Highlights
- •Medium, or high fat/cholesterol accelerates atherogenesis and death in Ldlr−/− mice.
- •Vitamin E (E) is not effective to reduce atherogenesis, even started from early age.
- •E supplementation also is not effective to reduce fat/cholesterol-induced mortality.
- •E is only effective when fat/cholesterol is reduced and E started from an early age.
Abstract
Objectives
Epidemiological and experimental evidence have indicated potential health benefits
of vitamin E supplementation on coronary heart disease (CHD), but several clinical
trials have reported no benefit from vitamin E supplementation on CHD. We hypothesized
that supplemental intake of vitamin E from an early age may prevent or retard the
development and progression of atherosclerosis and CHD mortality.
Methods
To test this hypothesis, 300 Ldlr−/− mice were divided into groups receiving Western style high fat/cholesterol (HFHC),
moderate fat/cholesterol (MFMC), or low fat/cholesterol (LFLC) diets all containing
50 IU of vitamin E. These dietary groups were further subdivided into four sub-groups
(n = 25) receiving their respective diets with no vitamin E supplementation or additionally
supplemented with vitamin E (500 IU/kg diet) starting at the early age of 5 wks, or
6 mo, or 12 mo. All mice remained on their assigned diets until age 18 mo. Body weight,
health status and survival rate of mice were monitored and recorded. After 18 mo of
dietary treatments, mice were sacrificed.
Results
Body weight was the highest in HFHC groups and the lowest in LFLC groups. Plasma concentration
of cholesterol and triglycerides was high in all dietary groups, and plasma vitamin
E was high in vitamin E supplemented groups. Fifty percent of mice fed Western style
HFHC diet and 53% of mice fed MFMC diet survived during the 18 mo, whereas 75% of
mice fed LFLC diet survived during the 18 mo dietary treatments. At the age of 18 mo,
all the Ldlr−/− mice, regardless of dietary treatments, had several advanced atherosclerotic lesions
in both aortic root and aortic tree. Within the LFLC groups, those that received vitamin
E supplements from age 5 wks up to 18 mo had a significantly higher survival rate
of 88% (p = 0.04) and lower mortality (12%) compared to mice that did not receive vitamin E
supplements (64%). This lower mortality rate and higher survival rate coincided with
significantly (p = 0.03) fewer aortic lesions in the vitamin E supplemented LFLC group (50%) compared
to LFLC mice that did not receive vitamin E supplements in their diets (65%). Subjective
immunohistochemical evaluation of aortic valves showed that LFLC mice that received
vitamin E supplements for 18 mo had less intima media thickness compared to LFLC mice
that did not receive vitamin E supplements in their diet. The LFLC mice that were
supplemented with vitamin E for 18 mo had the lowest mRNA expression of inflammatory
markers such as VCAM-1, MCP-1 and CD36 in samples obtained from lesion and non-lesionareas.
Conclusion
In conclusion, 500 mg vitamin E/kg diet in Ldlr−/− mice is not effective at reducing mortality and atherosclerosis when the diet contained
high or medium levels of fat and cholesterol. However, a relatively low dose and long-term
vitamin E supplementation started from an early age is effective in reducing mortality
and atherosclerotic lesions in genetically prone Ldlr−/− mice fed LFLC diet.
Keywords
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Article info
Publication history
Accepted:
December 9,
2013
Received in revised form:
October 31,
2013
Received:
July 1,
2013
Identification
Copyright
© 2014 Elsevier Ireland Ltd. Published by Elsevier Inc. All rights reserved.
