We evaluated the effects of vitamin E and beta-carotene on apolipoprotein (
apo)E +/- female mice, which develop atherosclerosis only when fed diets hi
gh in triglyceride and cholesterol. Mice were fed a nonpurified control die
t (5.3 g/100 g triglyceride, 0.2 g/100 g cholesterol), an atherogenic diet
alone (15.8 g/100 g triglyceride, 1.25 g/100 g cholesterol, 0.5 g/100 g Na
cholate) or the atherogenic diet supplemented with either 0.5 g/100 g (+)-a
lpha-tocopherol (mixed isomers); 0.5 g/100 g palm tocopherols palm-E; 33% a
lpha-tocopherol, 16.1% alpha-tocotrienol, 2.3% beta-tocotrienol, 32.2% gamm
a-tocotrienol, 16.1% delta-tocotrienol; 1.5 g/100 g palm-E; or 0.01 g/100 g
palm-carotenoids (58% beta-carotene, 33% alpha-carotene, 9% other caroteno
ids). Compared with mice fed the control diet, plasma cholesterol was fourf
old greater in mice fed the atherogenic diet. Mice fed the 1.5 g/100 g palm
-E supplement had 60% lower plasma cholesterol than groups fed the other at
herogenic diets. Mice fed the atherogenic diet had markedly higher VLDL, in
termediate density lipoprotein (IDL) and LDL cholesterol and markedly lower
HDL cholesterol than the controls. Lipoprotein patterns in mice supplement
ed with alpha-tocopherol or palm carotenoids were similar to those of the m
ice fed the atherogenic diet alone, but the pattern in mice supplemented wi
th 1.5 g/100 g palm-E was similar to that of mice fed the control diet. In
mice fed the atherogenic diet, the hepatic cholesterol plus cholesterol eat
er concentration was 4.4-fold greater than in mice fed the control diet. Su
pplementing with 1.5 g/100 g palm-E lowered hepatic cholesterol plus choles
terol ester concentration 66% compared with the atherogenic diet alone. Mic
e fed the atherogenic diet had large atherosclerotic lesions at the level o
f the aortic valve. With supplements of 0.5 g/100 g palm-E or 1.5 g/100 g p
alm-E, the size of the lesions was 92 or 98% smaller, respectively. The 0.5
g/100 g alpha-tocopherol and palm carotenoid supplements had no effect. Su
pplements did not alter mRNA abundance for apolipoproteins Al, E, and C3. T
he beneficial effect of tocotrienols on atherogenesis, the plasma lipoprote
in profile and accumulation of hepatic cholesterol esters cannot be attribu
ted to their antioxidant properties.