Long-term vitamin E supplementation reduces atherosclerosis and mortality in Ldlr−/− mice, but not when fed Western style diet

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-lesion areas. 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.

Vitamin E: Regulatory role in the cardiovascular system

“…Human aortic smooth muscle, HL-60 differentiated macrophage, THP-1 monocyte, and macrophage cells (18,19) Decrease in lipid accumulation and inflammatory response by inhibiting NFkB signaling pathway U937 macrophage (20) Protection against atherosclerotic lesion development and aorta damage LDLR −/− mice and Wistar rats (21), (22) Reduction of cholesterol-induced atherosclerotic lesions through inhibition of CD36, PKC signaling, MMP-1 and -9, c-jun phosphorylation as well as the induction of Nrf2, PPARγ, LXRα, and ABCA-1 levels ApoE −/− mice and hypercholesterolemic rabbits (23), (24), (25), (26), (27), (28) Reduction of mortality following acute myocardial infarction or heart failure Rat (29), (30) reduced atherosclerotic lesion size in the aorta of mice (33). Additionally, mice receiving vitamin E, together with Coenzyme Q10, showed attenuation in the progression of atherosclerosis at the aortic root, arch, and descending thoracic aorta (34).…”

Vitamin E Conditionally Inhibits Atherosclerosis in ApoE Knockout Mice by Anti‐oxidation and Regulation of Vasculature Gene Expressions

“…In addition, most of the previous animal studies focus on the preventive effect of vitamin E supplementation at early stages of atherosclerosis and reach the expected results [29,34,35]. Meydani et al [36] recently reported that the effect of vitamin E on atherosclerosis depends on the blood lipid levels, lesion degree and disease stages using the LDLR knockout mouse as an atherosclerosis model as well as duration and time point of vitamin supplementation. Clinically, the atherosclerotic pathology and mechanisms are more complicated and individualized, suggesting that experiments designed to dynamically investigate the effects of vitamin E on the different stages of atherosclerosis are needed [37].…”

Effect of the consumption on buriti oil on the metabolism of rats induced by iron overload

“…Due to that the fact that buriti oil is a source of monounsaturated fatty acids and vitamins A and E. (14,15,21) may have pre vented this increase in the triglyceride levels even in the group that received iron overload (EB), as it showed intermediate and similar TAG levels when compared to CB group, indicating a possible action of this oil on this biochemical parameter. The maintenance of the levels of triglycerides in groups that consumed buriti oil add ed to the diet (CB, EB) can be justified by the mech anism of vitamin A and vitamin E absorption, which after absorption is transported by chylomicrons and lipoproteins containing other dietary lipids (such as tri glycerides, phospholipids, cholesterol, and cholesteryl esters) and apolipoprotein B (apoB), which can quan titatively reduce the transport of these lipids (33,34).…”