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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 Other forms of vitamin B3 include the corresponding amide, nicotinamide ("niacinamide"), where the carboxyl group has been replaced by a carboxamide group (CONH2), as well as more complex amides and a variety of esters.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. Nicotinamide may be toxic to the liver at doses exceeding 3 g/day for adults. Niacin is a precursor to NADH, NAD+, NADP+ and NADPH, which play essential metabolic roles in living cells.[title=Lehninger principles of biochemistry ] 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.
HistoryNiacin 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."[ coauthors = Madden, R.J.; Strongandd, F.M. ] 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.[title=Raw versus processed corn in niacin-deficient diets ]
This process is known as nixtamalization.[ title = Vitamin B3 ]
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 needsDepending 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. 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 (Prakash et al., 2008). Common psychiatric symptoms of niacin deficiency 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 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. 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. However, it has been reported anecdotally by some as a pleasant feeling.
Hartnup’s disease is an heretitary nutritional disorder 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 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. 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, which are believed to be more reliable than plasma levels.
Lipid modifying effectsIn pharmacological doses, niacin has been proven to reduce total cholesterol, triglyceride, very-low-density lipoprotein, low-density lipoprotein, and increase high-density lipoprotein levels.
Niacin, prescribed in doses between 1000 and 2000 mg two to three times daily,[title=Niacin Monograph ] 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.[title=Basic and clinical pharmacology ]
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.[title=Taking aim at HDL-C. Raising levels to reduce cardiovascular risk ][title=Fifteen year mortality in Coronary Drug Project patients: long-term benefit with niacin ]
as of August 2008, a combination of niacin with laropiprant is tested in a clinical trial. Laropiprant reduces facial flushes induced by niacin.
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]
A clinical study, results of which were presented at the 2009 annual meeting of the American Heart Association and published in the New England Journal of Medicine suggest that in combination with statins, Niaspan, a form of niacin, is more effective than Zetia at reducing arterial buildup.
Anti-Alzheimer's symptomatic effectsVitamin B3 has been reported to prevent Alzheimer's-like symptoms in a mouse model of the disease.
Oily skinClinical trials using niacinamide topically have demonstrated a decrease in sebum output by the face epithelial cells, helping in the treatment of acne and related affections. Anecdotally there have been reports of successful control in cases of excessive output of sebum using dietary supplementation of Niacin (the flushing kind) at a dosage of 500mg to 1000mg a day.
ToxicityPharmacological 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 have also been reported.[title=Goodman & Gilman's the pharmacological basis of therapeutics ] 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. Slow- or "sustained"-release forms of niacin have been developed to lessen these side-effects.[ Flushing is often thought to involve histamine, but histamine has been shown not to be involved in the reaction.][
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