Long‐term vitamin E supplementation reduces atherosclerosis and mortality in LDLR−/ −mice

Epidemiological and experimental evidence indicated potential health benefits of vitamin E supplementation (+E) on coronary heart disease (CHD), but recent clinical trials reported no effect. We hypothesized that +E from early age may prevent or retard development and progression of atherosclerosis and CHD mortality. To test this hypothesis, 250 LDLR−/ − mice were divided into groups receiving high fat/chol diet (HFHC), moderate fat/chol (MFMC), or low fat/chol (LFLC) diets. The HFHC and MFMC groups were further subdivided into groups (N=25) receiving respective diets with +E (500 IU E/kg diet) for 0, 6, 12 and 18 mo. The diet of LFLC groups contained either +E or not (N=25). After 18 mo, plasma cholesterol was high in all dietary groups and plasma E was high in +E groups. Body weight was highest in HFHC groups and lowest in LFLC groups. Higher mortality was observed among mice treated with HFHC (48 %) and MFMC (49 %) than LFLC group (22 %). +E diets had no significant effect on mortality and extent of aortic lesions in HFHC or LFLC mice regardless of supplementation time and duration. However, mortality was significantly (p=0.04) lower among the LFLC mice receiving +E diet from early life than those that did not receive +E diet (2 vs. 9). This observation coincided with a lesser extent of aortic lesions in +E compared to LFLC mice without +E (50 vs. 65%, p=003). In conclusion, a relatively low dose and long‐term E supplementation is effective in reducing mortality and atherosclerotic lesions when the diet of genetically prone mice contains low fat and low cholesterol. Supported by NIH grant HL069897‐01A1.