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Minireview Exploring the Biological Cycle of Vitamin B3 and Its Influence on Oxidative Stress: Further Molecular and Clinical Aspects.
Doroftei, B, Ilie, OD, Cojocariu, RO, Ciobica, A, Maftei, R, Grab, D, Anton, E, McKenna, J, Dhunna, N, Simionescu, G
Molecules (Basel, Switzerland). 2020;(15)
Abstract
Vitamin B3, or niacin, is one of the most important compounds of the B-vitamin complex. Recent reports have demonstrated the involvement of vitamin B3 in a number of pivotal functions which ensure that homeostasis is maintained. In addition, the intriguing nature of its synthesis and the underlying mechanism of action of vitamin B3 have encouraged further studies aimed at deepening our understanding of the close link between the exogenous supply of B3 and how it activates dependent enzymes. This crucial role can be attributed to the gut microflora and its ability to shape human behavior and development by mediating the bioavailability of metabolites. Recent studies have indicated a possible interconnection between the novel coronavirus and commensal bacteria. As such, we have attempted to explain how the gastrointestinal deficiencies displayed by SARS-CoV-2-infected patients arise. It seems that the stimulation of a proinflammatory cascade and the production of large amounts of reactive oxygen species culminates in the subsequent loss of host eubiosis. Studies of the relationhip between ROS, SARS-CoV-2, and gut flora are sparse in the current literature. As an integrated component, oxidative stress (OS) has been found to negatively influence host eubiosis, in vitro fertilization outcomes, and oocyte quality, but to act as a sentinel against infections. In conclusion, research suggests that in the future, a healthy diet may be considered a reliable tool for maintaining and optimizing our key internal parameters.
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Lipid-Lowering Agents in Older Individuals: A Systematic Review and Meta-Analysis of Randomized Clinical Trials.
Ponce, OJ, Larrea-Mantilla, L, Hemmingsen, B, Serrano, V, Rodriguez-Gutierrez, R, Spencer-Bonilla, G, Alvarez-Villalobos, N, Benkhadra, K, Haddad, A, Gionfriddo, MR, et al
The Journal of clinical endocrinology and metabolism. 2019;(5):1585-1594
Abstract
BACKGROUND The efficacy of lipid-lowering agents on patient-important outcomes in older individuals is unclear. METHODS We included randomized trials that enrolled individuals aged 65 years or older and that included at least 1 year of follow-up.Pairs of reviewers selected and appraised the trials. RESULTS We included 23 trials that enrolled 60,194 elderly patients. For primary prevention, statins reduced the risk of coronary artery disease [CAD; relative risk (RR): 0.79, 95% CI: 0.68 to 0.91] and myocardial infarction (MI; RR: 0.45, 95% CI: 0.31 to 0.66) but not all-cause or cardiovascular mortality or stroke. These effects were imprecise in patients with diabetes, but there was no significant interaction between diabetes status and the intervention effect. For secondary prevention, statins reduced all-cause mortality (RR: 0.80, 95% CI: 0.73 to 0.89), cardiovascular mortality (RR: 0.68, 95% CI: 0.58 to 0.79), CAD (RR: 0.68, 95% CI: 0.61 to 0.77), MI (RR: 0.68, 95% CI: 0.59 to 0.79), and revascularization (RR: 0.68, 95% CI: 0.61 to 0.77). Intensive (vs less-intensive) statin therapy reduced the risk of CAD and heart failure. Niacin did not reduce the risk of revascularization, and fibrates did not reduce the risk of stroke, cardiovascular mortality, or CAD. CONCLUSION High-certainty evidence supports statin use for secondary prevention in older individuals. Evidence for primary prevention is less certain. Data in older individuals with diabetes are limited; however, no empirical evidence has shown a significant difference based on diabetes status.
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Assessment of the Role of Niacin in Managing Cardiovascular Disease Outcomes: A Systematic Review and Meta-analysis.
D'Andrea, E, Hey, SP, Ramirez, CL, Kesselheim, AS
JAMA network open. 2019;(4):e192224
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Abstract
IMPORTANCE Niacin remains a therapeutic option for patients with cardiovascular disease, but recent studies have called into question the effectiveness of other drugs that increase high-density lipoprotein cholesterol levels. OBJECTIVE To systematically review and evaluate the evidence supporting current US Food and Drug Administration-approved uses of niacin in cardiovascular disease prevention settings. DATA SOURCES MEDLINE, Embase, Cochrane Controlled Clinical Trial Register (Central), ClinicalTrials.gov, and TrialResults-center, from database inception to October 2017. STUDY SELECTION The systematic review included clinical trials involving niacin as a treatment for cardiovascular disease. The meta-analysis included randomized clinical trials reporting niacin's effect, as exposure, on at least 1 long-term cardiovascular disease outcome. DATA EXTRACTION AND SYNTHESIS Aggregate study-level data were extracted between November 2017 and January 2018 by 3 independent reviewers, and the analysis was performed in February 2018. Inverse-variance weighted methods were used to produce pooled risk ratios using random-effects models for between-study heterogeneity. Random effects-weighted metaregression analysis was used to assess the association of change in high-density lipoprotein cholesterol levels with the log risk ratio of the pooled results. MAIN OUTCOMES AND MEASURES Cardiovascular disease, coronary heart disease mortality, and other cardiovascular events, including acute coronary syndrome, fatal and nonfatal stroke, revascularization, and major adverse cardiac events. RESULTS Of 119 clinical trials, 17 documented niacin's effect on at least 1 cardiovascular disease outcome. The meta-analysis included 35 760 patients with histories of cardiovascular disease or dyslipidemia. Cumulative evidence found no preventive association of niacin with cardiovascular outcomes in secondary prevention. Stratified meta-analysis showed an association of niacin monotherapy with reduction of some cardiovascular events among patients without statin treatment (acute coronary syndrome: relative risk, 0.74; 95% CI, 0.58-0.96; stroke: relative risk, 0.74; 95% CI, 0.59-0.94; revascularization: relative risk, 0.51; 95% CI, 0.37-0.72). These results were mainly derived from 2 trials conducted in the 1970s and 1980s. CONCLUSIONS AND RELEVANCE Niacin may have some use in lipid control for secondary prevention as monotherapy, perhaps in patients intolerant to statins, but evidence is from older studies on a population potentially not representative of current-day patients.
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Role of niacin in current clinical practice.
Sharma, A, Madan, N
Minerva medica. 2019;(1):79-83
Abstract
Despite significant risk reduction with statin therapy, there remains a residual cardiovascular risk. It has been seen that aggressive statin therapy in high risk patients may not lower the low-density lipoprotein cholesterol to goal in up to 40% of patients. Niacin is a potent high-density lipoprotein cholesterol-raising drug, and has been proposed as an attractive approach to reduce cardiac events in patients with or at risk of atherosclerotic cardiovascular disease. However, previous evidence for niacin has been challenged by negative outcomes in two large, randomized, controlled trials comparing niacin to placebo with background statin therapy. In this review, summarize the currently available evidence for the role of niacin treatment for reducing the risk of cardiovascular events in current practice.
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Niacin induces miR-502-3p expression which impairs insulin sensitivity in human adipocytes.
Montastier, E, Beuzelin, D, Martins, F, Mir, L, Marqués, MA, Thalamas, C, Iacovoni, J, Langin, D, Viguerie, N
International journal of obesity (2005). 2019;(7):1485-1490
Abstract
MicroRNAs have been involved in insulin resistance (IR). As the mechanism whereby niacin, an anti-dyslipidemic agent, leads to IR remains elusive, we sought to identify differentially expressed microRNAs in adipose tissue (AT) of individuals receiving niacin and to explore the link between microRNAs, niacin and IR in human adipocytes.In a double-blind controlled study, 22 obese men received extended-release niacin or placebo over 8 weeks. Bioclinical data and subcutaneous AT biopsies were obtained before and after treatment. AT microRNA expression profiles were determined using RTqPCR for 758 human-specific microRNAs. hMADS adipocytes were treated with niacin, or acipimox (a niacin-like drug without effect on IR), or transfected with miR-502-3p. Glucose uptake and Western blotting were performed.In obese men, insulin sensitivity decreased after niacin treatment. In AT, the expression of 6 microRNAs including miR-502-3p was up-regulated. Treatment of hMADS adipocytes with niacin specifically increased miR-502-3p expression. Acipimox had no effect. Overexpression of miR-502-3p in adipocytes led to reduced insulin-induced glucose uptake and lower insulin-stimulated AKT phosphorylation.Long term niacin treatment altered microRNA expression levels in human AT. Increased miR-502-3p expression may play a role in the mediation of IR due to niacin in adipocytes.The study is registered in Clinical Trials NCT01083329 and EudraCT 2009-012124-85.
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Serious Adverse Effects of Extended-release Niacin/Laropiprant: Results From the Heart Protection Study 2-Treatment of HDL to Reduce the Incidence of Vascular Events (HPS2-THRIVE) Trial.
Haynes, R, Valdes-Marquez, E, Hopewell, JC, Chen, F, Li, J, Parish, S, Landray, MJ, Armitage, J, , , , , et al
Clinical therapeutics. 2019;(9):1767-1777
Abstract
PURPOSE The Heart Protection Study 2-Treatment of HDL to Reduce the Incidence of Vascular Events (HPS2-THRIVE) trial of patients at high risk of vascular disease found that adding extended-release niacin-laropiprant to intensive statin-based LDL-lowering therapy had no benefit on cardiovascular outcomes. However, the trial also identified previously unrecognized serious adverse effects (including new-onset diabetes, bleeding, and infection). Our objective was to explore the safety profile of niacin-laropiprant and examine whether any patients were at lower (or higher) risk of its adverse effects. METHODS HPS2-THRIVE was a randomized, double-blind trial of niacin-laropiprant (2000/40 mg/d) versus placebo among 25,673 patients at high risk of vascular disease. Information on all serious adverse events was collected during a median of 3.9 years of study treatment. Effects of niacin-laropiprant on new-onset diabetes, disturbances of diabetes control, bleeding, infection, and gastrointestinal upset were estimated by (1) time after randomization, (2) severity, (3) baseline characteristics, (4) baseline risk of the adverse event of interest, and (5) risk of major vascular event. FINDINGS The hazard ratio (HR) for new-onset diabetes with niacin/laropiprant was 1.32 (95% CI, 1.16-1.51; P < .001), which corresponded to an absolute excess of 4 people (95% CI, 2-6) developing diabetes per 1000 person-years in the study population as a whole. Among the 8299 participants with diabetes at baseline, the HR for serious disturbances in diabetes control was 1.56 (95% CI, 1.35-1.80), corresponding to an absolute excess of 12 (95% CI, 8-16) per 1000 person-years. The HR was 1.38 (95% CI, 1.17-1.63; P < .001) for serious bleeding, corresponding to an absolute excess of 2 (95% CI, 1-3) per 1000 person-years and 1.22 (95% CI, 1.11-1.34; P < .001) for serious infection, corresponding to an absolute excess of 4 (95% CI, 2-6) per 1000 person-years. The excess risks of these serious adverse events were larger in the first year after starting niacin-laropiprant therapy than in later years (except for the excess of infection, which did not appear to attenuate with time), and the risks of nonfatal and fatal events were similarly increased. The absolute excesses of each of these adverse effects were similar regardless of the baseline risk of the outcome. IMPLICATIONS Practitioners or patients considering the use of niacin (in addition to, or instead of, a statin) despite the lack of evidence of cardiovascular benefits (at least when added to effective statin therapy) should take account of the significant risks of these serious adverse effects when making such decisions. ClinicalTrials.gov identifier: NCT00461630.
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Clinical Inquiries: Does niacin decrease cardiovascular morbidity and mortality in CVD patients?
Lazzopina, P, Mounsey, A, Handler, L
The Journal of family practice. 2018;(5):314-316
Abstract
No. Niacin doesn't reduce cardiovascular disease (CVD) morbidity or mortality in patients with established disease (strength of recommendation [SOR]: A, meta-analyses of randomized controlled trials [RCTs] and subsequent large RCTs). Niacin may be considered as monotherapy for patients intolerant of statins (SOR: B, one well-done RCT).
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Effects of immediate-release niacin and dietary fatty acids on acute insulin and lipid status in individuals with metabolic syndrome.
Montserrat-de la Paz, S, Lopez, S, Bermudez, B, Guerrero, JM, Abia, R, Muriana, FJ
Journal of the science of food and agriculture. 2018;(6):2194-2200
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Abstract
BACKGROUND The nature of dietary fats profoundly affects postprandial hypertriglyceridemia and glucose homeostasis. Niacin is a potent lipid-lowering agent. However, limited data exist on postprandial triglycerides and glycemic control following co-administration of high-fat meals with a single dose of niacin in subjects with metabolic syndrome (MetS). The aim of the study was to explore whether a fat challenge containing predominantly saturated fatty acids (SFAs), monounsaturated fatty acids (MUFAs) or MUFAs plus omega-3 long-chain polyunsaturated (LCPUFAs) fatty acids together with a single dose of immediate-release niacin have a relevant role in postprandial insulin and lipid status in subjects with MetS. RESULTS In a randomized crossover within-subject design, 16 men with MetS were given a single dose of immediate-release niacin (2 g) and ∼15 cal kg-1 body weight meals containing either SFAs, MUFAs, MUFAs plus omega-3 LCPUFAs or no fat. At baseline and hourly over 6 h, plasma glucose, insulin, C-peptide, triglycerides, free fatty acids (FFAs), total cholesterol, and both high- and low-density lipoprotein cholesterol were assessed. Co-administered with niacin, high-fat meals significantly increased the postprandial concentrations of glucose, insulin, C-peptide, triglycerides, FFAs and postprandial indices of β-cell function. However, postprandial indices of insulin sensitivity were significantly decreased. These effects were significantly attenuated with MUFAs or MUFAs plus omega-3 LCPUFAs when compared with SFAs. CONCLUSION In the setting of niacin co-administration and compared to dietary SFAs, MUFAs limit the postprandial insulin, triglyceride and FFA excursions, and improve postprandial glucose homeostasis in MetS. © 2017 Society of Chemical Industry.
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A pilot study of the effects of niacin administration on free fatty acid and growth hormone concentrations in children with obesity.
Galescu, OA, Crocker, MK, Altschul, AM, Marwitz, SE, Brady, SM, Yanovski, JA
Pediatric obesity. 2018;(1):30-37
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Abstract
CONTEXT Children with obesity have low spontaneous growth hormone (GH) secretion. High circulating free fatty acid (FFA) concentration is believed to inhibit GH secretion in those with obesity. In adults, lipolytic inhibition with niacin lowers FFA and increases GH, but there are no prior studies in children with obesity. OBJECTIVE The objective of the study was to determine the dose and frequency of niacin administration required to lower FFA and stimulate GH in children with obesity. DESIGN Dose-finding study of nondiabetic children ages 6-12 years with body mass index (BMI) ≥ 95th percentile given niacin 250 mg q2h × 3 doses (n = 2), 500 mg q2h × 3 doses (n = 5) or 500 mg q1h × 4 doses (n = 5). PARTICIPANTS Eight boys and four girls (age 9.7 ± 1.8 years; BMI 26.4 ± 3.1 kg m-2 ; BMIz 2.2 ± .25) were studied. MAIN OUTCOME Percentage of serum FFA values that were below 0.2 mEq L-1 . GH, insulin and glucose were also measured serially. RESULTS FFA decreased as the dose and frequency of niacin increased (p = .01). Niacin 500 mg q1h 4 doses suppressed FFA < 0.2 mEq L-1 and significantly increased GH (p = .04). Adverse effects were flushing/warmth (100%), tingling (60%) and GI complaints (20-40%). CONCLUSIONS Niacin 500 mg q1h significantly lowered serum FFA and increased GH. These pilot data suggest that high FFA is an important suppressor of GH secretion in children with obesity.
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The niacin response biomarker as a schizophrenia endophenotype: A status update.
Messamore, E
Prostaglandins, leukotrienes, and essential fatty acids. 2018;:95-97
Abstract
Increasingly, it is recognized that the behavioral syndrome of schizophrenia is not a unitary disease with a single underlying cause. Rather, it may have several possible etiologies, and its symptoms may arise from multiple causes. Such heterogeneity could account for some of the difficulties in elucidating its genetics, and may also explain clinical observations of variable medication response in schizophrenia. The ability to categorize schizophrenia using objectively recognizable, physiologically-based subtypes promises to make our understanding of schizophrenia more comprehensive and could provide some clues for more personalized treatment. This paper will review the extent to which an abnormally blunted skin flush response to niacin satisfies the criteria for a schizophrenia endophenotype.