Nicotinamide (

INN Inns are generally establishments or buildings where travelers can seek lodging, and usually, food and drink. Inns are typically located in the country or along a highway. Before the advent of motorized transportation, they also provided accomm ...

, BAN ) or niacinamide (

USAN 280px, "Samguk Sagi" Book 04. Silla's Records. In 512, Usan-guk（于山國）was Ulleungdo（鬱陵島） Usan-guk, or the State of Usan, occupied Ulleung-do and the adjacent islands during the Korean Three Kingdoms period. According to t ...

) is a form of vitamin B₃ found in food and used as a

dietary supplement A dietary supplement is a manufactured product intended to supplement a person's diet by taking a pill (pharmacy), pill, capsule (pharmacy), capsule, tablet (pharmacy), tablet, powder, or liquid. A supplement can provide nutrients eithe ...

and medication. As a supplement, it is used orally (swallowed by mouth) to prevent and treat

pellagra Pellagra is a disease caused by a lack of the vitamin niacin (vitamin B3). Symptoms include inflamed skin, diarrhea, dementia, and sores in the mouth. Areas of the skin exposed to friction and radiation are typically affected first. Over tim ...

(niacin deficiency). While

nicotinic acid Nicotinic acid, or niacin, is an organic compound and a vitamer of vitamin B3, an essential human nutrient. It is produced by plants and animals from the amino acid tryptophan. Nicotinic acid is also a prescription medication. Amounts f ...

(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 Acne ( ), also known as ''acne vulgaris'', is a long-term Cutaneous condition, skin condition that occurs when Keratinocyte, dead skin cells and Sebum, oil from the skin clog hair follicles. Typical features of the condition include comedo, ...

, and has been observed in clinical studies to improve the appearance of aging skin by reducing

hyperpigmentation Hyperpigmentation, also known as the dark spots or circles on the skin, is the darkening of an area of Human skin, skin or nail (anatomy), nails caused by increased melanin. Causes Hyperpigmentation can be caused by sun damage, inflammation, or ...

and redness. It is a water-soluble vitamin. Side effects are minimal. At high doses,

liver problems Liver disease, or hepatic disease, is any of many diseases of the liver. If long-lasting it is termed chronic liver disease. Although the diseases differ in detail, liver diseases often have features in common. Liver diseases File:Ground gla ...

may occur. Normal amounts are safe for use during

pregnancy Pregnancy is the time during which one or more offspring gestation, gestates inside a woman's uterus. A multiple birth, multiple pregnancy involves more than one offspring, such as with twins. Conception (biology), Conception usually occurs ...

. Nicotinamide is in the

vitamin B B vitamins are a class of water-soluble vitamins that play important roles in cell metabolism and synthesis of red blood cells. They are a chemically diverse class of compounds. Dietary supplements containing all eight are referred to as a vita ...

family of medications, specifically the vitamin B₃ complex. It is an

amide In organic chemistry, an amide, also known as an organic amide or a carboxamide, is a chemical compound, compound with the general formula , where R, R', and R″ represent any group, typically organyl functional group, groups or hydrogen at ...

of nicotinic acid. Foods that contain nicotinamide include

yeast Yeasts are eukaryotic, single-celled microorganisms classified as members of the fungus kingdom (biology), kingdom. The first yeast originated hundreds of millions of years ago, and at least 1,500 species are currently recognized. They are est ...

meat Meat is animal Tissue (biology), tissue, often muscle, that is eaten as food. Humans have hunted and farmed other animals for meat since prehistory. The Neolithic Revolution allowed the domestication of vertebrates, including chickens, sheep, ...

, milk, and green vegetables. Nicotinamide was discovered between 1935 and 1937. It is on the

World Health Organization's List of Essential Medicines The WHO Model List of Essential Medicines (aka Essential Medicines List or EML), published by the World Health Organization (WHO), contains the medications considered to be most effective and safe to meet the most important needs in a health s ...

. Nicotinamide is available as a

generic medication A generic drug is a pharmaceutical drug that contains the same chemical substance as a drug that was originally protected by chemical patents. Generic drugs are allowed for sale after the patents on the original drugs expire. Because the active ch ...

and

over the counter Over-the-counter (OTC) drugs are medicines sold directly to a consumer without a requirement for a prescription from a healthcare professional, as opposed to prescription drugs, which may be supplied only to consumers possessing a valid pres ...

. Commercially, nicotinamide is made from either

(niacin) or nicotinonitrile. In some countries,

grains A grain is a small, hard, dry fruit ( caryopsis) – with or without an attached hull layer – harvested for human or animal consumption. A grain crop is a grain-producing plant. The two main types of commercial grain crops are cereals and le ...

have nicotinamide added to them. Extra-terrestrial nicotinamide has been found in

carbonaceous chondrite Carbonaceous chondrites or C chondrites are a class of chondritic meteorites comprising at least 8 known groups and many ungrouped meteorites. They include some of the most primitive known meteorites. The C chondrites represent only a small propo ...

meteorites.

Medical uses

Niacin deficiency

Nicotinamide is the preferred treatment for

, caused by niacin deficiency.

Acne

Nicotinamide

cream Cream is a dairy product composed of the higher-fat layer skimmed from the top of milk before homogenization. In un-homogenized milk, the fat, which is less dense, eventually rises to the top. In the industrial production of cream, this proces ...

is used as a treatment for

. It has anti-inflammatory actions, which may benefit people with inflammatory skin conditions. Nicotinamide increases the biosynthesis of

ceramide Ceramides are a family of waxy lipid molecules. A ceramide is composed of sphingosine and a fatty acid joined by an amide bond. Ceramides are found in high concentrations within the cell membrane of Eukaryote, eukaryotic cells, since they are co ...

s in human

keratinocyte Keratinocytes are the primary type of cell found in the epidermis, the outermost layer of the skin. In humans, they constitute 90% of epidermal skin cells. Basal cells in the basal layer (''stratum basale'') of the skin are sometimes referre ...

s in vitro and improves the epidermal permeability barrier in vivo. The application of 2% topical nicotinamide for 2 and 4 weeks has been found to be effective in lowering the

sebum A sebaceous gland or oil gland is a microscopic exocrine gland in the skin that opens into a hair follicle to secrete an oily or waxy matter, called sebum, which lubricates the hair and skin of mammals. In humans, sebaceous glands occur ...

excretion rate. Nicotinamide has been shown to prevent ''

Cutibacterium acnes ''Cutibacterium acnes'' (''Propionibacterium acnes'') is the relatively slow-growing, typically aerotolerant anaerobic, gram-positive bacterium (rod) linked to the skin condition of acne; it can also cause chronic blepharitis and endophthalmitis ...

''-induced activation of toll-like receptor 2, which ultimately results in the down-regulation of pro-inflammatory

interleukin-8 Interleukin 8 (IL-8 or chemokine (C-X-C motif) ligand 8, CXCL8) is a chemokine produced by macrophages and other cell types such as epithelial cells, airway smooth muscle cells and endothelial cells. Endothelial cells store IL-8 in their storage ...

production.

Skin cancer

Nicotinamide at doses of 500 to 1000mg a day decreases the risk of

skin cancer Skin cancers are cancers that arise from the Human skin, skin. They are due to the development of abnormal cells (biology), cells that have the ability to invade or metastasis, spread to other parts of the body. It occurs when skin cells grow ...

s, other than

melanoma Melanoma is the most dangerous type of skin cancer; it develops from the melanin-producing cells known as melanocytes. It typically occurs in the skin, but may rarely occur in the mouth, intestines, or eye (uveal melanoma). In very rare case ...

, in those at high risk.

Side effects

Nicotinamide has minimal side effects. At very high doses above 3g/ day acute

liver toxicity Hepatotoxicity (from ''hepatic toxicity'') implies chemical-driven liver damage. Drug-induced liver injury (DILI) is a cause of acute and chronic liver disease caused specifically by medications and the most common reason for a drug to be withdr ...

has been documented in at least one case. Normal doses are safe during

Chemistry

The structure of nicotinamide consists of a

pyridine Pyridine is a basic (chemistry), basic heterocyclic compound, heterocyclic organic compound with the chemical formula . It is structurally related to benzene, with one methine group replaced by a nitrogen atom . It is a highly flammable, weak ...

ring to which a

primary amide In organic chemistry, an amide, also known as an organic amide or a carboxamide, is a compound with the general formula , where R, R', and R″ represent any group, typically organyl groups or hydrogen atoms. The amide group is called a pe ...

group is attached in the ''meta'' position. It is an

. As an

aromatic compound Aromatic compounds or arenes are organic compounds "with a chemistry typified by benzene" and "cyclically conjugated." The word "aromatic" originates from the past grouping of molecules based on odor, before their general chemical properties were ...

, it undergoes

electrophilic substitution Electrophilic substitution reactions are chemical reactions in which an electrophile displaces a functional group in a compound, which is typically, but not always, aromatic. Aromatic substitution reactions are characteristic of aromatic compounds ...

reactions and transformations of its two

functional group In organic chemistry, a functional group is any substituent or moiety (chemistry), moiety in a molecule that causes the molecule's characteristic chemical reactions. The same functional group will undergo the same or similar chemical reactions r ...

s. Examples of these reactions reported in ''

Organic Syntheses ''Organic Syntheses'' is a peer-reviewed scientific journal that was established in 1921. It publishes detailed and checked procedures for the synthesis of organic compounds. A unique feature of the review process is that all of the data and expe ...

'' include the preparation of 2-chloronicotinonitrile by a two-step process via the ''N''-oxide, : Nicotinamide to 2-chloronicotinonitrile

from nicotinonitrile by reaction with

phosphorus pentoxide Phosphorus pentoxide is a chemical compound with molecular formula Phosphorus, P4Oxygen, O10 (with its common name derived from its empirical formula, P2O5). This white crystalline solid is the anhydride of phosphoric acid. It is a powerful desic ...

, and from

3-aminopyridine 3-Aminopyridine is an aminopyridine. It is a colorless solid. Preparation 3-Aminopyridine is prepared by heating nicotinamide with sodium hypobromite ( Hofmann rearrangement), which is in turn prepared ''in situ'' by the reaction of sodium hy ...

by reaction with a solution of sodium hypobromite, prepared ''in situ'' from

bromine Bromine is a chemical element; it has chemical symbol, symbol Br and atomic number 35. It is a volatile red-brown liquid at room temperature that evaporates readily to form a similarly coloured vapour. Its properties are intermediate between th ...

and

sodium hydroxide Sodium hydroxide, also known as lye and caustic soda, is an inorganic compound with the formula . It is a white solid ionic compound consisting of sodium cations and hydroxide anions . Sodium hydroxide is a highly corrosive base (chemistry), ...

Industrial production

The hydrolysis of nicotinonitrile is catalysed by the enzyme

nitrile hydratase Nitrile hydratases (NHases; ) are mononuclear iron or non-corrinoid cobalt enzymes that catalyse the hydration of diverse nitriles to their corresponding amides: : R-C≡N + → Metal cofactor Nitrile hydratases use Fe(III) or Co(III) at thei ...

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

is avoided. Nicotinamide can also be made from nicotinic acid. According to ''

Ullmann's Encyclopedia of Industrial Chemistry ''Ullmann's Encyclopedia of Industrial Chemistry'' is a major reference work related to Chemical industry, industrial chemistry by chemist Fritz Ullmann, first published in 1914, and exclusively in German as "Enzyklopädie der Technischen Chemie ...

'', worldwide 31,000 tons of nicotinamide were sold in 2014.

Biochemistry

Nicotinamide, as a part of the cofactor

nicotinamide adenine dinucleotide Nicotinamide adenine dinucleotide (NAD) is a Cofactor (biochemistry), coenzyme central to metabolism. Found in all living cell (biology), cells, NAD is called a dinucleotide because it consists of two nucleotides joined through their phosphat ...

(NADH / NAD⁺) is crucial to life. In cells, nicotinamide is incorporated into NAD⁺ and

nicotinamide adenine dinucleotide phosphate Nicotinamide adenine dinucleotide phosphate, abbreviated NADP or, in older notation, TPN (triphosphopyridine nucleotide), is a Cofactor (biochemistry), cofactor used in anabolic reactions, such as the Calvin cycle and lipid and nucleic acid synt ...

(NADP⁺). NAD⁺ and NADP⁺ are cofactors in a wide variety of enzymatic oxidation-reduction reactions, most notably

glycolysis Glycolysis is the metabolic pathway that converts glucose () into pyruvic acid, pyruvate and, in most organisms, occurs in the liquid part of cells (the cytosol). The Thermodynamic free energy, free energy released in this process is used to form ...

, the

citric acid cycle The citric acid cycle—also known as the Krebs cycle, Szent–Györgyi–Krebs cycle, or TCA cycle (tricarboxylic acid cycle)—is a series of chemical reaction, biochemical reactions that release the energy stored in nutrients through acetyl-Co ...

, and the

electron transport chain An electron transport chain (ETC) is a series of protein complexes and other molecules which transfer electrons from electron donors to electron acceptors via redox reactions (both reduction and oxidation occurring simultaneously) and couples th ...

. 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 A salvage pathway is a pathway in which a biological product is produced from intermediates in the degradative pathway of its own or a similar substance. The term often refers to nucleotide salvage in particular, in which nucleotides (purine and py ...

. However, the human body can produce NAD⁺ from the amino acid

tryptophan Tryptophan (symbol Trp or W) is an α-amino acid that is used in the biosynthesis of proteins. Tryptophan contains an α-amino group, an α-carboxylic acid group, and a side chain indole, making it a polar molecule with a non-polar aromat ...

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 Adenosine triphosphate (ATP) is a nucleoside triphosphate that provides energy to drive and support many processes in living cell (biology), cells, such as muscle contraction, nerve impulse propagation, and chemical synthesis. Found in all known ...

(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 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 the release of a hydride, and in the case of the electron transport chain, it assists in forming

. When one mole of NADH is oxidized, 158.2kJ of energy will be released.

Biological role

Nicotinamide occurs as a component of a variety of biological systems, including within the

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 active 1-Methylnicotinamide when there are sufficient methyl donors.

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 20–30mg of vitamin B₃ and it is also available in higher doses.

Compendial status

British Pharmacopoeia The ''British Pharmacopoeia'' (''BP'') is the national pharmacopoeia of the United Kingdom. It is an annually published collection of quality standards for medicinal substances in the UK, which is used by individuals and organisations involve ...

Japanese Pharmacopoeia The is the official pharmacopoeia of Japan. It is published by the . The first edition was published on 25 June 1886, with revisions being issued from time to time. The current revision is number 18, issued electronically on 7 June 2021. An off ...

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 Bullous pemphigoid (a type of pemphigoid) is an autoimmune pruritic skin disease that typically occurs in people aged over 60, that may involve the formation of blisters ( bullae) in the space between the epidermal and dermal skin layers. It is ...

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. Nicotinamide also inhibits poly(ADP-ribose)

polymerase In biochemistry, a polymerase is an enzyme (Enzyme Commission number, EC 2.7.7.6/7/19/48/49) that synthesizes long chains of polymers or nucleic acids. DNA polymerase and RNA polymerase are used to assemble DNA and RNA molecules, respectively, by ...

s ( 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 nicotinamide may play a role in the treatment of

HIV The human immunodeficiency viruses (HIV) are two species of '' Lentivirus'' (a subgroup of retrovirus) that infect humans. Over time, they cause acquired immunodeficiency syndrome (AIDS), a condition in which progressive failure of the im ...

Extra-terrestrial occurrence

Extra-terrestrial nicotinamide has been found in carbonaceous chondrite meteorites.

References

{{Authority control B vitamins CYP2D6 inhibitors CYP3A4 inhibitors GABAA receptor positive allosteric modulators GPER agonists World Health Organization essential medicines Wikipedia medicine articles ready to translate Skin whitening