Nicotinic acid Cholesterol

Of the water-soluble vitamins, intakes of nicotinic acid [59-67-6] on the order of 10 to 30 times the recommended daily allowance (RE)A) have been shown to cause flushing, headache, nausea, and moderate lowering of semm cholesterol with concurrent increases in semm glucose. Toxic levels of foHc acid [59-30-3] are ca 20 mg/d in infants, and probably approach 400 mg/d in adults. The body seems able to tolerate very large intakes of ascorbic acid [50-81-7] (vitamin C) without iH effect, but levels in excess of 9 g/d have been reported to cause increases in urinary oxaHc acid excretion. Urinary and blood uric acid also rise as a result of high intakes of ascorbic acid, and these factors may increase the tendency for formation of kidney or bladder stones. AH other water-soluble vitamins possess an even wider margin of safety and present no practical problem (82). 

Despite stmctural similarities, the pharmacological consequences of excesses of these substances are quite different. Due to the interest in the effects of nicotinic acid on atherosclerosis, and in particular its use based on its abiUty to lower semm cholesterol, the toxicity of large doses of nicotinic acid has been evaluated. Eor example, in a study designed to assess its abiUty to lower semm cholesterol, only 28% of the patients remained in the study after receiving a large initial dose of 4 g of nicotinic acid due to intolerance at these large doses (70). 

A limited number of pure substances are available from NIST, primarily clini-cally-relevant compounds such as cholesterol, urea, uric acid, creatinine, glucose, cortisol, tripalmitin, and bilirubin (NIST SRM website). These compounds are certified for purity (greater than 99 %) and are used as primary calibrants in definitive methods for these clinical analytes (see below). Several additional pure substances are available for specific applications such as microchemistry, i.e. elemental composition (acetanilide, anisic acid, cystine nicotinic acid, o-bromobenzoic acid, p-fluoro-benzoic acid, m-chlorobenzoic acid), polarimetric standards (sucrose and dextrose), acidimetric standard (benzoic acid and boric acid). Only three pure substance NIST RMs are available for environmental contaminants, namely the chlorinated pesticides, lindane, 4,4 -DDT, and 4,4 -DDE. 

Recently nicotinic acid has been found to lower serum cholesterol in hypercholesteremia, and also in normal persons and rabbits (A3, F2). It was shown that the hypercholesteremia, induced by a 48-hour fast, could be completely corrected by giving the animals large doses of nicotinic acid during the fast. In contrast to nicotinic acid, nicotinamide does not lower the cholesterol level (M10). Several explanations are offered for the action of nicotinic acid (1) it inhibits cholesterol biosynthesis, (2) it interferes with coenzyme A, and (3) it involves a hitherto unknown pharmacologic effect. The renewed clinical interest in nicotinic acid induced us to look for a more specific and sensitive assay for nicotinic acid (B7, M8). 

The laboratory must be informed when the therapeutic regimens include drugs specifically administered to change the blood level of a biochemical constituent. Cholestyramine resin, a nonabsorbable anion exchange resin administered orally to patients with hyperlipoproteinemia produced a 24% decline in serum cholesterol levels in 14 patients with essential hypercholesterolemia. In these patients the mean cholesterol fell from 414 98 mg/100 ml to 176 21 mg/100 ml (FI). Pectin added to the diet caused a 5% decrease in serum cholesterol values (K4), as did an oral hydrophobic colloid (G4). Levels fell in one case from 220 mg/ 100 ml to 160 mg/100 ml (G4). Nicotinic acid, neomycin, and p-chloro-phenoxyisobutyrate have all been used to reduce serum cholesterol (G7). 

Pharmacology Nicotinic acid (but not nicotinamide) in gram doses produces an average 10% to 20% reduction in total and LDL cholesterol, a 30% to 70% reduction in triglycerides, and an average 20% to 35% increase in HDL cholesterol. Nicotinic acid also decreases serum levels of apolipoprotein B-100, the major component of VLDL and LDL fractions. The mechanism by which nicotinic acid exerts these effects is not entirely understood but may involve several actions, including a decrease in esterification of hepatic triglycerides. 

Nicotinic acid (5.18), and related derivatives such as pyridylcarbinol (5.19), xanthinol nicotinate (5.20), acipimox (5.21), given in large doses, influence the lipoprotein ratio, decreasing the concentrations of very low and low-density lipoprotein, but have no effect on HDL-cholesterol complexes. Acipimox (5.21) is a new pyrazine derivative that is 20 times more active than nicotinic acid. When first administered, the use of these agents is associated with flushing and hypotension. 

N.A. Protein, linoleic, oleic, linolenic and palmitic acids, trigonelline, choline, coumarin, nicotinic acid.100117175 Reduce total cholesterol and triglycerides without affecting the HDL, reduce blood sugar. 

Nicotinic acid is an antilipidemic agent that effectively reduces serum concentrations of total cholesterol, low-density lipoprotein (LDL) cholesterol, very low density lipoprotein (VLDL) cholesterol, and triglycerides, and increases concentrations of high-density lipoprotein (HDL) cholesterol. It has been suggested that the marked lowering of serum cholesterol seen during treatment of dyslipidemia with nicotinic acid results from hepatotoxi-city (1). 

Effects of crystalline nicotinic acid-induced hepatic dysfunction on serum low-density lipoprotein cholesterol and lecithin cholesteryl acyl transferase. Am J Cardiol 1998 81(6) 805-7. 

Nicotinic acid in large doses can lower both cholesterol and triglyceride concentrations by inhibiting their synthesis. 

Prior to 1987, the lipid-lowering armamentarium was limited essentially to dietary changes (reductions in saturated fats and cholesterol), the bile acid sequestrants (cholestyramine and colestipol), nicotinic acid (niacin), the fibrates, and probucol. Unfortunately, all of these treatments have limited efficacy or tolerability or both. Substantial reductions in LDL cholesterol (up to 47%) accompanied by increases in HDL cholesterol of up to 32% could be achieved by the combination of a lipid-lowering diet, a bile acid sequestrant, and the subsequent addition of nicotinic acid (Illingworth et al., 1981). However, this therapy is not easy to administer or tolerate and was therefore often unsuc-... 

The principal routes of penetration are thus transcellular and intercellular. Currently there is considerable debate as to which of these predominates. Work with esters of nicotinic acid has shown that the intercellular channels are significant [5.] and considerable effort is being conducted to identify their exact nature and role. Microscopic examination shows that they contain structured lipids the chemical nature of which is complex [6J. Cholesterol esters, cerebrosides and sphingomyelins are present in association with other lipids in smaller concentrations. It is likely that the main barrier to skin penetration resides in the channels and that a diffusing drug molecule experiences a lipid environment which has considerable structure. Penetration enhancers may act by temporarily altering the nature of the structured lipids, perhaps by lowering their normal phase transition temperature which occurs around 38°C. 

It is clear from Equation (19.4) that saturated fat, not cholesterol, is the single most important factor that raises serum cholesterol. Some cases of hyperlipoproteinemia type IV (high VLDL) respond to low-carbohydrate diets, because the excess of VLDL comes from intestinal cells, where it is produced from dietary carbohydrate. Resins, such as cholestyramine and cholestipol, bind and cause the excretion of bile salts, forcing the organism to use more cholesterol. Lovastatin decreases endogenous cholesterol biosynthesis (see later), and niacin (nicotinic acid) apparently decreases the production of VLDL and, consequently, LDL. It also results in an HDL increase. Antioxidants that inhibit the conversion of LDL to oxidized LDL have also been used with some success. These are high doses of vitamin E and the drug probucol. 

Drugs used to increase HDL levels (fibrates, nicotinic acid, and statins) in otherwise normal people do not have the same effect in patients with Tangier disease. Therefore, it is necessary to identify and treat other risk factors associated with CAD. Exercise, weight reduction, dietary cholesterol and saturated fat reduction, and smoking cessation are the first line in management of low HDL cholesterol. Dietary management with low fat intake is beneficial in reducing the risk for CAD, as well... 

Nicotinic acid. This reduces the plasma levels of both VLDLs and LDLs by inhibiting hepatic VLDL secretion, as well as suppressing the flux of free-fatty-acid release from adipose tissue by inhibiting lipolysis. Because of its ability to cause large reductions in circulating levels of cholesterol, nicotinic acid is used to treat Type 11, HI, IV and V hyperlipopro-teinaemias. 

B3/4 complex (niacin, niacinamide) Water 20 mg ATP synthesis nicotinic acid may lower serum cholesterol... 

Nicotinic acid (but not nicotinamide) when adiriinistered in pharmacological doses of 2 - 4 g/day lowers plasma cholesterol levels and has been shown to be a useful therapeutic for hypercholesterolemia. The... 

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