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Vitamin B3 (Niacin)

Nutrient Names: Vitamin B3, niacin, niacinamide.
Synonyms: Niacin: Nicotinic acid, nicotinate. Niacinamide: Nicotinamide, nicotinic acid amide, nicotinic amide.
Related Substances: Hexaniacin, inositol hexaniacinate, inositol hexanicotinate, inositol nicotinate.
Other Synonyms: 3-Pyridine carboxamide, anti-blacktongue factor, antipellagra factor, benicot, nicamid, nicosedine, nicotylamidum, pellagra-preventing factor, vitamin G.
Trade Names Include: Efacin, Endur-Acin, Enduramide, Hexopal, Niaca, Niacor, Niasafe, Niaspan, Nicalex, Nicamin, Nico-400, Nicobid, Nicolar, Nicotinex, Nico-Span, Papulex, Slo-Niacin, Tega-Span, Tri-B3, Wampocap.

Summary Table
nutrient description

Chemistry and Forms

Niacin and niacinamide are the two principal forms of the water-soluble B-complex vitamin, B3. Nicotinic acid and nicotinamide are alternate names for niacin and niacinamide, respectively. Niacin was initially isolated from rice bran in 1911. Later, in 1934, Warburg and Christian isolated niacinamide, the amide of niacin, when coenzyme II (NADP) was extracted from equine erythrocytes. The structure of niacinamide consists of a pyridine ring with an amide group in position three. Inositol hexaniacinate is the hexanicotinic acid ester of meso-inositol; it also called inositol hexanicotinate or inositol nicotinate.

Niacin is extremely stable to heat, light, acid, alkali, and oxidation.

Physiology and Function

Although niacin and niacinamide have divergent pharmacological activities, they share the fundamental function that identifies them as B3, the vitamin activity that prevents pellagra. However, niacin does not meet the criteria for being defined as a vitamin in the strictest sense because it can be derived from tryptophan. However, at a 60:1 ratio for biosynthesis, this process is highly inefficient and depends on vitamins B1, B2, and B6as essential cofactors.

Niacin, as either nicotinamide or nicotinic acid, is rapidly absorbed in the proximal small intestine by facilitated diffusion (at low concentrations) and by passive diffusion (at high concentrations). A small proportion of niacinamide is metabolized to niacin, primarily through the activity of enteric flora. The pharmacokinetics of niacinamide vary significantly depending on dose, species, gender, and route of administration. In humans, peak serum concentrations of niacinamide are attained within 1 hour of oral ingestion because it is rapidly cleared from circulation and distributed. Niacin is primarily eliminated via the urine, but also appears in breast milk.

Nicotinamide adenine dinucleotide (NAD+, coenzyme I) and nicotinamide adenine dinucleotide phosphate (NADP+, coenzyme II) are the active forms of nicotinamide. The nicotinamide component of NAD and NADP plays a key role in hydrogen transfer reactions by acting as a hydride ion acceptor or donor in numerous intracellular oxidation-reduction (redox) reactions. Thus, they are required for the activity of more than 200 enzymes participating in a broad range of metabolic processes, including glycolysis, tissue respiration, and lipid, amino acid, and purine metabolism. Notably, NAD is required for the redox reactions in glycolysis and in Krebs cycle during oxidative phosphorylation, through which biological systems derive most of their energy from carbohydrates. NADPH is also involved in fatty acid and steroid synthesis as well as the pentose phosphate shunt pathway, one pathway by which ribose is synthesized. Consequently, niacin is essential to biosynthesis of hormones such as estrogen, progesterone, testosterone, and insulin, along with stress-related hormones in the adrenals. Niacinamide is known to stimulate gamma-aminobutyric acid (GABA) receptors, without binding to the receptor sites, an effect likened to that of benzodiazepines. Both NAD+ and NADP+ function as cofactors for numerous dehydrogenase enzymes (e.g., lactate and malate dehydrogenases) responsible for innumerable biochemical reactions in the body, including detoxifying alcohol and utilizing carbohydrates, fats, and proteins. Niacin is a precursor of glucose tolerance factor, and niacinamide facilitates beta-cell regeneration in vivo and in vitro.

Nicotinamide adenine dinucleotide is the substrate for mono–adenosine diphosphate (ADP)–ribosyltransferases and poly-ADP-ribose polymerase (PARPs), two classes of enzymes that separate the niacin moiety from NAD and transfer ADP-ribose units from NAD to acceptor proteins. Although their functions are not yet well understood, PARPs also appear to play an important role in DNA replication and repair, as well as cell differentiation. Niacinamide inhibits free-radical formation and acts as an antioxidant, at least in part by preventing NAD depletion during DNA repair by inhibiting PARP. In particular, niacinamide protects pancreatic islet cell lysis (e.g., after exposure to oxygen free radicals and nitric oxide) and suppresses cytokine-mediated induction of nitric oxide synthase. Through its inhibition of PARP, niacinamide also modulates major histocompatibility complex (MHC) class II expression and exerts an anti-inflammatory action affecting neutrophil chemotaxis.

nutrient in clinical practice

Known or Potential Therapeutic Uses

Within conventional medical practice, vitamin B3usage, typically as niacinamide, is primarily framed in terms of prophylaxis and treatment of frank vitamin B3deficiency states, particularly pellagra. However, the most common clinical application of niacin is treatment of primary hyperlipidemia, specifically type IIa/IIb, III, IV, or V hyperlipoproteinemia, where it is a first-line therapy, often in combination with an HMG-CoA reductase inhibitor, for reducing low-density lipoprotein cholesterol (LDL-C) concentrations and triglycerides and increasing high-density lipoprotein cholesterol (HDL-C) concentrations.

Supplementation with vitamin B3can play an essential role in treatment of individuals with malabsorption syndromes associated with pancreatic insufficiency and diseases of the small intestine, such as celiac and tropical sprue. Diabetes mellitus, hyperthyroidism, malignant carcinoid syndrome, and other pathophysiological states can increase metabolic requirements for B3and carry a significant risk for B3deficiency. Hartnup's disease is a rare autosomal recessive tryptophan metabolism disorder wherein inborn errors of metabolism cause tryptophan absorption and transport to be impaired and tryptophan to be diverted to form 5-hydroxytryptamine, thereby impairing conversion of tryptophan to niacin and increasing risk of niacin deficiency and the need for niacin (and tryptophan) intake.

Historical/Ethnomedicine Precedent

The use of lime or other alkalinating agents in the diets and cooking practices of many traditional cultures represents an institutionalized application of the empirical observation that bound niacin in many food sources, especially maize, needs to be liberated to supply adequate dietary intake of niacin.

Possible Uses

General

Burns, human immunodeficiency virus (HIV) support, postpartum support, pregnancy, schizophrenia, skin cancer.

Niacin

Anxiety, atherosclerosis, Bell's palsy, diabetes mellitus, dysmenorrhea, Hartnup's disease, high hypercholesterolemia, hyperlipidemia, hyperlipoproteinemia (type IIa/IIb, III, IV, V), hypertriglyceridemia, hypothyroidism, intermittent claudication, hypothyroidism, migraines, multiple sclerosis, myocardial infarction (recurrence), photosensitivity, Raynaud's disease, smoking cessation, tardive dyskinesia.

Niacinamide

Acne (topical), alcohol withdrawal support, anxiety, bursitis, cataracts, dermatitis herpetiformis (with tetracycline), diabetes mellitus (type 1; prevention), Hartnup's disease, hypoglycemia, osteoarthritis, pellagra, photosensitivity, Raynaud's disease, tardive dyskinesia.

Inositol Hexaniacinate

Hypercholesterolemia, intermittent claudication, peripheral vascular disease, Raynaud's disease.

Deficiency Symptoms

Niacin deficiency manifests pervasively, affecting every cell in the body. Symptoms of mild niacin deficiency include indigestion, fatigue, canker sores, vomiting, and depression. In its classic presentation as pellagra, severe niacin deficiency is characterized by cutaneous, mucous membrane, central nervous system (CNS), and gastrointestinal (GI) symptoms, alone or in combination; a pattern commonly described as the “four Ds”: dermatitis, diarrhea, dementia, and death. Nutritionally based pellagra usually involves a simultaneous tryptophan deficiency. The dermatitis caused by a niacin deficiency is characterized by cracked, thick, scaly skin forming a symmetrical, darkly pigmented rash and exacerbated by sun exposure, a phenomenon known as “mal del sol.” This condition is often complicated by other B-vitamin deficiencies. Scarlet glossitis and stomatitis are characteristic of acute deficiency. The tongue and mouth become inflamed, painful with a burning sensation, and take on a bright, beefy red appearance. Diarrhea results from decreased hydrochloric acid secretion accompanied by inflammation of the GI tract. Dementia caused by a lack of niacin begins with irritability, headaches, and insomnia, followed by mental confusion, amnesia, hallucinations, and severe depression. If untreated, pellagra is ultimately fatal.

The most common causes of niacin deficiency are alcoholism and inadequate intake of niacin (and tryptophan) with sufficient bioavailability; genetic, pathophysiological, and iatrogenic factors also constitute significant risks. High dietary intake of cereals (e.g., sorghum, corn) not processed with lime, to increase tryptophan bioavailability, is a common cause of niacin deficiency in settings of poverty and poor diet. However, a broad nutritional deficit is usually required, especially involving protein, tryptophan and/or thiamine, riboflavin, and pyridoxine. Excessive leucine intake (e.g, with high millet intake, as common in India) can lead to a niacin deficiency even with normal intake because leucine blocks NAD synthesis. Diarrhea, cirrhosis, and inadequate or imbalanced nutrient infusions during postoperative recovery are common causes of secondary niacin deficiency.

Dietary Sources

Liver, poultry, meat, fish, eggs, peanuts, brewer's yeast, torula yeast, rice bran, rice polishings, and wheat bran are rich dietary sources of vitamin B3. Legumes, mushrooms, nuts, sunflower seeds, and wheat germ can also serve as significant nutrient sources. In general, however, although whole grains and cereal products may contain some vitamin B3, fortification of white flour is the primary means of ensuring that commonly consumed grain products provide adequate niacin nutriture. Niacin tends to be bound to glycosides in mature cereal grains, such as corn and wheat, which significantly decreases its bioavailability. Alkali treatment of grains, such as with alkaline-cooking process using lime, may result in release of the bound niacin and increase its bioavailability; however, this has been disputed. Dietary tryptophan can be converted to niacin and can enhance available supplies, but evidence indicates that the 60:1 conversion ratio may be overly optimistic. 1

Food sources of B3often also contain thiamine, riboflavin, pantothenic acid, pyridoxine, cyanocobalamin, and folic acid. B-complex vitamins (especially B1, B2, and B6), vitamin C, magnesium, zinc, protein, and essential fatty acids enhance absorption of vitamin B3, whereas alcohol, coffee, excess sugar, antibiotics, and steroids reduce niacin absorption.

Nutrient Preparations Available

Vitamin B3as a nutritional supplement is primarily available as niacinamide (nicotinamide) or niacin (nicotinic acid). Multivitamin formulations typically contain some form of B3. Nicotinamide is the form of niacin most often used in nutritional supplements and in food fortification. Nicotinate and inositol hexaniacinate (the hexanicotinic acid ester of meso-inositol) are also available as nonprescription forms. Timed-release supplemental niacin (OTC) can produce fewer superficial adverse effects (e.g., flushing) but can also be more hepatotoxic. Nicotinic acid in a shorter-acting, timed-release preparation, sometimes referred to as “intermediate release” or “extended release,” is available by prescription. Limited but relatively consistent evidence indicates that inositol hexaniacinate may be the best-tolerated form of niacin, with minimal incidence of skin flushing, nausea, vomiting, agitation, and hepatotoxicity. 2-4

Within conventional medical practice the crystalline, immediate-release form (usually taken two to four times daily) and the extended-release form (once daily) are the two prescription formulations of niacin approved for treatment of dyslipidemia. The American Heart Association advises against using OTC supplemental niacin. 5

Note: Niacin dosage values for requirements and foods are described in niacin equivalents (NE), which are calculated by combining nicotinic acid and niacinamide intake and adding an estimate for tryptophan conversion. Niacin (mg equivalents)=Nicotinic acid (mg) + Nicotinamide (mg) + Tryptophan (mg)/60

Dosage Forms Available

Capsule, liquid, powder, tablet, effervescent tablet. Injectable forms are sometimes administered by health care professionals.

Source Materials for Nutrient Preparations

All B vitamins are predominantly synthesized, except for the “food form,” in which synthesized B vitamins are added to nutrient broth for yeast, which (supposedly) incorporates higher amounts of them into the cells, which are then dried and tableted.

Dosage Range

Adult

  • Dietary:   The U.S. dietary reference intake (DRI) for niacin is 16 mg niacin equivalents per day for men and 14 mg equivalents daily for women. 6 Pregnant or lactating women: 18 mg daily.

  • Supplemental/Maintenance:   100 mg daily, combined forms.

  • Pharmacological/Therapeutic:   500 mg three times daily.

  • Toxic:   U.S. tolerable upper limit (UL) established for nicotinic acid in adults is 35 mg per day; this level was selected to avoid the adverse effect of flushing in the general population, even though flushing and other adverse effects from nicotinamide are significantly less common. No separate tolerable UL has been established for nicotinamide. Reports of nicotinamide overdosage are not present in the literature.

  • Nicotinic acid/niacin:   Transient acute flushing symptoms can occur at 100 to 200 mg niacin. Elevated liver enzymes, jaundice, and other signs of hepatotoxicity have been observed at nicotinic acid intakes as low as 750 mg/day for less than 3 months. Timed-release nicotinic acid has been associated with chemical hepatitis at levels as low as 500 mg/day for 2 months, although most cases have involved significantly higher doses and longer periods of intake,

  • Nicotinamide/niacinamide:   Low toxicity generally characterizes the safety profile of nicotinamide. Intake of 3 g/day of nicotinamide for longer than 3 months has been associated with adverse effects such as nausea, vomiting, elevated liver enzymes, and jaundice. However, rare occurrences of liver toxicity have been reported at doses in excess of 1000 mg/day.

Pediatric (<18 Years)

Dietary:

  • Infants, birth to 6 months: 2 mg/day (AI, adequate intake)
  • Infants, 7 to 12 months: 4 mg/day (AI)
  • Children, 1 to 3 years: 6 mg/day (RDA)
  • Children, 4 to 8 years: 8 mg/day (RDA)
  • Children, 9 to 13 years: 12 mg/day (RDA)
  • Adolescents, 14 to 18 years: 14 mg (females) or 16 mg (males) daily (RDA)

  • Supplemental/Maintenance:   Usually not recommended for children under 12 years of age. Avoid extended-release forms.

  • Pharmacological/Therapeutic:   Usually not recommended for children under 12 years of age. Niacinamide has been administered in research and clinical settings involving prevention of type 1 diabetes mellitus in “high-risk” individuals at daily doses of 150 to 300 mg per year of the child's age, or 25 mg per kilogram body weight daily. Avoid extended-release forms.

  • Toxic:   No tolerable UL for niacin in infants has been proposed. The U.S. tolerable UL established for niacin in children age 1 to 8 years is 10 to 15 mg daily and 20 mg daily for children 9 to 13 years; for adolescents (14-18 years) it is 30 mg daily. These levels were selected to avoid the adverse effect of flushing in the general population; flushing from nicotinamide is unreported and not considered an associated effect.

Laboratory Values

Cellular NAD and NADP content: Some clinicians and researchers suggest this test may provide the most clinically relevant indicators of niacin nutritional status. 7

  • Erythrocyte nicotinamide adenine nucleotide (NAD):   This test can provide a sensitive indicator of niacin status.

  • Red blood cell (RBC) NAD/NADP ratio:   A ratio of RBC NAD to RBC nicotinamide nucleotide phosphate (NADP) less than 1.0 may indicate deficiency.

  • Urinary 1- N-methyl-nicotinamide (NMN) and 2- N-pyridone (2-N-P):   Excretion of less than 0.8 mg NMN per day and/or less than 1.0 mg 2-N-P per day indicates niacin deficiency. Although this measurement of excretion levels of major niacin metabolites can provide relatively accurate indices of niacin status, the results are often not conclusive.

  • Whole-blood niacin:   Reference range 1.2 to 2.9 µg/mL.

  • Abnormal liver function studies:   All individuals taking pharmacological doses of niacin should be monitored for liver function and enzyme levels; elevations in AST (SGOT) and ALT (SGPT) are common.

  • Lymphocytic growth response.

Niacin or nicotinic acid administration can alter findings from several laboratory tests.

Urinary catecholamine concentration measurements by fluorimetric methods may be falsely elevated by niacin.

  • Urine glucose determination using Benedict's reagent (cupric sulfate) may produce false-positive reactions. However, nicotinic acid may elevate blood glucose levels.
  • Nicotinic acid may falsely elevate blood growth hormone levels.
  • High-dose nicotinic acid may elevate blood uric acid levels.
  • Niacin may falsely elevate homocysteine (Hcy) levels (by interference with the assay). It can also truly elevate Hcy levels by consuming methyl donor nutrients in its metabolism.

Niacin may decrease high-sensitivity C-reactive protein (hsCRP).

safety profile

Overview

The safety profile for pharmacological preparations of vitamin B3varies significantly for different forms of the nutrient and exhibits a major differentiation between short-term, nonthreatening but uncomfortable adverse effects and longer-term toxicity. Evaluation of vitamin B3toxicity is further complicated by over 50 years of research findings and clinical observations that use varied preparations and poor methodology or that are inadequately powered, rendering contradictory and inconsistent conclusions, and that are often simply obsolete or clinically irrelevant.

Generally, adverse effects (predominantly flushing and itching) are significantly more likely with nicotinic acid than with nicotinamide, and, conversely, nicotinamide is better tolerated than nicotinic acid. Moreover, adverse reactions to niacinamide, at doses less than 1000 mg/day, are rare (and possibly linked to impure materials), and as such the nutrient is generally considered safe in most situations. 8-11However, the possibility exists that adverse effects of niacinamide have not been adequately documented because significantly fewer clinical trials have involved niacinamide and the lack of data simply reflects a study bias. No adverse effects are associated with intake of niacin from food sources in typically consumed forms. 6 Adverse effects ranging from minor discomfort to severe toxicity are possible with nicotinic acid. Close supervision and regular monitoring are warranted when administering doses of niacin greater than 1000 mg/day.

Nutrient Adverse Effects

General Adverse Effects

Niacin often causes skin flushing with burning and tingling sensations, especially in the face, at levels more than 100 mg, although some sensitive individuals can experience flushing with as low a dose as 10 to 20 mg. These symptoms are of rapid onset and limited duration and may be accompanied by stomach distress, itching, and headache. The vasodilatory response involved constitutes a significant mechanism of action in the therapeutic action of niacin and is considered beneficial by many who self-administer niacin. However, many patients who discontinue or refuse niacin do so to avoid this unpleasant effect. These niacin-induced adverse effects typically resolve with discontinuation. Tachyphalaxis also develops with continued daily use, although tolerance may disappear with breaks of just a few days, but is usually quickly reestablished shortly after daily intake is resumed.

Nausea and GI upset are usually the first signs of toxicity with both niacin and niacinamide. Niacin is excreted as methylated pyridones, the formation of which uses S-adenosylmethionine (SAMe), the primary physiological methyl donor. The resulting niacin-induced interference with methionine metabolism and depletion of SAMe impairs detoxification processes and contributes to many of niacin's adverse effects, including decreased levels of vitamin B6and increased plasma homocysteine concentrations. Changes in hepatic transaminase enzyme levels, indicating liver inflammation, are often the second detectable sign of niacin toxicity. Prudence warrants that aspartate transaminase (AST, SGOT) and alanine transaminase (ALT, SGPT) be monitored regularly during therapy with any form of niacin. Elevated liver enzymes, jaundice, and other signs of hepatotoxicity have been observed at nicotinic acid intakes as low as 500 mg/day for less than 3 months, although doses of 1500 to 3000 mg/day are more typically associated with clinically significant adverse effects. A significant body of evidence indicates that slow-release or extended-release forms of niacin are more likely to cause adverse effects and hepatic toxicity reactions. Niacin administration needs to be discontinued or the dose significantly reduced at first indication of adverse effects on liver function. When initiating pharmacological doses of time-release niacin, beginning with 500 mg and increasing by 500 mg each month up to the target dose (usually 1.5-3.0 g) improves tolerance to the therapy.

Other symptoms rarely or infrequently associated with niacin intake include headache, dizziness, anxiety, panic attacks, hypothyroidism, abnormal cardiac rhythms, heart palpitations, difficult breathing, lactic acidosis, myopathy, elevated creatine kinase levels, tooth or gum pain, macular swelling, blurred vision, and toxic amblyopia.

In a multicenter randomized, placebo-controlled trial, Garg et al. 12 found that niacin therapy, at 1000 mg or more per day, can substantially increase plasma homocysteine levels.

Niacinamide, at high dosage levels, has been associated with nausea, heartburn, vomiting, flatulence, and diarrhea. Parenteral administration of niacinamide has been reported to cause mild headaches and dizziness.

Rare occurrences of anaphylactic shock have been reported following intravenous or oral niacin therapy.

Adverse Effects Among Specific Populations

Individual characteristics that increase susceptibility to adverse effects from excess nicotinic acid intake include abnormal liver function or a history of liver disease, active peptic ulcer disease, alcohol abuse, diabetes, hypoglycemia, gout, cardiac arrhythmias, severe hypotension, inflammatory bowel disease, and migraine headaches.

Pregnancy and Nursing

Use of niacin supplementation during pregnancy or breastfeeding is not recommended because research on safety and effectiveness is insufficient. No problems have been reported.

Children

Use of niacin supplementation in children is not recommended because of insufficient research on safety and effectiveness and diminished hepatic detoxification capacity. No problems have been reported.

Contraindications

Vitamin B3is contraindicated in persons with hypersensitivity or allergy to niacin or niacin-containing substances and in children under 12 years of age, especially time-release forms.

Precautions and Warnings

Niacin should be avoided, or used only under close supervision and with appropriate monitoring, in patients with liver disease or compromised hepatic function, especially time-release forms.

Concomitant use of niacin and HMG-CoA reductase inhibitors (statins) significantly increases the risk of adverse effects, ranging from mild and reversible to severe and potentially fatal, especially in patients with compromised renal or hepatic function (see later discussion).

For decades, warnings have been voiced regarding potential risks for individuals with diabetes or hypoglycemia. Nicotinic acid can induce elevation in blood glucose and depletion of glycogen stores. Recent clinical trials found that niacin does not appear to raise blood glucose levels in patients with type 2 diabetes. 13,14Thus, although niacin may cause significant alterations in blood sugar levels and insulin, such effects warrant clinical management rather than avoidance. (See Nutrient-Drug Interactions.)

Niacin can increase uric acid production and elevate blood uric acid concentrations. Individuals with gout, or predisposition to gout, should be administered niacin only under close supervision, preferably within the context of a comprehensive approach to dietary change and risk reduction. This adverse effect is primarily theoretical and evidence preliminary or inconsistent.

Niacin may elevate plasma homocysteine levels and should only be used under close supervision and with appropriate monitoring by patients with hyperhomocysteinemia or elevated risk of stroke or heart disease.

High-dose niacin intake can aggravate peptic ulcer and should be avoided in these patients except under close supervision and with appropriate monitoring.

Rare occurrences of leukopenia and slightly increased blood eosinophils have been reported in individuals taking niacin. Caution is advised in patients with bleeding disorders or undergoing anticoagulant therapy.

interactions review

Strategic Considerations

With its long-standing role within standard practice of cardiovascular care, niacin is a nutrient that belies the labels of “alternative” and “conventional” and demonstrates the importance of an integrative approach to risk reduction and therapeutic intervention based on scientific evidence and clinical outcomes. The use of niacin with statins, resins, and fibrates is well established in conventional medicine. As such, niacin confirms the need for a multidisciplinary and collaborative model in both the benefits it conveys and the risks it amplifies when coadministered with various drug regimens and in the ways in which a strategic approach employing multiple nutrients can reduce adverse effects, optimize efficacy, and expand benefits.

Vitamin B3is among the most frequently researched nutrients in conventional medicine. However, a review of the available evidence illustrates that the combination of widespread usage and scientific research of limited character and narrow focus has resulted in an incomplete and unevenly distributed set of data characterized by many more speculative, ill-founded, or inadequately investigated “interactions” than thoroughly researched and well-documented ones.

Niacin can play an important role in a comprehensive strategy for reducing dyslipidemia and the risk of coronary disease, but low doses may be safer and just as effective as high doses. Also, there is an even greater need to coadminister vitamins B6and B12and folate, as well as methyl donor support through nutrients such as SAMe and betaine, to counter the tendencies to hepatoxicity and hyperhomocysteinemia, especially if statins are also employed. The issue of how antioxidants, singly or as networks, may interact with niacin to impair some of its therapeutic activity deserves focused research.

Two primary issues consistently arise regarding clinical application of niacin: toxicity and glucose control. The issue of toxicity is inherent to the nature of niacin and manifests primarily in adverse effects on the liver and interference with B6-tryptophan-methionine metabolism, leading to elevation of homocysteine (Hcy). The use of low-dose niacin or the alternative administration of nontoxic inositol hexaniacinate may adequately address the former. Coadministration of B2, B6, B12, folic acid, SAMe, and possibly betaine may diffuse the adverse effect on methyl donor supply and Hcy regulation.

The issue of interference with glucose control, particularly the often-asserted possibility of interference with oral hypoglycemic medications, may have been resolved with recent evidence indicating a lack of clinically significant interaction; nevertheless, continued research into potential benefits, drawbacks, and clinical implementation of coadministration is needed. Regular monitoring of liver enzyme levels, specifically AST and ALT, as well as plasma Hcy, is critical whenever administering niacin, especially in conjunction with statins.

The multiple concerns with niacin-induced toxicity highlight the need for further research into the efficacy of inositol hexaniacinate, or low-dose niacin, for treatment of dyslipidemias.

Likewise, the role of niacinamide in relation to insulin sensitivity, glucose tolerance, and dysglycemia suggests the need for integrative strategies that can both prevent the progression of dysfunction to disease and evolve within a multidisciplinary treatment strategy that responds flexibly to improvement or decline in the patient's condition.

In almost all its uses, vitamin B3exemplifies several fundamental principles operative in the clinical practice of integrative medicine. Less may do more, or enough, for any given agent. Static monotherapy using any agent is often less effective than flexible, personalized, and synergistic polypharmacy/polynutrient strategies crafted to the individual patient and evolving with their changing condition. Moreover, the spectrum of clinical applications for niacin and niacinamide and these agents’ interactions with various drugs emphasize the importance of the guiding principles in the management of most clinically significant interactions: the centrality of physician-patient trust and dialogue, the importance of collaboration among health care professionals bringing together various perspectives and expertises, the continuum of dosage from nutrient support to pharmacological intervention, the opportunities to emphasize therapeutic actions or mitigate adverse effects through combinations and dosage manipulation, and the essential need for ongoing supervision, monitoring, and titration.

nutrient-drug interactions
Acetylsalicylic Acid, Acetaminophen, and Related Nonsteroidal Anti-Inflammatory Drugs (NSAIDs)
Anticonvulsant Medications, Including Phenobarbital, Phenytoin, and Valproic Acid
Bile Acid Sequestrants
Gemfibrozil and Related Fibrates
HMG-CoA Reductase Inhibitors (Statins)
Insulin, Biguanides, Meglitinide Analog Oral Hypoglycemics
Isoniazid, Rifampin, and Related Antitubercular Agents
Mercaptopurine, Azathioprine, and Thioguanine (Thiopurines)
Tetracycline Antibiotics
Thioridazine and Related Phenothiazines
Tricyclic Antidepressants (TCAs)
Ursodeoxycholic Acid and Chenodeoxycholic Acid
Radiotherapy
theoretical, speculative, and preliminary interactions research, including overstated interactions claims
Adrenoreceptor Antagonists (Systemic)
Atypical Antipsychotics
Benzodiazepines
Benztropine
Carbidopa and Related Antiparkinsonian Agents
Fluorouracil (5-FU)
Ganglionic Blocking Agents
Griseofulvin
Guanethidine
Neomycin
Nicotine Transdermal Patches
Oral Contraceptives: Monophasic, Biphasic, and Triphasic Estrogen Preparations (Synthetic Estrogen and Progesterone Analogs)

Ethinyl estradiol and desogestrel (Desogen, Ortho-TriCyclen).

Ethinyl estradiol and ethynodiol (Demulen 1/35, Demulen 1/50, Nelulen 1/25, Nelulen 1/50, Zovia).

Ethinyl estradiol and levonorgestrel (Alesse, Levlen, Levlite, Levora 0.15/30, Nordette, Tri-Levlen, Triphasil, Trivora).

Ethinyl estradiol and norethindrone/norethisterone (Brevicon, Estrostep, Genora 1/35, GenCep 1/35, Jenest-28, Loestrin 1.5/30, Loestrin1/20, Modicon, Necon 1/25, Necon 10/11, Necon 0.5/30, Necon 1/50, Nelova 1/35, Nelova 10/11, Norinyl 1/35, Norlestin 1/50, Ortho Novum 1/35, Ortho Novum 10/11, Ortho Novum 7/7/7, Ovcon-35, Ovcon-50, Tri-Norinyl, Trinovum).

Ethinyl estradiol and norgestrel (Lo/Ovral, Ovral).

Mestranol and norethindrone (Genora 1/50, Nelova 1/50, Norethin 1/50, Ortho-Novum 1/50).

  • Related, internal application:

    Etonogestrel/ethinyl estradiol vaginal ring (Nuvaring).

Norethindrone Enanthate
Pargyline
Pyrazinamide
Selective Serotonin Reuptake Inhibitor and Serotonin-Norepinephrine Reuptake Inhibitor (SSRI and SSRI/SNRI) Antidepressants
Sulfinpyrazone and Probenecid
Warfarin and Other Anticoagulants
nutrient-nutrient interactions
Antioxidants
Betaine
Chromium
Phytosterols
Policosanol
S -Adenosylmethionine (SAMe)
Vitamin B 6 (Pyridoxine)
Zinc
Citations and Reference Literature
  • 1.Jacobson EL, Jacobson MK. Tissue NAD as a biochemical measure of niacin status in humans. Methods Enzymol 1997;280:221-230.View Abstract
  • 2.Welsh AL, Ede M. Inositol hexanicotinate for improved nicotinic acid therapy: preliminary report. Int Rec Med 1961;174:9-15.View Abstract
  • 3.Ziliotto GR, Lamberti G, Wagner A et al. [Comparative studies of the response of normolipemic and dyslipemic aged subjects to 2 forms of delayed-action nicotinic acid polyesters, pentaerythrotol tetranicotinate and inositol hexanicotinate: results of a controlled crossover trial]. Arch Sci Med (Torino) 1977;134:359-394.
  • 4.Head KA. Inositol hexaniacinate: a safer alternative to niacin. Alt Med Rev 1996;1:176-184.
  • 5.Mosca L, Appel LJ, Benjamin EJ et al. Evidence-based guidelines for cardiovascular disease prevention in women. Circulation 2004;109:672-693.View Abstract
  • 6.Food and Nutrition Board, Institute of Medicine. Niacin. Dietary Reference Intakes: Thiamin, Riboflavin, Niacin, Vitamin B6, Vitamin B12, Pantothenic Acid, Biotin, and Choline. Washington, DC: National Academy Press; 1998:123-149.
  • 7.Fu CS, Swendseid ME, Jacob RA, McKee RW. Biochemical markers for assessment of niacin status in young men: levels of erythrocyte niacin coenzymes and plasma tryptophan. J Nutr 1989;119:1949-1955.View Abstract
  • 8.Hoffer A. Safety, side effects and relative lack of toxicity of nicotinic acid and nicotinamide. Schizophrenia 1969;1:78-87.
  • 9.Winter SL, Boyer JL. Hepatic toxicity from large doses of vitamin B3 (nicotinamide). N Engl J Med 1973;289:1180-1182.View Abstract
  • 10.Pozzilli P, Visalli N, Signore A et al. Double blind trial of nicotinamide in recent-onset IDDM (the IMDIAB III study). Diabetologia 1995;38:848-852.View Abstract
  • 11.Knip M, Douek IF, Moore WP et al. Safety of high-dose nicotinamide: a review. Diabetologia 2000;43:1337-1345.View Abstract
  • 12.Garg R, Malinow M, Pettinger M et al. Niacin treatment increases plasma homocyst(e)ine levels. Am Heart J 1999;138:1082-1087.View Abstract
  • 13.Elam MB, Hunninghake DB, Davis KB et al. Effect of niacin on lipid and lipoprotein levels and glycemic control in patients with diabetes and peripheral arterial disease: the ADMIT study: a randomized trial. Arterial Disease Multiple Intervention Trial. JAMA 2000;284:1263-1270.View Abstract
  • 14.Grundy SM, Mok HY, Zech L, Berman M. Influence of nicotinic acid on metabolism of cholesterol and triglycerides in man. J Lipid Res 1981;22:24-36.View Abstract
  • 15.Ding RW, Kolbe K, Merz B et al. Pharmacokinetics of nicotinic acid–salicylic acid interaction. Clin Pharmacol Ther 1989;46:642-647.View Abstract
  • 16.Whelan AM, Price SO, Fowler SF, Hainer BL. The effect of aspirin on niacin-induced cutaneous reactions. J Fam Pract 1992;34:165-168.View Abstract
  • 17.Jungnickel PW, Maloley PA, Vander Tuin EL et al. Effect of two aspirin pretreatment regimens on niacin-induced cutaneous reactions. J Gen Intern Med 1997;12:591-596.View Abstract
  • 18.Bourgeois BF, Dodson WE, Ferrendelli JA. Interactions between primidone, carbamazepine, and nicotinamide. Neurology 1982;32:1122-1126.
  • 19.Kryzhanovskii GN, Shandra AA. [Effect of diazepam, carbamazepine, sodium valproate and their combinations with vitamin preparations on epileptic activity]. Biull Eksp Biol Med 1985;100:545-547.View Abstract
  • 20.Cashin-Hemphill L, Spencer CA, Nicoloff JT et al. Alterations in serum thyroid hormonal indices with colestipol-niacin therapy. Ann Intern Med 1987;107:324-329.View Abstract
  • 21.Nessim SA, Chin HP, Alaupovic P, Blankenhorn DH. Combined therapy of niacin, colestipol, and fat-controlled diet in men with coronary bypass: effect on blood lipids and apolipoproteins. Arteriosclerosis 1983;3:568-573.View Abstract
  • 22.Blankenhorn DH, Azen SP, Nessim SA. Treatment of hyperlipidaemia and progression of atherosclerosis. Lancet 1983;2:1193.View Abstract
  • 23.Blankenhorn DH, Johnson RL, Nessim SA et al. The Cholesterol Lowering Atherosclerosis Study (CLAS): design, methods, and baseline results. Control Clin Trials 1987;8:356-387.View Abstract
  • 24.Blankenhorn DH, Nessim SA, Johnson RL et al. Beneficial effects of combined colestipol-niacin therapy on coronary atherosclerosis and coronary venous bypass grafts. JAMA1987;257:3233-3240.View Abstract
  • 25.Cashin-Hemphill L, Mack WJ, Pogoda JM et al. Beneficial effects of colestipol-niacin on coronary atherosclerosis: a 4-year follow-up. JAMA1990;264:3013-3017.
  • 26.Blankenhorn DH, Azen SP, Crawford DW et al. Effects of colestipol-niacin therapy on human femoral atherosclerosis. Circulation 1991;83:438-447.View Abstract
  • 27.Blankenhorn DH, Selzer RH, Mack WJ et al. Evaluation of colestipol/niacin therapy with computer-derived coronary end point measures: a comparison of different measures of treatment effect. Circulation 1992;86:1701-1709.View Abstract
  • 28.Blankenhorn DH, Selzer RH, Crawford DW et al. Beneficial effects of colestipol-niacin therapy on the common carotid artery: two- and four-year reduction of intima-media thickness measured by ultrasound. Circulation 1993;88:20-28.View Abstract
  • 29.Blankenhorn DH, Hodis HN. Atherosclerosis: reversal with therapy. West J Med 1993;159:172-179.View Abstract
  • 30.Mack WJ, Selzer RH, Hodis HN et al. One-year reduction and longitudinal analysis of carotid intima-media thickness associated with colestipol/niacin therapy. Stroke 1993;24:1779-1783.View Abstract
  • 31.Azen SP, Mack WJ, Cashin-Hemphill L et al. Progression of coronary artery disease predicts clinical coronary events: long-term follow-up from the Cholesterol Lowering Atherosclerosis Study. Circulation 1996;93:34-41.View Abstract
  • 32.Blankenhorn DH, Alaupovic P, Wickham E et al. Prediction of angiographic change in native human coronary arteries and aortocoronary bypass grafts: lipid and nonlipid factors. Circulation 1990;81:470-476.View Abstract
  • 33.Azen SP, Cashin-Hemphill L, Pogoda J et al. Evaluation of human panelists in assessing coronary atherosclerosis. Arterioscler Thromb 1991;11:385-394.View Abstract
  • 34.Mack WJ, Selzer RH, Pogoda JM et al. Comparison of computer- and human-derived coronary angiographic end-point measures for controlled therapy trials. Arterioscler Thromb 1992;12:348-356.View Abstract
  • 35.Sprecher DL. Raising high-density lipoprotein cholesterol with niacin and fibrates: a comparative review. Am J Cardiol 2000;86:46L-50L.View Abstract
  • 36.Ascaso JF, Fernandez-Cruz A, Gonzalez Santos P et al. Significance of high density lipoprotein-cholesterol in cardiovascular risk prevention: recommendations of the HDL Forum. Am J Cardiovasc Drugs 2004;4:299-314.View Abstract
  • 37.Spencer GA, Wirebaugh S, Whitney EJ. Effect of a combination of gemfibrozil and niacin on lipid levels. J Clin Pharmacol 1996;36:696-700.View Abstract
  • 38.Andrews TC, Whitney EJ, Green G et al. Effect of gemfibrozil± niacin± cholestyramine on endothelial function in patients with serum low-density lipoprotein cholesterol levels <160 mg/dl and high-density lipoprotein cholesterol levels <40 mg/dl. Am J Cardiol 1997;80:831-835.View Abstract
  • 39.Zema MJ. Gemfibrozil, nicotinic acid and combination therapy in patients with isolated hypoalphalipoproteinemia: a randomized, open-label, crossover study. J Am Coll Cardiol 2000;35:640-646.View Abstract
  • 40.Sakai T, Kamanna VS, Kashyap ML. Niacin, but not gemfibrozil, selectively increases LP-AI, a cardioprotective subfraction of HDL, in patients with low HDL cholesterol. Arterioscler Thromb Vasc Biol 2001;21:1783-1789.View Abstract
  • 41.Whitney EJ, Krasuski RA, Personius BE et al. A randomized trial of a strategy for increasing high-density lipoprotein cholesterol levels: effects on progression of coronary heart disease and clinical events. Ann Intern Med 2005;142:95-104.View Abstract
  • 42.Dierkes J, Westphal S, Luley C. The effect of fibrates and other lipid-lowering drugs on plasma homocysteine levels. Expert Opin Drug Saf 2004;3:101-111.View Abstract
  • 43.Wald DS, Wald NJ, Morris JK, Law M. Folic acid, homocysteine, and cardiovascular disease: judging causality in the face of inconclusive trial evidence. BMJ 2006;333:1114-1117.View Abstract
  • 44.Bruno-Joyce J, Dugas JM, MacCausland OE. Cerivastatin and gemfibrozil-associated rhabdomyolysis. Ann Pharmacother 2001;35:1016-1019.View Abstract
  • 45.Shek A, Ferrill MJ. Statin-fibrate combination therapy. Ann Pharmacother 2001;35:908-917.View Abstract
  • 46.Sacks FM. The role of high-density lipoprotein (HDL) cholesterol in the prevention and treatment of coronary heart disease: expert group recommendations. Am J Cardiol 2002;90:139-143.View Abstract
  • 47.Boden WE. Therapeutic implications of recent ATP III guidelines and the important role of combination therapy in total dyslipidemia management. Curr Opin Cardiol 2003;18:278-285.View Abstract
  • 48.Kashyap ML, Tavintharan S, Kamanna VS. Optimal therapy of low levels of high density lipoprotein-cholesterol. Am J Cardiovasc Drugs 2003;3:53-65.View Abstract
  • 49.Morgan JM, Carey CM, Lincoff A, Capuzzi DM. The effects of niacin on lipoprotein subclass distribution. Prev Cardiol 2004;7:182-187; quiz 188.View Abstract
  • 50.Morgan J, Carey C, Lincoff A, Capuzzi D. High-density lipoprotein subfractions and risk of coronary artery disease. Curr Atheroscler Rep 2004;6:359-365.View Abstract
  • 51.Studer M, Briel M, Leimenstoll B et al. Effect of different antilipidemic agents and diets on mortality: a systematic review. Arch Intern Med 2005;165:725-730.View Abstract
  • 52.Wright RS, Bybee K, Miller WL et al. Reduced risks of death and CHF are associated with statin therapy administered acutely within the first 24 h of AMI. Int J Cardiol 2006;108:314-319.
  • 53.Knopp RH, d’Emden M, Smilde JG, Pocock SJ. Efficacy and safety of atorvastatin in the prevention of cardiovascular end points in subjects with type 2 diabetes: the Atorvastatin Study for Prevention of Coronary Heart Disease Endpoints in non-insulin-dependent diabetes mellitus (ASPEN). Diabetes Care 2006;29:1478-1485.
  • 54.Wilke RA, Moore JH, Burmester JK. Relative impact of CYP3A genotype and concomitant medication on the severity of atorvastatin-induced muscle damage. Pharmacogenet Genomics 2005;15:415-421.View Abstract
  • 55.Bilheimer DW. Long-term clinical tolerance of lovastatin and simvastatin. Cardiology 1990;77 Suppl 4:58-65.View Abstract
  • 56.LaRosa JC, Grundy SM, Waters DD et al. Intensive lipid lowering with atorvastatin in patients with stable coronary disease. N Engl J Med 2005;352:1425-1435.View Abstract
  • 57.Go AS, Lee WY, Yang J et al. Statin therapy and risks for death and hospitalization in chronic heart failure. JAMA 2006;296:2105-2111.View Abstract
  • 58.Basu TK, Mann S. Vitamin B-6 normalizes the altered sulfur amino acid status of rats fed diets containing pharmacological levels of niacin without reducing niacin’s hypolipidemic effects. J Nutr 1997;127:117-121.
  • 59.Stead LM, Au KP, Jacobs RL et al. Methylation demand and homocysteine metabolism: effects of dietary provision of creatine and guanidinoacetate. Am J Physiol Endocrinol Metab 2001;281:E1095-E1100.View Abstract
  • 60.Basu TK, Makhani N, Sedgwick G. Niacin (nicotinic acid) in non-physiological doses causes hyperhomocysteineaemia in Sprague-Dawley rats. Br J Nutr 2002;87:115-119.View Abstract
  • 61.Malloy MJ, Kane JP, Kunitake ST, Tun P. Complementarity of colestipol, niacin, and lovastatin in treatment of severe familial hypercholesterolemia. Ann Intern Med 1987;107:616-623.View Abstract
  • 62.Davignon J, Roederer G, Montigny M et al. Comparative efficacy and safety of pravastatin, nicotinic acid and the two combined in patients with hypercholesterolemia. Am J Cardiol 1994;73:339-345.View Abstract
  • 63.Jacobson TA, Jokubaitis LA, Amorosa LF. Fluvastatin and niacin in hypercholesterolemia: a preliminary report on gender differences in efficacy. Am J Med 1994;96:64S-68S.View Abstract
  • 64.O’Keefe JH Jr, Harris WS, Nelson J, Windsor SL. Effects of pravastatin with niacin or magnesium on lipid levels and postprandial lipemia. Am J Cardiol 1995;76:480-484.
  • 65.Jokubaitis LA. Fluvastatin in combination with other lipid-lowering agents. Br J Clin Pract Suppl 1996;77A:28-32.View Abstract
  • 66.Gardner SF, Marx MA, White LM et al. Combination of low-dose niacin and pravastatin improves the lipid profile in diabetic patients without compromising glycemic control. Ann Pharmacother 1997;31:677-682.
  • 67.Guyton JR, Goldberg AC, Kreisberg RA et al. Effectiveness of once-nightly dosing of extended-release niacin alone and in combination for hypercholesterolemia. Am J Cardiol 1998;82:737-743.View Abstract
  • 68.Goldberg AC. Clinical trial experience with extended-release niacin (Niaspan): dose-escalation study. Am J Cardiol 1998;82:35U-38U; discussion 39U-41U.View Abstract
  • 69.Goldberg A, Alagona P Jr, Capuzzi DM et al. Multiple-dose efficacy and safety of an extended-release form of niacin in the management of hyperlipidemia. Am J Cardiol 2000;85:1100-1105.View Abstract
  • 70.McKenney JM, McCormick LS, Schaefer EJ et al. Effect of niacin and atorvastatin on lipoprotein subclasses in patients with atherogenic dyslipidemia. Am J Cardiol 2001;88:270-274.View Abstract
  • 71.Brown BG, Zhao XQ, Chait A et al. Simvastatin and niacin, antioxidant vitamins, or the combination for the prevention of coronary disease. N Engl J Med 2001;345:1583-1592.View Abstract
  • 72.Brown BG, Cheung MC, Lee AC et al. Antioxidant vitamins and lipid therapy: end of a long romance? Arterioscler Thromb Vasc Biol 2002;22:1535-1546.
  • 73.Kashyap ML, McGovern ME, Berra K et al. Long-term safety and efficacy of a once-daily niacin/lovastatin formulation for patients with dyslipidemia. Am J Cardiol 2002;89:672-678.View Abstract
  • 74.Wink J, Giacoppe G, King J. Effect of very-low-dose niacin on high-density lipoprotein in patients undergoing long-term statin therapy. Am Heart J 2002;143:514-518.View Abstract
  • 75.Taylor AJ, Kent SM, Flaherty PJ et al. ARBITER: Arterial Biology for the Investigation of the Treatment Effects of Reducing Cholesterol: a randomized trial comparing the effects of atorvastatin and pravastatin on carotid intima medial thickness. Circulation 2002;106:2055-2060.View Abstract
  • 76.Taylor AJ, Sullenberger LE, Lee HJ et al. Arterial Biology for the Investigation of the Treatment Effects of Reducing Cholesterol (ARBITER) 2: a double-blind, placebo-controlled study of extended-release niacin on atherosclerosis progression in secondary prevention patients treated with statins. Circulation 2004;110:3512-3517.View Abstract
  • 77.Taylor AJ, Sullenberger LE, Lee HJ. Atherosclerosis regression during open-label extended-release niacin following ARBITER 2. American Heart Association Scientific Sessions 2005. Dallas, Texas; 2005.
  • 78.Stanek EJ, Sarawate C, Cziraky MJ, Charland SL. Impact of combined optimal lipid value achievement on risk of cardiovascular events in prevention, gender, and diabetes subgroups. American Heart Association Scientific Sessions 2005. Dallas, Texas; 2005.
  • 79.Reaven P, Witztum JL. Lovastatin, nicotinic acid, and rhabdomyolysis. Ann Intern Med 1988;109:597-598.View Abstract
  • 80.Norman DJ, Illingworth DR, Munson J, Hosenpud J. Myolysis and acute renal failure in a heart-transplant recipient receiving lovastatin. N Engl J Med 1988;318:46-47.View Abstract
  • 81.Langsjoen PH. Personal communication; 2005.
  • 82.Stockley IH. Drug Interactions. 6th ed. London: Pharmaceutical Press; 2002.
  • 83.Fuccella LM, Goldaniga G, Lovisolo P et al. Inhibition of lipolysis by nicotinic acid and by acipimox. Clin Pharmacol Ther 1980;28:790-795.View Abstract
  • 84.Randle PJ, Garland PB, Hales CN, Newsholme EA. The glucose fatty-acid cycle: its role in insulin sensitivity and the metabolic disturbances of diabetes mellitus. Lancet 1963;1:785-789.View Abstract
  • 85.Heller B, Wang ZQ, Wagner EF et al. Inactivation of the poly(ADP-ribose) polymerase gene affects oxygen radical and nitric oxide toxicity in islet cells. J Biol Chem 1995;270:11176-11180.View Abstract
  • 86.Vague P, Vialettes B, Lassmann-Vague V, Vallo JJ. Nicotinamide may extend remission phase in insulin-dependent diabetes. Lancet 1987;1:619-620.View Abstract
  • 87.Pozzilli P, Visalli N, Ghirlanda G et al. Nicotinamide therapy in patients with newly-diagnosed type 1 (insulin-dependent) diabetes. Diabetologia 1988;31:533A.
  • 88.Pozzilli P, Visalli N, Ghirlanda G et al. Nicotinamide increases C-peptide secretion in patients with recent onset type 1 diabetes. Diabet Med 1989;6:568-572.View Abstract
  • 89.Chase HP, Butler-Simon N, Garg S et al. A trial of nicotinamide in newly diagnosed patients with type 1 (insulin-dependent) diabetes mellitus. Diabetologia 1990;33:444-446.View Abstract
  • 90.Pozzilli P. The IMDIAB I multicentre study in newly diagnosed insulin dependent diabetic patients: final results. Diabetologia 1991;34:A29.
  • 91.Paskova M, I. Ikao I, Trozova D, et al. Nicotinamide treatment in children with newly diagnosed type 1 diabetes mellitus. Diabetologia 1992;35:A203.
  • 92.Elliott RB, Chase HP. Prevention or delay of type 1 (insulin-dependent) diabetes mellitus in children using nicotinamide. Diabetologia 1991;34:362-365.View Abstract
  • 93.Paul TL, Hramiak IM, Mahon JL et al. Nicotinamide and insulin sensitivity. Diabetologia 1993;36:369.View Abstract
  • 94.Herskowitz RD, Jackson RA, Soeldner JS, Eisenbarth GS. Pilot trial to prevent type I diabetes: progression to overt IDDM despite oral nicotinamide. J Autoimmun 1989;2:733-737.View Abstract
  • 95.Lampeter EF, Klinghammer A, Scherbaum WA et al. The Deutsche Nicotinamide Intervention Study: an attempt to prevent type 1 diabetes. DENIS Group. Diabetes 1998;47:980-984.View Abstract
  • 95a.Greenbaum CJ, Kahn SE, Palmer JP. Nicotinamide’s effects on glucose metabolism in subjects at risk for IDDM. Diabetes 1996;45(11):1631-1634.
  • 96.Bingley PJ, Caldas G, Bonfanti R, Gale EA. Nicotinamide and insulin secretion in normal subjects. Diabetologia 1993;36:675-677.View Abstract
  • 97.Polo V, Saibene A, Pontiroli AE. Nicotinamide improves insulin secretion and metabolic control in lean type 2 diabetic patients with secondary failure to sulphonylureas. Acta Diabetol 1998;35:61-64.View Abstract
  • 98.Berge KG. Side effects of nicotinic acid in treatment of hypercholesterolemia. Geriatrics 1961;16:416-422.
  • 99.Christensen NA, Achor RW, Berge KG, Mason HL. Nicotinic acid treatment of hypercholesteremia: comparison of plain and sustained-action preparations and report of two cases of jaundice. JAMA 1961;177:546-550.View Abstract
  • 100.Lange K, Mahl M. A long-term study of the effect of nicotinic acid medication on hypercholesteremia. Am J Med Sci 1963;246:673-677.View Abstract
  • 101.Carlson LA, Havel RJ, Ekelund LG, Holmgren A. Effect of nicotinic acid on the turnover rate and oxidation of the free fatty acids of plasma in man during exercise. Metabolism 1963;12:837-845.
  • 102.Molnar GD, Berge KG, Rosevear JW et al. The effect of nicotinic acid in diabetes mellitus. Metabolism 1964;13:181-190.View Abstract
  • 103.Miettinen TA, Taskinen MR, Pelkonen R, Nikkila EA. Glucose tolerance and plasma insulin in man during acute and chronic administration of nicotinic acid. Acta Med Scand 1969;186:247-253.
  • 104.Gaut ZN, Solomon HM, Miller ON. Influence of antilipemic doses of nicotinic acid on carbohydrate tolerance and plasma insulin levels in man. Diabetes 1970;19:385.
  • 105.Gaut ZN, Pocelinko R, Solomon HM, Thomas GB. Oral glucose tolerance, plasma insulin, and uric acid excretion in man during chronic administration of nicotinic acid. Metabolism 1971;20:1031-1035.
  • 106.Carlson LA, Oro L. Effect of treatment with nicotinic acid for one month on serum lipids in patients with different types of hyperlipidemia. Atherosclerosis 1973;18:1-9.View Abstract
  • 107.Luria MH. Effect of low-dose niacin on high-density lipoprotein cholesterol and total cholesterol/high-density lipoprotein cholesterol ratio. Arch Intern Med 1988;148:2493-2495.View Abstract
  • 108.Kahn SE, Beard JC, Schwartz MW et al. Increased beta-cell secretory capacity as mechanism for islet adaptation to nicotinic acid-induced insulin resistance. Diabetes 1989;38:562-568.View Abstract
  • 109.Henkin Y, Oberman A, Hurst DC, Segrest JP. Niacin revisited: clinical observations on an important but underutilized drug. Am J Med 1991;91:239-246.View Abstract
  • 110.Gray DR, Morgan T, Chretien SD, Kashyap ML. Efficacy and safety of controlled-release niacin in dyslipoproteinemic veterans. Ann Intern Med 1994;121:252-258.View Abstract
  • 111.Vega GL, Grundy SM. Lipoprotein responses to treatment with lovastatin, gemfibrozil, and nicotinic acid in normolipidemic patients with hypoalphalipoproteinemia. Arch Intern Med 1994;154:73-82.View Abstract
  • 112.Illingworth DR, Stein EA, Mitchel YB et al. Comparative effects of lovastatin and niacin in primary hypercholesterolemia: a prospective trial. Arch Intern Med 1994;154:1586-1595.View Abstract
  • 113.Guyton JR, Blazing MA, Hagar J et al. Extended-release niacin vs gemfibrozil for the treatment of low levels of high-density lipoprotein cholesterol. Niaspan-Gemfibrozil Study Group. Arch Intern Med 2000;160:1177-1184.View Abstract
  • 114.Hannan F, Davoren P. Use of nicotinic acid in the management of recurrent hypoglycemic episodes in diabetes. Diabetes Care 2001;24:1301.View Abstract
  • 114a.Elam M, Hunninghake DB, Davis KB, et al. Effects of niacin on lipid and lipoprotein levels and glycemic control in patients with diabetes and peripheral arterial disease: the ADMIT study: a randomized trial. Arterial Disease Multiple Intervention Trial. JAMA 2000;284:1263-1270.
  • 115.Grundy SM, Vega GL, McGovern ME et al. Efficacy, safety, and tolerability of once-daily niacin for the treatment of dyslipidemia associated with type 2 diabetes: results of the assessment of diabetes control and evaluation of the efficacy of niaspan trial. Arch Intern Med 2002;162:1568-1576.View Abstract
  • 116.Ishii N, Nishihara Y. Pellagra encephalopathy among tuberculous patients: its relation to isoniazid therapy. J Neurol Neurosurg Psychiatry 1985;48:628-634.
  • 117.Shibata K, Marugami M, Kondo T. In vivo inhibition of kynurenine aminotransferase activity by isonicotinic acid hydrazide in rats. Biosci Biotechnol Biochem 1996;60:874-876.View Abstract
  • 118.Bender DA, Russell-Jones R. Isoniazid-induced pellagra despite vitamin-B6 supplementation. Lancet 1979;2:1125-1126.View Abstract
  • 119.Darvay A, Basarab T, McGregor JM, Russell-Jones R. Isoniazid induced pellagra despite pyridoxine supplementation. Clin Exp Dermatol 1999;24:167-169.View Abstract
  • 120.DiLorenzo PA. Pellagra-like syndrome associated with isoniazid therapy. Acta Derm Venereol 1967;47:318-322.View Abstract
  • 121.Stadler R, Orfanos CE, Immel C. [Drug-induced pellagra]. Hautarzt 1982;33:276-280.View Abstract
  • 122.Bjornstad RT. [Pellagra during isoniazid therapy]. Tidsskr Nor Laegeforen 1972;92:640-641.
  • 123.Harrington CI. A case of pellagra induced by isoniazid therapy. Practitioner 1977;218:716-717.View Abstract
  • 124.Comaish JS, Felix RH, McGrath H. Topically applied niacinamide in isoniazid-induced pellagra. Arch Dermatol 1976;112:70-72.View Abstract
  • 125.Jarrett P, Duffill M, Oakley A, Smith A. Pellagra, azathioprine and inflammatory bowel disease. Clin Exp Dermatol 1997;22:44-45.View Abstract
  • 126.Gorbach SL. Bengt E. Gustafsson Memorial Lecture: Function of the normal human microflora. Scand J Infect Dis Suppl 1986;49:17-30.View Abstract
  • 127.De Simone C, Vesely R, Bianchi SB et al. The role of probiotics in modulation of the immune system in man and in animals. Int J Immunother 1993;9:23-28.
  • 128.Conly JM, Stein K, Worobetz L, Rutledge-Harding S. The contribution of vitamin K2 (menaquinones) produced by the intestinal microflora to human nutritional requirements for vitamin K. Am J Gastroenterol 1994;89:915-923.View Abstract
  • 129.Conly J, Stein K. Reduction of vitamin K2 concentrations in human liver associated with the use of broad-spectrum antimicrobials. Clin Invest Med 1994;17:531-539.View Abstract
  • 130.Cummings JH, Macfarlane GT. Role of intestinal bacteria in nutrient metabolism. JPEN J Parenter Enteral Nutr 1997;21:357-365.View Abstract
  • 131.Hill MJ. Intestinal flora and endogenous vitamin synthesis. Eur J Cancer Prev 1997;6 Suppl 1:S43-S45.View Abstract
  • 132.Cunningham-Rundles S, Ahrne S, Bengmark S et al. Probiotics and immune response. Am J Gastroenterol 2000;95:S22-S25.View Abstract
  • 133.Macfarlane GT, Cummings JH. Probiotics, infection and immunity. Curr Opin Infect Dis 2002;15:501-506.View Abstract
  • 134.Gill HS. Probiotics to enhance anti-infective defences in the gastrointestinal tract. Best Pract Res Clin Gastroenterol 2003;17:755-773.View Abstract
  • 135.Reid G, Sanders ME, Gaskins HR et al. New scientific paradigms for probiotics and prebiotics. J Clin Gastroenterol 2003;37:105-118.View Abstract
  • 136.Khumalo NP, Murrell DF, Wojnarowska F, Kirtschig G. A systematic review of treatments for bullous pemphigoid. Arch Dermatol 2002;138:385-389.View Abstract
  • 137.Omray A, Varma KC. Evaluation of pharmacokinetic parameters of tetracycline hydrochloride upon oral administration with vitamin C and vitamin B complex. Hindustan Antibiot Bull 1981;23:33-37.
  • 138.Peoples D, Fivenson DP. Linear IgA bullous dermatosis: successful treatment with tetracycline and nicotinamide. J Am Acad Dermatol 1992;26:498-499.View Abstract
  • 139.Chaffins ML, Collison D, Fivenson DP. Treatment of pemphigus and linear IgA dermatosis with nicotinamide and tetracycline: a review of 13 cases. J Am Acad Dermatol 1993;28:998-1000.View Abstract
  • 140.Zemtsov A, Neldner KH. Successful treatment of dermatitis herpetiformis with tetracycline and nicotinamide in a patient unable to tolerate dapsone. J Am Acad Dermatol 1993;28:505-506.View Abstract
  • 141.Sawai T, Kitazawa K, Danno K et al. Pemphigus vegetans with oesophageal involvement: successful treatment with minocycline and nicotinamide. Br J Dermatol 1995;132:668-670.View Abstract
  • 142.Kawahara Y, Hashimoto T, Ohata K, Nishikawa T. Eleven cases of bullous pemphigoid treated with combination of minocycline and nicotinamide. Eur J Dermatol 1996;6:427-429.
  • 143.Reiche L, Wojnarowska F, Mallon E. Combination therapy with nicotinamide and tetracyclines for cicatricial pemphigoid: further support for its efficacy. Clin Exp Dermatol 1998;23:254-257.
  • 144.Yomada M, Komai A, Hashimato T. Sublamina densa-type linear IgA bullous dermatosis successfully treated with oral tetracycline and niacianamide. Br J Dermatol 1999;141:608-609.View Abstract
  • 145.Shah SA, Ormerod AD. Dermatitis herpetiformis effectively treated with heparin, tetracycline and nicotinamide. Clin Exp Dermatol 2000;25:204-205.View Abstract
  • 146.Khanna N, Pandhi RK, Gupta S, Singh MK. Response of chronic bullous dermatosis of childhood to a combination of dapsone and nicotinamide. J Eur Acad Dermatol Venereol 2001;15:368.View Abstract
  • 147.Loo WJ, Dean D, Wojnarowska F. A severe persistent case of recurrent pemphigoid gestation is successfully treated with minocycline and nicotinamide. Clin Exp Dermatol 2001;26:726-727.
  • 148.Chaidemenos GC. Tetracycline and niacinamide in the treatment of blistering skin diseases. Clin Dermatol 2001;19:781-785.View Abstract
  • 149.Hoffer A. Megavitamin B-3 therapy for schizophrenia. Can Psychiatr Assoc J 1971;16:499-504.View Abstract
  • 150.Mohler H, Polc P, Cumin R et al. Nicotinamide is a brain constituent with benzodiazepine-like actions. Nature 1979;278:563-565.View Abstract
  • 151.Ananth JV, Saxena BM, Lehmann HE, Ban TA. Combined administration of thioridazine and nicotinic acid in the treatment of geriatric patients. Curr Ther Res Clin Exp 1971;13:158-161.View Abstract
  • 152.Boiullat JE, Saxena BM, Lehmann HE, Ban TA. Combined administration of thioridazine, nicotinic acid, and fluoxymesterone in the treatment of geriatric patients. Curr Ther Res Clin Exp 1971;13:541-544.View Abstract
  • 153.Lehmann HE, Ban TA, Saxena BM. Nicotinic acid, thioridazine, fluoxymesterone and their combinations in hospitalized geriatric patients: a systematic clinical study. Can Psychiatr Assoc J 1972;17:315-320.View Abstract
  • 154.Chouinard G, Young SN, Annable L, Sourkes TL. Tryptophan-nicotinamide, imipramine and their combination in depression: a controlled study. Acta Psychiatr Scand 1979;59:395-414.View Abstract
  • 155.Shaw DM, MacSweeney DA, Hewland R, Johnson AL. Tricyclic antidepressants and tryptophan in unipolar depression. Psychol Med 1975;5:276-278.View Abstract
  • 156.Walinder J, Skott A, Carlsson A et al. Potentiation of the antidepressant action of clomipramine by tryptophan. Arch Gen Psychiatry 1976;33:1384-1389.View Abstract
  • 157.Walinder J, Carlsson A, Persson R. 5-HT reuptake inhibitors plus tryptophan in endogenous depression. Acta Psychiatr Scand Suppl 1981;290:179-190.View Abstract
  • 158.Actigall: Ciba, US; 1988.
  • 159.Chenix: Reid-Rowell, US; 1988.
  • 160.Agote M, Viaggi M, Kreimann E et al. Influence of nicotinamide on the radiosensitivity of normal and goitrous thyroid in the rat. Thyroid 2001;11:1003-1007.View Abstract
  • 161.Denekamp J, Fowler JF. ARCON—current status: summary of a workshop on preclinical and clinical studies. Acta Oncol 1997;36:517-525.View Abstract
  • 162.Hawkins DR, Bortin AW, Runyon RP. Orthomolecular psychiatry: niacin and megavitamin therapy. Psychosomatics 1970;11:517-521.View Abstract
  • 163.Pauling L, Wyatt RJ, Klein DF, Lipton MA. On the orthomolecular environment of the mind: orthomolecular theory. Am J Psychiatry 1974;131:1251-1267.View Abstract
  • 164.Parkhomets PK, Kuchmerovskaia TM, Donchenko GV et al. [Role of nicotinic acid and its derivatives in disorders of nervous system function]. Ukr Biokhim Zh 1995;67:3-11.View Abstract
  • 165.Hoffer A. The vitamin paradigm wars. Townsend Lett Doctors Patients 1996:56-60.
  • 166.Green RG. Subclinical pellagra: its diagnosis and treatment. Schizophrenia 1970;2:70-79.
  • 167.Osmond H, Hoffer A. Massive niacin treatment in schizophrenia: review of a nine-year study. Lancet 1962;1:316-319.View Abstract
  • 168.Wittenborn JR, Weber ES, Brown M. Niacin in the long-term treatment of schizophrenia. Arch Gen Psychiatry 1973;28:308-315.View Abstract
  • 169.Hoffer A. Vitamin B-3 dependent child. Schizophrenia 1971;3.
  • 170.Autry JH 3rd. Workshop on orthomolecular treatment of schizophrenia: a report. Schizophr Bull 1975:94-103.View Abstract
  • 171.Petrie WM, Ban TA. Vitamins in psychiatry: do they have a role? Drugs 1985;30:58-65.
  • 172.Kramer MS, DiJohnson C, Davis P et al. l-Tryptophan in neuroleptic-induced akathisia. Biol Psychiatry 1990;27:671-672.View Abstract
  • 173.Bender DA, Smith WR. Inhibition of kynurenine hydrolase by benserazide, carbidopa and other aromatic hydrazine derivatives: evidence for sub-clinical iatrogenic niacin deficiency [proceedings]. Biochem Soc Trans 1978;6:120-122.View Abstract
  • 174.Bender DA, Earl CJ, Lees AJ. Niacin depletion in parkinsonian patients treated with l-dopa, benserazide and carbidopa. Clin Sci (Lond) 1979;56:89-93.View Abstract
  • 175.Stevens HP, Ostlere LS, Begent RH et al. Pellagra secondary to 5-fluorouracil. Br J Dermatol 1993;128:578-580.View Abstract
  • 176.Chen JS, Jan YY, Lin YC et al. Weekly 24 h infusion of high-dose 5-fluorouracil and leucovorin in patients with biliary tract carcinomas. Anticancer Drugs 1998;9:393-397.View Abstract
  • 177.Pasmans SG, Preesman AH, van Vloten WA. [Pellagra (deficiency of vitamin B3 or of the amino acid tryptophan): a disease still extant in The Netherlands]. Ned Tijdschr Geneeskd 1998;142:1880-1882.View Abstract
  • 178.Hegyi J, Schwartz RA, Hegyi V. Pellagra: dermatitis, dementia, and diarrhea. Int J Dermatol 2004;43:1-5.View Abstract
  • 179.Rasool AA, Hussain AA, Dittert LW. Solubility enhancement of some water-insoluble drugs in the presence of nicotinamide and related compounds. J Pharm Sci 1991;80:387-393.View Abstract
  • 180.Gurakar A, Hoeg JM, Kostner G et al. Levels of lipoprotein Lp(a) decline with neomycin and niacin treatment. Atherosclerosis 1985;57:293-301.View Abstract
  • 181.Turenne SD, Seeman M, Ross BM. An animal model of nicotinic-acid-induced vasodilation: effect of haloperidol, caffeine and nicotine upon nicotinic acid response. Schizophr Res 2001;50:191-197.
  • 182.Clarkes R. Niacin for nicotine? Lancet 1980;1:936.
  • 183.Rockwell KA Jr. Potential interaction between niacin and transdermal nicotine. Ann Pharmacother 1993;27:1283-1288.
  • 184.Sudan BJ. Comment: niacin, nicotine, and flushing. Ann Pharmacother 1994;28:1113.View Abstract
  • 185.Rose DP, Adams PW. Oral contraceptives and tryptophan metabolism: effects of oestrogen in low dose combined with a progestagen and of a low-dose progestagen (megestrol acetate) given alone. J Clin Pathol 1972;25:252-258.View Abstract
  • 186.Brown RR, Rose DP, Leklem JE, Linkswiler HM. Effects of oral contraceptives on tryptophan metabolism and vitamin B6 requirements in women. Acta Vitaminol Enzymol 1975;29:151-157.View Abstract
  • 187.Briggs M. Oral contraceptives and vitamin requirements [letter]. Med J Aust 1975;1:407.View Abstract
  • 188.Leklem JE, Brown RR, Rose DP et al. Metabolism of tryptophan and niacin in oral contraceptives users receiving controlled intakes of vitamin B6. Am J Clin Nutr 1975;28:146-156.View Abstract
  • 189.Driskell JA, Geders JM, Urban MC. Vitamin B6 status of young men, women, and women using oral contraceptives. J Lab Clin Med 1976;87:813-821.View Abstract
  • 190.Thorp VJ. Effect of oral contraceptive agents on vitamin and mineral requirements. J Am Diet Assoc 1980;76:581-584.View Abstract
  • 191.Webb JL. Nutritional effects of oral contraceptive use: a review. J Reprod Med 1980;25:150-156.View Abstract
  • 192.Veninga KS. Effects of oral contraceptives on vitamins B6, B12, C, and folacin. J Nurse Midwifery 1984;29:386-390.View Abstract
  • 193.Tyrer LB. Nutrition and the pill. J Reprod Med 1984;29:547-550.View Abstract
  • 194.Cervantes-Laurean D, McElvaney NG, Moss J. Niacin. In: Shils M, Olson JA, Shike M, Ross AC, eds. Nutrition in Health and Disease. 9th ed. Baltimore: Williams & Wilkins; 1999:401-411.
  • 195.Prasad AS, Oberleas D, Moghissi KS et al. Effect of oral contraceptive agents on nutrients. II. Vitamins. Am J Clin Nutr 1975;28:385-391.View Abstract
  • 196.Bamji MS, Safaya S, Prema K. Low-dose injectable contraceptive norethisterone enanthate 20mg monthly. II. Metabolic side effects. Contraception 1981;23:23-36.View Abstract
  • 197.Shibata K, Fukuwatari T, Sugimoto E. Effects of dietary pyrazinamide, an antituberculosis agent, on the metabolism of tryptophan to niacin and of tryptophan to serotonin in rats. Biosci Biotechnol Biochem 2001;65:1339-1346.View Abstract
  • 198.Dearing BD, Lavie CJ, Lohmann TP, Genton E. Niacin-induced clotting factor synthesis deficiency with coagulopathy. Arch Intern Med 1992;152:861-863.View Abstract
  • 199.Coppola A, Brady PG, Nord HJ. Niacin-induced hepatotoxicity: unusual presentations. South Med J 1994;87:30-32.View Abstract
  • 200.Philipp CS, Cisar LA, Saidi P, Kostis JB. Effect of niacin supplementation on fibrinogen levels in patients with peripheral vascular disease. Am J Cardiol 1998;82:697-699, A699.View Abstract
  • 201.Chesney CM, Elam MB, Herd JA et al. Effect of niacin, warfarin, and antioxidant therapy on coagulation parameters in patients with peripheral arterial disease in the Arterial Disease Multiple Intervention Trial (ADMIT). Am Heart J 2000;140:631-636.View Abstract
  • 202.Odetti P, Cheli V, Carta G et al. Effect of nicotinic acid associated with retinol and tocopherols on plasma lipids in hyperlipoproteinaemic patients. Pharmatherapeutica 1984;4:21-24.View Abstract
  • 203.Hodis HN, Mack WJ, LaBree L et al. Serial coronary angiographic evidence that antioxidant vitamin intake reduces progression of coronary artery atherosclerosis. JAMA 1995;273:1849-1854.View Abstract
  • 204.Cheung MC, Wolfbauer G, Kennedy H et al. Plasma phospholipid transfer protein activity in patients with low HDL and cardiovascular disease treated with simvastatin and niacin. Biochim Biophys Acta 2001;1537:117-124.View Abstract
  • 205.Cheung MC, Zhao XQ, Chait A et al. Antioxidant supplements block the response of HDL to simvastatin-niacin therapy in patients with coronary artery disease and low HDL. Arterioscler Thromb Vasc Biol 2001;21:1320-1326.View Abstract
  • 206.Matthan NR, Giovanni A, Schaefer EJ et al. Impact of simvastatin, niacin, and/or antioxidants on cholesterol metabolism in CAD patients with low HDL. J Lipid Res 2003;44:800-806.View Abstract
  • 207.Vivekananthan DP, Penn MS, Sapp SK et al. Use of antioxidant vitamins for the prevention of cardiovascular disease: meta-analysis of randomised trials. Lancet 2003;361:2017-2023.View Abstract
  • 208.McCarty MF. Co-administration of equimolar doses of betaine may alleviate the hepatotoxic risk associated with niacin therapy. Med Hypotheses 2000;55:189-194.View Abstract
  • 209.Urberg M, Zemel MB. Evidence for synergism between chromium and nicotinic acid in the control of glucose tolerance in elderly humans. Metabolism 1987;36:896-899.
  • 210.Lefavi RG, Anderson RA, Keith RE et al. Efficacy of chromium supplementation in athletes: emphasis on anabolism. Int J Sport Nutr 1992;2:111-122.View Abstract
  • 211.Hathcock JN. Vitamins and minerals: efficacy and safety. Am J Clin Nutr 1997;66:427-437.View Abstract
  • 212.Mertz W. Chromium research from a distance: from 1959 to 1980. J Am Coll Nutr 1998;17:544-547.View Abstract
  • 213.Bolkent S, Yanardag R, Doger MM. Beneficial effects of combined treatment with niacin and chromium on the liver of hyperlipemic rats. Biol Trace Elem Res 2004;101:219-229.View Abstract
  • 214.Keszthelyi Z, Past T, Lukats B et al. The central effect of chromium on glucose metabolism. Pharmacopsychiatry 2004;37:242.View Abstract
  • 215.Thomas VL, Gropper SS. Effect of chromium nicotinic acid supplementation on selected cardiovascular disease risk factors. Biol Trace Elem Res 1996;55:297-305.View Abstract
  • 216.Crawford V, Scheckenbach R, Preuss HG. Effects of niacin-bound chromium supplementation on body composition in overweight African-American women. Diabetes Obes Metab 1999;1:331-337.View Abstract
  • 217.Preuss HG, Bagchi D, Bagchi M. Protective effects of a novel niacin-bound chromium complex and a grape seed proanthocyanidin extract on advancing age and various aspects of syndrome X. Ann NY Acad Sci 2002;957:250-259.
  • 218.Yeganeh B, Moshtaghi-Kashanian GR, Declercq V, Moghadasian MH. Combination of dietary phytosterols plus niacin or fenofibrate: effects on lipid profile and atherosclerosis in apo E-KO mice. J Nutr Biochem 2005;16:222-228.View Abstract
  • 219.Gouni-Berthold I, Berthold HK. Policosanol: clinical pharmacology and therapeutic significance of a new lipid-lowering agent. Am Heart J 2002;143:356-365.View Abstract
  • 220.Janikula M. Policosanol: a new treatment for cardiovascular disease? Altern Med Rev 2002;7:203-217.
  • 221.Uribarri E, Laguna A, Sierra R, Ricardo Y. Physico-mechanical characterization of policosanol, a novel hypocholesterolemic drug. Drug Dev Ind Pharm 2002;28:89-93.View Abstract
  • 222.Cholesterol-lowering action of policosanol compares well to that of pravastatin and lovastatin. Cardiovasc J S Afr 2003;14:161.
  • 223.Castano G, Mas R, Fernandez L et al. Effects of policosanol and lovastatin in patients with intermittent claudication: a double-blind comparative pilot study. Angiology 2003;54:25-38.View Abstract
  • 224.Berthold HK, Unverdorben S, Degenhardt R et al. Effect of policosanol on lipid levels among patients with hypercholesterolemia or combined hyperlipidemia: a randomized controlled trial. JAMA2006;295:2262-2269.
  • 225.Ban TA. On-going national collaborative studies in Canada: niacin in the treatment of schizophrenias. Psychopharmacol Bull 1969;5:5-20.View Abstract
  • 226.Ananth JV, Ban TA, Lehmann HE. Potentiation of therapeutic effects of nicotinic acid by pyridoxine in chronic schizophrenics. Can Psychiatr Assoc J 1973;18:377-383.View Abstract
  • 227.Petrie WM, Ban TA, Ananth JV. The use of nicotinic acid and pyridoxine in the treatment of schizophrenia. Int Pharmacopsychiatry 1981;16:245-250.View Abstract
  • 228.Vannucchi H, Kutnink MD, Sauberlich M, Howerde E. Interaction among niacin, vitamin B6 and zinc in rats receiving ethanol. Int J Vitam Nutr Res 1986;56:355-362.
  • 229.Vannucchi H, Moreno FS. Interaction of niacin and zinc metabolism in patients with alcoholic pellagra. Am J Clin Nutr 1989;50:364-369.View Abstract
  • .[No authors listed.] Adult Treatment Panel III (ATP III) guidelines: NHLBI slide show. Available at: http://hin.nhlbi.nih.gov/ncep_slds/atpiii/slide101.htm. Accessed June 14, 2002.
  • .[No authors listed.] Clofibrate and niacin in coronary heart disease. JAMA 1975;231(4):360-381.
  • .[No authors listed.] Drug evaluations subscription: vol. II, section 10. Chicago: American Medical Association; 1994.
  • .[No authors listed.] Drug facts and comparisons. St Louis: Facts and Comparisons, Inc; 1999.
  • .[No authors listed.] Executive summary of the third report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA 2001;285(19):2486-2497.
  • .[No authors listed.] Lipid-lowering drugs. Med Lett Drugs Ther 1985;27(695):74-76.
  • .[No authors listed.] Product information: Actigall. Summit, NJ: Ciba; 1988.
  • .[No authors listed.] Product information: Baycol (TM), cerivastatin sodium. West Haven, CT: Bayer Corporation; 1997.
  • .[No authors listed.] Product information: Chenix. Marietta, GA: Reid-Rowell; 1988.
  • .[No authors listed.] Product information: Lipitor (TM), atorvastatin. Morris Plains, NJ: Parke-Davis; 1996.
  • .[No authors listed.] Product information: Niaspan(R), niacin, extended release tablet. Miami, FL: Kos Pharmaceuticals; 1997.
  • .[No authors listed.] Summary of the Second Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel II). JAMA 1993;269(23):3015-3023.
  • .[No authors listed.] Vitamin B complex, Niacin. In: McEvoy GK, ed. American Hospital Formulary Service Drug Information. Bethesda, MD: American Society of Hospital Pharmacists; 1995:1685-1687.
  • .Alderman JD, Pasternak RC, Sacks FM, et al. Effect of a modified, well-tolerated niacin regimen on serum total cholesterol, high density lipoprotein cholesterol and the cholesterol to high density lipoprotein ratio. Am J Cardiol 1989;64(12):725-729.
  • .Ames BN. A role for supplements in optimizing health: the metabolic tune-up. Arch Biochem Biophys 2004;423(1):227-234. (Review)
  • .Ames BN. DNA damage from micronutrient deficiencies is likely to be a major cause of cancer. Mutat Res 2001;475(1-2):7-20. (Review)
  • .Ames BN. Increasing longevity by tuning up metabolism: to maximize human health and lifespan, scientists must abandon outdated models of micronutrients. EMBO Rep 2005;6(Suppl 1):S20-24. (Review)
  • .Ames BN. Micronutrient deficiencies: a major cause of DNA damage. Ann N Y Acad Sci 1999;889:87-106. (Review)
  • .Ames BN. The metabolic tune-up: metabolic harmony and disease prevention. J Nutr 2003;133(5):1544S-1548S. (Review)
  • .Ames BN, Atamna H, Killilea DW. Mineral and vitamin deficiencies can accelerate the mitochondrial decay of aging. Mol Aspects Med 2005;26(4-5):363-378. (Review)
  • .Ames BN, Elson-Schwab I, Silver EA. High-dose vitamin therapy stimulates variant enzymes with decreased coenzyme binding affinity (increased K(m)): relevance to genetic disease and polymorphisms. Am J Clin Nutr 2002;75(4):616-658. (Review)
  • .Amiel SA, Caprio S, Sherwin RS, et al. Insulin resistance of puberty: a defect restricted to peripheral glucose metabolism. J Clin Endocrinol Metab 1991;72:277-282.
  • .Antoon AY, Donovan DK. Burn injuries. In: Behrman RE, Kliegman RM, Jenson HB, eds. Nelson textbook of pediatrics. Philadelphia: Saunders; 2000:287-294.
  • .Baggenstoss AH, Christensen NA, Berge KG, et al. Fine structural changes in the liver in hypercholesteremic patients receiving long-term nicotinic acid therapy. Mayo Clin Proc 1967;42(7):385-399.
  • .Ban TA. On-going national collaborative studies in Canada: niacin in the treatment of schizophrenias. Psychopharmacol Bull 1969;5(3):5-20. (Review)
  • .Bays HE, Dujovne CA. Drug interactions of lipid-altering drugs. Drug Safety 1998;19(5):355-371. (Review)
  • .Bechgaard H, Jespersen S. GI absorption of niacin in humans. J Pharm Sci 1977;66:871-872.
  • .Belalcazar LM, Ballantyne CM. Defining specific goals of therapy in treating dyslipidemia in the patient with low high-density lipoprotein cholesterol. Prog Cardiovasc Dis 1998;41:151-174. (Review)
  • .Berge KG, Canner PL. Coronary drug project: experience with niacin: Coronary Drug Project Research Group. Eur J Clin Pharmacol 1991;40(Suppl 1):S49-51.
  • .Berk MA, Lorincz AL. The treatment of bullous pemphigoid with tetracycline and niacinamide: a preliminary report. Arch Dermatol 1986;122:670-674.
  • .Berge KG. Side effects of nicotinic acid in treatment of hypercholesterolemia. Geriatrics 1961;16:416-422.
  • .Berge KG, Achor RW, Christensen NA, et al. Hypercholesteremia and nicotinic acid: a long term study. Am J Med 1961;31:24-36.
  • .Berthold HK, Unverdorben S, Degenhardt R, et al. Effect of policosanol on lipid levels among patients with hypercholesterolemia or combined hyperlipidemia: a randomized controlled trial. JAMA 2006;295:2262-2269.
  • .Björnsson E, Olsson R. Outcome and prognostic markers in severe drug-induced liver disease. Hepatology 2005;42(2):481-489.
  • .Boden WE. Therapeutic implications of recent ATP III guidelines and the important role of combination therapy in total dyslipidemia management. Curr Opin Cardiol 2003;18(4):278-285. (Review)
  • .Bohler A, Moll C, Schaffner A, et al. [Alcoholic pellagra encephalopathy: an underestimated treatable entity.] Schweiz Med Wochenschr 1994;124(17):720-724. [German]
  • .Boyonoski AC, Spronck JC, Gallacher LM, et al. Niacin deficiency decreases bone marrow poly(ADP-ribose) and the latency of ethylnitrosourea-induced carcinogenesis in rats. J Nutr 2002;132(1):108-114.
  • .Brody T. Nutritional biochemistry. 2nd ed. San Diego: Academic Press; 1999.
  • .Braham JE, Villareal A, Bressani R. Effect of lime treatment of corn on the availability of niacin for cats. J Nutr 1962;76:183-186.
  • .Bressani R, Gómez-Brenes R, Scrimshaw NS. Effect of processing on distribution and in vitro availability of niacin of corn (Zea mays). Food Technol 1961;15:450-454.
  • .Bressani R, Scrimshaw NS. Effect of lime treatment on in-vitro availability of essential amino acids and solubility of protein fractions in com. J Agric Food Chem 1958;6:774-778.
  • .Brown BG, Bardsley J, Poulin D, et al. Moderate dose, three-drug therapy with niacin, lovastatin, and colestipol to reduce low-density lipoprotein cholesterol <100 mg/dl in patients with hyperlipidemia and coronary artery disease. Am J Cardiol 1997;80(2):111-115.
  • .Brown BG, Zambon A, Poulin D, et al. Use of niacin, statins, and resins in patients with combined hyperlipidemia. Am J Cardiol 1998;81(4A):52B-59B.
  • .Brown RR, Ozaki Y, Datta SP, et al. Implications of interferon-induced tryptophan catabolism in cancer, auto-immune diseases and AIDS. Adv Exp Med Biol 1991;294:425-435.
  • .Brown WV. Niacin for lipid disorders: indications, effectiveness, and safety. Postgrad Med 1995;98(2):185-9, 192-193.
  • .Brunzell DH, Russell DS, Picciotto MR. In vivo nicotine treatment regulates mesocorticolimbic CREB and ERK signaling in C57Bl/6J mice. J Neurochem 2003;84(6):1431-1441.
  • .Bucher HC, Griffith LE, Guyatt GH. Systematic review on the risk and benefit of different cholesterol-lowering interventions. Arterioscler Thromb Vasc Biol 1999;19(2):187-195. (Review)
  • .Burkart V, Koike T, Brenner HH, et al. Oxygen radicals generated by the enzyme xanthine oxidase lyse rat pancreatic islet cells in vitro. Diabetologia 1992;35:1028-1034.
  • .Calabresi L, Villa B, Canavesi M, et al. An omega-3 polyunsaturated fatty acid concentrate increases plasma high-density lipoprotein 2 cholesterol and paraoxonase levels in patients with familial combined hyperlipidemia. Metabolism 2004;53:153-158.
  • .Calabro P, Yeh ET. The pleiotropic effects of statins. Curr Opin Cardiol 2005;20(6):541-546.
  • .Canner PL, Berge KG, Wenger NK, et al. Fifteen year mortality in Coronary Drug Project patients: long-term benefit with niacin. J Am Coll Cardiol 1986;8(6):1245-1255.
  • .Capuzzi DM, Guyton JR, Morgan JM, et al. Efficacy and safety of an extended-release niacin (Niaspan): a long-term study. Am J Cardiol 1998;82:74U-81U.
  • .Capuzzi DM, Morgan JM, Weiss RJ, et al. Beneficial effects of rosuvastatin alone and in combination with extended-release niacin in patients with a combined hyperlipidemia and low high-density lipoprotein cholesterol levels. Am J Cardiol 2003;91:1304-1310.
  • .Carlson LA, Havel RJ, Ekelund LG, et al. Effect of nicotinic acid on the turnover rate and oxydation of the free fatty acids of plasma in man during exercise. Metabolism 1963;12(9):837-845.
  • .Carlson LA, Oro L. Effect of treatment of nicotinic acid for one month on serum lipids in patients with different types of hyperlipidemia. Atherosclerosis 1973;18(1):1-9.
  • .Carlson LA, Rosenhamer G. Reduction of mortality in the Stockholm Ischaemic Heart Disease Secondary Prevention Study by combined treatment with clofibrate and nicotinic acid. Acta Med Scand 1988;223(5):405-418.
  • .Castiello RJ, Lynch PJ. Pellagra and the carcinoid syndrome. Arch Dermatol 1972;105(4):574-577.
  • .Cervantes-Laurean D, McElvaney NG, Moss J. Niacin. In: Shils M, Olson JA, Shike M, et al, eds. Nutrition in health and disease. 9th ed. Baltimore: Williams & Wilkins; 1999:401-411.
  • .Chan DC, Watts GF, Barrett PH, et al. Regulatory effects of HMG CoA reductase inhibitor and fish oils on apolipoprotein B-100 kinetics in insulin-resistant obese male subjects with dyslipidemia. Diabetes 2002;51(8):2377-2386.
  • .Chase HP, Butler-Simon N, Garg S, et al. A trial of nicotinamide in newly diagnosed patients with type 1 (insulin dependent) diabetes mellitus. Diabetolgia 1990;33:444-446.
  • .Cho S, Choi JC, Choi JH, et al. Wet pellagra. Int J Dermatol 2001;40(8):543-544.
  • .Christensen NA, Achor RW, Berge KG, et al. Nicotinic acid treatment of hypercholesterolemia, comparison of plain and sustained action preparations and report of two cases of jaundice. JAMA 1961;177:546-550.
  • .Cohen JC, Boerwinkle E, Mosley TH Jr, et al. Sequence variations in PCSK9, low LDL, and protection against coronary artery disease. N Engl J Med 2006;354:1264-1272.
  • .Cohen L, Morgan J. Effectiveness of individualized long-term therapy with niacin and probucol in reduction of serum cholesterol. J Fam Pract 1988;26:145-150.
  • .Cravioto RO, Massieu GH, Cravioto OY, et al. Effect of untreated corn and Mexican tortilla upon the growth of rats on a niacin-tryptophan deficient diet. J Nutr 1952;48:453-459.
  • .Crouse JR III. New developments in the use of niacin for treatment of hyperlipidemia: new considerations in the use of an old drug. Coron Artery Dis 1996;7:321-326.
  • .Cumming RG, Mitchell P, Smith W. Diet and cataract: the Blue Mountains Eye Study. Ophthalmology 2000;107(3):450-456.
  • .Cunningham JJ. Micronutrients as nutriceutical interventions in diabetes mellitus. J Am Coll Nutr 1998;17:7-10.
  • .Cupo MA, Donaldson WE. Effects of lead and niacin on tryptophan and serotonin metabolism. Drug Nutr Interact 1988;5(4):297-308.
  • .Darras BT, Ampola MG, Dietz WH, et al. Intermittent dystonia in Hartnup disease. Pediatr Neurol 1989;5:118-120.
  • .De-Souza DA, Greene LJ. Pharmacological nutrition after burn injury. J Nutr 1998;128:797-803.
  • .Denekamp J, Fowler JF. ARCON: current status: summary of a workshop on preclinical and clinical studies. Acta Oncol 1997;36:517-525.
  • .Dorner Von G, Fisher FW. [Zur Beinflussung der Serumlipide und -lipoproteine durch den Hexanicotinsaureester des m-Inositol.] Arzneimittelforschung 1961;11:110-113.
  • .Doyle W, Crawford MA, Wynn AH, et al. The association between maternal diet and birth dimensions. J Nutr Med 1990;1:9-17.
  • .Dragan L, Eng AM, Lam S, et al. Tetracycline and niacinamide: treatment alternatives in ocular cicatricial pemphigoid. Cutis 1999;63:181-183.
  • .Elam M, Hunninghake DB, Davis KB, et al. Effects of niacin on lipid and lipoprotein levels and glycemic control in patients with diabetes and peripheral arterial disease: the ADMIT study: a randomized trial: Arterial Disease Multiple Intervention Trial. JAMA 2000;284:1263-1270.
  • .Elliott RB, Chase HP. Prevention or delay of type 1 (insulin-dependent) diabetes mellitus in children using nicotinamide. Diabetologia 1991;34:362-365.
  • .Elliott RB, Pilcher CC, Fergusson DM, et al. A population based strategy to prevent insulin-dependent diabetes using nicotinamide. J Pediatr Endocrinol Metab 1996;9:501-509.
  • .Elliott RB, Pilcher CC, Stewart A, et al. The use of nicotinamide in the prevention of type 1 diabetes. Ann N Y Acad Sci 1993;696:333-341.
  • .Elvehjem CA, Madden RJ, Strong FM, et al. The isolation and identification of the anti-black tongue factor: 1937. J Biol Chem 2002;277(34):e22.
  • .Estep DL, Gay GR, Rappolt RT Sr. Preliminary report of the effects of propranolol HCl on the discomfiture caused by niacin. Clin Toxicol 1977;11(3):325-328.
  • .Flodin N. Pharmacology of micronutrients. New York: Alan R. Liss, Inc; 1988.
  • .Food and Nutrition Board, Institute of Medicine. Niacin: dietary reference intakes: thiamin, riboflavin, niacin, vitamin B-6, vitamin B-12, pantothenic acid, biotin, and choline. Washington, DC: National Academy Press; 1998:123-149.
  • .Foody JM, Shah R, Galusha D, et al. Statins and mortality among elderly patients hospitalized with heart failure. Circulation 2006;113(8):1086-1092.
  • .Forsyth LM, Preuss HG, MacDowell AL, et al. Therapeutic effects of oral NADH on the symptoms of patients with chronic fatigue syndrome. Ann Allergy Asthma Immunol 1999;82:185-191.
  • .Franceschi S, Bidoli E, Negri E, et al. Role of macronutrients, vitamins and minerals in the aetiology of squamous-cell carcinoma of the oesophagus. Int J Cancer 2000;86(5):626-631.
  • .Freedman JE. Antioxidant versus lipid-altering therapy: some answers, more questions. N Engl J Med 2001;345(22):1636-1637.
  • .Fu CS, Swendseid ME, Jacob RA, et al. Biochemical markers for assessment of niacin status in young men: levels of erythrocyte niacin coenzymes and plasma tryptophan. J Nutr 1989;119(12):1949-1955.
  • .Fuccella LM, Goldaniga G, Lovisco P, et al. Inhibition of lipolysis by nicotinic acid and acipimox. Clin Pharmacol Ther 1980;28:790-795.
  • .Gaby AR. Natural treatments for osteoarthritis. Altern Med Rev 1999;4(5):330-341.
  • .Garg A. Lipid-lowering therapy and macrovascular disease in diabetes mellitus. Diabetes 1992;41(Suppl 2):111-115.
  • .Garg A, Grundy SM. Nicotinic acid as therapy for dyslipidemia in non-insulin-dependent diabetes mellitus. JAMA 1990;264:723-726.
  • .Garg R, Malinow M, Pettinger M, et al. Niacin treatment increases plasma homocyst(e)ine levels. Am Heart J 1999;138:1082-1087.
  • .Gardner SF, Schneider EF, Granberry MC, et al. Combination therapy with low-dose lovastatin and niacin is as effective as higher-dose lovastatin. Pharmacotherapy 1996;16:419-423.
  • .Garnett WR. Interactions with hydroxymethylglutaryl-coenzyme A reductase inhibitors. Am J Health Syst Pharm 1995;52(15):1639-1645. (Review)
  • .Gascard E, Cherif AA, Moulard JC. [Pellagra and pellagroud syndromes: 21 cases.] Mars Med 1969;106(9):695-697. (Case reports) [French]
  • .Gaut ZN, Pocelinko R, Solomon HM, et al. Oral glucose tolerance, plasma insulin, and uric acid excretion in man during chronic administration of nicotinic acid. Metabolism 1971;20(11):1031-1035.
  • .Gaut ZN, Solomon HM, Miller ON. Influence of antilipemic doses of nicotinic acid on carbohydrate tolerance and plasma insulin levels in man. Diabetes 1970;19:385.
  • .Gensler HL, Williams T, Huang AC, et al. Oral niacin prevents photocarcinogenesis and photoimmunosuppression in mice. Nutr Cancer 1999;34(1):36-41.
  • .Gibbons LW, Gonzalez V, Gordon N, et al. The prevalence of side effects with regular and sustained-release nicotinic acid. Am J Med 1995;99(4):378-385.
  • .Glen AI, Cooper SJ, Rybakowski J, et al. Membrane fatty acids, niacin flushing and clinical parameters. Prostaglandins Leukot Essent Fatty Acids 1996;55(1-2):9-15.
  • .Go AS, Iribarren C, Chandra M et al; Atherosclerotic Disease, Vascular Function and Genetic Epidemiology (ADVANCE) Study: statin and beta-blocker therapy and the initial presentation of coronary heart disease. Ann Intern Med 2006;144(4):229-238.
  • .Go AS, Lee WY, Yang J, et al. Statin therapy and risks for death and hospitalization in chronic heart failure. JAMA 2006;296 2105-2111.
  • .Goldberg AC. Clinical trial experience with extended-release niacin (Niaspan): dose-escalation study. Am J Cardiol 1998;82(12A):35U-38U.
  • .Goldberg A, Alagona P Jr, Capuzzi DM, et al. Multiple-dose efficacy and safety of an extended-release form of niacin in the management of hyperlipidemia. Am J Cardiol 2000;85(9):1100-1105.
  • .Goldstein JA. Niacin and acute psychedelic psychosis. Biol Psychiatry 1984;19(2):272-273.
  • .Golomb BA. Implications of statin adverse effects in the elderly. Expert Opin Drug Safety 2005;4(3):389-397.
  • .Golomb BA, Kane T, Dimsdale JE. Severe irritability associated with statin cholesterol-lowering drugs. QJM 2004;97(4):229-235.
  • .Gomez de la Torre R, Blanco Zorroza B, Claros Gonzalez IJ, et al. [Pellagra: manifestations of a disease...not forgotten?] An Med Interna 2000;17(8):450-451. [Spanish]
  • .Gray DR, Morgan T, Chretien SD, et al. Efficacy and safety of controlled-release niacin in dyslipoproteinemic veterans. Ann Intern Med 1994;121(4):252-258.
  • .Green AR, Bloomfield MR, Woods HF, et al. Metabolism of an oral tryptophan load by women and evidence against the induction of tryptophan pyrrolase by oral contraceptives. Br J Clin Pharmacol 1978;5(3):233-241.
  • .Green RF. Subclinical pellagra and idiopathic hypogeusia. JAMA 1971;218(8):1303.
  • .Green RG. Subclinical pellagra: its diagnosis and treatment. Schizophrenia 1970;2:70-79.
  • .Greenbaum CJ, Kahn SE, Palmer JP. Nicotinamide’s effects on glucose metabolism in subjects at risk for IDDM. Diabetes 1996;45(11):1631-1634.
  • .Gregory JF III. Nutritional properties and significance of vitamin glycosides. Annu Rev Nutr 1998;18:277-296.
  • .Grundy SM, Mok HY, Zech L, et al. Influence of nicotinic acid on metabolism of cholesterol and triglycerides in man. J Lipid Res 1981;22(1):24-36.
  • .Grundy SM, Vega GL, McGovern ME, et al. Efficacy, safety, and tolerability of once-daily niacin for the treatment of dyslipidemia associated with type 2 diabetes: results of the assessment of diabetes control and evaluation of the efficacy of niaspan trial. Arch Intern Med 2002;162:1568-1576.
  • .Gugler R. Clinical pharmacokinetics of hypolipidaemic drugs. Clin Pharmacokinet 1978;3(6):425-439.
  • .Guyton JR. Effect of niacin on atherosclerotic cardiovascular disease. Am J Cardiol 1998;82:18U-23U, 39U-41U. (Review)
  • .Guyton JR, Blazing MA, Hagar J, et al. Extended-release niacin vs. gemfibrozil for the treatment of low levels of high-density lipoprotein cholesterol: Niaspan-Gemfibrozil Study Group. Arch Intern Med 2000;160(8):1177-1184.
  • .Guyton JR, Capuzzi DM. Treatment of hyperlipidemia with combined niacin-statin regimens. Am J Cardiol 1998;82(12A):82U-86U.
  • .Guyton JR, Goldberg AC, Kreisberg RA, et al. Effectiveness of once-nightly dosing of extended-release niacin alone and in combination for hypercholesterolemia. Am J Cardiol 1998;82:737-743.
  • .Hageman GJ, Stierum RH. Niacin, poly(ADP-ribose) polymerase-1 and genomic stability. Mutat Res 2001;475(1-2):45-56.
  • .Hageman GJ, Stierum RH, van Herwijnen MH, et al. Nicotinic acid supplementation: effects on niacin status, cytogenetic damage, and poly(ADP-ribosylation) in lymphocytes of smokers. Nutr Cancer 1998;32(2):113-120.
  • .Handfield-Jones S, Jones S, Peachey R. High dose nicotinamide in the treatment of necrobiosis lipoidica. Br J Dermatol 1988;118:693-696.
  • .Hannan F, Davoren P. Use of nicotinic acid in the management of recurrent hypoglycemic episodes in diabetes. Diabetes Care 2001;24(7):1301.
  • .Hakozaki T, Minwalla L, Zhuang J, et al. The effect of niacinamide on reducing cutaneous pigmentation and suppression of melanosome transfer. Br J Dermatol 2002;147:20-31.
  • .Hawkins DR, Bortin AW, Runyon RP. Orthomolecular psychiatry: niacin and megavitamin therapy. Psychosomatics 1970;11:517-521.
  • .Head A. Treatment of intermittent claudication with inositol nicotinate. Practitioner 1986;230:49-54.
  • .Head KA. Inositol hexaniacinate: a safer alternative to niacin. Alt Med Rev 1996;1(3):176-184. (Review)
  • .Hegyi J, Schwartz RA, Hegyi V. Pellagra: dermatitis, dementia, and diarrhea. Int J Dermatol 2004;43(1):1-5. (Review)
  • .Hendler SS, Rorvik DR, eds. PDR for nutritional supplements. Montvale, NJ: Medical Economics Company, Inc; 2001.
  • .Henkin Y, Oberman A, Hurst DC, et al. Niacin revisited: clinical observations on an important but underutilized drug. Am J Med 1991;91(3):239-246.
  • .Hermitte L, Vialettes B, Atlef N, et al. High dose nicotinamide fails to prevent diabetes in BB rats. Autoimmunity 1989;5(1-2):79-86.
  • .Hoffer A. Megavitamin B-3 therapy for schizophrenia. Can Psychiatr Assoc J 1971;16:499-504.
  • .Hoffer A. Safety, side effects and relative lack of toxicity of nicotinic acid and nicotinamide. Schizophrenia 1969;1:78-87.
  • .Hoffer A. The vitamin paradigm wars. Townsend Letters for Doctors and Patients 1996;56-60.
  • .Hoffer A. Vitamin B-3 dependent child. Schizophrenia 1971;3:107-113.
  • .Holt GA. Food and drug interactions. Chicago: Precept Press; 1998:82-83. (Review)
  • .Horrobin DF. Schizophrenia: a biochemical disorder? Biomedicine 1980;32(2):54-55.
  • .Hudgins AP. Niacin for dysmenorrhea. Am Pract Dig Treat 1952;3(11):892-893.
  • .Hudgins AP. Vitamins P, C and niacin for dysmenorrhea therapy. West J Surg Obstet Gynecol 1954;62(12):610-611.
  • .Hypponen E. Micronutrients and the risk of type 1 diabetes: vitamin D, vitamin E, and nicotinamide. Nutr Rev 2004;62(9):340-347. (Review)
  • .Illingworth DR, Stein EA, Mitchel YB, et al. Comparative effects of lovastatin and niacin in primary hypercholesterolemia: a prospective trial. Arch Intern Med 1994;154(14):1586-1595.
  • .Iribarren C, Belcher JD, Jacobs DR Jr, et al. Relationship of lipoproteins, apolipoproteins, triglycerides and lipid ratios to plasma total cholesterol in young adults: the CARDIA Study: Coronary Artery Risk Development in Young Adults. J Cardiovasc Risk 1996;3(4):391-396.
  • .Iribarren C, Folsom AR, Jacobs DR Jr, et al. Association of serum vitamin levels, LDL susceptibility to oxidation, and autoantibodies against MDA-LDL with carotid atherosclerosis: a case-control study. The ARIC Study Investigators: Atherosclerosis Risk in Communities. Arterioscler Thromb Vasc Biol 1997;17(6):1171-1177.
  • .Iribarren C, Jacobs DR, Sadler M, et al. Hemorrhagic stroke: is the association confined to elderly men? The Kaiser Permanente Medical Care Program. Stroke 1996;27(11):1993-1998.
  • .Iribarren C, Jacobs DR Jr, Sidney S, et al. Cohort study of serum total cholesterol and in-hospital incidence of infectious diseases. Epidemiol Infect 1998;121(2):335-347.
  • .Iribarren C, Jacobs DR Jr, Sidney S, et al. Serum total cholesterol and risk of hospitalization, and death from respiratory disease. Int J Epidemiol 1997;26(6):1191-1202.
  • .Iribarren C, Jacobs DR Jr, Slattery ML, et al. Epidemiology of low total plasma cholesterol concentration among young adults: the CARDIA study: Coronary Artery Risk Development in Young Adults. Prev Med 1997;26(4):495-507.
  • .Iribarren C, Reed DM, Burchfiel CM, et al. Serum total cholesterol and mortality: confounding factors and risk modification in Japanese-American men. JAMA 1995;273(24):1926-1932.
  • .Iribarren C, Reed DM, Chen R, et al. Low serum cholesterol and mortality: which is the cause and which is the effect? Circulation 1995;92(9):2396-2403.
  • .Iribarren C, Reed DM, Wergowske G, et al. Serum cholesterol level and mortality due to suicide and trauma in the Honolulu Heart Program. Arch Intern Med 1995;155(7):695-700.
  • .Iribarren C, Sharp D, Burchfiel CM, et al. Association of serum total cholesterol with coronary disease and all-cause mortality: multivariate correction for bias due to measurement error. Am J Epidemiol 1996;143(5):463-471.
  • .Isaac S. The “gauntlet” of pellagra. Int J Dermatol 1998;37(8):599.
  • .Jackson TM, Rawling JM, Roebuck BD, et al. Large supplements of nicotinic acid and nicotinamide increase tissue NAD+ and poly(ADP-ribose) levels but do not affect diethylnitrosamine-induced altered hepatic foci in Fischer-344 rats. J Nutr 1995;125:1455-1461.
  • .Jacob R, Swenseid M. Niacin. In: Ziegler EE, Filer LJ, eds. Present knowledge in nutrition. 7th ed. Washington, DC: ILSI Press; 1996:185-190.
  • .Jacobs DR Jr, Hebert B, Schreiner PJ, et al. Reduced cholesterol is associated with recent minor illness: the CARDIA Study: Coronary Artery Risk Development in Young Adults. Am J Epidemiol 1997;146(7):558-564.
  • .Jacobson EL. Niacin deficiency and cancer in women. J Am Coll Nutr 1993;12(4):412-416.
  • .Jacobson EL, Jacobson MK. Tissue NAD as a biochemical measure of niacin status in humans. Methods Enzymol 1997;280:221-230.
  • .Jacobson EL, Shieh WM, Huang AC. Mapping the role of NAD metabolism in prevention and treatment of carcinogenesis. Mol Cell Biochem 1999;193(1-2):69-74.
  • .Jacobson MK, Jacobson EL. Discovering new ADP-ribose polymer cycles: protecting the genome and more. Trends Biochem Sci 1999;24(11):415-417.
  • .Jacobson TA, Amorosa LF. Combination therapy with fluvastatin and niacin in hypercholesterolemia: a preliminary report on safety. Am J Cardiol 1994;73:25D-29D.
  • .Jacques PF, Chylack LT Jr, Hankinson SE, et al. Long-term nutrient intake and early age related nuclear lens opacities. Arch Ophthalmol 2001;119(7):1009-1019.
  • .Jenkins DJ, Kendall CW, Marchie A, et al. The effect of combining plant sterols, soy protein, viscous fibers, and almonds in treating hypercholesterolemia. Metabolism 2003;52(11):1478-1483.
  • .Johnsen SH, Mathiesen EB, Fosse E, et al. Elevated high-density lipoprotein cholesterol levels are protective against plaque progression: a follow-up study of 1952 persons with carotid atherosclerosis: The Tromso Study. Circulation 2005;112:498-504.
  • .Jonas WB, Rapoza CP, Blair WF. The effect of niacinamide on osteoarthritis: a pilot study. Inflamm Res 1996;45(7):330-334.
  • .Kahn SE, Beard JC, Schwartz MW, et al. Increased beta-cell secretory capacity as mechanism for islet adaptation to nicotinic acid-induced insulin resistance. Diabetes 1989;38(5):562-568.
  • .Kallmann B, Burkhart V, Kroncke KD, et al. Toxicity of chemically generated nitric oxide towards pancreatic islet cells can be prevented by nicotinamide. Life Sci 1992;51:671-678.
  • .Kanter AS, Spencer D et al. Supplemental multivitamins or vitamin B complex significantly delay progression to AIDS and death in South African patients infected with HIV: abstract 217. Conference of Retroviruses and Opportunistic Infections. Chicago, 1998.
  • .Karthikeyan K, Thappa DM. Pellagra and skin. Int J Dermatol 2002;41(8):476-481. (Review)
  • .Kashani A, Phillips CO, Foody JM, et al. Risks associated with statin therapy: a systematic overview of randomized clinical trials. Circulation 2006;114(25):2788-2797.
  • .Kashyap ML, Evans R, Simmons PD, et al. New combination niacin/statin formulation shows pronounced effects on major lipoproteins and is well tolerated. J Am Coll Cardiol 2000;35(Suppl A):326.
  • .Kaufman W. The common form of joint dysfunction: its incidence and treatment. Brattleboro, VT: EL Hildreth and Company; 1949.
  • .Kaufman W. The use of vitamin therapy to reverse certain concomitants of aging. J Am Geriatr Soc 1955;3(11):927-936.
  • .Kaur S, Goraya JS, Thami GP, et al. Pellagrous dermatitis induced by phenytoin. Pediatr Dermatol 2002;19(1):93. (Case report)
  • .Keenan JM, Fontaine PL, Wenz JB, et al. Niacin revisited: a randomized, controlled trial of wax-matrix sustained-release niacin in hypercholesterolemia. Arch Intern Med 1991;151:1424-1432.
  • .Kellman M. Bursitis: a new chemotherapeutic approach. J Am Osteopathic Assoc 1962;61:896-903.
  • .Kiff RS, Quick CR. Does inositol nicotinate (Hexopal) influence intermittent claudication? A controlled trial. Br J Clin Pract 1988;42:141-145.
  • .Kime CE. Bell’s palsy: a new syndrome associated with treatment by nicotinic acid: a guide to adequate medical therapy. AMA Arch Otolaryngol 1958;68(1):28-32.
  • .Knip M, Douek IF, Moore WP, et al. Safety of high dose nicotinamide: a review. Diabetologia 2000;43:1337-1345. (Review)
  • .Knopp RH. Drug treatment of lipid disorders. N Engl J Med 1999;341(7):498-511.
  • .Knopp RH. Evaluating niacin in its various forms. Am J Cardiol 2000;86(12A):51L-56L.
  • .Knopp RH. Niacin and hepatic failure. Ann Intern Med 1989;111:769. (Letter)
  • .Knopp RH, d’Emden M, Smilde JG, et al. Efficacy and safety of atorvastatin in the prevention of cardiovascular end points in subjects with type 2 diabetes: the Atorvastatin Study for Prevention of Coronary Heart Disease Endpoints in Non-Insulin-Dependent Diabetes Mellitus (ASPEN). Diabetes Care 2006;29(7):1478-1485.
  • .Knopp RH, Ginsberg J, Albers JJ, et al. Contrasting effects of unmodified and time-release forms of niacin on lipoproteins in hyperlipidemic subjects: clues to mechanism of action of niacin. Metabolism 1985;34(7):642-650.
  • .Krauss RM, Siri PW. Metabolic abnormalities: triglyceride and low-density lipoprotein. Endocrinol Metab Clin North Am 2004;33(2):405-415. (Review)
  • .Krauss RM, Yang H, Rieder MJ, et al. Haplotypes in the HMGCoA reductase gene influence plasma LDL level and LDL response to statin in African Americans and Caucasians: abstract 725. American Heart Association Scientific Sessions 2005. Dallas, Nov 14, 2005.
  • .Kunin RA. Manganese and niacin in the treatment of drug-induced tardive dyskinesias. J Orthomol Psychiatry 1976;5:4-27.
  • .Kuramitsu M, Okumura Y, Kuramitsu M, et al. [Alcoholic pellagra psychosis: six cases including an autopsied case.] Seishin Shinkeigaku Zasshi 1991;93(1):1-19. [Japanese]
  • .Kuroki F, Iida M, Tominaga M, et al. Multiple vitamin status in Crohn’s disease. Dig Dis Sci 1993;38(9):1614-1618.
  • .Kuzniarz M, Mitchell P, Cumming RG, et al. Use of vitamin supplements and cataract: the Blue Mountains Eye Study. Am J Ophthalmol 2001;132(1):19-26.
  • .Lal SM, Hewett JE, Petroski G, et al. Effects of nicotinic acid and lovastatin in renal transplant patients: a prospective, randomized, open-labeled crossover trial. Am J Kidney Dis 1995;25:616-622.
  • .Lemaitre RN, Psaty BM, Heckbert SR, et al. Therapy with hydroxymethylglutaryl coenzyme a reductase inhibitors (statins) and associated risk of incident cardiovascular events in older adults: evidence from the Cardiovascular Health Study. Arch Intern Med 2002;162(12):1395-1400.
  • .Lampeter EF, Klinghammer A, Scherbaum WA, et al. The Deutsche Nicotinamide Intervention Study: an attempt to prevent type 1 diabetes: DENIS Group. Diabetes 1998;47:980-984.
  • .Lei TC, Virador VM, Vieira WD, et al. A melanocyte-keratinocyte coculture model to assess regulators of pigmentation in vitro. Anal Biochem 2002;305:260-268.
  • .Lewis CM, Canafax DM, Sprafka JM, et al. Double-blind randomized trial of nicotinamide on early-onset diabetes. Diabetes Care 1992;15:121-123.
  • .LeWitt PA. The neurotoxicity of the rat poison vacor: a clinical study of 12 cases. N Engl J Med 1980:302(2):73-77.
  • .Lehmann HE, Ban TA, Saxena BM. Nicotinic acid, thioridazine, fluoxymesterone and their combinations in hospitalized geriatric patients: a systematic clinical study. Can Psychiatr Assoc J 1972;17(4):315-320.
  • .Leonard JV, Marrs TC, Addison JM, et al. Intestinal absorption of amino acids and peptides in Hartnup disorder. Pediatr Res 1976;10(4):246-249.
  • .Levy HB, Kohlhaas HK. Considerations for supplementing with coenzyme q10 during statin therapy. Ann Pharmacother 2006;40(2):290-294.
  • .Loscalzo J. Homocysteine trials: clear outcomes for complex reasons. N Engl J Med. 2006;354(15):1629-1632. (Editorial)
  • .Lu JY, Yu CL, Wu MZ. Pellagra in an immunocompetent patient with cytomegalovirus colitis. Am J Gastroenterol 2001;96(3):932-934.
  • .Ludvigsson J, Samuelsson U, Johansson C, et al. Treatment with antioxidants at onset of type 1 diabetes in children: a randomized, double-blind placebo-controlled study. Diabetes Metab Res Rev 2001;17:131-136.
  • .Luria MH. Effect of low-dose niacin on high-density lipoprotein cholesterol and total cholesterol/high-density lipoprotein cholesterol ratio. Arch Intern Med 1988;148(11):2493-2495.
  • .Mahon BE, Levy HL. Maternal Hartnup disorder. Am J Med Genet 1986;24(3):513-518.
  • .Mahl M, Lange K. A long term study of the effect of nicotinic acid medication on hypercholesterolemia. Am J Med Sci 1963;65:673.
  • .Malik S, Kashyap ML. Niacin, lipids, and heart disease. Curr Cardiol Rep 2003;5:470-476.
  • .Majamaa K, Rusanen H, Remes AM, et al. Increase of blood NAD+ and attenuation of lactacidemia during nicotinamide treatment of a patient with the MELAS syndrome. Life Sci 1996;58:691-699.
  • .Malik S, Kashyap ML. Niacin, lipids, and heart disease. Curr Cardiol Rep 2003;5:470-476.
  • .Mancinella G, Liuti G, Vartolo C, et al. [An infrequent complication of chronic alcoholic hepatopathy: pellagra.] Clin Ter 1980;92(6):671-678. [Italian]
  • .Manku MS, Horrobin DF, Morse N, et al. Reduced levels of prostaglandin precursors in the blood of atopic patients: defective delta-6-desaturase function as a biochemical basis for atopy. Prostaglandins Leukot Med 1982;(6):615-628.
  • .Marcus R, Coulston AM. Water-soluble vitamins: the vitamin B complex and ascorbic acid. In: Hardman JG, Limbird LE, Molinoff PB, et al, eds. The pharmacological basis of therapeutics. 9th ed. New York: McGraw Hill; 1995:1555-1571.
  • .Marks JB, Skyler JS. Clinical review 17: immunotherapy of type 1 diabetes mellitus. J Clin Endocrinol Metab 1991;72:3-9.
  • .Maron BA, Loscalzo J. Homocysteine. Clin Lab Med 2006;26(3):591-609, vi.
  • .Martin PD, Dane AL, Schneck DW, et al. An open-label, randomized, three-way crossover trial of the effects of coadministration of rosuvastatin and fenofibrate on the pharmacokinetic properties of rosuvastatin and fenofibric acid in healthy male volunteers. Clin Ther 2003;25:459-471.
  • .Marz R. Medical nutrition from Marz. 2nd ed. Portland, OR: Omni Press; 1997. (Review)
  • .Mason M, Ford J, Wu HL. Effects of steroid and nonsteroid metabolites on enzyme conformation and pyridoxal phosphate binding. Ann N Y Acad Sci 1969;166(1):170-183.
  • .Matsui MS, Rozovski SJ. Drug-nutrient interaction. Clin Ther 1982;4(6):423-440.
  • .May HT, Muhlestein JB, Carlquist JF, et al. Relation of serum total cholesterol, C-reactive protein levels, and statin therapy to survival in heart failure. Am J Cardiol 2006;98(5):653-658.
  • .McCarty MF, Russell AL. Niacinamide therapy for osteoarthritis: does it inhibit nitric oxide synthase induction by interleukin 1 in chondrocytes? Med Hypotheses 1999;53(4):350-360.
  • .McCreanor GM, Bender DA. The metabolism of high intakes of tryptophan, nicotinamide, and nicotinic acid in the rat. Br J Nutr 1986;56:577-586.
  • .McGovern ME. Taking aim at HDL-C: raising levels to reduce cardiovascular risk. Postgrad Med 2005;117(4):29-39. (Review)
  • .McKenney JM, Proctor JD, Harris S, et al. A comparison of the efficacy and toxic effects of sustained- vs immediate-release niacin in hypercholesterolemic patients. JAMA 1994;271(9):672-677.
  • .Mears E, Vessey MP, Andolsek L, et al. Preliminary evaluation of four oral contraceptives containing only progestogens. Br Med J 1969;1(659):730-734.
  • .Meyer NA, Muller MJ, Herndon DN. Nutrient support of the healing wound. N Horiz 1994;2(2):202-214.
  • .Meyers CD, Carr MC, Park S, et al. Varying cost and free nicotinic acid content in over-the-counter niacin preparations for dyslipidemia. Ann Intern Med 2003;139(12):996-1002.
  • .Meyers CD, Kamanna VS, Kashyap ML. Niacin therapy in atherosclerosis. Curr Opin Lipidol 2004;15(6):659-665. (Review)
  • .Miesel R, Kurpisz M, Kroger H. Modulation of inflammatory arthritis by inhibition of poly(ADP ribose) polymerase. Inflammation 1995;19:379-387.
  • .Miettinen TA, Taskinen MR, Pelkonen R, et al. Glucose tolerance and plasma insulin in man during acute and chronic administration of nicotinic acid. Acta Med Scand 1969;186(4):247-253.
  • .Mohler H, Polc P, Cumin R, et al. Nicotinamide is a brain constituent with benzodiazepine-like actions. Nature 1979;278(5704):563-565.

  • .Molnar GD, Berge KG, Rosevear JW, et al. The effect of nicotinic acid in diabetes mellitus. Metabolism 1964;13(2):181-189.
  • .Moore MT. Treatment of multiple sclerosis with nicotinic acid and vitamin B1. Arch Int Med 1940;65:18.
  • .Morgan JM, Capuzzi DM, Guyton JR, et al. Treatment effect of Niaspan, a controlled-release niacin, in patients with hypercholesterolemia: a placebo-controlled trial. J Cardiovasc Pharmacol Ther 1996;1:195-202.
  • .Morrow JD, Parsons WG III, Roberts LJ II. Release of markedly increased quantities of prostaglandin D2 in vivo in humans following the administration of nicotinic acid. Prostaglandins 1989;38:2:263-274.
  • .Murray M. Lipid-lowering drugs vs. inositol hexaniacinate. Am J Nat Med 1995;2:9-12.
  • .Murray M, Pizzorno J. Encyclopedia of natural medicine. Rocklin, CA: Prima Press; 1998, 354.
  • .Murray MF, Langan M, MacGregor RR. Increased plasma tryptophan in HIV-infected patients treated with pharmacologic doses of nicotinamide. Nutrition 2001;17(7-8):654-656.
  • .Negri E, Franceschi S, Bosetti C, et al. Selected micronutrients and oral and pharyngeal cancer. Int J Cancer 2000;86(1):122-127.
  • .Neumann R, Rappold E, Pohl-Markl H. Treatment of polymorphous light eruption with nicotinamide: a pilot study. Br J Dermatol 1986;115:77-80.
  • .Newbold HL, Mosher LR. Niacin and the schizophrenic patient. Am J Psychiatry 1970;127:535-536.
  • .Nicholls SJ, Tuzcu EM, Sipahi I, et al. Effects of obesity on lipid-lowering, anti-inflammatory, and antiatherosclerotic benefits of atorvastatin or pravastatin in patients with coronary artery disease (from the REVERSAL Study). Am J Cardiol 2006;97(11):1553-1557.
  • .Nistico G, Preziosi P. Contraceptives, brain serotonin, and liver tryptophan pyrrolase. Lancet 1970;2(7665):213.
  • .Nomikos IN, Prowse SJ, Carotenuto P, et al. Combined treatment with nicotinamide and desferrioxamine prevents islet allograft destruction in NOD mice. Diabetes 1986;35(11):1302-1304.
  • .O’Hara J, Jolly PN, Nicol CG. The therapeutic efficacy of inositol nicotinate (Hexopal) in intermittent claudication: a controlled trial. Br J Clin Pract 1988;42(9):377-383.
  • .Omar MA, Wilson JP. FDA adverse event reports on statin-associated rhabdomyolysis. Ann Pharmacother 2002;36:288-295.
  • .Osmond H, Hoffer A. Massive niacin treatment in schizophrenia: review of a nine-year study. Lancet 1962;1:316-319.
  • .Ovesen L. Vitamin therapy in the absence of obvious deficiency: what is the evidence? Drugs 1984;27(2):148-170.
  • .Park YK, Sempos CT, Barton CN, et al. Effectiveness of food fortification in the United States: the case of pellagra. Am J Public Health 2000;90(5):727-738.
  • .Parkhomets PK, Kuchmerovskaia TM, Donchenko GV, et al. [Role of nicotinic acid and its derivatives in disorders of nervous system function.] Ukr Biokhim Zh 1995;67:3-11. [Russian]
  • .Pasmans SG, Preesman AH, van Vloten WA. [Pellagra (deficiency of vitamin B3 or of the amino acid tryptophan): a disease still extant in the Netherlands.] Ned Tijdschr Geneeskd 1998;142(33):1880-1882. [Dutch]
  • .Pasternak RC, Brown LE, Stone PH, et al. Effect of combination therapy with lipid-reducing drugs in patients with coronary heart disease and “normal” cholesterol levels: a randomized, placebo-controlled trial: Harvard Atherosclerosis Reversibility Project (HARP) study group. Ann Intern Med 1996;125(7):529-540.
  • .Patterson DJ, Dew EW, Gyorkey F, et al. Niacin hepatitis. South Med J 1983;76:240-241.
  • .Pauling L. On the orthomolecular environment of the mind: orthomolecular theory. Am J Psychiatry 1974;131:1251-1257.
  • .Pearlman BL. The new cholesterol guidelines. Postgrad Med 2002;112(2):13-26. (Review)
  • .Pedersen TR, Faergeman O, Kastelein JJP, et al. High-dose atorvastatin vs usual-dose simvastatin for secondary prevention after myocardial infarction: the IDEAL Study: a randomized controlled trial. JAMA 2005;294:2437-2445.
  • .Petley A, Macklin B, Renwick AG, et al. The pharmacokinetics of nicotinamide in humans and rodents. Diabetes 1995;44:152-155.
  • .Petrie WM, Ban TA. Vitamins in psychiatry: do they have a role? Drugs 1985;30:58-65.
  • .Petrie WM, Ban TA, Ananth JV. The use of nicotinic acid and pyridoxine in the treatment of schizophrenia. Int Pharmacopsychiatry 1981;16(4):245-250.
  • .Philipp CS, Cisar LA, Saidi P, et al. Effect of niacin supplementation on fibrinogen levels in patients with peripheral vascular disease. Am J Cardiol 1998;82(5):697-699, A9.
  • .Picciotto MR, Brunzell DH, Caldarone BJ. Effect of nicotine and nicotinic receptors on anxiety and depression. Neuroreport 2002;13(9):1097-1106. (Review)
  • .Picciotto MR, Caldarone BJ, Brunzell DH, et al. Neuronal nicotinic acetylcholine receptor subunit knockout mice: physiological and behavioral phenotypes and possible clinical implications. Pharmacol Ther 2001;92(2-3):89-108. (Review)
  • .Pitsavas S, Andreou C, Bascialla F, et al. Pellagra encephalopathy following B-complex vitamin treatment without niacin. Int J Psychiatry Med 2004;34(1):91-95. (Case report)
  • .Pollack H. Nicotinic acid and diabetes. Diabetes 1962;11(2):144.
  • .Polo V, Saibene A, Pontiroli AE. Nicotinamide improves insulin secretion and metabolic control in lean type 2 diabetic patients with secondary failure to sulphonylureas. Acta Diabetol 1998;35:61-64.
  • .Pozzilli P, Browne PD, Kolb H. Meta-analysis of nicotinamide treatment in patients with recent-onset IDDM: the Nicotinamide Trialists. Diabetes Care 1996;19(12):1357-1363.
  • .Pozzilli P, Visalli N, Signore A, et al. Double blind trial of nicotinamide in recent-onset IDDM (the IMDIAB III study). Diabetologia 1995;38:848-852.
  • .Prasad PV, Babu A, Paul EK, et al. Myxoedema pellagra: a report of two cases. J Assoc Physicians India 2003;51:421-422.
  • .Price JM, Brown RR, Yess N. Testing the functional capacity of the tryptophan-niacin pathway in man by analysis of urinary metabolites. Adv Metab Disord 1965;2:159-225.
  • .Price JM, Thornton MJ, Mueller LM. Tryptophan metabolism in women using steroid hormones for ovulation control. Am J Clin Nutr 1967;20(5):452-456.
  • .Procter A. Enhancement of recovery from psychiatric illness by methylfolate. Br J Psychiatry 1991;159:271-272.
  • .Pronsky Z. Powers and Moore’s food-medications interactions. 9th ed. Pottstown, PA: Food-Medication Interactions; 1991. (Review)
  • .Rader JI, Calvert RJ, Hathcock JN. Hepatic toxicity of unmodified and time-release preparations of niacin. Am J Med 1992;92:77-81. (Review)
  • .Radons J, Heller B, Burkle A, et al. Nitric oxide toxicity in islet cells involves poly(ADP-ribose) polymerase activation and concomitant NAD+ depletion. Biochem Biophys Res Commun 1994;199:1270-1277.
  • .Rasool AA, Hussain AA, Dittert LW. Solubility enhancement of some water-insoluble drugs in the presence of nicotinamide and related compounds. J Pharm Sci 1991;80(4):387-393.

  • .Robinson C, Weigly E. Basic nutrition and diet therapy. New York: MacMillan; 1984.
  • .Roe DA. Diet and drug interactions. New York: Van Nostrand Reinhold; 1989. (Review)
  • .Roe DA. Drug and nutrient interactions in the elderly diabetic. Drug Nutr Interact 1988;5(4):195-203. (Review)
  • .Roe DA. Drug-induced nutritional deficiencies. 2nd ed. Westport, CT: Avi Publishing; 1985.
  • .Roe DA. Risk factors in drug-induced nutritional deficiencies. In: Roe DA, Campbell T, eds. Drugs and nutrients: the interactive effects. New York: Marcel Decker; 1984:505-523.
  • .Rose DP, Adams PW. Oral contraceptives and tryptophan metabolism: effects of oestrogen in low dose combined with a progestagen and of a low-dose progestagen (megestrol acetate) given alone. J Clin Pathol 1972; 25(3):252-258.
  • .Rubins HB, Robins SJ, Collins D, et al. Gemfibrozil for the secondary prevention of coronary heart disease in men with low levels of high-density lipoprotein cholesterol: Veterans Affairs High-Density Lipoprotein Cholesterol Intervention Trial Study Group. N Engl J Med 1999;341(6):410-418.
  • .Sandler S, Andersson A. Long-term effects of exposure of pancreatic islets to nicotinamide in vitro on DNA synthesis, metabolism and B-cell function. Diabetologia 1986;29:199-202.
  • .Schatz DA, Bingley PJ. Update on major trials for the prevention of type 1 diabetes mellitus: the American Diabetes Prevention Trial (DPT-1) and the European Nicotinamide Diabetes Intervention Trial (ENDIT). J Pediatr Endocrinol Metab 2001;14(Suppl 1):619-622.
  • .Schectman G, Hiatt J. Dose-response characteristics of cholesterol-lowering drug therapies: implications for treatment. Ann Intern Med 1996;125(12):990-1000.
  • .Schmitz W. [Psychopathology of pellagra in children.] Psychiatr Neurol Med Psychol (Leipz) 1971;23(3):159-166. [German]
  • .Schoch HK. The US Veterans Administration cardiology drug-lipid study: an interim report. Adv Exper Med Biol 1968;4:405-420.
  • .Schwab RA, Bachhuber BH. Delirium and lactic acidosis caused by ethanol and niacin co-ingestion. Am J Emerg Med 1991;9:363-365.
  • .Schwartz GG, Olsson AG, Ezekowitz MD. Effects of atorvastatin on early recurrent ischemic events in acute coronary syndromes: the MIRACL study: a randomized controlled trial. JAMA 2001;285(13):1711-1718.
  • .Sifton DW, ed. Physicians desk reference. Montvale, NJ: Medical Economics Company, Inc; 2000:1346-1349, 2071-2073.
  • .Spence JD, Bang H, Chambless LE, et al. Vitamin Intervention For Stroke Prevention trial: an efficacy analysis. Stroke 2005;36(11):2404-2409.
  • .Sperduto RD, Hu TS, Milton RC, et al. The Linxian cataract studies: two nutrition intervention trials. Arch Ophthamol 1993;111:1246-1253.
  • .Srikantia SG, Reddy MV, Krishnaswamy K. Electroencephalographic patterns in pellagra. Electroencephalogr Clin Neurophysiol 1968;25(4):386-388.
  • .Stadler R, Orfanos CE, Immel C. [Drug-induced pellagra.] Hautarzt 1982;33(5):276-280. (Case report) [German]
  • .Stockley IH. Drug Interactions. 6th ed. London: Pharmaceutical Press; 2002. (Review)
  • .Stratford MR, Dennis MF, Hoskin P, et al. Nicotinamide pharmacokinetics in humans: effect of gastric acid inhibition: comparison of rectal vs oral administration and the use of saliva for drug monitoring. Br J Cancer 1996;74:16-21.
  • .Stratigos JD, Katsambas AD. Pellagra: “a reappraisal.” Acta Vitaminol Enzymol 1982;4(1-2):115-121. (Review)
  • .Stratigos JD, Katsambas A. Pellagra: a still existing disease. Br J Dermatol 1977;96(1):99-106.
  • .Stratigos J, Katsambas A, Galanopoulou P. Pellagra, serotonin and 5-HIAA. Br J Dermatol 1974;90(4):451-452.
  • .Studer M, Briel M, Leimenstoll B, et al. Effect of different antilipidemic agents and diets on mortality: a systematic review. Arch Intern Med 2005;165:725-730. (Review)
  • .Suenaert P, Bulteel V, Den Hond E, et al. In vivo influence of nicotine on human basal and NSAID-induced gut barrier function. Scand J Gastroenterol 2003;38(4):399-408.
  • .Sunderland GT, Belch JJ, Sturrock RD, et al. A double blind randomised placebo controlled trial of hexopal in primary Raynaud’s disease. Clin Rheumatol 1988;7:46-49.
  • .Tahmoush AJ, Alpers DH, Feigin RD, et al. Hartnup disease: clinical, pathological, and biochemical observations. Arch Neurol 1976;33(12):797-807.
  • .Taketomo CK, Hodding JH, Kraus DM. Pediatric dosage handbook. 5th ed. Hudson, OH: Lexicomp; 1998:783.
  • .Tall AR. Protease variants, LDL, and coronary heart disease. N Engl J Med 2006;354:1310-1312. (Editorial)
  • .Tang AM, Graham NHM, Kirby AJ, et al. Dietary micronutrient intake and risk of progression to acquired immunodeficiency syndrome (AIDS) in human immunodeficiency virus type 1 (HIV-1)-infected homosexual men. Am J Epidemiol 1993;138:937-951.
  • .Tang AM, Graham NM, Saah AJ. Effects of micronutrient intake on survival in human immunodeficiency virus type 1 infection. Am J Epidemiol 1996;143(12):1244-1256.
  • .Thomas RG, Wysor WG Jr. Alteration of serotonin metabolism in rats deficient in niacin and tryptophan. Proc Soc Exp Biol Med 1967;126(2):374-379.
  • .Thompson PD, Clarkson P, Karas RH. Statin-associated myopathy. JAMA 2003;289:1681-1690.
  • .Threlkeld DS, ed. Diuretics and cardiovasculars, antihyperlipidemic agents, HMG-CoA reductase inhibitors. In: Facts and Comparisons drug information. St Louis: Facts and Comparisons; 1998. (Review)

  • .Torkos S. Drug-nutrient interactions: a focus on cholesterol-lowering agents. Int J Integrative Med. 2000;2(3):9-13. (Review)
  • .Tornvall P, Walldius G. A comparison between nicotinic acid and acipimox in hypertriglyceridaemia: effects on serum lipids, lipoproteins, glucose tolerance and tolerability. J Intern Med 1991;230(5):415-421.
  • .Trovato A, Nuhlicek DN, Midtling JE. Drug-nutrient interactions. Am Fam Physician 1991;44(5):1651-1658. (Review)
  • .Tsivgoulis G, Spengos K, Karandreas N, et al. Presymptomatic neuromuscular disorders disclosed following statin treatment. Arch Intern Med 2006;166:1519-1524.
  • .Tyson VC. Treatment of intermittent claudication. Practitioner 1979;223:121-126.
  • .USDA: Composition of foods: USDA handbook #8. Washington, DC: ARS, USDA; 1976-1986.
  • .Vega GL, Ma PT, Cater NB, et al. Effects of adding fenofibrate (200 mg/day) to simvastatin (10 mg/day) in patients with combined hyperlipidemia and metabolic syndrome. Am J Cardiol 2003;91:956-960.
  • .Velling DA, Dodick DW, Muir JJ. Sustained-release niacin for prevention of migraine headache. Mayo Clin Proc 2003;78(6):770-771.
  • .Visalli N, Cavallo MG, Signore A, et al. A multi-centre randomized trial of two different doses of nicotinamide in patients with recent-onset type 1 diabetes (the IMDIAB VI). Diabetes Metab Res Rev 1999;15(3):181-185.
  • .Wald DS, Wald NJ, Morris JK, Law M. Folic acid, homocysteine, and cardiovascular disease: judging causality in the face of inconclusive trial evidence. BMJ 2006;333(7578):1114-1117. (Editorial, Review)
  • .Waldo MC. Co-distribution of sensory gating and impaired niacin flush response in the parents of schizophrenics. Schizophr Res 1999;40:1:49-53.
  • .Wang D, Taylor, KD, Smith J, et al. IL1B and TRAF6 are associated with components of low-density lipoprotein cholesterol reduction during statin therapy: poster 3. American Heart Association Scientific Sessions 2005: Dallas, Nov 14, 2005.
  • .Wang TJ, Gona P, Larson MG, et al. Multiple biomarkers for the prediction of first major cardiovascular events and death. N Engl J Med 2006;355(25):2631-2639.
  • .Warburg O, Christian W. Co-ferment problem. Biochemie 1934;274:122-125.
  • .Ward PE, Sutherland J, Glen EM, et al. Niacin skin flush in schizophrenia: a preliminary report. Schizophr Res 1998;29(3):269-274.
  • .Ware JH. The limitations of risk factors as diagnostic tools. N Engl J Med 2006;355(25):2615-2617. (Editorial)
  • .Wei L, Murphy MJ, MacDonald TM. Impact on cardiovascular events of increasing high density lipoprotein cholesterol with and without lipid lowering drugs. Heart 2006;92(6):746-751.
  • .Weitberg AB. Effect of nicotinic acid supplementation in vivo on oxygen radical-induced genetic damage in human lymphocytes. Mutat Res 1989;216(4):197-201.
  • .Welch GN, Upchurch GR Jr, Loscalzo J. Homocysteine, oxidative stress, and vascular disease. Hosp Pract (Minneapolis) 1997;32(6):81-82, 85, 88-92. (Review)
  • .Welsh AL, Ede M. Inositol hexanicotinate for improved nicotinic acid therapy. Int Record Med 1961;174:9-15.
  • .Werbach MR. Foundations of nutritional medicine. Tarzana, CA: Third Line Press; 1997:210-211. (Review)
  • .Weterle R, Rybakowski J. [The niacin test in schizophrenia.] Psychiatr Pol 1990;24(2):116-120. [Polish]
  • .Whitney EJ, Krasuski RA, Personius BE, et al. A randomized trial of a strategy for increasing high-density lipoprotein cholesterol levels: effects on progression of coronary heart disease and clinical events. Ann Intern Med 2005;142(2):95-104.
  • .Wilcken B, Yu JS, Brown DA. Natural history of Hartnup disease. Arch Dis Child 1977;52(1):38-40.
  • .Wilke RA, Moore JH, Burmester JK. Relative impact of CYP3A genotype and concomitant medication on the severity of atorvastatin-induced muscle damage. Pharmacogenet Genomics 2005;15(6):415-421.
  • .Winter SL, Boyer JL. Hepatic toxicity from large doses of vitamin B3 (nicotinamide). N Engl J Med 1973;289:1180-1182.
  • .Wittenborn JR, Weber ES, Brown M. Niacin in the long-term treatment of schizophrenia. Arch Gen Psychiatry 1973;28:308-315.
  • .Wolfe ML, Vartanian SF, Ross JL, et al. Safety and effectiveness of Niaspan when added sequentially to a statin for treatment of dyslipidemia. Am J Cardiol 2001;87(4):476-9, A7.
  • .Wood B, Rademaker M, Oakley A, et al. Pellagra in a woman using alternative remedies. Australas J Dermatol 1998;39(1):42-44. (Case report)
  • .Wyatt RJ. On the orthomolecular environment of the mind: orthomolecular theory: comment. Am J Psychiatry 1974;131:1258-1262.
  • .Wynn V. Vitamins and oral contraceptive use. Lancet 1975;1:561-564.
  • .Yee HS, Fong NT, Atorvastatin in the treatment of primary hypercholesterolemia and mixed dyslipidemias. Ann Pharmacother 1998;32(10):1030-1043.
  • .Yeshurun D, Slobodin G, Keren D, et al. Statin escape phenomenon: does it really exist? Eur J Intern Med 2005;16(3):192-194.
  • .Yin S, Sato I, Yamaguchu K. Comparison of selenium level and glutathione peroxidase activity in tissues of vitamin B-6 deficient rats fed sodium selenite or DL-selonomethionine. J Nutr Biochem 1992;3:633-643.
  • .Yokoyama M, Origasa H, Matsuzaki M, et al. Effects of eicosapentaenoic acid (EPA) on major cardiovascular events in hypercholesterolemic patients: the Japan EPA Lipid Intervention Study (JELIS). American Heart Association Scientific Sessions 2005. Dallas, Nov 14, 2005.
  • .Yonemura Y, Takashima T, Miwa K, et al. Amelioration of diabetes mellitus in partially depancreatized rats by poly(ADP-ribose) synthetase inhibitors: evidence of islet B-cell regeneration. Diabetes 1984;33:401-404.
  • .Ziliotto GR, Lamberti G, Wagner A, et al. [Comparative studies of the response of normolipemic and dyslipemic aged subjects to 2 forms of delayed-action nicotinic acid polyesters: pentaerythrotol tetranicotinate and inositol hexanicotinate: results of a controlled cross-over trial.] Arch Sci Med (Torino) 1977;134(4):359-394. [Italian]