nicotinic acid amide
|Molar mass||122.13 g·mol−1|
|Melting point||129.5 °C (265.1 °F; 402.6 K)|
|Boiling point||334 °C (633 °F; 607 K)|
|Flash point||69 °C; 156 °F; 342 K|
|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).
|what is: / ?)(|
Nicotinamide, (ni-kə-tē-nə-mīd) also known as niacinamide and nicotinic amide, is the amide of nicotinic acid (vitamin B3 / niacin). 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, although nicotinamide may be toxic to the liver at doses exceeding 3 g/day for adults. 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. Commercial production of niacin and niacinamide (several thousand tons annually) is by hydrolysis or aminolysis of 3-cyanopyridine (nicotinonitrile).
Use in medicine
Nicotinamide has demonstrated anti-inflammatory actions that may be of benefit to patients with inflammatory skin conditions. 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 precipitate 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, AzerizinTM. 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. Unlike topical Erythromycin or Clindamycin it does not precipitate bacterial resistance in treating inflammatory acne. Nicotinamide acne treatment is also available as Nicotinamide pads and cream.
In a double-blind study of over 380 patients (average age 66) with at least two non-melanoma skin cancers in the last 5 years, the rates of new non-melanoma skin cancer diagnoses were 23% lower in the nicotinamide group (500mg bd) compared to the placebo group. The appearance of actinic keratoses were reduced in the supplement group as well by 11% at 3 months of treatment and by 20% at nine months. There was no effect beyond the 12-month treatment period, suggesting a rebound effect after the drug is stopped. There were no differences between the groups with regard to adverse events.
It is an activator of sirtuins (but inhibits at higher doses) and has been reported to restore cognition in Alzheimer's disease transgenic mice. A safety study of niacinamide for the treatment of Alzheimer's disease was begun in 2007[update] at the University of California, Irvine.
Nicotinamide conflicts as a chemo- and radio-sensitizing agent/cancer-growth-promoter by enhancing tumor blood flow, thus 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. PARP-1 appears to be an important target for triple negative breast cancers because the cells are sensitive to inhibition of PARP-1. Niacinamide is also used by some patients in combination with the popular but entirely unproven "intravenous vitamin C" treatment for cancer. It has also been seen to prevent immunosuppression caused by UVA and UVB radiation (so it could potentially be added to sunscreen).
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, and in Jurkat (human T-cell lymphoma cells) when oxidative stress is induced by sodium deoxycholate.
Nicotinamide reportedly increases the endurance of mice.
Nicotinamide occurs in trace amounts mainly in meat, fish, nuts, and mushrooms, as well as to a lesser extent in some vegetables.
Some countries require fortification with nicotinamide of some foods. For example, the UK requires fortification of flour and bread with nicotinamide.
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.
Notes and references
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- Manfred Eggersdorfer et al. (2000). "Vitamins". Ullmann's Encyclopedia of Industrial Chemistry. doi:10.1002/14356007.a27_443.
- Niren NM (2006). "Pharmacologic doses of nicotinamide in the treatment of inflammatory skin conditions: a review". Cutis 77 (1 Suppl): 11–6. PMID 16871774.
- Shalita AR, Smith JG, Parish LC, Sofman MS, Chalker DK (June 1995). "Topical nicotinamide compared with clindamycin gel in the treatment of inflammatory acne vulgaris". International Journal of Dermatology 34 (6): 434–7. doi:10.1111/j.1365-4362.1995.tb04449.x. PMID 7657446.
- Hakozaki T; Minwalla L; Zhuang J et al. (July 2002). "The effect of niacinamide on reducing cutaneous pigmentation and suppression of melanosome transfer". Br. J. Dermatol. 147 (1): 20–31. doi:10.1046/j.1365-2133.2002.04834.x. PMID 12100180.
- Navarrete-Solís J; Castanedo-Cázares JP; Torres-Álvarez B et al. (July 2011). "A Double-Blind, Randomized Clinical Trial of Niacinamide 4% versus Hydroquinone 4% in the Treatment of Melasma". Dermatol Res Pract. 2011 (379173): 1. doi:10.1155/2011/379173. PMC 3142702. PMID 21822427.
- Andrew James Martin; Andrew Chen; Bonita Choy; Pablo Fernandez Penas; Gary Halliday; Robyn Dalziell; Catriona McKenzie; Richard A Scolyer; Haryana M. Dhillon; Janette L. Vardy; Gaya St George; Nira Chinniah; Diona Damian (2015). "Oral nicotinamide to reduce actinic cancer: A phase 3 double-blind randomized controlled trial.". American Society of Clinical Oncology Annual Meeting, Chicago, 30 May 2015. J Clin Oncol 33, 2015 (suppl; abstr 9000).
- Tallman JF, Paul SM, Skolnick P, Gallager DW (1980). "Receptors for the age of anxiety: pharmacology of the benzodiazepines". Science 207 (4428): 274–81. doi:10.1126/science.6101294. PMID 6101294.
- Paul, SM; Marangos, PJ; Skolnick, P; Goodwin, FK (1982). "Biological substrates of anxiety: benzodiazepine receptors and endogenous ligands.". L'Encephale 8 (2): 131–44. PMID 6125374.
- Akhundov, RA; Sultanov, AA; Gadzhily, RA; Sadykhov, RV (May 1993). "[Psychoregulating role of nicotinamide].". Biulleten' eksperimental'noi biologii i meditsiny 115 (5): 487–91. PMID 7913840.
- Green KN, Steffan JS, Martinez-Coria H, Sun X, Schreiber SS, Thompson LM, LaFerla FM (2008-11-05). "Journal of Neuroscience - Nicotinamide Restores Cognition in Alzheimer's Disease Transgenic Mice via a Mechanism Involving Sirtuin Inhibition and Selective Reduction of Thr231-Phosphotau". Retrieved 2008-11-05..
- Safety Study of Nicotinamide to Treat Alzheimer's Disease, clinicaltrials.gov
- Definition of niacinamide, National Cancer Institute
- Efficacy of BSI-201, a poly (ADP-ribose) polymerase-1 (PARP1) inhibitor, in combination with gemcitabine/carboplatin (G/C) in patients with metastatic triple-negative breast cancer (TNBC): Results of a randomized phase II trial.
- Intravenously administered vitamin C as cancer therapy: three cases
- Damian DL, Patterson CR, Stapelberg M, Park J, Barnetson RS, Halliday GM (February 2008). "UV radiation-induced immunosuppression is greater in men and prevented by topical nicotinamide". J. Invest. Dermatol. 128 (2): 447–54. doi:10.1038/sj.jid.5701058. PMID 17882270.
- Bhansali SG, Brazeau DA, Sonee M, Mukherjee SK. (2006). Nicotinamide prevents apoptosis in human cortical neuronal cells. Toxicol Mech Methods 16(4):173-180. doi: 10.1080/15376520500194726. PMID 20021043
- Crowley CL, Payne CM, Bernstein H, Bernstein C, Roe D. (2000). The NAD+ precursors, nicotinic acid and nicotinamide protect cells against apoptosis induced by a multiple stress inducer, deoxycholate. Cell Death Differ 7(3):314-326. PMID 10745276
- Fukuwatari T, Shibata K, Ishihara K, Fushiki T, Sugimoto E (April 2001). "Elevation of blood NAD level after moderate exercise in young women and mice". J. Nutr. Sci. Vitaminol. 47 (2): 177–9. doi:10.3177/jnsv.47.177. PMID 11508711.
- Cosmetic Ingredient Review Expert Panel (2005). "Final report of the safety assessment of niacinamide and niacin". Int. J. Toxicol. 24 Suppl 5: 1–31. doi:10.1080/10915810500434183. PMID 16596767.
- British Pharmacopoeia Commission Secretariat (2009). "Index, BP 2009" (PDF). Retrieved 4 February 2010.
- "Japanese Pharmacopoeia, Fifteenth Edition" (PDF). 2006. Retrieved 4 February 2010.