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Nicotinamide

Nicotinamide (INN, BAN UK) or niacinamide (USAN US) (IUPAC name: 3-pyridinecarboxoamide) is a form of vitamin B3 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). This is not to be confused with niacin. While both are very similar, they have different behaviors on the body. While nicotinic acid (niacin) may be used for this purpose, nicotinamide 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 the appearance of aging skin by reducing hyperpigmentation and redness. It is a water-soluble vitamin.

Medical uses
Niacin deficiency Nicotinamide is the preferred treatment for pellagra, caused by niacin deficiency. Nicotinamide increases the biosynthesis of ceramides in human keratinocytes in vitro and improves the epidermal permeability barrier in vivo. The application of 2% topical nicotinamide for 2 and 4 weeks is effective in lowering the sebum excretion rate. Nicotinamide 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. Skin cancer Nicotinamide at doses of 500 to 1000mg a day decreases the risk of skin cancers, other than melanoma, in those at high risk. Eye health Nicotinamide has shown promise in slowing vision loss from glaucoma. == Side effects ==
Side effects
Nicotinamide has minimal side effects. At very high doses above 3 g per day acute liver toxicity has been documented in at least one case. Normal doses are safe during pregnancy. == Chemistry ==
Chemistry
The structure of nicotinamide consists of a pyridine ring to which a primary amide group is attached in the meta position. It is an amide of nicotinic acid. : 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. , contains the nicotinamide moiety (highlighted in red) Industrial production 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 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. 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+ is called a salvage pathway. However, the human body can produce NAD+ from the amino acid tryptophan and niacin without 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+, the nitrogen in the aromatic nicotinamide ring is covalently bonded to adenine dinucleotide. The shared electrons of the other carbon atoms in the aromatic ring stabilize the formal charge on the nitrogen. 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 by donating a hydride, and in the case of the electron transport chain, it assists in forming adenosine triphosphate. When one mole of NADH is oxidized, it releases 158.2kJ of energy. Biological role Nicotinamide occurs as a component of a variety of biological systems, including within the vitamin B family and specifically the vitamin B3 complex. It is also a critically important part of 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 inactive 1-methylnicotinamide when there are sufficient methyl donors. == Food sources ==
Food sources
Nicotinamide occurs in trace amounts mainly in meat, fish, nuts, and mushrooms, as well as to a lesser extent in some vegetables. It is commonly added to cereals and other foods. Many multivitamins contain 20–30 of vitamin B3, and it is also available in higher doses. == Compendial status ==
Compendial status
Research
A 2015 trial found nicotinamide to reduce the rate of new nonmelanoma skin cancers and actinic keratoses in a group of people at high risk for the conditions. Nicotinamide has been investigated for many additional disorders, including treatment of bullous pemphigoid and nonmelanoma skin cancers. Nicotinamide may be beneficial in treating psoriasis. There is tentative evidence for a potential role of nicotinamide in treating acne, rosacea, autoimmune blistering disorders, ageing skin, and atopic dermatitis. ARCON (accelerated radiotherapy plus carbogen inhalation and nicotinamide) has been studied in cancer. Research has suggested nicotinamide may play a role in the treatment of HIV. ==Extra-terrestrial occurrence==
Extra-terrestrial occurrence
Extra-terrestrial nicotinamide has been found in carbonaceous chondrite meteorites. == References ==
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