pellagra-preventive factor



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 Other forms of vitamin B3 include the corresponding amide, nicotinamide ("niacinamide"), where the carboxyl group has been replaced by an amide group (CONH2), as well as more complex amides and a variety of esters.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. 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 deficiences worldwide).


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", and that do not use lime 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.

Pharmacological uses

The recommended daily allowance (RDA) for niacin is 20 mg/day. The argument that niacin does not provide any benefits at doses above the RDA has been decisively disproven. There are two decisively proven uses of pharmacological doses of niacin. These are for heart disease and skin conditions. Extensive evidence combining known biochemical functions of vitamin B3, controlled trials, and clinical observations indicate that doses of niacin above the RDA speed wound healing and help the immune system fight off viral infections The available evidence supports the hypothesis that response is proportional to dose well past the side effect threshold. The side effect threshold for niacin varies dramatically from person to person, ranging from between 30 and 300 mg for the majority of the population.

Topical use

A fat-soluble derivative of niacin has been developed that efficiently penetrates the skin. This form of niacin has been shown to improve a variety of skin conditions in a number of controlled clinical trials

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." Scientific studies have shown it does not affect drug screenings, but can pose a risk of overdose, causing arrhythmias, metabolic acidosis, hyperglycemia, and other serious problems.


People taking pharmacological doses of niacin (1.5 - 6 g per day) often experience a 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. High-dose niacin may also elevate blood sugar, thereby worsening diabetes mellitus. 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 clear whether it is pharmacologically equivalent in its positive effect.


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.


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

Food sources

Animal products: Fruits and vegetables: Seeds: Fungi:


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