A 90-day feeding study with gerbils was conducted to evaluate the influence of dietary vitamin E levels (25 mg/kg diet, 75 mg/kg, 300 mg/kg, and 900 mg/kg), two levels of dietary methionione (casein or casein+L-methionine (1% w/w)) and two sources of lipid (soybean oil [20%] or soybean oil [4%]+coconut oil [16%, 1:4 w/w]) upon serum lipids (total cholesterol, HDL-cholesterol, LDL-cholesterol). In addition, this study examined the effects of diet-induced hyperhomocysteinemia and supplemental dietary vitamin E on the oxidation of low density lipoproteins. Tissue vitamin E (heart, liver, and plasma) demonstrated a dose response (P less than or equal to 0.001) following the supplementation with increasing dietary vitamin E (25, 75, 300, and 900 mg/kg). In addition, tissue vitamin E levels were found to be higher (P less than or equal to 0.001) in those animals receiving a combination of coconut oil+ soybean oil as compared to the group receiving soybean oil solely. Blood cholesterol profiles indicated an increase (P less than or equal to 0.001) in total cholesterol and LDL cholesterol by the influence of saturated fat and supplemental methionine. Low-density lipoprotein cholesterol profile demonstrated a reduction (P less than or equal to 0.001) at the higher dietary vitamin E levels (300 and 900 mg/kg) as compared to the 25 mg/kg and 75 mg/kg dietary vitamin E. Plasma protein carbonyls were not influenced by dietary vitamin E nor by supplemental methionine intake. In vitro oxidation of LDL showed that vitamin E delayed the lag time of the oxidation phase (P less than or equal to 0.001) and reduced total diene production (P less than or equal to 0.001). On the contrary, supplemental methionine decreased (P less than or equal to 0.001) the delay time of the lag phase, whereas total diene production was increased (P less than or equal to 0.001). Plasma lipid hydroperoxides were significantly reduced (P less than or equal to 0.05) with supplemental dietary vitamin E, whereas supplemental L-methionine (1%) resulted in a significant (P less than or equal to 0.05) increase in lipid plasma hydroperoxide formation. Plasma homocysteine was elevated (P less than or equal to 0.001) with supplemental dietary L-methionine (1%) as well as the inclusion of dietary saturated fat. The present data showed that 1) a combination of dietary lipids (saturated and unsaturated fatty acids) as well as vitamin E and methionine supplementation altered blood cholesterol lipoprotein profiles; 2) in vitro oxidation parameters including LDL (lag time and diene production) and plasma hydroperoxide formations were affected by vitamin E and methionine supplementation; and 3) plasma homocysteine concentrations were influenced by supplemental methionine and the inclusion of dietary saturated fat. (C) 2004 Elsevier Inc. All rights reserved.