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1.
N Engl J Med ; 367(15): 1397-406, 2012 Oct 11.
Artículo en Inglés | MEDLINE | ID: mdl-22998340

RESUMEN

BACKGROUND: The consumption of beverages that contain sugar is associated with overweight, possibly because liquid sugars do not lead to a sense of satiety, so the consumption of other foods is not reduced. However, data are lacking to show that the replacement of sugar-containing beverages with noncaloric beverages diminishes weight gain. METHODS: We conducted an 18-month trial involving 641 primarily normal-weight children from 4 years 10 months to 11 years 11 months of age. Participants were randomly assigned to receive 250 ml (8 oz) per day of a sugar-free, artificially sweetened beverage (sugar-free group) or a similar sugar-containing beverage that provided 104 kcal (sugar group). Beverages were distributed through schools. At 18 months, 26% of the children had stopped consuming the beverages; the data from children who did not complete the study were imputed. RESULTS: The z score for the body-mass index (BMI, the weight in kilograms divided by the square of the height in meters) increased on average by 0.02 SD units in the sugar-free group and by 0.15 SD units in the sugar group; the 95% confidence interval (CI) of the difference was -0.21 to -0.05. Weight increased by 6.35 kg in the sugar-free group as compared with 7.37 kg in the sugar group (95% CI for the difference, -1.54 to -0.48). The skinfold-thickness measurements, waist-to-height ratio, and fat mass also increased significantly less in the sugar-free group. Adverse events were minor. When we combined measurements at 18 months in 136 children who had discontinued the study with those in 477 children who completed the study, the BMI z score increased by 0.06 SD units in the sugar-free group and by 0.12 SD units in the sugar group (P=0.06). CONCLUSIONS: Masked replacement of sugar-containing beverages with noncaloric beverages reduced weight gain and fat accumulation in normal-weight children. (Funded by the Netherlands Organization for Health Research and Development and others; DRINK ClinicalTrials.gov number, NCT00893529.).


Asunto(s)
Bebidas , Sacarosa en la Dieta , Edulcorantes , Aumento de Peso , Tejido Adiposo , Bebidas/efectos adversos , Estatura , Índice de Masa Corporal , Niño , Preescolar , Sacarosa en la Dieta/administración & dosificación , Sacarosa en la Dieta/efectos adversos , Método Doble Ciego , Ingestión de Energía , Femenino , Humanos , Masculino , Países Bajos , Obesidad/etiología , Edulcorantes/administración & dosificación
2.
J Nutr ; 141(9): 1673-8, 2011 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-21753062

RESUMEN

Consumption of industrial trans fatty acids (iTFA) increases LDL cholesterol, decreases HDL cholesterol, and is strongly associated with a higher risk of cardiovascular disease (CVD). However, changes in circulating cholesterol cannot explain the entire effect. Therefore, we studied whether iTFA and conjugated linoleic acid (CLA) affect markers of inflammation and oxidative stress. Sixty-one healthy adults consumed each of 3 diets for 3 wk, in random order. Diets were identical except for 7% of energy provided by oleic acid (control diet), iTFA, or CLA. At the end of the 3 wk, we measured plasma inflammatory markers IL-6, C-reactive protein, tumor necrosis factor receptors I and II (TNF-RI and -RII), monocyte chemotactic protein-1 and E-selectin, and urinary 8-iso-PGF(2α), a marker of lipid peroxidation. Consumption of iTFA caused 4% lower TNF-RI concentrations and 6% higher E-selectin concentrations compared with oleic acid (control) and had no significant effect on other inflammatory markers. CLA did not significantly affect inflammatory markers. The urine concentration of 8-iso-PGF(2α) [geometric mean (95% CI)] was greater after the iTFA [0.54 (0.48, 0.60) nmol/mmol creatinine] and the CLA [1.2 (1.1, 1.3) nmol/mmol creatinine] diet periods than after the control period [0.45 (0.41, 0.50) nmol/mmol creatinine; P < 0.05]. In conclusion, high intakes of iTFA and CLA did not substantially affect plasma concentrations of inflammatory markers, but they increased the urine 8-iso-PGF(2α) concentration. However, it is unlikely this plays a major role in the mechanism by which iTFA increase the risk of CVD. However, more research is needed to fully understand the implications of these findings.


Asunto(s)
Biomarcadores/metabolismo , Grasas de la Dieta/efectos adversos , Inflamación/metabolismo , Estrés Oxidativo/fisiología , Ácidos Grasos trans/efectos adversos , Adolescente , Adulto , Estudios Cruzados , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven
3.
Am Heart J ; 159(4): 539-546.e2, 2010 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-20362710

RESUMEN

BACKGROUND: Weekly fish consumption has been related to a lower risk of fatal coronary heart disease (CHD) and incident stroke in populations with a low fish intake. This relation has mainly been attributed to n-3 fatty acids in fish, that is, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). It is at present unclear whether alpha-linolenic acid (ALA), a n-3 fatty acid from vegetable origin, could also be protective against cardiovascular diseases (CVDs). There is a need for food-based trials to establish the efficacy of low doses of n-3 fatty acids in CVD prevention. OBJECTIVES: The aim of the study was to evaluate the effect of an additional daily intake of 400 mg of EPA + DHA and 2 g of ALA on CVD morbidity and mortality in free-living subjects with a history of myocardial infarction. DESIGN: The multicenter Alpha Omega Trial is a randomized, double-blind, placebo-controlled trial with a 2 x 2 factorial design. Between May 2002 and December 2006, we enrolled a total of 4,837 men and women aged 60 through 80 who experienced a myocardial infarction within 10 years before entering the study. Subjects were randomized to 1 of 4 margarine spreads that were enriched with EPA + DHA and/or ALA, or placebo. Compliance was monitored via tub counts and assessment of n-3 fatty acids in plasma. Subjects were observed for 40 months for the occurrence of fatal and nonfatal CVD. RESULTS: The cohort was on average 69 years old at the start of the study and comprised 22% women. Subjects had their (last) myocardial infarction approximately 4 years before enrollment. Mean body mass index was 27.7 kg/m(2), and 17% smoked. Average serum total and high-density lipoprotein cholesterol were 4.7 and 1.3 mmol/L, respectively, and 85% used statins. Mean blood pressure was 142/80 mm Hg, and most subjects were on antihypertensive medication (88%). Diabetes mellitus was reported by 17% of the subjects, and 7% reported a history of stroke. The overall mortality rate during the trial period was 23 per 1,000 person-years, with approximately 40% due to CVD. CURRENT STATUS: Follow-up of the patients was completed in November 2009, and findings will be reported in the second part of 2010.


Asunto(s)
Enfermedades Cardiovasculares/tratamiento farmacológico , Enfermedades Cardiovasculares/prevención & control , Ácidos Grasos Omega-3/farmacología , Anciano , Anciano de 80 o más Años , Enfermedades Cardiovasculares/mortalidad , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/tratamiento farmacológico , Factores de Riesgo , Resultado del Tratamiento
5.
Eur Heart J ; 30(7): 820-6, 2009 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-19196720

RESUMEN

AIMS: To determine the effects of omega-3 polyunsaturated fatty acids (omega-3 PUFAs) from fish on the incidence of recurrent ventricular arrhythmia in implantable cardioverter defibrillator (ICD) patients by combining results from published trials. METHODS AND RESULTS: We searched in the Medline, EMBASE, and Cochrane databases and performed a meta-analysis on all three available trials on fish oil and ventricular arrhythmia. Furthermore, we pooled individual data of two of these randomized, double-blind, placebo-controlled trials (Raitt et al. Fish oil supplementation and risk of ventricular tachycardia and ventricular fibrillation in patients with implantable defibrillators: a randomized controlled trial. JAMA 2005;293:2884-2891 and Brouwer et al. Effect of fish oil on ventricular tachyarrhythmia and death in patients with implantable cardioverter defibrillators: the Study on Omega-3 Fatty Acids and Ventricular Arrhythmia (SOFA) randomized trial. JAMA 2006;295:2613-2619). The main outcome was time to first confirmed ventricular fibrillation (VF) or ventricular tachycardia (VT) combined with death for the meta-analysis, and time to first spontaneous confirmed VF or VT for the pooled analysis. The meta-analysis (n = 1148) showed no convincing protective effect of fish oil (RR 0.90; 95% CI 0.67-1.22). The hazard ratio for the subgroup of patients with coronary artery disease at baseline (0.79; 0.60-1.06) tended towards a protective effect. The pooled analysis (n = 722) showed that time to appropriate ICD intervention was similar for fish oil and placebo treatment (log-rank P = 0.79). CONCLUSION: These findings do not support a protective effect of omega-3 PUFAs from fish oil on cardiac arrhythmia in all patients with an ICD. Current data neither prove nor disprove a beneficial or a detrimental effect for subgroups of patients with specific underlying pathologies.


Asunto(s)
Desfibriladores Implantables , Ácidos Grasos Omega-3/uso terapéutico , Insuficiencia Cardíaca/prevención & control , Taquicardia Ventricular/terapia , Anciano , Suplementos Dietéticos , Femenino , Insuficiencia Cardíaca/mortalidad , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Ensayos Clínicos Controlados Aleatorios como Asunto , Prevención Secundaria , Taquicardia Ventricular/mortalidad , Resultado del Tratamiento
6.
Am J Epidemiol ; 170(11): 1415-21, 2009 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-19889709

RESUMEN

Observational studies have shown an association between low plasma cholesterol levels and increased risk of cancer, whereas most randomized clinical trials involving cholesterol-lowering medications have not shown this association. Between 1997 and 2002, the authors assessed the association between plasma cholesterol levels and cancer risk, free from confounding and reverse causality, in a Mendelian randomization study using apolipoprotein E (ApoE) genotype. ApoE genotype, plasma cholesterol levels, and cancer incidence and mortality were measured during a 3-year follow-up period among 2,913 participants in the Prospective Study of Pravastatin in the Elderly at Risk. Subjects within the lowest third of plasma cholesterol level at baseline had increased risks of cancer incidence (hazard ratio (HR) = 1.90, 95% confidence interval (CI): 1.34, 2.70) and cancer mortality (HR = 2.03, 95% CI: 1.23, 3.34) relative to subjects within the highest third of plasma cholesterol. However, carriers of the ApoE2 genotype (n = 332), who had 9% lower plasma cholesterol levels than carriers of the ApoE4 genotype (n = 635), did not have increased risk of cancer incidence (HR = 0.86, 95% CI: 0.50, 1.47) or cancer mortality (HR = 0.70, 95% CI: 0.30, 1.60) compared with ApoE4 carriers. These findings suggest that low cholesterol levels are not causally related to increased cancer risk.


Asunto(s)
Apolipoproteínas E/genética , Colesterol/sangre , Análisis de la Aleatorización Mendeliana , Neoplasias/epidemiología , Anciano , Anciano de 80 o más Años , Apolipoproteína E2/genética , Apolipoproteína E3/genética , Apolipoproteína E4/genética , Intervalos de Confianza , Femenino , Genotipo , Humanos , Modelos Lineales , Masculino , Neoplasias/genética , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Factores de Riesgo
7.
Lancet ; 369(9557): 208-16, 2007 Jan 20.
Artículo en Inglés | MEDLINE | ID: mdl-17240287

RESUMEN

BACKGROUND: Low folate and raised homocysteine concentrations in blood are associated with poor cognitive performance in the general population. As part of the FACIT trial to assess the effect of folic acid on markers of atherosclerosis in men and women aged 50-70 years with raised plasma total homocysteine and normal serum vitamin B12 at screening, we report here the findings for the secondary endpoint: the effect of folic acid supplementation on cognitive performance. METHODS: Our randomised, double blind, placebo controlled study took place between November, 1999, and December, 2004, in the Netherlands. We randomly assigned 818 participants 800 mug daily oral folic acid or placebo for 3 years. The effect on cognitive performance was measured as the difference between the two groups in the 3-year change in performance for memory, sensorimotor speed, complex speed, information processing speed, and word fluency. Analysis was by intention-to-treat. This trial is registered with clinicaltrials.gov with trial number NCT00110604. FINDINGS: Serum folate concentrations increased by 576% (95% CI 539 to 614) and plasma total homocysteine concentrations decreased by 26% (24 to 28) in participants taking folic acid compared with those taking placebo. The 3-year change in memory (difference in Z scores 0.132, 95% CI 0.032 to 0.233), information processing speed (0.087, 0.016 to 0.158) and sensorimotor speed (0.064, -0.001 to 0.129) were significantly better in the folic acid group than in the placebo group. INTERPRETATION: Folic acid supplementation for 3 years significantly improved domains of cognitive function that tend to decline with age.


Asunto(s)
Cognición/efectos de los fármacos , Ácido Fólico/uso terapéutico , Complejo Vitamínico B/uso terapéutico , Anciano , Apolipoproteínas E/genética , Método Doble Ciego , Femenino , Ácido Fólico/sangre , Homocisteína/sangre , Humanos , Modelos Lineales , Masculino , Memoria/efectos de los fármacos , Metilenotetrahidrofolato Reductasa (NADPH2)/genética , Persona de Mediana Edad , Países Bajos , Pruebas Psicológicas , Complejo Vitamínico B/sangre
8.
J Nutr ; 138(8): 1456-61, 2008 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-18641191

RESUMEN

The recommended dietary allowance (RDA) differs between men and women for some vitamins, but not for folate. The RDA for folate is derived mainly from metabolic studies in women. We assessed if men differ from women in their response of erythrocyte folate to folic acid supplementation. We used data from 2 randomized placebo-controlled trials with folic acid: a 3-y trial in which subjects ingested 800 mug/d of folic acid (294 men and 112 women) and a 12-wk trial in which 187 men and 129 women ingested 0, 50, 100, 200, 400, 600, or 800 microg/d of folic acid in a parallel design (n = 38-42 per treatment group). In the 3-y trial, the erythrocyte folate concentration increased 10% (143 nmol/L, [95%CI 46, 241]) less in men than in women. In the 12-wk trial, regression analysis showed that the response of erythrocyte folate upon folic acid intake for men was 47 nmol/L lower than for women (P for beta(gender) = 0.022); for an intake of 800 microg/d folic acid, this resulted in a 5% lower response in men than in women. Differences in lean body size explained 56% of the difference in response of erythrocyte folate between men and women in the 3-y trial and 70% in the 12-wk trial. Men need more folic acid than women to achieve the same erythrocyte folate concentration, mainly because men have a larger lean body mass. This could be an indication that the RDA for folate should be higher for men than for women, or that the RDA should be expressed per kilogram of lean body mass.


Asunto(s)
Tamaño Corporal/fisiología , Eritrocitos/efectos de los fármacos , Eritrocitos/metabolismo , Ácido Fólico/administración & dosificación , Ácido Fólico/sangre , Caracteres Sexuales , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , Política Nutricional
9.
Br J Nutr ; 100(4): 794-800, 2008 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-18315890

RESUMEN

Very long-chain n-3 PUFA from fish are suggested to play a role in the development of the brain. Fish oil feeding results in higher proportions of n-3 PUFA in the brains of newborn piglets. However, the effect of fish oil on the fatty acid composition of specific cerebral brain lobes in juvenile pigs is largely uninvestigated. This study examined the effect of a fish oil diet on the fatty acid composition of the frontal, parietal, temporal and occipital brain lobes in juvenile pigs (7 weeks old). Pigs were randomly allocated to a semipurified pig diet containing either 4% (w/w) fish oil (n 19) or 4% (w/w) high-oleic acid sunflower oil (HOSF diet, n 18) for a period of 8 weeks. The fish oil diet resulted in significantly higher proportions (%) of DHA in the frontal (10.6 (SD1.2)), parietal (10.2 (SD1.5)) and occipital brain lobes (9.9 (SD 1.3)), but not in the temporal lobe (7.7 (SD1.6)), compared with pigs fed the HOSF diet (frontal lobe, 7.5 (SD1.0); parietal lobe, 8.1 (SD 1.3); occipital lobe, 7.3 (SD1.2), temporal lobe, 6.6 (SD1.2). Moreover, the proportion of DHA was significantly lower in the temporal lobe compared with the frontal, parietal and occipital brain lobes in pigs fed a fish oil diet. In conclusion, the brains of juvenile pigs appear to be responsive to dietary fish oil, although the temporal brain lobe is less responsive compared with the other three brain lobes. The functional consequences of these differences are a challenging focus for future investigation.


Asunto(s)
Encéfalo/metabolismo , Grasas de la Dieta/administración & dosificación , Ácidos Grasos Omega-3/administración & dosificación , Aceites de Pescado , Porcinos/metabolismo , Alimentación Animal , Animales , Ácidos Grasos Omega-3/análisis , Ácidos Grasos Omega-6/administración & dosificación , Ácidos Grasos Omega-6/análisis , Lóbulo Frontal/química , Masculino , Lóbulo Occipital/química , Lóbulo Parietal/química , Aceites de Plantas/administración & dosificación , Distribución Aleatoria , Aceite de Girasol , Lóbulo Temporal/química
10.
Mol Endocrinol ; 21(7): 1603-16, 2007 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-17456796

RESUMEN

Cafestol, a diterpene present in unfiltered coffee brews such as Scandinavian boiled, Turkish, and cafetière coffee, is the most potent cholesterol-elevating compound known in the human diet. Several genes involved in cholesterol homeostasis have previously been shown to be targets of cafestol, including cholesterol 7alpha-hydroxylase (CYP7A1), the rate-limiting enzyme in bile acid biosynthesis. We have examined the mechanism by which cafestol elevates serum lipid levels. Changes in several lipid parameters were observed in cafestol-treated APOE3Leiden mice, including a significant increase in serum triglyceride levels. Microarray analysis of these mice identified alterations in hepatic expression of genes involved in lipid metabolism and detoxification, many of which are regulated by the nuclear hormone receptors farnesoid X receptor (FXR) and pregnane X receptor (PXR). Further studies demonstrate that cafestol is an agonist ligand for FXR and PXR, and that cafestol down-regulates expression of the bile acid homeostatic genes CYP7A1, sterol 12alpha-hydroxylase, and Na(+)-taurocholate cotransporting polypeptide in the liver of wild-type but not FXR null mice. Cafestol did not affect genes known to be up-regulated by FXR in the liver of wild-type mice, but did increase expression of the positive FXR-target genes intestinal bile acid-binding protein and fibroblast growth factor 15 (FGF15) in the intestine. Because FGF15 has recently been shown to function in an enterohepatic regulatory pathway to repress liver expression of bile acid homeostatic genes, its direct induction in the gut may account for indirect effects of cafestol on liver gene expression. PXR-dependent gene regulation of cytochrome P450 3A11 and other targets by cafestol was also only seen in the intestine. Using a double FXR/PXR knockout mouse model, we found that both receptors contribute to the cafestol-dependent induction of intestinal FGF15 gene expression. In conclusion, cafestol acts as an agonist ligand for both FXR and PXR, and this may contribute to its impact on cholesterol homeostasis.


Asunto(s)
Proteínas de Unión al ADN/agonistas , Diterpenos/farmacología , Receptores Citoplasmáticos y Nucleares/agonistas , Receptores de Esteroides/agonistas , Factores de Transcripción/agonistas , Animales , Apolipoproteína E3/genética , Colesterol 7-alfa-Hidroxilasa/genética , Café/química , Proteínas de Unión al ADN/deficiencia , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/metabolismo , Diterpenos/efectos adversos , Diterpenos/metabolismo , Femenino , Factores de Crecimiento de Fibroblastos/genética , Humanos , Hipercolesterolemia/inducido químicamente , Técnicas In Vitro , Ligandos , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Ratones Transgénicos , Modelos Biológicos , Receptor X de Pregnano , ARN Mensajero/genética , ARN Mensajero/metabolismo , Receptores Citoplasmáticos y Nucleares/deficiencia , Receptores Citoplasmáticos y Nucleares/genética , Receptores Citoplasmáticos y Nucleares/metabolismo , Receptores de Esteroides/deficiencia , Receptores de Esteroides/genética , Receptores de Esteroides/metabolismo , Factores de Transcripción/deficiencia , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Activación Transcripcional/efectos de los fármacos
11.
Prog Lipid Res ; 45(4): 357-67, 2006 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-16678270

RESUMEN

n-3 Polyunsaturated fatty acids (n-3 PUFA) are suggested to prevent cardiac death via inhibition of cardiac arrhythmia. In this review we discuss the results of human studies on intake of n-3 PUFAs and heart disease and, more specifically, on cardiac arrhythmia. Observational studies indicate that intake of fish is associated with a lower incidence of fatal coronary heart disease in several populations. These studies are fairly consistent, but people that have a high intake of fatty fish might have a healthier lifestyle in general, and such confounding is difficult to remove completely with statistical adjustments and corrections. Evidence from trials is less clear. In two open label trials in patients with a previous myocardial infarction intake of fish or fish oil prevented fatal coronary heart disease. In contrast, a trial in patients with angina suggested a higher risk of sudden cardiac death in patients taking fish oil. Furthermore, results of trials in patients with an implantable cardioverter defibrillator (ICD) that investigated effects of fish oil on arrhythmia in patients already suffering from ventricular tachycardia are not consistent. Also, studies on relationships between intake of n-3 PUFA from fish and less life-threatening forms of arrhythmia, such as atrial fibrillation and premature ventricular complexes (PVCs) are equivocal. Thus, after 35 years of research the question whether fish prevents heart disease remains unanswered, and an anti-arrhythmic effect of fish oil remains unproven although the idea is still viable and is being actively tested in further trials.


Asunto(s)
Arritmias Cardíacas/prevención & control , Enfermedad Coronaria/prevención & control , Dieta/estadística & datos numéricos , Ácidos Grasos Omega-3/administración & dosificación , Animales , Antiarrítmicos/uso terapéutico , Ensayos Clínicos como Asunto , Enfermedad Coronaria/mortalidad , Ácidos Grasos Omega-3/uso terapéutico , Peces , Humanos , Alimentos Marinos
12.
Cardiovasc Res ; 73(2): 386-94, 2007 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-17116294

RESUMEN

OBJECTIVE: Dietary supplementation with fish oil-derived n-3 fatty acids reduces mortality in patients with myocardial infarction, but may have adverse effects in angina patients. The underlying electrophysiologic mechanisms are poorly understood. We studied the arrhythmias and the electrophysiologic changes during regional ischemia in hearts from pigs fed a diet rich in fish oil. METHODS: Pigs received diets rich in fish oil, in sunflower oil, or a control diet for 8 weeks. Hearts were isolated and perfused. Ischemia was created by occluding the left anterior descending artery. Diastolic stimulation threshold, refractory period, conduction velocity, activation recovery intervals and the maximum downstroke velocity of 176 electrograms were measured in the ischemic zone. Spontaneous arrhythmias during 75 min of regional ischemia were counted. RESULTS: More episodes of spontaneous ischemia-induced sustained ventricular tachycardia and ventricular fibrillation occurred in the fish oil and sunflower oil group than in the control group. More inexcitable myocardium was present in the ischemic zone in the group fed fish oil or sunflower oil than in the control group after 20 min of ischemia. After 40 min of ischemia, more block occurred in the control group than in the other groups. The downstroke velocity of the electrograms in the ischemic border zone was lower in the fish oil group and sunflower oil group than in the control after 20 min. CONCLUSIONS: A diet rich in fish oil results in proarrhythmia compared to a control diet during regional ischemia in pigs. Myocardial excitability is reduced in the fish oil and sunflower oil group during the early phase of arrhythmogenesis. In the late phase of arrhythmogenesis, excitability is more reduced in the control group than in the fish oil and sunflower oil group.


Asunto(s)
Arritmias Cardíacas/inducido químicamente , Ácidos Grasos Omega-3/administración & dosificación , Animales , Arritmias Cardíacas/fisiopatología , Suplementos Dietéticos , Ácidos Docosahexaenoicos/análisis , Ácidos Docosahexaenoicos/sangre , Ácido Eicosapentaenoico/análisis , Ácido Eicosapentaenoico/sangre , Electrocardiografía , Corazón/fisiopatología , Masculino , Isquemia Miocárdica/metabolismo , Isquemia Miocárdica/fisiopatología , Perfusión , Aceites de Plantas/administración & dosificación , Aceite de Girasol , Porcinos
13.
Am J Clin Nutr ; 85(2): 465-73, 2007 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-17284745

RESUMEN

BACKGROUND: The bioavailability of natural food folates is lower than that of synthetic folic acid, but no agreement exists as to the extent of the difference. OBJECTIVE: In a 4-wk dietary intervention study, we determined the aggregate bioavailability of food folates from fruit, vegetables, and liver relative to that of folic acid. DESIGN: Seventy-two healthy adults were randomly divided into 4 treatment groups. Group A (n = 29) received a high-folate diet with 369 mug food folate/d and a placebo capsule; groups B, C, and D (n = 14 or 15) received a low-folate diet with 73 microg food folate/d and folic acid capsules. These capsules contained 92 microg folic acid/d for group B, 191 microg for group C, and 289 microg for group D. In addition, all 72 subjects daily ingested a capsule with 58 microg [(13)C(11)]-labeled folic acid. We measured the percentage of [(13)C(11)]-labeled folate in plasma folate at the end of the intervention and ascertained the changes in serum folate concentrations over the 4 wk of the intervention. RESULTS: Bioavailability of food folate relative to that of folic acid was 78% (95% CI: 48%, 108%) according to [(13)C(11)]-labeled folate and 85% (52%, 118%) according to changes in serum folate concentrations. CONCLUSIONS: The aggregate bioavailability of folates from fruit, vegetables, and liver is approximately 80% of that of folic acid. The consumption of a diet rich in food folate can improve the folate status of a population more efficiently than is generally assumed.


Asunto(s)
Dieta , Ácido Fólico/administración & dosificación , Ácido Fólico/farmacocinética , Alimentos , Adulto , Relación Dosis-Respuesta a Droga , Femenino , Ácido Fólico/síntesis química , Análisis de los Alimentos , Humanos , Masculino , Persona de Mediana Edad , Valor Nutritivo
15.
BMC Microbiol ; 7: 84, 2007 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-17850650

RESUMEN

BACKGROUND: Salmonella enteritidis is suggested to translocate in the small intestine. In vivo it induces gene expression changes in the ileal mucosa and Peyer's patches. Stimulation of Salmonella translocation by dietary prebiotics fermented in colon suggests involvement of the colon as well. However, effects of Salmonella on colonic gene expression in vivo are largely unknown. We aimed to characterize time dependent Salmonella-induced changes of colonic mucosal gene expression in rats using whole genome microarrays. For this, rats were orally infected with Salmonella enteritidis to mimic a foodborne infection and colonic gene expression was determined at days 1, 3 and 6 post-infection (n = 8 rats per time-point). As fructo-oligosaccharides (FOS) affect colonic physiology, we analyzed colonic mucosal gene expression of FOS-fed versus cellulose-fed rats infected with Salmonella in a separate experiment. Colonic mucosal samples were isolated at day 2 post-infection. RESULTS: Salmonella affected transport (e.g. Chloride channel calcium activated 6, H+/K+ transporting Atp-ase), antimicrobial defense (e.g. Lipopolysaccharide binding protein, Defensin 5 and phospholipase A2), inflammation (e.g. calprotectin), oxidative stress related genes (e.g. Dual oxidase 2 and Glutathione peroxidase 2) and Proteolysis (e.g. Ubiquitin D and Proteosome subunit beta type 9). Furthermore, Salmonella translocation increased serum IFN gamma and many interferon-related genes in colonic mucosa. The gene most strongly induced by Salmonella infection was Pancreatitis Associated Protein (Pap), showing >100-fold induction at day 6 after oral infection. Results were confirmed by Q-PCR in individual rats. Stimulation of Salmonella translocation by dietary FOS was accompanied by enhancement of the Salmonella-induced mucosal processes, not by induction of other processes. CONCLUSION: We conclude that the colon is a target tissue for Salmonella, considering the abundant changes in mucosal gene expression.


Asunto(s)
Antígenos de Neoplasias/metabolismo , Biomarcadores de Tumor/metabolismo , Expresión Génica , Intestino Delgado/metabolismo , Lectinas Tipo C/metabolismo , Salmonella enteritidis/fisiología , Administración Oral , Animales , Antígenos de Neoplasias/genética , Biomarcadores de Tumor/genética , Intestino Delgado/microbiología , Lectinas Tipo C/genética , Análisis de Secuencia por Matrices de Oligonucleótidos , Proteínas Asociadas a Pancreatitis , Ratas , Salmonelosis Animal/microbiología , Salmonella enteritidis/química , Salmonella enteritidis/genética , Salmonella enteritidis/inmunología
16.
Circulation ; 112(13): 1945-52, 2005 Sep 27.
Artículo en Inglés | MEDLINE | ID: mdl-16172267

RESUMEN

BACKGROUND: The effect of fish oil on heart rate (HR), a major risk factor for sudden death, is not well established. We calculated this effect in a meta-analysis of randomized, double-blind, placebo-controlled trials in humans. METHODS AND RESULTS: Randomized trials of fish oil that evaluated HR were identified through MEDLINE (1966 through January 2005), hand-searching of references, and contact with investigators for unpublished results. Two investigators independently extracted trial data. A pooled estimate was calculated from random-effects meta-analysis. Predefined stratified meta-analyses and meta-regression were used to explore potential heterogeneity. Of 197 identified articles, 30 met inclusion criteria. Evidence for publication bias was not present. In the overall pooled estimate, fish oil decreased HR by 1.6 bpm (95% CI, 0.6 to 2.5; P=0.002) compared with placebo. Between-trial heterogeneity was evident (Q test, P<0.001). Fish oil reduced HR by 2.5 bpm (P<0.001) in trials with baseline HR > or =69 bpm (median) but had little effect (0.04-bpm reduction; P=0.56) in trials with baseline HR <69 bpm (P for interaction=0.03). Fish oil reduced HR by 2.5 bpm (P<0.001) in trials with duration > or =12 weeks but had less effect (0.7-bpm reduction; P=0.27) in trials with duration <12 weeks (P for interaction=0.07). HR reduction with fish oil intake did not significantly vary by fish oil dose (range, 0.81 to 15 g/d), type of HR measure, population age, population health, parallel versus crossover design, type of control oil, or study quality by Delphi criteria (P for interaction >0.25 for each). CONCLUSIONS: In randomized controlled trials in humans, fish oil reduces HR, particularly in those with higher baseline HR or longer treatment duration. These findings provide firm evidence that fish oil consumption directly or indirectly affects cardiac electrophysiology in humans. Potential mechanisms such as effects on the sinus node, ventricular efficiency, or autonomic function deserve further investigation.


Asunto(s)
Aceites de Pescado/farmacología , Frecuencia Cardíaca/efectos de los fármacos , Adulto , Anciano , Método Doble Ciego , Humanos , Persona de Mediana Edad , Ensayos Clínicos Controlados Aleatorios como Asunto
17.
Am J Clin Nutr ; 84(1): 44-53, 2006 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-16825680

RESUMEN

BACKGROUND: Human in vivo data on dietary determinants of alpha-linolenic acid (ALA; 18:3n-3) metabolism are scarce. OBJECTIVE: We examined whether intakes of ALA or linoleic acid (LA; 18:2n-6) or their ratio influences ALA metabolism. DESIGN: During 4 wk, 29 subjects received a control diet (7% of energy from LA, 0.4% of energy from ALA, ALA-to-LA ratio = 1:19). For the next 6 wk, a control diet, a low-LA diet (3% of energy from LA, 0.4% of energy from ALA, ratio = 1:7), or a high-ALA diet (7% of energy from LA, 1.1% of energy from ALA, ratio = 1:7) was consumed. Ten days before the end of each dietary period, [U-13C]ALA was administered orally for 9 d. ALA oxidation was determined from breath. Conversion was estimated by using compartmental modeling of [13C]- and [12C]n-3 fatty acid concentrations in fasting plasma phospholipids. RESULTS: Compared with the control group, ALA incorporation into phospholipids increased by 3.6% in the low-LA group (P = 0.012) and decreased by 8.0% in the high-ALA group (P < 0.001). In absolute amounts, it increased by 34.3 mg (P = 0.020) in the low-LA group but hardly changed in the high-ALA group. Nearly all ALA from the plasma phospholipid pool was converted into eicosapentaenoic acid. Conversion of eicosapentaenoic acid into docosapentaenoic acid and docosahexaenoic acid hardly changed in the 3 groups and was <0.1% of dietary ALA. In absolute amounts, it was unchanged in the low-LA group, but increased from 0.7 to 1.9 mg (P = 0.001) in the high-ALA group. ALA oxidation was unchanged by the dietary interventions. CONCLUSION: The amounts of ALA and LA in the diet, but not their ratio, determine ALA conversion.


Asunto(s)
Ácidos Grasos Insaturados/metabolismo , Ácido Linoleico/metabolismo , Fosfolípidos/metabolismo , Ácido alfa-Linolénico/metabolismo , Pruebas Respiratorias , Isótopos de Carbono , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Ácidos Grasos Insaturados/análisis , Ácidos Grasos Insaturados/sangre , Femenino , Humanos , Ácido Linoleico/administración & dosificación , Ácido Linoleico/sangre , Masculino , Persona de Mediana Edad , Oxidación-Reducción , Fosfolípidos/análisis , Fosfolípidos/sangre , Ácido alfa-Linolénico/administración & dosificación , Ácido alfa-Linolénico/sangre
18.
Am J Clin Nutr ; 84(5): 1128-33, 2006 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-17093166

RESUMEN

BACKGROUND: The bioavailability of dietary folate may be hampered by the need of the glutamate moieties to be deconjugated before absorption. Previous studies comparing the bioavailabilities of polyglutamyl and monoglutamyl folic acid had inconsistent results. OBJECTIVE: The objective was to estimate the bioavailability of polyglutamyl relative to that of monoglutamyl folic acid by using a sensitive stable-isotope approach that allowed for the administration of multiple low doses in humans. DESIGN: Twenty subjects aged 20-50 y ingested 2 capsules daily for 28 d; each capsule contained approximately 50 nmol [(13)C(6)]hexaglutamyl and approximately 50 nmol [(13)C(11)]monoglutamyl folic acid. Amounts of the isotopically labeled compounds in the capsules were verified by various methods. The degrees of isotopic enrichment of plasma 5-methyltetrahydrofolate with (13)C(6) and (13)C(11) were measured by using liquid chromatography tandem mass spectrometry, and the ratio of (13)C(6) to (13)C(11) ((13)C(6):(13)C(11)) in plasma on day 28 was used as a measure of their relative bioavailability. RESULTS: The (13)C(11):(13)C(6) in plasma 5-methyltetrahydrofolate reached equilibrium on day 4 and was 0.66 (95% CI: 0.58, 0.74) on day 28. The (13)C(11):(13)C(6) content in the capsules varied between 1.18 and 1.96. After correction for this ratio, the estimated bioavailability of hexaglutamyl relative to that of monoglutamyl folic acid was >/=78%. CONCLUSION: Multiple dosing of low amounts of labeled folic acid is a sensitive, accurate, and efficient method of measuring the relative bioavailability of folic acid compounds, provided that the administered doses can be reliably assessed.


Asunto(s)
Ácido Fólico/farmacocinética , Absorción Intestinal/efectos de los fármacos , Tetrahidrofolatos/sangre , Complejo Vitamínico B/farmacocinética , Administración Oral , Adulto , Área Bajo la Curva , Disponibilidad Biológica , Isótopos de Carbono , Cromatografía Liquida/métodos , Suplementos Dietéticos , Relación Dosis-Respuesta a Droga , Femenino , Ácido Fólico/administración & dosificación , Ácido Fólico/química , Humanos , Masculino , Persona de Mediana Edad , Ácidos Pteroilpoliglutámicos/administración & dosificación , Ácidos Pteroilpoliglutámicos/farmacocinética , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Espectrometría de Masas en Tándem/métodos , Complejo Vitamínico B/análisis , Complejo Vitamínico B/química
19.
Atheroscler Suppl ; 7(2): 63-6, 2006 May.
Artículo en Inglés | MEDLINE | ID: mdl-16713390

RESUMEN

Lowering the intake of trans fatty acids (TFA) probably reduces the incidence of coronary heart disease. Estimates of the reduction vary from 4% based on changes in plasma LDL and HDL concentrations alone, to > 20% based on epidemiological associations when TFA intake is lowered by 2% of energy (5 g/day). Even the lowest estimate represents enough cases to justify measures to reduce TFA intake. In The Netherlands, a major reduction in TFA content of retail foods has been achieved in the 1990s through efforts of industry; government intervention has been minimal. Societal pressure is now helping to reduce the TFA content of fast foods. McDonald's French fries in The Netherlands now have less than 4% trans and 24% saturates, as opposed to 21% trans and 21% saturates in the USA. This illustrates the feasibility of reducing TFA in fast foods without increasing saturates. As a result of these developments, dairy and meat have become the major remaining source of TFA in Europe. The question whether these ruminant TFA have the same effect on coronary heart disease risk as industrial TFA has not been settled.


Asunto(s)
Grasas Insaturadas en la Dieta , Industria de Alimentos/legislación & jurisprudencia , Legislación Alimentaria , Control Social Formal , Ácidos Grasos trans , Enfermedad Coronaria/epidemiología , Enfermedad Coronaria/etiología , Enfermedad Coronaria/prevención & control , Grasas Insaturadas en la Dieta/efectos adversos , Industria de Alimentos/historia , Historia del Siglo XX , Historia del Siglo XXI , Humanos , Legislación Alimentaria/historia , Países Bajos , Ácidos Grasos trans/efectos adversos , Estados Unidos
20.
Nutr Rev ; 64(6): 275-9, 2006 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-16808113

RESUMEN

Mensink and Katan showed in 1990 that trans fats reduce high- and increase low-density lipoprotein cholesterol. Unilever aided this study because the company considered knowledge on trans fats incomplete in spite of their long history of safe use. The decision in 1994 to remove trans fats from Unilever's retail spreads was triggered by media events, but it was built on a solid understanding of the nutritional and technological aspects of trans fats. Over the next 14 years, manufacturers worldwide followed suit. This experience illustrates that food companies need to know about the health effects of their products and how to apply that knowledge.


Asunto(s)
Tecnología de Alimentos , Lípidos/sangre , Margarina/efectos adversos , Margarina/análisis , Ácidos Grasos trans/efectos adversos , Grasas Insaturadas en la Dieta/administración & dosificación , Grasas Insaturadas en la Dieta/efectos adversos , Humanos
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