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1.
BMC Cardiovasc Disord ; 20(1): 178, 2020 04 16.
Artigo em Inglês | MEDLINE | ID: mdl-32299366

RESUMO

BACKGROUND: Heart failure is associated with ventricular dyssynchrony and energetic inefficiency, which can be alleviated by cardiac resynchronization therapy (CRT) with approximately one-third of non-response rate. Thus far, there is no specific biomarker to predict the response to CRT in patients with heart failure. In this study, we assessed the role of the blood metabolomic profile in predicting the response to CRT. METHODS: A total of 105 dilated cardiomyopathy patients with severe heart failure who received CRT were included in our two-stage study. Baseline blood samples were collected prior to CRT implantation. The response to CRT was defined according to echocardiographic criteria. Metabolomic profiling of serum samples was carried out using ultrahigh performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry. RESULTS: Seventeen metabolites showed significant differences in their levels between responders and non-responders, and these metabolites were primarily involved in six pathways, including linoleic acid metabolism, Valine, leucine and isoleucine biosynthesis, phenylalanine metabolism, citrate cycle, tryptophan metabolism, and sphingolipid metabolism. A combination of isoleucine, tryptophan, and linoleic acid was identified as an ideal metabolite panel to distinguish responders from non-responders in the discovery set (n = 51 with an AUC of 0.981), and it was confirmed in the validation set (n = 54 with an AUC of 0.929). CONCLUSIONS: Mass spectrometry based serum metabolomics approach provided larger coverage of metabolome which can help distinguish CRT responders from non-responders. A combination of isoleucine, tryptophan, and linoleic acid may associate with significant prognostic values for CRT.


Assuntos
Terapia de Ressincronização Cardíaca , Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/terapia , Isoleucina/sangue , Ácido Linoleico/sangue , Metabolômica , Triptofano/sangue , Idoso , Biomarcadores/sangue , Terapia de Ressincronização Cardíaca/efeitos adversos , Cromatografia Líquida de Alta Pressão , Feminino , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/fisiopatologia , Humanos , Masculino , Espectrometria de Massas , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Recuperação de Função Fisiológica , Índice de Gravidade de Doença , Resultado do Tratamento
2.
BMC Cardiovasc Disord ; 20(1): 122, 2020 03 10.
Artigo em Inglês | MEDLINE | ID: mdl-32156256

RESUMO

BACKGROUND: Serum fatty acid (s-FA) compositions and their correlation with serum lipids (s-LPs) such as total cholesterol (T-CHO) and triglycerides (TG) have been reported in healthy young subjects. However, little is known about such features in acute ischaemic stroke (AIS). The aim of our study was to investigate s-FA characteristics and their correlation with AIS in elderly patients. METHODS: We conducted a cross-sectional study of patients aged 50 years or older who were admitted between September 2015 and March 2017 within 24 h of the first AIS onset. We evaluated concentrations and compositions of s-FAs and their association with s-LPs, age, and ischaemic stroke subtypes, including large-artery atherosclerosis (LAA), small-vessel occlusion (SVO), and cardioembolism (CE) or others. RESULTS: One hundred ninety-one patients met our inclusion criteria. Their average age was 74.4 years, mean T-CHO and median TG were 203.4 and 94.5 mg/dl, respectively, and median or mean concentrations of palmitic acid (PA), oleic acid (OlA), linoleic acid (LiA), and docosahexaenoic acid (DHA) were 680.7, 602.5, 795.2, and 136.9 µg/ml, respectively, with mean compositions of 23.7, 21.3, 27.1, and 4.4%, respectively. PA, OlA, and LiA concentrations were weakly negatively associated with age and positively correlated with TG. In LAA or SVO (LAA_SVO) and CE or others (CE_O), mean age was 71.9 and 77.4 years (p < 0.001), mean T-CHO was 213.9 and 191.2 mg/dl (p < 0.0001), median TG was 106.5 and 88.5 mg/dl (p < 0.01), median PA was 717.2 and 648.4 µg/ml (p < 0.01), median OlA was 638.2 and 567.5 µg/ml (p < 0.01), and median LiA was 844.7 and 728.5 µg/ml (p < 0.01), respectively. DHA composition was weakly positively correlated with age. There were no differences in PA, OlA, LiA, and DHA compositions between LAA_SVO and CE_O. CONCLUSIONS: In AIS elderly patients, concentrations, rather than compositions of PA, OlA, and LiA, correlated with age, TG, and ischaemic stroke subtypes. Patients with LAA_SVO were younger and had higher concentrations of PA, OlA, and LiA than those with CE_O. There were no differences in such compositions between LAA_SVO and CE_O.


Assuntos
Isquemia Encefálica/sangue , Ácidos Graxos/sangue , Acidente Vascular Cerebral/sangue , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Isquemia Encefálica/diagnóstico , Estudos Transversais , Feminino , Humanos , Ácido Linoleico/sangue , Masculino , Pessoa de Meia-Idade , Ácido Oleico/sangue , Ácido Palmítico/sangue , Estudos Retrospectivos , Acidente Vascular Cerebral/diagnóstico
3.
Am J Clin Nutr ; 111(5): 1068-1078, 2020 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-32167131

RESUMO

BACKGROUND: Unexplained heterogeneity in clinical trials has resulted in questions regarding the effectiveness of É£-linolenic acid (GLA)-containing botanical oil supplements. This heterogeneity may be explained by genetic variation within the fatty acid desaturase (FADS) gene cluster that is associated with circulating and tissue concentrations of arachidonic acid (ARA) and dihomo-É£-linolenic acid (DGLA), both of which may be synthesized from GLA and result in proinflammatory and anti-inflammatory metabolites, respectively. OBJECTIVES: The objective of this study was to prospectively compare the capacity of a non-Hispanic white cohort, stratified by FADS genotype at the key single-nucleotide polymorphism (SNP) rs174537, to metabolize 18-carbon omega-6 (n-6) PUFAs in borage oil (BO) and soybean oil (SO) to GLA, DGLA, and ARA. METHODS: Healthy adults (n = 64) participated in a randomized, double-blind, crossover intervention. Individuals received encapsulated BO (Borago officinalis L.; 37% LA and 23% GLA) or SO [Glycine max (L.) Merr.; 50% LA and 0% GLA] for 4 wk, followed by an 8-wk washout period, before consuming the opposite oil for 4 wk. Serum lipids and markers of inflammation (C-reactive protein) were assessed for both oil types at baseline and during weeks 2 and 4 of the intervention. RESULTS: SO supplementation failed to alter circulating concentrations of any n-6 long-chain PUFAs. In contrast, a modest daily dose of BO elevated serum concentrations of GLA and DGLA in an rs174537 genotype-dependent manner. In particular, DGLA increased by 57% (95% CI: 0.38, 0.79) in GG genotype individuals, but by 141% (95% CI: 1.03, 2.85) in TT individuals. For ARA, baseline concentrations varied substantially by genotype and increased modestly with BO supplementation, suggesting a key role for FADS variation in the balance of DGLA and ARA. CONCLUSIONS: The results of this study clearly suggest that personalized and population-based approaches considering FADS genetic variation may be necessary to optimize the design of future clinical studies with GLA-containing oils. This trial was registered at clinicaltrials.gov as NCT02337231.


Assuntos
Ácidos Graxos Dessaturases/genética , Ácido Linoleico/sangue , Óleos Vegetais/metabolismo , Óleo de Soja/metabolismo , Ácido gama-Linolênico/sangue , Ácido 8,11,14-Eicosatrienoico/sangue , Adulto , Idoso , Estudos de Coortes , Método Duplo-Cego , Grupo com Ancestrais do Continente Europeu/genética , Ácidos Graxos Dessaturases/metabolismo , Ácidos Graxos Insaturados/sangue , Feminino , Genótipo , Humanos , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Estudos Prospectivos , Adulto Jovem , Ácido gama-Linolênico/metabolismo
4.
Neurobiol Aging ; 91: 167.e11-167.e19, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32204957

RESUMO

With the steadily increasing prevalence of Alzheimer's disease (AD) and great difficulties encountered for AD drug development presently, much interest has been devoted to identifying modifiable risk factors to lower the risk of AD, while the causal associations between risk factors and AD remain inconclusive. The present study conducted a comprehensive evaluation of the causal associations between risk factors and AD development by taking the recent advancements of Mendelian randomization (MR). Inverse variance weighted (IVW), MR-Egger, weighted median, and weighted mode were used for complementary calculation. A total of 45 risk factors and corresponding studies were covered in the study. This two-sample MR (2SMR) analysis provided a suggestive association between genetically predicted higher years of schooling and reduced risks of AD, and each standard deviation (3.71 years) increased in years of schooling was associated with a 41% reduction in the risk of AD (IVW, OR: 0.59, 95% CI: 0.45-0.77). At the same time, it was genetically predicted that urate might be a risk factor in AD, and it was found that each standard deviation increase in urate levels (1.33 mg/dL) was associated with a 0.09-fold increase in the risk of AD (IVW, OR: 1.09, 95% CI: 1.01-1.18). To summarize, the 2SMR analysis indicated a suggestive association between genetically predicted higher years of schooling and reduced risks of AD, and between genetically predicted higher urate levels and increased risks of AD. The findings provide useful clues to help combat AD and warrants future studies.


Assuntos
Doença de Alzheimer/etiologia , Escolaridade , Análise da Randomização Mendeliana/métodos , Ácido Úrico/sangue , Doença de Alzheimer/genética , Estatura , Cobre/sangue , Estudo de Associação Genômica Ampla , Hipocampo/patologia , Humanos , Ácido Linoleico/sangue , Tamanho do Órgão , Polimorfismo de Nucleotídeo Único , Fatores de Risco
5.
Lipids ; 55(1): 53-62, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31943229

RESUMO

The interest in the amount of polyunsaturated fatty acids (PUFA) in the umbilical cord blood (UCB) is increasing, but the stability of erythrocyte PUFA in these samples during storage and washing of the erythrocytes has not been directly evaluated. The purpose of this study was to analyze the effect of the lapse of time on the fatty acid (FA) content from UCB sample collection and maintained at 4 °C (0-12 h) until erythrocyte separation and washing. Palmitic acid (16:0), stearic acid (18:0), 18:1n-7/n-9, linoleic acid (18:2n-6), arachidonic acid (20:4n-6), 22:4n-6, eicosapentaenoic acid (20:5n-3), docosapentaenoic acid (22:5n-3), and docosahexaenoic acid (22:6n-3) together accounted for 87% of the FA profile in the umbilical vein erythrocytes. No difference was observed in the concentration of any of the FA studied, nor in the sum of saturated fatty acids (SFA), PUFA, or LC-PUFA in umbilical erythrocytes obtained at delivery and stored up to 12 h before the separation of erythrocytes. However, if a washing step was included in the processing of the erythrocytes, a decrease in the concentration of 16:0, 18:0, 18:3n-3, 20:4n-6, 22:4n-6, total SFA, PUFA, LC-PUFA, and n-6 LC-PUFA was evidenced, compared to unwashed erythrocytes. The FA concentration in umbilical cord erythrocytes did not change between samples stored from 0 to 12 h until erythrocyte separation. Erythrocyte washing before storage decreased the concentration of significant individual and total SFA, PUFA, and LC-PUFA. These results should be considered when planning the collection of UCB samples for the study of fatty acid concentration due to the nonscheduled timing of deliveries.


Assuntos
Eritrócitos/química , Ácidos Graxos/sangue , Sangue Fetal/citologia , Ácido Araquidônico/sangue , Ácidos Docosa-Hexaenoicos/sangue , Ácido Eicosapentaenoico/sangue , Ácidos Graxos/isolamento & purificação , Ácidos Graxos Insaturados/sangue , Feminino , Sangue Fetal/química , Idade Gestacional , Humanos , Ácido Linoleico/sangue , Ácido Palmítico/sangue , Gravidez , Ácidos Esteáricos/sangue
6.
Diabetes Care ; 43(2): 358-365, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31727685

RESUMO

OBJECTIVE: To study plasma and dietary linoleic acid (LA) in relation to type 2 diabetes risk in post-myocardial infarction (MI) patients. RESEARCH DESIGN AND METHODS: We included 3,257 patients aged 60-80 years (80% male) with a median time since MI of 3.5 years from the Alpha Omega Cohort and who were initially free of type 2 diabetes. At baseline (2002-2006), plasma LA was measured in cholesteryl esters, and dietary LA was estimated with a 203-item food-frequency questionnaire. Incident type 2 diabetes was ascertained through self-reported physician diagnosis and medication use. Hazard ratios (with 95% CIs) were calculated by Cox regressions, in which dietary LA isocalorically replaced the sum of saturated (SFA) and trans fatty acids (TFA). RESULTS: Mean ± SD circulating and dietary LA was 50.1 ± 4.9% and 5.9 ± 2.1% energy, respectively. Plasma and dietary LA were weakly correlated (Spearman r = 0.13, P < 0.001). During a median follow-up of 41 months, 171 patients developed type 2 diabetes. Plasma LA was inversely associated with type 2 diabetes risk (quintile [Q]5 vs. Q1: 0.44 [0.26, 0.75]; per 5%: 0.73 [0.62, 0.86]). Substitution of dietary LA for SFA+TFA showed no association with type 2 diabetes risk (Q5 vs. Q1: 0.78 [0.36, 1.72]; per 5% energy: 1.18 [0.59, 2.35]). Adjustment for markers of de novo lipogenesis attenuated plasma LA associations. CONCLUSIONS: In our cohort of post-MI patients, plasma LA was inversely related to type 2 diabetes risk, whereas dietary LA was not related. Further research is needed to assess whether plasma LA indicates metabolic state rather than dietary LA in these patients.


Assuntos
Diabetes Mellitus Tipo 2/etiologia , Gorduras na Dieta/administração & dosagem , Ácido Linoleico/administração & dosagem , Ácido Linoleico/sangue , Infarto do Miocárdio/sangue , Infarto do Miocárdio/complicações , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Estudos de Coortes , Diabetes Mellitus Tipo 2/sangue , Dieta , Gorduras na Dieta/sangue , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/epidemiologia , Inquéritos Nutricionais , Estudos Prospectivos , Fatores de Risco , Ácidos Graxos Trans/administração & dosagem , Ácidos Graxos Trans/sangue
7.
Nutrients ; 11(12)2019 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-31817859

RESUMO

Whether circulating fatty acids (FAs) play a causal role in the development of cardiovascular disease (CVD) remains unclear. We conducted a Mendelian randomisation study to explore the associations between plasma phospholipid FA levels and 15 CVDs. Summary-level data from the CARDIoGRAMplusC4D, MEGASTROKE, and Atrial Fibrillation consortia and UK Biobank were used. Sixteen single-nucleotide polymorphisms (SNPs) associated with ten plasma FAs were used as instrumental variables. SNPs in or close to the FADS1 gene were associated with most FAs. We performed a secondary analysis of the association between a functional variant (rs174547) in FADS1, which encodes ?5-desaturase (a key enzyme in the endogenous FA synthesis), and CVD. Genetic predisposition to higher plasma α-linolenic, linoleic, and oleic acid levels was associated with lower odds of large-artery stroke and venous thromboembolism, whereas higher arachidonic and stearic acid levels were associated with higher odds of these two CVDs. The associations were driven by SNPs in or close to FADS1. In the secondary analysis, the minor allele of rs174547 in FADS1 was associated with significantly lower odds of any ischemic stroke, large-artery stroke, and venous thromboembolism and showed suggestive evidence of inverse association with coronary artery disease, abdominal aortic aneurysm and aortic valve stenosis. Genetically higher plasma α-linolenic, linoleic, and oleic acid levels are inversely associated with large-artery stroke and venous thromboembolism, whereas arachidonic and stearic acid levels are positively associated with these CVDs. The associations were driven by FADS1, which was also associated with other CVDs.


Assuntos
Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/genética , Ácidos Graxos Dessaturases/genética , Ácidos Graxos/sangue , Fosfolipídeos/sangue , Alelos , Ácido Araquidônico/sangue , Doenças Cardiovasculares/classificação , Análise de Dados , Predisposição Genética para Doença , Humanos , Ácido Linoleico/sangue , Análise da Randomização Mendeliana , Razão de Chances , Ácido Oleico/sangue , Polimorfismo de Nucleotídeo Único , Fatores de Proteção , Fatores de Risco , Ácidos Esteáricos/sangue , Ácido alfa-Linoleico/sangue
8.
Nutrients ; 11(10)2019 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-31590264

RESUMO

Good sources of the long-chain n-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) include cold-water fish and seafood; however, vegan diets (VGNs) do not include animal-origin foods. Typically, US omnivores obtain enough dietary EPA and DHA, but unless VGNs consume algal n-3 supplements, they rely on endogenous production of long-chain fatty acids. VGN diets have several possible concerns: (1) VGNs have high intakes of linoleic acid (LA) as compared to omnivore/non-vegetarian diets. (2) High intakes of LA competitively interfere with the endogenous conversion of alpha-linolenic acid (ALA) to EPA and DHA. (3) High somatic levels of LA/low ALA indicate a decreased ALA conversion to EPA and DHA. (4) Some, not all VGNs meet the Dietary Reference Intake Adequate Intake (DRI-AI) for dietary ALA and (5) VGN diets are high in fiber, which possibly interferes with fat absorption. Consequently, health professionals and Registered Dietitians/Registered Dietitian Nutritionists working with VGNs need specific essential fatty acid diet guidelines. The purpose of this review was: (1) to suggest that VGNs have a DRI-AI Special Consideration requirement for ALA and LA based on VGN dietary and biochemical indicators of status and (2) to provide suggestions to ensure that VGNs receive adequate intakes of LA and ALA.


Assuntos
Dieta Vegana , Ácido Linoleico/análise , Estado Nutricional , Valor Nutritivo , Recomendações Nutricionais , Ácido alfa-Linoleico/análise , Ácidos Docosa-Hexaenoicos/sangue , Ácido Eicosapentaenoico/sangue , Humanos , Ácido Linoleico/sangue , Ácido alfa-Linoleico/sangue
9.
PLoS One ; 14(9): e0222061, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31532795

RESUMO

BACKGROUND: The double-blind OMEGA-REMODEL placebo-controlled randomized trial of high-dose omega-3 fatty acids (O-3FA) post-acute myocardial infarction (AMI) reported improved cardiac remodeling and attenuation of non-infarct myocardial fibrosis. Fatty acid desaturase 2 (FADS2) gene cluster encodes key enzymes in the conversion of essential omega-3 and omega-6 fatty acids into active arachidonic (ArA) and eicosapentaenoic acids (EPA), which influence cardiovascular outcomes. METHODS AND RESULTS: We tested the hypothesis that the genotypic status of FADS2 (rs1535) modifies therapeutic response of O-3FA in post-AMI cardiac remodeling in 312 patients. Consistent with known genetic polymorphism of FADS2, patients in our cohort with the guanine-guanine (GG) genotype had the lowest FADS2 activity assessed by arachidonic acid/linoleic acid (ArA/LA) ratio, compared with patients with the adenine-adenine (AA) and adenine-guanine (AG) genotypes (GG:1.62±0.35 vs. AA: 2.01±0.36, p<0.0001; vs. AG: 1.76±0.35, p = 0.03). When randomized to 6-months of O-3FA treatment, GG patients demonstrated significant lowering of LV end-systolic volume index (LVESVi), N-terminal prohormone of brain natriuretic peptide (NT-proBNP), and galectin-3 levels compared to placebo (-4.4 vs. 1.2 ml/m2, -733 vs. -181 pg/mL, and -2.0 vs. 0.5 ng/mL; p = 0.006, 0.006, and 0.03, respectively). In contrast, patients with either AA or AG genotype did not demonstrate significant lowering of LVESVi, NT-proBNP, or galectin-3 levels from O-3FA treatment, compared to placebo. The odds ratios for improving LVESVi by 10% with O-3FA treatment was 7.2, 1.6, and 1.2 in patients with GG, AG, and AA genotypes, respectively. CONCLUSION: Genetic profiling using FADS2 genotype can predict the therapeutic benefits of O-3FA treatment against adverse cardiac remodeling during the convalescent phase of AMI. CLINICAL TRIAL REGISTRATION INFORMATION: clinicaltrials.gov Identifier: NCT00729430.


Assuntos
Ácidos Graxos Dessaturases/genética , Ácidos Graxos Ômega-3/administração & dosagem , Infarto do Miocárdio/tratamento farmacológico , Remodelação Ventricular/efeitos dos fármacos , Idoso , Ácido Araquidônico/sangue , Método Duplo-Cego , Ácidos Graxos Ômega-3/farmacologia , Feminino , Humanos , Ácido Linoleico/sangue , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/sangue , Infarto do Miocárdio/genética , Variantes Farmacogenômicos , Polimorfismo de Nucleotídeo Único , Estudos Prospectivos , Centros de Atenção Terciária , Resultado do Tratamento
10.
Artigo em Inglês | MEDLINE | ID: mdl-31492428

RESUMO

Long-chain polyunsaturated fatty acids (LCPUFAs) are important constituents of biomembranes. Observation of blood fatty acids indicated that LCPUFA biosynthesis is affected by aging and FADS polymorphisms. This study examined the effects of aging and FADS polymorphisms on LCPUFA biosynthetic capacity via direct quantification using [U-13C]linoleic acid. Healthy young (25-34 years) and elderly (65-74 years) participants were administered [U-13C]linoleate, and its metabolites were monitored for 14 days. The time of maximum plasma concentration of 13C-arachidonic acid (ARA) was 4-5 days. The area under the curve of the 13C-ARA concentration differed by FADS1 rs174547 polymorphism (TT [100%] > TC [57%] > CC [37%]). Among C allele carriers, 13C-ARA formation was 32% lower in elderly than in young participants. This is the first report to directly demonstrate that LCPUFA biosynthetic capacity is regulated by FADS1 polymorphisms and decreased by aging in FADS1 C allele carriers.


Assuntos
Envelhecimento/genética , Ácidos Graxos Dessaturases/genética , Ácidos Graxos Insaturados/biossíntese , Ácido Linoleico/administração & dosagem , Polimorfismo de Nucleotídeo Único , Adulto , Fatores Etários , Idoso , Envelhecimento/metabolismo , Alelos , Ácido Araquidônico/sangue , Área Sob a Curva , Ácidos Graxos Insaturados/sangue , Feminino , Voluntários Saudáveis , Humanos , Ácido Linoleico/sangue , Masculino
11.
Artigo em Inglês | MEDLINE | ID: mdl-31421523

RESUMO

Cardiovascular disease is a known risk factor for the development of psychiatric disorder and about 20% of patients with acute coronary syndrome (ACS) develop depression. Our previous prospective study showed that serum linoleic acid (LA) level at baseline (admission) is a risk factor for the development of psychiatric disorder 3 months later. However, it was unclear whether serum LA could predict psychiatric disorders after 3 months. Thus, we examined the effects of polyunsaturated fatty acid (PUFA) levels at ACS onset on comorbid psychiatric disorders at 6 months. The study involved a follow-up investigation of the previous prospective cohort study of ACS patients. The sample with complete participant data at 6 months post-ACS comprised 100 patients. On admission, serum n-3 and n-6 PUFA levels were measured by gas chromatography and patients were interviewed to obtain medical information. Eight patients (8%) showed psychiatric disorder at 6 months. The association between psychiatric disorder and serum PUFA concentrations at ACS onset was examined by multivariable logistic regression analysis. Psychiatric disorders were predicted by baseline serum LA level (odds ratio = 7.27, 95% confidence interval = 1.11-47.76), indicating that it is a significant risk factor for the development of psychiatric disorder at 6 months. Thus, dietary education to reduce the intake of LA-containing foods might be useful for preventing psychiatric disorder in the population at high risk for ACS. However, the prevalence of psychiatric disorder, particularly depressive disorder, may have been too low to identify significant differences in PUFA analysis.


Assuntos
Síndrome Coronariana Aguda/complicações , Transtorno Depressivo/epidemiologia , Transtorno Depressivo/etiologia , Ácidos Graxos Ômega-3/sangue , Ácido Linoleico/sangue , Adulto , Idoso , Dieta , Suplementos Nutricionais , Feminino , Seguimentos , Humanos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Prospectivos , Fatores de Risco
12.
Nutrients ; 11(7)2019 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-31331006

RESUMO

Available evidence on the associations of dietary and circulating levels of long-chain n-3 fatty acids, which have potential antiarrhythmic properties, and other fatty acids with atrial fibrillation is conflicting and limited. We conducted a Mendelian randomization study to assess the associations between plasma phospholipid fatty acid levels and atrial fibrillation. Summary-level data of atrial fibrillation were available from 65,446 cases and 522,744 non-cases included in the Atrial Fibrillation Consortium. Sixteen single-nucleotide polymorphisms associated with ten fatty acids at significance level of p < 5 × 10-8 were identified as instrumental variables from the hitherto largest genome-wide association studies for plasma fatty acids. The fixed-effects inverse-variance weighted method was used to assess the association of individual plasma fatty acids and atrial fibrillation risk. The random-effects inverse-variance weighted method, weighted median method, and Mendelian randomization (MR)-Egger method were employed as the sensitivity analyses. Genetic predisposition to higher levels of any of the ten individual fatty acids was not associated with atrial fibrillation risk.


Assuntos
Fibrilação Atrial/sangue , Ácidos Graxos/sangue , Análise da Randomização Mendeliana , Fosfolipídeos/sangue , Fibrilação Atrial/genética , Ácidos Graxos/genética , Ácidos Graxos Ômega-3/sangue , Ácidos Graxos Ômega-3/genética , Predisposição Genética para Doença/genética , Estudo de Associação Genômica Ampla , Humanos , Ácido Linoleico/sangue , Ácido Linoleico/genética , Polimorfismo de Nucleotídeo Único/genética , Fatores de Risco
13.
Arab J Gastroenterol ; 20(3): 121-126, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31272909

RESUMO

BACKGROUND AND STUDY AIMS: Evidence shows that vitamin D and cyclooxygenase type 2 (COX-2) might play role in aetiology/progression of cancer. It is suggested that antitumour effect of vitamin D depends on vitamin D-receptor (VDR) expression. Aim of the study was to determine vitamin D and polyunsaturated fatty acids in colorectal cancer patients. PATIENTS AND METHODS: A total of 39 patients with colorectal cancer (mean ±â€¯SD age: 65.5 ±â€¯6.8 years) and 25 controls (mean ±â€¯SD age: 51.0 ±â€¯6.9 years) were studied. 25-hydroxycholecalciferol-25(OH)D3 in serum was quantitatively determined by high-performance liquid chromatography (HPLC). Levels of linoleic acid (LA) and arachidonic acid (AA) of serum phospholipids were measured by gas-chromatography (GC). Expression of VDR and COX-2 in normal colonic mucosa and tumour tissue was measured by real time polymerase chain reaction (RT-PCR). RESULTS: The mean value of 25(OH)D3 was significantly lower in the colorectal cancer patients with early stages of the disease and in patients with tumour confined to the rectum compared to control group (p < 0.02, p < 0.03, respectively). The higher concentration of AA (patients with early stages of the disease) and lower concentration of LA (patients with the advanced stages of the disease) was noticed compared to the control group. For the patients with the early stages of the disease the higher mean fold change of mRNA VDR and the lower mean fold change of mRNA COX-2 was noticed (p < 0.03, p < 0.02, respectively). CONCLUSION: The assessment of vitamin D status in patients with colorectal cancer should include measurement of mRNA VDR expression in tumour tissue.


Assuntos
Neoplasias do Colo/sangue , Neoplasias do Colo/patologia , Neoplasias Retais/sangue , Neoplasias Retais/patologia , Idoso , Ácido Araquidônico/sangue , Calcifediol/sangue , Estudos de Casos e Controles , Colo , Neoplasias do Colo/metabolismo , Ciclo-Oxigenase 2/metabolismo , Progressão da Doença , Feminino , Humanos , Mucosa Intestinal/metabolismo , Ácido Linoleico/sangue , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Receptores de Calcitriol/metabolismo , Neoplasias Retais/metabolismo
14.
Circulation ; 139(21): 2422-2436, 2019 05 21.
Artigo em Inglês | MEDLINE | ID: mdl-30971107

RESUMO

BACKGROUND: Global dietary recommendations for and cardiovascular effects of linoleic acid, the major dietary omega-6 fatty acid, and its major metabolite, arachidonic acid, remain controversial. To address this uncertainty and inform international recommendations, we evaluated how in vivo circulating and tissue levels of linoleic acid (LA) and arachidonic acid (AA) relate to incident cardiovascular disease (CVD) across multiple international studies. METHODS: We performed harmonized, de novo, individual-level analyses in a global consortium of 30 prospective observational studies from 13 countries. Multivariable-adjusted associations of circulating and adipose tissue LA and AA biomarkers with incident total CVD and subtypes (coronary heart disease, ischemic stroke, cardiovascular mortality) were investigated according to a prespecified analytic plan. Levels of LA and AA, measured as the percentage of total fatty acids, were evaluated linearly according to their interquintile range (ie, the range between the midpoint of the first and fifth quintiles), and categorically by quintiles. Study-specific results were pooled using inverse-variance-weighted meta-analysis. Heterogeneity was explored by age, sex, race, diabetes mellitus, statin use, aspirin use, omega-3 levels, and fatty acid desaturase 1 genotype (when available). RESULTS: In 30 prospective studies with medians of follow-up ranging 2.5 to 31.9 years, 15 198 incident cardiovascular events occurred among 68 659 participants. Higher levels of LA were significantly associated with lower risks of total CVD, cardiovascular mortality, and ischemic stroke, with hazard ratios per interquintile range of 0.93 (95% CI, 0.88-0.99), 0.78 (0.70-0.85), and 0.88 (0.79-0.98), respectively, and nonsignificantly with lower coronary heart disease risk (0.94; 0.88-1.00). Relationships were similar for LA evaluated across quintiles. AA levels were not associated with higher risk of cardiovascular outcomes; in a comparison of extreme quintiles, higher levels were associated with lower risk of total CVD (0.92; 0.86-0.99). No consistent heterogeneity by population subgroups was identified in the observed relationships. CONCLUSIONS: In pooled global analyses, higher in vivo circulating and tissue levels of LA and possibly AA were associated with lower risk of major cardiovascular events. These results support a favorable role for LA in CVD prevention.


Assuntos
Ácido Araquidônico/sangue , Doenças Cardiovasculares/sangue , Dieta Saudável , Gorduras na Dieta/sangue , Ácido Linoleico/sangue , Prevenção Primária/métodos , Comportamento de Redução do Risco , Idoso , Biomarcadores/sangue , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/mortalidade , Doenças Cardiovasculares/prevenção & controle , Gorduras na Dieta/administração & dosagem , Feminino , Humanos , Ácido Linoleico/administração & dosagem , Masculino , Pessoa de Meia-Idade , Valor Nutritivo , Estudos Observacionais como Assunto , Fatores de Proteção , Recomendações Nutricionais , Medição de Risco , Fatores de Risco
15.
JPEN J Parenter Enteral Nutr ; 43(6): 717-725, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30900274

RESUMO

BACKGROUND: Intravenous fish oil (FO) treats pediatric intestinal failure-associated liver disease (IFALD). There are concerns that a lipid emulsion composed of ω-3 fatty acids will cause an essential fatty acid deficiency (EFAD). This study's objective was to quantify the risk for abnormal fatty acid concentrations in children treated with FO. METHODS: Inclusion criteria for this prospective study were children with intestinal failure. Intravenous soybean oil (SO) was replaced with FO for no longer than 6 months. Serum fatty acids were analyzed using linear and logistic models, and compared with age-based norms to determine the percentage of subjects with low and high concentrations. RESULTS: Subjects (n = 17) started receiving FO at a median of 3.6 months (interquartile range 2.4-9.6 months). Over time, α-linolenic, linoleic, arachidonic, and Mead acid decreased, whereas docosahexaenoic and eicosapentaenoic acid increased (P < 0.001 for all). Triene-tetraene ratios remained unchanged (P = 1). Although subjects were 1.8 times more likely to develop a low linoleic acid while receiving FO vs SO (95% CI: 1.4-2.3, P < 0.01), there was not a significant risk for low arachidonic acid. Subjects were 1.6 times more likely to develop high docosahexaenoic acid while receiving FO vs SO; however, this was not significant (95% CI: 0.9-2.6, P = 0.08). CONCLUSION: In this cohort of parenteral nutrition-dependent children, switching from SO to FO led to a decrease in essential fatty acid concentrations, but an EFAD was not evident. Low and high levels of fatty acids developed. Further investigation is needed to clarify if this is clinically significant.


Assuntos
Emulsões Gordurosas Intravenosas/administração & dosagem , Ácidos Graxos Essenciais/deficiência , Ácidos Graxos/sangue , Óleos de Peixe/efeitos adversos , Enteropatias/complicações , Hepatopatias/terapia , Ácido 8,11,14-Eicosatrienoico/análogos & derivados , Ácido 8,11,14-Eicosatrienoico/sangue , Ácido Araquidônico/sangue , Ácidos Docosa-Hexaenoicos/sangue , Ácido Eicosapentaenoico/sangue , Ácidos Graxos Ômega-3/administração & dosagem , Feminino , Óleos de Peixe/administração & dosagem , Humanos , Lactente , Ácido Linoleico/sangue , Hepatopatias/etiologia , Masculino , Nutrição Parenteral , Estudos Prospectivos , Óleo de Soja/administração & dosagem
16.
Nutrients ; 11(3)2019 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-30845776

RESUMO

The growing interest in potential health effects of long-chain polyunsaturated fatty acids (PUFAs) makes it important to evaluate the method used to assess the fatty acid intake in nutrition research studies. We aimed to validate the questionnaire-based dietary intake of selected PUFAs: eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), α-linolenic acid (ALA), linoleic acid (LA), and arachidonic acid (AA) within the Danish National Birth Cohort (DNBC), by comparing 345 women's reported intake with concentration of plasma biomarkers. The applied questionnaire- and biomarker data reflect dietary intake from around the same time point in mid-pregnancy and relationships were investigated by use of Pearson and Spearman correlation and linear regression statistics. We demonstrated moderate but consistent adjusted correlations between dietary intake estimates and the corresponding plasma biomarker concentrations (differences in plasma concentration per 100 mg/day greater intake of 0.05 (95% CI: 0.02; 0.08)) and 0.05 (95% CI: 0.01; 0.08) percentage of total plasma fatty acids for EPA and DHA, respectively). The associations strengthened when restricting the analyses to women with ALA intake below the median intake. We found a weak correlation between the dietary intake of ALA and its plasma biomarker with a difference in plasma concentration of 0.07 (95% CI: 0.03; 0.10) percent of total plasma fatty acids per 1 g/day greater intake, while the dietary intake of LA and AA did not correlate with their corresponding biomarkers.


Assuntos
Inquéritos sobre Dietas/normas , Dieta/estatística & dados numéricos , Gorduras Insaturadas na Dieta/análise , Ácidos Graxos Insaturados/sangue , Testes para Triagem do Soro Materno/estatística & dados numéricos , Adulto , Biomarcadores/sangue , Dinamarca , Inquéritos sobre Dietas/métodos , Ácidos Docosa-Hexaenoicos/sangue , Ingestão de Alimentos , Ácido Eicosapentaenoico/sangue , Feminino , Humanos , Modelos Lineares , Ácido Linoleico/sangue , Gravidez , Reprodutibilidade dos Testes , Estatísticas não Paramétricas , Ácido alfa-Linoleico/sangue
17.
J Affect Disord ; 249: 301-306, 2019 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-30797122

RESUMO

BACKGROUND: Previous studies on health effects of trans fatty acids (TFA) have focused mainly on cardiovascular health. Little is known about the association of TFA with brain or mental health. In this study, we examined the associations of objectively-measured plasma TFA concentrations with depression in a large population-based cross-sectional study among U.S. adults. METHODS: We included 2136 non-pregnant participants aged 20 years or older from the National Health and Nutrition Examination Survey 2009-2010. Four major TFAs, including palmitelaidic acid (C16:1n-7t), elaidic acid (C18:1n-9t), vaccenic acid (C18:1n-7t), and linoelaidic acid (C18:2n-6t, 9t), were measured in fasting plasma using gas chromatography/mass spectrometry. Depressive symptoms were assessed using the validated Patient Health Questionnaire-9. RESULTS: Participants with depressive symptoms had a higher plasma concentration of total TFA compared with those without depressive symptoms (6.6 vs 6.0 µmol/g lipids, P = 0.046). After adjustment for other major risk factors, the odds ratio (OR) of depressive symptoms comparing the highest with lowest tertile of TFAs was 1.44 (95% CI, 0.86-2.39) for total TFAs (P for trend 0.15). For each individual type of TFA, the corresponding OR was 1.78 (1.03-3.07) for elaidic acid (P for trend 0.049), 1.23 (0.76-2.00) for linoelaidic acid (P for trend 0.37), 1.19 (0.75-1.87) for palmitelaidic acid (P for trend 0.46), and 1.20 (0.75-1.94) for vaccenic acid (P for trend 0.43). LIMITATIONS: The cross-sectional study design limited causal inferences of the findings. CONCLUSIONS: In a nationally representative population, plasma elaidic acid, a major trans fatty acid, was positively associated with depressive symptoms in adults. A positive but non-significant association of depressive symptoms was observed for total TFAs, linolelaidic acid, palmitelaidic acid, and vaccenic acid.


Assuntos
Depressão/sangue , Ácidos Oleicos/sangue , Adulto , Idoso , Estudos Transversais , Depressão/epidemiologia , Jejum , Ácidos Graxos Monoinsaturados/sangue , Feminino , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Ácido Linoleico/sangue , Masculino , Pessoa de Meia-Idade , Inquéritos Nutricionais , Questionário de Saúde do Paciente , Fatores de Risco , Estados Unidos/epidemiologia
18.
Nutr Metab Cardiovasc Dis ; 29(4): 343-350, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30718141

RESUMO

BACKGROUND AND AIMS: Population-based studies often use plasma fatty acids (FAs) as objective indicators of FA intake, especially for n-3 FA and linoleic acid (LA). The relation between dietary and circulating FA in cardiometabolic patients is largely unknown. We examined whether dietary n-3 FA and LA were reflected in plasma lipid pools in post-myocardial infarction (MI) patients. METHODS AND RESULTS: Patients in Alpha Omega Cohort filled out a 203-item food-frequency questionnaire from which eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), alpha-linolenic acid (ALA), and LA intake were calculated. Circulating individual FA (% total FA) were assessed in cholesteryl esters (CE; n = 4066), phospholipids (PL; n = 838), and additionally in total plasma for DHA and LA (n = 739). Spearman correlation coefficients (rs) were calculated for dietary vs. circulating FA. Circulating FA were also compared across dietary FA quintiles, overall and in subgroups by sex, obesity, diabetes, statin use, and high alcohol intake. Patients were on average 69 years old and 79% was male. Moderate correlations between dietary and circulating levels were observed for EPA (rs∼0.4 in CE and PL) and DHA (rs ∼0.5 in CE and PL, ∼0.4 in total plasma), but not for ALA (rs ∼0.0). Weak correlations were observed for LA (rs 0.1 to 0.2). Plasma LA was significantly lower in statin users and in patients with a high alcohol intake. CONCLUSIONS: In post-MI patients, dietary EPA and DHA were well reflected in circulating levels. This was not the case for LA, which may partly be influenced by alcohol use and statins.


Assuntos
Ácidos Docosa-Hexaenoicos/sangue , Ácido Eicosapentaenoico/sangue , Comportamento Alimentar , Ácido Linoleico/sangue , Infarto do Miocárdio/sangue , Idoso , Idoso de 80 Anos ou mais , Consumo de Bebidas Alcoólicas/sangue , Biomarcadores/sangue , Estudos Transversais , Registros de Dieta , Feminino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/tratamento farmacológico , Países Baixos , Estudos Prospectivos
19.
Am J Clin Nutr ; 109(1): 165-175, 2019 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-30624587

RESUMO

Background: The health benefits of substituting dietary polyunsaturated fatty acids (PUFAs) for saturated fatty acids are well known. However, limited information exists on how the response to dietary intake of linoleic acid (LA; 18:2n-6) is modified by polymorphisms in the fatty acid desaturase (FADS) gene cluster. Objectives: The aim of the current study was to test the hypothesis that the FADS1 rs174550 genotype modifies the effect of dietary LA intake on the fatty acid composition of plasma lipids, fasting glucose, and high-sensitivity C-reactive protein (hsCRP). Methods: Associations were investigated between genotype, plasma PUFAs, fasting glucose, and hsCRP concentrations in the cross-sectional, population-based Metabolic Syndrome in Men cohort (n = 1337). In addition, 62 healthy men from the cohort who were homozygotes for the TT or CC genotype of the FADS1 rs174550 were recruited to a 4-wk intervention (FADSDIET) with an LA-enriched diet. The fatty acid composition of plasma PUFAs and concentrations of plasma fasting glucose, serum hsCRP, and plasma lipid mediators (eicosanoids and related analogs) were measured at the beginning and end of the 4-wk intervention period. Results: In the FADSDIET trial, the plasma LA proportion increased in both genotype groups in response to an LA-enriched diet. Responses in concentrations of serum hsCRP and plasma fasting glucose and the proportion of arachidonic acid (20:4n-6) in plasma phospholipids and cholesteryl esters differed between genotype groups (interaction of diet × genotype, P < 0.05). In TT homozygous subjects, plasma eicosanoid concentrations correlated with the arachidonic acid proportion in plasma and with hsCRP (r = 0.4-0.7, P < 0.05), whereas in the CC genotype there were no correlations. Conclusions: Our findings show that the FADS1 genotype modifies metabolic responses to dietary LA. The emerging concept that personalized dietary counseling should be modified by the FADS1 genotype needs to be tested in larger randomized trials. The study was registered at clinicaltrials.gov as NCT02543216.


Assuntos
Dieta , Ácidos Graxos Dessaturases/genética , Genótipo , Inflamação/induzido quimicamente , Ácido Linoleico/administração & dosagem , Idoso , Glicemia/análise , Proteína C-Reativa/análise , Estudos Transversais , Jejum , Ácidos Graxos , Ácidos Graxos Ômega-6/sangue , Ácidos Graxos Insaturados/sangue , Finlândia , Homozigoto , Humanos , Inflamação/sangue , Inflamação/genética , Ácido Linoleico/sangue , Lipídeos/sangue , Masculino , Síndrome Metabólica , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único/genética
20.
Nutrients ; 12(1)2019 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-31905662

RESUMO

The prevalence of obesity and dyslipidemia has increased worldwide. The role of trace elements in the pathogenesis of these conditions is not well understood. This study examines the relationship between dietary zinc (Zn) intake and plasma concentrations of Zn, copper (Cu) and iron (Fe) with lipid profile indicators, fatty acid composition in plasma phospholipids and desaturase enzyme activities in a dyslipidemic population. The role of the newly proposed biomarker of Zn status, the linoleic:dihomo-gama-linolenic acid (LA:DGLA) ratio, in predicting Zn status of dyslipidemic subjects has been explored. The study included 27 dyslipidemic adults, 39-72 years old. Trace elements were determined using atomic absorption spectrometry and fatty acid composition by a liquid gas chromatography. Desaturase activities were calculated from product-precursor fatty acid ratios. Dietary data were obtained using 24 h recall questionnaires. Insufficient dietary intake of Zn, low plasma Zn concentrations and an altered Cu:Zn ratio is related to modified fatty acid profile in subjects with dyslipidemia. Plasma Zn status was associated with obesity. There was no correlation between dietary Zn intake and plasma Zn status. The LA:DGLA ratio was inversely linked to dietary Zn intake. Cu, in addition to Zn, may directly or indirectly, affect the activity of desaturase enzymes.


Assuntos
Dislipidemias/sangue , Ácidos Graxos Dessaturases/metabolismo , Ácidos Graxos/sangue , Zinco/administração & dosagem , Zinco/sangue , Adulto , Idoso , Biomarcadores/sangue , Cobre/sangue , Estudos Transversais , Dislipidemias/enzimologia , Comportamento Alimentar , Feminino , Humanos , Ferro/sangue , Ácido Linoleico/sangue , Masculino , Pessoa de Meia-Idade , Estado Nutricional , Ensaios Clínicos Controlados Aleatórios como Assunto , Inquéritos e Questionários , Zinco/deficiência , Ácido gama-Linolênico/sangue
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