carbromal
Capuride
Ectylurea
Neuroactive steroids
Acebrochol
Allopregnanolone (brexanolone)
Alfadolone
Alfaxalone
Androstenol
Androsterone
Certain anabolic-androgenic steroids
DHDOC
3α-DHP
5β-DHP
Ganaxolone
Hydroxydione
Minaxolone
ORG-20599
Pregnanolone (eltanolone)
Renanolone
SAGE-105
THDOC
Zuranolone
Nonbenzodiazepines
Cyclopyrrolones: Eszopiclone
Pagoclone
Pazinaclone
Suproclone
Suriclone
Imidazopyridines: Alpidem
Necopidem
Saripidem
Pyrazolopyrimidines: Divaplon
Fasiplon
Indiplon
Lorediplon
Ocinaplon
Panadiplon
Taniplon
Others: Adipiplon
CGS-8216
CGS-13767
CL-218,872
ELB-139
GBLD-345
Imepitoin
JM-1232
L-838,417
Lirequinil (Ro41-3696)
NS-2664
NS-11394
Pipequaline
ROD-188
RWJ-51204
SB-205,384
SX-3228
TGSC01AA
TP-003
TPA-023
TP-13
Viqualine
Y-23684
Piperidinediones
Glutethimide
Methyprylon
Piperidione
Pyrithyldione
Pyrazolopyridines
Cartazolate
Etazolate
ICI-190,622
Tracazolate
Quinazolinones
Afloqualone
Cloroqualone
Diproqualone
Etaqualone
Mebroqualone
Mecloqualone
Methylmethaqualone
Nitromethaqualone
Volatiles/gases
Aliflurane
Centalun
Chloral betaine
Cryofluorane
Desflurane
Dichloralphenazone
Enflurane
Ethyl chloride
Fluroxene
Halopropane
Isoflurane
Kerosine
Methoxyflurane
Methoxypropane
Norflurane
Paraldehyde
Roflurane
Synthane
Teflurane
Trichloroethane (methyl chloroform)
Vinyl ether
Others/unsorted
3-Hydroxybutanal
α-EMTBL
AA-29504
Avermectins (e.g., ivermectin)
Bromide compounds (e.g., lithium bromide, potassium bromide, sodium bromide)
Chloralose
Chlormezanone
Clomethiazole
DEABL
Dihydroergolines (e.g., dihydroergocryptine, dihydroergosine, dihydroergotamine, ergoloid (dihydroergotoxine))
Etazepine
Etifoxine
Fenamates (e.g., flufenamic acid, mefenamic acid, niflumic acid, tolfenamic acid)
Hopantenic acid
Lignans (e.g., 4-O-methylhonokiol, honokiol, magnolol, obovatol)
Loreclezole
Menthyl isovalerate (validolum)
Monastrol
Nicotinamide (niacinamide)
Org 25,435
Propanidid
Retigabine (ezogabine)
Seproxetine
Stiripentol
Sulfonylalkanes (e.g., sulfonmethane (sulfonal), tetronal, trional)
Terpenoids (e.g., borneol)
Topiramate
Valerian constituents (e.g., isovaleric acid, isovaleramide, valerenic acid, valerenol)
Unsorted benzodiazepine site positive modulators: α-Pinene
MRK-409 (MK-0343)
TCS-1105
See also: Receptor/signaling modulators • GABA receptor modulators • GABA metabolism/transport modulators
Retrieved from "https://en.wikipedia.org/w/index.php?title=Niacin&oldid=999587476"
AbbVie brands
Aromatic acids
GABAA receptor positive allosteric modulators
GPER agonists
Hypolipidemic agents
CS1 errors: missing periodical
Use dmy dates from July 2019
ECHA InfoCard ID from Wikidata
Drug has EMA link
Chembox having GHS data
Drugs with non-standard pregnancy category
Chemical articles with unknown parameter in Infobox drug
Infobox drug container only
Infobox drug articles with non-default infobox title


text:
Protokół podatkowy – dokument służący do rejestrowania czynności i zdarzeń występujących w ramach przeprowadzanej kontroli podatkowej. Sporządzany jest zgodnie z przepisami Ordynacji Podatkowej na dzień zakończenia kontroli podatkowej.
Zawiera informacje na temat:

 podmiotu, który jest kontrolowany,
 instytucji, która dokonuje kontroli,
 miejsca i czasu przeprowadzenia kontroli,
 przedmiotu i zakresu kontroli,
 oceny prawnej jaka jest przedmiotem kontroli,
 zgromadzonej dokumentacji.

Podmiot kontrolowany ma prawo zapoznać się z treścią sporządzonego protokołu, który powinien jasno określać czy podmiot wywiązuje się z obowiązków podatkowych. Do protokołu załącza się dokumentacje w postaci kopii dokumentów księgowych, wydruków kont księgowych, protokołów z zeznań świadków, przeprowadzonych oględzin, opinii biegłych.

Prawo podatkowe

redpajama_set_name: RedPajamaWikipedia


text:
Home Past Times
Viv Richards: When West Indies cricket ace made it game, set and match in Broughty Ferry
By Craig Millar
December 2 2021, 11.45am Updated: December 2 2021, 6.17pm
The West Indies heroes had a brilliant time in Dundee back in 1980.
For a certain generation, the late 1970s and early '80s are something of a golden age of cricket.
Even if it was only to hear Richie Benaud on BBC Television's test match coverage, a commentator par excellence whose Aussie tones and almost hypnotic on-camera demeanour sparked a thousand impersonations.
Or to listen to the ultra-dry and laconic Yorkshireman Jim Laker who joined him behind the microphone
And then, on radio, there was the incomparable and quintessential Englishman, John Arlott.
On the field at the time, it could be reasonably argued that the West Indies were the best team in the world.
And in July 1980 they were heading to Broughty Ferry.
Douglas Walker preparing the Forhill wicket for the Scotland versus West Indies cricket match.
The home of Forfarshire Cricket Club at Forthill had been chosen as the venue for a two day match between the "Windies" and Scotland.
It was an encounter which would see one of the greatest ever batsmen dragged off the tennis courts to play his innings, one of Forfarshire's finest almost achieve an incredible cricketing hat-trick, and the visiting players being fortified by a local fish and chip shop.
West Indies superstars in Broughty Ferry
Forthill had staged eight internationals before the arrival of the West Indies, dating back to 1924.
But this was something else.
The men from the Caribbean had a team of genuine superstars.
Their line-up included dazzling batsmen like Gordon Greenidge, Desmond Haynes and the extravagantly gifted Viv Richards.
If the batsmen were a formidable force, the array of West Indies bowlers was a fearsome sight for opposition players.
Michael Holding, Andy Roberts, Malcolm Marshall, Colin Croft and Joel Garner could deliver the ball with murderous pace.
The West Indies had broken off from test matches and one-day internationals against England to travel north.
Their impending arrival caused a frisson of excitement at Forthill.
For those who met the West Indians, it was an unforgettable experience – and not just because of the cricket.
Dallas Moir towers over West Indian Test star Alvin Kallicharran before the match at Forthill in 1980.
"I think as a club, the players and the people to do with the running of it were obviously very excited," recalled Rae McLelland, a long-serving Forfarshire seam bowler.
"But it probably didn't get quite the publicity it would get nowadays."
However, to the huge frustration of everyone involved, the first day's play on Thursday July 17 was a washout.
Rain stopped play after Gordon Greenidge and Desmond Haynes ran up a score of 70 for no wicket.
It was then decided to play a separate one-day game on the Friday.
Fish and chicken suppers
But events away from the cricket pitch became part of Forfarshire folklore.
"There was an amazing amount of work done by people at the club in preparation for the West Indies coming," said Rae.
"But when their captain Clive Lloyd saw the lunch for the players being laid out on the first day when it was raining he said: 'My boys don't like salad'.
"It turned out they were meat and fish eaters."
The Scotland and West Indies team join forces for a photograph before the big match.
That was when club officials, probably John and Charles Allardyce, who both served as Forfarshire presidents, came to the rescue.
Arrangements were made for around 20 fish and chicken suppers to be ordered and delivered from a nearby chip shop.
"And my goodness, did these guys devour them," said Rae.
Today's sports scientists, fitness coaches and dieticians would not have approved and there were other signs that this was cricket in a different age.
The West Indians appeared to have a rather relaxed approach.
"These guys had an Australian trainer and from what I can remember, he had a bit of difficulty in getting them to warm up and limber up," said Rae.
"It would be fair to say they were somewhat different from what you would expect a modern sports team to be."
But no-one could question their talent and as the 50-over Friday match began before a sizeable crowd, Scotland's players braced themselves for the onslaught.
Alex Steele
As it happened, the Scots did rather well and at one point a major shock was on the cards as they took four wickets for only 31 runs.
Forfarshire's legendary wicketkeeper Alex Steele was playing for Scotland and it was a noteworthy day for him, to say the least.
Steele, who racked up 33 caps for Scotland, excelled and took a major scalp by stumping the outstanding batsman Desmond Haynes.
Alec Steele with a picture of his historic moment against the West Indies at Forthill in 1980.
During his career, Haynes scored 7,487 runs in 116 test matches and made 18 test match centuries.
Only a few weeks before, he had a knock of 184 against England.
His score against Scotland at Forthill was five.
Alex still remembers the fine details of a moment that will live with him forever.
"Jack Clark was one of Scotland's fast bowlers," he said.
"It's normally the case that wicket keepers stand back to quick bowlers but l noticed that Desmond Haynes moved out of his crease when he played the ball down the leg side.
"I told Jack and our captain Richard Swan that I was going to stand up to the stumps because of Desmond's movements and very shortly after Jack pitched the ball eight or nine inches outside leg stump .
"Desmond missed the ball but moved out of his crease and l whipped the bails off.
"Euphoria!
"Desmond was out and it was one of the most magnificent feelings I've ever had.
"I've been told it was the only time Haynes had been stumped while playing for the West Indies!"
It was also an unforgettable moment for Gordon Walker, a Forfarshire off-spin bowler to this day.
He said: "Steelie stumped him and Haynes turned round to him and just said: 'Man that was class'"
Alex also stumped Colin Croft later in the game but in between times he had a fair claim to have done the same to the great Viv Richards.
Sir Viv, as he became, was further down the West Indies batting order than normal but not for tactical reasons.
He was playing tennis on the adjacent courts at Forthill and word was he had told Clive Lloyd he wanted to finish his game before batting.
His masterful 69 helped the West Indies to win by 80 runs but the quick reflexes of Alex came close to stopping that happening.
However, he was denied in controversial fashion.
"I remember the Scottish lads had taken quite a number of quick wickets and the West Indies were not expecting that to happen and Viv Richards was on the tennis courts at the back of the club," said Alex.
"There was a rapid change into his clothes and Viv came out to face bowler Willie Donald.
"Viv's foot was on the line and I whipped the bails off and I just about disintegrated my vocal chords with the loudest appeal.
"Charlie Cormack was the umpire.
"He gave not out.
"There were about 3,000 people at the ground and he said: 'Alex that was absolutely great but they haven't come to see you keep wicket, they've come to see Viv Richards play so it was definitely not out'.
"I wasn't a happy bunny.
"I was absolutely convinced he was out."
But the consolation was stumping Haynes.
Now 80, it was Alex Steele's "most precious moment in cricket" and he looks back on the day as "an absolutely marvellous experience."
The match gave Alec enough memories to last a lifetime.
But after mingling with the players, the West Indies experience turned to the surreal for Gordon Walker when he was visited by the man known as Big Bird.
At six foot eight inches in height, Joel Garner was a physical colossus as well as a devastating bowler.
When he went into the pavilion at Forthill, he had to bend down to get his head below the wooden lintel above the bar.
Gordon, who was then living with his parents near the ground, had met the West Indies players during the day.
"About midnight my doorbell rang," he said.
"When I opened the door all I could see was this maroon blazer, the West Indies colours.
"It was Joel Garner.
"He asked if it was okay for him to come in for a drink and he came in with Faoud Bacchus and Andy Roberts.
"Viv Richards was driving their car and he decided to go nightclubbing.
"Joel Garner sat on my father's big armchair and they stayed until about four in the morning drinking gin and tonics!
"There were a few of the younger boys from the cricket team there. It was quite a special occasion for all of us."
The West Indies players enamoured themselves to the Scots.
And the feeling was mutual.
On the pitch, the Scots managed to bowl out a truly formidable side and performed extremely well against the best bowling attack in the world at the time.
For the record, the West Indies were 233 all out while Scotland scored 153 for seven wickets after 50 overs.
The "special occasion" that Gordon Walker mentions is perhaps an understatement.
The two days that the West Indies came to Broughty Ferry were truly historic.
Bermuda cricket hero Nigel Hazel fired Strathmore to success and fell in love with Forfar
Does north-east cricket have anything to learn from Yorkshire racism scandal?
Nostalgic Christmas Gift Ideas
Scottish Gifts they'll love this Christmas
Dundee Memories: 5 Nostalgic photos in the Tele's 2022 Calendar
12 Scottish Football Books Looking Back at a Different Era
10 Nostalgia books taking a wonderful trip down memory lane
forthill
Thank you for your interest in commenting – this feature is currently under development.
More from The Courier Past Times team
Billy Mackenzie: The Associates singer's forgotten duet with Annie Lennox
Original Star Wars comic art on show at new Dundee University exhibition
General Sikorski in St Andrews? Rare wartime pictures found in forgotten roll of film
St Johnstone boss Callum Davidson says he picks a system to suit his players and doesn't rule out a back 4
VIDEO: Emergency fire crews rush to house blaze in Perth
Emergency crews called out due to 'unusual odour' in Dundee city centre
Friday court round-up — Buckfast, petrol, gas and glue
JIM SPENCE: Scottish clubs are regularly ripped off when selling their prized assets
Yobs throw stones and hurl abuse at 'terrified' Dundee dog owner

redpajama_set_name: RedPajamaCommonCrawl


Just Ink Tees. respects your privacy and the purpose for which our site visitors provide us information. We do not share, sell, or rent any of the information collected to any third parties and do not intend to do so in the future.
Custom screen printed or embroidered items cannot be returned. We will gladly exchange or replace the item(s) if the item is defective or the decorating is severly different than what was approved in a proof. In such cases we will need the item(s) back and we would replace the item(s) for free. We must be notified of the exchange request within 48 hours of date of delivery. Items with noticeable wear cannot be returned. Items must be in like new condition to be eligible for return.


text:
Home>Politics>Charity Commission considers 'misleading' RHI claims
Charity Commission considers 'misleading' RHI claims
October 4, 2018 Arun Menon480
Inquiry chairman Sir Patrick Coghlin said the "inescapable inference" from Michael Doran's testimony was that Action Renewables had misled the Charity Commission
The Charity Commission is "carefully considering" claims that a leading renewable heat group may have misled a commission investigation linked to NI's flawed green energy scheme.
It follows Wednesday's evidence at the Renewable Heat Incentive (RHI) inquiry.
Michael Doran runs Action Renewables, a charity promoting energy efficiency.
The RHI scheme was set up in 2012 to encourage uptake of eco-friendly heat systems, but overgenerous subsidies left NI taxpayers with a £490m bill.
The scheme's failings led to the establishment of a public inquiry in January 2017.
Action Renewables, which helps businesses switch from fossil fuels to green energy, was involved in facilitating about a quarter of all applications to the RHI scheme.
In order to be eligible for the most lucrative subsidy, firms were better to install multiple smaller boilers instead of one large boiler, which would have been more energy efficient – but would not have provided as great a rate of return.
A similar scheme in Great Britain had cost controls included so that it could not be manipulated for profit: the Northern Ireland scheme did not.
On Wednesday, Mr Doran told the inquiry his organisation was aware of this flaw from the outset, but did not flag it with Stormont officials, in case it led to a delay in the introduction of RHI.
Cover-up denial
In early 2017, the Charity Commission began an investigation into Mr Doran's organisation after an Irish News report pointed out that it had handled RHI applications, in spite of Mr Doran's knowledge of the absence of cost controls.
Timothy Johnston is a former special adviser to three first ministers: Ian Paisley, Peter Robinson and Arlene Foster
The commission closed the file after meeting the charity's trustees, who said they did not know about the problems until December 2016.
But on Wednesday, the inquiry's chairman, Sir Patrick Coghlin, said in light of Mr Doran's admission that he knew about the flaws much earlier than he initially claimed, the "inescapable inference" was that Action Renewables was misleading the Charity Commission.
Mr Doran accepted that it seemed that way, but denied accusations of a "cover-up".
The Charity Commission said it was now considering Mr Doran's evidence at the inquiry.
Skip Twitter post by @CharityCommNI
1/2 The Charity Commission for Northern Ireland is aware of the witness evidence provided to the RHI inquiry in relation to the charity Action Renewables Ltd (NIC100806). The Commission will carefully consider this evidence. #rhiinquiry #rhi
— CharityCommissionNI (@CharityCommNI) October 4, 2018
End of Twitter post by @CharityCommNI
It said it is an offence for charities to "knowingly or recklessly supply" false or misleading information.
On Thursday afternoon, the DUP's chief executive is to return to the inquiry to finish giving evidence.
Timothy Johnston – who was an adviser to three Northern Ireland first ministers – appeared in front of the inquiry panel for the first time last week.
When problems with the RHI scheme became public knowledge in late 2016, he was advising then First Minister Arlene Foster.
Mr Johnston is one of the most high-profile witnesses to give evidence at the inquiry, as he was accused of being involved in a decision to delay cost controls to the ill-fated scheme; a decision that did major damage to the public purse.
'Soften controls'
In summer 2015, officials in Stormont's enterprise department, which had set up the scheme, had realised there were major budgetary problems and were looking at plans to bring it under control.
Ultimately, the proposed October introduction of cost controls was delayed by four weeks, meaning the tariffs did not come into force until November, allowing a huge spike in applications.
Mr Johnston has denied any knowledge of how that delay occurred, and has said he is "absolutely certain" he never instructed anyone to "delay, soften or reduce" cost controls.
Hundreds of millions of pounds of public money could be wasted as a result of the RHI scheme
His evidence directly contradicts claims from Timothy Cairns, a former adviser to ex-DUP Enterprise Minister Jonathan Bell, who said he was told by Mr Johnston in June 2015, to work with another adviser, Andrew Crawford, to find an alternative or to seek the latest date possible for implementing cost controls,
Mr Johnston said he had only "suggested as a practical, sensible thing to do" that Mr Cairns should refer to Mr Crawford – his predecessor as the ministerial adviser in the enterprise department – on general matters he needed help with.
Mr Johnston has also faced questions from the panel about how special advisers were appointed within the DUP and the relationship they had with ministers; claims of a "hierarchy" of advisers within the party and about that key period of summer 2015 when cost controls were being considered.
He has consistently denied any involvement in attempting to frustrate plans to close or keep the flawed scheme open.
The former chair of Stormont's enterprise committee, SDLP assembly member Patsy McGlone, also appeared at the inquiry on Thursday to give more evidence.
'Meetings at Moy Park'
He said members were kept in the dark by officials about huge problems with the scheme, and they might have been better informed had they held their meetings "at Moy Park".
Mr McGlone was in charge of the enterprise committee, which was tasked with scrutinising the enterprise department – it held responsibility for the RHI scheme.
He said civil servants were never forthcoming about the problems in the scheme, even as they were drafting emergency changes to it.
"It appears that others outside the assembly were much better informed than elected officials were," he said.
"Perhaps we should have had our meetings at Moy Park."
That refers to evidence already heard by the inquiry that the poultry giant – whose suppliers made up the majority of RHI claimants – was getting regular updates from departmental officials about impending changes.
Patsy McGlone chaired Stormont's enterprise scrutiny committee, which did not spot that the enterprise department had failed to spot critical flaws in the RHI scheme
It was also being kept informed by former DUP special adviser, Andrew Crawford.
Mr McGlone told the inquiry that when he asked about the need for major changes to the scheme in November 2015, he was told there were a few "procedural, financial and legal issues to tidy up".
At that stage, the department was frantically trying to bring the scheme's major overspend under control.
Mr McGlone said the sense his committee got from everything it had been told, was that there was "nothing to worry about".
Later, Mr McGlone conceded that with hindsight, the committee could have done "much, much more" in holding the enterprise department to account.
Inquiry counsel David Scoffield asked if he felt the committee had provided a "sufficiently effective oversight of the department".
Mr McGlone said on reflection it could have done more, but said his view was "heavily qualified and tainted with a degree of cynicism".
'Paddling in disturbance'
He said that was because even when departmental officials gave the committee details of plans to introduce much-needed cost controls in autumn 2015, there was "no sense of urgency" communicated to the committee.
Mr McGlone said the picture being presented by the department was that "everything was calm above water, and everything was padding in disturbance beneath the water".
Funding issues should have been brought to the committee's attention much sooner, he added.
"Even if we had asked for more information, would that have been presented to us in a fulsome, proper and professional way?" he said.
"When I asked about the urgency of the situation in 2015, it was a fairly blasé response I got."
He said the enterprise committee only had elected representatives and four staff members, in comparison to "400 at the department", and said it appeared "they still can't do the job properly".
Extra resources would be of benefit to the committee to provide further scrutiny, he added.
Brexit: Hammond vows to oppose '£90bn no-deal hit'
[ad_1] Image copyright PA Media Chancellor Philip Hammond has signalled he would be prepared to vote against a no-deal Brexit
No-deal Brexit plans discussed at British Irish Council
[ad_1] Image copyright VFKA Image caption Guernsey is hosting the summit Ireland is to step up preparations for a no-deal
Brexit: Theresa May denies 'giving up' on better deal
November 27, 2018 Arun Menon
[ad_1] Image copyright Getty Images Theresa May has denied claims from DUP leader Arlene Foster that she has "given up"
Transfer Talk Arsenal line up Aaron Ramsey replacement Spurs chasing 'Chucky'
Prithvi Shaw's debut ton headlines India's dominant day


Craft beer breweries are drying up in the UK Welcome to the world of femtech: Your employer can monitor your entire pregnancy with this app Researchers devise new deadline trick: decide which deadlines are actually important This tobacco company is offering life insurance discounts to smokers who quit That bad restaurant review you read on Yelp may have been influenced by this odd thing If your coworker does this when they speak, they may be a psychopath This iconic (and tiny) fashion trend will be all over your office this summer Emotional intelligence: what is it and how can you improve yours?
The Clinical Research Director/Sr. Clinical Research Director provides medical input to all aspects of product development, for new and innovative treatments being developed in patients. Will serve as scientific and medical member for clinical team(s) working closely with clinical project lead, the regulatory Lead, and the operational lead(s) for overall programs within the therapeutic area. Develops clinical study concepts based on thorough scientific review and consultation with internal and external experts as well as senior scientists. Acts as author/developer of clinical summary and other supporting documents for regulatory submissions and for publications.
Collaborates with colleagues in clinical development and operations, research, bioPharma development and manufacturing, regulatory affairs, and product safety to participate in protocol development and the design of studies, statistical design, CRO selection and management, site monitoring, safety, clinical support of regulatory interaction, study reporting for new products that will ensure regulatory approval and commercial success.
Ensures that study design is scientifically robust, suitable to test the trial's hypothesis, and likely to meet the objectives of the study while ensuring the safety of the patients participating in the Company's sponsored clinical trials.
Interacts closely with the pre-clinical team, to understand the scientific basis of targeted therapy, and to apply this knowledge to articulating therapeutic strategies and comprehending biomarker exploration and provides clinical and medical perspective to preclinical development programs.
Responsible for medical components of the design, execution, and reporting of study protocols as well as (in collaboration with other team members) labeling and regulatory communications under the direction of the clinical leader or delegate.
Directly develops or guides development of scientific/medical portions of clinical study reports, safety reports, and regulatory submissions to assure production of high quality documents.
Directs protocol implementation, including site identification and communication, attend investigators' meetings, correspond with sites including IRBs, and interact with operations teams.
Supports data analysis and assembly, including clinical study report writing, contribution to the preparation of abstracts, presentations, and manuscripts.
Organizes clinical advisory boards, steering committees and data safety monitoring boards as required.
Acts as primary developer of clinical/scientific content for communications with regulatory agencies and IRBs/ethics boards.
Ensures the feasibility of the study by incorporating study design elements that are ethical and consistent with standard of care and applicable local practices.
Responsible for establishing and maintaining communications with prominent clinical investigators in his/her particular field of expertise.
Works with international colleagues and with external Alliance partners on research initiatives and regulatory issues.
Serving as an information resource to the Company with regard to the science of the field, the competitive landscape in research, and the current state of treatment in areas of unmet medical need.
Oversees and provides leadership to colleagues involved in clinical trial execution.
Ensures consistent practices with the highest ethical standards in compliance with internal SOPs, local regulations, and laws.
Prior clinical development experience for/in the pharmaceutical/biotechnology industry or academic medical setting.
Two years of clinical development experience for/in the pharmaceutical/biotechnology industry setting.


*Link to an article Poker. Nostalgia.
The best possible hand in Texas hold'em is the combination of ten, jack, queen, king, ace, all of the same suit.
Five cards of the same suit in sequential order.
Any four numerically matching cards.
Combination of three of a kind and a pair in the same hand.
Five cards of the same suit, in any order.
Five cards of any suit, in sequential order.
Any three numerically matching cards.
Two different pairs in the same hand.
Any two numerically matching cards.
Any hand that does not qualify under a category listed above.