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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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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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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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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.
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Role of Niacin in Current Clinical Practice: A Systematic Review.
Garg, A, Sharma, A, Krishnamoorthy, P, Garg, J, Virmani, D, Sharma, T, Stefanini, G, Kostis, JB, Mukherjee, D, Sikorskaya, E
The American journal of medicine. 2017;(2):173-187
Abstract
BACKGROUND Niacin, a potent high-density lipoprotein cholesterol-raising drug, seems 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 recently by negative outcomes in 2 large, randomized, controlled trials comparing niacin to placebo with background statin therapy. We studied the currently available evidence for the role of niacin treatment for reducing the risk of cardiovascular events in current practice. METHODS A systematic review of randomized controlled trials in the MEDLINE, EMBASE, CINAHL, and Cochrane databases comparing niacin alone or combined with statin therapy was performed. We extracted trial level data, including basic characteristics and number of patients enrolled, duration of follow up, occurrence of adverse events, and cardiovascular-related outcomes. Random effects meta-analysis was conducted to estimate the risk ratio (RR) for individual trial endpoints. RESULTS Thirteen trials (N = 35,206) were selected for final analysis. The mean follow-up duration was 32.8 months. Overall, niacin led to significant increases in serum high-density lipoprotein cholesterol levels from baseline trial enrolment by 21.4%, 9.31 (95% confidence interval [CI] 5.11-13.51) mg/dL. However, we did not observe any differences in all-cause mortality rates (RR 0.99; 95% CI 0.88-1.12) between niacin and control arms. Further, niacin treatment was associated with a trend toward lower risk of cardiovascular mortality (RR 0.91; 95% CI 0.81-1.02), coronary death (RR 0.93; 95% CI 0.78-1.10), nonfatal myocardial infarction (RR 0.85; 95% CI 0.73-1.0), revascularization (coronary and noncoronary) (RR 0.83; 95% CI 0.65-1.06), and stroke (RR 0.89; 95% CI 0.72-1.10), compared with control. CONCLUSION Niacin therapy does not lead to significant reductions in total or cause-specific mortality or recurrent cardiovascular events among persons with or at risk of atherosclerotic cardiovascular disease.
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Niacin and heart disease prevention: Engraving its tombstone is a mistake.
Superko, HR, Zhao, XQ, Hodis, HN, Guyton, JR
Journal of clinical lipidology. 2017;(6):1309-1317
Abstract
Niacin (nicotinic acid) has been used for primary and secondary coronary heart disease prevention for over 40 years. Until recently clinical trials incorporating niacin as part of an intervention strategy consistently demonstrated reduction in clinical events and lesion improvement, including ≥6% absolute mortality reduction. Two large clinical event trials in 2011 (Atherothrombosis Intervention in Metabolic Syndrome With Low HDL/High Triglycerides and Impact on Global Health Outcomes) and 2014 (Heart Protection Study 2-Treatment of HDL to Reduce the Incidence of Vascular Events) concluded that niacin added to statin therapy did not provide clinical event benefit over statin alone. This has prompted some individuals to call for an end to the use of niacin in statin-treated patients and the US Food and Drug Administration to halt marketing of statin/niacin combination tablets. There are significant differences between the earlier clinical trials that revealed cardiovascular benefit of niacin and the 2 trials that failed to demonstrate a benefit. These differences include dyslipidemia types, niacin formulation, dosing, and timing. In general, the patient population that benefits the most from incorporating niacin in their treatment regimen can be defined by elevations in low-density lipoprotein cholesterol and triglycerides, and reduced high-density lipoprotein cholesterol. The niacin formulation and dose should be capable of achieving adequate lipoprotein change. Mealtime dosing of niacin, as opposed to bedtime dosing, may avoid a counter-regulatory hormone response, including catecholamines, because of altered fuel supply potentially leading to unexpected cardiovascular outcomes.
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Definition of a tolerable upper intake level of niacin: a systematic review and meta-analysis of the dose-dependent effects of nicotinamide and nicotinic acid supplementation.
Minto, C, Vecchio, MG, Lamprecht, M, Gregori, D
Nutrition reviews. 2017;(6):471-490
Abstract
CONTEXT Nicotinic acid and nicotinamide are soluble compounds of the vitamin B group, widely used to regulate the lipid profile in hyperlipidemic individuals. Higher doses of nicotinic acid are associated with adverse effects, especially flushing. A unique tolerable upper intake level (UL) of nicotinic acid has not been defined. OBJECTIVE This meta-analysis aims to evaluate adverse effects and their incidence after supplementation with different doses of nicotinic acid and nicotinamide, comparing results with current ULs in Europe and the United States. DATA SOURCES PubMed was searched for articles providing detailed information about nicotinic acid or nicotinamide supplementation and related outcomes. STUDY SELECTION A total of 2670 citations were selected for screening. Two primary outcomes were considered: occurrence of adverse effects following nicotinic acid or nicotinamide supplementation, and dose at which adverse effects occurred. DATA EXTRACTION Details on study population, type and duration of treatment, dosage of vitamins, association with lipid-influencing drugs, length of follow-up, and incidence and type of adverse events were extracted. RESULTS After screening, 47 articles involving 11 741 individuals were included. Meta-analysis was based on estimation of benchmark doses for the probability of adverse effects after supplementation. In individuals with dyslipidemia or cardiovascular disease, nicotinic acid monotherapy seems to be protective against any adverse effects considered, as adverse events occurred at doses above those used with other treatments. In healthy individuals treated with nicotinic acid alone, major adverse effects occurred at doses below 1000 mg/d. CONCLUSIONS Results may indicate a high degree of conservativeness in the UL of nicotinic acid, fixed at 35 mg/d in United States and 10 mg/d in Europe. Reconsideration of the UL of nicotinic acid for nutritional supplements, possibly differentiating between ULs in healthy and unhealthy individuals, may be warranted.
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Long-chain omega-3 fatty acids, fibrates and niacin as therapeutic options in the treatment of hypertriglyceridemia: a review of the literature.
Ito, MK
Atherosclerosis. 2015;(2):647-56
Abstract
Hypertriglyceridemia affects approximately 33% of the US population. Elevated triglyceride levels are independently associated with cardiovascular disease (CVD) risk, and severe hypertriglyceridemia is a risk factor for acute pancreatitis. Guidelines for the management of severe hypertriglyceridemia (≥5.6 mmol/L [≥500 mg/dL]) recommend immediate use of triglyceride-lowering agents; however, statins remain the first line of therapy for the management of mild to moderate hypertriglyceridemia (1.7-5.6 mmol/L [150-499 mg/dL]). Statins primarily target elevated low-density lipoprotein cholesterol levels, but have also been shown to reduce mean triglyceride levels by up to 18% (or 43% in patients with triglyceride levels≥3.1 mmol/L [≥273 mg/dL]). However, individuals with hypertriglyceridemia may need additional reduction in triglyceride-rich lipoproteins and remnant particles to further reduce residual CVD risk. A number of guidelines recommend the addition of fibrates, niacin, or long-chain omega-3 fatty acids if elevated triglyceride or non-high-density lipoprotein cholesterol levels persist despite the use of high-intensity statin therapy. This review evaluates the impact of fibrates, niacin, and long-chain omega-3 fatty acids on lipid profiles and cardiovascular outcomes in patients with hypertriglyceridemia. It also assesses the adverse effects and drug-drug interactions associated with these triglyceride-lowering agents, because although they have all been shown to effectively reduce triglyceride levels in patients with hypertriglyceridemia, they differ with regard to their associated benefit-risk profiles. Long-chain omega-3 fatty acids may be a well-tolerated and effective alternative to fibrates and niacin, yet further large-scale clinical studies are required to evaluate their effects on cardiovascular outcomes and CVD risk reduction in patients with hypertriglyceridemia.
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Niacin Therapy, HDL Cholesterol, and Cardiovascular Disease: Is the HDL Hypothesis Defunct?
Mani, P, Rohatgi, A
Current atherosclerosis reports. 2015;(8):43
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Abstract
High-density lipoprotein cholesterol (HDL-C) has been shown in epidemiologic studies to be associated with cardiovascular (CV) risk and thus significant efforts have been focused on HDL-C modulation. Multiple pharmaceutical agents have been developed with the goal of increasing HDL-C. Niacin, the most widely used medication to raise HDL-C, increases HDL-C by up to 25 % and was shown in multiple surrogate end point studies to reduce CV risk. However, two large randomized controlled trials of niacin, AIM-HIGH and HPS2-THRIVE, have shown that despite its effects on HDL-C, niacin does not decrease the incidence of CV events and may have significant adverse effects. Studies of other classes of agents such as cholesteryl ester transfer protein (CETP) inhibitors have also shown that even dramatic increases in HDL-C do not necessarily translate to reduction in clinical events. While these findings have cast doubt upon the importance of HDL-C modulation on CV risk, it is becoming increasingly clear that HDL function-related measures may be better targets for CV risk reduction. Increasing ApoA-I, the primary apolipoprotein associated with HDL, correlates with reduced risk of events, and HDL particle concentration (HDL-P) inversely associates with incident CV events adjusted for HDL-C and LDL particle measures. Cholesterol efflux, the mechanism by which macrophages in vessel walls secrete cholesterol outside cells, correlates with both surrogate end points and clinical events. The effects of niacin on these alternate measures of HDL have been conflicting. Further studies should determine if modulation of these HDL function markers translates to clinical benefits. Although the HDL cholesterol hypothesis may be defunct, the HDL function hypothesis is now poised to be rigorously tested.
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Niacin as antidyslipidemic drug.
Julius, U
Canadian journal of physiology and pharmacology. 2015;(12):1043-54
Abstract
Niacin is an important vitamin (B3) that can be used in gram doses to positively modify pathogenetically relevant lipid disorders: elevated LDL cholesterol, elevated non-HDL cholesterol, elevated triglycerides, elevated lipoprotein(a), and reduced HDL cholesterol. This review reports the latest published findings with respect to niacin's mechanisms of action on these lipids and its anti-inflammatory and anti-atherosclerotic effects. In the pre-statin era, niacin was shown to have beneficial effects on cardiovascular end-points; but in recent years, two major studies performed in patients whose LDL cholesterol levels had been optimized by a statin therapy did not demonstrate an additional significant effect on these end-points in the groups where niacin was administered. Both studies have several drawbacks that suggest that they are not representative for other patients. Thus, niacin still plays a role either as an additive to a statin or as a substitute for a statin in statin-intolerant patients. Moreover, patients with elevated triglyceride and low HDL cholesterol levels and patients with elevated lipoprotein(a) concentrations will possibly benefit from niacin, although currently the study evidence for these indications is rather poor. Niacin may be useful for compliant patients, however possible side effects (flushing, liver damage) and contraindications should be taken into consideration.