Nicotinamide

Niacin deficiency

Nicotinamide is the preferred treatment for niacin deficiency (pellagra). A patient's diagnosis of Pellagra is based on their history, as well as a presence of dermatitis, diarrhea, and dementia. While nicotinic acid (niacin) may be used nicotinamide has the benefit of not causing skin flushing.

Acne

Nicotinamide in the form of a cream is used as a treatment for acne.

It has anti-inflammatory actions. These may be of benefit to people with inflammatory skin conditions.

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 has been found to be effective in lowering the sebum excretion rate in study participants. Nictotinamide has been shown to prevent Propionibacterium acnes-induced activation of toll-like receptor (TLR)-2, which ultimately results in the down-regulation of pro-inflammatory IL-8 production.

Side effects

Side effects are minimal. At high doses liver problems may occur. Normal amounts are safe for use during pregnancy. Foods that contain nicotinamide include yeast, meat, milk, and green vegetables.

Nicotinamide lacks the vasodilator, gastrointestinal, hepatic, and hypolipidemic actions of nicotinic acid. As such, nicotinamide has not been shown to produce the flushing, itching, and burning sensations of the skin as is commonly seen when large doses of nicotinic acid are administered orally. High-dose nicotinamide should still, however, be considered as a drug with toxic potential at adult doses in excess of 3 g/day and unsupervised use should be discouraged. Overall, however, it rarely causes side effects, and is considered generally safe as a food additive, and as a component in cosmetics and medication.

Structure

The structure of nicotinamide consists of an aromatic ring with an amido group attached to the third carbon. One of the atoms in the six membered aromatic ring is nitrogen, a trivalent molecule. Nitrogen is most stable when it is bonded to only three other atoms, however in the molecule nicotinamide adenine dinucleotide (NAD+), nitrogen is bonded to four other atoms, and thus has a positive formal charge. Each carbon molecule in this ring is bound to a hydrogen atom except for the third carbon, which is covalently bonded to an amido group. The amido group adds to the stabilization of the molecule through a form of stability called conjugation. Conjugation stability is added when there are multiple pi (double) bonds in series. It allows for the electron density in a certain part of the molecule to have more freedom, and adds more molecular stability.

The structure of this molecule helps to determine its biological function, as the forming and breaking of an aromatic ring increases and decreases a molecules stability. The systems of the body pick up electrons, and add energy to NAD+ during Glycolysis and the Citric acid cycle, and then they release it in the Electron transport chain, forming Adenosine triphosphate, the primary energy currency of the cell.

Biochemistry

Nicotinamide, as a part of the coenzyme Nicotinamide adenine dinucleotide(NAD+) is crucial to life. In cells, nicotinamide is incorporated into Nicotinamide adenine dinucleotide (NAD+) and nicotinamide adenine dinucleotide phosphate (NADP+). NAD+ and NADP+ are coenzymes in a wide variety of enzymatic oxidation-reduction reactions the most notable being 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+ 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, ATP. In oxidation-reduction reactions, the active part of the coenzyme 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.

For every one mole of NADH that is oxidized, 158.2 KJ of energy will be released.

Production

Commercially nicotinamide is made from either nicotinic acid or 3-cyanopyridine. In 2014 31,000 tons of nicotinamide were sold.

Compendial status

Research

There is tentative evidence that it may reduce the risk of nonmelanoma skin cancers among people who have had a previous basal cell carcinoma or squamous cell carcinoma. There is also tentative evidence for its effective use to treat bullous pemphigoid. Nicotinamide may aid chemotherapy-and-radiation therapy by acting as a sensitizing agent/cancer-growth-promoter resulting in enhanced blood flow to tumors and thus increased oxygen supply to tumors, thereby reducing tumor hypoxia. Niacinamide also inhibits poly(ADP-ribose) polymerases (PARP-1), enzymes involved in the rejoining of DNA strand breaks induced by radiation or chemotherapy. There is also evidence that niacinamide is beneficial in treating psoriasis.