Niacin
From Wikipedia, the free encyclopedia
| Niacin | |
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| IUPAC name |
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| Other names | pyridine-3-carboxylic acid, nicotinic acid, nicotinamide, niacinamide, vitamin B3 |
| Identifiers | |
| CAS number | [] |
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| Properties | |
| Molecular formula | C6H5NO2 |
| Molar mass | 123.11 g/mol |
| Melting point |
236.6 °C, 510 K, 458 °F |
| Boiling point |
decomposes |
| Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa) Infobox references |
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Niacin, also known as vitamin B3 or nicotinic acid, is a water-soluble vitamin that prevents the deficiency disease pellagra. It is an organic compound with the molecular formula C6H5NO2. It is a derivative of pyridine, with a carboxyl group (COOH) at the 3-position. Other forms of vitamin B3 include the corresponding amide, nicotinamide ("niacinamide"), where the carboxyl group has been replaced by a carboxamide group (CONH2), as well as more complex amides and a variety of esters. The terms niacin, nicotinamide, and vitamin B3 are often used interchangeably to refer to any one of this family of molecules, since they have a common biochemical activity.
Niacin is converted to nicotinamide and then to NAD and NADP in vivo. Although the two are identical in their vitamin activity, nicotinamide does not have the same pharmacological effects as niacin, which occur as side-effects of niacin's conversion. Thus nicotinamide does not reduce cholesterol or cause flushing,[1] although nicotinamide may be toxic to the liver at doses exceeding 3 g/day for adults.[2] Niacin is a precursor to NADH, NAD, NAD+, NADP and NADPH, which play essential metabolic roles in living cells.[3] Niacin is involved in both DNA repair, and the production of steroid hormones in the adrenal gland.
Niacin is one of five vitamins associated with a pandemic deficiency disease: these are niacin (pellagra), vitamin C (scurvy), thiamin (beriberi), vitamin D (rickets), and vitamin A deficiency, a syndrome which has no common name but is one of the most common symptomatic deficiencies worldwide.
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[edit] History
Niacin was first described by Hugo Weidel in 1873 in his studies of nicotine.[4] The original preparation remains useful: the oxidation of nicotine using nitric acid.[5] Niacin was extracted from livers by Conrad Elvehjem who later identified the active ingredient, then referred to as the "pellagra-preventing factor" and the "anti-blacktongue factor."[6] When the biological significance of nicotinic acid was realized, it was thought appropriate to choose a name to dissociate it from nicotine, in order to avoid the perception that vitamins or niacin-rich food contains nicotine, or that cigarettes contain vitamins. The resulting name 'niacin' was derived from nicotinic acid + vitamin.
Carpenter found in 1951 that niacin in corn is biologically unavailable and can only be released in very alkali lime water of pH 11.[7] This process is known as nixtamalization.[8]
Niacin is referred to as Vitamin B3 because it was the third of the B vitamins to be discovered. It has historically been referred to as "vitamin PP."
[edit] Dietary needs
Depending on the definition used, niacin is one of between 40 to 80 essential human nutrients.
Currently niacin deficiency is rarely seen in developed countries and is usually apparent in conditions of poverty and malnutrition and chronic alcoholism (Pitsavas et al., 2004). Alcoholic patients typically experience increased intestinal permeability leading to negative health outcomes. Studies have indicated that in patients with alcoholic pellagra, niacin deficiency may be an important factor influencing both the onset and severity of this condition (Junqueira-Franco et al., 2006).Severe deficiency of niacin in the diet causes the disease pellagra. Pellagra is characterized by diarrhea, dermatitis and dementia as well as “necklace” lesions on the lower neck, hyperpigmentation, thickening of the skin, inflammation of the mouth and tongue, digestive disturbances, amnesia, delirium, and eventually death if left untreated (Prakash et al., 2008). Common psychiatric symptoms include irritability, poor concentration, anxiety, fatigue, restlessness, apathy, and depression (Prakash et al., 2008). Mild niacin deficiency has been shown to slow metabolism, causing decreased tolerance to the cold. Dietary niacin deficiency tends to occur in areas where people eat maize ("corn") as a staple food. Maize is the only grain low in niacin and nixtamalization is needed to increase the bioavaiability of niacin during meal/flour production. Nixtamalization refers to the process of alkaline cooking maize with lime. This is the primary processing step during the manufacture of maize products including chips, tortillas, and taco shells. The basic pre-Columbian technique involves cooking whole maize in water for 12–16 hours in large tanks. The steeped maize is referred to as nixtamal and the cooked liquid is nejayote. This process functions to soften the pericarp of the maize and allows the endosperm to absorb water, enabling its milling. The nixtamal is washed and then stone-ground to produce masa which is used to produce a variety of products with improved bioavailability of niacin (Sefa-Dedeh et al., 2004).
The recommended daily allowance of niacin is 2–12 mg/day for children, 14 mg/day for women, 16 mg/day for men, and 18 mg/day for pregnant or breast-feeding women.[9][unreliable source?]. The upper limit for adult men and women is 35 mg/day which is based on flushing as the critical adverse effect.
Hartnup’s disease is an inherited nutritional disorder involving an in-born error of metabolism resulting in niacin deficiency (Prakash et al., 2008). This condition was first identified in the 1950’s by the Hartnup family in London. It is due to a deficit in the intestines and kidneys, making it difficult for the body to break down and absorb dietary tryptophan. The result is a similar condition to pellagra including symptoms of red, scaly rash and sensitivity to sunlight. Oral niacin is given as a treatment in this condition in doses ranging from 40-200 mg with a good prognosis if identified and treated early (Prakash et al., 2008). Niacin synthesis is also deficient in carcinoid syndrome because of metabolic diversion of its precursor, tryptophan, to form serotonin.
Niacin status is generally tested through urinary biomarkers,[10] which are believed to be more reliable than plasma levels.[11]
[edit] Pharmacological uses
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Vitamin B3 has been reported to prevent Alzheimer's-like symptoms in a mouse model of the disease.[12][13]
[edit] Lipid modifying effects
In pharmacological doses niacin has been proven to reduce total cholesterol, triglyceride, very-low-density lipoprotein, low-density lipoprotein, and increase high-density lipoprotein levels (Kamanna et al., 2008). Niacin, prescribed in doses between 1000 and 2000 mg two to three times daily, [14] blocks the breakdown of fats in adipose tissue, more specifically the very-low-density lipoprotein (VLDL), precursor of low-density lipoprotein (LDL) or "bad" cholesterol. Because niacin blocks breakdown of fats, it causes a decrease in free fatty acids in the blood and, as a consequence, decreased secretion of VLDL and cholesterol by the liver.[15]
By lowering VLDL levels, niacin also increases the level of high-density lipoprotein (HDL) or "good" cholesterol in blood, and therefore it is sometimes prescribed for patients with low HDL, who are also at high risk of a heart attack.[16][17]
As of August 2008[update], a combination of niacin with laropiprant is tested in a clinical trial. Laropiprant reduces facial flushes induced by niacin.[citation needed]
[edit] Toxicity
People taking pharmacological doses of niacin (1.5 - 6 g per day) often experience side-effects that can include dermatological complaints such as skin flushing and itching, dry skin, skin rashes including acanthosis nigricans. Gastrointestinal complaints, such as dyspepsia (indigestion) and liver toxicity (fulminant hepatic failure) have also been reported. Also reports include hyperglycemia, cardiac arrhythmias, birth defects, and orthostasis.[18]
- Skin flushing is the most commonly reported side effect.[19] It lasts for about 15 to 30 minutes, and is sometimes accompanied by a prickly or itching sensation, particularly in areas covered by clothing. This effect is mediated by prostaglandin and can be blocked by taking 300 mg of aspirin half an hour before taking niacin, or by taking one tablet of ibuprofen per day. Taking the niacin with meals also helps reduce this side effect. After 1 to 2 weeks of a stable dose, most patients no longer flush.[citation needed] Slow- or "sustained"-release forms of niacin have been developed to lessen these side-effects.[15][20] One study showed the incidence of flushing was significantly lower with a sustained release formulation[21] though doses above 2 g per day have been associated with liver damage, particularly with slow-release formulations.[18]
- High-dose niacin may also elevate blood sugar, thereby worsening diabetes mellitus.[18]
- Hyperuricemia is another side-effect of taking high-dose niacin, and may exacerbate gout.[22]
- Niacin at doses used in lowering cholesterol has been associated with birth defects in laboratory animals, with possible consequences for infant development in pregnant women.[18]
Niacin at extremely high doses can have life-threatening acute toxic reactions.[23] Extremely high doses of niacin can also cause niacin maculopathy, a thickening of the macula and retina which leads to blurred vision and blindness. This maculopathy is reversible after stopping niacin intake.[24]
[edit] Inositol hexanicotinate
One popular form of dietary supplement is inositol hexanicotinate, usually sold as "flush-free" or "no-flush" niacin in units of 250, 500 or 1000 mg/tablet or capsule. While this form of niacin does not cause the flushing associated with the immediate release products, the evidence that it has lipid modifying functions is contradictory, at best. As the clinical trials date from the early 1960s (Dorner, Welsh) or the late 1970s (Ziliotto, Kruse, Agusti) it is difficult to assess them by today's standards.[25] A more recent placebo-controlled trial was small (n=11/group), but results after three months at 1500 mg/day showed no trend for improvements in total cholesterol, LDL-C, HDL-C or triglycerides (AM Benjo; Atherosclerosis 2006;187:116-122). Thus, so far there is not enough evidence to recommend inositol hexanicotinate to treat dyslipidemia. Furthermore, the American Heart Association and the National Cholesterol Education Program both take the position that only prescription niacin should be used to treat dyslipidemias, and only under the management of a physician. The reason given is that niacin at effective intakes of 1500-3000 mg/day can also potentially have severe adverse effects. Monitoring of liver enzymes is necessary.
[edit] Biosynthesis and chemical synthesis
The liver can synthesize niacin from the essential amino acid tryptophan, requiring 60 mg of tryptophan to make one mg of niacin.[26] The 5-membered aromatic heterocycle of tryptophan is cleaved and rearranged with the alpha amino group of tryptophan into the 6-membered aromatic heterocycle of niacin.
Several million kilograms of niacin are manufactured each year, starting from 3-methylpyridine.
[edit] Receptor
The receptor for niacin is a G protein-coupled receptor called HM74A.[27] It couples to Gi alpha subunit.[28]
[edit] Food sources
Niacin is found in variety of foods including liver, chicken, beef, fish, cereal, peanuts and legumes and is also synthesized by tryptophan, which is found in meat, dairy and eggs. In order to convert 1 mg of niacin, 60 mg of tryptophan is required.
Animal products:
Fruits and vegetables:
Seeds:
Fungi:
[edit] References
- ^ Jaconello P (October 1992). "Niacin versus niacinamide". CMAJ 147 (7): 990. PMID 1393911.
- ^ Knip M, Douek IF, Moore WP, et al. (2000). "Safety of high-dose nicotinamide: a review". Diabetologia 43 (11): 1337–45. doi:. PMID 11126400.
- ^ Cox, Michael; Lehninger, Albert L; Nelson, David R. (2000). Lehninger principles of biochemistry. New York: Worth Publishers. ISBN 1-57259-153-6.
- ^ Weidel, H (1873). "Zur Kenntniss des Nicotins". Justus Liebig's Annalen der Chemie und Pharmacie 165: 330–349. doi:.
- ^ Samuel M. McElvain (1941). "Nicotinic Acid". Org. Synth.; Coll. Vol. 1: 385.
- ^ Elvehjem, C.A.; Madden, R.J.; Strongandd, F.M.. "W. WOOLLEY 1938 The isolation and identification of the anti-blacktongue factor J". J. Biol. Chem 123: 137.
- ^ LAGUNA J, CARPENTER KJ (September 1951). "Raw versus processed corn in niacin-deficient diets". J. Nutr. 45 (1): 21–8. PMID 14880960. http://jn.nutrition.org/cgi/pmidlookup?view=long&pmid=14880960.
- ^ "Vitamin B3". University of Maryland Medical Center. 2002-01-04. http://www.umm.edu/altmed/articles/vitamin-b3-000335.htm. Retrieved on 2008-03-31.
- ^ Jane Higdon, "Niacin", Micronutrient Information Center, Linus Pauling Institute
- ^ Institute of Medicine. (2006). Dietary Reference Intakes Research Synthesis: Workshop Summary, p. 37. National Academies Press.
- ^ Jacob RA, Swendseid ME, McKee RW, Fu CS, Clemens RA (April 1989). "Biochemical markers for assessment of niacin status in young men: urinary and blood levels of niacin metabolites". J. Nutr. 119 (4): 591–8. PMID 2522982. http://jn.nutrition.org/cgi/pmidlookup?view=long&pmid=2522982.
- ^ Green, Kim N.; Joan S. Steffan, Hilda Martinez-Coria, Xuemin Sun, Steven S. Schreiber, Leslie Michels Thompson, and Frank M. LaFerla (November 5, 2008). "Nicotinamide Restores Cognition in Alzheimer's Disease Transgenic Mice via a Mechanism Involving Sirtuin Inhibition and Selective Reduction of Thr231-Phosphotau". The Journal of Neuroscience 28 (45): 11500–11510. doi:. PMID 18987186. http://www.jneurosci.org/cgi/content/abstract/28/45/11500. Retrieved on January 20, 2009.
- ^ Dotinga, Randy (November 5, 2008). "Vitamin Holds Promise for Alzheimer's Disease". Washington Post. http://www.washingtonpost.com/wp-dyn/content/article/2008/11/05/AR2008110502796.html. Retrieved on 2009-01-21.
- ^ Marks, Jay W. (2005). "Niacin Monograph". MedicineNet, Inc..
- ^ a b Katzung, Bertram G. (2006). Basic and clinical pharmacology. New York: McGraw-Hill Medical Publishing Division. ISBN 0071451536. http://www.medicinenet.com/niacin/article.htm.
- ^ McGovern ME (2005). "Taking aim at HDL-C. Raising levels to reduce cardiovascular risk". Postgrad Med 117 (4): 29–30, 33–5, 39 passim. PMID 15842130.
- ^ Canner PL, Berge KG, Wenger NK, et al. (1986). "Fifteen year mortality in Coronary Drug Project patients: long-term benefit with niacin". J. Am. Coll. Cardiol. 8 (6): 1245–55. PMID 3782631.
- ^ a b c d Keith Parker; Laurence Brunton; Goodman, Louis Sanford; Lazo, John S.; Gilman, Alfred (2006). Goodman & Gilman's the pharmacological basis of therapeutics. New York: McGraw-Hill. ISBN 0071422803.
- ^ McGee, W (2007-02-01). "Medical Encyclopedia: Niacin". MedlinePlus. http://www.nlm.nih.gov/medlineplus/ency/article/002409.htm. Retrieved on 2008-03-31.
- ^ Barter, P (2006). "Options for therapeutic intervention: How effective are the different agents?". European Heart Journal Supplements 8 (F): F47–F53. doi:.
- ^ Chapman MJ, Assmann G, Fruchart JC, Shepherd J, Sirtori C (2004). "Raising high-density lipoprotein cholesterol with reduction of cardiovascular risk: the role of nicotinic acid--a position paper developed by the European Consensus Panel on HDL-C". Curr Med Res Opin 20 (8): 1253–68. doi:. PMID 15324528.
- ^ Capuzzi DM, Morgan JM, Brusco OA, Intenzo CM (2000). "Niacin dosing: relationship to benefits and adverse effects". Curr Atheroscler Rep 2 (1): 64–71. doi:. PMID 11122726.
- ^ Mittal MK, Florin T, Perrone J, Delgado JH, Osterhoudt KC (2007). "Toxicity from the use of niacin to beat urine drug screening". Ann Emerg Med 50 (5): 587–90. doi:. PMID 17418450.
- ^ Gass JD (2003). "Nicotinic acid maculopathy. 1973". Retina (Philadelphia, Pa.) 23 (6 Suppl): 500–10. PMID 15035390.
- ^ Taheri, R (2003-01-15). "No-Flush Niacin for the Treatment of Hyperlipidemia". Medscape. http://www.medscape.com/viewarticle/447528. Retrieved on 2008-03-31.
- ^ Jacobson, EL (2007). "Niacin". Linus Pauling Institute. http://lpi.oregonstate.edu/infocenter/vitamins/niacin/. Retrieved on 2008-03-31.
- ^ Zhang Y, Schmidt RJ, Foxworthy P, et al. (2005). "Niacin mediates lipolysis in adipose tissue through its G-protein coupled receptor HM74A". Biochem. Biophys. Res. Commun. 334 (2): 729–32. doi:. PMID 16018973.
- ^ Zellner C, Pullinger CR, Aouizerat BE, et al. (2005). "Variations in human HM74 (GPR109B) and HM74A (GPR109A) niacin receptors". Hum. Mutat. 25 (1): 18–21. doi:. PMID 15580557.
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