RESUMO
BACKGROUND AND AIMS: Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) found in fish oil are postulated to have favourable effects on platelet, endothelial and vascular function. We investigated whether EPA has differential effects on in vivo platelet aggregation and other markers of cardiovascular risk compared to DHA. METHODS AND RESULTS: Following a 2 wk run-in taking encapsulated refined olive oil, 48 healthy young men were randomly allocated using a parallel design to receive EPA-rich (3.1 g EPA/d) or DHA-rich (2.9 g DHA/d) triglyceride concentrates or refined olive oil (placebo), for a total supplementary lipid intake of 5 g/d. The specified primary outcome was change in platelet monocyte aggregates (PMA); secondary outcomes were capillary density, augmentation index, digital pulse volume measurements, 24 h ambulatory BP, plasma 8-isoprostanes-F2α. Changes in the proportions of DHA and EPA in erythrocytes and non-esterified fatty acid composition indicated compliance to the intervention. There was no significant treatment effect on PMA (P = 0.382); mean changes (%) (95% CI) were placebo -0.5 (-2.0, 1.04), EPA 0.4 (-0.8, 1.6), DHA 0.3 (-1.5, 2.0). R-QUICKI, an index of insulin sensitivity, was greater following EPA compared to placebo (P < 0.05). No other significant differences were noted. CONCLUSION: Neither EPA- nor DHA-rich fish oil supplementation influence platelet-monocyte aggregation or several markers of vascular function after 6 wk in healthy young males. This trial was registered at clinicaltrials.gov as NCT01735357.
Assuntos
Plaquetas/efeitos dos fármacos , Suplementos Nutricionais , Ácidos Docosa-Hexaenoicos/administração & dosagem , Ácidos Eicosanoicos/administração & dosagem , Endotélio Vascular/efeitos dos fármacos , Monócitos/efeitos dos fármacos , Adesividade Plaquetária/efeitos dos fármacos , Adolescente , Adulto , Biomarcadores/sangue , Plaquetas/metabolismo , Cápsulas , Endotélio Vascular/metabolismo , Voluntários Saudáveis , Humanos , Resistência à Insulina , Londres , Masculino , Adesão à Medicação , Monócitos/metabolismo , Organização e Administração , Método Simples-Cego , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
ORCTL3 is a member of a group of genes, the so-called anticancer genes, that cause tumour-specific cell death. We show that this activity is triggered in isogenic renal cells upon their transformation independently of the cells' proliferation status. For its cell death effect ORCTL3 targets the enzyme stearoyl-CoA desaturase-1 (SCD1) in fatty acid metabolism. This is caused by transmembrane domains 3 and 4, which are more efficacious in vitro than a low molecular weight drug against SCD1, and critically depend on their expression level. SCD1 is found upregulated upon renal cell transformation indicating that its activity, while not impacting proliferation, represents a critical bottleneck for tumourigenesis. An adenovirus expressing ORCTL3 leads to growth inhibition of renal tumours in vivo and to substantial destruction of patients' kidney tumour cells ex vivo. Our results indicate fatty acid metabolism as a target for tumour-specific apoptosis in renal tumours and suggest ORCTL3 as a means to accomplish this.
Assuntos
Apoptose , Neoplasias Renais/terapia , Transportadores de Ânions Orgânicos/genética , Estearoil-CoA Dessaturase/fisiologia , Adenoviridae/genética , Animais , Transformação Celular Neoplásica , Células Cultivadas , Estresse do Retículo Endoplasmático , Feminino , Humanos , Neoplasias Renais/patologia , Camundongos , Transportadores de Ânions Orgânicos/fisiologia , Estrutura Terciária de ProteínaRESUMO
AIMS: To investigate the relationship between adiposity and plasma free fatty acid levels and the influence of total plasma free fatty acid level on insulin sensitivity and ß-cell function. METHODS: An insulin sensitivity index, acute insulin response to glucose and a disposition index, derived from i.v. glucose tolerance minimal model analysis and total fasting plasma free fatty acid levels were available for 533 participants in the Reading, Imperial, Surrey, Cambridge, Kings study. Bivariate correlations were made between insulin sensitivity index, acute insulin response to glucose and disposition index and both adiposity measures (BMI, waist circumference and body fat mass) and total plasma free fatty acid levels. Multivariate linear regression analysis was performed, controlling for age, sex, ethnicity and adiposity. RESULTS: After adjustment, all adiposity measures were inversely associated with insulin sensitivity index (BMI: ß = -0.357; waist circumference: ß = -0.380; body fat mass: ß = -0.375) and disposition index (BMI: ß = -0.215; waist circumference: ß = -0.248; body fat mass: ß = -0.221) and positively associated with acute insulin response to glucose [BMI: ß = 0.200; waist circumference: ß = 0.195; body fat mass ß = 0.209 (P values <0.001)]. Adiposity explained 13, 4 and 5% of the variation in insulin sensitivity index, acute insulin response to glucose and disposition index, respectively. After adjustment, no adiposity measure was associated with free fatty acid level, but total plasma free fatty acid level was inversely associated with insulin sensitivity index (ß = -0.133), acute insulin response to glucose (ß = -0.148) and disposition index [ß = -0.218 (P values <0.01)]. Plasma free fatty acid concentration accounted for 1.5, 2 and 4% of the variation in insulin sensitivity index, acute insulin response to glucose and disposition index, respectively. CONCLUSIONS: Plasma free fatty acid levels have a modest negative association with insulin sensitivity, ß-cell secretion and disposition index but no association with adiposity measures. It is unlikely that plasma free fatty acids are the primary mediators of obesity-related insulin resistance or ß-cell dysfunction.
Assuntos
Adiposidade , Diabetes Mellitus Tipo 2/etiologia , Ácidos Graxos não Esterificados/sangue , Resistência à Insulina , Células Secretoras de Insulina/metabolismo , Insulina/metabolismo , Obesidade/sangue , Adulto , Idoso , Índice de Massa Corporal , Estudos de Coortes , Estudos Transversais , Diabetes Mellitus Tipo 2/epidemiologia , Inglaterra/epidemiologia , Feminino , Humanos , Secreção de Insulina , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Obesidade/metabolismo , Obesidade/fisiopatologia , Fatores de Risco , Circunferência da CinturaRESUMO
BACKGROUND/OBJECTIVES: Dietary triacylglycerols containing palmitic acid in the sn-2 position might impair insulin release and increase plasma glucose. SUBJECTS/METHODS: We used a cross-over designed feeding trial in 53 healthy Asian men and women (20-50 years) to test this hypothesis by exchanging 20% energy of palm olein (PO; control) with randomly interesterified PO (IPO) or high oleic acid sunflower oil (HOS). After a 2-week run-in period on PO, participants were fed PO, IPO and HOS for 6 week consecutively in randomly allocated sequences. Fasting (midpoint and endpoint) and postprandial blood at the endpoint following a test meal (3.54 MJ, 14 g protein, 85 g carbohydrate and 50 g fat as PO) were collected for the measurement of C-peptide, insulin, glucose, plasma glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1, lipids and apolipoproteins; pre-specified primary and secondary outcomes were postprandial changes in C-peptide and plasma glucose. RESULTS: Low density lipoprotein cholesterol was 0.3 mmol/l (95% confidence interval (95% CI)) 0.1, 0.5; P<0.001) lower on HOS than on PO or IPO as predicted, indicating good compliance to the dietary intervention. There were no significant differences (P=0.58) between diets among the 10 male and 31 female completers in the incremental area under the curve (0-2 h) for C-peptide in nmol.120 min/l: GM (95% CI) were PO 220 (196, 245), IPO 212 (190, 235) and HOS 224 (204, 244). Plasma glucose was 8% lower at 2 h on IPO vs PO and HOS (both P<0.05). CONCLUSION: Palmitic acid in the sn-2 position does not adversely impair insulin secretion and glucose homeostasis.
Assuntos
Glicemia/metabolismo , Dieta , Gorduras na Dieta/efeitos adversos , Insulina/metabolismo , Ácido Palmítico/efeitos adversos , Óleos de Plantas/efeitos adversos , Triglicerídeos/efeitos adversos , Adulto , Área Sob a Curva , Arecaceae/química , Proteína C-Reativa/metabolismo , LDL-Colesterol/sangue , Estudos Cross-Over , Gorduras na Dieta/farmacologia , Esterificação , Feminino , Humanos , Secreção de Insulina , Masculino , Pessoa de Meia-Idade , Ácido Oleico/farmacologia , Óleo de Palmeira , Óleos de Plantas/farmacologia , Óleo de Girassol , Adulto JovemRESUMO
OBJECTIVES: To examine the relations between haemostatic factors and lipoproteins with mortality in British Europeans, African-Caribbeans (AfC) and Gujarati Indians. METHODS: A prospective cohort study of 331 subjects (40-79 years), followed-up over 26 years for mortality. Apolipoprotein-A1 (Apo-A1), apolipoprotein-B (Apo-B), factor VII coagulant activity (FVIIc), fibrinogen and von Willebrand Factor (vWF) were measured at baseline in 118 Europeans, 100 AfC and 113 Gujaratis. Aortic pulse wave velocity (aPWV) was measured in 174 participants. RESULTS: 147 (44.4%) subjects died during a median of 24 years follow-up with 69 cardiovascular deaths. Women at baseline had higher, and AfC males the lowest FVIIc and Apo-A1 levels. Baseline age-sex and ethnicity adjusted FVIIc levels were higher in those who died (131.0 vs. 117.4%; P = 0.048). In similarly adjusted partial correlations, Apo-A1 was inversely related to arterial stiffness (ρ = -0.23, P = 0.04). Over the 26 years follow-up, participants below the median (i.e. with lower concentration) of FVIIc, Fibrinogen, Apo-B and vWF had better survival rates than those with higher concentrations; those with higher concentrations of Apo-A1 had better survival. In Cox multivariable regression analyses including sex, ethnicity and aPWV, independently increased risk of all-cause mortality came only from SBP (per 5 mmHg); P = 0.011), age (per year); P < 0.0001 and FVIIc at 7% (per 10-unit; HR 1.07 (1.02, 1.12); P = 0.008. Separately, Apo-A1 (HR 0.12 (0.02, 0.75; P = 0.029) was independently associated with a very significant 88% reduction in all-cause mortality. CONCLUSIONS: Despite a relatively small sample size, long-term follow-up suggests an independent effect of the prothrombotic state (via FVIIc) and apo-A1 (a constituent of HDL) on mortality.
Assuntos
Antígenos/sangue , Apolipoproteína A-I/sangue , Apolipoproteínas B/sangue , Doenças Cardiovasculares/etnologia , Mortalidade , Fator de von Willebrand/análise , Adulto , Idoso , Antropometria , População Negra/estatística & dados numéricos , Região do Caribe/etnologia , Etnicidade/estatística & dados numéricos , Europa (Continente)/etnologia , Fator VII , Feminino , Fibrinogênio/análise , Seguimentos , Humanos , Índia/etnologia , Estimativa de Kaplan-Meier , Londres/epidemiologia , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Prospectivos , Fatores de Risco , Estudos de Amostragem , Trombofilia/sangue , Trombofilia/etnologia , Rigidez Vascular , População Branca/estatística & dados numéricosRESUMO
BACKGROUND/OBJECTIVES: Dietary triacylglycerols (TAGs) containing palmitic acid in the sn-2 position might impair insulin release and increase plasma glucose. We tested this hypothesis by comparing postprandial responses to fats with varying proportions of palmitic acid in the sn-2 position. SUBJECTS/METHODS: Using a crossover-designed randomized controlled trial in healthy men (n=25) and women (n=25), we compared four meals on postprandial changes in glucose (primary outcome), insulin, C-peptide, glucose, glucose-dependent insulinotropic polypeptide (GIP) and polypeptide YY (PYY) concentrations. The meals provided 14 g protein, 85 g carbohydrate and 50 g test fat, supplied as high oleic sunflower (HOS) oil (control), palm olein (PO), interesterified palm olein (IPO) and lard containing 0.6, 9.2, 39.1 and 70.5 mol% palmitic acid at sn-2, respectively. RESULTS: No differences in plasma glucose, insulin and C-peptide response between meals were found. GIP release was lower (P<0.001) for IPO and lard compared with HOS and PO meals; the maximal increments (geometric mean and 95% confidence interval) for HOS, PO, IPO and lard were 515 (468, 569), 492 (448, 540), 398 (350, 452) and 395 (364, 429) ng/l, respectively. There was a trend for the postprandial increase in PYY to be lower in women on the IPO and lard meals than those on the HOS and PO meals. CONCLUSIONS: Dietary TAGs with an increased proportion of palmitic acid in the sn-2 position do not have acute adverse effects on the insulin and glucose response to meals in healthy men and women, but they decrease GIP release.
Assuntos
Glicemia/metabolismo , Polipeptídeo Inibidor Gástrico/metabolismo , Insulina/sangue , Ácido Palmítico/efeitos adversos , Adolescente , Adulto , Peptídeo C/sangue , Estudos Cross-Over , Gorduras na Dieta/administração & dosagem , Método Duplo-Cego , Feminino , Polipeptídeo Inibidor Gástrico/sangue , Voluntários Saudáveis , Humanos , Masculino , Refeições , Pessoa de Meia-Idade , Ácido Oleico/administração & dosagem , Ácido Palmítico/administração & dosagem , Ácido Palmítico/química , Peptídeo YY/sangue , Óleos de Plantas/administração & dosagem , Período Pós-Prandial/fisiologia , Óleo de Girassol , Triglicerídeos/administração & dosagem , Adulto JovemRESUMO
BACKGROUND: Effective nutrition health interventions are theory-based, as well as being drawn from practice and research, aiming to successfully accomplish dietary behavioural changes. However, the integration of theory, research and practice to develop community dietary educational programmes is a challenge that many interventionists feel ill equipped to achieve. METHODS: In the present study, a community-based education programme was designed for Bangladeshi patients with chronic kidney disease and hypertension. The goal of this programme was to reduce dietary salt intake in this population group, with a view to reducing their blood pressure and slowing kidney disease progression. RESULTS: The present study sets out the first four steps of a six-step model for creating a behaviour change programme. CONCLUSIONS: These four steps were concerned with the translation of theory and evidence into intervention objectives, and illustrate how a practical, community-based intervention was developed from behavioural theory, relevant research, knowledge of practice and the target patient group. Steps 5 and 6, which are concerned with implementation and evaluation, will be reported separately.
Assuntos
Pressão Sanguínea , Dieta Hipossódica , Comportamentos Relacionados com a Saúde , Educação em Saúde , Hipertensão/dietoterapia , Insuficiência Renal Crônica/dietoterapia , Cloreto de Sódio na Dieta/administração & dosagem , Bangladesh , Comportamento Alimentar , Humanos , Hipertensão/complicações , Ciências da Nutrição , Insuficiência Renal Crônica/complicações , Pesquisa , Características de Residência , Pesquisa Translacional BiomédicaRESUMO
BACKGROUND/OBJECTIVES: Breakfast is an important source of micronutrients in the diet and its consumption has been linked to positive health outcomes. The present analysis investigated the contribution that breakfast cereals make to the nutrient intakes of the materially deprived (low income) UK population. SUBJECTS/METHODS: Data for 3728 respondents aged 2 years and over from the UK Low Income Diet and Nutrition Survey (2003-2005) were analysed. Nutrient intakes of consumers and non-consumers of breakfast cereal were compared. RESULTS: Breakfast cereals were consumed by 49% of men, 58% of women, 80% of boys and 80% of girls, and median intakes were: 35, 25, 29 and 21 g/d, respectively. Consumers of breakfast cereals had higher intakes of thiamin, riboflavin, niacin, biotin, folate, vitamin B(6), vitamin B(12), iron and zinc than non-consumers. Breakfast cereal consumption was also related to higher intakes of calcium, attributable to higher milk consumption. The intake of wholegrain and high-fibre breakfast cereals was associated with a higher intake of non-starch polysaccharides. Intakes of niacin, biotin, calcium and zinc were higher but that of vitamin B(6) was lower among consumers of exclusively wholegrain and high-fibre breakfast cereals compared with consumers of other breakfast cereals. There were no significant differences observed in intakes of non-milk extrinsic sugars according to type of breakfast cereal consumed. CONCLUSIONS: Breakfast cereals make a significant contribution to the micronutrient intake of the low-income UK population.
Assuntos
Dieta/normas , Grão Comestível , Comportamento Alimentar , Avaliação Nutricional , Pobreza , Adolescente , Adulto , Fatores Etários , Idoso , Criança , Pré-Escolar , Fast Foods , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Nutritivo , Fatores Sexuais , Reino UnidoRESUMO
OBJECTIVE: SNPs identified from genome-wide association studies associate with lipid risk markers of cardiovascular disease. This study investigated whether these SNPs altered the plasma lipid response to diet in the 'RISCK' study cohort. METHODS: Participants (n=490) from a dietary intervention to lower saturated fat by replacement with carbohydrate or monounsaturated fat, were genotyped for 39 lipid-associated SNPs. The association of each individual SNP, and of the SNPs combined (using genetic predisposition scores), with plasma lipid concentrations was assessed at baseline, and on change in response to 24 weeks on diets. RESULTS: The associations between SNPs and lipid concentrations were directionally consistent with previous findings. The genetic predisposition scores were associated with higher baseline concentrations of plasma total (P=0.02) and LDL (P=0.002) cholesterol, triglycerides (P=0.001) and apolipoprotein B (P=0.004), and with lower baseline concentrations of HDL cholesterol (P<0.001) and apolipoprotein A-I (P<0.001). None of the SNPs showed significant association with the reduction of plasma lipids in response to the dietary interventions and there was no evidence of diet-gene interactions. CONCLUSION: Results from this exploratory study have shown that increased genetic predisposition was associated with an unfavourable plasma lipid profile at baseline, but did not influence the improvement in lipid profiles by the low-saturated-fat diets.
Assuntos
Gorduras na Dieta/administração & dosagem , Ácidos Graxos/administração & dosagem , Predisposição Genética para Doença , Lipídeos/sangue , Adulto , Idoso , Apolipoproteína A-I/sangue , Colesterol/sangue , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Dislipidemias/genética , Feminino , Estudo de Associação Genômica Ampla , Humanos , Masculino , Pessoa de Meia-Idade , Triglicerídeos/sangueRESUMO
Compelling evidence exists for the cardioprotective benefits resulting from consumption of fatty acids from fish oils, EPA (20:5n-3) and DHA (22:6n-3). EPA and DHA alter membrane fluidity, interact with transcription factors such as PPAR and sterol regulatory element binding protein, and are substrates for enzymes including cyclooxygenase, lipoxygenase and cytochrome P450. As a result, fish oils may improve cardiovascular health by altering lipid metabolism, inducing haemodynamic changes, decreasing arrhythmias, modulating platelet function, improving endothelial function and inhibiting inflammatory pathways. The independent effects of EPA and DHA are poorly understood. While both EPA and DHA decrease TAG levels, only DHA appears to increase HDL and LDL particle size. Evidence to date suggests that DHA is more efficient in decreasing blood pressure, heart rate and platelet aggregation compared to EPA. Fish oil consumption appears to improve arterial compliance and endothelial function; it is not yet clear as to whether differences exist between EPA and DHA in their vascular effects. In contrast, the beneficial effect of fish oils on inflammation and insulin sensitivity observed in vitro and in animal studies has not been confirmed in human subjects. Further investigation to clarify the relative effects of consuming EPA and DHA at a range of doses would enable elaboration of current understanding regarding cardioprotective effects of consuming oily fish and algal sources of long chain n-3 PUFA, and provide clearer evidence for the clinical therapeutic potential of consuming either EPA or DHA-rich oils.
Assuntos
Doenças Cardiovasculares/prevenção & controle , Sistema Cardiovascular/efeitos dos fármacos , Ácidos Docosa-Hexaenoicos/uso terapêutico , Ácido Eicosapentaenoico/uso terapêutico , Lipídeos/sangue , Ácidos Docosa-Hexaenoicos/farmacologia , Ácido Eicosapentaenoico/farmacologia , Humanos , Fatores de RiscoRESUMO
BACKGROUND: People of Bangladeshi origin have the highest mortality ratio from coronary heart disease of any minority ethnic group in UK and their rate of kidney disease is three- to five-fold higher than that of the European UK population. However, there is little information regarding their dietary customs or knowledge, beliefs and attitudes towards health and nutrition. This multi-method qualitative study aimed to identify: (i) barriers and facilitators to dietary sodium restriction; (ii) traditional and current diet in the UK; and (iii) beliefs and attitudes towards development of hypertension, and the role of sodium. METHODS: Methods included focus group discussions, vignettes and food diaries. Twenty female chronic kidney disease patients attended four focus group discussions and maintained food diaries; ten responded to vignettes during telephone interviews. Triangulation of the results obtained from the three methods identified categories and themes from qualitative thematic analysis. RESULTS: Identified barriers to sodium restriction were deeply-rooted dietary beliefs, attitudes and a culturally-established taste for salt. Facilitators of change included acceptable strategies for cooking with less salt without affecting palatability. Dietary practices were culturally determined but modified by participants' prosperity in the UK relative to their previous impoverished agrarian lifestyles in Bangladesh. CONCLUSIONS: Cultural background and orientation were strong determinants of the group's dietary practices and influenced their reception and response to health communication messages. Efforts to understand their cultural mores, interpret and convey health-promotion messages in culturally-appropriate ways met with a positive response.
Assuntos
Dieta Hipossódica , Comportamento Alimentar/etnologia , Conhecimentos, Atitudes e Prática em Saúde , Falência Renal Crônica/dietoterapia , Sódio na Dieta/administração & dosagem , Aculturação , Atitude Frente a Saúde , Bangladesh/etnologia , Dieta Hipossódica/etnologia , Comportamento Alimentar/psicologia , Feminino , Grupos Focais , Humanos , Falência Renal Crônica/epidemiologia , Masculino , Pessoa de Meia-Idade , Motivação , Reino Unido/epidemiologiaRESUMO
BACKGROUND/OBJECTIVES: Vegans, and to a lesser extent vegetarians, have low average circulating concentrations of vitamin B12; however, the relation between factors such as age or time on these diets and vitamin B12 concentrations is not clear. The objectives of this study were to investigate differences in serum vitamin B12 and folate concentrations between omnivores, vegetarians and vegans and to ascertain whether vitamin B12 concentrations differed by age and time on the diet. SUBJECTS/METHODS: A cross-sectional analysis involving 689 men (226 omnivores, 231 vegetarians and 232 vegans) from the European Prospective Investigation into Cancer and Nutrition Oxford cohort. RESULTS: Mean serum vitamin B12 was highest among omnivores (281, 95% CI: 270-292 pmol/l), intermediate among vegetarians (182, 95% CI: 175-189 pmol/l) and lowest among vegans (122, 95% CI: 117-127 pmol/l). In all, 52% of vegans, 7% of vegetarians and one omnivore were classified as vitamin B12 deficient (defined as serum vitamin B12 <118 pmol/l). There was no significant association between age or duration of adherence to a vegetarian or a vegan diet and serum vitamin B12. In contrast, folate concentrations were highest among vegans, intermediate among vegetarians and lowest among omnivores, but only two men (both omnivores) were categorized as folate deficient (defined as serum folate <6.3 nmol/l). CONCLUSION: Vegans have lower vitamin B12 concentrations, but higher folate concentrations, than vegetarians and omnivores. Half of the vegans were categorized as vitamin B12 deficient and would be expected to have a higher risk of developing clinical symptoms related to vitamin B12 deficiency.
Assuntos
Dieta Vegetariana , Dieta , Deficiência de Ácido Fólico/epidemiologia , Ácido Fólico/sangue , Deficiência de Vitamina B 12/epidemiologia , Vitamina B 12/sangue , Adulto , Fatores Etários , Idoso , Estudos de Coortes , Estudos Transversais , Ácido Fólico/administração & dosagem , Deficiência de Ácido Fólico/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos Nutricionais , Necessidades Nutricionais , Estado Nutricional , Estudos Prospectivos , Fatores de Tempo , Reino Unido/epidemiologia , Vitamina B 12/administração & dosagem , Deficiência de Vitamina B 12/sangue , Complexo Vitamínico B/sangue , Adulto JovemAssuntos
Dieta , Gorduras na Dieta/metabolismo , Ácidos Graxos/metabolismo , Metabolismo dos Lipídeos/fisiologia , Doenças Cardiovasculares/epidemiologia , Ensaios Clínicos como Assunto , Gorduras na Dieta/administração & dosagem , Endotélio Vascular/fisiologia , Ácidos Graxos/administração & dosagem , Feminino , Genótipo , Hemodinâmica , Hemostasia , Humanos , Inflamação/metabolismo , Resistência à Insulina , Lipídeos/sangue , Masculino , Estresse Oxidativo , Fatores de RiscoRESUMO
BACKGROUND AND AIMS: A low dietary folate intake can cause genomic DNA hypomethylation and may increase the risk of colorectal neoplasia. The hypothesis that folic acid supplementation increases DNA methylation in leucocytes and colorectal mucosa was tested in 31 patients with histologically confirmed colorectal adenoma using a randomised, double blind, placebo controlled, parallel design. METHODS: Subjects were randomised to receive either 400 microg/day folic acid supplement (n = 15) or placebo (n = 16) for 10 weeks. Genomic DNA methylation, serum and erythrocyte folate, and plasma homocysteine concentrations were measured at baseline and post intervention. RESULTS: Folic acid supplementation increased serum and erythrocyte folate concentrations by 81% (95% confidence interval (CI) 57-104%; p<0.001 v placebo) and 57% (95% CI 40-74%; p<0.001 v placebo), respectively, and decreased plasma homocysteine concentration by 12% (95% CI 4-20%; p = 0.01 v placebo). Folic acid supplementation resulted in increases in DNA methylation of 31% (95% CI 16-47%; p = 0.05 v placebo) in leucocytes and 25% (95% CI 11-39%; p = 0.09 v placebo) in colonic mucosa. CONCLUSIONS: These results suggest that DNA hypomethylation can be reversed by physiological intakes of folic acid.
Assuntos
Adenoma/genética , Neoplasias Colorretais/genética , Metilação de DNA/efeitos dos fármacos , Suplementos Nutricionais , Ácido Fólico/farmacologia , Idoso , Neoplasias Colorretais/metabolismo , DNA de Neoplasias/genética , Método Duplo-Cego , Eritrócitos/metabolismo , Feminino , Ácido Fólico/sangue , Homocisteína/sangue , Humanos , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Leucócitos/efeitos dos fármacos , Leucócitos/metabolismo , Masculino , Pessoa de Meia-Idade , Reto/efeitos dos fármacos , Reto/metabolismoRESUMO
DNA hypomethylation may increase the risk of colorectal cancer. The main aim of this study was to assess the influence of folate status (serum and erythrocyte folate and plasma homocysteine concentrations) on DNA methylation. Methylenetetrahydrofolate reductase (MTHFR 677C --> T and 1298A --> C), methionine synthase (MS 2756A --> G) and cystathionine synthase (CBS 844ins68) polymorphisms were measured to account for potential confounding effects on folate status and DNA methylation. A total of 68 subjects (33 men and 35 women, 36-78 years) free from colorectal polyps or cancer were recruited in a cross-sectional study. Tissue biopsies were obtained at colonoscopy for the determination of DNA methylation in colonic mucosa using an in vitro radiolabelled methyl acceptance assay. Serum and erythrocyte folate were inversely correlated with plasma homocysteine (r=-0.573, P<0.001 and r=-0.307, P=0.01 respectively) and DNA hypomethylation in colonic mucosa (r=-0.311, P=0.01 and r=-0.356, P=0.03). After adjusting for gender, age, body mass index, smoking and genotype, there were weak negative associations between serum and erythrocyte folate and colonic DNA hypomethylation (P=0.07 and P=0.08, respectively).
Assuntos
5-Metiltetra-Hidrofolato-Homocisteína S-Metiltransferase/genética , Colo/citologia , Cistationina beta-Sintase/genética , Metilação de DNA , DNA/genética , Ácido Fólico/sangue , Mucosa Intestinal/citologia , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Consumo de Bebidas Alcoólicas , Colo/enzimologia , Colonoscopia , Eritrócitos/metabolismo , Feminino , Homocisteína/sangue , Humanos , Mucosa Intestinal/enzimologia , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Valores de ReferênciaRESUMO
OBJECTIVE: Although psychiatrists are aware of weight gain induced by atypical antipsychotics, only few studies on behavioural interventions in this patient group are published. This review aims to summarize the evidence on effectiveness of behavioural interventions for weight gain in the general population and in-patients treated with atypical antipsychotics. METHOD: Medline and Cochrane databases search for evidence on effectiveness of behavioural interventions. RESULTS: In general, behavioural approaches including, diet, exercise and drug treatments may be effective. There were only 13 studies of behavioural interventions for patients taking antipsychotic medication. No study met the criteria for a RCT. Calorie restriction in a controlled ward environment, structured counselling combined with cognitive behavioural therapy and counselling on life style and provision of rewards may potentially lead to weight loss. CONCLUSION: Currently only limited, methodologically flawed, evidence is available that behavioural interventions in overweight patients treated with antipsychotics, although intuitively appealing, actually work.
Assuntos
Antipsicóticos/uso terapêutico , Terapia Cognitivo-Comportamental , Obesidade/induzido quimicamente , Obesidade/terapia , Aumento de Peso , Aconselhamento , Dieta , Medicina Baseada em Evidências , Exercício Físico , HumanosRESUMO
OBJECTIVE: High concentrations of plasma deoxycholic acid (DCA) are found in human breast cyst fluid and it has been hypothesised that this may be related to risk of breast cancer. The aim of this pilot study was to ascertain whether plasma bile acid concentrations were greater in women with breast cancer. DESIGN: A case-control study comparing postmenopausal women with breast cancer with healthy controls was conducted. SUBJECTS: Twenty Caucasian postmenopausal breast cancer patients were recruited at the time of diagnosis together with 20 healthy controls matched for age and body mass index. Exclusion criteria included any treatment for breast cancer, use of hormone replacement therapy in the last 12 months, diabetes mellitus, a history of liver or gall bladder disease or abnormal liver function. MEASUREMENTS: Fasting plasma bile acid concentrations were determined by gas-liquid chromatography/mass spectrometry. RESULTS: The mean plasma DCA concentration was 52% higher (P=0.012) in patients with breast cancer compared with controls. CONCLUSION: These results support the hypothesis that DCA may be involved in the aetiology of breast cancer.
Assuntos
Neoplasias da Mama/sangue , Neoplasias da Mama/etiologia , Ácido Desoxicólico/efeitos adversos , Ácido Desoxicólico/sangue , Pós-Menopausa/sangue , Idoso , Estudos de Casos e Controles , Feminino , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Pessoa de Meia-IdadeRESUMO
Obesity is associated with considerable morbidity and decreased life expectancy. Weight gain is a commonly encountered problem associated with antipsychotic treatment. We reviewed the literature regarding the mechanisms of weight gain in response to these agents and eight substances implicated as potential obesity prevention or treatment: orlistat, sibutramine, fluoxetine, topiramate, amantadine, nizatidine and cimetidine, and metformin. Weight gain in response to antipsychotic treatment may be mediated through serotonergic, dopaminergic, adrenergic, cholinergic, histaminergic and glutaminergic receptors. Sex hormone dysregulation and altered insulin sensitivity have also been implicated. Two compounds, orlistat and sibutramine, have been shown to help prevent weight gain following a hypocaloric diet, but orlistat requires compliance with a fat-reduced diet, and sibutramine is unsuitable for patients taking serotonergic agents. The weight reducing effect of fluoxetine, even in conjunction with a hypocaloric diet, is only transient. Topiramate, amantadine and metformin may have adverse side-effects potentially outweighing the weight reducing potential. The effectiveness of cimetidine and nizatedine remains unclear. The hazards of these agents in a psychiatric population are discussed. It is concluded that the current evidence does not support the general use of pharmacological interventions for overweight patients treated with antipsychotic medication, although individually selected patients may benefit.
Assuntos
Antipsicóticos/efeitos adversos , Frutose/análogos & derivados , Obesidade/induzido quimicamente , Amantadina/efeitos adversos , Antipsicóticos/uso terapêutico , Cimetidina/efeitos adversos , Ciclobutanos/efeitos adversos , Fluoxetina/efeitos adversos , Frutose/efeitos adversos , Humanos , Lactonas/efeitos adversos , Metformina/efeitos adversos , Nizatidina/efeitos adversos , Obesidade/tratamento farmacológico , Orlistate , Topiramato , Aumento de Peso/efeitos dos fármacosRESUMO
Secondary bile acids produced by the action of the colonic microflora may increase risk of colorectal cancer. Serum bile acid concentrations reflect the faecal bile acid profile and may be of value as biomarkers of risk of colorectal cancer. In a pilot investigation we examined: (i) the reproducibility of measurements of serum bile acids in two blood samples collected several years apart; and (ii) the hypothesis that relatively high levels of secondary bile acids, particularly deoxycholic acid, would be positively associated with an increased risk of colorectal cancer in a prospective study of 3680 women in Guernsey. There was poor reproducibility between repeat measurements of absolute serum concentrations of bile acids, but there was moderately good reproducibility for the ratios of serum concentrations of deoxycholic/cholic acid, lithocholic/chenodeoxycholic and secondary/primary bile acid concentrations (duplicate blood samples were available for 30 women). There were no significant differences in ratios of serum secondary to primary bile acids or in absolute concentrations of bile acids between the 46 women who developed colorectal cancer and their matched controls, although there was a suggestion that an increased risk was associated with a high ratio of deoxycholic/cholic acid (relative risk in top third compared to lower third=3.92 (95% CI 0.91-17.0, P for trend=0.096). These findings suggest that the ratios of serum bile acid concentrations are sufficiently reproducible for epidemiological studies, but that a larger study than our own is needed to adequately test the hypothesis of their relation to cancer risk.