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Niacin
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Niacin, also known as vitamin B3, is a water-soluble vitamin which 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 Other forms of vitamin B3 include the corresponding amide, nicotinamide ("niacinamide"), where the carboxyl group has been replaced by a carboxamide group (CONH2), as well as more complex amides and a variety of esters.
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Encyclopedia
Niacin, also known as vitamin B3, is a water-soluble vitamin which 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 Other forms of vitamin B3 include the corresponding amide, nicotinamide ("niacinamide"), where the carboxyl group has been replaced by a carboxamide group (CONH2), as well as more complex amides and a variety of esters.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 of niacin, which occur as side-effects of 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. Niacin is a precursor to NADH, NAD, NAD+, NADP and NADPH, which play essential metabolic roles in living cells. 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 (no common name, but one of the most common symptomatic deficiencies worldwide).
History
Niacin was first described by Hugo Weidel in 1873 in his studies of nicotine. The original preparation remains useful: the oxidation of nicotine using nitric acid. 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." 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. 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.
This process is known as nixtamalization.
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."
Dietary needs
Depending on the definition used, niacin is one of between 40 and 80 essential human nutrients.
Severe deficiency of niacin in the diet causes the disease pellagra, whereas mild deficiency slows the metabolism, causing decreased tolerance to cold. Dietary niacin deficiency tends to occur only in areas where people eat corn [maize, the only grain low in niacin] as a staple food without lime added during meal/flour production.
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.
Note: Niacin synthesis is deficient in carcinoid syndrome because of metabolic diversion of its precursor, tryptophan, to form serotonin.
Niacin status is generally tested through urinary biomarkers, which are believed to be more reliable than plasma levels.
Pharmacological uses
Vitamin B3 has been reported to prevent Alzheimer's-like symptoms in a mouse model of the disease.
Lipid modifying effects
Niacin, prescribed in doses between 1000 and 2000 mg two to three times daily, 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.
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.
, a combination of niacin with laropiprant is tested in a clinical trial. Laropiprant reduces facial flushes induced by niacin.
Niacin and drug screening tests
Niacin is sometimes consumed in large quantities by people who wish to fool drug screening tests, particularly for lipid soluble drugs such as marijuana. It is believed to "promote metabolism" of the drug and cause it to be "flushed out". There is no scientific evidence indicating effectiveness in masking drug use, and overdose may result in arrhythmias, metabolic acidosis, hyperglycemia, and other serious problems.
Toxicity
People taking pharmacological doses of niacin (1.5 - 6 g per day) often experience side-effects that can include dermatological complaints such as facial 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 reported include hyperglycemia, cardiac arrhythmias, birth defects, and orthostasis.
- Facial flushing is the most commonly reported side effect. 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. Slow- or "sustained"-release forms of niacin have been developed to lessen these side-effects. One study showed the incidence of flushing was significantly lower with a sustained release formulation though doses above 2 g per day have been associated with liver damage, particularly with slow-release formulations.
- Hyperuricemia is another side-effect of taking high-dose niacin, and may exacerbate gout.
- 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.
Niacin at extremely high doses can have life-threatening acute toxic reactions. 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.
Inositol hexanicotinate
One popular form of dietary supplement is inositol hexanicotinate, usually sold as "flush-free" or "no-flush" niacin (although those terms are also used for regular sustained-release.) While this form of niacin does not cause the flushing associated with the nicotinic acid form, it is not pharmacologically equivalent in its positive effect. Prescription grade niacin is available and is proven to reduce cholesterol. Thus far there is not enough evidence to recommend inositol hexanicotinate to treat dyslipidemia. Niacin when taken in slowly increasing doses will cause far less flushing.
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. 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.
Receptor
The receptor for niacin is a G protein-coupled receptor called HM74A. It couples to Gi alpha subunit.
Food sources
Niacin is essentially found in meat, wheat germ, dairy products, and yeast.
Animal products:
Fruits and vegetables:
Seeds:
Fungi:
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