Vitamin E, one of the most important lipid-soluble antioxidant nutrients, is found in nut oils, sunflower seeds, whole grains, wheat germ, and spinach. Severe deficiency, as may occur in persons with abetalipoproteinemia or fat malabsorption, profoundly affects the central nervous system and can cause ataxia and a peripheral neuropathy resembling Friedreich ataxia. [1, 2, 3, 4, 5] Patients receiving large doses of vitamin E may experience a halt in the progression of the disease. Vitamin E overdose is difficult to achieve and, thus, is extremely uncommon.
This vitamin is thought to have a role in preventing atherosclerosis by inhibiting the oxidation of low-density lipoprotein (LDL). [6, 7] Several epidemiologic studies have indicated that high dietary intake of vitamin E is associated with high serum concentrations of alpha tocopherol, as well as with lower rates of ischemic heart disease. [8, 9] However, although the Cambridge Heart Antioxidant Study supported this hypothesis, a subsequent report, the prospective Heart Outcomes Prevention Evaluation Study, did not. [7, 10, 11]
Vitamin deficiencies related to cystic fibrosis, chronic cholestatic liver disease, abetalipoproteinemia, short-bowel syndrome, isolated vitamin E deficiency syndrome, and other malabsorption syndromes may lead to varying degrees of neurologic deficits. [2, 4, 5] One milligram is equivalent to 1.5 international units (IU).
Abnormalities relating vitamin E deficiency progress from hyporeflexia, ataxia, limitation in upward gaze, and strabismus to long-tract defects, including visual-field constriction and profound muscle weakness.  Complete blindness, cardiac arrhythmia, and dementia may occur in patients in whom vitamin E deficiency has been prolonged and severe.
Mechanism of action
Vitamin E appears to act within membranes by preventing the propagated oxidation of saturated fatty acids. [8, 14, 15, 16] Oxidized LDL particles are taken up more readily by macrophages than by native LDLs, which leads to the formation of cholesterol-laden foam cells found in the fatty streak of early atherosclerosis. It is hypothesized that vitamin E reduces atherosclerosis and subsequent coronary heart disease by preventing oxidative changes to LDLs.
Atherogenesis also may be promoted by the following activities of oxidized LDLs: (1) chemotactic action on monocytes, (2) cytotoxicity to endothelial cells, (3) stimulation of the release of growth factors and cytokines, (4) immunogenicity, and (5) possible arterial vasoconstrictor actions. Notwithstanding the attractiveness of these hypotheses, the Heart Outcomes Prevention Evaluation prospective study failed to confirm the efficacy of vitamin E in reducing coronary artery disease. 
Vitamin E appears to enhance lymphocyte proliferation, decrease the production of immunosuppressive prostaglandin E2, and decrease levels of immunosuppressive serum lipid peroxides. 
Vitamin E has been demonstrated to inhibit platelet adhesion, as measured by a laminar flow chamber when blood from patients who have taken vitamin E supplements is tested. This effect appears to be related to a reduced development of pseudopodia, which normally occurs upon platelet activation. It may be related to changes in fatty acylation of platelet structural proteins. Although vitamin E inhibits platelet aggregation in vitro, its effect in vivo has not been consistent.
Chemical evidence of lipid oxidation is apparent at all stages of atherosclerosis, especially in macrophage-rich and early atherosclerotic lesions. Alpha tocopherol, the most active form of vitamin E, is the predominant lipophilic antioxidant for LDL. However, patients with advanced coronary atherosclerosis are at a much greater risk of myocardial infarction, which usually occurs as a result of rupture of mature atheromatous plaques.
The prevailing hypothesis of how antioxidants may contribute to the reduction of coronary heart disease is that they protect LDL from oxidative modification. However, another effect of vitamin E in vitro is modulation of prostaglandin metabolism, leading to inhibition of platelet aggregation. In vivo, vitamin E appears to inhibit platelet adhesion effectively and to inhibit platelet aggregation weakly. Vitamin E also inhibits protein kinase C activity, which can contribute to the proliferation of smooth-muscle cells in arterial walls.
Several studies on the effect of vitamin E on heart disease and its risk factors show protective effects associated with intakes well above the recommended daily allowance (RDA). Although vitamin E has been used as a preventive agent for heart disease,  this use has not been approved by the FDA.
Epidemiologic evidence indicates a strong dose response between decreased risk of heart disease and increased vitamin E intakes from supplements and diet.
Significant protection is thought to be gained beginning at daily intakes of 67 mg/d of alpha-tocopherol equivalents (1 mg is equivalent to 1.5 IU). LDL cholesterol oxidation decreased significantly in blood taken from subjects receiving no more than 400 IU/d but not less than 200 IU/d. Again, note that the prospective Heart Outcomes Prevention Evaluation study did not validate these previous studies.