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94-452: Niacin , also known as nicotinic acid , is an organic compound and a vitamer of   vitamin B 3 , an essential human nutrient . It is produced by plants and animals from the amino acid tryptophan . Niacin is obtained in the diet from a variety of whole 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. Niacin as

188-588: A dietary supplement is used to treat pellagra , a disease caused by niacin deficiency. Signs and symptoms of pellagra include skin and mouth lesions, anemia, headaches, and tiredness. Many countries mandate its addition to wheat flour or other food grains , thereby reducing the risk of pellagra. 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 are identical in their vitamin activity, nicotinamide does not have

282-457: A pyridine ring to which a primary amide group is attached in the meta position. It is an amide of nicotinic acid . As an aromatic compound , it undergoes electrophilic substitution reactions and transformations of its two functional groups . Examples of these reactions reported in Organic Syntheses include the preparation of 2-chloronicotinonitrile by a two-step process via

376-455: A by-product, which is a potent greenhouse gas. In 2018, it was discovered that a niacin factory in Visp , Switzerland, was responsible for around one percent of the country's greenhouse gas emissions. Eventually, catalytic scrubbing technology that eliminates most of the emissions was installed in 2021. This colorless, water-soluble solid is a derivative of pyridine , with a carboxyl group (COOH) at

470-417: A diet low in this essential amino acid , so it is not specific to confirming vitamin status. 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

564-409: A disease caused by lack of the vitamin. When niacin is used as a medicine to treat elevated cholesterol and triglycerides , daily doses range from 500 to 3,000 mg/day. High-dose nicotinamide does not have this medicinal effect. Severe deficiency of niacin in the diet causes the disease pellagra , characterized by diarrhea , sun-sensitive dermatitis involving hyperpigmentation and thickening of

658-507: A few classes of carbon-containing compounds (e.g., carbonate salts and cyanide salts ), along with a few other exceptions (e.g., carbon dioxide , and even hydrogen cyanide despite the fact it contains a carbon-hydrogen bond), are generally considered inorganic . Other than those just named, little consensus exists among chemists on precisely which carbon-containing compounds are excluded, making any rigorous definition of an organic compound elusive. Although organic compounds make up only

752-575: A history of liver disease because both, but especially Niaspan, have been associated with instances of serious, on occasion fatal, liver failure. Both products are contraindicated for people with existing peptic ulcer disease , or other bleeding problems because niacin lowers platelet count and interferes with blood clotting. Both products are also contraindicated for women who are pregnant or expecting to become pregnant because safety during pregnancy has not been evaluated in human trials. These products are contraindicated for women who are lactating because it

846-552: A lesser extent in some vegetables. It is commonly added to cereals and other foods. Many multivitamins contain 20–30   mg of vitamin B 3 and it is also available in higher doses. A 2015 trial found niacinamide to reduce the rate of new nonmelanoma skin cancers and actinic keratoses in a group of people at high risk for the conditions. Niacinamide has been investigated for many additional disorders, including treatment of bullous pemphigoid nonmelanoma skin cancers. Niacinamide may be beneficial in treating psoriasis. There

940-518: A limit to avoid the skin flush reaction. This explains why for EFSA, the recommended daily intake can be higher than the UL. 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. For U.S. food and dietary supplement labeling purposes

1034-404: A more selective synthesis as further hydrolysis of the amide to nicotinic acid is avoided. Nicotinamide can also be made from nicotinic acid. According to Ullmann's Encyclopedia of Industrial Chemistry , worldwide 31,000 tons of nicotinamide were sold in 2014. Nicotinamide, as a part of the cofactor nicotinamide adenine dinucleotide (NADH / NAD ) is crucial to life. In cells, nicotinamide

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1128-474: A regulative force must exist within living bodies. Berzelius also contended that compounds could be distinguished by whether they required any organisms in their synthesis (organic compounds) or whether they did not ( inorganic compounds ). Vitalism taught that formation of these "organic" compounds were fundamentally different from the "inorganic" compounds that could be obtained from the elements by chemical manipulations in laboratories. Vitalism survived for

1222-501: 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. 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. Both niacin and niacinamide are rapidly absorbed from

1316-452: A short period after the formulation of modern ideas about the atomic theory and chemical elements . It first came under question in 1824, when Friedrich Wöhler synthesized oxalic acid , a compound known to occur only in living organisms, from cyanogen . A further experiment was Wöhler's 1828 synthesis of urea from the inorganic salts potassium cyanate and ammonium sulfate . Urea had long been considered an "organic" compound, as it

1410-404: A single element and so not generally considered chemical compounds . The word "organic" in this context does not mean "natural". Vitalism was a widespread conception that substances found in organic nature are formed from the chemical elements by the action of a "vital force" or "life-force" ( vis vitalis ) that only living organisms possess. In the 1810s, Jöns Jacob Berzelius argued that

1504-634: A small percentage of Earth's crust , they are of central importance because all known life is based on organic compounds. Living things incorporate inorganic carbon compounds into organic compounds through a network of processes ( the carbon cycle ) that begins with the conversion of carbon dioxide and a hydrogen source like water into simple sugars and other organic molecules by autotrophic organisms using light ( photosynthesis ) or other sources of energy. Most synthetically-produced organic compounds are ultimately derived from petrochemicals consisting mainly of hydrocarbons , which are themselves formed from

1598-421: A transition metal and to oxygen, and are often prepared directly from metal and carbon monoxide . Nickel tetracarbonyl is typically classified as an organometallic compound as it satisfies the broad definition that organometallic chemistry covers all compounds that contain at least one carbon to metal covalent bond; it is unknown whether organometallic compounds form a subset of organic compounds. For example,

1692-1692: A variety of ways. One major distinction is between natural and synthetic compounds. Organic compounds can also be classified or subdivided by the presence of heteroatoms , e.g., organometallic compounds , which feature bonds between carbon and a metal , and organophosphorus compounds , which feature bonds between carbon and a phosphorus . Another distinction, based on the size of organic compounds, distinguishes between small molecules and polymers . Natural compounds refer to those that are produced by plants or animals. Many of these are still extracted from natural sources because they would be more expensive to produce artificially. Examples include most sugars , some alkaloids and terpenoids , certain nutrients such as vitamin B 12 , and, in general, those natural products with large or stereoisometrically complicated molecules present in reasonable concentrations in living organisms. Further compounds of prime importance in biochemistry are antigens , carbohydrates , enzymes , hormones , lipids and fatty acids , neurotransmitters , nucleic acids , proteins , peptides and amino acids , lectins , vitamins , and fats and oils . Compounds that are prepared by reaction of other compounds are known as " synthetic ". They may be either compounds that are already found in plants/animals or those artificial compounds that do not occur naturally . Most polymers (a category that includes all plastics and rubbers ) are organic synthetic or semi-synthetic compounds. Many organic compounds—two examples are ethanol and insulin —are manufactured industrially using organisms such as bacteria and yeast. Typically,

1786-575: A week. Because deficiencies of other B-vitamins may be present, the WHO recommends a multi-vitamin in addition to the niacinamide. Hartnup disease is a hereditary nutritional disorder resulting in niacin deficiency. It is named after an English family with a genetic disorder that resulted in a failure to absorb the essential amino acid tryptophan , tryptophan being a precursor for niacin synthesis. The symptoms are similar to pellagra, including red, scaly rash and sensitivity to sunlight. Oral niacin or niacinamide

1880-425: Is a form of vitamin B 3 found in food and used as a dietary supplement and medication. As a supplement, it is used orally (swallowed by mouth) to prevent and treat pellagra (niacin deficiency). While nicotinic acid (niacin) may be used for this purpose, niacinamide has the benefit of not causing skin flushing . As a cream, it is used to treat acne , and has been observed in clinical studies to improve

1974-524: Is a measure of niacin deficiency. 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. For humans, the efficiency of conversion is estimated as requiring 60   mg of tryptophan to make 1   mg of niacin. Riboflavin , vitamin B 6 and iron are required for

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2068-602: Is achieved. Immediate-release doses can be as high as 3,000 mg/day; sustained-release as high as 2,000 mg/day. Despite the proven lipid changes, niacin has not been found useful for decreasing the risk of cardiovascular disease in those already on a statin . A 2010 review had concluded that niacin was effective as a mono-therapy, but a 2017 review incorporating twice as many trials concluded that prescription niacin, while affecting lipid levels, did not reduce all-cause mortality, cardiovascular mortality, myocardial infarctions, nor fatal or non-fatal strokes. Prescription niacin

2162-562: Is an amide of nicotinic acid. Foods that contain niacinamide include yeast , meat , milk, and green vegetables . Niacinamide was discovered between 1935 and 1937. It is on the World Health Organization's List of Essential Medicines . Niacinamide is available as a generic medication and over the counter . Commercially, niacinamide is made from either nicotinic acid (niacin) or nicotinonitrile . In some countries, grains have niacinamide added to them. Niacinamide

2256-972: Is any compound that contains a significant amount of carbon—even though many of the organic compounds known today have no connection to any substance found in living organisms. The term carbogenic has been proposed by E. J. Corey as a modern alternative to organic , but this neologism remains relatively obscure. The organic compound L -isoleucine molecule presents some features typical of organic compounds: carbon–carbon bonds , carbon–hydrogen bonds , as well as covalent bonds from carbon to oxygen and to nitrogen. As described in detail below, any definition of organic compound that uses simple, broadly-applicable criteria turns out to be unsatisfactory, to varying degrees. The modern, commonly accepted definition of organic compound essentially amounts to any carbon-containing compound, excluding several classes of substances traditionally considered "inorganic". The list of substances so excluded varies from author to author. Still, it

2350-494: Is blood vessel dilation due to elevation in prostaglandin GD 2 ( PGD2 ) and serotonin . Flushing was often thought to involve histamine, but histamine has been shown not to be involved in the reaction. Flushing is sometimes accompanied by a prickly or itching sensation, in particular, in areas covered by clothing. Prevention of flushing requires altering or blocking the prostaglandin-mediated pathway. Aspirin taken half an hour before

2444-412: Is called a salvage pathway . However, the human body can produce NAD from the amino acid tryptophan and niacin without our ingestion of nicotinamide. NAD acts as an electron carrier that mediates the interconversion of energy between nutrients and the cell's energy currency, adenosine triphosphate (ATP). In oxidation-reduction reactions, the active part of the cofactor is the nicotinamide. In NAD ,

2538-438: Is continued. However, less commonly, the sustained release form of the drug can lead to serious hepatotoxicity , with onset in days to weeks. Early symptoms of serious liver damage include nausea, vomiting and abdominal pain, followed by jaundice and 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

2632-408: 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. Niacin and nicotinamide are both converted into the coenzyme NAD. NAD converts to NADP by phosphorylation in the presence of the enzyme NAD+ kinase . High energy requirements (brain) or high turnover rate (gut, skin) organs are usually

2726-710: Is generally agreed upon that there are (at least) a few carbon-containing compounds that should not be considered organic. For instance, almost all authorities would require the exclusion of alloys that contain carbon, including steel (which contains cementite , Fe 3 C ), as well as other metal and semimetal carbides (including "ionic" carbides, e.g, Al 4 C 3 and CaC 2 and "covalent" carbides, e.g. B 4 C and SiC , and graphite intercalation compounds, e.g. KC 8 ). Other compounds and materials that are considered 'inorganic' by most authorities include: metal carbonates , simple oxides of carbon ( CO , CO 2 , and arguably, C 3 O 2 ),

2820-418: Is generated by oxidation of 3-picoline. Oxidation can be effected by air, but ammoxidation is more efficient. In the latter process, nicotinonitrile is produced by ammoxidation of 3-methylpyridine . Nitrile hydratase is then used to catalyze nicotinonitrile to nicotinamide, which can be converted to niacin. Alternatively, ammonia, acetic acid and paraldehyde are used to make 5-ethyl-2-methyl-pyridine , which

2914-413: Is given as a treatment for this condition in doses ranging from 50 to 100 mg twice a day, with a good prognosis if identified and treated early. Niacin synthesis is also deficient in carcinoid syndrome , because of metabolic diversion of its precursor tryptophan to form serotonin . Plasma concentrations of niacin and niacin metabolites are not useful markers of niacin status. Urinary excretion of

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3008-446: Is important in catabolism of fat, carbohydrate, protein, and alcohol, as well as cell signaling and DNA repair, and NADP mostly in anabolism reactions such as fatty acid and cholesterol synthesis. Vitamin intake recommendations made by several countries are that intakes of 14–18 mg/day are sufficient to meet the needs of healthy adults. Niacin but also nicotinamide (niacinamide) are used for prevention and treatment of pellagra ,

3102-458: Is incorporated into NAD and nicotinamide adenine dinucleotide phosphate (NADP ). NAD and NADP are cofactors in a wide variety of enzymatic oxidation-reduction reactions, most notably glycolysis , the citric acid cycle , and the electron transport chain . If humans ingest nicotinamide, it will likely undergo a series of reactions that transform it into NAD, which can then undergo a transformation to form NADP . This method of creation of NAD

3196-505: Is involved in DNA repair. Niacin is both a vitamin, i.e., an essential nutrient, marketed as a dietary supplement, and in the US, a prescription medicine. As a vitamin, it is precursor of the coenzymes nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP). These compounds are coenzymes for many dehydrogenases, participating in many hydrogen transfer processes. NAD

3290-431: 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. The most common adverse effects of medicinal niacin ( 500–3000 mg ) are flushing (e.g., warmth, redness, itching or tingling) of

3384-573: Is largely bound to polysaccharides and glycopeptides, making it only about 30% bioavailable. Fortified food ingredients such as wheat flour have niacin added, which is bioavailable. Among whole food sources with the highest niacin content per 100 grams: 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. Niacin naturally found in food

3478-463: Is not sufficient evidence to identify a dietary intake level that is sufficient to meet the nutrient requirements of most people. (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

3572-479: Is on a carbon atom. For historical reasons discussed below, a few types of carbon-containing compounds, such as carbides , carbonates (excluding carbonate esters ), simple oxides of carbon (for example, CO and CO 2 ) and cyanides are generally considered inorganic compounds . Different forms ( allotropes ) of pure carbon, such as diamond , graphite , fullerenes and carbon nanotubes are also excluded because they are simple substances composed of

3666-551: Is reversible after niacin intake ceases. Niaspan, the slow-release product, has been associated with a reduction in platelet content and a modest increase in prothrombin time. Activating HCA 2 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. Niacin inhibits cytochrome P450 enzymes CYP2E1 , CYP2D6 and CYP3A4 . Niacin produces

3760-499: 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. Niacin as a chemical compound was first described by chemist Hugo Weidel in 1873 in his studies of nicotine , but that predated by many years

3854-524: 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. Countries fortify foods with nutrients to address known deficiencies. As of 2020, 54 countries required food fortification of wheat flour with niacin or niacinamide; 14 also mandate fortification of maize flour, and 6 mandate fortification of rice. From country to country, niacin fortification ranges from 1.3 to 6.0 mg/100 g. In

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3948-467: Is tentative evidence for a potential role of niacinamide in treating acne, rosacea, autoimmune blistering disorders, ageing skin, and atopic dermatitis. Niacinamide also inhibits poly(ADP-ribose) polymerases ( PARP-1 ), enzymes involved in the rejoining of DNA strand breaks induced by radiation or chemotherapy. ARCON (accelerated radiotherapy plus carbogen inhalation and nicotinamide) has been studied in cancer. Research has suggested niacinamide may play

4042-476: Is the preferred treatment for pellagra , caused by niacin deficiency. Niacinamide cream is used as a treatment for acne . It has anti-inflammatory actions, which may benefit people with inflammatory skin conditions. Niacinamide increases the biosynthesis of ceramides in human keratinocytes in vitro and improves the epidermal permeability barrier in vivo. The application of 2% topical niacinamide for 2 and 4 weeks has been found to be effective in lowering

4136-533: Is then oxidized to niacin. New "greener" catalysts are being tested using manganese-substituted aluminophosphates that use acetyl peroxyborate as non-corrosive oxidant, avoiding producing nitrogen oxides as do traditional ammoxidations. 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. The production of niacin creates nitrous oxide as

4230-442: The N -oxide , from nicotinonitrile by reaction with phosphorus pentoxide , and from 3-aminopyridine by reaction with a solution of sodium hypobromite , prepared in situ from bromine and sodium hydroxide . The hydrolysis of nicotinonitrile is catalysed by the enzyme nitrile hydratase from Rhodococcus rhodochrous J1, producing 3500 tons per annum of nicotinamide for use in animal feed. The enzyme allows for

4324-539: The DNA of an organism is altered to express compounds not ordinarily produced by the organism. Many such biotechnology -engineered compounds did not previously exist in nature. A great number of more specialized databases exist for diverse branches of organic chemistry. The main tools are proton and carbon-13 NMR spectroscopy , IR Spectroscopy , Mass spectrometry , UV/Vis Spectroscopy and X-ray crystallography . Nicotinamide Niacinamide or nicotinamide

4418-781: The allotropes of carbon, cyanide derivatives not containing an organic residue (e.g., KCN , (CN) 2 , BrCN , cyanate anion OCN , etc.), and heavier analogs thereof (e.g., cyaphide anion CP , CSe 2 , COS ; although carbon disulfide CS 2 is often classed as an organic solvent). Halides of carbon without hydrogen (e.g., CF 4 and CClF 3 ), phosgene ( COCl 2 ), carboranes , metal carbonyls (e.g., nickel tetracarbonyl ), mellitic anhydride ( C 12 O 9 ), and other exotic oxocarbons are also considered inorganic by some authorities. Nickel tetracarbonyl ( Ni(CO) 4 ) and other metal carbonyls are often volatile liquids, like many organic compounds, yet they contain only carbon bonded to

4512-424: The risk of cerebral hemorrhage , ischemic stroke , gastrointestinal ulceration and bleeding , diabetes , dyspepsia , and diarrhea. 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

4606-600: The sebum excretion rate. Niacinamide has been shown to prevent Cutibacterium acnes -induced activation of toll-like receptor 2 , which ultimately results in the down-regulation of pro-inflammatory interleukin-8 production. Niacinamide at doses of 500 to 1000   mg a day decreases the risk of skin cancers , other than melanoma , in those at high risk. Niacinamide has minimal side effects. At very high doses above 3g/ day acute liver toxicity has been documented in at least one case. Normal doses are safe during pregnancy . The structure of nicotinamide consists of

4700-406: The "maximum daily intake unlikely to cause adverse health effects." Regulatory agencies from different countries do not always agree. For the US, 30 or 35 mg for teenagers and adults, less for children. 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

4794-429: The 3-position. Other forms of vitamin B 3 include the corresponding amide nicotinamide (niacinamide), where the carboxyl group has been replaced by a carboxamide group ( CONH 2 ). Niacin is incorporated into multi-vitamin and sold as a single-ingredient dietary supplement. The latter can be immediate or slow release. Nicotinamide (niacinamide) is used to treat niacin deficiency because it does not cause

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4888-570: 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. Prescription immediate release (Niacor) and extended release (Niaspan) niacin are contraindicated for people with either active or

4982-553: 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. Organic compound Due to carbon's ability to catenate (form chains with other carbon atoms ), millions of organic compounds are known. The study of the properties, reactions, and syntheses of organic compounds comprise the discipline known as organic chemistry . For historical reasons,

5076-610: 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). ULs are established by identifying amounts of vitamins and minerals that cause adverse effects, and then selecting as an upper limit amounts that are

5170-572: 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 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

5264-449: The United States, prescription niacin, in immediate-release and slow-release forms, is used to treat primary hyperlipidemia and hypertriglyceridemia . It is used either as a monotherapy or in combination with other lipid-modifying drugs. Dosages start at 500 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

5358-408: The activation of G protein-coupled receptors , including hydroxycarboxylic acid receptor 2 (HCA 2 )and hydroxycarboxylic acid receptor 3 (HCA 3 ), which are highly expressed in body fat . HCA 2 and HCA 3 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

5452-403: 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 ; these hepatotoxic effects of niacin occur more often when extended-release dosage forms are used. The long-term use of niacin at greater than or equal to 2 grams per day also significantly increases

5546-566: 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. 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. A table of

5640-419: The appearance of aging skin by reducing hyperpigmentation and redness. It is a water-soluble vitamin . Niacinamide is the supplement name, while nicotinamide is the scientific name. Side effects are minimal. At high doses, liver problems may occur. Normal amounts are safe for use during pregnancy . Niacinamide is in the vitamin B family of medications, specifically the vitamin B 3 complex . It

5734-557: The bioavailability of niacin during maize meal/flour production. For this reason, people who consume maize as tortillas or hominy are at less risk of niacin deficiency. For treating deficiency, the World Health Organization (WHO) recommends administering niacinamide i.e., nicotinamide, instead of niacin, to avoid the flushing side effect commonly caused by the latter. Guidelines suggest using 300 mg/day for three to four weeks. Dementia and dermatitis show improvement within

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5828-605: The blood-circulating lipids in question. 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. Niacin also directly inhibits the action of diacylglycerol O-acyltransferase 2 (DGAT2) a key enzyme for triglyceride synthesis. 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

5922-580: The breakdown of this protein, which is a component of HDL-C. It also inhibits HDL-C hepatic uptake by suppressing production of the cholesterol ester transfer protein (CETP) gene. It stimulates the ABCA1 transporter in monocytes and macrophages and upregulates peroxisome proliferator-activated receptor gamma , resulting in reverse cholesterol transport. Extended release niacin was combined with lovastatin (Advicor), and with simvastatin (Simcor), as prescription drug combinations. The combination niacin/lovastatin

6016-450: The concept of food components other than protein, fat and carbohydrates that were essential for life. Vitamin nomenclature was initially alphabetical, with Elmer McCollum calling these fat-soluble A and water-soluble B. Over time, eight chemically distinct, water-soluble B vitamins were isolated and numbered, with niacin as vitamin B 3 . Corn (maize) became a staple food in the southeast United States and in parts of Europe. A disease that

6110-472: 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

6204-938: The evidence of covalent Fe-C bonding in cementite , a major component of steel, places it within this broad definition of organometallic, yet steel and other carbon-containing alloys are seldom regarded as organic compounds. Thus, it is unclear whether the definition of organometallic should be narrowed, whether these considerations imply that organometallic compounds are not necessarily organic, or both. Metal complexes with organic ligands but no carbon-metal bonds (e.g., (CH 3 CO 2 ) 2 Cu ) are not considered organometallic; instead, they are called metal-organic compounds (and might be considered organic). The relatively narrow definition of organic compounds as those containing C-H bonds excludes compounds that are (historically and practically) considered organic. Neither urea CO(NH 2 ) 2 nor oxalic acid (COOH) 2 are organic by this definition, yet they were two key compounds in

6298-596: The face, neck and chest, headache, abdominal pain, diarrhea, dyspepsia , nausea, vomiting, rhinitis , pruritus and rash. These can be minimized by initiating therapy at low dosages, increasing dosage gradually, and avoiding administration on an empty stomach. 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 . With long-term use,

6392-463: The flushing adverse reaction seen with niacin. Nicotinamide may be toxic to the liver at doses exceeding 3   g/day for adults. 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

6486-404: The high pressure and temperature degradation of organic matter underground over geological timescales. This ultimate derivation notwithstanding, organic compounds are no longer defined as compounds originating in living things, as they were historically. In chemical nomenclature, an organyl group , frequently represented by the letter R, refers to any monovalent substituent whose open valence

6580-466: The injury is severe, and progresses to liver failure. The high doses of niacin used to treat hyperlipidemia have been shown to elevate fasting blood glucose in people with type 2 diabetes . Long-term niacin therapy was also associated with an increase in the risk of new-onset type 2 diabetes. 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

6674-541: The methylated metabolite N1-methyl-nicotinamide is considered reliable and sensitive. The measurement requires a 24-hour urine collection. For adults, a value of less than 5.8 μmol/day represent deficient niacin status and 5.8 to 17.5 μmol/day represents low. According to the World Health Organization, an alternative mean of expressing urinary N1-methyl-nicotinamide is as mg/g creatinine in a 24-hour urine collection, with deficient defined as <0.5, low 0.5-1.59, acceptable 1.6-4.29, and high >4.3 Niacin deficiency occurs before

6768-601: The mineral mellite ( Al 2 C 6 (COO) 6 ·16H 2 O ). A slightly broader definition of the organic compound includes all compounds bearing C-H or C-C bonds. This would still exclude urea. Moreover, this definition still leads to somewhat arbitrary divisions in sets of carbon-halogen compounds. For example, CF 4 and CCl 4 would be considered by this rule to be "inorganic", whereas CHF 3 , CHCl 3 , and C 2 Cl 6 would be organic, though these compounds share many physical and chemical properties. Organic compounds may be classified in

6862-549: The most susceptible to their deficiency. In the liver, niacinamide is converted to storage nicotinamide adenine dinucleotide (NAD). As needed, liver NAD is hydrolyzed to niacinamide and niacin for transport to tissues, there reconverted to NAD to serve as an enzyme cofactor. Excess niacin is methylated in the liver to N-methylnicotinamide (NMN) and excreted in urine as such or as the oxidized metabolites N-methyl-2-pyridone-5-carboxamide and N1-Methyl-4-pyridone-3-carboxamide (2PY and 4PY). Decreased urinary content of these metabolites

6956-443: The niacin deficiency. Niacin deficiency is rarely seen in developed countries, and it is more typically associated with poverty, malnutrition or malnutrition secondary to chronic alcoholism . It also tends to occur in less developed areas where people eat maize (corn) as a staple food, as maize is the only grain low in digestible niacin. A cooking technique called nixtamalization i.e., pretreating with alkali ingredients, increases

7050-537: The niacin prevents flushing, as does ibuprofen . Taking niacin with meals also helps reduce this side effect. Acquired tolerance will also help reduce flushing; after several weeks of a consistent dose, most people no longer experience flushing. Slow- or "sustained"-release forms of niacin have been developed to lessen these side effects. Niacin in medicinal doses can cause modest elevations in serum transaminase and unconjugated bilirubin , both biomarkers of liver injury. The increases usually resolve even when drug intake

7144-401: The nitrogen in the aromatic nicotinamide ring is covalently bonded to adenine dinucleotide. The formal charge on the nitrogen is stabilized by the shared electrons of the other carbon atoms in the aromatic ring. When a hydride atom is added onto NAD to form NADH, the molecule loses its aromaticity, and therefore a good amount of stability. This higher energy product later releases its energy with

7238-531: 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 . 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, legumes and grains provide about 2–5 mg niacin per serving, although in some grain products this naturally present niacin

7332-437: The process. Pellagra is a consequence of a corn-dominant diet because the niacin in corn is poorly bioavailable and corn proteins are low in tryptophan compared to wheat and rice proteins. Nicotinic acid was first synthesized in 1867 by oxidative degradation of nicotine with potassium chromate and sulfuric acid — this is the origin of the name. Niacin is prepared by hydrolysis of nicotinonitrile , which, as described above,

7426-407: 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

7520-409: The release of a hydride, and in the case of the electron transport chain, it assists in forming adenosine triphosphate . When one mole of NADH is oxidized, 158.2   kJ of energy will be released. Nicotinamide occurs as a component of a variety of biological systems, including within the vitamin B family and specifically the vitamin B 3 complex . It is also a critically important part of

7614-691: The risk of hepatotoxicity compared to the immediate release drug. Prescription niacin preparations in combination with statin drugs (discontinued) are described above. A combination of niacin and laropiprant had been approved for use in Europe and marketed as Tredaptive. Laropiprant is a prostaglandin D2 binding drug shown to reduce niacin-induced vasodilation and flushing side effects. A clinical trial showed no additional efficacy of Tredaptive in lowering cholesterol when used together with other statin drugs, but did show an increase in other side effects. The study resulted in

7708-423: 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 . 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. Niacin is also a prescription medication. Amounts far in excess of

7802-405: The signs and symptoms of pellagra appear. Erythrocyte nicotinamide adenine dinucleotide (NAD) concentrations potentially provide another sensitive indicator of niacin depletion, although definitions of deficient, low and adequate have not been established. Lastly, plasma tryptophan decreases on a low niacin diet because tryptophan converts to niacin. However, low tryptophan could also be caused by

7896-453: The skin (see image), inflammation of the mouth and tongue, delirium, dementia, and if left untreated, death. Common psychiatric symptoms include irritability, poor concentration, anxiety, fatigue, loss of memory, restlessness, apathy, and depression. The biochemical mechanism(s) for the observed deficiency-caused neurodegeneration are not well understood, but may rest on: A) the requirement for nicotinamide adenine dinucleotide (NAD+) to suppress

7990-445: The stomach and small intestine. Absorption is facilitated by sodium-dependent diffusion, and at higher intakes, via passive diffusion. Unlike some other vitamins, the percent absorbed does not decrease with increasing dose, so that even at amounts of 3-4 grams, absorption is nearly complete. With a one gram dose, peak plasma concentrations of 15 to 30 μg/mL are reached within 30 to 60 minutes. Approximately 88% of an oral pharmacologic dose

8084-483: The structures of NADH and NAD , where the N -substituted aromatic ring in the oxidised NAD form undergoes reduction with hydride attack to form NADH. The NADPH/NADP structures have the same ring, and are involved in similar biochemical reactions. Nicotinamide can be methylated in the liver to biologically active 1-Methylnicotinamide when there are sufficient methyl donors. Niacinamide occurs in trace amounts mainly in meat, fish, nuts, and mushrooms, as well as to

8178-588: The supervision of a health care professional, and because manufacture of dietary supplement niacin is not as well-regulated by the FDA as prescription niacin. More than 30 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. In

8272-795: The targeted lipid changes (lower LDL-C and triglycerides, and higher HDL-C). Prescriptions in the US peaked in 2009, at 9.4   million and had declined to 800   thousand by 2020. 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 in patients already taking statins. Reported side effects include an increased risk of new-onset type 2 diabetes. Niacin reduces synthesis of low-density lipoprotein cholesterol (LDL-C), very low-density lipoprotein cholesterol (VLDL-C), lipoprotein(a) and triglycerides , and increases high-density lipoprotein cholesterol (HDL-C). The lipid-therapeutic effects of niacin are partly mediated through

8366-577: The vitalism debate. However, the IUPAC Blue Book on organic nomenclature specifically mentions urea and oxalic acid as organic compounds. Other compounds lacking C-H bonds but traditionally considered organic include benzenehexol , mesoxalic acid , and carbon tetrachloride . Mellitic acid , which contains no C-H bonds, is considered a possible organic compound in Martian soil. Terrestrially, it, and its anhydride, mellitic anhydride , are associated with

8460-405: The withdrawal of Tredaptive from the international market. 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. 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

8554-450: Was approved by the U.S. Food and Drug Administration (FDA) in 2001. The combination niacin/simvastatin was approved by the FDA in 2008. Subsequently, large outcome trials using these niacin and statin therapies were unable to demonstrate incremental benefit of niacin beyond statin therapy alone. The FDA withdrew approval of both drugs in 2016. The reason given: "Based on the collective evidence from several large cardiovascular outcome trials,

8648-499: Was characterized by dermatitis of sunlight-exposed skin was described in Spain in 1735 by Gaspar Casal . He attributed the cause to poor diet. In northern Italy it was named "pellagra" from the Lombard language ( agra = holly -like or serum -like; pell = skin). In time, the disease was more closely linked specifically to corn. In the US, Joseph Goldberger was assigned to study pellagra by

8742-445: Was known to occur only in the urine of living organisms. Wöhler's experiments were followed by many others, in which increasingly complex "organic" substances were produced from "inorganic" ones without the involvement of any living organism, thus disproving vitalism. Although vitalism has been discredited, scientific nomenclature retains the distinction between organic and inorganic compounds. The modern meaning of organic compound

8836-429: Was shown to cause hepatotoxicity and increase risk of type 2 diabetes . Niacin prescriptions in the U.S. had peaked in 2009 at 9.4   million, declining to 800   thousand by 2020. Niacin has the formula C 6 H 5 NO 2 and belongs to the group of the pyridinecarboxylic acids . As the precursor for nicotinamide adenine dinucleotide and nicotinamide adenine dinucleotide phosphate , niacin

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