Alternative Medicine Review 1999 (Dec); 4 (6): 414–423 ~ FULL TEXT
Randall A. Swain, MD, and Barbara Kaplan-Machlis, PharmD
Coronary artery disease is the number one cause of death in the United States and other industrialized countries. Hence, correspondingly greater attention is being focused on prevention of this chronic degenerative disease. In this arena, antioxidants such as vitamin E may serve an important role.
Vitamin E acts as an antioxidant by donating an electron to neutralize
reactive oxygen species and prevent oxidative damage thought to be responsible
for atherosclerosis, oncogenesis, various neurologic problems and ophthalmic
disorders. As a result, vitamin E is being investigated as a potential
preventive nutrient for these common clinical disorders. Vitamin E has
a favorable side effect profile and relatively low cost, making it an ideal
part of a disease prevention program, provided it is indeed efficacious.
This review examines the available scientific evidence for vitamin E administration
in the prevention of coronary artery, and cerebro- and peripheral vascular
Vitamin E Metabolism and Deficiency States
Vitamin E is a lipid soluble micronutrient containing eight active,
naturally occurring plant constituents - tocopherols and tocotrienols.
Vitamin E is an essential element of human nutrition and exerts its effects
in the body via a number of different mechanisms. The most abundant and
active isomer is d-alpha-tocopherol, which is used to calculate the vitamin
E content of food; other tocopherols include the beta, gamma, and delta
isomers. Vitamin E functions primarily as an antioxidant, protecting cellular
membranes from oxidative damage or destruction, and red blood cells from
hemolysis. Vitamin E is also thought to enhance vitamin A utilization and,
at high doses, may be involved in the inhibition of platelet aggregation.
Foods rich in vitamin E include vegetable oils, green vegetables, nuts,
wheat germ, and whole grains. Vitamin E distributes to all body tissues,
especially adipose tissue where it is stored. Tocopherols are metabolized
by the liver to glucuronides and eliminated in feces and bile.
Vitamin E deficiency in the United States is rare. Murphy et al reported
that 96 percent of men and 88 percent of women achieved the RDA through
diet alone in their population-based report. 
Dietary manipulations are largely unsuccessful in increasing serum vitamin
E levels significantly.  However, absorption
may be as low as 10 percent, even when doses of 200 mg are administered
(1 mg=1.5 IU).  In general, vitamin E absorption
(unless taken as a water-miscible supplement) is dependent on pancreatic
enzymes and bile salts which enhance absorption of fats in the small intestine.
Two general patient populations are at risk for vitamin E deficiency: premature,
very low birth-weight infants, and patients with fat malabsorption syndromes
(e.g., pancreatic insufficiency, cystic fibrosis, betalipoproteinemia,
or small intestinal resection). Premature neonates are at risk due to low
fat stores, low transmission of fat across the placenta, and initial problems
with intestinal absorption. Infants may develop hemolytic anemia or retrolental
fibroplasia, a severe retinal disease thought to originate from oxygen
therapy, in the absence of sufficient internal antioxidants.
Characteristics of vitamin E deficiency include a variety of symptoms
such as areflexia, psychological syndromes, cognitive dysfunction, nystagmus,
ataxia, muscle weakness, and sensory loss in the arms or legs. 
Manifestations of vitamin E deficiency may not be completely reversible.
Diagnosis is often made using serum vitamin E levels obtained as a result
of clinical suspicion in high-risk individuals.
Vitamin E is well tolerated in large oral doses; up to 3200 IU per day
have been administered to humans without adverse effects. 
Historically, experts thought vitamin E would increase the effects of warfarin
by causing vitamin K deficiency. In a recent study of patients on chronic
warfarin treatment, no significant effect on prothrombin times was observed
when 800-1200 mg of vitamin E per day was administered. 
Conversely, if tissues are already vitamin K deficient, some experts suggest
alpha-tocopherol may increase bleeding tendency through its mild effect
on platelet aggregation at larger dosages (> 800 IU/day). 
Even though vitamin E is relatively nontoxic, the potential risks of long-term,
mega-dose therapy (> 1000 IU/day) are unknown.
Natural source vitamin E (d-alpha-tocopherol) differs from synthetic
vitamin E (dl-alpha-tocopherol) in its stereoisomer formation. Synthetic
vitamin E is a mixture of isomers. It is thought that the bioavailability
of synthetic vitamin E is essentially one-half that of natural vitamin