Vitamin B3: Wikis


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CAS number 59-67-6 Yes check.svgY
PubChem 938
ChemSpider 913
MeSH Niacin
Molecular formula C6H5NO2
Molar mass 123.11 g/mol
Melting point

236.6 °C, 510 K, 458 °F

Boiling point


 Yes check.svgY (what is this?)  (verify)
Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa)
Infobox references

Niacin, also known as vitamin B3 or nicotinic acid, is an organic compound with the formula C5H4NCO2H. This colourless, water-soluble solid 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 Other forms of vitamin B3 include the corresponding amide, nicotinamide ("niacinamide"), where the carboxyl group has been replaced by a carboxamide group (CONH2), as well as more complex amides and a variety of esters.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 member of this family of compounds, since they have the same 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. Nicotinamide does not reduce cholesterol or cause flushing.[1] Nicotinamide may be toxic to the liver at doses exceeding 3 g/day for adults.[2] Niacin is a precursor to NADH, 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. In larger doses, niacin can reverse atherosclerosis by lowering low density lipoprotein (LDL) and favorably affecting other compounds.[4]



Niacin was first described by Hugo Weidel in 1873 in his studies of nicotine.[5] The original preparation remains useful: the oxidation of nicotine using nitric acid.[6] 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."[7] When the biological significance of nicotinic acid was realized, it was thought appropriate to choose a name to dissociate it from nicotine, 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 alkaline lime water of pH 11.[8] This process is known as nixtamalization.[9]

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" or "vitamin P-P".

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[10]. 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 .

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[11]. Common psychiatric symptoms of niacin deficiency include irritability, poor concentration, anxiety, fatigue, restlessness, apathy, and depression[11]. 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 cooking maize with alkaline 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.[12] The upper limit for adult men and women is 35 mg/day which is based on flushing as the critical adverse effect, this dose-dependent flushing effect consists of a single episode 10 to 20 minutes after niacin is taken. Skin flushing isn't technically considered a side effect as such; this flushing is caused by increased blood flow caused by the niacin and generally ceases after several days of taking it.

Hartnup’s disease is a hereditary nutritional disorder resulting in niacin deficiency[11]. 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 resulting condition is similar to pellagra, including symptoms of red, scaly rash and sensitivity to sunlight. Oral niacin is given as a treatment for this condition in doses ranging from 40–200 mg with a good prognosis if identified and treated early[11]. 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,[13] which are believed to be more reliable than plasma levels.[14]


Lipid modifying effects

In pharmacological doses, niacin has been proven to reverse atherosclerosis by reducing total cholesterol, triglyceride, very-low-density lipoprotein (VLDL), and low-density lipoprotein (LDL); and increasing high-density lipoprotein (HDL). It has been proposed that niacin has the ability to lower Lipoprotein(a) which is beneficial at reducing thrombotic tendency.[15]

Niacin, prescribed in doses between 1000 and 2000 mg two to three times daily,[16] 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.[17]

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.[18][19]

The ARBITER 6-HALTS study, reported at the 2009 annual meeting of the American Heart Association and in the New England Journal of Medicine[20] concluded that, when added to statins, 2000 mg/day slow-release niacin was more effective than Ezetimibe (Zetia) in reducing carotid intima-media thickness, a marker of atherosclerosis.[21]

As of August 2008, a combination of niacin with laropiprant is tested in a clinical trial. Laropiprant reduces facial flushes induced by niacin. [22] Taking 650 mg of aspirin 20–30 minutes prior to taking niacin has also been proven to prevent flushing in 90% of patients, presumably by suppressing prostaglandin synthesis,[2] and while this regimen also increases the risk of gastrointestinal bleeding,[3] the increased risk is less than 1 percent. [4]

Anti-Alzheimer's symptomatic effects

Vitamin B3 has been reported to prevent Alzheimer's-like symptoms in a mouse model of the disease.[23]


Pharmacological doses of niacin (1.5 - 6 g per day) often lead to 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. Side effects of hyperglycemia, cardiac arrhythmias and "birth defects in experimental animals" have also been reported.[24] The flush 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 several weeks of a consistent dose, most patients no longer flush.[25] Slow- or "sustained"-release forms of niacin have been developed to lessen these side-effects.[17][26] One study showed the incidence of flushing was significantly lower with a sustained release formulation[27] though doses above 2 g per day have been associated with liver damage, particularly with slow-release formulations.[24] Flushing is often thought to involve histamine, but histamine has been shown not to be involved in the reaction.[28] Prostaglandin (PGD2) is the primary cause of the flushing reaction, with serotonin appearing to have a secondary role in this reaction.[28]

High-dose niacin may also elevate blood sugar, thereby worsening diabetes mellitus.[24]

Hyperuricemia is another side-effect of taking high-dose niacin, and may exacerbate gout.[29]

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.[24]

Niacin at extremely high doses can have life-threatening acute toxic reactions.[30] 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.[31]

Inositol hexanicotinate

One popular form of dietary supplement is inositol hexanicotinate, which is inositol that has been esterified with niacin on all six of inositol's alcohol groups. Inositol hexanicotinate is usually sold as "flush-free" or "no-flush" niacin in units of 250, 500 or 1000 mg/tablet or capsule. It is sold as an over-the-counter formulation and often marketed and labeled as niacin, thus unfortunately misleading the consumer into thinking they are getting the active form of the medication, which they are not. 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.[32] One of the last of those studies affirmed the superiority of inositol and xantinol esters of nicotinic acid for reducing serum free fatty acid. [33] 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. [34] 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.

Biosynthesis and chemical synthesis

Biosynthesis: Tryptophankynurenine → niacin

The liver can synthesize niacin from the essential amino acid tryptophan, requiring 60 mg of tryptophan to make one mg of niacin.[35] 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.


The receptor for niacin is a G protein-coupled receptor called HM74A.[36] It couples to Gi alpha subunit.[37]

Food sources

Niacin is found in variety of foods including liver, chicken, beef, fish, cereal, peanuts and legumes and is also synthesized from tryptophan, which is found in meat, dairy and eggs.

Animal products:

shirms of mystick milk

Fruits and vegetables:





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