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this is want a learn today Niacin (also known as vitamin B3 or nicotinic acid) is an organic compound with the formula C 6H 5NO 2 and depending on the definition used, one of the 20 to 80 essential human nutrients.

Insufficient niacin in the diet can cause nausea, skin and mouth lesions, anemia, headaches, and tiredness. Chronic niacin deficiency leads to a disease called pellagra. The lack of niacin may also be observed in pandemic deficiency disease, which is caused by a lack of five crucial vitamins (niacin, vitamin C, thiamin, vitamin D, and vitamin A) and is usually found in areas of widespread poverty and malnutrition. Niacin has not been found to be useful in decreasing the risk of cardiovascular disease in those already on a statin[3] but appears to be effective in those not taking a statin.[4]

This colorless, 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forms of vitamin B3 include the corresponding amide and nicotinamide ("niacinamide"), where the carboxyl group has been replaced by a carboxamide group (CONH 2), as well as more complex amides and a variety of esters.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 8,500 tonnes per year in the 1980s to 40,000 in recent years.[5]

Niacin cannot be directly converted to nicotinamide, but both compounds are precursors of the coenzymes nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP) in vivo.[6] NAD converts to NADP by phosphorylation in the presence of the enzyme NAD+ kinase. NADP and NAD are coenzymes for many dehydrogenases, participating in many hydrogen transfer processes.[7] NAD is important in catabolism of fat, carbohydrate, protein, and alcohol, as well as cell signaling and DNA repair, and NADP mostly in anabolism reactions such as fatty acid and cholesterol synthesis.[7] High energy requirements (brain) or high turnover rate (gut, skin) organs are usually the most susceptible to their deficiency.[8] 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.[9] Niacin is involved in both DNA repair and the production of steroid hormones in the adrenal gland.

Contents [hide] 1 Dietary needs 2 Deficiency 3 Medical uses 4 Toxicity 5 Mechanism of action 6 Nicotinamide 7 Inositol hexanicotinate 8 Biosynthesis and chemical synthesis 9 Food sources 10 Preparations 11 History 12 References 13 External links

Dietary needs[edit]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.[10] 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,[11] which are believed to be more reliable than plasma levels.[12]

Deficiency[edit]Main article: Pellagra Between 1906 and 1940 more than 3 million Americans were affected by pellagra with more than 100,000 deaths. Dr. Joseph Goldberger was assigned to study pellagra by the Surgeon General of the United States and produced good results. In the late 1930s, studies by Dr. Tom Spies, Marion Blankenhorn, and Clark Cooper established that niacin cured pellagra in humans. The disease was greatly reduced as a result.

A man with pellagra, which is caused by a chronic lack of vitamin B3 in the dietAt present, niacin deficiency is sometimes seen in developed countries, and it is usually apparent in conditions of poverty, malnutrition, and chronic alcoholism.[13] It also tends to occur in areas where people eat maize (corn) as a staple food, since it is the only grain low in digestible niacin. 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.[14] Common psychiatric symptoms of niacin deficiency include irritability, poor concentration, anxiety, fatigue, restlessness, apathy, and depression.[14] 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.[14] 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.[14] Niacin synthesis is also deficient in carcinoid syndrome, because of metabolic diversion of its precursor tryptophan to form serotonin.

Medical uses[edit]A 2014 review of niacin did not find that it affected either cardiovascular disease or risk of death in those already taking a statin.[3] Niacin alone appears to reduce the risk of cardiovascular disease.[15][16]

The National Cholesterol Education Program (NCEP) in 2002 recommended niacin alone for cardiovascular and atherogenic dyslipidemia in mild or normal LDL levels or in combination for higher LDL levels.[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 people with low HDL, who are also at high risk of a heart attack.[18]

Toxicity[edit]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.[citation needed] 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.[19]

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.[20][21] Langerhans cells use cyclooxygenase type 1 (COX-1) for PGE2 production and are more responsible for acute flushing while keratinocytes are COX-2 dependent and are in active continued vaso-dilation.[22][23] To reduce flushing many studies focused on altering or blocking the prostaglandin mediated pathway.[24] 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.[25] Slow- or "sustained"-release forms of niacin have been developed to lessen these side effects.[26][27] One study showed the incidence of flushing was significantly lower with a sustained release formulation[28] though doses above 2 g per day have been associated with liver damage, in particular, with slow-release formulations.[19] Flushing is often thought to involve histamine, but histamine has been shown not to be involved in the reaction.[29] Prostaglandin (PGD2) is the primary cause of the flushing reaction, with serotonin appearing to have a secondary role in this reaction.[29]

Hepatotoxicity is another side effect of niacin. This is possibly related to metabolism via amidation resulting in NAD production.[30] The time-release form has a lower therapeutic index for lowering serum lipids relative to this form of toxicity.[31]

Although high doses of niacin may elevate blood sugar, thereby worsening diabetes mellitus,[19] 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 overall, 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.[32]

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.[19]

Niacin, particularly the time-release variety, at extremely high doses can cause acute toxic reactions.[33] 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.[34]

Mechanism of action[edit]Niacin therapeutic effect is mostly through its binding to G protein coupled receptors, niacin receptor 1 (NIACR1) and niacin receptor 2 (NIACR2), that are highly expressed in adipose tissue, spleen, immune cells and keratinocytes but not in other expected organs such as liver, kidney, heart or intestine.[35][36] NIACR1 inhibits cyclic adenosine monophosphate (cAMP) production and thus fat breakdown in adipose tissue and free fatty acids available for liver to produce triglycerides and very-low-density lipoproteins (VLDL) and consequently low-density lipoprotein (LDL) or "bad" cholesterol.[30][37] 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.[38] 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 increases apolipoprotein A1 levels due to anti catabolic effects resulting in higher reverse cholesterol transport. It also inhibits HDL hepatic uptake, down-regulating production of the cholesterol ester transfer protein (CETP) gene.[39] Finally, it stimulates the ABCA1 transporter in monocytes and macrophages and up-regulates peroxisome proliferator-activated receptor γ results in reverse cholesterol transport.[40]

It reduces secondary outcomes associated with atherosclerosis, such as low density lipoprotein cholesterol (LDL), very low-density lipoprotein cholesterol (VLDL-C), and triglycerides (TG), but increases high density lipoprotein cholesterol (HDL).[39] Despite the importance of other cardiovascular risk factors, high HDL was associated with fewer cardiovascular events independent of LDL reduction.[41][42] Other effects include anti-thrombotic and vascular inflammation, improving endothelial function, and plaque stability.[43] 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.[44]

Nicotinamide[edit]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).[45]

Nicotinamide may be toxic to the liver at doses exceeding 3 g/day for adults.[46]

Inositol hexanicotinate[edit]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.[47] One of the last of those studies affirmed the superiority of inositol and xantinol esters of nicotinic acid for reducing serum free fatty acid,[48] but other studies conducted during the same period found no benefit.[49] 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.[50] 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). bye love pants•$\langle\rangle$