In fact, niacin has been associated with an increase in hdl by as much as 30%. Clinical trial evidence demonstrates its ability to raise hdlc and lower ldlc, lipoprotein a, and triglycerides. The liver is a major organ for the production and secretion of apo b, its associated lipids, and subsequently vldl, ldl, and lpa particles. The mechanism of action of vitamin b12 in the human body. Niacin for treatment of nonalcoholic fatty liver disease. How niacin may treat depression mechanisms of action it is possible that niacin might be an effective standalone andor adjunct treatment for depression in a subset of individuals, however, since it hasnt been wellresearched for this purpose, its hypothetical mechanism of antidepressant action remains unclear. Use of niacin for primary or secondary prevention of. Although niacin treatment is effective in children, adverse reactions are common. It prevents liver fibrosis in animals and decreases collagen in cultured human stellate cells. As pharmacologic agents, however, they differ markedly. The mechanism behind niacin increasing hdl is not totally understood, but. Nicotinic acid has key action sites in both the liver and adipose tissue. The mechanism for niacin associated flushing and hepatotoxicity. Introduction niacin is the vitamin b 3 and has fundamental roles as part of reductionoxidation coenzymes involved in energy metabolism, amino acid metabolism, and detoxification reactions for drugs and other substances.
There has been renewed interest in nicotinic acid owing to the need for improved prevention of. Although niacin has been commonly used to increase plasma hdl levels, the mechanisms by which niacin exerts its action is not clearly understood, wrote the authors from the university of california, irvine and. It has the formula c 6 h 5 no 2 and belongs to the group of the pyridinecarboxylic acid niacin is obtained in the diet from a variety of whole and processed foods, with highest contents in fortified packaged foods, meat, poultry, red fish such as tuna. Recently, a number of laboratories have reported nonlipoprotein mediated effects of niacin that may have a bearing on atherosclerosis progression and risk. Niacin acts directly on peripheral vessels, dilating cutaneous vessels and increasing blood flow, predominantly in the face, neck, and chest. Current evidence indicates that the posttranslational apob degradative processes regulate the. Both brands contained mg of niacin and 20 mg of laropiprant in each tablet. Mechanism of action of niacin request pdf researchgate. Your body stores some vitamin b12 in your liver, but you also need to consume 2.
Although niacin has been commonly used to increase plasma hdl levels, the mechanism s by which niacin exerts its action is not clearly understood, wrote the authors from the university of california, irvine and the atherosclerosis research center, va healthcare system in long beach. Mechanisms of flushing due to niacin and abolition of these. Na is the only lipid lowering agent that can improve all lipid risk factors tc, hdl. The new study moves us closer to an answer, and should. Nicotinic acid inhibits lipolysis in adipose tissues. Dietary requirements for niacin can be met by the ingestion of either nicotinic acid or nicotinamide. Niacin mechanism of action thomas dayspring md, facp 11 niacin through mechanisms that are not well understood, but almost certainly related to its ppar gamma agonism has multiple pleiotropic effects such as increasing adiponectin, reducing creactive protein especially when combined with a statin and lipoprotein associated phospholipase a2. Its unlikely that you have a deficiency of niacin also known as vitamin b3 if youre including meat, dairy and fortified grains in your diet and dont have a specific difficulty with absorbing it. After week 8, titrate to patient response and tolerance. Hall found that the benefits of niacin were most pronounced when taken on an empty. It may involve several actions including partial inhibition of release of free fatty acids from adipose tissue, and increased lipoprotein lipase activity, which may increase the rate of chylomicron triglyceride removal from plasma.
Nicotinic acid niacin has been used for decades to prevent and treat atherosclerosis. Acute niacin administration results in a rapid reduction of plasma ffa concentrations and reverses insulin resistance induced by lipid overload. Mechanism of action of niacin to modulate tg synthesis and secretion of vldl and ldl particles by liver. Because the mevalonate metabolism generates a series of isoprenoids vital for different cellular functions, from cholesterol synthesis to the control of cell growth and differentiation, hmgcoa reductase inhibition has beneficial pleiotropic effects. Furthermore, continued exposure to niacin at above flush threshold doses usually leads to disappearance of the flush response in a few days or weeks. Two case reports on the treatment of acute migraine with. Longterm niacin treatment induces insulin resistance and. The action of aspirin in preventing the niacin flush and. Mechanism of action tap to return to kiosk menu niacin nicotinic acidna is the first lipid lowering agent shown to reduce asvd events and long term mortality. It is generally accepted that the increased concentrations of apolipoprotein apo b containing very lowdensity lipoproteins vldl and lowdensity lipoproteins ldl, and decreased levels of apo ai containing highdensity lipoproteins hdl are correlated to atherosclerotic cardiovascular disease. Niacin has diverse mechanisms of action 9, including inhibition of diacylglycerol acyltransferase dgat 2, which results in decreased hepatic vldl production 51 52 53 55. Niacin, after undergoing biochemical reactions in the mitochondria with nicotinamide, and tryptophan. Coq10 supplements are sometimes used to treat statinassociated myopathy, though evidence of their efficacy is lacking as of 2017.
Niaspan niacin extendedrelease tablet, film coated, extended release for oral use. There has been renewed interest in nicotinic acid owing to the need for improved prevention of atherosclerosis in patients already taking. Pharmacological doses of nicotinic acid induce a profound change in the plasma levels of various lipids and lipoproteins. Niacin mechanism of action thomas dayspring md, facp acylcholesterol acyl transferase acat, and upregulation of several membrane sterol efflux transporters of the atp biding cassette abc transporter family. Druginduced liver injury can occur through direct hepatotoxicity or an immunemediated hepatotoxic mechanism. Mechanism of action of niacin on lipoprotein metabolism. The cell study indicates that niacin may reduce the removal of hdl good cholesterol by about 35 per cent, according to findings published in the journal of lipid research. In the liver, nicotinic acid inhibits diacylglycerol acyltransferase2 resulting in decreased. Introduction mechanisms of action multiple tissuecellular target sites of action of niacin clinical utilization of niacin clinical outcome trials wit.
Coenzyme q10 ubiquinone levels are decreased in statin use. It has been proven effective at lowering vldl, ldl, total cholesterol and triglyceride levels while raising hdl levels. Niacin inhibits and reverses hepatic steatosis and inflammation in animals and liver cell cultures. The action of aspirin in preventing the niacin flush and its. New findings indicate that niacin directly and noncompetitively inhibits hepatocyte diacylglycerol acyltransferase2, a key enzyme for tg. Niacin lowers cholesterol and triglyceride levels by an unknown mechanism. A further mechanism of action of niacin consists of the ability of nicotinic acid to stimulate the activity of lipoprotein lipase, thus increasing the clearance of vldl. You should not take niacin if you have severe liver disease, a stomach ulcer, or active bleeding. Mechanisms of flushing due to niacin and abolition of.
Vitamin b12 has several mechanisms of action in your body that are crucial to maintaining your well being. In addition, lipid overload in the form of high ffa concentrations in nonadipose tissues has been linked to insulin resistance in muscles, but details of the mechanism are still controversial. Although decreased free fatty acid mobilization from adipose tissue via the g proteincoupled receptor 109a niacin receptor has been a widely suggested. Sep 23, 2011 nicotinic acid niacin has been used for decades to prevent and treat atherosclerosis. Niacin thus seems to induce decreased adipocyte insulin responsiveness via more than one mechanism. Current evidence indicates that the posttranslational apob. Niacin, also known as nicotinic acid, is an organic compound and a form of vitamin b3. The most recent data on niacins mechanism of action indicate that it directly inhibits hepatic diacylglycerol acyltransferase 2, resulting in an inhibition of triglyceride synthesis and decreased apolipoprotein bcontaining lipoproteins. Mechanism of action of niacin american journal of cardiology. The hepatotoxicity of niacin is most associated with the sustainedrelease formulation and the production of nicotinamide adenine dinucleotide via the amidation. Niacin can cause certain side effects, such as flushing warmth, itching, redness, or tingly feeling under your skin. Niacin is an antilipemic agent used to treat dyslipidemia. Vitamin b3 niacin niacin is found in, and critical for the health of every cell in your body.
Mechanism of action, and pleiotropic effects sylvia christakos, puneet dhawan, annemieke verstuyf, lieve verlinden, and geert carmeliet department of microbiology, biochemistry and molecular genetics, rutgers, the state university of new jersey, new jersey medical school, newark, new jersey. Nadh is the reduced form of nad nicotinamide adenine dinucleotide, making it the active form which can donate electrons nadh is the primary carrier of electrons from glucose and lactate for atp synthesis. The isolation and identification of the antiblacktongue factor j pdf. The welldocumented antiatherogenic activity is believed to result from its antidyslipidemic effects, which are accompanied by unwanted effects, especially a flush. The ability of nicotinic acid to strongly increase the plasma concentration of highdensity lipoprotein hdl cholesterol has in recent years led to an increased interest in the pharmacological potential of nicotinic acid. Although decreased free fatty acid mobilization from adipose tissue via the g proteincoupled receptor 109a niacin receptor has been a widely suggested mechanism of niacin to decrease tgs. Niacin mechanism of action thomas dayspring md, facp. It is generally accepted that the increased concentrations of apolipoprotein apo b containing very lowdensity lipoproteins vldl and lowdensity lipopr. Aims to summarise the metabolic responses to niacin that can lead to flushing and to critically evaluate flushing mitigation research. Learn more about niacin and niacinamide vitamin b3 uses, effectiveness, possible side effects, interactions, dosage, user ratings and products that contain niacin and niacinamide vitamin b3. By upregulating lipase expression from adipose tissue, niacin increases vldl clearance 51,55. The precise mechanism of action of nicotinic acid has not been elucidated fully, but the bulk of the evidence supports the view that the biosynthesis of cholesterol perhaps other lipids is impaired by nicotinic acid administration. Thus it seems likely that modulation of the inflammatory mechanisms is a basic part of the pharmacological action of megadose niacin therapy.
Read mechanism of action of niacin on lipoprotein metabolism, current atherosclerosis reports on deepdyve, the largest online rental service for scholarly research with thousands of academic publications available at your fingertips. Introduction mechanisms of action multiple tissuecellular target sites of action of niacin clinical utilization of. However, your doctor or naturopath might prescribe niacin to treat blood lipid disorders, such as high cholesterol and high triglycerides, as an alternative to statins. Pubmed was searched from 1960 to 2008 using the terms niacin, flushing, laropiprant, prostaglandins and aspirin.
Consequently, statins reduce significantly the incidence of coronary. Niacin effects on cholesterol mechanism of action youtube. Although decreased free fatty acid mobilization from adipose tissue via the g proteincoupled receptor 109a niacin receptor has been a widely suggested mechanism of niacin to decrease tgs, physiologically and clinically, this pathway may be only a minor factor in explaining the lipid effects of niacin. One slowrelease niacin product, niaspan nicotinic acid in an ion. Niacin favorably affects all lipids and lipoproteins when given in pharmacological doses. If response to mgday is inadequate, increase dose to 1500 mgday po at bedtime. Na is the only lipid lowering agent that can improve all lipid risk factors tc. Niacin may be metabolized by either a conjugative or amidation pathway. See text below for more information about niacin and its effects on lipids overall. In adipocytes, it inhibits the lipolysis of triglycerides and retards the mobilisation of free fatty acids ffas to the plasma. Niacin favorably affects apolipoprotein apo bcontaining lipoproteins eg, verylowdensity lipoprotein vldl, lowdensity lipoprotein ldl, lipoproteina and increases apo aicontaining lipoproteins highdensity lipoprotein hdl. Component of two coenzymes necessary for lipid metabolism, tissue respiration, glycogenolysis, inhibition of very lowdensity lipoprotein vldl synthesis. Nicotinic acid niacin has long been used for the treatment of lipid disorders and cardiovascular disease. Niacin may also be used for purposes not listed in this medication guide.
On the mechanism of action of nicotinic acid in lowering. Nadh is the primary carrier of electrons from glucose and lactate for atp synthesis. The ability of nicotinic acid to strongly increase the plasma concentration of high density lipoprotein hdl cholesterol has in recent years led to. Niacin fda prescribing information, side effects and uses. Abstract niacin has long been prescribed for the treatment of various cardiovascular conditions, particularly the hyperlipidemias. Its mechanism of action is by oxidative stress reduction and inhibition of diacylglycerol acyltransferase 2 and other possible targets. Pharmacological effects and mechanisms of action pharmacological doses of nicotinic acid induce a profound change in the.
Specifically, abca1 transporters efflux cholesterol from within cells into a cholesterol acceptor protein, namely apoai. Niacin is one of the essential nutrients for the human body. Sep 20, 2017 see text below for more information about niacin and its effects on lipids overall. Highlights of prescribing information these highlights do not include all the information needed to use niaspan safely and effectively. Niacin, also referred to as vitamin b3 or nicotinic acid, is recognized as a cardioprotective agent, primarily due to its action in inhibiting triglyceride synthesis,1 resulting in both an increased hdl, and a lowered triglyceride level. The risk of statininduced rhabdomyolysis increases with older age, use of interacting medications such as fibrates, and hypothyroidism. It has the formula c 6 h 5 no 2 and belongs to the group of the pyridinecarboxylic acid. Jun 01, 2019 niacin extendedrelease tablets usp also contain the inactive ingredients. Niacin, also known as nicotinic acid, is an organic compound and a form of vitamin b3, an essential human nutrient. Tenyear mortality from cardiovascular disease in relation to. The mechanism and mitigation of niacininduced flushing. In conclusion, longterm niacin treatment resulted in insulin resistance and increased. Nicotinic acid, nicotinamide, and inositol hexanicotinate.
230 979 424 865 881 754 759 340 1394 213 1048 559 810 507 246 868 1245 513 375 17 650 1394 1386 548 1112 295 101 793 51