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Niacin Technical Reports


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Number

Title

Karl Loren Comments

One Membrane fatty acids, niacin flushing and clinical parameters. Here is a technical, but useful, mechanical explanation of "flushing."
Two Release of markedly increased quantities of prostaglandin D2 in vivo in humans following the administration of nicotinic acid. More on the mechanics of the "flush."
Three A comparison between nicotinic acid and acipimox in hypertriglyceridaemia--effects on serum lipids, lipoproteins, glucose tolerance and tolerability. The dose was stupid -- 3,000 mg per day!  But, the study at least shows that niacin reduces cholesterol levels.
Four Preliminary report of the effects of propranolol HCl on the discomfiture caused by niacin. They have found a way to reduce the flush from niacin -- thereby losing the most important advantage of niacin!
Five Reduced levels of prostaglandin precursors in the blood of atopic patients: defective delta-6-desaturase function as a biochemical basis for atopy.  
Six Schizophrenia: a biochemical disorder?  
Seven Drug and nutrient interactions in the elderly diabetic.  
Eight New developments in the use of niacin for treatment of hyperlipidemia: new considerations in the use of an old drug. A very favorable report on how niacin reduces cholesterol levels -- with an absurd dosage being administered.  And, the "required" warning that the flush is bad.  Here's a quote.

"Niacin has been used for many years to treat hyperlipidemia. It has been shown to reduce coronary death and non-fatal myocardial infarction and, in a separate analysis of long-term (15-year) follow-up, all cause mortality. It reduces total cholesterol, low density lipoprotein cholesterol (LDL-C) and triglycerides and increases high densit lipoprotein cholesterol (HDL-C)."

Nine Fluvastatin with and without niacin for hypercholesterolemia. Another favorable report on niacin -- but, again, coupled with warnings.   This report, like many others, shows that a "regular" cholesterol-lowering drug works "better" with niacin added.
Ten Combination of low-dose niacin and pravastatin improves the lipid profile in diabetic patients without compromising glycemic control. Another report on how a drug works better with niacin added.
Eleven Bioavailability of niacin. Report Is Missing -- references only.
Twelve Niacin for lipid disorders. Indications, effectiveness, and safety. "Niacin can be very effective and safe in lowering low-density lipoprotein cholesterol and triglyceride levels and also in increasing high-density lipoprotein cholesterol levels. In combination with other lipid-lowering drugs (eg, bile acid sequestrants), it has reduced the incidence of cardiovascular events and stopped the progression of coronary artery lesions. It may be the most cost-effective lipid-lowering agent currently available. At lower doses, sustained-release forms of niacin may also improve patient compliance. "
 

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Record 1
Title
Membrane fatty acids, niacin flushing and clinical parameters.
Author
Glen AI; Cooper SJ; Rybakowski J; Vaddadi K; Brayshaw N; Horrobin DF
Address
Highland Psychiatric Research Group, Craig Dunain Hospital, Inverness, UK.
Source
Prostaglandins Leukot Essent Fatty Acids, 1996 Aug, 55:1-2, 9-15
Abstract
Clinical definitions of schizophrenia are unreliable and difficult to use. The niacin flush test, which involves prostaglandin-induced vasodilatation, offers a method of exploring essential fatty acid metabolism in schizophrenic patients and may serve to define a subgroup of patients. In a multicentre study of schizophrenic patients with negative symptoms, we have examined the clinical accompaniments of the niacin response. Patients failing to flush with niacin showed significantly reduced levels of arachidonic and docosahexaenoic acids. Conversion from non-flushing to flushing during the 6 month supplementation period was predicted by an increase in arachidonic acid levels in red blood cell membranes irrespective of nature of supplementation. In this study, patients were selected for their negative symptoms and, therefore, it was not surprising that further measures of negative or positive symptoms did not predict flushing. However, an increased score for affective symptoms was significantly associated with a positive flush response. The stability of the niacin test needs to be examined in relation to the periodicity of symptoms in schizophrenia and manic depressive illness. New information on the anandamide system suggests that it may be associated with periodic phenomena and should be investigated in relation to the niacin test.
Language of Publication
English
Unique Identifier
97042919

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Record 2

 Title

Release of markedly increased quantities of prostaglandin D2 in vivo in humans following the administration of nicotinic acid.
Author
Morrow JD; Parsons WG 3d; Roberts LJ 2d
Address
Department of Pharmacology, Vanderbilt University, Nashville, TN 37232.
Source
Prostaglandins, 1989 Aug, 38:2, 263-74
Abstract
Nicotinic acid (niacin) is a B vitamin which is also a potent hypolipidemic agent. However, intense flushing occurs following ingestion of pharmacologic doses of niacin which greatly limits its usefulness in treating hyperlipidemias. Previous studies have demonstrated that niacin-induced flushing can be substantially attenuated by pre-treatment with cyclooxygenase inhibitors, suggesting that the vasodilation is mediated by a prostaglandin. However, the prostaglandin that presumably mediates the flush has not been conclusively determined. In this study we report the finding that ingestion of niacin evokes the release of markedly increased quantities of PGD2 in vivo in humans. PGD2 release was assessed by quantification of the PGD2 metabolite, 9 alpha, 11 beta-PGF2, in plasma by gas chromatography mass spectrometry. Following ingestion of 500 mg of niacin in three normal volunteers, intense flushing occurred and plasma levels of 9 alpha, 11 beta-PGF2 were found to increase dramatically by 800, 430, and 535-fold. Levels of 9 alpha, 11 beta-PGF2 reached a maximum between 12 and 45 min. after ingesting niacin and subsequently declined to near normal levels by 2-4 hours. Levels of 9 alpha, 11 beta-PGF2 in plasma correlated with the intensity and duration of flushing that occurred in the 3 volunteers. Release of PGD2 was not accompanied by a release of histamine which was assessed by quantification of plasma levels of the histamine metabolite, N tau-methylhistamine. This suggests that the origin of the PGD2 release is not the mast cell. Only a modest increase (approximately 2-fold) in the urinary excretion of the prostacyclin metabolite, 2,3-dinor-6-keto-PGF1 alpha, occurred following ingestion of niacin and no increase in the excretion of the major urinary metabolite of PGE2 was found. These results indicate that the major vasodilatory PG released following ingestion of niacin is PGD2. The fact that markedly increased quantities of PGD2 are released suggests that PGD2 is the mediator of niacin-induced vasodilation in humans.
Language of Publication
English
Unique Identifier
89367978

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Record 3

 Title

A comparison between nicotinic acid and acipimox in hypertriglyceridaemia--effects on serum lipids, lipoproteins, glucose tolerance and tolerability.
Author
Tornvall P; Walldius G
Address
Department of Internal Medicine, Karolinska Hospital, Stockholm, Sweden.
Source
J Intern Med, 1991 Nov, 230:5, 415-21
Abstract
Serum and lipoprotein lipid levels, oral glucose tolerance and side-effects were compared in an open cross-over study of 31 non-diabetic patients with hypertriglyceridaemia (type II B and IV) before and after 6 weeks of treatment with nicotinic acid (3 g daily) and acipimox (0.75 g daily), a new nicotinic acid-like drug, respectively. Acipimox was about equally potent in reducing serum and VLDL lipid levels and in increasing HDL cholesterol levels. Acipimox had no significant negative effects on glucose metabolism measured by an oral glucose tolerance test compared with nicotinic acid, which decreased the late glucose tolerance as well as the area under the glucose curve (P less than 0.05 for the difference between the two treatments). The incidence and severity of flush or any other recorded side-effects was higher after nicotinic acid treatment than after acipimox. In addition, no effects on laboratory parameters such as liver enzymes and uric acid were seen after treatment with acipimox. The results of this study demonstrate that acipimox is a satisfactory alternative to nicotinic acid in patients with hypertriglyceridaemia.
Language of Publication
English
Unique Identifier
92044282

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Record 4

 Title

Preliminary report of the effects of propranolol HCl on the discomfiture caused by niacin.
Author
Estep DL; Gay GR; Rappolt RT Sr
Source
Clin Toxicol, 1977, 11:3, 325-8
Abstract
Subjective discomfort caused by nausea and hot, pruritic skin has been described in patients after ingestion of therapeutic dosages of niacin is shown by this study to be alleviated by propranolol HC1. A dosage of 2 mg, I.V., given incrementally, in a clinical trial of six patients is described. The peripheral vasodilator effects of niacin were attenuated in some subjects but not in others. However, all subjects reported relief of unpleasant symptoms. Serial vital signs were taken and no significant changes were found. It is postulated that propranolol HC1 exerts a calmative effect at the CNS level. In a series that utilized doses of 40 and 80 mg of propranolol HC1 taken orally 30 min prior to the ingestion of 500 or 1000 mg of niacin, a progressive increase in the onset of the niacin flush was observed. It is proposed that as the available plasma level of propranolol HC1 falls, the ratio of niacin to propranolol HC1 increases, exceeding the threshold at which the flush occurs. Both these studies suggest that further work is indicated to establish the possible therapeutic efficacy of propranolol HC1.
Language of Publication
English
Unique Identifier
78023258

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Record 5
Title
Reduced levels of prostaglandin precursors in the blood of atopic patients: defective delta-6-desaturase function as a biochemical basis for atopy.
Author
Manku MS; Horrobin DF; Morse N; Kyte V; Jenkins K; Wright S; Burton JL
Source
Prostaglandins Leukot Med, 1982 Dec, 9:6, 615-28
Abstract
In the plasma phospholipids of a group of 50 young adults with atopic eczema, there was an elevation of cis-linoleic acid associated with a deficit of gamma-linolenic acid and of the prostaglandin precursors, dihomogammalinolenic acid and arachidonic acid. This suggests that atopics have a deficit in the function of the delta-6-desaturase enzyme which converts linoleic acid to gamma-linolenic acid. Carriers of cystic fibrosis tend to be phenotypically atopic, supporting previous suggestions that in homozygote cystic fibrosis patients the key defect may be in the delta-6-desaturase enzyme. Atopic patients may be exceptionally sensitive to side effects of non-steroidal anti-inflammatory agents. They fail to flush in response to application of niacin compounds to the skin, a reaction mediated by prostaglandins. A deficit of prostaglandin precursors would explain both of these observations. That the observed biochemical deficit plays a causative role in the manifestations of atopy was indicated by the fact that in a double-blind, placebo-controlled crossover trial, gamma-linolenic acid in the form of evening primrose oil (Efamol), partially corrected both the biochemical abnormalities and the clinical state.
Language of Publication
English
Unique Identifier

To The Top
Record 6

 Title

Schizophrenia: a biochemical disorder?
Author
Horrobin DF
Source
Biomedicine, 1980 May, 32:2, 54-5
Abstract
There is evidence that schizophrenia may be related to excess biological activity of dopamine, deficient synthesis of a prostaglandin and to the presence of a normal opioid in excess or of an abnormal opioid. These three groups of observations seem to be interrelated since opioids are able to inhibit the formation of prostaglandin E1 and prostaglandin E1 and dopamine inhibit each other's effects. A low prostaglandin E1 level will therefore produce and apparent dopamine excess. Niacin causes flushing, apparently by stimulating production of prostaglandin E1. Much larger doses of oral niacin are required to produce flushing in schizophrenics than in normal individuals. Most schizophrenics do not flush when given 250 mg orally and this may be a simple biochemically-based test for a major group of schizophrenics.
Language of Publication
English
Unique Identifier
80221358

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Record 7
Title
Drug and nutrient interactions in the elderly diabetic.
Author
Roe DA
Address
Division of Nutritional Sciences, Cornell University, Ithaca, NY 14853.
Source
Drug Nutr Interact, 1988, 5:4, 195-203
Abstract
Elderly diabetics take more drugs than other groups of elderly patients. Their multiple drug use is largely explained by the drugs that they take for complications of their primary disease; these include cardiovascular drugs for macrovascular disease and antibiotics for secondary infections. They also take more drugs for control of other conditions that are etiologically associated with the development and progression of their diabetes, including antihypertensive agents, antilipemic agents and steroids, and nonsteroidal antiinflammatory drugs (NSAIDs), which are taken for relief of joint pain that is intensified by arthritic joints bearing excess weight. Drugs taken by elderly diabetics that contribute to the high prevalence of drug-nutrient interactions include those taken as antidiabetic agents, including both insulin and sulfonylureas as well as calcium channel blockers; they also include thiazides, loop diuretics, sulfa drugs, cephalosporin antibiotics, tetracyclines, antifungal agents, cholestyramine and colestipol, niacin, prednisone and other corticosteroids, and NSAIDs. These drugs and drug combinations contribute to the risk of hyperglycemia, which can cause nonketotic hyperglycemia in the elderly; to the risk of hypoglycemia, which in the elderly carries the risk of inducing pseudo-stroke; to the risk of drug-induced nutritional deficiencies from antilipemics and cephalosporins, which can induce vitamin K deficiency; to the risk of acute incompatibility reactions, including flush reactions from chlorpropamide, niacin, and calcium channel blockers; and to the risk of edema, anemia, and hyperkalemia from NSAIDs.(ABSTRACT TRUNCATED AT 250 WORDS)
Language of Publication
English
Unique Identifier
89196223

HealthGate Documents

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Record 8 from database: MEDLINE

Title
New developments in the use of niacin for treatment of hyperlipidemia: new considerations in the use of an old drug.
Author
Crouse JR 3rd
Address
Bowman Gray School of Medicine, Winston Salem, North Carolina 27157, USA.
Source
Coron Artery Dis, 1996 Apr, 7:4, 321-6
Abstract
Niacin has been used for many years to treat hyperlipidemia. It has been shown to reduce coronary death and non-fatal myocardial infarction and, in a separate analysis of long-term (15-year) follow-up, all cause mortality. It reduces total cholesterol, low density lipoprotein cholesterol (LDL-C) and triglycerides and increases high densit lipoprotein cholesterol (HDL-C). Sustained-release niacin may be associated with more dramatic changes in LDL-C and triglyceride, whereas the short acting preparation causes greater increases in HDL-C. The increase of HDL-C occurs at a lower dose (1500 mg/day) than the reduction of LDL-C (> 1500 mg/day). Niacin also favorably influences other lipid parameters including lipoprotein(a) [Lp(a)], alimentary lipemia, familial defective apolipoprotein B-100 and small dense LDL. Combination of niacin with a bile acid sequestrant or a reductase inhibitor represents a powerful lipid-altering regimen. Whereas the reductase inhibitors and bile acid binding resins primarily affect LDL-C, the combined therapy has a synergistic effect to reduce LDL-C and, in addition, the niacin reduces triglycerides and increases HDL-C. The major drawback in the use of niacin is associated side effects (flushing and palpitations) and toxicity (worsening of diabetes control, exacerbation of peptic ulcer disease, gout, hepatitis). Niacin has a long history of use as a lipid lowering agent and has several attractive features. Unfortunately, the side effect profile of this agent warrants its use only in patients with marked dyslipidemia in whom side effects and potential toxicity are closely monitored.
Language of Publication
English
Unique Identifier
97006291

MeSH Heading (Major)
Antilipemic Agents|AD/PD/*TU; Hyperlipidemia|*DT; Niacin|AD/AE/PD/*TU
MeSH Heading
Apolipoproteins B|BL; Cholesterol|BL; Follow-Up Studies; Human; Lipoprotein(a)|BL; Lipoproteins, HDL Cholesterol|BL; Lipoproteins, LDL Cholesterol|BL; Triglycerides|BL

Publication Type
JOURNAL ARTICLE; REVIEW; REVIEW LITERATURE
ISSN
0954-6928
Country of Publication
UNITED STATES

Record 9 from database: MEDLINE

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Title
Fluvastatin with and without niacin for hypercholesterolemia.
Author
Jacobson TA; Chin MM; Fromell GJ; Jokubaitis LA; Amorosa LF
Address
Department of Medicine, Emory University School of Medicine, Atlanta, Georgia 30303.
Source
Am J Cardiol, 1994 Jul, 74:2, 149-54
Abstract
Seventy-four patients with plasma low-density lipoprotein cholesterol levels > or = 160 mg/dl after an American Heart Association phase 1 diet were randomized to double-blind treatment with fluvastatin, 20 mg/day, or placebo for 6 weeks. Immediate-release niacin was then added to both treatment regimens and titrated to a maximum of 3 g/day for a further 9 weeks. After 6 weeks of fluvastatin monotherapy, low-density lipoprotein cholesterol levels decreased by 21% (p < 0.001 vs placebo), and after the addition of niacin, response was potentiated to 40% compared with 25% for the niacin control group at study end point (p < 0.001). Fluvastatin, alone and in combination with niacin, also significantly improved high-density lipoprotein cholesterol (increases of about 30%) and triglyceride profiles (decreases of approximately 28%) from baseline. Lipoprotein(a) decreased by 37% in those receiving fluvastatin-niacin but was unaltered in those receiving fluvastatin alone. No serious adverse events were ascribed to fluvastatin, and no cases of myositis were observed. Small, transient, asymptomatic increases in aspartate aminotransferase were noted with fluvastatin-niacin treatment but were not considered clinically relevant. Although the fluvastatin-niacin combination in this study was without evidence of significant transaminitis, myopathy, or rhabdomyolysis, it would seem prudent to continue to monitor its safety with longer term use. In conclusion, fluvastatin, both as monotherapy and in combination with niacin, proved to be an effective, safe, and well-tolerated therapeutic alternative for hypercholesterolemia.
Language of Publication
English
Unique Identifier
94295511

MeSH Heading (Major)
Anticholesteremic Agents|AD/AE/*TU; Fatty Acids, Monounsaturated|AD/AE/*TU; Hypercholesterolemia|BL/DH/*DT; Indoles|AD/AE/*TU; Niacin|AD/AE/*TU
MeSH Heading
Adult; Aged; Alanine Transaminase|BL; Aspartate Transaminase|BL; Cholesterol|BL; Double-Blind Method; Drug Combinations; Drug Tolerance; Female; Follow-Up Studies; Human; Lipoprotein(a)|BL; Lipoproteins, HDL Cholesterol|BL; Lipoproteins, LDL Cholesterol|BL; Male; Middle Age; Patient Compliance; Placebos; Triglycerides|BL

Publication Type
CLINICAL TRIAL; JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL
ISSN
0002-9149
Country of Publication
UNITED STATES

Record 10 from database: MEDLINE

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Title
Combination of low-dose niacin and pravastatin improves the lipid profile in diabetic patients without compromising glycemic control.
Author
Gardner SF; Marx MA; White LM; Granberry MC; Skelton DR; Fonseca VA
Address
Department of Pharmacy Practice, College of Pharmacy, University of Arkansas for Medical Sciences, Little Rock 72205, USA. gardner@cop.uams.edu
Source
Ann Pharmacother, 1997 Jun, 31:6, 677-82
Abstract
OBJECTIVE: To determine the efficacy and tolerability of the addition of low-dose niacin (1.5 g/d) in a diabetic hypercholesterolemic population who were unable to attain desired lipid control with low-dose (20 mg) pravastatin monotherapy. RESEARCH DESIGN AND METHODS: This was a prospective, open-label study conducted over a 14-week period. Twenty-three diabetic patients with low-density lipoprotein (LDL) cholesterol concentrations of at least 150 mg/dL after dietary therapy were recruited from the outpatient diabetes clinic of a university teaching hospital. After 4 weeks of dietary stabilization and baseline determination of the lipid profile and glycemic control, patients received pravastatin 20 mg once daily for 4 weeks. Laboratory parameters were reassessed and niacin was added to the regimen in qualifying patients. Over 2 weeks, patients' regimens were titrated to a maximal dosage of 500 mg tid. Patients continued to receive the combination regimen for 4 weeks and were reassessed. MEASUREMENTS AND MAIN RESULTS: Sixteen patients (14 non-insulin-dependent diabetes mellitus, 2 insulin-dependent diabetes mellitus) completed the study. Mean fasting blood sugar and fructosamine concentrations were unchanged throughout the study. Five patients required minor alterations (3 increased, 2 decreased) in their hypoglycemic regimens during the study. The addition of low-dose niacin to pravastatin therapy resulted in a significant lowering of LDL cholesterol compared with pravastatin monotherapy. CONCLUSIONS: Low-dose niacin is a promising addition to hydroxymethylglutaryl-coenzyme A reductase inhibitor therapy in the treatment of hypercholesterolemia in patients with diabetes mellitus.
Language of Publication
English
Unique Identifier
97328158

MeSH Heading (Major)
Anticholesteremic Agents|AD/AE/*TU; Diabetes Mellitus, Insulin-Dependent|BL/CO/*DT; Diabetes Mellitus, Non-Insulin-Dependent|BL/CO/*DT; Enzyme Inhibitors|AD/AE/*TU; Niacin|AD/AE/*TU; Pravastatin|AD/AE/*TU
MeSH Heading
Adult; Aged; Blood Glucose|ME; Comparative Study; Drug Therapy, Combination; Female; Fructosamine|BL; Human; Hypercholesterolemia|DT/ET; Lipoprotein(a)|BL; Lipoproteins, LDL Cholesterol|BL; Male; Middle Age; Prospective Studies; Support, Non-U.S. Gov't

Publication Type
CLINICAL TRIAL; JOURNAL ARTICLE
ISSN
1060-0280
Country of Publication
UNITED STATES

Record 11 from database: MEDLINE

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Title
Bioavailability of niacin.
Author
van den Berg H
Address
TNO Nutrition and Food Research Institute, Zeist, The Netherlands.
Source
Eur J Clin Nutr, 1997 Jan, 51 Suppl 1:, S64-5
Abstract
Abstract unavailable online.
Language of Publication
English
Unique Identifier
97175911

MeSH Heading (Major)
Niacin|AD/DF/PH/*PK
MeSH Heading
Animal; Biological Availability; Food; Human; Intestinal Absorption

Publication Type
JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL
ISSN
0954-3007
Country of Publication
ENGLAND

Record 12 from database: MEDLINE

To The Top
Title
Niacin for lipid disorders. Indications, effectiveness, and safety.
Author
Brown WV
Address
Division of Arteriosclerosis and Lipid Metabolism, Emory University School of Medicine, Atlanta, USA.
Source
Postgrad Med, 1995 Aug, 98:2, 185-9, 192-3
Abstract
Niacin can be very effective and safe in lowering low-density lipoprotein cholesterol and triglyceride levels and also in increasing high-density lipoprotein cholesterol levels. In combination with other lipid-lowering drugs (eg, bile acid sequestrants), it has reduced the incidence of cardiovascular events and stopped the progression of coronary artery lesions. It may be the most cost-effective lipid-lowering agent currently available. At lower doses, sustained-release forms of niacin may also improve patient compliance.
Language of Publication
English
Unique Identifier
95357279

MeSH Heading (Major)
Antilipemic Agents|*TU; Hyperlipidemia|*DT; Niacin|AE/CT/*TU
MeSH Heading
Drug Eruptions|ET; Female; Human; Liver|DE; Male

Publication Type
JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL
ISSN
0032-5481
Country of Publication
UNITED STATES

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