Combination Of Niacin Research Articles

Enhancing Volatile Oil in Mentha piperita L. Through the Application of Nano Iron Oxide and Vitamin B3 (Niacin) Spraying Treatments

This study aimed to investigate the effect of nano iron oxide and vitamin B3 (niacin) application on the volatile oil of Mentha piperita L. plant. Nano iron oxide was used at concentrations of 0, 40, 80, and 120 mg. L−1, while vitamin B3 (niacin) was applied at 0, 50, and 100 mg.L−1 in distilled water. The results demonstrated that spraying the combination of nano iron oxide (120 mg.L−1) and niacin (100 mg.L−1) in distilled water led to a significant increase in the effective compounds of the volatile oil represented by Menthol, Menthone, Menthofurane, Cis-carane, 1.8 Cineole, Limonene, β-Pinene and Trans-caryophylline, at concentrations of 75.575, 43.473, 43.792, 42.941, 35.601, 33.705, 33.500, and 29.925 mg/ml, respectively. These findings highlight the potential benefits of nano iron oxide and niacin application in enhancing volatile oil in Mentha piperita L. plant.

Niacin exacerbates β cell lipotoxicity in diet-induced obesity mice through upregulation of GPR109A and PPARγ2: Inhibition by incretin drugs.

The widely used lipid-lowering drug niacin was reported to increase blood glucose in diabetes. How does niacin regulate β Cell function in diabetic patients remains unclear. This study aimed to investigate the effect of niacin on β cell lipotoxicity in vitro and in vivo. Niacin treatment sensitized the palmitate-induced cytotoxicity and apoptosis in INS-1 cells. In addition, palmitate significantly increased the niacin receptor GPR109A and PPARγ2 levels, which could be further boosted by niacin co-treatment, creating a vicious cycle. In contrast, knocking down of GPR109A could reverse both PPARγ2 expression and niacin toxicity in the INS-1 cells. Interestingly, we found that GLP-1 receptor agonist exendin-4 showed similar inhibitive effects on the GPR109A/PPARγ2 axis and was able to reverse niacin induced lipotoxicity in INS-1 cells. In diet-induced obesity (DIO) mouse model, niacin treatment resulted in elevated blood glucose, impaired glucose tolerance and insulin secretion, accompanied by the change of islets morphology and the decrease of β cell mass. The combination of niacin and DPP-4 inhibitor sitagliptin can improve glucose tolerance, insulin secretion and islet morphology and β cell mass, even better than sitagliptin alone. Our results show that niacin increased β cell lipotoxicity partially through upregulation of GPR109A and PPARγ2, which can be alleviated by incretin drugs. We provide a new mechanism of niacin toxicity, and suggest that the combination of niacin and incretin may have better blood glucose and lipid control effect in clinical practice.

ENHANCED ANTICANCER POTENTIAL OF IMIPRAMINE IN CONJUGATION WITH NIACIN IN DENA INDUCED HEPATOCELLULAR CARCINOMA

Hepatocellular carcinoma (HCC) is constantly seeking the interest of researchers as an untreatable and fatal disease, attaining second position so far worldwide. Our study provides us an opportunity to explore new potential therapeutic combinations in this regard. We hypothesized that the anticancer activity of imipramine, which is used as an antidepressant drug, can be potentiated with an adjuvant, niacin, thereby providing a better treatment approach. The combination turned out to show beneficial alterations in various liver function test, caspase 3 (antiapoptotic) activity, tumor growth and survival profile of animals, precisely in our therapeutic group involving imipramine and niacin combination post diethyl nitrosamine (DENA) dose and hepatocellular carcinoma induction. Results demonstrated a remarkable restoration in all liver enzymes in the therapeutic groups.

Potential role of Niacin as Adjuvant to Sevelamer on Serum levels of Inorganic phosphorus, Calcium and Calcium-phosphorus product in Hemodialysis patients with Hyperphosphatemia

Hyperphosphatemia is a serious biochemical abnormality that affected almost patients undergoing maintenance hemodialysis and has independent association with high risk of mortality due to cardiovascular diseases. The mechanism linking hyperphosphatemia to cardiovascular mortality is vascular calcification that it is promoted by elevated serum phosphorus level. The control of hyperphosphatemia remains a major challenge. All currently phosphate binders have requirement for dosing with each meals that contributed to high pill burden and reduce patient compliance. Calcium-based binders preferred to be avoided due to their high risk of vascular classification, while the expensiveness of non-calcium based binder represent their major drawbacks. Niacin; a naturally occurring water-soluble vitamin and the first used antidyslipidemic drug, has been demonstrated to show therapeutic potential for hyperphosphatemia treatment in hemodialysis patients. It decreases phosphorus absorption in the GIT, thereby lowering serum phosphorus level. This study is designed to evaluate the efficacy of niacin as adjuvant therapy to sevelamer carbonate (as a phosphate binder) in hemodialysis patients. This prospective, randomized clinical trial was conducted among patients with hyperphosphatemia. Seventy nine patients were enrolled in this study; only 39 patients completed the study. Thirty nine patients were assigned randomly into two groups; group (1) 19 patients treated with sevelamer alone (2400mg/day), group (2) 20 patients treated with a combination of sevelamer (2400mg/day) and niacin (1000 mg/day) for 2 months . Clinical outcomes (Pi, Ca, Ca x P product) serum levels were evaluated at time of enrolment, after 1 month and after 2 month of treatment. Results of this study showed that the patients who administered orally niacin as adjuvant to sevelamer had the superiority over using sevelamer alone in the reduction of both serum phosphorus level and (Ca x P) product level (-30% and -37%) respectively after 2 months of treatment in respect to baseline levels. Meanwhile, there was no statistically significant difference observed in serum calcium level. Administration of niacin for hemodialysis patients is an effective strategy for reducing the serum levels of inorganic phosphorus and calcium-phosphorus product which subsequently reduce risks of cardiovascular diseases associated with hyperphosphatemia.

Clinical analysis of alcoholic pellagra: A single‐center retrospective study

Pellagra caused by niacin deficiency in alcoholics can be easily misdiagnosed because of similar symptoms to other alcohol-related diseases and the lack of the classical triad of signs. This study aimed to define the clinical presentation of alcoholic pellagra for early diagnosis and timely treatment. The clinical data of 16 alcohol-dependent patients who had pellagra and treated in our hospital from January 2002 to December 2019 were retrospectively analyzed. The local medical ethics committee approval (Medical Ethics Committee of Affiliated Hospital of XuZhou Medical University, XYFY2020-KL247-02) for this study has been obtained. The main complaints of the 16 patients were skin lesions (six cases), diarrhea (six cases), and mental disorders (four cases). Then, 13 cases had typical skin lesions, and 3 patients had a full spectrum of diarrhea, dementia, and dermatitis (3D). In terms of the main diagnosis, 2 patients had pellagra and Wernicke's encephalopathy, 3 patients had pellagra and alcohol-withdrawal syndrome, and the other patients had pellagra. After sufficient amounts of niacin and multivitamin B were given, clinical symptoms improved rapidly, and no sequelae were observed during follow-up. Pellagra is rarely manifested as a full 3D spectrum, with only one or two characteristics, which lack diagnostic specificity, especially in individuals with alcoholism. Physicians should maintain a high degree of suspicion of niacin deficiency in alcoholics. Alcohol-dependent patients with pellagra may be accompanied by complications of Wernicke's encephalopathy and alcohol-withdrawal syndrome. Prompt identification and timely treatment with a sufficient amount of niacin in combination with other vitamins and a certain amount of Zn can achieve a good prognosis of pellagra.

Effect of GSH and niacin combination on protein oxidation, ER stress, glycation and aggregation in HLE cells under high glucose condition

AIM: To evaluate the effects of reduced glutathione (GSH) and niacin combination on protein oxidative stress, endoplasmic reticulum (ER) stress, glycation, and aggregation of the αβ crystalline in human lens epithelial (HLE) cells treated with high glucose levels. METHODS: HLE cells were cultured and exposed to 25 mmol/L glucose to promote high glucose conditions. Groups of cells were co-treated with three different combinations of dosages: 10 μmol/L GSH+25 μmol/L niacin (P1), 30 μmol/L GSH+25 μmol/L niacin (P2), and 100 μmol/L GSH+25 μmol/L niacin (P3). After 72h incubation, protein carbonyl content (PCC) and glucose reactive protein (GRP78) content were assessed using ELISA examinations. After two-week incubation, advanced glycation end products (AGEs) were also assessed and the expression of αβ crystalline was measured using Western blot examination. RESULTS: PCC and GRP78 levels in the co-treated groups were not significantly reduced compared to control (P>0.05). In contrast, there was a significant decrease of the AGEs levels in all groups co-treated with GSH and niacin when compared with the control group (P<0.05). In addition, the αβ crystalline expression increased after high dose glucose administration, but decreased in all groups co-treated with GSH and combinations of GSH and niacin. CONCLUSION: Combinations of GSH and niacin inhibit the aggregation of proteins and prevent glycation in hyperglycemic HLE cells. This study shows that this combination may play an active role in preventing diabetic cataract mainly from the AGEs pathway.

Clinical Evaluation of Niacin in Hemodialysis Patients with Hyperphosphatemia as Adjuvant to Calcium Carbonate

Background: The complications of End Stage Renal Disease ESRD attributed to high morbidity and mortality such as hyperphosphatemia and vascular disease. Vascular smooth muscle cells (VSMCs) are sensitive to elevation in serum phosphate levels and have the ability to modify their functions in response to this
 
 elevation through h many processes that promote calcification. Vascular calcification is highly correlated with the major events of cardiovascular mortality which are included heart failure, sudden cardiac death, and ischemic heart disease. The control of hyperphosphatemia in HD patients remains poor in spite of the effectiveness of all the available phosphate binders. However, calcium based binder may promote the aggravation of vascular calcification while Aluminum- based binder associated with osteomalacia, and encephalopathy. Calcium/aluminum free phosphate binder may cause gastrointestinal adverse effect in addition to their high cost of treatment. The active phosphate transport inhibitors are the newest interesting agents in the management of hyperphosphatemia alone or as add-on therapy to the existing phosphate binders. Niacin is one of this novel drug classes that has been demonstrated to show promising therapeutic potential in the treatment of hyperphosphatemia in HD patients.
 Aim of study: This study is designed to evaluate the efficacy of niacin as adjuvant therapy to calcium carbonate (as a phosphate binder) in hemodialysis patients.
 Method: In this prospective, randomized interventional study, 56 patients confirmed with end stage renal disease (ESRD) and hyperphosphatemia on regular hemodialysis were included. Only 40 patients completed the study and were classified randomly into two groups: group (1); composed of 19 patients who received 1500 mg/day of calcium carbonate tablets, and group (2); composed 21 patients who received 1500 mg/day calcium carbonate tablets plus niacin both for 2 months’ duration. Blood sample was taken thrice, at baseline, after 1 month and at the end of month 2 for measurement of serum study parameters: (inorganic phosphorus (Pi), calcium (Ca), Calcium-Phosphorus product (Ca x P) .
 Results: Results of this study showed that the patients who administered orally niacin as adjuvant to calcium had the superiority over using calcium alone in the reduction of serum phosphorus level (-20.3% and -13.5%) respectively after 2 months of treatment in respect to baseline levels. Meanwhile, there was a marked increase in serum Ca level in both groups after 2 months of treatment however, it was non-significant. In addition, treatment with combination of calcium and niacin resulted in more reduction in serum (Ca x P) product level at the end of study than with calcium alone compared to baseline, nevertheless the change was non-significant.
 Conclusion: Administration of niacin for hemodialysis patients is an effective strategy for reducing the serum levels of inorganic phosphorus and calcium-phosphorus product which may lead to reduce the risks of cardiovascular diseases associated with hyperphosphatemia.

Statins combined with niacin reduce the risk of peripheral neuropathy.

Statins are a class of lipid-lowering medications that reduce illness and mortality in those who are at a high risk of developing cardiovascular disease. They are the most common cholesterol-lowering drugs. A case control study published in 2002 indicated that statins may increase the risk of peripheral neuropathy. Statin users were 14-fold more likely to develop peripheral neuropathy than non-users, although the overall risk of developing neuropathy was minimal. However, a number of other studies have produced conflicting results regarding neuropathy and statins. Statins are frequently combined with niacin (vitamin B3). Due to its beneficial effects on lipid profiles, niacin has been prescribed for the prevention of heart disease for >40 years. Among the B vitamins, niacin has long been recognized as a key mediator of neuronal development and survival, and may be of value for the treatment of neuropathy. The present study aimed to assess whether the combination of niacin and statin may reduce the risk of peripheral neuropathy attributed to statins. For this purpose, data from MedWatch, the Food and Drug Administration (FDA) Safety Information and Adverse Event Reporting Program were analyzed. The online tool OpenVigil 2.1 was used to query the databases. The results revealed that the majority of statins alone were related to neuropathy. Pitavastatin was the only exception. The association with neuropathy was most pronounced in the lipophilic statins: Atorvastatin and fluvastatin. The association was weaker for other lipophilic statins, such as lovastatin and simvastatin. Two hydrophilic statins, rosuvastatin and pravastatin, exhibited a similarly weaker association with neuropathy, while no reports of any association of pitavastatin with neuropathy were found. Statins + niacin were unrelated to neuropathy. On the whole, the findings of the present study demonstrate that the controversial association of statins with neuropathy may be due to the fact that previous studies have not included the use of niacin and the potential neuroprotective effects of niacin. Multiple reports have stated that niacin is no longer beneficial for the management of hyperlipidemia and should be abandoned. However, given the apparent ability of niacin to reduce the risk of neuropathy, perhaps niacin should not be discarded before further studies are performed to provide more in depth information.

Potential therapeutic effects of antagonizing adenosine A2A receptor, curcumin and niacin in rotenone-induced Parkinson's disease mice model.

Parkinson's disease (PD) is the second common age-related neurodegenerative disease. It is characterized by control loss of voluntary movements control, resting tremor, postural instability, bradykinesia, and rigidity. The aim of the present work is to evaluate curcumin, niacin, dopaminergic and non-dopaminergic drugs in mice model of Parkinson's disease through behavioral, biochemical, genetic and histopathological observations. Mice treated with rotenone rerecorded significant increase in adenosine A2A receptor (A2AR) gene expression, α synuclein, acetylcholinesterase (AchE), malondialdehyde (MDA), angiotensin-II (Ang-II), c-reactive protein (CRP), interleukin-6 (IL-6), caspase-3 (Cas-3) and DNA fragmentation levels as compared with the control group. While, significant decrease in dopamine (DA), norepinephrine (NE), serotonin (5-HT), superoxide dismutase (SOD), reduced glutathione (GSH), ATP, succinate and lactate dehydrogenases (SDH &LDH) levels were detected. Treatment with curcumin, niacin, adenosine A2AR antagonist; ZM241385 and their combination enhanced the animals' behavior and restored all the selected parameters with variable degrees of improvement. The brain histopathological features of hippocampal and substantia nigra regions confirmed our results. In conclusion, the combination of curcumin, niacin and ZM241385 recorded the most potent treatment effect in Parkinsonism mice followed by ZM241385, as a single treatment. ZM241385 succeeded to antagonize adenosine A2A receptor by diminishing its gene expression andameliorating all biochemical parameters under investigation. The newly investigated agent; ZM241385 has almost the same pattern of improvement as the classical drug; Sinemet®. This could shed the light to the need of detailed studies on ZM241385 for its possible role as a promising treatment against PD. Additionally, food supplements such as curcumin and niacin were effective in Parkinson's disease eradication.

Monounsaturated Fatty Acids in a High-Fat Diet and Niacin Protect from White Fat Dysfunction in the Metabolic Syndrome.

Obesity is a principal causative factor of metabolic syndrome. Niacin potently regulates lipid metabolism. Replacement of saturated fatty acids by MUFAs or inclusion of omega-3 long-chain PUFAs in the diet improves plasma lipid levels. However, the potential benefits of niacin in combination with MUFAs or omega-3 long-chain PUFAs against white adipose tissue (WAT) dysfunction in the high fat diet (HFD)-induced metabolic syndrome are unknown. Male Lepob/ob LDLR-/- mice are fed a chow diet or HFDs based on milk cream (21%kcal), olive oil (21%kcal), or olive oil (20%kcal) plus 1%kcal from eicosapentaenoic and docosahexaenoic acids, including immediate-release niacin (1% w/v) in drinking water, for 8 weeks. Mice are then phenotyped. Dietary MUFAs are identified as positive regulators of adipose NAD+ signaling pathways by triggering NAD+ biosynthesis via the salvage pathway. This coexists with overexpression of genes involved in recognition of NAD+ and fatty acids, a surrounding lipid environment dominated by exogenous oleic acid and an alternatively activated macrophage profile, which culminate in a healthy expansion of WAT and improvement of several hallmarks that typify the metabolic syndrome. Niacin in combination with dietary MUFAs can favor WAT homeostasis in the development of HFD-induced obesity and metabolic syndrome.

HYPERLIPIDEMIC PATIENTS;

Objectives: Role of niacin in decreasing cardiovascular accidents by lowering the levels of Apo-B in hyperlipidemic patients. Background: In hyperlipidemia, there are high levels of atherogenic lipoproteins leading to higher risk of atherosclerotic cardiovascular events. Patients with dyslipidemia use statins as a mainstay of therapy over last many decades. Recent studies show that apolipoproteins play a major role in formation of atheromatous plaque, thus there is an urgent need to study the effects of lipid lowering medication on apolipoprotiens levels. Study Design: Cross sectional analytical study. Setting: Sheikh Zayed Hospital Lahore (Department of Biochemistry and Chemical Pathology). Period: 12 weeks from July to Sep 2014. Materials and Methods: Recently diagnosed hyperlipidemic patients (n=44) were selected for the study purpose and divided into two equal groups; A and B. Each group was given different medication. Group A took only statin while group B took a combination of statin and niacin. Blood samples were taken at the start of medication and then after completion of 12 week time period. Results: At the start of the treatment there was no significant difference in the Apo B cholesterol level between the two groups (p value 0.972). However, after the end of 12 week duration, there was a significant reduction in the Apo level of group B taking statin and niacin as compared to group A taking statin alone (p value 0.003). Conclusions: Niacin has cardio-protective role when used in combination with niacin.

Safety assessment of niacin in the US Food and Drug Administration's mini-sentinel system.

The Heart Protection Study 2-Treatment of HDL to Reduce the Incidence of Vascular Events (HPS2-THRIVE) trial found higher incidence rates of adverse reactions, including bleeding, in patients receiving the combination of extended-release niacin and laropiprant versus placebo. It is not known whether these adverse events are attributable to laropiprant, not approved in the USA, or to extended-release niacin. We compared rates of major gastrointestinal bleeding and intracranial hemorrhage among initiators of extended-release niacin and initiators of fenofibrate. We used Mini-Sentinel (now Sentinel) to conduct an observational, new user cohort analysis. We included data from 5 Data Partners covering the period from January 1, 2007 to August 31, 2013. Individuals who initiated extended-release niacin were propensity score-matched to individuals who initiated fenofibrate. Within the matched cohorts, we used Cox proportional hazards models to compare rates of hospitalization for major gastrointestinal bleeding events and intracranial hemorrhage assessed using validated claims-based algorithms. A total of 234242 eligible extended-release niacin initiators were identified, of whom 210 389 (90%) were 1:1 propensity score-matched to eligible fenofibrate initiators. In propensity score-matched analyses, no differences were observed between exposure groups in rates of major gastrointestinal bleeding (hazard ratio [HR], 0.98; 95% confidence interval [CI], 0.82 to 1.18) or intracranial hemorrhage (HR, 1.21; 95% CI, 0.66 to 2.22). Results were similar in pre-specified sensitivity and subgroup analyses. We did not observe evidence for an association between extended-release niacin versus fenofibrate and rates of major gastrointestinal bleeding or intracranial hemorrhage.

Niacin for primary and secondary prevention of cardiovascular events.

Nicotinic acid (niacin) is known to decrease LDL-cholesterol, and triglycerides, and increase HDL-cholesterol levels. The evidence of benefits with niacin monotherapy or add-on to statin-based therapy is controversial. To assess the effectiveness of niacin therapy versus placebo, administered as monotherapy or add-on to statin-based therapy in people with or at risk of cardiovascular disease (CVD) in terms of mortality, CVD events, and side effects. Two reviewers independently and in duplicate screened records and potentially eligible full texts identified through electronic searches of CENTRAL, MEDLINE, Embase, Web of Science, two trial registries, and reference lists of relevant articles (latest search in August 2016). We included all randomised controlled trials (RCTs) that either compared niacin monotherapy to placebo/usual care or niacin in combination with other component versus other component alone. We considered RCTs that administered niacin for at least six months, reported a clinical outcome, and included adults with or without established CVD. Two reviewers used pre-piloted forms to independently and in duplicate extract trials characteristics, risk of bias items, and outcomes data. Disagreements were resolved by consensus or third party arbitration. We conducted random-effects meta-analyses, sensitivity analyses based on risk of bias and different assumptions for missing data, and used meta-regression analyses to investigate potential relationships between treatment effects and duration of treatment, proportion of participants with established coronary heart disease and proportion of participants receiving background statin therapy. We used GRADE to assess the quality of evidence. We included 23 RCTs that were published between 1968 and 2015 and included 39,195 participants in total. The mean age ranged from 33 to 71 years. The median duration of treatment was 11.5 months, and the median dose of niacin was 2 g/day. The proportion of participants with prior myocardial infarction ranged from 0% (4 trials) to 100% (2 trials, median proportion 48%); the proportion of participants taking statin ranged from 0% (4 trials) to 100% (12 trials, median proportion 100%).Using available cases, niacin did not reduce overall mortality (risk ratio (RR) 1.05, 95% confidence interval (CI) 0.97 to 1.12; participants = 35,543; studies = 12; I2 = 0%; high-quality evidence), cardiovascular mortality (RR 1.02, 95% CI 0.93 to 1.12; participants = 32,966; studies = 5; I2 = 0%; moderate-quality evidence), non-cardiovascular mortality (RR 1.12, 95% CI 0.98 to 1.28; participants = 32,966; studies = 5; I2 = 0%; high-quality evidence), the number of fatal or non-fatal myocardial infarctions (RR 0.93, 95% CI 0.87 to 1.00; participants = 34,829; studies = 9; I2 = 0%; moderate-quality evidence), nor the number of fatal or non-fatal strokes (RR 0.95, 95% CI 0.74 to 1.22; participants = 33,661; studies = 7; I2 = 42%; low-quality evidence). Participants randomised to niacin were more likely to discontinue treatment due to side effects than participants randomised to control group (RR 2.17, 95% CI 1.70 to 2.77; participants = 33,539; studies = 17; I2 = 77%; moderate-quality evidence). The results were robust to sensitivity analyses using different assumptions for missing data. Moderate- to high-quality evidence suggests that niacin does not reduce mortality, cardiovascular mortality, non-cardiovascular mortality, the number of fatal or non-fatal myocardial infarctions, nor the number of fatal or non-fatal strokes but is associated with side effects. Benefits from niacin therapy in the prevention of cardiovascular disease events are unlikely.

DIFFERENTIAL TREATMENT EFFECTS OF EXTENDED-RELEASE NIACIN AND PLACEBO ON BASELINE AND ONE-YEAR LIPOPROTEIN SUBFRACTIONS AND THEIR RELATIONSHIP TO CARDIOVASCULAR OUTCOMES: POST HOC SUBSET ANALYSIS OF AIM-HIGH TRIAL PATIENTS WITH HIGH TRIGLYCERIDE AND LOW HDL-C

The AIM-HIGH trial failed to show incremental clinical benefit for the combination of extended-release niacin (ERN) vs. placebo (PBO) with simvastatin in 3,414 patients with established cardiovascular (CV) disease and low baseline HDL-C. A post hoc analysis showed CV event reduction in the high-risk

Simultaneous Quantification of Simvastatin and Simvastatin Acid in Human Plasma with a Highly Sensitive LC-ESI-MS/MS Method: Application to a Pharmacokinetic Study in Healthy Chinese Volunteers with a Fixed Dose of Simvastatin and Extended-Release Niacin Combination Tablet

Simvastatin, a pro-drug lactone whose major hydroxy acid metabolite, simvastatin acid, inhibits the activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase, combined with extended-release (ER) niacin decreases LDL cholesterol and increases HDL cholesterol to a greater extent than either treatment alone. This study developed a highly sensitive LC-MS/MS method for the simultaneous quantification of SV and SVA in human plasma. The plasma samples were pretreated by liquid–liquid extraction with ethyl ether/dichloromethane (3:2, v/v). Chromatographic analysis was conducted using isocratic elution on a Zorbax Eclipse XDB-C18 column (4.6 mm × 150 mm, 5 μm) with a mobile phase of methanol/10 mM ammonium acetate/formic acid (90:10:0.02, v/v/v). The flow rate was 1.0 mL/min (split 0.5:0.5). An API 4000 triple quadrupole mass spectrometer was used for detection with an electrospray ionization interface. The ion transitions used were m/z 435.4→319.0 for SVA in the negative ion mode and 419.1→199.1 for SV in the positive mode. This method exhibited linearity within the concentration range of 0.05 to 15 ng/mL for SV and SVA. The LLOQ was 0.05 ng/mL with acceptable precision and accuracy. The intra- and inter-day precisions were all less than 14.7% (RSD, %). The accuracies were within ±1.85% (RE, %). Compared with earlier reports, this validated method offered a higher sensitivity and smaller cost for the quantification of SV and its metabolite SVA in human plasma. It was successfully applied for the evaluation of a pharmacokinetic study using a fixed dose of a simvastatin and ER niacin combination tablet (10 mg/500 mg) in healthy Chinese volunteers. Keywords: Simvastatin, simvastatin acid, simvastatin and ER niacin combination tablet, LC-MS/MS, quantification, pharmacokinetics.

Statin Intolerance in a Patient with Gilberts Syndrome and Hypercholesterolemia

Abstract Background: Statin intolerance especially myalgias can be a serious problem. Whilst it is well know that drugs that compete for Cytochrome 450 system can result in myalgias there is sparse data on the role of glucuronidation of statins contributing to statin intolerance We report on a 60 year old male with Hypercholesterolemia (HC) who was referred for management of his HC since he had statin intolerance manifesting as myalgias and was shown to have Gilbert’s Syndrome. Case Report: Investigation of this patient revealed he had Familial Combined Hyperlipidemia with a LDL-cholesterol of 189 mg/dl. He was also diagnosed with Gilbert’s Syndrome since he had elevated unconjugated bilirubin with no evidence of liver disease or hemolysis. The combination of Niacin, Cholestyramine and ezetimibe resulted in a successful decrease in his LDL-cholesterol to 114 mg/dl. Discussion: We believe that his Gilberts Syndrome resulted in an impairment in glucuronidation of statin drugs resulting in an increase in free drug levels and myalgias. We caution that clinicians should consider this possibility when confronted with a patient with both isolated elevations of unconjugated bilirubin and increase LDL-cholesterol levels before commencing statin therapy.

A Therapeutic Insight of Niacin and Coenzyme Q10 Against Diabetic Encephalopathy in Rats.

Diabetes mellitus (DM) is characterized by hyperglycemia due to insulin inactivity or insufficiency with increasing risk of developing specific complications, including retinopathy, nephropathy, neuropathy, and atherosclerosis. The aim of the present study is to evaluate the efficacy of coenzyme Q10 (CoQ10), niacin, as well as their combination in ameliorating brain disorders associated with streptozotocin (STZ)-induced diabetes in rats. Glibenclamide, a reference diabetic drug, and donepezil, an acetylcholine inhibitor drug, were also evaluated. Diabetes was induced by single intraperitoneal injection of STZ (60mg/kg body weight (b.wt)). One-month diabetic rats were treated with the selected drugs daily for another two consecutive weeks. The evaluation was done through the estimation of the levels of blood glucose, serum insulin, and oxidative stress markers: malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione (GSH); neurotransmitters: acetylcholinesterase (AchE) and dopamine (DA); vasoconstrictor indices: intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1(VCAM-1), and angiotensin II (Ang II); and apoptosis markers: tumor necrosis factor-α (TNF-α) and caspase-3 as well as the histopathological picture of the cerebellum region of the brain. The results revealed that the combination of niacin and CoQ10 improved most of the measured parameters with variable degrees. In conclusion, niacin and CoQ10 are promising dietary supplements in the management of diabetic encephalopathy.

Combination of Loperamide and Niacin modify DENA induced altered Liver enzymes

Hepatocellular Carcinoma (HCC) is among the most lethal cancers which makes it the third most frequent cause of cancer related deaths. Diethylnitrosamine (DENA) is a potent initiator and hepatocarcinogen in rats. DENA induced Hepatocellular damage clearly demonstrates by the elevated levels of liver enzymes serum glutamate oxaloacetate transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT), serum alkaline phosphatase (ALP), and a-feto protein (AFP). This work is an attempt to test the hypothesis that Loperamide (5mg/kg) and Niacin in combination restores the DENA (160mg/kg) induced altered enzymes after single i.p administration in Wistar rats. The ability to alter the enzymes was measured by comparing biochemical serum markers and AFP. The results have confirmed the significant elevation of these parameters in DENA control group compared to normal control and the therapeutic groups. Therapeutic group significantly reveals that Loperamide and Niacin restores the altered hepatic enzymes towards the Normal. Key messages: Our data reveals and confirms that this remarkable combination possess the potential for the treatment of hepatocellular carcinomas in rats exposed to DENA. Administration of Loperamide + Niacin relatively improved the biochemical parameters to values approximating those of the normal controls.

Effects of Niacin, Statin, and Fenofibrate on Circulating Proprotein Convertase Subtilisin/Kexin Type 9 Levels in Patients With Dyslipidemia

Recent trials demonstrated substantial improvement in lipid parameters with inhibition of proprotein convertase subtilisin-like/kexin type 9 (PCSK9). Although statins and fibrates have been reported to increase plasma PCSK9 levels, the effect of niacin on PCSK9 is unknown. We investigated the impact of niacin, atorvastatin, and fenofibrate on PCSK9 levels in 3 distinct studies. A statin-only study randomized 74 hypercholesterolemic patients to placebo, atorvastatin 10 mg/day, or atorvastatin 80 mg/day for 16 weeks. A dose-related increase in PCSK9 was noted such that atorvastatin 80 mg increased PCSK9 by a mean +27% (95% confidence interval [CI] +12 to +42), confirming the effect of statin therapy on raising PCSK9. A second study randomized 70 patients with carotid atherosclerosis to simvastatin 20 mg/day, simvastatin 80 mg/day, or simvastatin 20 mg/extended-release (ER) niacin 2 g/day. PCSK9 levels were increased with statin therapy, but decreased with the simvastatin 20 mg/ER niacin combination (mean -13%, CI -3 to -23). A final study involved 19 dyslipidemic participants on atorvastatin 10 mg with serial addition of fenofibric acid 135 mg followed by ER niacin 2 g/day. Fenofibric acid led to a +23% (CI +10 to +36, p = 0.001) increase in PCSK9; the addition of niacin resulted in a subsequent -17% decrease (CI -19 to -5, p = 0.004). A positive association was noted between change in PCSK9 and low-density lipoprotein cholesterol levels (r = 0.62, p = 0.006) with the addition of niacin. In conclusion, niacin therapy offsets the increase in PCSK9 levels noted with statin and fibrate therapy. A portion of the low-density lipoprotein cholesterol reduction seen with niacin therapy may be due to reduction in PCSK9.

Paraoxonase responses to exercise and niacin therapy in men with metabolic syndrome

Our purpose was to characterize changes in paraoxonase 1 (PON1) activity and concentration after single aerobic exercise sessions conducted before and after 6 weeks of niacin therapy in men with metabolic syndrome (MetS). Twelve men with MetS expended 500 kcal by walking at 65% of VO2max before and after a 6-week regimen of niacin. Niacin doses were titrated by 500 mg/week from 500 to 1500 mg/day and maintained at 1500 mg/day for the last 4 weeks. Fasting blood samples were collected before and 24 hours after each exercise session and analyzed for PON1 activity, PON1 concentration, myeloperoxidase (MPO), apolipoprotein A1, oxidized low-density lipoprotein (oLDL), lipoprotein particle sizes and concentrations. PON1 activity, PON1 concentration, MPO, and oLDL were unaltered following the independent effects of exercise and niacin (P > 0.05 for all). High-density lipoprotein particle size decreased by 3% (P = 0.040) and concentrations of small very low-density lipoprotein increased (P = 0.016) following exercise. PON1 activity increased 6.1% (P = 0.037) and PON1 concentrations increased 11.3% (P = 0.015) with the combination of exercise and niacin. Exercise and niacin works synergistically to increase PON1 activity and concentration with little or no changes in lipoproteins or markers of lipid oxidation.