Vitamin E is an important antioxidant which protects cells from free radical damage, thereby prolonging cell life and slowing the aging process. Research has shown this nutrient plays a vital role in the prevention and treatment of cardiovascular disease, cancer, immune system disorders, and aging-related degenerative diseases.

Three major clinical studies (The Nurses' Health Study, The Physicians' Health Study, and a study done by the University of Texas Southwestern Medical Center) have provided evidence supporting the benefits of vitamin E supplementation in the prevention of heart disease. Vitamin E blocks the oxidation of LDL cholesterol, thereby reducing arterial damage and plaque formation. A study at the University of South Carolina School of Medicine showed that 100 IU of vitamin E daily actually may have reversed arterial blockage. A World Health Organization study showed that supplemental vitamin E was more likely to prevent fatal heart attacks by lowering blood cholesterol, presumably because it prevents oxidation of cholesterol into its most toxic form.

Vitamin E has long been recognized as an anticlotting agent, thereby reducing risk of heart attack and stroke. Studies have shown vitamin E's important role in cancer prevention and in the benefits of use during cancer treatment. Animal and human studies have concluded that the nutrient blocks the initiation of carcinogenesis and reduces the incidence of skin, oral, stomach, colon, and breast cancer. Other studies have suggested that vitamin E may also reduce the risk of lung, esophageal, and cervical cancer. Researchers have found that during cancer treatment, vitamin E supplementation protects normal cells from the damaging effects of chemotherapy without protecting the cancer cells, which reduces side effects without reducing efficacy. New research suggests that vitamin E interferes with oxygen-controlled signals which promote cancer cell growth.

The most recent studies have shown vitamin E supplementation may reduce the incidence of prostate cancer, reverse diabetic neuropathy in Type II diabetics, may increase/improve insulin's effect in Type II diabetes, and significantly improve immune status in aging adults. Preliminary research suggests the nutrient may slow or prevent the progress of degenerative brain diseases.

Food sources of vitamin E include wheat germ oil, margarine, soybean oil, almonds, safflower oil, hazelnuts, corn oil, peanuts, cottonseed oil, walnuts, canola oil, mayonnaise, sunflower seeds, spinach, kale, sweet potatoes, and yams.

Vitamin E is destroyed when vegetable oils are processed and bleached; only cold-pressed vegetable oils are a good source. Wheat germ oil is the richest source of natural vitamin E.

Vitamin E occurs in several forms with varying biologic activity. Alpha-tocopherol is the most common, most potent, and best absorbed form. Other forms include beta-, delta-, and gamma-tocopherol, and alphatocotrienol.

Supplemental vitamin E is available in both natural and synthetic forms.

• Natural vitamin E (d-alpha-tocopherol) has been the preferred form, and it is available with mixed tocopherols added.
• The synthetic form is dl-alpha-tocopherol.
• Standard preparations are available in 50 IU, 100 IU, 200 IU, 400 IU, 500 IU, 600 IU, and 1,000 IU softgels, tablets, and capsules.
• Vitamin E succinate ("dry-E") is water soluble and best tolerated by those with fat malabsorption syndromes.

Vitamin E may have the following therapeutic effects.

• Slows the aging process of all cells/tissues
• Protection against environmental pollutants and toxins
• Protects integrity of red blood cells and aids in prevention of hemolytic anemia
• Supplementation indicated for all fat malabsorption disorders, including celiac disease, tropical sprue, cystic fibrosis, and pancreatic disease
• Indicated for use in the treatment of most skin disorders, e.g., acne, eczema, psoriasis
• Prevention against atherosclerosis or its progression by helping reduce/reverse plaque formation
• Prevents oxidation of LDL cholesterol
• Improves arterial response when atherosclerosis is present
• Reduces tissue damage associated with ischemia during heart surgery; indicated for use before and after any surgery
• Promotes proper wound healing
• Anticlotting agent useful in prevention of pulmonary embolism, thrombosis, and stroke; indicated for use for angina, atherosclerosis, intermittent claudication, and for women using hormonal contraceptives
• Aids in prevention of cataracts and macular degeneration
• Indicated for use in all reproductive disorders
• Reduces symptoms associated with premenstrual syndrome
• Effective against fibrocystic breast disease
• Protects against initiation of carcinogenesis
• Indicated for use in cancer prevention and treatment
• May slow progression of mental deterioration associated with Alzheimer's, degenerative, or arteriosclerotic brain disease
• Significantly improves age-related immune response dysfunction
• Indicated for use in Type II diabetes
• Significantly decreases symptoms of lupus erythematosus with dose of 1,200 IU/day

Recommended dietary allowances (RDAs) are as follows.

• Neonates to 6 months: 4 IU
• Infants 6 months to 1 year: 6 IU
• Children 1 to 3 years: 9 IU
• Children 4 to 10 years: 10 IU
• Children over 10 years and adults: 12 IU for females, 15 IU for males.

Note: 1 mg vitamin E equals 1.5 IU.

Based on clinical trials, the recommended dose for disease prevention and treatment for adults is 400 to 800 IU/day.

Vitamin E is relatively nontoxic. Adverse effects which may occur with very high doses (more than 1,200 IU/day) include nausea, flatulence, diarrhea, and heart palpitations.

• Increased blood pressure. Individuals with hypertension may show an increase in blood pressure if starting dose is too high. Recommendation is for initial dose of 100 IU/day, increasing as tolerated up to 400 IU/day with monitoring as dosage is increased.
• Prolonged bleeding time
• High doses of vitamin E may interfere with vitamin K activity.
• Caution with warfarin use
• Extreme doses (more than 800 IU) over time may have detrimental effects, although toxicity per se has not been documented.

A double-blind, randomized study evaluated the interaction between an antiaggregating agent with vitamin E in 100 patients at risk for transient ischemic attacks (TIAs) (Steiner et al. 1995). Patients were administered either aspirin (325 mg) or aspirin plus vitamin E (400 IU/day) for two years. The group receiving combination therapy had a significant reduction in ischemic events and platelet adhesiveness. However, the incidence of hemorrhagic stroke was not affected by treatment. The combination of vitamin E and aspirin appears to be safe and may benefit patients at risk for TIAs.

Vitamin E inhibits drug uptake in a dose-dependent manner in human cultured fibroblasts exposed to single and repetitive doses of chloroquine and other cationic amphiphilic drugs (Scuntaro et al. 1996). Cationic amphiphilic drugs encompass a variety of therapeutic classes of medications including antiarrhythmics, antidepressants, and neuroleptics.

Vitamin E inhibits drug uptake in a dose-dependent manner in human cultured fibroblasts exposed to single and repetitive doses of chlorpromazine and other cationic amphiphilic drugs (Scuntaro et al. 1996). Cationic amphiphilic drugs encompass a variety of therapeutic classes of medications including antiarrhythmics, antidepressants, and neuroleptics.

A study with ten healthy subjects evaluated the interaction between water-soluble vitamin E and cyclosporine (Chang et al. 1996). After two doses of cyclosporine (10 mg/kg po), oral vitamin E was randomly administered with the drug. Concomitant administration of vitamin E and cyclosporine significantly decreased the clearance and steady-state volume of distribution for the drug. The combination therapy increased the area under the curve (AUC) for cyclosporine. The increased AUC may be the result of enhanced bioavailability. However, a subsequent in vitro study suggested that vitamin E and cyclosporine antagonize one another (Van Rensburg et al. 1998).

Vitamin E inhibits drug uptake in a dose-dependent manner in human cultured fibroblasts exposed to single and repetitive doses of desipramine and other cationic amphiphilic drugs (Scuntaro et al. 1996). Cationic amphiphilic drugs encompass a variety of therapeutic classes of medications including antiarrhythmics, antidepressants, and neuroleptics.

Preliminary findings indicate that hormone replacement therapy (HRT) may preserve the content of vitamin E in LDL particles that, in turn, reduce the amount of oxidized LDL (Clemente et al. 1996). Concomitant administration of vitamin E with transdermal estradiol was shown to improve LDL, HDL, and total cholesterol status in postmenopausal women (Inal et al. 1997). Most studies showing a benefit from vitamin E on heart disease risk have used quantities of vitamin E (400 to 800 IU/day) that are much higher than RDA values (Emmert and Kircher 1999).

There are conflicting reports regarding the effect of gemfibrozil on vitamin E status in hyperlipidemic patients. In one study, gemfibrozil treatment in men with combined hyperlipidemia reduced serum ubiquinone-10 and gamma- and alpha-tocopherol levels (Aberg et al. 1998). In another study, gemfibrozil had no effect on vitamin E status and increased the LDL vitamin E/lipid peroxide ratio concentrations (Yoshida et al. 1998).

HMG-CoA reductase therapy may decrease the antioxidant capacity of vitamin E on LDL cholesterol (Palomaki et al. 1998). However, coadministration of vitamin E (300 IU) with simvastatin (20 mg) improved markers of blood vessel elasticity in hypercholesterolemic patients more than simvastatin monotherapy (Neunteufl et al. 1998). Similar benefits may be observed with fluvastatin and other HMG-CoA reductase inhibitors.

Oral contraceptives reduce some of the vitamins and enzymes involved in the oxidative defense system (Ciavatti and Renaud 1991; Tangney and Driskell 1978). Impaired antioxidant status can increase the susceptibility to lipid peroxidation and possibly thrombosis in women (Ciavatti and Renaud 1991). Some of these effects can be counteracted by vitamin E supplements.

Vitamin E inhibits drug uptake in a dose-dependent manner in human cultured fibroblasts exposed to single and repetitive doses of propranolol and other cationic amphiphilic drugs (Scuntaro et al. 1996). Cationic amphiphilic drugs encompass a variety of therapeutic classes of medications including antiarrhythmics, antidepressants, and neuroleptics.

An in vitro study suggested that vitamin E antagonized the chemosensitizing effects of verapamil (Van Rensburg et al. 1998). Tests performed using the human small cell lung cancer line demonstrated that the inclusion of alpha-tocopherol (25 mcg/mL) prevented the ability of verapamil (2 mcg/mL) to sensitize the cells to the effects of doxorubicin and vinblastine.

Vitamin E does not appear to enhance the pharmacologic effects of warfarin (Kim and White 1996). However, the administration of high doses of vitamin E to individuals with reduced levels of vitamin K may potentiate a vitamin K deficiency and increase the anticoagulant effect of warfarin (Corrigan 1982). Although the mechanism of this interaction is unclear, vitamin E may affect the carboxylation of prothrombin, a vitamin-K-dependent step in the production of coagulation factors.

Antiviral activity and bone marrow toxicity of zidovudine (AZT) were evaluated in the presence of water-soluble vitamin E (alpha-D-tocopherol acid succinate (ATS)) in two cell test systems (Gogu et al. 1989). In the MT4 cell line, ATS displayed a dose-dependent increase in anti-HIV activity that was six times greater than when AZT was also administered. In addition, vitamin E showed significant protection against AZT-induced toxicity in murine bone marrow cells.

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