Vitamin E in neural and visual function.

A rat model of vitamin E (alpha-tocopherol) deficiency with similar "clinical," electrophysiological, and neuropathological abnormalities to those seen in man was used to investigate the effects of various amounts and forms of alpha-tocopheryl acetate (alphaTA) on neural and visual function. Electrophysiological techniques provide an objective, non-invasive measure of neural and visual function. These techniques were used in the animal model to determine the minimum dietary requirement of vitamin E necessary to prevent neural and visual abnormalities. They were also used to compare the biological activities of the natural (RRR-) and synthetic (all-rac-) forms of alpha-tocopherol in neural tissues. The results were as follows: (1) Significant differences in neural and visual function were observed between deficient and control rats after approximately 8 months. (2) An intake of 1.0 mg/kg all-rac- or 0.75 mg/kg RRR-alphaTA was observed to marginally protect nerves from vitamin E deficiency. (3) The biological activity of all-rac-alpha-tocopherol in neural tissues was approximately 75% of RRR-alpha-tocopherol. (4) The concentration of free malondialdehyde (an indicator of lipid peroxidation) was significantly increased in tissues from the deficient compared to the control animals. These results are consistent with a deficiency of alpha-tocopherol causing increased lipid peroxidation leading to abnormal neural electrophysiology. They could also be explained by more specific but as yet undefined function(s) of alpha-tocopherol in neural tissues.

The effects of different levels of all-rac- and RRR-alpha-tocopheryl acetate (vitamin E) on visual function in rats.

OBJECTIVE: A rat model of vitamin E (alpha-tocopherol) deficiency with similar "clinical", electrophysiological and neuropathological abnormalities to that seen in man was used to investigate the effects of various dietary intakes of synthetic (all-rac-) and natural (RRR-) alpha-tocopheryl acetate (alphaTA) on visual function. METHODS: Longitudinal measurements of the electroretinogram (ERG) and visual evoked potentials (VEPs) were made monthly for 14 months in 9 groups of rats (n=12/group) receiving different amounts and types of alphaTA. The animals were then killed for biochemical analyses. RESULTS: (1) The first significant abnormalities of both the ERG and VEP were found after 8 months of deficiency. (2) A diet containing 1.25 mg/kg of alphaTA provided marginal protection. (3) The biological activity of all-rac- was approximately 75% of RRR-alphaTA. (4) The concentration of free malondialdehyde (a measure of lipid peroxidation) was significantly increased in all tissues, including the eye, from deficient compared to control rats. CONCLUSIONS: These results are consistent with alpha-tocopherol deficiency causing increased lipid peroxidation leading to abnormal visual function but could also be explained by more specific but undefined function(s) of alpha-tocopherol in the eye.

Glu298Asp endothelial nitric oxide synthase gene polymorphism interacts with environmental and dietary factors to influence endothelial function.

An endothelial nitric oxide synthase (eNOS) gene polymorphism (Glu298Asp) has been associated with cardiovascular disease. We investigated whether carriage of the polymorphism was associated with functional changes in the endothelium, and how genotype altered the harmful and beneficial impact of environmental influences on the endothelium. Endothelium-dependent, flow-mediated brachial artery dilatation (FMD) and endothelium-independent dilatation response to glyceryl trinitrate were measured using high-resolution ultrasound in 248 subjects (131 female, 117 male, aged 20 to 28) genotyped for the Glu298Asp polymorphism. Vascular function was compared between genotype groups and interactions with the proatherogenic risk factor, smoking, and the antiatherogenic influence of n-3 fatty acids (n-3FA) were investigated. Vascular function was not related to genotype in the group as a whole or within sexes. However, among males, smoking was associated with lower FMD in Asp298 carriers (nonsmokers 0.125+/-0.085 mm versus smokers 0.070+/-0.060 mm, P=0.006) but not in Glu298 homozygotes (nonsmokers 0.103+/-0.090 mm versus smokers 0.124+/-0.106, P=0.5). In the whole group, n-3FA levels were positively related to FMD in Asp298 carriers (reg coeff=0.023 mm/%, P=0.04, r=0.20) but not in Glu298 homozygotes (reg coeff=-0.019 mm/%, P=0.1). These differences between genotype groups were significant in interaction models. The Glu298Asp polymorphism is associated with differences in endothelial responses to both smoking and n-3 FA in healthy young subjects. These findings raise the possibility of genotype-specific prevention strategies in cardiovascular disease.

Relationship between circulating n-3 fatty acid concentrations and endothelial function in early adulthood.

AIMS: Fish consumption is inversely associated with cardiovascular mortality, presumably because of n-3 fatty acids in fish. Whether the protection of n-3 fatty acids extends beyond clinical coronary disease to influence the early vascular biology of atherosclerosis remains unclear. This study determined whether circulating levels of n-3 fatty acids are associated with vascular endothelial function in early adulthood. METHODS AND RESULTS: Three hundred and twenty-six adults (157 males, 169 females, aged 20 to 28 years) had high-resolution ultrasound measurements of flow-mediated brachial artery dilatation (FMD) (endothelium-dependent) and arterial response to glyceryl trinitrate (endothelium-independent). Levels of the n-3 fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid in plasma and erythrocyte membranes of subjects were measured. n-3 Fatty acid levels were not related to vascular function in the whole group. In smokers, however, n-3 fatty acids were positively related to flow-mediated dilatation (plasma DHA vs. FMD: 0.045 mm. %(-1), 95% CI 0.011 to 0.079, P=0.01). Flow-mediated dilatation was also associated with n-3 fatty acid levels in subjects in the top third of the insulin, glucose and triglyceride distributions. CONCLUSION: In young smokers and those with higher fasting insulin, glucose or triglyceride concentrations (factors associated with endothelial dysfunction), n-3 fatty acid levels were positively associated with flow-mediated dilatation. This raises the possibility that physiological levels of circulating n-3 fatty acids may protect the endothelium from early adulthood.

Plasma vitamin E, total antioxidant status and vascular function in young adults.

BACKGROUND: Epidemiological studies have reported an inverse relationship between vitamin E status and coronary heart disease. This relationship has not, however, been confirmed by the majority of intervention studies, which have been carried out relatively late in the disease process. The protective effects of vitamin E may be more important earlier in life, before vascular changes have become established. This study investigated whether dietary vitamin E could prevent preclinical arterial changes in young adults relevant to the development of cardiovascular disease. MATERIALS AND METHODS: Measures of vascular function (arterial distensibility and endothelial-dependent and -independent vascular responses) were assessed by noninvasive high resolution ultrasound and related to plasma vitamin E and total antioxidant concentrations in 326 adults, aged 20-28 years. RESULTS: Neither vitamin E (alone or adjusted for lipids) nor total antioxidant status were significantly related to vascular endothelial function or arterial distensibility in either sex. There was no threshold level of vitamin E above which vascular function improved and neither vitamin E nor total antioxidant status interacted with any risk factor, such as smoking or increased low-density lipoprotein concentrations. CONCLUSIONS: Neither plasma vitamin E concentrations nor total antioxidant status achieved by dietary intake during young adulthood were related to vascular endothelial function or arterial distensibility.