Nicotinic acid

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style="background: #F8EABA; text-align: center;" colspan="2"	Nicotinic acid
File:Niacinstr.png
IUPAC name nicotinic acid
Identifiers
CAS number	59-67-6
PubChem	938
MeSH	Niacin
SMILES	C1=CC(=CN=C1)C(=O)O
Properties
Molecular formula	C6H5NO2
Molar mass	123.11
Melting point	236.6 °C
Hazards
style="background: #F8EABA; text-align: center;" colspan="2"	Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa) Infobox disclaimer and references

Niacin, also known as nicotinic acid and vitamin B₃, is the organic compound with the formula HO₂CC₅H₄N. This water-soluble, colourless solid is a derivative of pyridine, featuring a carboxylic acid functional group at the 3-position. The designation vitamin B₃ also includes the corresponding amide nicotinamide ("niacinamide"), wherein the CO₂H group has been replaced by a CONH₂ group. Niacin is a precursor to NADH, NAD, NAD⁺, and NADP, which play essential metabolic roles in living cells. Among its many functions, niacin derivatives are involved with detoxification of xenochemicals, DNA repair, and the production of steroid hormones in the adrenal gland.

History

Niacin was first described by 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 "ni"cotinic "ac"id + vitam"in."

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

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, and that do not use lime during meal/flour production. Alkali lime releases the tryptophan from the corn in a process called nixtamalization so that it can be absorbed in the intestine, and converted to niacin.

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.

Pharmacological uses

Niacin, when taken in large doses, blocks the breakdown of fats in adipose tissue, thus altering blood lipid levels. Niacin is used in the treatment of hyperlipidemia because it reduces very-low-density lipoprotein (VLDL), a 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. An extended release formulation of niacin for this indication is marketed by Abbott Laboratories under the trade name Niaspan by prescription in the United States; Slo-Niacin, made by Upsher-Smith Laboratories, is available over the counter.

Niacin is sometimes consumed in large quantities by people who wish to fool drug screening tests, particularly for lipid soluble drugs such as marijuana.

• dermatological complaints
  • facial flushing and itching
  • dry skin
  • skin rashes including acanthosis nigricans
• gastrointestinal complaints
  • dyspepsia (indigestion)
• liver toxicity
  • fulminant hepatic failure
• hyperglycemia
• cardiac arrhythmias
• birth defects

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. This effect is mediated by prostaglandins 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 4.5x lower (1.9 vs. 8.6 episodes in the first month) with a sustained-release formulation.

Doses above 2 g per day have been associated with liver damage, particularly with slow-release formulations.

High-dose niacin may also elevate blood sugar, thereby worsening diabetes mellitus. Hyperuricemia is another side-effect of taking high-dose niacin; thus niacin may worsen gout^{[How to reference and link to summary or text]}.

Niacin at doses used in lowering cholesterol has been associated with birth defects in laboratory animals and should not be taken by pregnant women.

Niacin at extremely high doses can have life-threatening acute toxic reactions. One patient suffered vomiting after taking eleven 500-milligram niacin tablets over 36 hours, and another was unresponsive for several minutes after taking five 500-milligram tablets over two days. Extremely high doses of niacin can also cause niacin maculopathy, a thickening of the macula and retina which leads to blurred vision and blindness.

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 clear whether it is pharmacologically equivalent in its positive effect.

Biosynthesis

The liver can synthesize niacin from the essential amino acid tryptophan (see below), but the synthesis is extremely inefficient; 60 mg of tryptophan are required to make one milligram of niacin.

The 5-membered aromatic heterocycle of the essential amino acid, tryptophan, is cleaved and rearranged with the alpha amino group of tryptophan into the 6-membered aromatic heterocycle of niacin by the following reaction:

Biosynthesis: Tryptophan → kynurenine → niacin

Receptor

The receptor for niacin is a G-protein coupled receptor called HM74A. It couples to G_i.

Food sources

Animal products:	Fruits and vegetables:	Seeds:	Fungi:
liver, heart and kidney chicken beef fish: tuna, salmon milk eggs	leaf vegetables broccoli tomatoes carrots dates sweet potatoes asparagus avocados	nuts whole grain products legumes saltbush seeds	mushrooms brewer's yeast

External links

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