Vitamin E, comprising mixed tocopherols and tocotrienols, has been investigated for its potential role in preventing or treating arteriosclerosis (also known as atherosclerosis). The scientific rationale comes from Vitamin E's function as a lipid-soluble antioxidant, which can potentially inhibit the oxidative modification of low-density lipoprotein (LDL) cholesterol—a major step in the development of arterial plaques. Early epidemiological studies suggested an inverse relationship between Vitamin E intake and cardiovascular disease risk. However, large-scale randomized controlled trials (RCTs) and meta-analyses have, for the most part, failed to show clear benefit. For example, the HOPE and GISSI-Prevenzione trials found that Vitamin E supplementation did not significantly reduce major cardiovascular events. Some observational data and small studies do indicate possible minor benefits, but these are inconsistent and may be confounded by other factors.

Tocotrienols, a less-studied form of Vitamin E, have demonstrated some promise in preclinical studies for reducing cholesterol synthesis and inhibiting vascular smooth muscle cell proliferation. However, robust clinical evidence in humans is lacking. Current guidelines from major cardiology organizations do not recommend Vitamin E supplements for arteriosclerosis prevention or treatment due to insufficient and inconsistent evidence. In summary, while there is a plausible biological mechanism and some limited supportive data, the overall scientific evidence is weak and does not justify routine use of Vitamin E for arteriosclerosis.