Skin reactions such as contact dermatitis and eczema have been reported with topical vitamin E preparations, such as ointments or vitamin E containing-deodorants. Individuals with known or suspected hypersensitivity to vitamin E should avoid these products.
Side Effects and Warnings
Recent evidence suggests that regular use of high-dose vitamin E may increase the risk of death (from "all causes") by a small amount. These conclusions have been criticized by some experts because they are based on re-calculations (meta-analyses) of the results of prior smaller studies, which were of mixed quality, with variable results, and often in patients with chronic illnesses. Nonetheless, this is the best available scientific evidence currently, and therefore chronic use of vitamin E should be used cautiously and high-dose vitamin E should be avoided. Acute overdose of vitamin E is very uncommon.
For short periods of time, vitamin E supplementation is generally considered safe at doses up to the recommended tolerable upper intake level (UL). However, vitamin E is possibly unsafe when used orally at doses exceeding the tolerable upper intake level. The Recommended Dietary Allowance (RDA) obtained through food consumption is considered to be safe and beneficial.
Skin reactions, such as contact dermatitis and eczema, have been reported with topical vitamin E preparations, such as ointments or vitamin E containing-deodorants.
In rare cases, vitamin E supplementation has been associated with abdominal pain, diarrhea, nausea, diarrhea, or flu-like symptoms (particularly when taken at high doses). The risk of necrotizing enterocolitis may be increased with large doses of vitamin E.
In rare cases, vitamin E supplementation has been associated with gonadal dysfunction and diminished kidney function.
High doses of vitamin E might increase the risk of bleeding, due to inhibition of platelet aggregation and antagonism of vitamin K-dependent clotting factors (particularly in patients with vitamin K deficiency). In studies of vitamin E, a small increase in rate of hemorrhagic (bleeding) stroke and gum bleeding has been observed, particularly which used in humans with aspirin. Increased risk of bleeding when used with warfarin (Coumadin®) has been noted in animal studies. However, other studies have not observed a greater incidence of bleeding. Bleeding has been observed in patients given high repeated doses of intravenous all-rac-alpha-tocopherol (synthetic vitamin E). Caution is advised in patients with bleeding disorders or taking drugs that may increase the risk of bleeding. Dosing adjustments may be necessary.
In rare cases, vitamin E supplementation has been associated with dizziness, fatigue, headache, weakness, or blurred vision (particularly when used in high doses).
Oral vitamin E should be avoided in patients with retinitis pigmentosa, as is does not appear to slow visual decline, and may be associated with more rapid loss of visual acuity, although the validity of this finding has been questioned.
Pregnancy and Breastfeeding
Many prenatal vitamins contain small amounts of vitamin E. Natural forms of vitamin E may be preferable to synthetic forms.
Use beyond the Recommended Dietary Allowance (RDA) level in otherwise healthy pregnant women is generally not recommended. There is otherwise insufficient evidence regarding the safety of higher doses of oral, topical, or injected vitamin E during pregnancy and breastfeeding, and therefore it is not recommended.
Foods that contain vitamin E include: eggs, fortified cereals, fruit, green leafy vegetables (such as spinach), meat, nuts/nut oils, poultry, vegetable oils (corn, cottonseed, safflower, soybean, sunflower), argan oil, olive oil, wheat germ oil, and whole grains. Cooking and storage may destroy some of the vitamin E in foods.
Most individuals in the United States are believed to obtain sufficient vitamin E from dietary sources, although individuals with very low-fat diets or intestinal malabsorption disorders may require supplementation. Recommended Dietary Allowances (RDAs) for vitamin E are provided in Alpha-Tocopherol Equivalents (ATE) to account for the different biological activities of the various forms of vitamin E, as well as in International Units (IU), which food and supplement labels often use. For conversion, 1 milligram ATE = 1.5 IU. The RDA for men or women older than 14 years old is 15 milligrams (or 22.5 IU); for pregnant women of any age is 15 milligrams (or 22.5 IU); and for breastfeeding women of any age is 19 milligrams (or 28.5 IU).
For adults older than 18 years, the tolerable upper limit of dosing for supplementary alpha-tocopherol recommended by the U.S. Institute of Medicine is 1,000 milligrams per day (equivalent to 1,500 IU). This limit recommendation is not altered during pregnancy or breastfeeding.
Treatment of vitamin E deficiency should be under medical supervision, tailored to the underlying cause of the deficiency, and may include either oral or injected vitamin E. If the cause is due to chronic malnutrition and there is no evidence of malabsorption, an oral dose that is between 2-5 times greater than the RDA may be considered. If the cause is malabsorption that cannot be corrected, then injections of vitamin E may be necessary. Dosing recommendations vary by the underlying cause.
No specific dosing of vitamin E has been established for other conditions, and there is recent evidence suggesting possible adverse health effects of long-term use of daily supplementation with 400 IU or greater daily. Although controversial, the use of long-term vitamin E supplementation should be approached cautiously until further evidence from prospective clinical trials is available. Various doses and durations have been evaluated in clinical trials, although many have not been proven as effective or safe. Patents are recommended to discuss the choice of dosing and duration with a licensed healthcare professional.
Children (under 18 years old)
Recommended Dietary Allowances (RDAs) for vitamin E are provided in Alpha-Tocopherol Equivalents (ATE) to account for the different biological activities of the various forms of vitamin E, as well as in International Units (IU), because food and supplement labels often use this system. For conversion, 1 milligram ATE = 1.5 IU. There is no RDA for infants, but there is a recommended Adequate Intake (AI) for healthy breastfeeding infants ages 0-6 months old of 4 milligrams per day (6 IU), and for infants ages 7-12 months old of 5 milligrams per day (7.5 IU). The RDA for children ages 1-3 years old is 6 milligrams per day (9 IU); for ages 4-8 years old is 7 milligrams per day (10.5 IU); for ages 9-13 years old is 11 milligrams per day (16.5 IU); for ages greater than 14 years old is 15 milligrams per day (22.5 IU); for pregnant women of any age is 15 milligrams (22.5 IU); and for breastfeeding women of any age is 19 milligrams (28.5 IU).
An upper limit for infants up to 12 months of age has not been established. The tolerable daily upper limit of dosing for ages 1-3 years old is 200 milligrams (300 IU); for ages 4-8 years old is 300mg (450 IU); for ages 9-13 years old is 600 milligrams (900 IU); and for ages 14-18 is 800 milligrams (1,200 IU).
Treatment of vitamin E deficiency should be under medical supervision, tailored to the underlying cause of the deficiency, and may include either oral or injected vitamin E. Selected doses in specific conditions are noted above under adult dosing. Vitamin E absorption may improve if given with meals, and in small doses.
No specific dosing of vitamin E has been well established for other conditions.
Interactions with Drugs
The amount of bleeding risk associated with vitamin E remains an area of controversy, and caution is warranted in patients with a history of bleeding disorders or taking blood-thinning drugs such as aspirin, anticoagulants such as warfarin (Coumadin®) or heparin, anti-platelet drugs such as clopidogrel (Plavix®), and non-steroidal anti-inflammatory drugs such as ibuprofen (Motrin®, Advil®) or naproxen (Naprosyn®, Aleve®).
Concern has been raised that antioxidants may interfere with some chemotherapy agents (such as alkylating agents, anthracyclines, or platinums), which themselves can depend on oxidative damage to tumor cells for their anti-cancer effects. Studies on the effects of antioxidants on cancer therapies have yielded mixed results, with some reporting interference, others noting benefits, and most suggesting no significant interaction. However, until additional scientific evidence is available, high-dose antioxidants should be avoided during chemotherapy administration, unless otherwise decided in discussion with the treating oncologist.
Cholestyramine (Questran ®), colestipol (Colestid®), orlistat (Xenical®), isoniazid (INH, Lanizid®, Nydrazid®), olestra (Olean® fat substitute), and sucralfate (Carafate®) can reduce dietary vitamin E absorption and blood levels of vitamin E. Gemfibrozil (Lopid®) may decrease serum levels of both alpha- and gamma-tocopherol, although clinical significance is not clear. Anticonvulsant drugs such as phenobarbital, phenytoin, or carbamazepine may decrease blood levels of vitamin E.
Vitamin E use with cyclosporine appears to increase the area under the blood concentration-time curve of cyclosporine. A water-soluble form of vitamin E, tocopheryl succinate polyethylene glycol, may improve the absorption of cyclosporine (observed after liver transplantation).
Vitamin E may have additive effects with cholesterol-lowering medications.
Interactions with Herbs and Dietary Supplements
High doses of oral or injected vitamin E may increase the risk of bleeding including hemorrhagic stroke (bleeding into the brain), and caution is warranted in patients with a history of bleeding disorders or taking herbs or supplements that may also increase the risk of bleeding. For example, multiple cases of bleeding have been reported with the use of Ginkgo biloba, and fewer cases with garlic or saw palmetto.
Vitamin E may have additive effects with cholesterol-lowering herbs and supplements.
Mineral oil may reduce dietary vitamin E absorption. Blood levels of vitamin E may be decreased with zinc deficiency. Increased intake of omega-6 fatty acids may increase vitamin E requirements, particularly at high doses.
Vitamin E is involved in the absorption, storage, and utilization of vitamin A in the body and contributes to avoiding toxicity with vitamin A intake. Large doses of vitamin E may deplete vitamin A stores.
Aloe is reported to slow the rate of vitamin E absorption, allowing sustained release of vitamin E into the bloodstream.
Vitamin E has been proposed to improve the bioavailability of iron.