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1.
PLoS Med ; 16(9): e1002910, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31518348

RESUMO

BACKGROUND: Despite dietary recommendations of polyunsaturated fatty acids (PUFAs) for cardiometabolic health, n-3 and n-6 PUFAs and their interplay in relation to diabetes risk remain debated. Importantly, data among pregnant women are scarce. We investigated individual plasma phospholipid n-3 and n-6 PUFAs in early to midpregnancy in relation to subsequent risk of gestational diabetes mellitus (GDM). METHODS AND FINDINGS: Within the National Institute of Child Health and Human Development (NICHD) Fetal Growth Studies-Singleton Cohort (n = 2,802), individual plasma phospholipid n-3 and n-6 PUFAs levels were measured at gestational weeks (GWs) 10-14, 15-26, 23-31, and 33-39 among 107 GDM cases (ascertained on average at GW 27) and 214 non-GDM controls. Conditional logistic regression was used, adjusting for major risk factors for GDM. After adjusting for covariates, individual n-3 eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA) were inversely correlated with insulin-resistance markers, whereas individual n-6 dihomo-gamma-linolenic acid (DGLA) was positively correlated with insulin-resistance markers. At GW 15-26, a standard deviation (SD) increase in total n-3 PUFAs and individual n-3 DPA was associated with a 36% (adjusted odds ratio 0.64; 95% CI 0.42-0.96; P = 0.042) and 33% (0.67; 95% CI 0.45-0.99; P = 0.047) lower risk of GDM, respectively; however, the significance did not persist after post hoc false-discovery rate (FDR) correction (FDR-corrected P values > 0.05). Associations between total n-6 PUFAs and GDM were null, whereas associations with individual n-6 PUFAs were differential. Per SD increase, gamma-linolenic acid (GLA) at GWs 10-14 and DGLA at GWs 10-14 and 15-26 were significantly associated with a 1.40- to 1.95-fold higher risk of GDM, whereas docosatetraenoic acid (DTA) at GW 15-26 was associated with a 45% (0.55; 95% CI 0.37-0.83) lower risk of GDM (all FDR-corrected P values < 0.05). Null associations were observed for linoleic acid (LA) in either gestational window in relation to risk of GDM. Women with high (≥median) n-3 PUFAs and low (

Assuntos
Glicemia/metabolismo , Diabetes Gestacional/sangue , Ácidos Graxos Ômega-3/sangue , Ácidos Graxos Ômega-6/sangue , Fenômenos Fisiológicos da Nutrição Materna , Estado Nutricional , Fosfolipídeos/sangue , Adolescente , Adulto , Biomarcadores/sangue , Estudos de Casos e Controles , Diabetes Gestacional/diagnóstico , Diabetes Gestacional/etiologia , Feminino , Idade Gestacional , Humanos , Insulina/sangue , Resistência à Insulina , Estudos Longitudinais , Gravidez , Estudos Prospectivos , Medição de Risco , Fatores de Risco , Adulto Jovem
2.
Nutrients ; 11(9)2019 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-31540208

RESUMO

Anorexia nervosa (AN) is a psychiatric disorder affected by psychological, environmental, and biological factors. Individuals with AN avoid high-fat, high-calorie diets and have shown abnormal metabolism of fatty acids (FAs), which are essential for brain and cognitive/neuropsychiatric health. To clarify the relationship between FAs and AN, fasting and postprandial plasma FAs in AN patients and age-matched control women were analyzed via mass-spectrometry. Clinical phenotypes were assessed using Becker Anxiety Inventory and Becker Depression Inventory. AN patients and controls exhibited different FA signatures at both fasting and postprandial timepoints. Lauric acid, eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and alpha-linoleic acid (ALA) were higher in AN than in controls (lauric acid: 15,081.6 ± 14,970.2 vs. 8257.4 ± 4740.2 pmol/mL; ALA at fasting: 2217.7 ± 1587.6 vs. 1087.9 ± 821.2 pmol/mL; ALA at postprandial: 1830.9 ± 1115.6 vs. 1159.4 ± 664.7 pmol/mL. EPA: 33,788.3 ± 17,487.5 vs. 22,860.6 ± 12,642.4 pmol/mL; DPA: 32,664.8 ± 16,215.0 vs. 20,969.0 ± 12,350.0 pmol/mL. FDR-adjusted p-values < 0.05). Food intake and AN status modified the correlations of FAs with body mass index (BMI), depression, and anxiety. Desaturases SCD-18 and D6D showed lower activities in AN compared to controls. Altered FA signature, specifically correlations between elevated n-3 FAs and worsened symptoms, illustrate metabolic underpinnings in AN. Future studies should investigate the mechanisms by which FA dysregulation, specifically elevated n-3 FAs, affects AN risk and outcome.


Assuntos
Anorexia Nervosa/sangue , Ingestão de Alimentos/fisiologia , Ácidos Graxos/sangue , Adulto , Anorexia Nervosa/psicologia , Ansiedade/sangue , Depressão/sangue , Ácido Eicosapentaenoico/sangue , Jejum , Ácidos Graxos Dessaturases , Ácidos Graxos Ômega-3/sangue , Ácidos Graxos Ômega-6/sangue , Ácidos Graxos Insaturados/sangue , Feminino , Humanos , Período Pós-Prandial
3.
Nutrients ; 11(6)2019 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-31167445

RESUMO

Fatty acids (FAs) are crucial in child growth and development. In Uganda, antiretroviral therapy (ART) has drastically reduced perinatal human immunodeficiency virus (HIV) infection of infants, however, the interplay of FAs, ART, and HIV in relation to child growth is not well understood. To investigate this, serum was collected from 240 children between 6-10 years old in Uganda and analyzed for FAs using gas-chromatography mass-spectrometry. HIV status and anthropometric measurements were taken, and relationships with FAs were assessed. No significant differences in growth parameters or serum FAs were found between HIV uninfected children with and without exposure to ART. HIV positive children had significantly lower height-for-age-z-scores (HAZ) than uninfected children (p < 0.001). HIV-positive children had higher arachidonic acid than uninfected children (p = 0.003). Total omega-6 FAs were significantly associated with HAZ regardless of HIV status (p = 0.035). Mean total omega-3 FAs (2.90%) were low in this population compared to other cohorts in Africa. These results provide reference serum FA values for 6-10-year-old children in Uganda and may be used to inform lipid supplementation programs to promote child growth. Future studies should investigate the relationships between child growth trajectories in relation to HIV status and serum FAs.


Assuntos
Desenvolvimento Infantil , Ácidos Graxos Ômega-6/sangue , Infecções por HIV/sangue , Criança , Estudos Transversais , Feminino , Infecções por HIV/epidemiologia , Humanos , Masculino , Uganda/epidemiologia
4.
Dig Dis Sci ; 64(7): 1878-1892, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31076986

RESUMO

BACKGROUND: Alcohol-related liver disease is one of the most prevalent chronic liver diseases worldwide. Mechanisms involved in the pathogenesis of alcohol-related liver disease are not well understood. Oxylipins play a crucial role in numerous biological processes and pathological conditions. Nevertheless, oxylipins are not well studied in alcohol-related liver disease. AIMS: (1) To characterize the patterns of bioactive ω-3 and ω-6 polyunsaturated fatty acid metabolites in alcohol use disorder and alcoholic hepatitis patients and (2) to identify associations of serum oxylipins with clinical parameters in patients with alcohol-related liver disease. METHODS: We performed a comprehensive liquid chromatography with tandem mass spectrometry (LC-MS/MS) analysis of serum and fecal oxylipins derived from ω-6 arachidonic acid, ω-3 eicosapentaenoic acid, and docosahexaenoic acid in a patient cohort with alcohol-related liver disease. RESULTS: Our results show profound alterations in the serum oxylipin profile of patients with alcohol use disorder and alcoholic hepatitis compared to nonalcoholic controls. Spearman correlation of the oxylipins with clinical parameters shows a link between different serum oxylipins and intestinal permeability, aspartate aminotransferase, bilirubin, albumin, international normalized ratio, platelet count, steatosis, fibrosis and model for end-stage liver disease score. Especially, higher level of serum 20-HETE was significantly associated with decreased albumin, increased hepatic steatosis, polymorphonuclear infiltration, and 90-day mortality. CONCLUSIONS: Patients with alcohol-related liver disease have different oxylipin profiles. Future studies are required to confirm oxylipins as disease biomarker or to connect oxylipins to disease pathogenesis.


Assuntos
Alcoolismo/sangue , Ácidos Graxos Ômega-3/sangue , Ácidos Graxos Ômega-6/sangue , Fezes/química , Hepatite Alcoólica/sangue , Oxilipinas/sangue , Adulto , Idoso , Alcoolismo/diagnóstico , Biomarcadores/sangue , Cromatografia Líquida de Alta Pressão , Cromatografia de Fase Reversa , Feminino , Hepatite Alcoólica/diagnóstico , Humanos , Masculino , Metabolômica/métodos , Pessoa de Meia-Idade , Espectrometria de Massas por Ionização por Electrospray , Espectrometria de Massas em Tandem
5.
Nutrients ; 11(4)2019 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-31003520

RESUMO

While studies revealed that the omega-3 polyunsaturated fatty acids (n-3 PUFA) and their mediators would be able to regulate several biological processes involved into the development of postpartum depression (PPD), evidence from observational studies remains mixed. The aim of the present study was to investigate the association between maternal erythrocyte n-3 PUFA, measured in early pregnancy, and the risk of PPD. A Belgian cohort of 72 healthy women was screened. Erythrocyte fatty acids were analysed using gas chromatography. PPD was assessed using the Bromley Postnatal Depression Scale by phone interview one year after delivery. We observed a significant negative association between docosahexaenoic acid (DHA) levels and the risk of postpartum depression in the adjusted model (p = 0.034). Higher n-6/n-3 and arachidonic acid (AA)/eicosapentaenoic acid (EPA) ratios were significantly associated with an increased odds of PPD (p = 0.013 and p = 0.043, respectively). Women with an omega-3 index <5% had a 5-fold increased risk of depressive episode than did those with an omega-3 index ≥5% (OR 5.22 (95%CI 1.24-21.88)). A low n-3 PUFA status, alone and combined with high n-6 PUFA status, in early pregnancy was associated with a greater risk of PPD. Management of maternal n-3 PUFA deficiency can be a simple, safe and cost-effective strategy for the prevention of this major public health issue.


Assuntos
Depressão Pós-Parto/sangue , Depressão Pós-Parto/epidemiologia , Ácidos Graxos Ômega-3/sangue , Ácidos Graxos Ômega-6/sangue , Adulto , Bélgica/epidemiologia , Biomarcadores , Estudos de Coortes , Feminino , Humanos , Gravidez , Estudos Prospectivos , Fatores de Risco , Adulto Jovem
6.
Mol Nutr Food Res ; 63(7): e1800990, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30702198

RESUMO

SCOPE: Some studies suggest that a high dietary intake of omega-6 fatty acids is pro-inflammatory. However, whether omega-6 fatty acids actually cause pathogenic inflammation in humans is debated. Therefore, the associations between expression of immunology-related genes in peripheral blood mononuclear cells (PBMCs) and serum total omega-6 PUFA status are investigated. METHODS AND RESULTS: Serum fatty acid profile and expression of 460 immunology-related genes in PBMCs from 58 healthy children (6-13 years) is measured, and examined the expression differences between children with high or low total omega-6 PUFA status (upper vs lower tertile). Taken together, both univariate analyses and integrated omics analyses support that while high omega-6 PUFA level associated with higher expressing of genes related to innate immune responses, it also associated with lower expression of several genes related to adaptive immune responses. CONCLUSION: Omega-6 PUFA status associated both positively and negatively with expression of specific immunology-related genes in PBMCs in healthy children. The results may suggest a nuanced role for omega-6 fatty acids in the interphase of lipids and inflammation, and warrants further examination in gene-environment studies and randomized controlled trials.


Assuntos
Imunidade Adaptativa/genética , Ácidos Graxos Ômega-6/sangue , Expressão Gênica , Imunidade Inata/genética , Leucócitos Mononucleares/fisiologia , Adolescente , Criança , Estudos Transversais , Ácidos Graxos Ômega-6/genética , Feminino , Expressão Gênica/imunologia , Humanos , Leucócitos Mononucleares/imunologia , Masculino
7.
Osteoporos Int ; 30(5): 1071-1078, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30719549

RESUMO

The plasma n-3 fatty acid level was 26.2% lower in patients with osteoporotic hip fracture than in those with osteoarthritis. In all patients, n-3 fatty acid was positively associated with bone mineral density and inversely associated with tartrate-resistant acid phosphatase-5b level in bone marrow aspirates, reflecting the bone microenvironment. INTRODUCTION: Despite the potential beneficial role of n-3 fatty acid (FA) on bone metabolism, the specific mechanisms underlying these effects in humans remain unclear. Here, we assessed whether the plasma n-3 level, as an objective indicator of its status, is associated with osteoporosis-related phenotypes and bone-related markers in human bone marrow (BM) samples. METHODS: This was a case-control and cross-sectional study conducted in a clinical unit. n-3 FA in the blood and bone biochemical markers in the BM aspirates were measured by gas chromatography/mass spectrometry and immunoassay, respectively. BM fluids were collected from 72 patients who underwent hip surgery because of either osteoporotic hip fracture (HF; n = 28) or osteoarthritis (n = 44). RESULTS: After adjusting for confounders, patients with HF had 26.2% lower plasma n-3 levels than those with osteoarthritis (P = 0.006), and each standard deviation increment in plasma n-3 was associated with a multivariate-adjusted odds ratio of 0.40 for osteoporotic HF (P = 0.010). In multivariate analyses including all patients, a higher plasma n-3 level was associated with higher bone mass at the lumbar spine (ß = 0.615, P = 0.002) and total femur (ß = 0.244, P = 0.045). Interestingly, the plasma n-3 level was inversely associated with the tartrate-resistant acid phosphatase-5b level (ß = - 0.633, P = 0.023), but not with the bone-specific alkaline phosphatase level, in BM aspirates. CONCLUSIONS: These findings provide clinical evidence that n-3 FA is a potential inhibitor of osteoclastogenesis that favors human bone health.


Assuntos
Densidade Óssea/fisiologia , Ácidos Graxos Ômega-3/sangue , Fraturas do Quadril/fisiopatologia , Fraturas por Osteoporose/fisiopatologia , Fosfatase Ácida Resistente a Tartarato/metabolismo , Idoso , Idoso de 80 Anos ou mais , Medula Óssea/metabolismo , Reabsorção Óssea/fisiopatologia , Estudos de Casos e Controles , Estudos Transversais , Ácidos Graxos Ômega-3/fisiologia , Ácidos Graxos Ômega-6/sangue , Feminino , Fêmur/fisiopatologia , Fraturas do Quadril/sangue , Humanos , Vértebras Lombares/fisiopatologia , Masculino , Fraturas por Osteoporose/sangue
8.
Nutrients ; 11(2)2019 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-30744123

RESUMO

Lipoprotein apheresis reliably reduces low-density lipoprotein (LDL) cholesterol in patients with atherosclerotic disease and therapy-refractory hypercholesterolemia or elevated lipoprotein (a) (Lp(a)). Besides lowering lipoproteins and triglycerides, apheresis also decreases levels of essential omega-6 and omega-3 polyunsaturated fatty acids (n-6 and n-3 PUFAs) in blood plasma. In contrast, heparin-induced extracorporeal low-density lipoprotein precipitation (HELP) lipid apheresis might increase the formation of potentially pro-inflammatory and pro-thrombotic lipid mediators derived from n-6 and n-3 PUFAs. The study presented here analyzed lipid mediator profiles in the plasma of patients with hyperlipidemia treated by one of three different apheresis methods, either HELP, direct absorption (DA), or membrane filtration (MDF), in a direct pre- and post-apheresis comparison. Using gas chromatography and liquid chromatography tandem mass spectrometry (LC-MS/MS) we were able to analyze fatty acid composition and the formation of lipid mediators called oxylipins. Our data illustrate-particularly in HELP-treated patients-significant decreases of essential omega-6 and omega-3 polyunsaturated fatty acids in blood plasma but significant increases of PUFA-derived lipoxygenase-, as well as cyclooxygenase- and cytochrome P450-derived lipid mediators. Given that n-3 PUFAs in particular are presumed to be cardioprotective and n-3 PUFA-derived lipid mediators might limit inflammatory reactions, these data indicate that n-3 PUFA supplementation in the context of lipid apheresis treatment might have additional benefits through apheresis-triggered protective n-3 PUFA-derived lipid mediators.


Assuntos
Remoção de Componentes Sanguíneos/métodos , Ácidos Graxos Ômega-3/isolamento & purificação , Ácidos Graxos Ômega-6/isolamento & purificação , Lipoproteínas LDL/isolamento & purificação , Remoção de Componentes Sanguíneos/efeitos adversos , Cromatografia Líquida , Ácidos Graxos Ômega-3/sangue , Ácidos Graxos Ômega-6/sangue , Feminino , Cromatografia Gasosa-Espectrometria de Massas , Heparina , Humanos , Lipoproteínas LDL/sangue , Masculino , Pessoa de Meia-Idade , Espectrometria de Massas em Tandem
9.
PLoS One ; 14(1): e0211537, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30703151

RESUMO

BACKGROUND: Liver cirrhosis is associated with profound immunodysfunction, i.e. a parallel presence of chronic systemic inflammation and immunosuppression, which can result in acute-on-chronic liver failure (ACLF). Omega-3 fatty acids are precursors of pro-resolving mediators and support the resolution of inflammation. OBJECTIVE: The aim of this study was to determine plasma levels of omega-3 fatty acids in patients with liver cirrhosis and ACLF. METHODS: Patients with liver cirrhosis with and without ACLF were enrolled in a prospective cohort study and analyzed post-hoc for the present sub-study. Clinical data and biomaterials were collected at baseline and at day 7, 28 and after 3 months of follow-up. Plasma concentrations of arachidonic acid (ARA) and docosahexaenoic acid (DHA), which represent key omega-6 and -3 fatty acids, respectively, were quantified and associated with markers of systemic inflammation and severity of liver cirrhosis. RESULTS: A total of 117 patients were included in the present analyses. Of those, 26 (22.2%), 51 (43.6%) and 40 (34.2%) patients had compensated or decompensated liver cirrhosis, and ACLF. Plasma levels of ARA and DHA were similar in patients with compensated cirrhosis, decompensated cirrhosis, and ACLF. Furthermore, no significant association between plasma ARA or DHA and C-reactive protein or peripheral blood leukocytes were observed (P>0.05). CONCLUSION: In our study plasma levels of key omega-3 and omega-6 fatty acid are neither associated with the severity of liver cirrhosis nor with liver-cirrhosis-associated systemic inflammation.


Assuntos
Insuficiência Hepática Crônica Agudizada/diagnóstico , Biomarcadores/sangue , Ácidos Graxos Ômega-3/sangue , Ácidos Graxos Ômega-6/sangue , Inflamação/diagnóstico , Cirrose Hepática/complicações , Insuficiência Hepática Crônica Agudizada/sangue , Insuficiência Hepática Crônica Agudizada/etiologia , Feminino , Humanos , Inflamação/sangue , Inflamação/etiologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos
10.
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
11.
An Pediatr (Barc) ; 91(2): 88-95, 2019 Aug.
Artigo em Espanhol | MEDLINE | ID: mdl-30660389

RESUMO

INTRODUCTION: Cognitive impairment is a common consequence of epilepsy in children. This study aimed to assess the ratio of omega-6 to omega-3 fatty acid levels and its impact on cognitive function in children with idiopathic epilepsy. PATIENTS AND METHODS: We performed a case-control study in 30 children with idiopathic epilepsy and 20 healthy children. We measured levels of alpha-linolenic acid (omega-3) and linoleic acid (omega-6) by means of gas-liquid chromatography. We assessed cognitive function with the Arabic version of the fourth edition of the Stanford-Binet test and the P300 component of event-related potentials. All children had an intelligent quotient greater than 70. RESULTS: Children with epilepsy had lower levels of omega-3 and higher levels of omega-6 fatty acids and an abnormal omega-6/omega-3 ratio compared to non-epileptic children. We found a significant positive correlation of serum omega-3 levels and a significant negative correlation of serum omega-6 levels with cognitive function scores and P300 latency in children with epilepsy. CONCLUSION: Children with epilepsy have abnormal ratios of omega-6 to omega-3 fatty acid serum levels, which is associated with impaired cognitive function in these children.


Assuntos
Disfunção Cognitiva/etiologia , Epilepsia/complicações , Ácidos Graxos Ômega-3/sangue , Ácidos Graxos Ômega-6/sangue , Adolescente , Estudos de Casos e Controles , Criança , Pré-Escolar , Cognição/fisiologia , Disfunção Cognitiva/sangue , Epilepsia/sangue , Feminino , Humanos , Masculino
12.
Molecules ; 24(2)2019 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-30669503

RESUMO

Few high-performance liquid chromatography⁻tandem mass spectrometry (LC-MS/MS) methods have been developed for the full quantitation of fatty acids from human plasma without derivatization. Therefore, we propose a method that requires fewer sample preparation steps, which can be used for the quantitation of several polyunsaturated fatty acids in human plasma. The method offers rapid, accurate, sensitive, and simultaneous quantification of omega 3 (α-linolenic, eicosapentaenoic, and docosahexaenoic acids) and omega 6 fatty acids (arachidonic and linoleic acids) using high-performance LC-MS/MS. The selected fatty acids were analysed in lipid extracts from both free and total forms. Chromatographic separation was achieved using a reversed phase C18 column with isocratic flow using ammonium acetate for improving negative electrospray ionization (ESI) response. Mass detection was performed in multiple reaction monitoring (MRM) mode, and deuterated internal standards were used for each target compound. The limits of quantification were situated in the low nanomolar range, excepting linoleic acid, for which the limit was in the high nanomolar range. The method was validated according to the U.S. Department of Health and Human Services guidelines, and offers a fast, sensitive, and reliable quantification of selected omega 3 and 6 fatty acids in human plasma.


Assuntos
Bioensaio/métodos , Ácidos Graxos Ômega-3/sangue , Ácidos Graxos Ômega-6/sangue , Cromatografia Líquida de Alta Pressão/métodos , Ácidos Graxos Ômega-3/metabolismo , Ácidos Graxos Ômega-6/metabolismo , Humanos , Limite de Detecção , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Espectrometria de Massas por Ionização por Electrospray/métodos , Espectrometria de Massas em Tandem/métodos
13.
Nutr Neurosci ; 22(7): 474-487, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29215971

RESUMO

OBJECTIVES: We investigated whether a Mediterranean-style diet (MedDiet) supplemented with fish oil can improve mental health in adults suffering depression. METHODS: Adults with self-reported depression were randomized to receive fortnightly food hampers and MedDiet cooking workshops for 3 months and fish oil supplements for 6 months, or attend social groups fortnightly for 3 months. Assessments at baseline, 3 and 6 months included mental health, quality of life (QoL) and dietary questionnaires, and blood samples for erythrocyte fatty acid analysis. RESULTS: n = 152 eligible adults aged 18-65 were recruited (n = 95 completed 3-month and n = 85 completed 6-month assessments). At 3 months, the MedDiet group had a higher MedDiet score (t = 3.95, P < 0.01), consumed more vegetables (t = 3.95, P < 0.01), fruit (t = 2.10, P = 0.04), nuts (t = 2.29, P = 0.02), legumes (t = 2.41, P = 0.02) wholegrains (t = 2.63, P = 0.01), and vegetable diversity (t = 3.27, P < 0.01); less unhealthy snacks (t = -2.10, P = 0.04) and red meat/chicken (t = -2.13, P = 0.04). The MedDiet group had greater reduction in depression (t = -2.24, P = 0.03) and improved mental health QoL scores (t = 2.10, P = 0.04) at 3 months. Improved diet and mental health were sustained at 6 months. Reduced depression was correlated with an increased MedDiet score (r = -0.298, P = 0.01), nuts (r = -0.264, P = 0.01), and vegetable diversity (r = -0.303, P = 0.01). Other mental health improvements had similar correlations, most notably for increased vegetable diversity and legumes. There were some correlations between increased omega-3, decreased omega-6 and improved mental health. DISCUSSION: This is one of the first randomized controlled trials to show that healthy dietary changes are achievable and, supplemented with fish oil, can improve mental health in people with depression.


Assuntos
Depressão/dietoterapia , Depressão/psicologia , Dieta Mediterrânea , Óleos de Peixe/administração & dosagem , Saúde Mental , Adolescente , Adulto , Idoso , Depressão/sangue , Suplementos Nutricionais , Ácidos Graxos Ômega-3/sangue , Ácidos Graxos Ômega-6/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Resultado do Tratamento , Adulto Jovem
14.
Eur J Nutr ; 58(2): 731-742, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29594475

RESUMO

PURPOSE: Obesity leads to the clustering of cardiovascular (CV) risk factors and the metabolic syndrome (MetS) also in children and is often accompanied by non-alcoholic fatty liver disease. Quality of dietary fat, beyond the quantity, can influence CV risk profile and, in particular, omega-3 fatty acids (FA) have been proposed as beneficial in this setting. The aim of the study was to evaluate the associations of individual CV risk factors, characterizing the MetS, with erythrocyte membrane FA, markers of average intake, in a group of 70 overweight/obese children. METHODS: We conducted an observational study. Erythrocyte membrane FA were measured by gas chromatography. Spearman correlation coefficients (rS) were calculated to evaluate associations between FA and features of the MetS. RESULTS: Mean content of Omega-3 FA was low (Omega-3 Index = 4.7 ± 0.8%). Not omega-3 FA but some omega-6 FA, especially arachidonic acid (AA), were inversely associated with several features of the MetS: AA resulted inversely correlated with waist circumference (rS = - 0.352), triglycerides (rS = - 0.379), fasting insulin (rS = - 0.337) and 24-h SBP (rS = - 0.313). Total amount of saturated FA (SFA) and specifically palmitic acid, correlated positively with waist circumference (rS = 0.354), triglycerides (rS = 0.400) and fasting insulin (rS = 0.287). Fatty Liver Index (FLI), a predictive score of steatosis based on GGT, triglycerides and anthropometric indexes, was positively correlated to palmitic acid (rS = 0.515) and inversely to AA (rS = - 0.472). CONCLUSIONS: Our data suggest that omega-6 FA, and especially AA, could be protective toward CV risk factors featuring the MetS and also to indexes of hepatic steatosis in obese children, whereas SFA seems to exert opposite effects.


Assuntos
Membrana Eritrocítica/metabolismo , Ácidos Graxos/sangue , Síndrome Metabólica/sangue , Obesidade Pediátrica/sangue , Adolescente , Ácido Araquidônico/sangue , Criança , Pré-Escolar , Cromatografia Gasosa , Ácidos Graxos Ômega-6/sangue , Feminino , Humanos , Masculino
15.
Neuroimage ; 188: 239-251, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30529508

RESUMO

A central aim of research in the psychological and brain sciences is to establish therapeutic interventions to promote healthy brain aging. Accumulating evidence indicates that diet and the many bioactive substances present in food are reasonable interventions to examine for dementia prevention. However, interdisciplinary research that applies methods from nutritional epidemiology and network neuroscience to investigate the role of nutrition in shaping functional brain network efficiency remains to be conducted. The present study therefore sought to combine methods across disciplines, applying nutrient biomarker pattern (NBP) analysis to capture the effects of plasma nutrients in combination and to examine their collective influence on measures of functional brain network efficiency (small-world propensity). We examined the contribution of NBPs to multiple indices of cognition and brain health in non-demented elders (n = 116), investigating performance on measures of general intelligence, executive function, and memory, and resting-state fMRI measures of brain network efficiency within seven intrinsic connectivity networks. Statistical moderation investigated whether NBPs influenced network efficiency and cognitive outcomes. The results revealed five NBPs that were associated with enhanced cognitive performance, including biomarker patterns high in plasma: (1) ω-3 and ω-6 polyunsaturated fatty acids (PUFAs), (2) lycopene, (3) ω-3 PUFAs, (4) carotenoids, and (5) vitamins B (riboflavin, folate, B12) and D. Furthermore, three NBPs were associated with enhanced functional brain network efficiency, including biomarker patterns high in plasma: (1) ω-6 PUFAs, (2) ω-3 PUFAs, and (3) carotene. Finally, ω-3 PUFAs moderated the fronto-parietal network and general intelligence, while ω-6 PUFAs and lycopene moderated the dorsal attention network and executive function. In sum, NBPs account for a significant proportion of variance in measures of cognitive performance and functional brain network efficiency. The results motivate a multidisciplinary approach that applies methods from nutritional epidemiology (NBP analysis) and cognitive neuroscience (functional brain network efficiency) to characterize the impact of nutrition on human health, aging, and disease.


Assuntos
Envelhecimento/fisiologia , Encéfalo/fisiologia , Conectoma , Dieta , Fenômenos Fisiológicos da Nutrição do Idoso/fisiologia , Processos Mentais/fisiologia , Rede Nervosa/fisiologia , Idoso , Envelhecimento/sangue , Atenção/fisiologia , Biomarcadores/sangue , Encéfalo/diagnóstico por imagem , Carotenoides/sangue , Cognição/fisiologia , Função Executiva/fisiologia , Ácidos Graxos Ômega-3/sangue , Ácidos Graxos Ômega-6/sangue , Feminino , Humanos , Inteligência/fisiologia , Licopeno/sangue , Imagem por Ressonância Magnética , Masculino , Rede Nervosa/diagnóstico por imagem , Complexo Vitamínico B/sangue , Vitamina D/sangue
16.
Nutrition ; 58: 194-200, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30553106

RESUMO

OBJECTIVES: The aim of this study was to assess the association of plasma and erythrocyte ω-3 and ω-6 fatty acids with multiple oxidative stress biomarkers in breast cancer patients. METHODS: Ninety-five women with recently diagnosed breast cancer and no previous treatment were selected for this study. The socioeconomic, clinical, and demographic profile of the patients was determined using a structured questionnaire and medical records. Body weight and height were measured to calculate body mass index. Blood samples were drawn after a 12-h fast for biochemical analyses. The oxidative stress biomarkers low-density lipoprotein (-) and its anti-low-density lipoprotein (-) antibodies, α-tocopherol, ß-carotene, high-density lipoprotein cholesterol, thiobarbituric acid reactive substance, and adiponectin were measured. Plasma and erythrocyte fatty acids were assessed by gas chromatography. Factor and principal component analysis was used to identify three factors called factor 1 (anti-inflammatory), factor 2 (antioxidant), and factor 3 (oxidant). Linear regression, adjusted for confounding variables, was used to estimate the association of these factors with plasma and erythrocyte ω-3 and ω-6 fatty acids and their ratios. RESULTS: ω-3 series fatty acids showed a positive association with Factor 1. A positive association of plasma and erythrocyte ω-6 fatty acids with factors 1 and 2, respectively, was found. ω-6/ω-3 ratio (plasma) was inversely associated with the anti-inflammatory factor. CONCLUSION: Polyunsaturated fatty acids of the plasma and erythrocyte ω-3 and ω-6 series were associated with multiple inflammatory and oxidative stress biomarkers in breast cancer.


Assuntos
Neoplasias da Mama/sangue , Ácidos Graxos Ômega-3/sangue , Ácidos Graxos Ômega-6/sangue , Inflamação/sangue , Estresse Oxidativo , Adulto , Biomarcadores Tumorais/sangue , Neoplasias da Mama/complicações , Eritrócitos , Feminino , Humanos , Inflamação/complicações , Pessoa de Meia-Idade , Adulto Jovem
17.
Nutrients ; 10(12)2018 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-30513730

RESUMO

The fatty acid (FA) composition of red blood cell (RBC) membrane phospholipids of cancer patients can reflect tumor status, dietary intakes, and cancer type or therapy. However, the characteristic membrane profiles have so far not yet defined as a potential biomarker to monitor disease evolution. The present work provides the first evidence of cancer metabolic signatures affecting cell membranes that are independent of nutritional habits. From the Oncology Outpatient Unit of the Onkologikoa hospital, two groups of cancer patients (n = 54) and healthy controls (n = 37) were recruited, and mature RBCs membrane phospholipids were analyzed for FA profiling (GC-MS). Dietary habits were evaluated using a validated food frequency questionnaire. The adjusted Analysis of Covariance Test (ANCOVA) model revealed cancer patients to have a lower relative percentage of saturated fatty acids (SFA) (C16:0 (5.7%); C18:0 (15.9%)), and higher monounsaturated fatty acids (MUFA) (9c-C18:1 (12.9%) and 11c-C18:1 (54.5%)), compared to controls. In line with this, we observe that the desaturase enzymatic index (delta-9 desaturase (Δ9D), +28.3%) and the membrane saturation index (SI = SFA/MUFA; -27.3%) were similarly modulated. Polyunsaturated fatty acids (PUFA) families showed an increase of n-6 C18:2 and C20:3 (15.7% and 22.2% respectively), with no differences in n-6 C20:4 and n-3 PUFA (docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA)). Importantly, these changes were found independent of foods and fat intakes from the diet. The membrane lipid profile in RBC was useful to ascertain the presence of two main metabolic signatures of increased desaturation activity and omega-6 in cancer patients, statistically independent from dietary habits.


Assuntos
Membrana Eritrocítica/metabolismo , Ácidos Graxos Monoinsaturados/sangue , Ácidos Graxos Ômega-3/sangue , Ácidos Graxos Ômega-6/sangue , Neoplasias/metabolismo , Fosfolipídeos/sangue , Adulto , Inquéritos sobre Dietas , Ácidos Graxos , Ácidos Graxos Insaturados/sangue , Comportamento Alimentar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estearoil-CoA Dessaturase/sangue
18.
Nutrients ; 10(12)2018 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-30572606

RESUMO

BACKGROUND: The prognostic value of erythrocyte levels of n-6 fatty acids (FAs) for total mortality and cardiovascular disease (CVD) outcomes remains an open question. METHODS: We examined cardiovascular (CV) outcomes and death in 2500 individuals in the Framingham Heart Study Offspring cohort without prevalent CVD (mean age 66 years, 57% women) as a function of baseline levels of different length n-6 FAs (18 carbon, 20 carbon, and 22 carbon) in the erythrocyte membranes. Clinical outcomes were monitored for up to 9.5 years (median follow up, 7.26 years). Cox proportional hazards models were adjusted for a variety of demographic characteristics, clinical status, and red blood cell (RBC) n-6 and long chain n-3 FA content. RESULTS: There were 245 CV events, 119 coronary heart disease (CHD) events, 105 ischemic strokes, 58 CVD deaths, and 350 deaths from all causes. Few associations between either mortality or CVD outcomes were observed for n-6 FAs, with those that were observed becoming non-significant after adjusting for n-3 FA levels. CONCLUSIONS: Higher circulating levels of marine n-3 FA levels are associated with reduced risk for incident CVD and ischemic stroke and for death from CHD and all-causes; however, in the same sample little evidence exists for association with n-6 FAs. Further work is needed to identify a full profile of FAs associated with cardiovascular risk and mortality.


Assuntos
Doenças Cardiovasculares , Eritrócitos/química , Ácidos Graxos Ômega-6/sangue , Idoso , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/mortalidade , Feminino , Humanos , Estudos Longitudinais , Masculino , Fatores de Risco
19.
Am J Clin Nutr ; 108(5): 1135-1144, 2018 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-30475958

RESUMO

Background: Adequate availability of long-chain polyunsaturated fatty acids (LC-PUFAs) is important for human health from pregnancy to adulthood. Previous studies on fatty acid desaturase (FADS) gene single-nucleotide polymorphisms (SNPs) have been performed predominantly in Western populations and showed that FADS SNPs had a marked impact on LC-PUFA composition in blood and tissues. Objectives: We aimed to investigate the influence of fetal FADS genotypes on LC-PUFA composition in umbilical artery plasma lipids in Indonesian infants. Design: We performed a cross-sectional study to assess for these associations. Results: A total of 12 cord plasma n-6 (ω-6) and n-3 (ω-3) fatty acids were analyzed for associations with 18 FADS gene cluster SNPs from 390 women with single parturition from the Indonesian Prospective Study of Atopic Dermatitis in Infants (ISADI). Fetal FADS genotypes influenced cord plasma LC-PUFA composition, but, in contrast to previous studies from Western populations, the quantitatively predominant SNPs were associated with lower LC-PUFA content. Conclusion: To our knowledge, this study was the first in South East Asia on FADS genotypes and arterial cord blood fatty acids to show an association between fetal LC-PUFA composition and fetal FADS SNPs. The FADS genotype distribution differs markedly between different geographical populations. This trial was registered at clinicaltrials.gov as NCT02401178.


Assuntos
Grupo com Ancestrais do Continente Asiático/genética , Ácidos Graxos Dessaturases/genética , Ácidos Graxos Ômega-3/sangue , Ácidos Graxos Ômega-6/sangue , Sangue Fetal/metabolismo , Genótipo , Polimorfismo de Nucleotídeo Único , Adulto , Ásia Sudeste , Feminino , Feto , Humanos , Indonésia , Lactente , Recém-Nascido , Masculino
20.
Nutrients ; 10(11)2018 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-30400671

RESUMO

Obesity is often accompanied by metabolic and haemodynamic disorders such as hypertension, even during childhood. Arachidonic acid (AA) is metabolized by cytochrome P450 (CYP450) enzymes to epoxyeicosatrienoic acids (EETs) and 20-hydroxyeicosatetraenoic acid (20-HETE), vasoactive and natriuretic metabolites that contribute to blood pressure (BP) regulation. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) omega-3 polyunsaturated fatty acids may compete with AA for CYP450-dependent bioactive lipid mediator formation. We aimed at investigating the role of AA, EPA and DHA and their CYP450-dependent metabolites in BP control and vascular function in 66 overweight/obese children. Fatty acid profile moderately correlated with the corresponding CYP450-derived metabolites but their levels did not differ between children with normal BP (NBP) and high BP (HBP), except for higher EPA-derived epoxyeicosatetraenoic acids (EEQs) and their diols in HBP group, in which also the estimated CYP450-epoxygenase activity was higher. In the HBP group, EPA inversely correlated with BP, EEQs inversely correlated both with systolic BP and carotid Intima-Media Thickness (cIMT). The DHA-derived epoxydocosapentaenoic acids (EDPs) were inversely correlated with diastolic BP. Omega-3 derived epoxymetabolites appeared beneficially associated with BP and vascular structure/function only in obese children with HBP. Further investigations are needed to clarify the role of omega-3/omega-6 epoxymetabolites in children's hemodynamics.


Assuntos
Pressão Sanguínea , Sistema Enzimático do Citocromo P-450/metabolismo , Ácidos Graxos Ômega-3/sangue , Ácidos Graxos Ômega-6/sangue , Obesidade Pediátrica/sangue , Ácido 8,11,14-Eicosatrienoico/metabolismo , Adolescente , Antropometria , Ácido Araquidônico/metabolismo , Espessura Intima-Media Carotídea , Criança , Pré-Escolar , Estudos Transversais , Eritrócitos/metabolismo , Feminino , Hemodinâmica , Humanos , Ácidos Hidroxieicosatetraenoicos/metabolismo , Masculino
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