Nicotinamide

Nicotinamide

Names
IUPAC name pyridine-3-carboxamide
Other names 3-pyridinecarboxamide niacinamide nicotinamide nicotinic acid amide Vitamin PP
Identifiers
CAS Number	98-92-0 Y
ChEBI	CHEBI:17154 N
ChEMBL	ChEMBL1140 Y
ChemSpider	911 Y
DrugBank	DB02701 N
EC Number	202-713-4
Jmol interactive 3D	Image
KEGG	D00036 Y
PubChem	936
UNII	25X51I8RD4 Y
InChI InChI=1S/C6H6N2O/c7-6(9)5-2-1-3-8-4-5/h1-4H,(H2,7,9) Y Key: DFPAKSUCGFBDDF-UHFFFAOYSA-N Y InChI=1/C6H6N2O/c7-6(9)5-2-1-3-8- 4-5/h1-4H,(H2,7,9)/f/h7H2 InChI=1/C6H6N2O/c7-6(9)5-2-1-3-8-4-5/h1-4H,(H2,7,9) Key: DFPAKSUCGFBDDF-UHFFFAOYAZ
SMILES c1cc(cnc1)C(=O)N
Properties
Chemical formula	C6H6N2O
Molar mass	122.13 g·mol−1
Density	1.4463g/cm3
Melting point	129.5 °C (265.1 °F; 402.6 K)
Boiling point	334 °C (633 °F; 607 K)
log P	-.37
Vapor pressure	1.3*10−4mmHg
Pharmacology
ATC code	A11HA01
Hazards
NFPA 704	0 1 0
Flash point	69 °C; 156 °F; 342 K
Autoignition temperature	249 °C; 480 °F; 522 K
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
N verify (what is YN ?)
Infobox references

Nicotinamide, (ni-kə-tē-nə-mīd) also known as niacinamide^[1][2] and nicotinic amide, is the amide of nicotinic acid (vitamin B₃ / niacin).^[1][2] Nicotinamide is a water-soluble vitamin and is part of the vitamin B group. Nicotinic acid, also known as niacin, is converted to nicotinamide in vivo, and, though the two are identical in their vitamin functions, nicotinamide does not have the same pharmacological and toxic effects of niacin, which occur incidental to niacin's conversion. Thus nicotinamide does not reduce cholesterol or cause flushing,^[3] although nicotinamide may be toxic to the liver at doses exceeding 3 g/day for adults.^[4] In cells, niacin is incorporated into nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP), although the pathways for nicotinic acid amide and nicotinic acid are very similar. NAD+ and NADP+ are coenzymes in a wide variety of enzymatic oxidation-reduction reactions.^[5] Commercial production of niacin and niacinamide (several thousand tons annually) is by hydrolysis or aminolysis of 3-cyanopyridine (nicotinonitrile).^[6]

Small intestinal bacterial overgrowth is one known cause of nicotinamide deficiency.^[7]

Use in medicine

Acne Vulgaris

Nicotinamide has anti-inflammatory actions. These may be of benefit to patients with inflammatory skin conditions.^[8] These conditions include acne vulgaris, and the compound can suppress antigen-induced, lymphocytic transformation and inhibit 3',5'-cyclic-AMP phosphodiesterase. Nicotinamide has demonstrated the ability to block the inflammatory actions of iodides known to cause or exacerbate inflammatory acne.

NicAzel and Nicomide are the names of oral acne medications that include nicotinamide as their most predominant ingredient, based on this area of research. Nicotinamide is also found as part of a new adjunct supplement combination called, Azerizin^TM. According to the makers of Azerizin, this adjunct is part of their prescription dietary supplement product, which they claim helps manage inflammatory skin conditions. Nicotinamide is also used topically as a 4% or 5% gel or cream - as effective as topical 1% clindamycin (8-week double-blind trial) performed at the New York University College of Medicine.^[9] Unlike topical Erythromycin or Clindamycin it does not lead to bacterial resistance to these antibiotics, when used to treat inflammatory acne. Nicotinamide acne treatment is also available as Nicotinamide pads and cream.

A 2013 double blinded clinical trial in the International Journal of Dermatology showed that topical 4% nicotinamide gel was as effective as 1% clindamycin gel in the treatment of moderate inflammatory acne vulgaris.^[10] The study also showed that clindamycin worked better in people with non-oily (normal, dry) skin types, while nicotinamide worked better in people with oily skin types.

Nicotinamide increases the biosynthesis of ceramides in human keratinocytes in vitro and improves the epidermal permeability barrier in vivo.^[11] 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.^[12] 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.^[13] These are some of the possible mechanisms by which nicotinamide may help in acne vulgaris.

Skin cancer

A phase II double-blinded randomized controlled trial done at the Royal Prince Alfred Hospital Dermatology clinics in Sydney, Australia showed that oral nicotinamide may be effective at preventing actinic keratoses (AKs). Patients included in the study had significant skin cancer histories and were required to have at least 4 visible AKs at the time of entry into the study. Nicotinamide dosed at 500 mg twice daily showed a 35% reduction in AK count at 2 months and 4 months. Dosed at 500 mg once daily, a 15% reduction in AK count was seen at 2 months and 29% reduction at 4 months.^[14]

A phase III double-blinded, randomized, and controlled trial investigating possible roles of nicotinamide in the prevention of non-melanoma skin cancer was performed by the same researchers who carried out the phase II trial referenced above. The trial enrolled 386 patients, who had at least two non-melanoma skin cancers in the last 5 years. The rates of new non-melanoma skin cancer diagnosed during the study period were 23% lower in the nicotinamide group (500 mg twice a day) compared to the placebo group. The study also showed that those in the nicotinamide group, AKs were reduced by 11% at 3 months, 20% at nine months, and 13% at 12 months compared to the placebo group. There was no added effect beyond the 12-month treatment period, suggesting that continuous dosing is necessary to see benefit. There were no differences between the groups with regard to adverse effects.^[15]

Anxiety

Studies show that nicotinamide has anxiolytic (anti-anxiety) properties. It may work in a way similar to benzodiazepines.^{[16][17][18][19]}

Alzheimer's disease

Nicotinamide is an activator of sirtuins (but can be an inhibitor at higher doses) and has been reported to restore cognition in Alzheimer's disease transgenic mice.^[20] A study of niacinamide safety when used for the treatment of Alzheimer's disease was begun in 2007 at the University of California, Irvine.^[21]

Cancer

Nicotinamide can counteract 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.^[22] PARP-1 appears to be an important target for triple negative breast cancers because the cells are sensitive to inhibition of PARP-1.^[23] Niacinamide is also used by some patients in combination with the popular but entirely unproven "intravenous vitamin C" treatment for cancer.^[24] Niacinamide has also been reported as preventing suppression of the immune system caused by UVA and UVB radiation (so it could potentially be added to sunscreen).^[25]

Bullous Pemphigoid

In an open label randomized trial with twenty patients having bullous pemphigoid (BP) tetracycline combined with oral nictotinamide was shown to be as effective as prednisone in treating BP.^[26] There are several case reports which support the efficacy of this therapy.^[27] It is considered to be a steroid sparing regimen. Recommended dosing is tetracycline 500 mg four times daily or doxycycline100mg twice daily or minocycline 100 mg twice daily, combined with nicotinamide 500 mg four times daily.^[28]

Apoptosis

Nicotinamide can prevent apoptosis (programmed cell death) in cells exposed to agents that induce oxidative stress. Thus nicotinamide prevents apoptosis in human cortical neuronal cells when oxidative stress is induced by tertiary butylhydroperoxide,^[29] and in Jurkat (human T-cell lymphoma cells) when oxidative stress is induced by sodium deoxycholate.^[30]

Other

Nicotinamide reportedly increases the endurance of mice.^[31]

Nicotinamide is also reported to be an effective skin whitener in topical application.^[32][33]

Food sources

Nicotinamide occurs in trace amounts mainly in meat, fish, nuts, and mushrooms, as well as to a lesser extent in some vegetables.^[34]

Some countries require fortification with nicotinamide of some foods. For example, the UK requires fortification of flour and bread with nicotinamide.

Toxicity

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.^[4] Overall, however, it rarely causes side effects, and is considered generally safe as a food additive, and as a component in cosmetics and medication.^[35]

Compendial status

• British Pharmacopoeia^[36]
• Japanese Pharmacopoeia^[37]

See also

• Nicotinamide adenine dinucleotide
• Isonicotinamide

Notes and references

External links

• DrugBank.ca Drug Card for Nicotinamide