Niacinamide or Nicotinamide (NAM) is a form of vitamin B₃ found in food and used as a dietary supplement and medication. As a supplement, it is used 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 Flushing is to become markedly red in the face and often other areas of the skin, from various physiological conditions. Flushing is generally distinguished, despite a close physiological relation between them, from blushing, which is milder, gene ...

. As a cream, it is used to treat

acne Acne, also known as ''acne vulgaris'', is a long-term skin condition that occurs when dead skin cells and oil from the skin clog hair follicles. Typical features of the condition include blackheads or whiteheads, pimples, oily skin, and ...

. It is a water-soluble vitamin. Niacinamide is the supplement name while Nicotinamide (NAM) 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 B₃ complex. It is an

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 organic groups or hydrogen atoms. The amide group is called a peptide bond when it i ...

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 Nicotinonitrile or 3-cyanopyridine is an organic compound with the formula NCC5H4N. The molecule consists of a pyridine ring with a nitrile group attached to the 3-position. A colorless solid, it is produced by ammoxidation of 3-methylpyridine: ...

. In a number of countries grains have niacinamide added to them.

Medical uses

Niacin deficiency

Niacinamide is the preferred treatment for pellagra, caused by niacin deficiency. while

niacin Niacin, also known as nicotinic acid, is an organic compound and a form of vitamin B3, an essential human nutrient. It can be manufactured by plants and animals from the amino acid tryptophan. Niacin is obtained in the diet from a variet ...

may be used, niacinamide has the benefit of not causing

Acne

Niacinamide cream is used as a treatment for

. 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 the

sebum A sebaceous 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 in the greatest nu ...

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. Other skin benefits from topical niacinamide may include relief to a stripped moisture barrier in the skin, reduced irritation, increase of collagen production, and the lessening of

hyperpigmentation Hyperpigmentation is the darkening of an area of skin or nails caused by increased melanin. Causes Hyperpigmentation can be caused by sun damage, inflammation, or other skin injuries, including those related to acne vulgaris.James, William; Be ...

in one's skin.

Skin cancer

Niacinamide at doses of 500 to 1000 mg a day decreases the risk of skin cancers, other than melanoma, in those at high risk.

Side effects

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

acute liver toxicity Acute may refer to: Science and technology * Acute angle ** Acute triangle ** Acute, a leaf shape in the glossary of leaf morphology * Acute (medicine), a disease that it is of short duration and of recent onset. ** Acute toxicity, the adverse eff ...

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

Chemistry

The structure of nicotinamide consists of a pyridine ring to which a

primary 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 organic compound, organic functional group, groups or hydrogen atoms ...

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

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 ''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 exp ...

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

from

by reaction with phosphorus pentoxide, 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 which is in turn prepared ''in situ'' by the reaction of sodium hydroxide and bromine at 70&nb ...

by reaction with a solution of sodium hypobromite, prepared ''in situ'' from bromine and sodium hydroxide. Nicotinamide highlighted in NAD+

Industrial production

The hydrolysis of

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.

Biochemistry

Nicotinamide, as a part of the cofactor nicotinamide adenine dinucleotide (NADH / NAD⁺) is crucial to life. In cells, nicotinamide 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 The citric acid cycle (CAC)—also known as the Krebs cycle or the TCA cycle (tricarboxylic acid cycle)—is a series of chemical reactions to release stored energy through the oxidation of acetyl-CoA derived from carbohydrates, fats, and prot ...

, 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⁺ 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 helps with 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 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 adenosine triphosphate. When one mole of NADH is oxidized, 158.2 kJ of energy will be released.

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 active 1-Methylnicotinamide when there's sufficient methyl donors.

Food sources

Niacinamide 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 mg of vitamin B₃ and it is also available in higher doses.

Compendial status

* British Pharmacopoeia * Japanese Pharmacopoeia

Research

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 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 a role in the treatment of HIV.

References

External links

* * {{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