Addition Of Niacin Research Articles

Hericium erinaceus, in combination with natural flavonoid/alkaloid and B3/B8 vitamins, can improve inflammatory burden in Inflammatory bowel diseases tissue: an ex vivo study.

Hericium erinaceus, berberine, and quercetin are effective in experimental colitis. It is unknown whether they can ameliorate inflammatory bowel diseases in humans. This ex vivo study aimed to evaluate the anti-inflammatory potential of a nutraceutical compound of HBQ-Complex® (H. erinaceus, berberine, and quercetin), biotin, and niacin in inflammatory bowel disease patients. Tissue specimens were obtained either from Normal-Appearing Mucosa (NAM) or from Inflamed Mucosa (IM) in 20 patients with inflammatory bowel disease. mRNA and protein expression of COX-2, IL-10, and TNF-α were determined in NAM and IM biopsy samples (T0). IM samples were then incubated in HBQ-Complex® (with the addition of niacin and biotin), and COX-2, IL-10, and TNF-α tissue levels were evaluated at 120 minutes (T1) and 180 minutes (T2). Incubation with this compound resulted in a progressive decrease in gene and protein COX-2 and TNF-α expression at T1/T2 in the IM. IL-10 showed an opposite trend, with a progressive increase of mRNA and protein expression over the same time window. HBQ-Complex® (with the addition of niacin and biotin) decreased the expression of proinflammatory cytokines at the mRNA and protein levels in IBD tissue. On the contrary, mRNA and protein expression of the anti-inflammatory cytokine IL-10 showed a progressive increase.

Niacin Status Indicators and Their Relationship with Metabolic Parameters in Dairy Cows during Early Lactation.

Simple SummaryThe active forms of niacin that represent niacin status are nicotinamide adenine dinucleotide (NAD), nicotinamide adenine dinucleotide phosphate (NADP) and the NAD:NADP ratio. Previous studies have shown metabolic changes in the function of niacin form and dose, but it has not been determined whether there are changes in the function of active form of niacin that indicate the vitamin status in the body. In this study, we examined differences in NAD, NADP and NAD:NADP concentration in blood and their relationship with metabolic parameters in cows receiving and not receiving additional niacin in food. We concluded that NAD and NADP are good indicators of the ability of an additional niacin source to create functional cofactors due to their concentration changes, while the NAD:NADP ratio is a good indicator of the biological effects of additional niacin due to correlation with many metabolites.Previous experimental models on cows have examined the difference in the metabolic adaptation in cows after niacin administration, without identifying the most important mediators between niacin administration and its biological effects, namely active forms of niacin. All tissues in the body convert absorbed niacin into its main metabolically active form, the coenzyme nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP). The aim of this study was to determine the influence of niacin administration in periparturient period on NAD, NADP and the NAD:NADP ratio and to determine relationship between these indicators of an active form of niacin with metabolic parameters in cow blood. The study included 90 healthy cows: 45 cows receiving niacin and 45 cows were negative control. The niacin group was treated with nicotinic acid for two weeks before, as well as two weeks after parturition. Nicotinic acid was applied per os with feed. In cows receiving niacin, there was a significantly higher concentration of NAD and NADP, but the NAD:NADP ratio did not differ compared with control. All three indicators were able to separate cows who received and who did not receive additional niacin. NAD and NADP are good indicators of the availability of niacin from additional sources. The NAD:NADP ratio is a good indicator of the biological effect of applied niacin on metabolites in cows due to its correlation with a number of metabolites: positive correlation with glucose, insulin, glucose to insulin ratio and the revised quantitative insulin sensitivity check index (RQUICKIBHB) of insulin resistance, triglycerides and cholesterol, and a negative correlation with nonesterified fatty acid (NEFA), beta hydroxybutyrate (BHB), gamma-glutamyltranspherase (GGT) and urea in cows receiving niacin. The same amount of added niacin in feed can produce different concentrations of NAD, NADP and NAD:NADP in the blood, and this was not related to their concentration before the addition of niacin. The change in the concentration of the active form of niacin (NAD, NADP and NAD:NADP) further correlates with the concentration of metabolic parameters, which indicates that the intensity of the biological effect of additional niacin can be accurately determined only if we know the concentrations of its active forms in blood. Under basal conditions (without additional niacin), active forms of niacin that already exist in the blood do not show significant correlations with metabolic parameters.

Effect of supplementation of niacin on physiological and blood biochemical parameters in crossbred cows during heat stress

In order to investigate the effect of different levels of niacin supplementation on physiological and blood biochemical parameters during heat stress period (April to August; 120 days), eighteen crossbred early lactating cows (2nd to 4th lactation; 11.56±1.74 days in milk) were divided into three groups of six animals each. The basal ration was fed same to all cows (Green fodder, straw and concentrate was fed as per NRC, 2001), except the addition of niacin @ 600 and 800 mg/kg dry matter intake (DMI) in T1 and T2 groups, respectively. The temperature humidity index (THI) was calculated at 07:30 am and 02:30 pm daily. Fortnightly physiological parameters were recorded and blood was collected from the jugular vein at day 0 and subsequently at 15–day interval from all the experimental animals to study blood biochemical parameters. The results revealed that animals were in either moderate or severe stress at morning, whereas during afternoon the animals were in very severe stress during the entire trial. Supplementation of niacin @ 800 ppm niacin decreased significantly skin temperature, respiration rate, cortisol, super oxide dismutase (SOD) and catalase (P<0.05). Plasma NEFA was significantly low in both niacin supplemented groups (P<0.05). Plasma urea was found significantly (P<0.05) high in T2 (26.59) in comparison to control (24.90) and T1 (25.37). It is concluded that 800 ppm niacin supplementation to lactating crossbred cows resulted in better stress alleviation as indicated by the improved biomarker values viz., SOD, catalase, cortisol and skin temperature.

Niacin Promotes Cardiac Healing after Myocardial Infarction through Activation of the Myeloid Prostaglandin D2 Receptor Subtype 1.

Niacin is a well established drug used to lower cholesterol and prevent cardiovascular disease events. However, niacin also causes cutaneous flushing side effects due to release of the proresolution mediator prostaglandin D2 (PGD2). Recent randomized clinical trials have demonstrated that addition of niacin with laropiprant [a PGD2 receptor subtype 1 (DP1) blocker] to statin-based therapies does not significantly decrease the risk of cardiovascular disease events, but increases the risk of serious adverse events. Here, we tested whether, and how, niacin beneficial effects on myocardial ischemia require the activation of the PGD2/DP1 axis. Myocardial infarction (MI) was reproduced by ligation of the left anterior descending branch of the coronary artery in mice. We found that niacin increased PGD2 release in macrophages and shifted macrophages to M2 polarization both in vitro and in vivo by activation of DP1 and accelerated inflammation resolution in zymosan-induced peritonitis in mice. Moreover, niacin treatment facilitated wound healing and improved cardiac function after MI through DP1-mediated M2 bias and timely resolution of inflammation in infarcted hearts. In addition, we found that niacin intake also stimulated M2 polarization of peripheral monocytes in humans. Collectively, niacin promoted cardiac functional recovery after ischemic myocardial infarction through DP1-mediated M2 polarization and timely resolution of inflammation in hearts. These results indicated that DP1 inhibition may attenuate the cardiovascular benefits of niacin.

Adverse reactions of Achilles tendon xanthomas in three hypercholesterolemic patients after treatment intensification with niacin and bile acid sequestrants

Multiple cholesterol-reducing therapies have been shown to induce the regression of tendon xanthoma in patients with familial hypercholesterolemia. We present 3 cases of adverse reactions in Achilles tendon xanthomas after the addition of niacin and bile acid sequestrants to ongoing statin therapy. Reduction in tendon dimensions and marked softening of xanthomas were interpreted as cholesterol removal from heavily infiltrated tissue sites. In 2 cases, changes in the xanthomas occurred despite only minor lipoprotein improvements, raising the possibility of direct drug effects in cholesterol-infiltrated tissue. Intriguingly, recent studies have described niacin receptor-mediated effects in macrophages. In summary, although adverse reactions in Achilles tendon xanthomas appear to be infrequent, clinicians should be aware of this phenomenon in their patients after intensifying lipid treatments, especially with the use of niacin in patients with familial hypercholesterolemia. Xanthoma responses may provide clues to new pharmacologic effects in cholesterol-infiltrated tissues.

The role of niacin in raising high-density lipoprotein cholesterol to reduce cardiovascular events in patients with atherosclerotic cardiovascular disease and optimally treated low-density lipoprotein cholesterol: Rationale and study design. The Atherothrombosis Intervention in Metabolic syndrome with low HDL/high triglycerides: Impact on Global Health outcomes (AIM-HIGH)

The aim of this study was to test the hypothesis that patients with atherosclerotic cardiovascular (CV) disease optimally treated on a statin but with residual atherogenic dyslipidemia (low high-density lipoprotein cholesterol [HDL-C] and high triglycerides) will benefit from addition of niacin with fewer CV events compared with placebo. Statin monotherapy trials have found 25%-35% CV risk reduction relative to placebo, leaving significant residual risk. Patients with atherogenic dyslipidemia have substantially increased CV risk. Participants were men and women with established CV disease and atherogenic dyslipidemia. Lipid entry criteria varied by gender and statin dose at screening. All participants received simvastatin (or simvastatin plus ezetimibe) at a dose sufficient to maintain low-density lipoprotein cholesterol (LDL-C) 40-80 mg/dL (1.03-2.07 mmol/L). Participants were randomized to extended-release niacin or matching placebo. The primary end point was time to occurrence of the first of the following: coronary heart disease death, nonfatal myocardial infarction, ischemic stroke, hospitalization for acute coronary syndrome, or symptom-driven coronary or cerebral revascularization. This event-driven trial will have 85% power to show a 25% reduction in primary event frequency after 850 patients have experienced a primary outcome event. AIM-HIGH completed enrollment in April 2010. Follow-up is expected to continue through 2012. AIM-HIGH was designed to determine whether treating residual dyslipidemia with niacin further reduces cardiovascular events in patients with CV disease on a statin at target levels of low-density lipoprotein cholesterol.

Adjunctive Lipid Lowering Therapy in the Era of Surrogate Endpoints

Statins have been shown to reduce cardiovascular events. However, despite widespread use of statin therapy, residual cardiovascular risk remains, and this has left clinicians searching for an effective adjunctive therapy to optimize lipid profiles and reduce risk further. Given the cost and duration of large event driven trials, adjunctive lipid lowering therapy options have largely been evaluated through surrogate measures of atherosclerosis, making clinical practice decisions regarding combination therapy difficult. Two common approaches that have been evaluated almost entirely by surrogate outcome trials include the addition of ezetimibe or the addition of niacin. Our article attempts to place these surrogate end point trials in their proper context, providing clinicians with a practical approach to making clinical practice decisions regarding adjunctive therapy in the absence of clinical outcomes data. Although definitive changes to lipid lowering guidelines should be based on clinical outcomes trials, in the absence of clinical outcomes data, it is reasonable to make individualized clinical practice decisions on the basis of surrogate measures of disease as long as there is corroboration among the effect on atherosclerosis and lipid parameters as adjunctive therapy, and clinical outcomes as monotherapy. Given that niacin fits these criteria, it seems prudent to support the use of niacin as adjunctive therapy in combination with maximally tolerated dose of statin in patients with low high-density lipoprotein-cholesterol and known coronary artery disease. Three ongoing clinical outcomes trials evaluating niacin and ezetimibe in combination with statin will provide more definitive word regarding the safety and efficacy of these agents as adjunctive therapy.

Interaction Between Enfuvirtide, an Injectable Fusion Inhibitor, and Niacin in an HIV-Infected Patient

To report a potential drug-drug interaction between enfuvirtide, an injectable HIV fusion inhibitor, and niacin in an HIV-infected man with dilated cardiomyopathy. A 47-year-old HIV-infected man with dilated cardiomyopathy and prolonged QT syndrome with an automatic implantable cardiovascular defibrillator device was prescribed subcutaneous enfuvirtide 90 mg twice daily as part of his antiretroviral regimen and oral extended-release niacin 500 mg/day for a high-density lipoprotein level of 8 mg/dL. After 1 week of concomitant therapy, the patient began experiencing extreme redness, edema, and swelling at the injection site that corresponded with the flushing sensation due to niacin. This interfered with his daily activities, leading to self-discontinuation of both agents. As the patient had tolerated enfuvirtide therapy prior to the addition of niacin, we reinitiated enfuvirtide with close follow-up, and the patient has been maintained on this agent since then without consequence. Based on the Horn Drug Interaction Probability Scale, a probable interaction occurred between enfurvirtide and niacin. We hypothesize that a drug-drug interaction occurs between enfuvirtide and niacin related to prostaglandin synthesis and mobilization of inflammatory cells, specifically Langerhans cells. A theoretical mechanism for this interaction is that the Langerhans cells in the epidermis function improperly due to the presence of HIV and the attachment of enfuvirtide. When these cells are exposed to nicotinic acid, an exaggerated immune response is produced that may lead to pain, redness, and swelling at the injection site. Prostaglandins, cytokines, and other inflammatory molecules may all have a role in this interaction. Caution should be used when coadministering enfuvirtide and niacin to HIV-infected patients.

Combination regimens with statin, niacin, and intestinally active LDL-lowering drugs: alternatives to high-dose statin therapy?

To summarize recent studies on combination regimens that employ a statin with added niacin, ezetimibe, and/or bile acid sequestrants, and to understand the implications of these studies for clinical practice. Combinations of statin, niacin, and/or intestinally active LDL-lowering drug have demonstrated safety and favorable effects on plasma low and high-density lipoproteins. Niacin and bile acid sequestrants appear to exert beneficial effects on atherosclerotic lesions, whereas results with ezetimibe are uncertain. Moreover, the use of niacin and bile acid sequestrants is supported by clinical outcome results from large monotherapy trials and small combination therapy trials. Three large randomized trials currently are evaluating clinical outcomes with the addition of niacin or ezetimibe to statin treatment. Until the results of ongoing trials are known, it is reasonable to favor the use of niacin and bile acid sequestrants in combination with statins, based on safety and efficacy with regard to effects on lipoproteins, atherosclerotic lesions, and, to a limited extent, clinical outcomes. The effect of ezetimibe on carotid atherosclerosis is indeterminate, but ezetimibe can be reasonably added to statin therapy as a secondary option for LDL-lowering.

Niacin's role in the statin era

Importance of the field: The combination use of niacin and HMG Co-A reductases (statins) is increasing. While statin therapy reduces the risk of adverse cardiovascular events, additional therapies are needed to decrease event rates further. High-density lipoprotein cholesterol (HDL-C) is of interest as a potential therapeutic target as epidemiologic evidence demonstrates that low HDL-C is a strong predictor of incident coronary events. Niacin is the most effective agent available at present to increase HDL-C.Areas covered in this review: This review focuses on the efficacy and safety of niacin in combination with statins, along with the combination's effects on cardiovascular end points and clinical outcomes. We systematically reviewed studies, dating from 2001 to the present, identified through MEDLINE and searches of reference lists, which contained a combination statin and niacin group.What the reader will gain: The reader will gain an understanding of the rationale and results of using niacin and statin therapy concurrently.Take home message: The addition of niacin to statin therapy results in multiple favorable effects on lipid levels, and the combination seems to be as safe as the individual drugs separately. Current evidence indicates that adding niacin to statin therapy has the potential to result in substantial reductions in risk for adverse cardiovascular events. However, large-scale clinical outcome trials are needed to confirm the benefits of this combination.

Dyslipidemia and cardiovascular risk: the importance of early prevention.

Strategies aimed at primary prevention provide an outstanding opportunity for reducing the onset and burden of cardiovascular (CV) disease. Lipid abnormalities, including high levels of low-density lipoprotein cholesterol (LDL-C), elevated triglycerides and low levels of high-density lipoprotein cholesterol (HDL-C), are associated with an increased risk of CV events, thereby serving as contributors to this process. By consensus, lowering LDL-C, generally with statin therapy, is the primary target of lipid-lowering therapy. However, statin therapy may be insufficient for patients with mixed dyslipidemia, especially those with insulin resistance syndromes. While the addition of niacin, fibrate or omega-3 fatty acids may be useful in this setting, outcomes data are lacking. Therefore, data from ongoing prospective studies will hopefully resolve this issue and facilitate identification of optimal strategies to augment CV risk reduction.

The Residual Risk Reduction Initiative: A Call to Action to Reduce Residual Vascular Risk in Patients with Dyslipidemia

Despite achieving targets for low-density lipoprotein (LDL) cholesterol, blood pressure, and glycemia in accordance with current standards of care, patients with dyslipidemia remain at high residual risk of vascular events. Atherogenic dyslipidemia, characterized by elevated triglycerides and low levels of high-density lipoprotein (HDL) cholesterol, often with elevated apolipoprotein B and non-HDL cholesterol, is common in patients with established cardiovascular disease (CVD), type 2 diabetes mellitus, or metabolic syndrome and contributes to both macrovascular and microvascular residual risk. However, atherogenic dyslipidemia is largely underdiagnosed and undertreated in clinical practice. The Residual Risk Reduction Initiative (R³i) was established to address this highly relevant clinical issue. The aims of this position paper are (1) to highlight evidence that atherogenic dyslipidemia is associated with residual macrovascular and microvascular risk in patients at high risk for CVD, despite current standards of care for dyslipidemia and diabetes; and (2) to recommend therapeutic intervention for reducing this residual vascular risk supported by evidence and expert consensus. Lifestyle modification with nutrition and exercise is an important, effective, and underutilized first step in reducing residual vascular risk. Therapeutic intervention aimed at achievement of all lipid targets is also often required. Combination lipid-modifying therapy, with the addition of niacin, a fibrate, or omega-3 fatty acids to statin therapy, increases the probability of achieving all lipid goals. Outcomes studies are in progress to evaluate whether these combination treatment strategies translate to a clinical benefit greater than that achieved with statins alone. The R³i highlights the need to address with lifestyle and/or pharmacotherapy the high level of residual risk of CVD events and microvascular complications among patients with dyslipidemia receiving therapy for high levels of LDL cholesterol and for diabetes in accordance with current standards of care.

The Deadly Double Standard (The Saga of Screening for Subclinical Atherosclerosis)

T i o w T C a c Preventive cardiology has been on the verge of a major reakthrough for the past decade, only to be stymied by the pplication of a double standard that may have resulted in eath and disability for hundreds of thousands of patients ver this time span. There are 565,000 myocardial infarcions annually as the first symptom of coronary artery disase, and 50% of men and 64% of women who die suddenly f coronary disease have no previous symptoms. If the pool f patients at high risk from which 95% of these events merge could be readily identified and treated, events would e reduced by 25% with aggressive statin therapy to educe low-density lipoprotein (LDL) cholesterol and sigificantly more by the addition of niacin or fibrates to raise igh-density lipoprotein cholesterol. Coronary artery calium (CAC) scanning by computed tomography has proided this capability for 15 years, accumulating a massive atabase unequivocally establishing its superiority to conentional National Cholesterol Education Program and Fraingham risk factor guided stratification.

Targeting cardiovascular risk in patients with diabetes: management of dyslipidemia

The management of dyslipidemia in patients with diabetes is a key component of cardiovascular risk reduction. In particular, the atherogenic dyslipidemia of diabetes often requires combination therapy to target aspects of the lipid profile beyond low-density lipoprotein cholesterol. This article will review the characteristics of dyslipidemia in diabetes, and discuss guidelines and strategies for treatment to reduce cardiovascular disease risk. A number of clinical outcomes trials supports the use of statins to reduce cardiovascular events in patients with type 2 diabetes mellitus. The disappointing results of clinical trials involving torcetrapib to increase high-density lipoprotein levels may lead to renewed interest and utilization of niacin for the management of atherogenic dyslipidemia. Long-term use of fibrate therapy in patients with atherogenic dyslipidemia has recently been associated with reduction in all-cause, cancer, and cardiovascular mortality rates. Ongoing trials are investigating whether addition of niacin or fibrate to statin therapy is superior to statin therapy alone in preventing cardiovascular events. Aggressive low-density lipoprotein control continues to be the primary goal of therapy in dyslipidemia management. Given the growing body of evidence showing the cardiovascular benefits of treating other lipid components, however, it is easy to anticipate that full normalization of the lipid profile may become the standard of care for diabetic dyslipidemia.

Heart positive: Design of a randomized controlled clinical trial of intensive lifestyle intervention, niacin and fenofibrate for HIV lipodystrophy/dyslipidemia

Dyslipidemia and insulin resistance occur in a large proportion of HIV-infected patients treated with highly active antiretroviral therapy (HAART); anthropomorphic changes, such as lipoatrophy and central obesity, occur in a subset of patients. This cluster of clinical features, which is termed HIV lipodystrophy, places patients at increased risk for cardiovascular disease. Currently, there is no consensus on the appropriate therapy for the management of HIV lipodystrophy for which the underlying defects are enhanced lipolysis, impaired fat oxidation, increased hepatic VLDL-triglyceride synthesis and secretion, and impaired disposal of intestinally-derived lipoprotein-triglycerides. We describe the design of a randomized, placebo-controlled trial to compare the effects of usual care to diet, exercise and lipid-lowering drugs on lipid profiles of patients with HIV lipodystrophy. The trial will randomize 200 patients into five groups. Outcomes of usual care, diet and exercise alone or in combination with niacin, fenofibrate or both medications will be compared after six months. Unique aspects of the design include an interactive Internet Diet Management system to increase ATP-III recommended dietary compliance for metabolic syndrome, and a supervised program of aerobic and resistance exercises. The study is powered to detect a 20% decrease in triglycerides with the lifestyle intervention and an additional 20% improvement with the addition of niacin and/or fenofibrate. Secondary outcomes include assessment of lipid profile changes, LDL and HDL particle size, plasma cholesterol ester transport protein activity, visceral and subcutaneous fat distribution, glucose tolerance, insulin resistance, and leptin and adiponectin levels.

Effects of micronutrient niacin on treatment efficiency of textile wastewater

Textile wastewater is well known as one of the wastewaters to be most difficultly treated. The effects of niacin on textile wastewater treatment efficiency were studied by continuous addition of 1.0 mg·L−1 niacin, the physical and chemical indexes of the water samples, such as COD, ammonia and dehydrogenase activities, were analyzed every day with standard methods, and obvious improvement in wastewater treatment performance was achieved. The exact results showed that: ① Niacin could improve the COD removal efficiency significantly with removal rates being 1.31 times as to those of the control system; ② under this experimental condition, addition of niacin had almost no effect on the removal of ammonia; ③ Addition of niacin could improve the activity of dehydrogenase by 130%. It proved that the biological treatment performance of textile wastewater treatment system probably could be optimized through micronutrient niacin supplement.

Triglyceride modulation by acifran analogs: activity towards the niacin high and low affinity G protein-coupled receptors HM74A and HM74

Niacin is known to exert profound beneficial effects on cholesterol levels in humans, although its use is somewhat hampered by the gram quantities necessary to exert effects and the prevalence of compliance-limiting skin flushing side effects that occur. Recently, two G protein-coupled receptors (GPCRs) for niacin were identified and characterized as high (HM74A; GPR109A) and low (HM74; GPR109B) affinity receptors based on the binding affinities of niacin. These receptors also bind acifran (AY-25,712), which is known to modulate lipid levels like niacin, with similar affinities. Twelve analogs of acifran were chemically synthesized. One analogue demonstrated a dose-dependent decrease in serum triglycerides in rats within 3 h of oral administration. Next, the acifran analogs were assessed for their activity towards the high and low affinity niacin receptors expressed in CHO-K1 cells. Constructs expressing HM74A or HM74 were stably transfected into CHO-K1 cells and shown to elicit phosphorylation of p42 and p44 mitogen-activated protein kinase (ERK1/ERK2) phosphorylation upon addition of niacin or acifran. The presence of functionally coupled GPCRs was further confirmed using Pertussis toxin, which completely inhibited the ability of either niacin or acifran to elicit phospho-ERK1/ERK2. The EC 50 of p-ERK1/ERK2 for niacin for the high and low affinity receptors was 47 nM and indeterminate (i.e., >100 μM), respectively, while the EC 50 for acifran was 160 and 316 nM, respectively. Two chemical analogs of acifran demonstrated robust phosphorylation of ERK1/ERK2. Collectively, these data suggest that the synthesis of acifran analogs may be a suitable path for developing improved HM74A agonists.

Niacin-ER and lovastatin treatment of hypercholesterolemia and mixed dyslipidemia.

To review the currently available information on the once-daily combination of niacin extended-release (ER)/lovastatin in the treatment of patients with hypercholesterolemia and mixed dyslipidemia at high risk for cardiovascular events. MEDLINE (1966-July 2002) was searched for primary and review articles. Data from the manufacturer were also included. All articles and product labeling deemed relevant to the combination of niacin and statins (i.e., lovastatin) were included for review. English-language studies selected for inclusion were limited to those with human subjects. The Food and Drug Administration approved a new fixed-dose combination of niacin-ER/lovastatin, which is administered once daily. The efficacy and safety of the combined agent have been proven to be similar to either component used alone or in combination for management of hyperlipidemia and mixed dyslipidemia. Elevated low-density lipoprotein cholesterol (LDL-C) is independently associated with a higher risk for cardiovascular events. Lowering of elevated LDL-C concentrations with statin monotherapy may be insufficient in patients at high risk for cardiovascular events. In fact, consideration of elevated triglycerides (TGs) and/or low concentrations of high-density lipoprotein cholesterol (HDL-C) in patients with elevated LDL-C places them at greater risk. The addition of niacin may enhance or improve the lipid profile of those who require a further decrease of TGs and/or increase of HDL-C even after stable statin therapy. Niacin-ER offers efficacy similar to that of immediate-release niacin, but minimal myopathy and hepatotoxicity (compared with sustained-release niacin). Although no clinical outcomes are available, current evidence shows that the combination product offers adequate lowering of LDL-C and TGs and increasing HDL-C. The data suggest that therapy with the niacin-ER and lovastatin combination product is safe and does not increase the incidence of adverse effects.

Response of Lactating Cows to Supplemental Unsaturated Fat and Niacin

Responses to supplemental unsaturated fat or niacin in a 2 × 2 factorial arrangement were evaluated with 16 lactating Holstein cows in a replicated Latin square with 4-wk periods. Total mixed diets contained (dry matter basis) 25% alfalfa hay, 25% corn silage, and 50% concentrate mixture. Diets were the control or the control supplemented with unsaturated fat (3% of dry matter of the total mixed diet from extruded soybeans, which replaced soybean meal and portions of the corn and barley in other concentrates), niacin (12 g/d of nicotinic acid), or both unsaturated fat and niacin. Milk production increased with the addition of fat but was unaffected by the addition of niacin (31.9, 35.1, 32.2, and 35.5 kg/d). Milk fat percentages were unaffected by the addition of fat or niacin to the diet, but proportions of both unsaturated and long-chain fatty acids increased with supplemental fat and were further increased with niacin in addition to fat; however, niacin was ineffective without fat. Milk protein percentages were lower with supplemental fat but were unaffected by niacin. Dry matter intake; ruminal volatile fatty acids, pH, and ammonia; serum urea; plasma glucose; and plasma amino acids were unaffected by supplemental fat or niacin. The first-limiting amino acid for milk protein synthesis was lysine for control diets and methionine for diets with supplemental fat. Supplementation of the diet with an unsaturated fat source increased milk production and the proportion of unsaturated fatty acids in milk, but niacin supplementation had no substantial influence on milk production and only a minor influence on milk fatty acid content.

Fluvastatin with and without niacin for hypercholesterolemia

Seventy-four patients with plasma low-density lipoprotein cholesterol levels ≥160 mg/dl after an American Heart Association phase 1 diet were randomized to double-blind treatment with fluvastatin, 20 mg/day, or placebo for 6 weeks. Immediate-release niacin was then added to both treatment regimens and titrated to a maximum of 3 g/day for a further 9 weeks. After 6 weeks of fluvastatin monotherapy, low-density lipoprotein cholesterol levels decreased by 21% (p <0.001 vs placebo), and after the addition of niacin, response was potentiated to 40% compared with 25% for the niacin control group at study end point (p <0.001). Fluvastatin, alone and in combination with niacin, also significantly improved high-density lipoprotein cholesterol (increases of about 30%) and triglyceride profiles (decreases of approximately 28%) from baseline. Lipoprotein(a) decreased by 37% in those receiving fluvastatin-niacin but was unaltered in those receiving fluvastatin alone. No serious adverse events were ascribed to fluvastatin, and no cases of myosrtis were observed. Small, transient, asymptomatic increases in aspartate aminotransferase were noted with fluvastatinniacin treatment but were not considered clinically relevant. Although the fluvastatin-niacin combination in this study was without evidence of significant transaminitis, myopathy, or rhabdomyolysis, it would seem prudent to continue to monitor its safety with longer term use. In conclusion, fluvastatin, both as monotherapy and in combination with niacin, proved to be an effective, safe, and well-tolerated therapeutic alternative for hypercholesterolemia.