RESUMO
BACKGROUND: Various mechanisms have been proposed to explain the association between plasma total homocysteine (tHcy) and risk of cardiovascular disease, including oxidative activity of homocysteine. OBJECTIVE: To explore the putative role of reactive oxygen species in the association between plasma tHcy and risk of cardiovascular disease in healthy individuals. DESIGN: A double-blind, placebo-controlled crossover intervention to increase folate intake through diet (increased consumption of folate-rich foods) and supplement (400 micro g folic acid) was carried out in 126 healthy men and women. Measurements were made of antioxidant activity in red blood cells and plasma, and products of oxidant damage in plasma. RESULTS: Diet and supplement-based interventions led to an increase in measures of folate status and a reduction in plasma tHcy. This was not associated with any significant change in measures of antioxidant activity (plasma and red blood cell glutathione peroxidase activity and red blood cell superoxide dismutase activity) or oxidant damage (plasma malondialdehyde), although an improvement in plasma total antioxidant capacity just failed to reach significance. CONCLUSIONS: In healthy individuals lowering plasma tHcy does not have any functional implications regarding oxidative damage.
Assuntos
Antioxidantes/metabolismo , Doenças Cardiovasculares/sangue , Ácido Fólico/administração & dosagem , Homocisteína/sangue , Adulto , Idoso , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/metabolismo , Estudos Cross-Over , Suplementos Nutricionais , Método Duplo-Cego , Feminino , Ácido Fólico/sangue , Ácido Fólico/metabolismo , Glutationa Peroxidase/metabolismo , Homocisteína/metabolismo , Humanos , Masculino , Malondialdeído/metabolismo , Pessoa de Meia-Idade , Estado Nutricional , Oxirredução , Espécies Reativas de Oxigênio , Fatores de Risco , Método Simples-Cego , Superóxido Dismutase/metabolismoRESUMO
OBJECTIVE: To assess and compare the effects of natural folate (100 micro g) with those of folic acid from fortified sources (100 micro g/day) on plasma folate and homocysteine. DESIGN: Randomized controlled trial (parallel groups). SETTING: Men and women living in South Wales, UK. SUBJECTS: A total of 135 healthy individuals recruited from the local workforce and blood donor sessions. All subjects possessed the 'wild-type' CC genotype for C677T polymorphism in methylenetetrahydrofolate reductase (MTHFR). INTERVENTIONS: Subjects underwent one of the following dietary interventions for 4 months: (1) fortified diet-usual diet plus 100 microg/day folic acid from fortified foods; (2) natural folate diet-usual diet plus 100 microg/day folate from natural sources; (3) control-usual diet. RESULTS: The fortified group increased reported intake of folic acid from fortified foods compared to other groups (P<0.001) achieving an extra 98 microg/day (95% CI 88-108). The natural folate group increased reported intake of natural source folates compared with the other two groups (P<0.001), but achieved a mean increase of only 50 microg/day (95% CI 34-66). Plasma folate increased (P<0.01) by a similar amount in both intervention groups compared to controls (fortified group 2.97, 95% CI 0.8-5.1; natural group 2.76, 95% CI 0.6-4.9. Plasma homocysteine, vitamins B(6) and B(12) were not significantly changed. CONCLUSIONS: Subjects achieved increases in folate intake using fortified foods more easily than by folate-rich foods, however both sources increased plasma folate by a similar amount. These levels of intake were insufficient to reduce homocysteine concentrations in MTHFR CC homozygotes, but may be more effective in other genotypes.
Assuntos
Ácido Fólico/sangue , Ácido Fólico/farmacologia , Alimentos Fortificados , Frutas , Homocisteína/sangue , Política Nutricional , Verduras , Adolescente , Adulto , Idoso , Registros de Dieta , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valores de Referência , Reino UnidoAssuntos
Ácido Fólico/farmacologia , Homocisteína/sangue , Oxirredutases atuantes sobre Doadores de Grupo CH-NH/genética , Vitamina B 12/sangue , Dieta , Feminino , Ácido Fólico/administração & dosagem , Ácido Fólico/sangue , Genótipo , Humanos , Masculino , Metilenotetra-Hidrofolato Redutase (NADPH2)RESUMO
OBJECTIVES: We sought to study the effect of low-dose folic acid supplementation or optimization of dietary folate intake on plasma homocysteine and endothelial function in healthy adults. BACKGROUND: Elevated homocysteine is associated with cardiovascular disease, but it is not known whether this relationship is causal. Individuals homozygous (TT) for the C677T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene ( approximately 12% of the population) have increased homocysteine levels, particularly in association with suboptimal folate intake. METHODS: Healthy subjects (n = 126; 42 of each MTHFR genotype) were included in this cross-over study of three interventions of four months each: 1) placebo plus natural diet; 2) daily 400-microg folic acid supplement plus natural diet; and 3) increased dietary folate intake to 400 microg/day. RESULTS: At baseline, homocysteine was inversely related to plasma folate and was higher in TT homozygotes. For the whole group, plasma folate increased by 46% after dietary folate and by 79% after supplementation, with reductions of homocysteine of 14% and 16%, respectively. Within the genotype, TT homozygotes exhibited the most marked changes in these variables. Brachial artery endothelial function, as determined by a change in end-diastolic diameter in response to increased flow, was not changed by increased folate intake (98 +/- 73 microm at baseline, 110 +/- 69 microm after a high-folate diet, 114 +/- 59 microm after supplementation and 118 +/- 68 microm after placebo). Plasma von Willebrand factor antigen was unaltered. CONCLUSIONS: Optimization of dietary folate or low-dose folic acid supplementation reduces plasma homocysteine but does not enhance endothelial function, irrespective of the MTHFR (C667T) genotype.
Assuntos
Endotélio Vascular/efeitos dos fármacos , Ácido Fólico/administração & dosagem , Genótipo , Homocisteína/sangue , Oxirredutases atuantes sobre Doadores de Grupo CH-NH/genética , Adolescente , Adulto , Idoso , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Ácido Fólico/sangue , Homozigoto , Humanos , Masculino , Metilenotetra-Hidrofolato Redutase (NADPH2) , Pessoa de Meia-Idade , Necessidades Nutricionais , Valores de Referência , Resistência Vascular/genética , Resistência Vascular/fisiologiaRESUMO
Homocysteine is a risk factor for coronary artery disease (CAD). Folic acid lowers homocysteine and may improve endothelial function in CAD, although the mechanism is unclear. We investigated the effect of folic acid on endothelial function, homocysteine, and oxidative stress in patients with CAD. We also examined the acute effect of 5-methyltetrahydrofolate (5-MTHF), the principal circulating folate, on endothelial function in vivo and on intracellular superoxide in cultured endothelial cells. A randomized crossover study of folic acid (5 mg daily) for 6 weeks was undertaken in 52 patients with CAD. Ten further patients were given intra-arterial 5-MTHF. Endothelial function was assessed by flow-mediated dilatation (FMD). Folic acid increased plasma folate (P<0.001), lowered homocysteine by 19% (P<0.001), and improved FMD (P<0.001). FMD improvement did not correlate with homocysteine reduction. Malondialdehyde and total plasma antioxidant capacity, markers of oxidative stress, were unchanged. 5-MTHF acutely improved FMD (P<0.001) without altering homocysteine (P=0.47). In vitro, 5-MTHF abolished homocysteine-induced intracellular superoxide increase (P<0.001); this effect was also observed with folic acid and tetrahydrobiopterin. Our data support the beneficial effect of folic acid on endothelial function in CAD but suggest that the mechanism is independent of homocysteine. Reduction of intracellular endothelial superoxide may have contributed to the effect.