Effect of Nicotinic Acid on Gastric Secretion of Acid in Human Subjects and in Dogs

This article is available online at http://www.jlr.org the only approved drug with such an effect ( 1 ). It has proven to be an attractive option for those intolerant of statin treatment. It has been demonstrated to reduce risk of atherosclerotic cardiovascular disease ( 4 ). The clinical use of niacin has been markedly limited by cutaneous fl ushing. The molecular target of niacin responsible for lipid metabolic changes and fl ushing was unknown until 2003 ( 5-7 ), when the niacin receptor, namely HM74A in humans and PUMA-G in mice, was discovered. The niacin receptor, also known as GPR109A, was shown to be activated by niacin and to mediate its antilipolytic effect as well as the fl ushing effect ( 8-10 ). Interest in niacin has risen because there is still signifi cant residual risk in patients with intensive statin therapy ( 11 ). However, recent outcome trials ( 11, 12 ) failed to show niacin's benefi t on top of statin therapy in lipid-targeted approaches to reduce major cardiovascular events in high-risk patients. In this review we will summarize the pharmacology of niacin, with a particular emphasis on recent outcome trials, including discussion of their limitations . NIACIN'S LIPID EFFECTSNiacin has long been shown to have effects on lipids ( 13 ). Niacin increases high density lipoprotein cholesterol (HDLc), but reduces low density lipoprotein cholesterol (LDLc), VLDL cholesterol, and triglycerides (TGs) ( 14 ) Niacin is also known as vitamin B3. Chronic dietary defi ciency of niacin can cause pellagra ( 1 ). It is a precursor to NAD+/NADH and NADP+/NADPH, both of which play essential metabolic roles in living cells ( 2 ). Niacin has been used for more than half a century in the treatment of dyslipidemia. When Altschul, Hoffer, and Stephen ( 3 ) discovered that niacin could lower plasma levels of cholesterol, it was

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“…This has been widely observed in experimental and outcome studies ( 11,97 ). The mechanism for these gastrointestinal symptoms is not clear.…”

Section: Gastrointestinalmentioning

confidence: 99%

Niacin, an old drug with a new twist

Song

FitzGerald

2013

Journal of Lipid Research

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“…Gastric secretion was studied in 10 patients with basal secretion of acid. In nine of these, the secretion of acid increased between 10% and 200% in response to 500 mg of nicotinic acid orally [75]. Also, in Pavlov pouch dogs, intravenous infusion of nicotinic acid caused a significant increase in gastric acid output [75].…”

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confidence: 99%

“…In nine of these, the secretion of acid increased between 10% and 200% in response to 500 mg of nicotinic acid orally [75]. Also, in Pavlov pouch dogs, intravenous infusion of nicotinic acid caused a significant increase in gastric acid output [75]. Further studies are needed to elucidate the role of the stimulation of secretion of acid for gastrointestinal side effects.…”

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confidence: 99%

Nicotinic acid: the broad‐spectrum lipid drug. A 50th anniversary review

Carlson

2005

Journal of Internal Medicine

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525

354

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Nicotinic acid has, like the Roman God Janus, two faces. One is the vitamin. The other is the broad-spectrum lipid drug. The Canadian pathologist Rudolf Altschul discovered 50 years ago that nicotinic acid in gram doses lowered plasma levels of cholesterol. From the point of view of treatment of the dyslipidaemias that are risk factors for clinical atherosclerosis nicotinic acid is a miracle drug. It lowers the levels of all atherogenic lipoproteins--VLDL and LDL with subclasses as well as Lp(a)--and in addition it raises more than any other drug the levels of the protective HDL lipoproteins. Trials have shown that treatment with nicotinic acid reduces progression of atherosclerosis, and clinical events and mortality from coronary heart disease. The new combination treatment with statin-lowering LDL and nicotinic acid-raising HDL is reviewed. A basic effect of nicotinic acid is the inhibition of fat-mobilizing lipolysis in adipose tissue leading to a lowering of plasma free fatty acids, which has many metabolic implications which are reviewed. The very recent discovery of a nicotinic acid receptor and the finding that the drug stimulates the expression of the ABCA 1 membrane cholesterol transporter have paved the way for exciting and promising new 50 years in the history of nicotinic acid.

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“…It seemed to have no permanent deleterious effect on the isolated gland over the time tested in these experiments. No effects of nicotinic acid on pancreatic function have previously been published, though it apparently causes stimulation of gastric acid secretion in humans and dogs with Pavlov pouches (Andersson, Carlson, Oro & Richards, 1971). Alloxanate has a strong inhibitory effect on basal and stimulated pancreatic adenylate cyclase activity.…”

Section: Discussionmentioning

confidence: 99%

The Effects of Alloxanate, Nicotinic Acid and Imidazole on Secretory Processes and the Activities of Adenylate Cyclase and 3‘,5’‐amp Phosphodiesterase in Cat Pancreas

Bonting

Pont

Kempen

et al. 1977

British J Pharmacology

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1 Nicotinic acid and alloxanate inhibited water and electrolyte secretion in a dose-dependent fashion when added to the perfusate of the isolated saline-perfused pancreas of the cat stimulated by a supramaximal dose of secretin.2 There were no changes in the concentration of sodium or potassium secreted into the juice, but the anions exhibited changes which were related to flow rate. As the flow rate declined the chloride concentration increased with a reciprocal decrease in bicarbonate concentration. 3 Nicotinic acid and alloxanate inhibited enzyme secretion stimulated by carbachol. 4 Imidazole inhibited pancreatic electrolyte secretion, but stimulated amylase secretion. Atropine (0.14 ,UM) reduced the secretion of amylase but did not abolish the effect. 5 Adenylate cyclase prepared from cat pancreas, was stimulated by the octapeptide of cholecystokinin-pancreozymin, secretin and sodium fluoride. 6 Alloxanate strongly inhibited both basal and hormone-stimulated adenylate cyclase activity.Nicotinic acid and imidazole stimulated basal adenylate cyclase activity but had little effect on secretin-stimulated activity. 7 Alloxanate, nicotinic acid and imidazole were all without effect on phosphodiesterase when tested in the presence of micromolar concentrations of adenosine 3',5'-monophosphate (cyclic AMP). At higher cyclic AMP concentrations (2 mM) alloxanate and nicotinic acid were without effect, whereas imidazole had a slight stimulatory effect at 10 mM which was more marked at 50 mM. 8 Alloxanate (10 mM) strongly inhibited both basal and secretin-stimulated adenylate cyclase activity. 9 It is concluded that the effects of nicotinic acid, alloxanate and imidazole on pancreatic secretion are not mediated entirely through their effects on the adenylate cyclase or phosphodiesterase enzyme systems.

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Effect of Nicotinic Acid on Gastric Secretion of Acid in Human Subjects and in Dogs

Cited by 6 publications

References 8 publications

Niacin, an old drug with a new twist

Niacin, an old drug with a new twist

Nicotinic acid: the broad‐spectrum lipid drug. A 50th anniversary review

The Effects of Alloxanate, Nicotinic Acid and Imidazole on Secretory Processes and the Activities of Adenylate Cyclase and 3‘,5’‐amp Phosphodiesterase in Cat Pancreas

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