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1.
Physiol Rep ; 12(8): e16019, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38627220

RESUMO

Inactivity can lead to muscle atrophy and capillary regression in skeletal muscle. Niacin (NA), known for inducing hypermetabolism, may help prevent this capillary regression. In this study involving adult female Sprague-Dawley rats, the animals were randomly assigned to one of four groups: control (CON), hindlimb unloading (HU), NA, and HU with NA supplementation (HU + NA). For a period of 2 weeks, the rats in the HU and HU + NA groups underwent HU, while those in the NA and HU + NA groups received NA (750 mg/kg) twice daily through oral administration. The results demonstrated that HU lowered capillary number, luminal diameter, and capillary volume, as well as decreased succinate dehydrogenase activity, slow fiber composition, and PGC-1α expression within the soleus muscle. However, NA supplementation prevented these alterations in capillary structure due to unloading by stimulating PGC-1α factors and inhibiting mitochondrial dysfunction. Therefore, NA supplementation could serve as a potential therapeutic approach for preserving the capillary network and mitochondrial metabolism of muscle fibers during periods of inactivity.


Assuntos
Niacina , Ratos , Feminino , Animais , Ratos Sprague-Dawley , Niacina/farmacologia , Niacina/metabolismo , Niacina/uso terapêutico , Músculo Esquelético/metabolismo , Atrofia Muscular/metabolismo , Suplementos Nutricionais , Elevação dos Membros Posteriores/métodos
2.
PLoS One ; 19(2): e0296052, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38408107

RESUMO

HDL-apolipoprotein A-I exchange (HAE) measures a functional property associated with HDL's ability to mediate reverse cholesterol transport. HAE has been used to examine HDL function in case-control studies but not in studies of therapeutics that alter HDL particle composition. This study investigates whether niacin and omega-3 fatty acids induce measurable changes in HAE using a cohort of fifty-six subjects with metabolic syndrome (MetS) who were previously recruited to a double-blind trial where they were randomized to 16 weeks of treatment with dual placebo, extended-release niacin (ERN, 2g/day), prescription omega-3 ethyl esters (P-OM3, 4g/day), or the combination. HAE was assessed at the beginning and end of the study. Compared to placebo, ERN and P-OM3 alone significantly increased HAE by 15.1% [8.2, 22.0] (P<0.0001) and 11.1% [4.5, 17.7] (P<0.0005), respectively, while in combination they increased HAE by 10.0% [2.5, 15.8] (P = 0.005). When HAE was evaluated per unit mass of apoA-I ERN increased apoA-I specific exchange activity by 20% (2, 41 CI, P = 0.02) and P-OM3 by 28% (9.6, 48 CI, P<0.0006). However the combination had no statistically significant effect, 10% (-9, 31 CI, P = 0.39). With regard to P-OM3 therapy in particular, the HAE assay detected an increase in this property in the absence of a concomitant rise in HDL-C and apoA-I levels, suggesting that the assay can detect functional changes in HDL that occur in the absence of traditional biomarkers.


Assuntos
Ácidos Graxos Ômega-3 , Síndrome Metabólica , Niacina , Humanos , Ácidos Graxos Ômega-3/farmacologia , Ácidos Graxos Ômega-3/uso terapêutico , Niacina/uso terapêutico , Apolipoproteína A-I/uso terapêutico , Síndrome Metabólica/tratamento farmacológico , HDL-Colesterol , Método Duplo-Cego
3.
J Pediatr Urol ; 20(2): 281.e1-281.e7, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38212166

RESUMO

INTRODUCTION: The testicular ischemia-reperfusion (I/R) injury is characterized by the excessive aggregation of un-scavenged reactive oxygen species, leading to the heightened levels of oxidative stress. This phenomenon plays a pivotal role in the pathophysiology of testicular torsion damage. OBJECTIVE: The current study aimed to detect the prophylactic and therapeutic effects of niacin on testicular I/R injury. STUDY DESIGN: Twenty-four healthy adult male Sprague Dawley rats were randomly allocated into three groups as follows: (1) sham group, (2) torsion/detorsion (T/D) group, and (3) treatment group which received 200 mg/kg niacin along with testicular T/D. Torsion/detorsion was induced by 2 h of torsion followed by 10 days of reperfusion period. In the treatment group, niacin was injected 30 min before the reperfusion period intraperitoneally and continued for 10 days by oral gavage. RESULTS: T/D was associated with marked decreases in terms of sperm count, viability, and kinematic parameters versus the sham group (P < 0.05), which niacin significantly reverted the kinematic parameters (P < 0.05). I/R injury caused a significant increase in the number of abnormal epididymal sperms compared to the sham group (P < 0.05). Niacin decreased the epididymal sperm abnormality significantly compared to the T/D group (P < 0.05). Tissue abnormalities in T/D group, such as edema, hyperemia, inflammation, and necrosis were completely visible histopathologically, while the histological changes in the niacin-treated group were better than those in the T/D group. Regarding the pathological parametric evaluations, I/R injury significantly reduced the mean testicular biopsy score (MTBS), germinal epithelial cell thickness (GECT), and mean seminiferous tubular diameter (MSTD), and increased the tubular hypoplasia/atrophy (THA) compared to the sham group (P < 0.05), which niacin treatment significantly improved the MTBS and GECT compared to the T/D group (P < 0.05). T/D significantly increased the oxidative stress index (OSI) and lipid peroxidation (MDA) (P < 0.05). Niacin significantly reduced the OSI and MDA levels compared to the T/D group (P < 0.05). DISCUSSION: The current study found that niacin has preventive/therapeutic effects against the elevation of oxidative stress markers and depletion of antioxidants during I/R injury. Following administration of niacin, a reduction in histologic injury was observed in rats. In our study, we showed the antioxidant properties of niacin and its capacity to protect against I/R damage. CONCLUSION: The findings of the present investigation revealed that niacin, as an antioxidant agent, can suppress the oxidative stress induced by testicular I/R injury, and can be used as a supplementary agent in the treatment of those undergoing testicular torsion surgery.


Assuntos
Niacina , Traumatismo por Reperfusão , Torção do Cordão Espermático , Masculino , Ratos , Animais , Humanos , Testículo/patologia , Torção do Cordão Espermático/complicações , Torção do Cordão Espermático/tratamento farmacológico , Torção do Cordão Espermático/patologia , Niacina/farmacologia , Niacina/uso terapêutico , Niacina/metabolismo , Antioxidantes/uso terapêutico , Ratos Sprague-Dawley , Sêmen , Traumatismo por Reperfusão/prevenção & controle , Estresse Oxidativo , Isquemia , Malondialdeído/metabolismo
4.
Neurotherapeutics ; 20(4): 1037-1054, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37084148

RESUMO

Niacin (vitamin B3) is an essential nutrient that treats pellagra, and prior to the advent of statins, niacin was commonly used to counter dyslipidemia. Recent evidence has posited niacin as a promising therapeutic for several neurological disorders. In this review, we discuss the biochemistry of niacin, including its homeostatic roles in NAD+ supplementation and metabolism. Niacin also has roles outside of metabolism, largely through engaging hydroxycarboxylic acid receptor 2 (Hcar2). These receptor-mediated activities of niacin include regulation of immune responses, phagocytosis of myelin debris after demyelination or of amyloid beta in models of Alzheimer's disease, and cholesterol efflux from cells. We describe the neurological disorders in which niacin has been investigated or has been proposed as a candidate medication. These are multiple sclerosis, Alzheimer's disease, Parkinson's disease, glioblastoma and amyotrophic lateral sclerosis. Finally, we explore the proposed mechanisms through which niacin may ameliorate neuropathology. While several questions remain, the prospect of niacin as a therapeutic to alleviate neurological impairment is promising.


Assuntos
Doença de Alzheimer , Doenças do Sistema Nervoso , Neurologia , Niacina , Pelagra , Humanos , Niacina/uso terapêutico , Niacina/metabolismo , Peptídeos beta-Amiloides , Pelagra/metabolismo
5.
BMC Cancer ; 22(1): 1173, 2022 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-36376861

RESUMO

BACKGROUND: The vitamin niacin is used as a lipid-regulating supplement, but it is unknown whether niacin has a positive influence on cancer prognosis. In this study, we examine the relationship between niacin intake and mortality among patients with cancer. METHODS: Our study utilized all available continuous data from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2014. Multivariable Cox regression models were applied in order to investigate dietary niacin intake's association with mortality. We compared the survival probability between groups of low and high niacin intake by plotting Kaplan-Meier curves. An analysis of subgroups was used to investigate heterogeneity sources. RESULTS: A total of 3504 participants were included in the cohort, with 1054 deaths. One thousand eight hundred forty-seven participants (52.3%) were female, 2548 participants (73.4%) were white, and the mean age (SE) was 65.38 years (0.32). According to multivariate logistic regression analysis, niacin intake was negatively associated with mortality outcomes in patients with cancer, with P values below 0.05 in all models. In subgroup analyses based on sex, age, and BMI, the association persisted. The Kaplan-Meier curves indicate that high niacin intake groups have better survival rates than low intake groups. Niacin supplementation improved cancer mortality but not all-cause mortality. CONCLUSION: According to our study, higher dietary niacin intake was associated with lower mortality in cancer patients. Niacin supplements improved cancer survival rates, but not all causes of mortality.


Assuntos
Neoplasias , Niacina , Humanos , Feminino , Idoso , Masculino , Niacina/uso terapêutico , Inquéritos Nutricionais , Estudos Retrospectivos , Vitaminas , Dieta , Neoplasias/tratamento farmacológico , Neoplasias/induzido quimicamente
6.
Mol Oncol ; 16(9): 1795-1815, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35278276

RESUMO

Metabolic dysregulation is an important hallmark of cancer. Nicotinamide (NAM), a water-soluble amide form of niacin (vitamin B3), is currently available as a supplement for maintaining general physiologic functions. NAM is a crucial regulator of mitochondrial metabolism and redox reactions. In this study, we aimed to identify the mechanistic link between NAM-induced metabolic regulation and the therapeutic efficacy of NAM in triple-negative breast cancer (TNBC). The combined analysis using multiomics systems biology showed that NAM decreased mitochondrial membrane potential and ATP production, but increased the activities of reverse electron transport (RET), fatty acid ß-oxidation and glycerophospholipid/sphingolipid metabolic pathways in TNBC, collectively leading to an increase in the levels of reactive oxygen species (ROS). The increased ROS levels triggered apoptosis and suppressed tumour growth and metastasis of TNBC in both human organoids and xenograft mouse models. Our results showed that NAM treatment leads to cancer cell death in TNBC via mitochondrial dysfunction and activation of ROS by bifurcating metabolic pathways (RET and lipid metabolism); this provides insights into the repositioning of NAM supplement as a next-generation anti-metabolic agent for TNBC treatment.


Assuntos
Niacina , Neoplasias de Mama Triplo Negativas , Animais , Apoptose , Linhagem Celular Tumoral , Reposicionamento de Medicamentos , Humanos , Metabolismo dos Lipídeos , Camundongos , Niacina/farmacologia , Niacina/uso terapêutico , Niacinamida/farmacologia , Niacinamida/uso terapêutico , Espécies Reativas de Oxigênio/metabolismo , Neoplasias de Mama Triplo Negativas/patologia
7.
J Am Coll Cardiol ; 78(16): 1635-1654, 2021 10 19.
Artigo em Inglês | MEDLINE | ID: mdl-34649702

RESUMO

Coronavirus disease-2019 (COVID-19) is associated with systemic inflammation, endothelial activation, and multiorgan manifestations. Lipid-modulating agents may be useful in treating patients with COVID-19. These agents may inhibit viral entry by lipid raft disruption or ameliorate the inflammatory response and endothelial activation. In addition, dyslipidemia with lower high-density lipoprotein cholesterol and higher triglyceride levels portend worse outcomes in patients with COVID-19. Upon a systematic search, 40 randomized controlled trials (RCTs) with lipid-modulating agents were identified, including 17 statin trials, 14 omega-3 fatty acids RCTs, 3 fibrate RCTs, 5 niacin RCTs, and 1 dalcetrapib RCT for the management or prevention of COVID-19. From these 40 RCTs, only 2 have reported preliminary results, and most others are ongoing. This paper summarizes the ongoing or completed RCTs of lipid-modulating agents in COVID-19 and the implications of these trials for patient management.


Assuntos
Tratamento Farmacológico da COVID-19 , COVID-19/prevenção & controle , Ácidos Graxos Ômega-3/uso terapêutico , Ácidos Fíbricos/uso terapêutico , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Niacina/uso terapêutico , Amidas/farmacologia , Amidas/uso terapêutico , Ésteres/farmacologia , Ésteres/uso terapêutico , Ácidos Graxos Ômega-3/farmacologia , Ácidos Fíbricos/farmacologia , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Reguladores do Metabolismo de Lipídeos/farmacologia , Reguladores do Metabolismo de Lipídeos/uso terapêutico , Niacina/farmacologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Compostos de Sulfidrila/farmacologia , Compostos de Sulfidrila/uso terapêutico
8.
Epilepsia ; 62(12): 2968-2980, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34590314

RESUMO

OBJECTIVE: Antiseizure medication (ASM) use interacts with vitamin B status in nonpregnant epilepsy populations. We aimed to examine the association between ASM and vitamin B status in pregnant women with epilepsy. METHODS: We performed a cross-sectional study of pregnancies in women with epilepsy enrolled in the Norwegian Mother, Father and Child Cohort Study from 1999 to 2008. Data on ASM and vitamin supplement use were collected from questionnaires. We analyzed maternal plasma concentrations of ASM and metabolites of folate, including unmetabolized folic acid (UMFA), riboflavin (vitamin B2), pyridoxine (vitamin B6), and niacin (vitamin B3) during gestational weeks 17-19. RESULTS: We included 227 singleton pregnancies exposed to ASM with available plasma samples (median maternal age 29 years, range 18 to 41 years). From the preconception period to gestational week 20, any supplement of folic acid was reported in 208 of pregnancies (94%), riboflavin in 72 (33%), pyridoxine in 77 (35%), and niacin in 45 (20%). High ASM concentrations correlated with high concentrations of UMFA and inactive folate metabolites, and with low concentrations of riboflavin and metabolically active pyridoxine. There was no association between ASM and niacin status. SIGNIFICANCE: ASM concentrations during pregnancy were associated with vitamin B status in pregnant women with epilepsy. Additional studies are needed to determine the clinical impact of these findings, and to define the optimal vitamin doses that should be recommended to improve pregnancy outcomes.


Assuntos
Epilepsia , Niacina , Complexo Vitamínico B , Adolescente , Adulto , Criança , Estudos de Coortes , Estudos Transversais , Epilepsia/tratamento farmacológico , Feminino , Ácido Fólico/uso terapêutico , Humanos , Niacina/uso terapêutico , Gravidez , Gestantes , Piridoxina/uso terapêutico , Riboflavina/uso terapêutico , Complexo Vitamínico B/metabolismo , Complexo Vitamínico B/uso terapêutico , Adulto Jovem
9.
Eur J Clin Pharmacol ; 77(8): 1133-1145, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33604752

RESUMO

PURPOSE: To compare the impact of different statins therapies on the reduction of carotid intima-media thickness (CIMT) may reflect their cardiovascular benefits which is useful in clinical decision. METHODS: PubMed, EMBASE, Cochrane Library, and Web of Science were searched, and 3539 articles published from 1992 to 2020 were retrieved. CIMT in randomized controlled trials for statins therapies were included for traditional and network meta-analyses analyzed by Stata 16. The quality of included studies was assessed by the Cochrane Collaboration's tool. RESULTS: Thirty-three randomized controlled trials (n=8762) were eligible for network meta-analysis, of which 18 randomized controlled trials (n=5252) were included for comparison between statins and no statins and 11 randomized controlled trials (n=1338) were included for comparison between high-intensity statins or combination with niacin/ezetimibe and moderate/low-intensity statins in 2 traditional meta-analyses. In the traditional meta-analyses, the statins groups significantly reduce CIMT compared to no statins (standard mean difference=-0.207, 95% confidence interval: -0.291 to -0.123, p<0.001), while high-intensity statins or combination with niacin/ezetimibe performed significant CIMT reduction compared to moderate/low-intensity statins (standard mean difference=-0.287, 95% confidence interval: -0.460 to -0.114, p=0.001). In the network meta-analysis, a relative rank for the ability to reduce CIMT was given as follows: combination therapy with niacin (mean rank: 1.7), high-intensity statins, combination therapy with ezetimibe, and moderate/low-intensity statins. CONCLUSION: Statins combined with niacin performed a greater CIMT reduction compared to high-intensity statins alone and combination therapies with ezetimibe. The advantage of niacin-combined statins therapies to improve cardiovascular endpoint needs further validation through randomized controlled trials. CLINICAL TRIAL REGISTRATION: PROSPERO, CRD42020175972.


Assuntos
Espessura Intima-Media Carotídea , Ezetimiba/uso terapêutico , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hipolipemiantes/uso terapêutico , Niacina/uso terapêutico , Quimioterapia Combinada , Ezetimiba/administração & dosagem , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Hipolipemiantes/administração & dosagem , Metanálise em Rede , Niacina/administração & dosagem , Ensaios Clínicos Controlados Aleatórios como Assunto
10.
Nutrients ; 13(1)2020 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-33374784

RESUMO

Dysbiosis is implicated by many studies in the pathogenesis of Parkinson's disease (PD). Advances in sequencing technology and computing have resulted in confounding data regarding pathogenic bacterial profiles in conditions such as PD. Changes in the microbiome with reductions in short-chain fatty acid (SCFA)-producing bacteria and increases in endotoxin-producing bacteria likely contribute to the pathogenesis of PD. GPR109A, a G-protein coupled receptor found on the surface of the intestinal epithelium and immune cells, plays a key role in controlling intestinal permeability and the inflammatory cascade. The absence of GPR109A receptors is associated with decreased concentration of tight junction proteins, leading to increased intestinal permeability and susceptibility to inflammation. In inflammatory states, butyrate acts via GPR109A to increase concentrations of tight junction proteins and improve intestinal permeability. Niacin deficiency is exacerbated in PD by dopaminergic medications. Niacin supplementation has been shown to shift macrophage polarization from pro-inflammatory to an anti-inflammatory profile. Niacin and butyrate, promising nutrients and unique ligands for the G protein-coupled receptor GPR109A, are reviewed in this paper in detail.


Assuntos
Butiratos/uso terapêutico , Suplementos Nutricionais , Disbiose/tratamento farmacológico , Mucosa Intestinal/efeitos dos fármacos , Niacina/uso terapêutico , Doença de Parkinson/tratamento farmacológico , Animais , Butiratos/metabolismo , Disbiose/metabolismo , Microbioma Gastrointestinal/efeitos dos fármacos , Humanos , Mucosa Intestinal/metabolismo , Niacina/metabolismo , Doença de Parkinson/metabolismo , Permeabilidade/efeitos dos fármacos
12.
Am Fam Physician ; 102(6): 347-354, 2020 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-32931217

RESUMO

Hypertriglyceridemia, defined as fasting serum triglyceride levels of 150 mg per dL or higher, is associated with increased risk of cardiovascular disease. Severely elevated triglyceride levels (500 mg per dL or higher) increase the risk of pancreatitis. Common risk factors for hypertriglyceridemia include obesity, metabolic syndrome, and type 2 diabetes mellitus. Less common risk factors include excessive alcohol use, physical inactivity, being overweight, use of certain medications, and genetic disorders. Management of high triglyceride levels (150 to 499 mg per dL) starts with dietary changes and physical activity to lower cardiovascular risk. Lowering carbohydrate intake (especially refined carbohydrates) and increasing fat (especially omega-3 fatty acids) and protein intake can lower triglyceride levels. Moderate- to high-intensity physical activity can lower triglyceride levels, as well as improve body composition and exercise capacity. Calculating a patient's 10-year risk of atherosclerotic cardiovascular disease is pertinent to determine the role of medications. Statins can be considered for patients with high triglyceride levels who have borderline (5% to 7.4%) or intermediate (7.5% to 19.9%) risk. For patients at high risk who continue to have high triglyceride levels despite statin use, high-dose icosapent (purified eicosapentaenoic acid) can reduce cardiovascular mortality (number needed to treat = 111 to prevent one cardiovascular death over five years). Fibrates, omega-3 fatty acids, or niacin should be considered for patients with severely elevated triglyceride levels to reduce the risk of pancreatitis, although this has not been studied in clinical trials. For patients with acute pancreatitis associated with hypertriglyceridemia, insulin infusion and plasmapheresis should be considered if triglyceride levels remain at 1,000 mg per dL or higher despite conservative management of acute pancreatitis.


Assuntos
Hipertrigliceridemia/tratamento farmacológico , Medicina de Família e Comunidade , Ácidos Graxos Ômega-3/uso terapêutico , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Niacina/uso terapêutico , Padrões de Prática Médica
13.
Medicine (Baltimore) ; 99(29): e21235, 2020 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-32702899

RESUMO

BACKGROUND: Lipid profiles and glycemic control play a critical role in subsequent atherosclerotic cardiovascular disease for patients with type 2 diabetes mellitus (T2DM). This study aimed to evaluate the effectiveness of niacin supplementation on lipid profiles and glycemic control for patients with T2DM. METHODS: The PubMed, Embase, and the Cochrane Library databases were searched to identify randomized controlled trials (RCTs) that investigated the effects of niacin supplementation for patients with T2DM throughout December 2019. The weighted mean differences (WMDs) with 95% confidence intervals (CIs) were applied to calculate the pooled effect estimates using a random-effects model. RESULTS: Eight RCTs comprised a total of 2110 patients with T2DM who were selected for final quantitative analysis. The patients' niacin supplementation was associated with lower levels of total cholesterol (WMD, -0.28; 95% CI, -0.44 to -0.12; P = .001), triglyceride (WMD, -0.37; 95% CI, -0.52 to -0.21; P < .001), and low-density lipoprotein (WMD, -0.42; 95% CI, -0.50 to -0.34; P < .001). Moreover, the level of high-density lipoprotein was significantly increased when niacin supplementation (WMD, 0.33; 95% CI, 0.21 to 0.44; P < .001) was provided. However, niacin supplementation produced no significant effects on plasma glucose (WMD, 0.18; 95% CI, -0.14 to 0.50; P = .275) and hemoglobin A1c (HbA1c) levels (WMD, 0.39; 95% CI, -0.15 to 0.94; P = .158). CONCLUSIONS: This study found that niacin supplementation could improve lipid profiles without affecting the glycemic levels for patients with T2DM. Additional large-scale RCTs should be conducted to evaluate the long-term effectiveness of niacin supplementation.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Suplementos Nutricionais , Niacina/uso terapêutico , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/sangue , Humanos , Lipídeos/sangue , Niacina/administração & dosagem , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
14.
Curr Opin Clin Nutr Metab Care ; 23(2): 138-144, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31977336

RESUMO

PURPOSE OF REVIEW: This is a review of the research on the effectiveness of vitamin supplementation for alcoholism and alcohol-related illnesses. The focus is on research, both clinical and basic on alcohol treatment and nutritional effectiveness of these vital nutrients. RECENT FINDINGS: Most of the research involves basic experiments exploring the impact of vitamin depletion or deficits on physiological systems, especially liver and brain, in rodents. These often include behavioral measures that use cognitive, learning/memory and motivation experiments that model clinical studies. These provide support for hypotheses concerning the impact of such deficiencies in clinical populations. Clinical studies are rare and involve evaluation of the outcome of supplementation usually in the context of a treatment program. Specific vitamins, dosages and treatment programs vary. Deficiencies in retinoids (vitamin A), thiamine (B1) and niacin (B3) are the most frequently investigated. However, there is a greater need for further research on other vitamins, and for more uniform supplementation and treatment procedures. SUMMARY: The literature is primarily basic research on specific vitamins. There are very significant findings with individual vitamin supplementation and combinations that show promise of our understanding of the role of vitamins in the disease of alcoholism and its treatment.


Assuntos
Alcoolismo/terapia , Deficiência de Vitaminas/terapia , Suplementos Nutricionais , Vitaminas/uso terapêutico , Alcoolismo/complicações , Animais , Deficiência de Vitaminas/etiologia , Modelos Animais de Doenças , Humanos , Niacina/uso terapêutico , Estado Nutricional , Tiamina/uso terapêutico , Resultado do Tratamento , Vitamina A/uso terapêutico
15.
Circulation ; 140(16): 1308-1317, 2019 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-31530008

RESUMO

BACKGROUND: Randomized trials of therapies that primarily lowered triglycerides have not consistently shown reductions in cardiovascular events. METHODS: We performed a systematic review and trial-level meta-regression analysis of 3 classes of lipid-lowering therapies that reduce triglycerides to a greater extent than they do low-density lipoprotein cholesterol (LDL-C): fibrates, niacin, and marine-derived omega-3 fatty acids. Key inclusion criteria were a randomized controlled trial that reported major vascular events. We also incorporated data from a previous meta-regression of 25 statin trials. The main outcome measure was the risk ratio (RR) for major vascular events associated with absolute reductions in lipid parameters. RESULTS: A total of 197 270 participants from 24 trials of nonstatin therapy with 25 218 major vascular events and 177 088 participants from 25 trials of statin therapy with 20 962 major vascular events were included, for a total of 374 358 patients and 46 180 major cardiovascular events. Starting with non-high-density lipoprotein cholesterol, a surrogate for very-low-density lipoproteins and low-density lipoproteins, the RR per 1-mmol/L reduction in non-high-density lipoprotein cholesterol was 0.79 (95% CI, 0.76-0.82; P<0.0001; 0.78 per 40 mg/dL). In a multivariable meta-regression model that included terms for both LDL-C and triglyceride (surrogates for low-density lipoproteins and very-low-density lipoproteins, respectively), the RR was 0.80 (95% CI, 0.76-0.85; P<0.0001) per 1-mmol/L (0.79 per 40 mg/dL) reduction in LDL-C and 0.84 (95% CI, 0.75-0.94; P=0.0026) per 1-mmol/L (0.92 per 40 mg/dL) reduction in triglycerides. REDUCE-IT (Reduction of Cardiovascular Events With Icosapent Ethyl-Intervention Trial) was a significant outlier and strongly influential trial in the meta-regression. When removed, the RRs became 0.79 (95% CI, 0.76-0.83; P<0.0001) per 1-mmol/L (0.78 per 40 mg/dL) reduction in LDL-C and 0.91 (95% CI, 0.81-1.006; P=0.06) per 1-mmol/L (0.96 per 40 mg/dL) reduction in triglycerides. In regard to omega-3 dose, each 1 g/d eicosapentaenoic acid administered was associated with a 7% relative risk reduction in major vascular events (RR, 0.93 [95% CI, 0.91-0.95]; P<0.0001), whereas there was no significant association between the dose of docosahexaenoic acid and the relative risk reduction in major vascular events (RR 0.96 [95% CI, 0.89-1.03]). CONCLUSIONS: In randomized controlled trials, triglyceride lowering is associated with a lower risk of major vascular events, even after adjustment for LDL-C lowering, although the effect is less than that for LDL-C and attenuated when REDUCE-IT is excluded. Furthermore, the benefits of marine-derived omega-3 fatty acids, particularly high-dose eicosapentaenoic acid, appear to exceed their lipid-lowering effects.


Assuntos
Doenças Cardiovasculares/tratamento farmacológico , Ácidos Graxos Ômega-3/uso terapêutico , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Doenças Cardiovasculares/patologia , LDL-Colesterol/sangue , Humanos , Niacina/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Risco , Triglicerídeos/sangue
16.
Curr Opin Lipidol ; 30(5): 364-369, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31348023

RESUMO

PURPOSE OF REVIEW: Recently, a high level of triglycerides has attracted much attention as an important residual risk factor of cardiovascular events. We will review and show the mechanisms underlying the association of endothelial dysfunction with hypertriglyceridemia and present clinical evidence for a relationship between endothelial function and triglycerides. RECENT FINDINGS: Clinical studies have shown that hypertriglyceridemia is associated with endothelial dysfunction. It is likely that hypertriglyceridemia impairs endothelial function through direct and indirect mechanisms. Therefore, hypertriglyceridemia is recognized as a therapeutic target in the treatment of endothelial dysfunction. Although experimental and clinical studies have shown that fibrates and omega-3 fatty acids not only decrease triglycerides but also improve endothelial function, the effects of these therapies on cardiovascular events are controversial. SUMMARY: Accumulating evidence suggests that hypertriglyceridemia is an independent risk factor for endothelial dysfunction. Triglycerides should be considered more seriously as a future target to reduce cardiovascular events. Results of ongoing studies may show the benefit of lowering triglycerides and provide new standards of care for patients with hypertriglyceridemia possibly through improvement in endothelial function.


Assuntos
Doenças Cardiovasculares/tratamento farmacológico , Células Endoteliais/metabolismo , Hipertrigliceridemia/tratamento farmacológico , Triglicerídeos/metabolismo , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/patologia , Ácidos Graxos Ômega-3/uso terapêutico , Ácidos Fíbricos/uso terapêutico , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hipertrigliceridemia/metabolismo , Hipertrigliceridemia/patologia , Hipolipemiantes/uso terapêutico , Niacina/uso terapêutico , Fatores de Risco , Triglicerídeos/genética
17.
Expert Opin Pharmacother ; 20(14): 1719-1729, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31232617

RESUMO

Introduction: Cardiovascular disease is an important cause of morbidity and mortality in persons with human immunodeficiency virus (PWH). The risk of atherosclerotic cardiovascular disease (ASCVD) is higher in PWH compared to uninfected persons. Dyslipidemia is a critical link in the pathogenesis of ASCVD in PWH. Chronic inflammation associated with HIV infection may drive both dyslipidemia and ASCVD. Areas covered: The authors review the evidence for using lipid-lowering therapy in PWH and includes an overview of the utility and complexity of using statins in PWH, in particular, drug interactions, safety, and efficacy. In addition, data covering alternate therapies like omega-3 fatty acids, fibrates, niacin, ezetimibe, and PCSK-9 inhibitors are reviewed. Expert opinion: Dyslipidemia is a common problem in PWH. The risk of ASCVD is higher in PWH. Lipid-lowering therapy reduces the risk of ASCVD, but clinical endpoint trials are lacking in PWH. Statin therapy is the mainstay of primary prevention for ASCVD. The timing of when to initiate primary prevention with statins in PWH is unclear. Beyond statins, there are limited data that other lipid-lowering agents have utility in PWH. Ongoing trials like the REPRIEVE trial will inform the community about the optimal approach to lipid-lowering therapy in PWH.


Assuntos
Dislipidemias/tratamento farmacológico , Infecções por HIV/patologia , Hipolipemiantes/uso terapêutico , Antirretrovirais/efeitos adversos , Antirretrovirais/química , Antirretrovirais/uso terapêutico , Interações Medicamentosas , Dislipidemias/etiologia , Ezetimiba/uso terapêutico , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/química , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Niacina/uso terapêutico , Medição de Risco
18.
Nutrients ; 11(4)2019 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-31010085

RESUMO

Because age-related hearing loss (ARHL) is irreversible, prevention is very important. Thus, investigating modifying factors that help prevent ARHL is critical for the elderly. Nutritional status or nutritional factors for the elderly are known to be associated with many problems related to aging. Emerging studies suggest that there was the interaction between nutrition and ARHL. We aimed to investigate the possible impact of dietary nutrients on ARHL using data from the fifth Korean National Health and Nutrition Examination Survey (KNHANES) which included 4742 subjects aged ≥ 65 years from 2010 to 2012. All participants underwent an otologic examination, audiologic evaluation, and nutritional survey. The associations between ARHL and nutrient intake were analyzed using simple and multiple regression models with complex sampling adjusted for confounding factors, such as BMI, smoking status, alcohol consumption, and history of hypertension and diabetes. Higher intake groups of riboflavin, niacin and retinol was inversely associated with ARHL prevalence (riboflavin aOR, 0.71; 95% CI, 0.54-0.94; p = 0.016, niacin aOR, 0.72; 95% CI, 0.54-0.96; p = 0.025, retinol aOR 0.66; 95% CI, 0.51-0.86; p = 0.002, respectively). Our findings suggest the recommended intake levels of riboflavin, niacin, and retinol may help reduce ARHL in the elderly.


Assuntos
Envelhecimento , Dieta , Perda Auditiva/prevenção & controle , Niacina/uso terapêutico , Estado Nutricional , Riboflavina/uso terapêutico , Vitamina A/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Ingestão de Energia , Feminino , Perda Auditiva/etiologia , Humanos , Masculino , Niacina/administração & dosagem , Niacina/farmacologia , Inquéritos Nutricionais , Razão de Chances , Análise de Regressão , República da Coreia , Riboflavina/administração & dosagem , Riboflavina/farmacologia , Vitamina A/administração & dosagem , Vitamina A/farmacologia , Vitaminas/administração & dosagem , Vitaminas/farmacologia , Vitaminas/uso terapêutico
19.
Alcohol Alcohol ; 54(2): 148-151, 2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-30721993

RESUMO

AIM: To define the prevalence and clinical presentation of pellagra, a multi-systemic disease caused by the deficiency of niacin, in patients admitted to a tertiary addiction treatment centre in southern India, with alcohol dependence syndrome (ADS)-(ICD10). METHODS: Review of the health records of 2947 patients who received inpatient care for ADS between 2015 and 2017. RESULTS: Out of 2947, 31 (1%) were diagnosed with pellagra. Nearly two-thirds (64.5%) of those with pellagra were from a low-income group. Of the clinical-triad of pellagra, all patients had dermatitis, more than half (58%) had delirium, a minority (19%) had diarrhoea. Nearly two-thirds (61%) had presented in a complicated-withdrawal state. Associated conditions included peripheral neuropathy (32%); Wernicke's encephalopathy (26%); seizures (16%).Seventeen (54%) had BMI <18.5 kg/m2. Treatment was a high dose of parenteral vitamins including niacin (mean dose: 1500 mg/day) for an average of 7.5 days followed by oral multivitamin supplements. All had complete resolution of pellagrous symptoms by the end of the three weeks of inpatient care. CONCLUSIONS: Pellagra is an acute medical condition, frequently encountered in the context of alcohol dependence and poverty. It often presents with other disabling and life-threatening comorbidities like delirium tremens and Wernicke's encephalopathy. The classical triad of pellagra is only seen in a minority of cases. Thus a high index of suspicion is required lest pellagra may remain undiagnosed. Prompt identification and treatment with a high dose of niacin in combination with other vitamins result in complete recovery.


Assuntos
Delirium por Abstinência Alcoólica/epidemiologia , Alcoolismo/epidemiologia , Síndrome de Korsakoff/epidemiologia , Pelagra/epidemiologia , Adulto , Alcoolismo/complicações , Comorbidade , Humanos , Índia/epidemiologia , Síndrome de Korsakoff/complicações , Niacina/uso terapêutico , Pelagra/complicações , Pelagra/diagnóstico , Pelagra/tratamento farmacológico , Pobreza/estatística & dados numéricos , Prevalência , Centros de Tratamento de Abuso de Substâncias/estatística & dados numéricos , Atenção Terciária à Saúde/estatística & dados numéricos , Vitaminas/uso terapêutico , Adulto Jovem
20.
Curr Atheroscler Rep ; 21(1): 2, 2019 01 12.
Artigo em Inglês | MEDLINE | ID: mdl-30637567

RESUMO

PURPOSE OF REVIEW: Treatment of hypercholesterolemia with statins results in significant reductions in cardiovascular risk; however, individuals with well-controlled low-density lipoprotein cholesterol (LDL-C) levels, but persistent high triglycerides (TG), remain at increased risk. Genetic and epidemiologic studies have shown that elevated fasting TG levels are associated with incident cardiovascular events. At effective doses, omega-3 fatty acids, such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), lower TG levels but may have additional atheroprotective properties compared to other TG-lowering therapies such as niacin and fibrates. The purpose of this review is to evaluate mechanisms related to the potential benefits of omega-3 fatty acids in atherothrombotic disease. RECENT FINDINGS: Large randomized clinical trials are currently under way to test the cardiovascular benefits of omega-3 fatty acids at a pharmacologic dosage (4 g/day). A large randomized trial with a prescription EPA-only formulation was shown to reduce a composite of cardiovascular events by 25% in statin-treated patients with established cardiovascular disease or diabetes and other CV risk factors. EPA and DHA have distinct tissue distributions as well as disparate effects on membrane structure and lipid dynamics, rates of lipid oxidation, and signal transduction pathways. Compared to other TG-lowering therapies, EPA has been found to inhibit cholesterol crystal formation, inflammation, and oxidative modification of atherogenic lipoprotein particles. The anti-inflammatory and endothelial benefits of EPA are enhanced in combination with a statin. Omega-3 fatty acids like EPA only at a pharmacologic dose reduce fasting TG and interfere with mechanisms of atherosclerosis that results in reduced cardiovascular events. Additional mechanistic trials will provide further insights into their role in reducing cardiovascular risk in subjects with well-managed LDL-C but elevated TG levels.


Assuntos
Aterosclerose/tratamento farmacológico , Trombose Coronária/tratamento farmacológico , Ácidos Docosa-Hexaenoicos/uso terapêutico , Ácido Eicosapentaenoico/uso terapêutico , Hipercolesterolemia/tratamento farmacológico , Hipertrigliceridemia/tratamento farmacológico , Membrana Celular/metabolismo , LDL-Colesterol/metabolismo , Ácidos Docosa-Hexaenoicos/metabolismo , Ácido Eicosapentaenoico/metabolismo , Células Endoteliais/metabolismo , Fenofibrato/uso terapêutico , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Niacina/uso terapêutico , Fatores de Risco , Triglicerídeos/efeitos adversos , Triglicerídeos/metabolismo
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