Vitamin E dietary supplementation significantly affects multiple risk factors for cardiovascular disease in baboons

BACKGROUND: Oxidative stress is a widely accepted risk factor for cardiovascular disease (CVD), but the CVD benefit of dietary antioxidants, such as vitamin E, is controversial. OBJECTIVE: Therefore, we have investigated, in the baboon model, the effects of dietary vitamin E supplementation on risk factors for CVD. DESIGN: Pedigreed baboons (n = 251) were fed 2 atherogenic diets, high in fat and cholesterol, that differed in vitamin E concentrations. After 7 wk on each diet, blood samples were taken, and a panel of CVD risk factor traits (ie, indicators of lipoprotein metabolism and oxidative stress) were measured. RESULTS: Vitamin E supplementation caused significantly higher total antioxidant status (TAS) and lower oxidized LDL as expected. In addition, vitamin E caused 2 paradoxical effects on HDL metabolism: higher apolipoprotein A-I (apo A-I) concentrations and lower HDL sizes. We calculated a difference (Delta) variable for each trait as the value on the high-vitamin E diet minus that on the low-vitamin E diet and determined that several HDL concentration Delta variables were significantly correlated with Delta TAS, but only one, Delta apo A-I, was independently correlated. Genetic analyses showed that 2 Delta variables, Delta paraoxonase and Delta HDL(2), were significantly heritable, but that neither Delta TAS nor Delta apo A-I were heritable. CONCLUSIONS: Thus, our data show that dietary vitamin E improves TAS and LDL quality. They also show 2 apparently paradoxical effects on HDL metabolism: lower HDL(2), which is mediated by genes, and higher apo A-I, which is not. These effects have contrasting associations with CVD risk and may help account for the mixed results from clinical trials of dietary vitamin E.