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PubMed2005

Influence of extended-release nicotinic acid on nonesterified fatty acid flux in the metabolic syndrome with atherogenic dyslipidemia.

Nicotinic acid has favorable effects on atherogenic dyslipidemia. However, in some patients who have diabetes, crystalline nicotinic acid decreases glycemic control; this effect could be due to a marked rebound of nonesterified fatty acids (NEFAs) observed after nicotinic acid suppression of lipolysis in adipose tissue. Recent reports have indicated that small doses of extended-release nicotinic acid do not cause a substantial decrease in glucose levels. Therefore, in this study, we examined whether 2 g/day of extended-release nicotinic acid abolishes the NEFA rebound that is reported with crystalline nicotinic acid. Seventeen men who had the metabolic syndrome (8 did not have type 2 diabetes and 9 did) were treated for 4 months. At baseline and at 4 months, measurements were made of plasma glucose, insulin, and NEFA during an oral glucose tolerance test. At 3 months, effects of extended-release nicotinic acid on NEFA levels and flux rates were determined on 3 separate days at 3 separate intervals after the final dose of nicotinic acid (4, 9, and 28 hours). Values obtained at 28 hours were taken as baseline (i.e., no nicotinic acid remaining in the circulation). After 4 hours (percent baseline), NEFA levels were -30% without diabetes and -37% with diabetes, and flux rates were -21% without diabetes and -25% with diabetes; after 9 hours, NEFA levels were 43% without diabetes and 50% with diabetes, and flux rates were 38% without diabetes and 70% with diabetes. Extended-release nicotinic acid did not abolish NEFA rebound. Nonetheless, the rebound was much less than previously reported for crystalline nicotinic acid. Moreover, after 4 months of nicotinic acid therapy, levels of NEFA, glucose, and insulin during the oral glucose tolerance test were not significantly different from those before institution of nicotinic acid therapy, suggesting minimal changes in insulin sensitivity.

Adult↗
PubMed1989

Fate of excess nicotinamide and nicotinic acid differs in rats.

Rats administered excess nicotinamide and nicotinic acid were studied to determine the metabolic fate of pharmacological levels of these compounds. When a large amount of nicotinamide (500 mg/kg body wt) was intraperitoneally injected into rats, 32% of the dose was excreted as nicotinamide, 11% as N1-methylnicotinamide (MNA), 10% as nicotinuric acid, 5% as nicotinic acid, 3% as N1-methyl-4-pyridone-3-carboxamide (4-pyr) and 2% as N1-methyl-2-pyridone-5-carboxamide (2-pyr) during d 1 after the injection. Urinary excretion of these compounds gradually decreased with time and returned to normal by d 3. Urinary excretion of nicotinic acid and nicotinuric acid was observed only on d 1. When a large amount of nicotinic acid (500 mg/kg body wt) was intraperitoneally injected into rats, 55% of the dose was excreted as nicotinic acid and 15% as nicotinuric acid during d 1, and no excretion of these compounds was observed thereafter. The increase in excretion of nicotinamide, MNA, 2-pyr and 4-pyr was slight even on d 1. Excretion of nicotinic acid, nicotinuric acid, nicotinamide, MNA, 2-pyr and 4-pyr returned to normal levels on d 2. From these results, the different fates of excess nicotinamide and nicotinic acid are discussed.

Animals↗
PubMed2006

Clinical evidence for use of acetyl salicylic acid in control of flushing related to nicotinic acid treatment.

Nicotinic acid (NA) is highly effective and widely used in the management of dyslipidaemia. For many patients, the side effect of flushing of the face and upper body leads to discontinuation. Flushing with NA is mediated by prostaglandins, and as acetyl salicylic acid (ASA, 'aspirin') is a highly effective inhibitor of prostaglandin synthesis, there is a rationale for its use to prevent or reduce the severity of NA-related flushing. This literature survey identified four studies specifically exploring the utility of ASA in preventing NA-related flushing in healthy volunteers. Twenty-three NA studies, where ASA was mandatory or optional within the protocol, and four studies, where background ASA therapy was reported in most participants, were also identified. Although the incidence of flushing in studies using ASA was often high, discontinuation rates due to flushing were low (mean 7.7%). This figure compares favourably with discontinuation rates with NA commonly reported in the literature (up to approximately 40%). There is good supportive evidence for the use of ASA in reducing the severity of NA-related flushing.

Aspirin↗
PubMed1978

The relation between carbohydrate extraction by the forearm and arterial free fatty acid concentration in man. I. Forearm work with nicotinic acid infusion.

To see if the magnitude of carbohydrate extraction by working skeletal muscle in man is inversely correlated with the arterial free fatty acid (FFA) concentration as in the heart, eighteen healthy men were studied during dynamic forearm work with and without nicotinic acid. The extraction or release of glucose, lactate and pyruvate was determined by the simultaneous sampling of blood from the brachial artery (a) and a deep vein (dv) of the active forearm. Nicotinic acid decreased the arterial FFA concentration from 498 +/- 53 to 134 +/- 12 mumol per litre plasma and this caused a decrease in calculated extraction of FFA. However, it did not affect the extraction of glucose, which was of a magnitude similar to one third of the oxidative metabolism in both situations. One of the possible reasons of this difference compared to the human heart muscle is that the exercising skeletal muscle may utilize stored substrate to a greater extent, which makes possible shifts in substrate utilized for oxidation without changes in substrate extraction. Another reason may be that FFA utilization covers a far smaller proportion of oxidative metabolism in skeletal than in heart muscle already before nicotinic acid.

Adult↗
PubMed2001

Comparative studies on nicotinic acid derivatives as hypolipoproteinemic agents.

Nicotinic acid and its related compounds are well known lipid lowering agents but the use of nicotinic acid in clinical practice is limited because of its side effects. To reduce the unwanted effects, new derivatives of nicotinic acid have been synthesized and tested in control and pathological animals for their antilipoproteinemic effects. Two newly synthesized derivatives of nicotinic acid i.e. 3-methoxy phenacyl nicotinium bromide (T1) and 2-methoxy phenacyl nicotinium bromide (T2) have been screened for their hypolipoproteinemic effects in white male rabbits. The compounds were administered in the doses of 30 mg/day and the results were compared with aspirin taken as the reference drug. The present work revealed that both of these synthesize compounds exhibited marked effects on plasma lipoproteins assuming that these compounds exerted their action by inhibiting hepatic production of very low density lipoprotins (VLDL), ultimately leading to reduction in low density lipoprotein. Clofibrate and aspirin are taken as standards to evaluate the potentials of these agents for their effects on lipid.

Journal Article↗
PubMed1997

Effect of nicotinic acid on zinc and iron metabolism.

Nicotinic acid has functional groups capable of forming complexes with trace metals. The present study examines the effect of nicotinic acid supplementation on absorption and utilization of zinc and iron. In vitro zinc uptake by human erythrocytes was studied using blood samples of 10 healthy subjects. It was found that 8 mumoles nicotinic acid or NADP increased 65Zn uptake by 38.9% and 43.1% in fasting, and by 70.9% and 28.1% in postprandial conditions. In animal experiments, nicotinic acid supplementation to finger millet based diet resulted in significant enhancement of percent zinc absorption, liver zinc and growth of weanling mice (P < 0.05). When mice were fed with nicotinic acid-deficient, -adequate and -excess synthetic diets for four weeks it was observed that, in comparison with the nicotinic acid-deficient diet, percent zinc absorption, intestinal zinc, percent haeomoglobin and liver iron increased significantly under nicotinic acid-adequate and -excess conditions. The results obtained suggested that nicotinic acid, in addition to its known effect on growth and metabolism, may be playing an important role in enhancing zinc and iron utilization.

Animals↗
PubMed1991

The bioavailability of sustained release nicotinic acid formulations.

1. The bioavailability of three nicotinic acid formulations was investigated in a randomized cross-over study. 2. Single doses of nicotinic acid (500 mg) were given to seven healthy volunteers. The concentrations of nicotinic acid and its main metabolite nicotinuric acid were measured in serum up to 8 h and in urine up to 24 h. 3. The relative bioavailability of unchanged nicotinic acid from two slow release formulations compared with a rapid-release form was only 1% and 25%, respectively. Relative values of AUC (0.8 h) for nicotinuric acid were 15% and 58%, and relative urinary recoveries were 18% and 59%, respectively. Facial flushing was less when slow release formulations were used. 4. The bioavailability of unchanged nicotinic acid is low and the ratio of nicotinuric acid to nicotinic acid in serum and urine is high when slow release formulations are used.

Adult↗
PubMed1979

Nocturnal inhibition of lipolysis in man by nicotinic acid and derivatives.

The effect of nicotinic acid and several derivatives on the nocturnal level of free fatty acids was studied in 12 healthy young women and men. Free fatty acids are an important precursor of plasma triglycerides and their concentration is highest at night. The drugs used were nictinic acid, beta-pyridyl-carbinol, mesoinositol hexanicotinate and xantinol nicotinate. The highest plasma nicotinic acid level was observed with beta-pyridyl-carbinol, but significant reduction in free fatty acids during the entire night was only achieved with inositolhexanicotinate and xantinol nicotinate. There was no correlation between the plasm levels of free fatty acids and nicotinic acid at any sampling time. If prolonged reduction in free fatty acid concentration is desired in the therapy of hyperlipidemias, the inositol and xantinol esters of nicotinic acid appear to be superior to the other preparations.

Adult↗