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Group Members: Billy Sheehan
All Music Guide:
Having played straightforward hard rock with Mr. Big since the tail end of the '80s, bass virtuoso Billy Sheehan formed Niacin as an outlet for his jazz fusion and prog rock inclinations during the mid-'90s. The trio also featured keyboardist John Novello and drummer Dennis Chambers, both musicians who had crossed frequently between the worlds of jazz and rock during their careers. With Niacin, Novello devoted himself especially to the Hammond B-3 organ, a longtime mainstay of both jazz and prog rock. The band recorded a self-titled debut album in 1996, following it up in 1998 with High Bias. An import-only concert recording, Live!: Blood, Sweat and Beers, surfaced later that year as well. For their next album, Niacin moved from Stretch to Magna Carta, the label that became virtually synonymous with technique-oriented neo-prog rock at the turn of the millennium. Deep was released in 2000 and featured the group's first vocal track, courtesy of special guest Glenn Hughes (Deep Purple), as well as Toto guitarist and session ace Steve Lukather.
Niacin (also known as vitamin B, nicotinic acid and vitamin PP) is an organic compound with the formula NO and, depending on the definition used, one of the 40 to 80 essential human nutrients.
Niacin is one of five vitamins (when lacking in human diet) associated with a pandemic deficiency disease: niacin deficiency (pellagra), vitamin C deficiency (scurvy), thiamin deficiency (beriberi), vitamin D deficiency (rickets and osteomalacia), vitamin A deficiency (night blindness and other symptoms). Niacin has been used for over 50 years to increase levels of HDL in the blood and has been found to modestly decrease the risk of cardiovascular events in a number of controlled human trials.
This colorless, water-soluble solid is a derivative of pyridine, with a carboxyl group (COOH) at the 3-position. Other forms of vitamin B include the corresponding amide, nicotinamide ("niacinamide"), where the carboxyl group has been replaced by a carboxamide group (CONH), as well as more complex amides and a variety of esters. Nicotinic acid and niacinamide are convertible to each other with steady world demand rising from 8500 tonnes per year in 1980s to 40,000 in recent years.
Niacin cannot be directly converted to nicotinamide, but both compounds could be converted to NAD and NADP in vivo. Nicotinic acid, nicotinamid, and tryptophan (via quinoline acid) are co-factors for nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP). NAD converts to NADP by phosphorylation in the presence of the enzyme NAD-kinase. NADP and NAD are coenzyme for many dehydrogenases, participating in many hydrogen transfer processes. NAD is important in catabolism of fat, carbohydrate, protein and alcohol as well as cell signaling and DNA repair and NADP mostly in anabolism reaction such as fatty acid and cholesterol synthesis. High energy requirements (brain) or high turnover rate (gut, skin) organs are usually the most susceptible to their deficiency. Although the two are identical in their vitamin activity, nicotinamide does not have the same pharmacological effects (lipid modifying effects) as niacin. 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 NAD+/NADH and NADP+/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.
Dietary needs 
One 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. Tolerable upper intake levels (UL) for adult men and women is considered to be 35 mg/day by the Dietary Reference Intake system to avoid flushing. In general, niacin status is tested through urinary biomarkers, which are believed to be more reliable than plasma levels.
At present, niacin deficiency is sometimes seen in developed countries, and it is usually apparent in conditions of poverty, malnutrition, and chronic alcoholism. It also tends to occur in areas where people eat maize (corn, the only grain low in digestible niacin) as a staple food. A special cooking technique called nixtamalization is needed to increase the bioavailability of niacin during maize meal/flour production.
Mild niacin deficiency has been shown to slow metabolism, causing decreased tolerance to cold.
Severe deficiency of niacin in the diet causes the disease pellagra, which is characterized by diarrhea, dermatitis, and dementia, as well as “Casal's 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. Common psychiatric symptoms of niacin deficiency include irritability, poor concentration, anxiety, fatigue, restlessness, apathy, and depression. 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. Patients with alcoholism typically experience increased intestinal permeability, leading to negative health outcomes.
Hartnup’s disease is a hereditary nutritional disorder resulting in niacin deficiency. This condition was first identified in the 1950s 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.
Therapeutic effects 
In 1955, Altschul et al. (1955) described niacin as lipid lowering property for the first time that followed by subsequent studies. Niacin is the oldest lipid lowering drug with unique anti atherosclerotic property. It reduces traditional parameters such as low density lipoprotein cholesterol (LDL), very low-density lipoprotein cholesterol (VLDL-C) and triglycerides (TG) but effectively increases high density lipoprotein cholesterol (HDL). Despite the importance of other cardiovascular risk factors, high HDL correlated to lower cardiovascular event independent of LDL reduction Other effects include anti-thrombotic and vascular inflammation, improving endothelial function and plaque stability. Niacin alone or in combination with other lipid lowering agents such as statin or ezetimibe significantly reduces risk of cardiovascular disease and arthrosclerosis progression. Niacin therapeutic effect is mostly through its specific G protein coupled receptor (GPR109A and GPR109B) recently named as hydroxyl carboxylic acid (HCA) receptor 2 that highly expressed in adipose tissue, spleen, immune cells and keratinocytes but not in other expected organs such as liver, kidney, heart or intestine. GPR109A inhibits cyclic adenosine monophosphate production and thus lipolysis and free fatty acids available for liver to produce TG and VLDL and consequently LDL. Decrease in free fatty acids also suppress hepatic expression of apolipoprotein C3 (APOC3) and PPARg coactivator-1b (PGC-1b) thus increase VLDL turn over and reduce its production. It also inhibits diacylglycerol acyltransferase-2 (important hepatic TG synthesis). The mechanism behind increasing HDL is not totally understood but it seems to be done in various ways. Niacin increase apolipoprotein A1 levels due to anti catabolic effects resulting in higher reverse cholesterol transport. It also inhibits HDL hepatic uptake, down regulating production of cholesterol ester transfer protein (CETP) gene. Finally, it stimulates ABCA1 transporter in monocytes and macrophages and up regulates peroxisome proliferator-activated receptor γ results in reverse cholesterol transport. Improving vascular endothelial function has been reported in few experiments using niacin. In an experiment on type 2 diabetes, nicotinic acid improved endothelial function comparing with control. Daily dose of 1 g niacin shows significant lipid modifying properties and reach the plateau using 2 grams. GPR109A in immune cells such as monocytes, macrophages, and dendritic cells is responsible for atherosclerosis effects of niacin by reducing the immune cells’ infiltration of vessel wall It also down regulates endothelial adhesion molecules such as vascular cell adhesion molecule 1 (VCAM-1) or of chemokines such as monocyte chemotactic protein 1 (MCP-1) and inflammatory proteins which results in atherosclerotic stabilization and antithrombotic effects. The changes in adhesion molecules and chemokines might be through activation of receptor GPR109A on immune cells. Adipokines are the adipocytes’ produced mediators. Some adipokines such as tumor necrosis factor (TNF)-a, interleukins and chemokines, have pro-inflammatory effect and some others such as adiponectin have anti-inflammatory effect that regulates inflammatory process, decrease vascular progression and atherosclerosis. Nicotinic acid increase adiponectin plasma levels in humans and mice but inhibits pro-inflammatory chemokines such as MCP-1 and fractalkin. Other recently explored therapeutic effect of nicotinic acid are neuroprotective and anti-inflammatory effects, beneficial in animal models of arthritis, chronic renal failure or sepsis however more work needed in this area. Following Coronary Drug Project (CDP) as one of the first experiments being done to study long term clinical lipid lowering effect of niacin in 1960’s to early 1970’s, (JAMA, 1975) many other experiments been done. Their result been summarized in two most recent meta analysis concluded that therapeutic doses of niacin alone or in combination with other lipid modifying agents such as statin reduce cardiovascular event and arthrosclerosis progression significantly. This agrees with current Nation Cholesterol Education Program (NCEP) on high cholesterol treatment. NCEP recommends niacin alone for cardiovascular and atherogenic dyslipidemia in mild or normal LDL levels or in combination for higher LDL levels (NCEP, 2002). 1500 mg Immediate release niacin daily results in 13% LDL, 20% LP, 10% TG reduction and 19% HDL increase comparing to placebo. Extended release niacin alone or with anti-flushing agent (laropiprant) shows similar effects.
Niacin binds to and stimulates a G-protein-coupled receptor, GPR109A, which causes the inhibition of fat breakdown in adipose tissue. Nicotinamide does not bind this receptor which explains why it does not affect blood lipid levels. Lipids that are liberated from adipose tissue are normally used to build very-low-density lipoproteins (VLDL) in the liver, which are precursors of low-density lipoprotein (LDL) or "bad" cholesterol. Because niacin blocks the breakdown of fats, it causes a decrease in free fatty acids in the blood and, as a consequence, decreases the 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 people with low HDL, who are also at high risk of a heart attack.
The ARBITER 6-HALTS study, reported at the 2009 annual meeting of the American Heart Association and in the New England Journal of Medicine concluded that, when added to statins, 2000 mg/day of extended-release niacin was more effective than ezetimibe (Zetia) in reducing carotid intima-media thickness, a marker of atherosclerosis. Additionally, a recent meta-analysis covering 11 randomized controlled clinical trials found positive effects of niacin alone or in combination on all cardiovascular events and on atherosclerosis evolution.
However, a 2011 study (AIM-HIGH) was halted early because patients showed no decrease in cardiovascular events, but did experience an increase in the risk of stroke. These patients already had LDL levels well controlled by a statin drug, and the aim of the study was to evaluate extended-release niacin (2000 mg per day) to see if raising HDL levels had an additional positive effect on risk. In this study, it did not have such an effect, and appeared to increase stroke risk. The role of niacin in patients whose LDL is not well-controlled (as in the majority of previous studies with niacin) is still under study and debate. However, it does not seem to offer benefits via raising HDL, in patients already lowering LDL by taking a statin.
Niacin prescriptions 
Different niacin prescriptions are in the market. Immediate release that is quickly absorbed has more flushing effect and less hepatotoxic. Extended release (Niapsen) with more balanced metabolism which absorbs in 8–12 hours and results in less flushing and lower hepatotoxicity. New Niapsen called R-Niapsen has even lower flushing intensity and duration and could be consumed with aspirin. Laropiprant (Merck & Co., Inc.) is another recent niacin formulation with prostaglandin D2 binding capacity that mediated vaso-dilation and reduced flushing up to 73% that has been approved in Europe but awaiting Food and Drug Administration (FDA) approval. There are few over-the counter niacin dietary supplements which lack the safety and efficacy data required for FDA regulatory approval. For example, the type “no flush” contains several non convertible niacin compounds with little clinical activity or “slow release” has higher hepatotoxic activity hence non-prescription niacin is not recommended due to potential harm.
Pharmacological doses of niacin (1.5 - 6 g per day) lead to side effects that can include dermatological conditions such as skin flushing and itching, dry skin, and skin rashes including eczema exacerbation and acanthosis nigricans. Some of these symptoms are generally related to niacin's role as the rate limiting cofactor in the histidine decarboxylase enzyme which converts l-histidine into histamine. H1 and H2 receptor mediated histamine is metabolized via a sequence of mono (or di-) amine oxidase and COMT into methylhistamine which is then conjugated through the liver's CYP450 pathways. Persistent flushing and other symptoms may indicate deficiencies in one or more of the cofactors responsible for this enzymatic cascade. Gastrointestinal complaints, such as dyspepsia (indigestion), nausea 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.
Flushing usually lasts for about 15 to 30 minutes, though it can sometimes last up to two hours. It is sometimes accompanied by a prickly or itching sensation, in particular, in areas covered by clothing. Flushing is mediated by prostaglandin E2 and D2 due to GPR109A activation of epidermal langerhans’ cells and keratinocytes. Langerhans use cyclooxygenase type 1 (COX-1) for PGE2 production and are more responsible for acute flushing while keratinocutes are COX-2 dependent and are in active continued vaso-dilation. To reduce flushing many studies focused on altering or blocking the prostaglandin mediated pathway. This effect is mediated by GPR109A-mediated prostaglandin release from the Langerhans cells of the skin and can be blocked by taking 300 mg of aspirin half an hour before taking niacin, by taking one tablet of ibuprofen per day or by co-administering the prostaglandin receptor antagonist laropiprant. 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. 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, in particular, with slow-release formulations. Flushing is often thought to involve histamine, but histamine has been shown not to be involved in the reaction. Prostaglandin (PGD) is the primary cause of the flushing reaction, with serotonin appearing to have a secondary role in this reaction.
Hepatotoxicity is another side effect of niacin. Metabolizing niacin occurs in liver in 2 ways one through conjugation pathway producing nicotinuric acid metabolite related to flushing the other is amidation resulting in NAD production related to hepatotoxicity.
Although high doses of niacin may elevate blood sugar, thereby worsening diabetes mellitus, recent studies show the actual effect on blood sugar to be only 5–10%. Patients with diabetes who continued to take anti-diabetes drugs containing niacin did not experience major blood glucose changes. Thus looking at the big picture, niacin continues to be recommended as a drug for preventing cardiovascular disease in patients with diabetes.
Hyperuricemia is another side effect of taking high-dose niacin, and may exacerbate gout.
Niacin in doses used to lower cholesterol levels has been associated with birth defects in laboratory animals, with possible consequences for infant development in pregnant women.
Niacin, particularly the time-release variety, at extremely high doses can cause 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 niacin intake ceases.
Nicotinamide may be obtained from the diet where it is present primarily as NAD+ and NADP+. These are hydrolysed in the intestine and the resulting nicotinamide is absorbed either as such, or following its hydrolysis to nicotinic acid. Nicotinamide is present in nature in only small amounts. In unprepared foods, niacin is present mainly in the form of the cellular pyridine nucleotides NAD and NADP. Enzymatic hydrolysis of the co-enzymes can occur during the course of food preparation. Boiling releases most of the total niacin present in sweet corn as nicotinamide (up to 55 mg/kg).
Inositol hexanicotinate 
One form of dietary supplement is inositol hexanicotinate (IHN), which is inositol that has been esterified with niacin on all six of inositol's alcohol groups. IHN is usually sold as "flush-free" or "no-flush" niacin in units of 250, 500, or 1000 mg/tablets or capsules. It is sold as an over-the-counter formulation, and often is marketed and labeled as niacin, thus misleading consumers into thinking they are getting the active form of the medication. 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. One of the last of those studies affirmed the superiority of inositol and xantinol esters of nicotinic acid for reducing serum free fatty acid, but other studies conducted during the same period found no benefit. Studies explain that this is primarily because "flush-free" preparations do not contain any free nicotinic acid. 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. Thus, so far there is not enough evidence to recommend IHN 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. Thus liver function tests to monitor liver enzymes are necessary when taking therapeutic doses of niacin, including alkaline phosphatase (ALP), aspartate transaminase (AST), and alanine transaminase (ALT).
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. Riboflavin, vitamin B and iron are required in some of the reactions involved in the conversion of tryptophan to NAD.
Several million kilograms of niacin are manufactured each year, starting from 3-methylpyridine.
In addition to its effects as NAD and NADP, niacin may have additional effects by receptor activation. The receptor for niacin is a G protein-coupled receptor called HM74A. It couples to the Gi alpha subunit.
Food sources 
Niacin is found in variety of foods, including liver, chicken, beef, fish, cereal, peanuts and legumes, and is also synthesized from tryptophan, an essential amino acid found in most forms of protein.
Animal products:liver, heart and kidney (9 – 15 mg niacin per 100 grams)chicken, chicken breast (6.5 mg)beef (5 – 6 mg)fish: tuna, salmon, halibut (2.5 – 13 mg)eggs (0.1 mg)
Fruits and vegetables:avocados (1 mg niacin per 100 grams)dates (2 mg)tomatoes (0.7 mg)leaf vegetables (0.3 - 0.4 mg)broccoli (0.6 mg)carrots (0.3 - 0.6 mg)sweet potatoes (0.5 - 0.6 mg)asparagus (0.4 mg)
Seeds:nuts (2 mg niacin per 100 grams)whole grain products (4 - 29.5 mg)legumes (0.4 – 16 mg)saltbush seeds
Fungi:mushrooms, shiitake mushrooms (3.5 – 4 mg niacin per 100 grams)brewer's yeast (36 mg)
Other:Monster Energy drink (40 mg per 16 ounces)Rockstar Energy (100% in the Super Sours flavors)Red Bull Energy Drink (28 mg per 12 ounces)Five Hour Energy drink (30 mg per 1.93 ounces)Ovaltine (18 mg)Peanut butter (15 mg)TofuSoy sauce (0.4 mg)Vegemite (from spent brewer's yeast) (110 mg niacin per 100 grams)
Niacin was first described by chemist 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 biochemist Conrad Elvehjem in 1937, who later identified the active ingredient, then referred to as the "pellagra-preventing factor" and the "anti-blacktongue factor." Soon after, in studies conducted in Alabama and Cincinnati, Dr. Tom Spies found that nicotinic acid cured the sufferers of pellagra.
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 be released only in very alkaline lime water of pH 11. This process, known as nixtamalization, was discovered by the prehistoric civilizations of Mesoamerica.
Niacin is referred to as vitamin B 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".
As of August 2008, a combination of niacin with laropiprant is being tested in a clinical trial. Laropiprant reduces facial flushes induced by niacin.