Vitamin E and atherosclerosis: investigation of novel biological activities and metabolism of gamma-tocopherol in humans

Jason Wu

    Research output: ThesisDoctoral Thesis

    115 Downloads (Pure)

    Abstract

    [Truncated abstract] Current understanding of atherosclerosis suggests that it is a chronic inflammatory disease, and that increased oxidative stress may be an important pathological event contributing to the disease process. There has been interest in the ability of dietary derived nutrients such as vitamin E, to act as antioxidants and protect against atherosclerosis. Despite promising epidemiological data which suggested benefits from a higher intake of α-tocopherol (&alphaT), one of the major forms of dietary vitamin E, for protection against atherosclerosis, large scale, randomised controlled trials have generally shown no protective effect of high dose &alphaT supplementation. Recent studies suggest that the other major dietary tocopherol isomer, γ-tocopherol (&gammaT), may possess biological activities not shared by &alphaT. Supplementation with &gammaT, or mixtures of tocopherols rich in &gammaT, have shown biological activities that may help protect against atherosclerosis. The aim of this PhD project is to further characterise the biological relevance of ?T for protection against CVD... Both ?- and mixed tocopherol supplementation resulted in reduced plasma F2-isoprostanes (P <0.001 and P = 0.001, respectively) but did not affect 24 hour urinary F2-isoprostanes and erythrocyte antioxidant enzyme activities. Neither &alphaT nor mixed tocopherol supplementation affected any measured plasma markers of inflammation. The tocopherol supplementation also did not affect COX-2 activity as assessed by 14 stimulated whole blood prostaglandin E2 synthesis, and urinary prostacyclin metabolite output. Compared to the placebo group, stimulated neutrophil leukotriene B4 (LTB4) production decreased significantly in the mixed tocopherol group (P=0.02) but not in the &alphaT group (P=0.15). The ability of both pure &alphaT and mixed tocopherol supplementation to reduce systemic lipid peroxidation in patients with type 2 diabetes, suggests potential benefits of vitamin E supplementation in this population. However, despite decreasing oxidative stress, our results also suggests that in populations with well controlled type 2 diabetes, supplementation with either &alphaT, or mixed tocopherol rich in &gammaT, is unlikely to confer further benefits in reducing systemic inflammation. Future research into the possible unique biological activity of different tocopherol isomers other than &alphaT, for example, their ability to affect the 5-LO pathway and production of inflammatory mediators such as LTB4, is warranted.
    Original languageEnglish
    QualificationDoctor of Philosophy
    Publication statusUnpublished - 2006

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