Vitamin E supplementation has been shown in controlled trials to increase both walking distance and blood flow through arteries of the lower legs in people with intermittent claudication.^1,2 Increasing dietary intake of vitamin E was also associated with better blood flow to the legs.³ Some early studies did not find vitamin E useful. Possibly this failure was due to the short duration of the studies,⁴ as one review article suggested that a minimum of four to six months of vitamin E supplementation may be necessary before significant improvement is seen.⁵ Most clinical trials of vitamin E and intermittent claudication used 400 to 600 IU per day, although one study used 2,400 IU per day.

Hemolytic anemia refers to a category of anemia in which red blood cells become fragile and undergo premature death. Vitamin E deficiency, though quite rare, can cause hemolytic anemia because vitamin E protects the red blood cell membrane from oxidative damage. Vitamin E deficiency anemia usually affects only premature infants and children with cystic fibrosis.^6,7 Preliminary studies have reported that large amounts (typically 800 IU per day) of vitamin E improve hemolytic anemia caused by a genetic deficiency of the enzyme glucose-6-phosphate dehydrogenase (G6PD)^8,9,10 and anemia caused by kidney dialysis.^11,12

Dietary vitamin E is necessary for cardiovascular health, and observational studies have linked higher intake of vitamin E with lower risk of high blood pressure.^18,19 Nevertheless, most clinical trials have found no benefit from vitamin E supplementation at doses of 200–600 IU per day in people with high blood pressure, though it may be effective in those with mild hypertension.²⁰ A meta-analysis of 18 randomized controlled trials with a combined total of 839 participants found vitamin E supplementation mildly lowered systolic blood pressure but had no impact on diastolic blood pressure.²¹

Vitamin E is a naturally occurring complex made up of multiple tocopherols and tocotrienols, each of which may have unique properties in the body.²⁰ Some evidence suggests tocotrienols have greater antioxidant capacity than tocopherols and may have stronger benefits in cardiovascular and metabolic disease, but most supplements contain only alpha-tocopherol.²³

Low levels of antioxidant vitamins in the blood, particularly vitamin E, are associated with greater rates of angina.²³ This is true even when smoking and other risk factors for angina are taken into account. Early short-term studies using 300 IU (International Units) per day of vitamin E could not find a beneficial action on angina.²⁴ A later study supplementing small amounts of vitamin E (50 IU per day) for longer periods of time showed a minor benefit in people suffering angina.²⁵ Those affected by variant angina have been found to have the greatest deficiency of vitamin E compared with other angina patients.²⁶

Several studies[REF][REF] including two double-blind trials[REF][REF] have reported that 400 to 800 IU of natural vitamin E reduces the risk of heart attacks. However, other recent double-blind trials have found either limited benefit,[REF] or no benefit at all from supplementation with synthetic vitamin E.[REF] One of the negative trials used 400 IU of natural vitamin E[REF]—a similar amount and form to previous successful trials. In attempting to make sense of these inconsistent findings the following is clear: less than 400 IU of synthetic vitamin E, even when taken for years, does not protect against heart disease. Whether 400 to 800 IU of natural vitamin E is or is not protective remains unclear.

Taking antioxidant supplements may improve the outcome for people who have already had a heart attack. In one double-blind trial, people were given 50,000 IU of vitamin A per day, 1,000 mg of vitamin C per day, 600 IU of vitamin E per day, and approximately 41,500 IU of beta-carotene per day or placebo.²⁷ After 28 days, the infarct size of those receiving antioxidants was significantly smaller than the infarct size of the placebo group.

Men with intermittent claudication consumed a fortified milk product or regular milk daily for one year. The fortified product provided daily 130 mg of eicosapentaenoic acid and 200 mg of docosahexaenoic acid (EPA and DHA, two fatty acids in fish oil), small amounts of supplemental vitamin E, folic acid, and vitamin B6, and additional amounts of oleic acid and alpha-linolenic acid. Compared with regular milk, the fortified milk product significantly increased the distance the participants could walk before the onset of pain.²⁸

Vitamin E is an antioxidant that serves to protect LDL from oxidative damage²⁹ and has been linked to prevention of heart disease in double-blind research.³⁰ Many doctors recommend 400–800 IU of vitamin E per day to lower the risk of atherosclerosis and heart attacks. However, some leading researchers suggest taking only 100–200 IU per day, as studies that have explored the long-term effects of different supplemental levels suggest no further benefit beyond that amount, and research reporting positive effects with 400–800 IU per day have not investigated the effects of lower intakes.³¹ In a double-blind trial, people with high cholesterol who took 136 IU of natural vitamin E per day for three years had 10% less progression of atherosclerosis compared with those taking placebo.³²

Narrowing of the neck arteries (carotid stenosis) caused by atherosclerosis is a risk factor for stroke. Preliminary diet studies have found that people who eat foods high in antioxidants such as vitamin C and vitamin E have less carotid stenosis.^33,34

In a double-blind trial, people with atherosclerosis in the carotid arteries were given a palm oil extract containing 160–240 mg of tocotrienols (a vitamin E-like supplement) and approximately 100–150 IU vitamin E per day. After 18 months, they had significantly less atherosclerosis or less progression of atherosclerosis compared to a group receiving placebo.³⁵ Vitamin E plus aspirin, has been more effective in reducing the risk of strokes and other related events than has aspirin, alone.³⁶ However, most preliminary trials have shown no protective effects from antioxidant supplementation.^{37,38,39,40,41,42} A large Finnish trial concluded that supplementation with either vitamin E or beta-carotene conferred no protection against stroke in male smokers,⁴³ although a later review of the study found that those smokers who have either hypertension (high blood pressure) or diabetes do appear to have a reduced risk of stroke when taking vitamin E.⁴⁴

People with high risk for stroke, such as those who have had TIAs or who have a heart condition known as atrial fibrillation,⁴⁵ are often given aspirin or anticoagulant medication to reduce blood clotting tendencies. Some natural inhibitors of blood clotting such as garlic,^46,47,48fish oil,⁴⁹ and vitamin E,^50,51 may have protective effects, but even large amounts of fish oil are known to be less potent than aspirin.⁵² Whether any of these substances is an adequate substitute to control risk of stroke in high-risk people is unknown, and anyone taking anticoagulant medication should advise their prescribing doctor before beginning use of these natural substances.

Antioxidants may protect the skin from sunburn due to free radical–producing ultraviolet rays.⁵³ Combinations of 1,000 to 2,000 IU per day of vitamin E and 2,000 to 3,000 mg per day of vitamin C, but neither given alone, have a significant protective effect against ultraviolet rays, according to double-blind studies.^54,55,56

Oral synthetic beta-carotene alone was not found to provide effective protection when given in amounts of 15 mg per day or for only a few weeks’ time in larger amounts of 60 to 90 mg per day, but it has been effective either in very large (180 mg per day) amounts or in smaller amounts (30 mg per day) in combination with topical sunscreen.^{57,58,59,60,61}

Natural sources of beta-carotene or other carotenoids have been more consistently shown to protect against sunburn. One controlled study found that taking a supplement of natural carotenoids (almost all of which was beta-carotene) in daily amounts of 30 mg, 60 mg, and 90 mg gave progressively more protection against ultraviolet rays.⁶² In another controlled study, either 24 mg per day of natural beta-carotene or 24 mg per day of a carotenoid combination of equal amounts beta-carotene, lutein, and lycopene helped protect skin from ultraviolet rays.⁶³ A preliminary study compared synthetic lycopene (10.1 mg per day), a natural tomato extract containing 9.8 mg of lycopene per day plus additional amounts of other carotenoids, and a solubilized tomato drink (designed to increase lycopene absorption) containing 8.2 mg of lycopene plus additional amounts of other carotenoids. After 12 weeks, only the two tomato-based products were shown to give significant protection against burning by ultraviolet light.⁶⁴

Still other trials have tested combinations of several antioxidants. One preliminary study found that a daily combination of beta-carotene (6 mg), lycopene (6 mg), vitamin E (15 IU), and selenium for seven weeks protected against ultraviolet light.⁶⁵ However, a double-blind trial of a combination of smaller amounts of several carotenoids, vitamins C and E, selenium, and proanthocyanidins did not find significant UV protection compared with placebo.⁶⁶ Similarly, in a controlled trial, a combination of selenium, copper, and vitamins was found to be ineffective.⁶⁷

It should be noted that while oral protection from sunburn has been demonstrated with several types of antioxidants, the degree of protection (typically less than an SPF of 2) is much less than that provided by currently available topical sunscreens. On the other hand, these modest effects will provide some added protection to skin areas where sunscreen is also used and will give a small amount of protection to sun-exposed areas where sunscreen is not applied. However, oral protection from sunburn is not instantaneous; maximum effects are not reached until these antioxidants have been used for about eight to ten weeks.^68,69

Antioxidants have been studied as topical agents for protection against sunburn. Animal studies have found sunscreen-like effects from topical application of a vitamin C and vitamin E combination, and a controlled human study reported ultraviolet protection from the use of a lotion containing 0.02% to 0.05% of the selenium-containing amino acid known as selenomethionine.^70,71 The topical use of the hormone melatonin has been shown to protect human skin against ultraviolet rays in double-blind research.^72,73 A double-blind human trial tested topical vitamins C and E and melatonin, alone and in combinations, and found the highest degrees of protection from combination formulations containing 2% vitamin E, 5% vitamin C, and 1% to 2.5% melatonin.⁷⁴ Other studies in which topical antioxidants were applied after ultraviolet exposure have found no benefits.^75,76

Antioxidants have been studied as topical agents for protection against sunburn. Animal studies have found sunscreen-like effects from topical application of a vitamin C and vitamin E combination, and a controlled human study reported ultraviolet protection from the use of a lotion containing 0.02% to 0.05% of the selenium-containing amino acid known as selenomethionine.^77,78 The topical use of the hormone melatonin has been shown to protect human skin against ultraviolet rays in double-blind research.^79,80 A double-blind human trial tested topical vitamins C and E and melatonin, alone and in combinations, and found the highest degrees of protection from combination formulations containing 2% vitamin E, 5% vitamin C, and 1% to 2.5% melatonin.⁸¹ Other studies in which topical antioxidants were applied after ultraviolet exposure have found no benefits.^82,83

Animal studies have shown that supplementing with vitamin E can decrease the formation of unwanted adhesions following a surgical wound. In addition, wound healing was more rapid in animals fed a vitamin E-rich diet than in those fed a standard diet.⁸⁴ In another study, however, wound healing was inhibited by supplementation with a massive amount of vitamin E (equivalent to about 35,000 IU).⁸⁵ This adverse effect of vitamin E was prevented by supplementation with vitamin A. Although the relevance of these studies to humans is not clear, many doctors recommend supplementing with both vitamins A and E in order to enhance wound healing and prevent adhesion formation. Typical amounts recommended are 25,000 IU of vitamin A per day and 400 IU of vitamin E per day, beginning two weeks prior to surgery and continuing for four weeks after surgery.

Topical application of vitamin E is sometimes recommended for preventing or treating post-injury scars, although only three controlled studies have been reported. Two of these trials found no effect on scar prevention after surgery,^86,87 and one trial found vitamin E improved the effect of silicon bandages on large scars called keloids.⁸⁸

A deficiency in the selenium-containing antioxidant enzyme known as glutathione peroxidase has been reported in DH.^89,90 Preliminary⁸⁹ and double-blind⁹⁰ trials suggest that supplementation with 10 IU of vitamin E and 200 mcg of selenium per day for six to eight weeks corrected this deficiency but did not lead to symptom improvement in the double-blind trial.

Despite a lack of research on the subject, using vitamin E topically on minor burns is a popular remedy. This makes sense, because some of the damage done to the skin is oxidative, and vitamin E is an antioxidant. Some doctors suggest simply breaking open a capsule of vitamin E and applying it to the affected area two or three times per day. Vitamin E forms are listed as either “tocopherol” or “tocopheryl” followed by the name of what is attached to it, as in “tocopheryl acetate.” While both forms are active when taken by mouth, the skin utilizes the tocopheryl forms very slowly.^91,92 Therefore, those planning to apply vitamin E to the skin should buy the tocopherol form.

In a double-blind trial, supplementation with 500 IU of vitamin E per day for two months, beginning two days before menstruation and continuing for three days after the onset of menstruation, was significantly more effective than a placebo at relieving menstrual pain.⁹³ Similar benefits were seen in four-month double-blind trial using 400 IU per day, beginning two days before the expected start of menstruation and continuing through the first three days of bleeding.⁹⁴

Many years ago, researchers studied the effects of vitamin E supplementation in reducing symptoms of menopause. Most,^{95,96,97,98,99} but not all,¹⁰⁰ studies found vitamin E to be helpful, and the benefit of vitamin E was confirmed more recently in a double-blind trial.¹⁰¹ Many doctors suggest that women going through menopause take 400 to 800 IU per day of vitamin E for a trial period of at least three months to see if symptoms are reduced. If helpful, this amount may be continued or a lower amount may be tried for maintenance.

Although women with PMS do not appear to be deficient in vitamin E,¹⁰² a double-blind trial reported that 300 IU of vitamin E per day may decrease symptoms of PMS.¹⁰³

While several studies report that 200–600 IU of vitamin E per day, taken for several months, reduces symptoms of FBD,^105,106 most double-blind trials have found that vitamin E does not relieve FBD symptoms.^107,108 Nonetheless, many women take 400 IU of vitamin E for three months to see if it helps.

Vitamin E deficiency in animals leads to infertility.¹⁰⁹ In a preliminary human trial, infertile couples given vitamin E (200 IU per day for the female and 100 IU per day for the male) showed a significant increase in fertility.¹¹⁰

In a study of women with menorrhagia associated with the use of an intrauterine device (IUD) for birth control, supplementing with 100 IU of vitamin E every other day corrected the problem in all cases within ten weeks (63% responded within four weeks).¹¹¹ The cause of IUD-induced menstrual blood loss is different from that of other types of menorrhagia; therefore, it’s possible that vitamin E supplements might not help with menorrhagia not associated with IUD use.

Some doctors recommend vitamin E (taken orally, topically, or vaginally) for certain types of vaginitis. Vitamin E as a suppository in the vagina or vitamin E oil can be used once or twice per day for 3 to 14 days to soothe the mucous membranes of the vagina and vulva. Some doctors recommend vaginal administration of vitamin A to improve the integrity of the vaginal tissue and to enhance the function of local immune cells. Vitamin A can be administered vaginally by inserting a vitamin A capsule or using a prepared vitamin A suppository. Vitamin A used this way can be irritating to local tissue, so it should not be used more than once per day for up to seven consecutive days.

Women with cervical dysplasia may have lower blood levels of beta-carotene and vitamin E^112,113 compared to healthy women.

Most,^114,115 but not all,¹¹⁶ double-blind studies have shown that elderly people have better immune function and reduced infection rates when taking a multiple vitamin-mineral formula. In one double-blind trial, supplements of 100 mcg per day of selenium and 20 mg per day of zinc, with or without additional vitamin C, vitamin E, and beta-carotene, reduced infections in elderly people, though vitamins without minerals had no effect.¹¹⁷ Burn victims have also experienced fewer infections after receiving trace mineral supplements in double-blind research.¹¹⁸ These studies suggest that trace minerals may be the most important micronutrients for enhancing immunity and preventing infections in the elderly.

In a preliminary trial, a piece of cotton saturated with vitamin E oil was applied to newly erupted cold sores and held in place for 15 minutes. The first application was performed in the dentist’s office. Participants were instructed to repeat the procedure every three hours for the rest of that day, and then three times daily for two more days. In nearly all cases, pain disappeared in less than eight hours. Application of vitamin E oil appeared to accelerate healing of the cold sores.¹¹⁹ Similar results were reported in another study.¹²⁰

Some studies of surgery patients,^121,122 though not all, ¹²³ have found that blood levels of vitamin E decrease during and after surgery. Animal research suggests that vitamin E may prevent skin scarring when used topically after surgery,¹²⁴ but a human study reported disappointing results.¹²⁵ Vitamin E taken by mouth may interfere with blood clotting¹²⁶; therefore, use of vitamin E before surgery should be discussed with the surgeon. No research on either the usefulness or hazards of vitamin E supplementation around surgery has been done.

Vitamin C and vitamin E may prevent oxidative damage to the lung lipids by environmental pollution and cigarette smoke exposure. It has been suggested that amounts in excess of the RDA (recommended dietary allowance) are necessary to protect against the air pollution levels currently present in North America,¹²⁷ although it is not known how much vitamin E is needed to produce that protective effect.

In test-tube studies, vitamin E improved the effectiveness of the anti-HIV drug zidovudine (AZT) while reducing its toxicity.¹²⁸Similarly, animal research suggests that zinc and NAC supplementation may protect against AZT toxicity.¹²⁹ It is not known whether oral supplementation with these nutrients would have similar effects in people taking AZT.

In a double-blind trial, supplementation with 500 IU of vitamin E per day for two months, beginning two days before menstruation and continuing for three days after the onset of menstruation, was significantly more effective than a placebo at relieving menstrual pain.¹³⁰ Similar benefits were seen in four-month double-blind trial using 400 IU per day, beginning two days before the expected start of menstruation and continuing through the first three days of bleeding.¹³¹

Although women with PMS do not appear to be deficient in vitamin E,¹³² a double-blind trial reported that 300 IU of vitamin E per day may decrease symptoms of PMS.¹³³

In a study of women with menorrhagia associated with the use of an intrauterine device (IUD) for birth control, supplementing with 100 IU of vitamin E every other day corrected the problem in all cases within ten weeks (63% responded within four weeks).¹³⁵ The cause of IUD-induced menstrual blood loss is different from that of other types of menorrhagia; therefore, it’s possible that vitamin E supplements might not help with menorrhagia not associated with IUD use.

People with RA have been reported to have an impaired antioxidant system, making them more susceptible to free radical damage.¹³⁶Vitamin E is an important antioxidant, protecting many tissues, including joints, against oxidative damage. Low vitamin E levels in the joint fluid of people with RA have been reported.¹³⁷ In a double-blind trial, approximately 1,800 IU per day of vitamin E was found to reduce pain from RA.¹³⁸ Two other double-blind trials (using similar high levels of vitamin E) reported that vitamin E had approximately the same effectiveness in reducing symptoms of RA as anti-inflammatory drugs.^139,140 In other double-blind trials, 600 IU of vitamin E taken twice daily was significantly more effective than placebo in reducing RA, although laboratory measures of inflammation remained unchanged.^141,142

People who have osteoarthritis and eat large amounts of antioxidants in food have been reported to exhibit a much slower rate of joint deterioration, particularly in the knees, compared with people eating foods containing lower amounts of antioxidants.¹⁴³ Of the individual antioxidants, only vitamin E has been studied as a supplement in controlled trials. Vitamin E supplementation has reduced symptoms of osteoarthritis in both single-blind¹⁴⁴ and double-blind research.^145,146 In these trials, 400 to 1,600 IU of vitamin E per day was used. Clinical effects were obtained within several weeks. However, in a six-month double-blind study of patients with osteoarthritis of the knee, 500 IU per day of vitamin E was no more effective than a placebo.¹⁴⁷

Many decades ago, researchers investigated the effects of taking vitamin E to treat Dupuytren’s contracture. Several studies reported that taking 200–2,000 IU of vitamin E per day for several months was helpful.¹⁴⁸ Other studies, however, did not find it useful.¹⁴⁹ Overall, there are more positive trials than negative ones,¹⁵⁰ although none of the published research is recent. Nonetheless, some doctors believe that a three-month trial using very high amounts of vitamin E (2,000 IU per day) is helpful in some cases.

In a preliminary trial, a piece of cotton saturated with vitamin E oil was applied to newly erupted cold sores and held in place for 15 minutes. The first application was performed in the dentist’s office. Participants were instructed to repeat the procedure every three hours for the rest of that day, and then three times daily for two more days. In nearly all cases, pain disappeared in less than eight hours. Application of vitamin E oil appeared to accelerate healing of the cold sores.¹⁵¹ Similar results were reported in another study.¹⁵²

According to a review of clinical trials, the combination of beta-carotene and vitamin E has led to complete or partial remissions in six of eight trials studying people with leukoplakia.¹⁵⁴ In one trial, administration of 50,000 IU of beta-carotene, 1 gram of vitamin C, and 800 IU of vitamin E per day for nine months led to improvement in 56% of people with leukoplakia, with stronger effects in those who also stopped using tobacco and alcohol.¹⁵⁵ In a double-blind trial, a group of men with leukoplakia was given a combination of vitamin A (100,000 IU per week), beta-carotene approximately 67,000 IU per day), and vitamin E (80 IU per week).¹⁵⁶ A 38% decrease in the incidence of leukoplakia was observed after six months of treatment.

Although vitamin E has been used in successful trials in which patients are also given beta-carotene, few trials have investigated the effects of vitamin E when taken by itself. One trial used 400 IU of vitamin E two times per day.¹⁵⁷ After 24 weeks, 46% showed some improvement in signs or symptoms of leukoplakia or related conditions and 21% showed microscopic evidence of improvement.

Nutritional supplements recommended by some doctors for prevention and treatment of periodontitis include vitamin C (people with periodontitis are often found to be deficient),¹⁵⁸vitamin E, selenium, zinc, coenzyme Q10, and folic acid.¹⁵⁹ Folic acid has also been shown to reduce the severity of gingivitis when taken as a mouthwash.¹⁶⁰

Animal studies have shown that supplementing with vitamin E can decrease the formation of unwanted adhesions following a surgical wound. In addition, wound healing was more rapid in animals fed a vitamin E-rich diet than in those fed a standard diet.¹⁶¹ In another study, however, wound healing was inhibited by supplementation with a massive amount of vitamin E (equivalent to about 35,000 IU).¹⁶² This adverse effect of vitamin E was prevented by supplementation with vitamin A. Although the relevance of these studies to humans is not clear, many doctors recommend supplementing with both vitamins A and E in order to enhance wound healing and prevent adhesion formation. Typical amounts recommended are 25,000 IU of vitamin A per day and 400 IU of vitamin E per day, beginning two weeks prior to surgery and continuing for four weeks after surgery.

Topical application of vitamin E is sometimes recommended for preventing or treating post-injury scars, although only three controlled studies have been reported. Two of these trials found no effect on scar prevention after surgery,^163,164 and one trial found vitamin E improved the effect of silicon bandages on large scars called keloids.¹⁶⁵

One early preliminary study described the use of vitamin E supplements in the treatment of “fibrositis”—the rough equivalent of what is today called fibromyalgia. Several dozen individuals were treated with vitamin E using amounts ranging from 100–300 IU per day. The results were positive and sometimes dramatic.¹⁶⁶ Double-blind trials are needed to confirm these preliminary observations.

Some doctors have found vitamin E to be effective for people with postherpetic neuralgia—even those who have had the problem for many years.^167,168 The recommended amount of vitamin E by mouth is 1,200–1,600 IU per day. In addition, vitamin E oil (30 IU per gram) can be applied to the skin. Several months of continuous vitamin E use may be needed in order to see an improvement. Not all studies have found a beneficial effect of vitamin E;¹⁶⁸ however, in the study that produced negative results, vitamin E may not have been used for a long enough period of time.

Despite a lack of research on the subject, using vitamin E topically on minor burns is a popular remedy. This makes sense, because some of the damage done to the skin is oxidative, and vitamin E is an antioxidant. Some doctors suggest simply breaking open a capsule of vitamin E and applying it to the affected area two or three times per day. Vitamin E forms are listed as either “tocopherol” or “tocopheryl” followed by the name of what is attached to it, as in “tocopheryl acetate.” While both forms are active when taken by mouth, the skin utilizes the tocopheryl forms very slowly.^169,170 Therefore, those planning to apply vitamin E to the skin should buy the tocopherol form.

Antioxidant supplements, including vitamin C and vitamin E, may help prevent exercise-related muscle injuries by neutralizing free radicals produced during strenuous activities.¹⁷¹ Controlled research, some of it double-blind, has shown that 400–3,000 mg per day of vitamin C may reduce pain and speed up muscle strength recovery after intense exercise.^172,173 Reductions in blood indicators of muscle damage and free radical activity have also been reported for supplementation with 400–1,200 IU per day of vitamin E in most studies,^174,175,176 but no measurable benefits in exercise recovery have been reported.¹⁷⁷ A combination of 90 mg per day of coenzyme Q10 and a very small amount of vitamin E did not produce any protective effects in one double-blind trial.¹⁷⁸

Free radicals have been implicated in the development and progression of several forms of retinopathy.¹⁸² Retrolental fibroplasia, a retinopathy that occurs in some premature infants who have been exposed to high levels of oxygen, is an example of free radical-induced damage to the retina. In an analysis of the best published trials, large amounts of vitamin E were found to reduce the incidence of severe retinopathy in premature infants by over 50%.^183,184 Some of the evidence supporting the use of vitamin E in the prevention of retrolental fibroplasia comes from trials that have used 100 IU of vitamin E per 2.2 pounds of body weight in the form of oral supplementation.¹⁸⁵ Use of large amounts of vitamin E in the prevention of retrolental fibroplasia requires the supervision of a pediatrician.

Vitamin E has also been found to prevent retinopathy in people with a rare genetic disease known as abetalipoproteinemia.¹⁸⁶ People with this disorder lack a protein that transports fat-soluble nutrients, and can therefore develop deficiencies of vitamin E and other nutrients.

In one trial, vitamin E failed to improve vision in people with diabetic retinopathy,¹⁸⁷ although in a double-blind trial, people with type 1 diabetes given very high amounts of vitamin E were reported to show a normalization of blood flow to the retina.¹⁸⁸ This finding has made researchers hopeful that vitamin E might help prevent diabetic retinopathy. However, no long-term trials have yet been conducted with vitamin E in the actual prevention of diabetic retinopathy.

Because oxidation damage is believed to play a role in the development of retinopathy, antioxidant nutrients might be protective. One doctor has administered a daily regimen of 500 mcg selenium, 800 IU vitamin E, 10,000 IU vitamin A, and 1,000 mg vitamin C for several years to 20 people with diabetic retinopathy. During that time, 19 of the 20 people showed either improvement or no progression of their retinopathy.¹⁸⁹ People who wish to supplement with more than 250 mcg of selenium per day should consult a healthcare practitioner.

People with low blood levels of vitamin E are more likely to develop type 1 and type 2 diabetes.^202,203 Vitamin E supplementation has improved glucose tolerance in people with type 2 diabetes in most,^204,205,206 but not all,²⁰⁷ double-blind trials. Vitamin E has also improved glucose tolerance in elderly people without diabetes.^208,209 Three months or more of at least 900 IU of vitamin E per day may be required for benefits to become apparent.

In one of the few trials to find vitamin E supplementation ineffective for glucose intolerance in people with type 2 diabetes, damage to nerves caused by the diabetes was nonetheless partially reversed by supplementing with vitamin E for six months.²⁰⁷ Animal and preliminary human data indicate that vitamin E supplementation may protect against diabetic retinopathy and nephropathy,^211,212 serious complications of diabetes involving the eyes and kidneys, respectively, though no long-term trials in humans have confirmed this preliminary evidence.

Glycosylation is an important measurement of diabetes; it refers to how much sugar attaches abnormally to proteins. Excessive glycosylation appears to be one of the causes of the organ damage that occurs in diabetes. Vitamin E supplementation has reduced the amount of glycosylation in many,^{213,214,206,216,217} although not all,^218,212,220 studies.

In one report, vitamin E was found to impair glucose tolerance in obese patients with diabetes.²²¹ The reason for the discrepancy between reports is not known.

Vitamin E appears to lower the risk of cerebral infarction, a type of stroke, in people with diabetes who smoke. A review of a large Finnish study of smokers concluded that smokers with diabetes (or hypertension) can benefit from small amounts of vitamin E (50 IU per day).²²²

People with low blood levels of vitamin E are more likely to develop type 1 and type 2 diabetes.^220,221 Vitamin E supplementation has improved glucose tolerance in people with type 2 diabetes in most,^222,223,224 but not all,²²⁵ double-blind trials. Vitamin E has also improved glucose tolerance in elderly people without diabetes.^226,227 Three months or more of at least 900 IU of vitamin E per day may be required for benefits to become apparent.

In one of the few trials to find vitamin E supplementation ineffective for glucose intolerance in people with type 2 diabetes, damage to nerves caused by the diabetes was nonetheless partially reversed by supplementing with vitamin E for six months.²²⁵ Animal and preliminary human data indicate that vitamin E supplementation may protect against diabetic retinopathy and nephropathy,^229,230 serious complications of diabetes involving the eyes and kidneys, respectively, though no long-term trials in humans have confirmed this preliminary evidence.

Glycosylation is an important measurement of diabetes; it refers to how much sugar attaches abnormally to proteins. Excessive glycosylation appears to be one of the causes of the organ damage that occurs in diabetes. Vitamin E supplementation has reduced the amount of glycosylation in many,^{231,232,224,234,235} although not all,^236,230,238 studies.

In one report, vitamin E was found to impair glucose tolerance in obese patients with diabetes.²³⁹ The reason for the discrepancy between reports is not known.

Vitamin E appears to lower the risk of cerebral infarction, a type of stroke, in people with diabetes who smoke. A review of a large Finnish study of smokers concluded that smokers with diabetes (or hypertension) can benefit from small amounts of vitamin E (50 IU per day).²⁴⁰

Research has shown that supplementing with chromium (200 mcg per day)²⁴¹ or magnesium (340 mg per day)²⁴² can prevent blood sugar levels from falling excessively in people with hypoglycemia. Niacinamide (vitamin B3) has also been found to be helpful for hypoglycemic people.²⁴³ Other nutrients, including vitamin C, vitamin E, zinc, copper, manganese, and vitamin B6, may help control blood sugar levels in diabetics.²⁴⁴ Since there are similarities in the way the body regulates high and low blood sugar levels, these nutrients might be helpful for hypoglycemia as well, although the amounts needed for that purpose are not known.

Free radicals have been implicated in the development and progression of several forms of retinopathy.²⁴⁵ Retrolental fibroplasia, a retinopathy that occurs in some premature infants who have been exposed to high levels of oxygen, is an example of free radical-induced damage to the retina. In an analysis of the best published trials, large amounts of vitamin E were found to reduce the incidence of severe retinopathy in premature infants by over 50%.^246,247 Some of the evidence supporting the use of vitamin E in the prevention of retrolental fibroplasia comes from trials that have used 100 IU of vitamin E per 2.2 pounds of body weight in the form of oral supplementation.²⁴⁸ Use of large amounts of vitamin E in the prevention of retrolental fibroplasia requires the supervision of a pediatrician.

Vitamin E has also been found to prevent retinopathy in people with a rare genetic disease known as abetalipoproteinemia.²⁴⁹ People with this disorder lack a protein that transports fat-soluble nutrients, and can therefore develop deficiencies of vitamin E and other nutrients.

In one trial, vitamin E failed to improve vision in people with diabetic retinopathy,²⁵⁰ although in a double-blind trial, people with type 1 diabetes given very high amounts of vitamin E were reported to show a normalization of blood flow to the retina.²⁵¹ This finding has made researchers hopeful that vitamin E might help prevent diabetic retinopathy. However, no long-term trials have yet been conducted with vitamin E in the actual prevention of diabetic retinopathy.

Because oxidation damage is believed to play a role in the development of retinopathy, antioxidant nutrients might be protective. One doctor has administered a daily regimen of 500 mcg selenium, 800 IU vitamin E, 10,000 IU vitamin A, and 1,000 mg vitamin C for several years to 20 people with diabetic retinopathy. During that time, 19 of the 20 people showed either improvement or no progression of their retinopathy.²⁵² People who wish to supplement with more than 250 mcg of selenium per day should consult a healthcare practitioner.

Many years ago, researchers studied the effects of vitamin E supplementation in reducing symptoms of menopause. Most,^{254,255,256,257,258} but not all,²⁵⁹ studies found vitamin E to be helpful, and the benefit of vitamin E was confirmed more recently in a double-blind trial.²⁶⁰ Many doctors suggest that women going through menopause take 400 to 800 IU per day of vitamin E for a trial period of at least three months to see if symptoms are reduced. If helpful, this amount may be continued or a lower amount may be tried for maintenance.

In a double-blind trial, supplementation with a specific probiotic strain (Bifidobacterium longum strain BB536) during the pollen season significantly decreased symptoms such as sneezing, runny nose, nasal blockage, compared with a placebo.²⁶¹

There is some evidence that combinations of antioxidants such as vitamin E, vitamin C, and selenium may help improve symptoms of asthma throught to be caused by air pollution.²⁶² In one double-blind study, 46 Dutch bicyclists were randomly assigned to receive a placebo or 100 mg of vitamin E and 500 mg of vitamin C daily for 15 weeks.²⁶³ Lung function was measured before and after each training session on 380 different occasions, and ambient ozone concentrations were measured during each training session. After analysis, researchers concluded that bicyclists with the vitamins C and E blunted the adverse effects of ozone on measures of lung function. In another double-blind study, 17 adults (18 to 39 years old) were randomly assigned to receive either 400 IU per day of vitamin E and 500 mg per day of vitamin C or a placebo for five weeks.²⁶⁴ Tests showing improved measures of lung function led researchers to conclude that supplementation with vitamins C and E inhibited the decline in pulmonary function induced in asthmatics by exposure to air pollutants. Also using a double-blind design, another study of 158 children with asthma living in Mexico City were randomly assigned to receive, a daily supplement containing 50 mg of vitamin E and 250 mg of vitamin C or a placebo.²⁶⁵ Tests results suggested that supplementing with vitamins C and E may reduce the adverse effect of ozone exposure on lung function of children with moderate to severe asthma.

In a preliminary study, people who used antioxidant supplements (vitamin C or vitamin E) had a lower risk of Alzheimer’s disease compared with people who did not take antioxidants.²⁶⁶ Other preliminary research shows that higher blood levels of vitamin E correlate with better brain functioning in middle-aged and older adults.²⁶⁷ The possible protective effect of antioxidants may be explained by the observation that oxidative damage appears to play a role in the development of dementia.²⁶⁸ Large amounts of supplemental vitamin E may slow the progression of Alzheimer’s disease. A double-blind trial found that 2,000 IU of vitamin E per day for two years extended the length of time people with moderate Alzheimer’s disease were able to continue caring for themselves (e.g., bathing, dressing, and other necessary daily functions), compared with people taking a placebo.²⁶⁹ Another double-blind study found that 2,000 IU per day of vitamin E taken for an average of 2.3 years slowed the rate of decline in people with mild-to-moderate Alzheimer's disease.²⁷⁰

Sunlight triggers oxidative damage in the eye, which in turn can cause macular degeneration.²⁷¹ Animals given antioxidants—which protect against oxidative damage—have a lower risk of this vision problem.²⁷² People with high blood levels of antioxidants also have a lower risk.²⁷³ Those with the highest levels (top 20th percentile) of the antioxidants selenium, vitamin C, and vitamin E may have a 70% lower risk of developing macular degeneration, compared with people with the lowest levels of these nutrients (bottom 20th percentile).²⁷⁴ People who eat fruits and vegetables high in beta-carotene, another antioxidant, are also at low risk.²⁷⁵ Some doctors recommend antioxidant supplements to reduce the risk of macular degeneration; reasonable adult levels include 200 mcg of selenium, 1,000 mg of vitamin C, 400 IU of vitamin E, and 25,000 IU of natural beta-carotene per day. However, a preliminary study found no association between age-related macular degeneration and intake of antioxidants, either from the diet, from supplements, or from both combined.²⁷⁶ Moreover, in a double-blind study of male cigarette smokers, supplementing with vitamin E (50 IU per day), synthetic beta-carotene (about 33,000 IU per day), or both did not reduce the incidence of age-related macular degeneration.²⁷⁷ Another double-blind trial found that supplementing with 600 IU of vitamin E every other day did not reduce the incidence of age-related macular degeneration in healthy women.²⁷⁸

Use of vitamin C or vitamin E supplements, or both, has been associated with better cognitive function and a reduced risk of certain forms of dementia (not including Alzheimer’s disease).²⁷⁹ Clinical trials of these antioxidants are needed to confirm the possible benefits suggested by this study.

Relatively high blood levels of vitamin E have been associated with relatively low levels of hormones linked to prostate cancer.²⁸⁰ In a double-blind trial studying smokers, vitamin E supplementation (50 IU per day for an average of six years) led to a 32% decrease in prostate cancer incidence and a 41% decrease in prostate cancer deaths.²⁸¹ Both findings were statistically significant.²⁸¹ However, in a double-blind study of 35,533 healthy men, supplementing with 400 IU per day of vitamin E for an average of 5.5 years (with a total follow-up period of 7 years) significantly increased the incidence of prostate cancer by 17%.²⁸³ The effects of vitamin E have yet to be studied in men already diagnosed with prostate cancer.

The conflicting results in these studies may be due to the fact that all of the studies used pure alpha-tocopherol, which is only one of the four different forms of vitamin E that occur naturally in food (alpha-, beta-, gamma-, and delta-tocopherol). Treatment with large doses of alpha-tocopherol by itself (such as 400 IU per day or more) has been shown to deplete gamma-tocopherol, potentially upsetting the natural balance of the different forms of vitamin E in the body. "Mixed tocopherols," on the other hand, a supplement that contains all four types of vitamin E, would not be expected to cause such an imbalance.

Both alpha-tocopherol and gamma-tocopherol have been found to inhibit the growth of human prostate cancer cells in a test tube, but gamma-tocopherol was the more potent of the two.²⁸⁴ In another study, higher blood levels of alpha-tocopherol and gamma-tocopherol were each associated a lower risk of developing prostate cancer, but the protective effect of gamma-tocopherol was greater than that of alpha-tocopherol.²⁸⁵ These observations raise the possibility that both alpha- and gamma-tocopherol have a protective effect against prostate cancer. However, when alpha-tocopherol is given by itself in large doses (such as 400 IU per day or more), it depletes gamma-tocopherol, which could more than negate any beneficial effect that alpha-tocopherol might have. If that is the case, then taking vitamin E as mixed tocopherols would not be expected to increase prostate cancer risk, and might even help prevent prostate cancer. Further research is needed to examine that possibility.

Sunlight triggers oxidative damage in the eye, which in turn can cause macular degeneration.²⁸⁵ Animals given antioxidants—which protect against oxidative damage—have a lower risk of this vision problem.²⁸⁶ People with high blood levels of antioxidants also have a lower risk.²⁸⁷ Those with the highest levels (top 20th percentile) of the antioxidants selenium, vitamin C, and vitamin E may have a 70% lower risk of developing macular degeneration, compared with people with the lowest levels of these nutrients (bottom 20th percentile).²⁸⁸ People who eat fruits and vegetables high in beta-carotene, another antioxidant, are also at low risk.²⁸⁹ Some doctors recommend antioxidant supplements to reduce the risk of macular degeneration; reasonable adult levels include 200 mcg of selenium, 1,000 mg of vitamin C, 400 IU of vitamin E, and 25,000 IU of natural beta-carotene per day. However, a preliminary study found no association between age-related macular degeneration and intake of antioxidants, either from the diet, from supplements, or from both combined.²⁹⁰ Moreover, in a double-blind study of male cigarette smokers, supplementing with vitamin E (50 IU per day), synthetic beta-carotene (about 33,000 IU per day), or both did not reduce the incidence of age-related macular degeneration.²⁹¹ Another double-blind trial found that supplementing with 600 IU of vitamin E every other day did not reduce the incidence of age-related macular degeneration in healthy women.²⁹²

Free radicals have been implicated in the development and progression of several forms of retinopathy.²⁹³ Retrolental fibroplasia, a retinopathy that occurs in some premature infants who have been exposed to high levels of oxygen, is an example of free radical-induced damage to the retina. In an analysis of the best published trials, large amounts of vitamin E were found to reduce the incidence of severe retinopathy in premature infants by over 50%.^294,295 Some of the evidence supporting the use of vitamin E in the prevention of retrolental fibroplasia comes from trials that have used 100 IU of vitamin E per 2.2 pounds of body weight in the form of oral supplementation.²⁹⁶ Use of large amounts of vitamin E in the prevention of retrolental fibroplasia requires the supervision of a pediatrician.

Vitamin E has also been found to prevent retinopathy in people with a rare genetic disease known as abetalipoproteinemia.²⁹⁷ People with this disorder lack a protein that transports fat-soluble nutrients, and can therefore develop deficiencies of vitamin E and other nutrients.

In one trial, vitamin E failed to improve vision in people with diabetic retinopathy,²⁹⁸ although in a double-blind trial, people with type 1 diabetes given very high amounts of vitamin E were reported to show a normalization of blood flow to the retina.²⁹⁹ This finding has made researchers hopeful that vitamin E might help prevent diabetic retinopathy. However, no long-term trials have yet been conducted with vitamin E in the actual prevention of diabetic retinopathy.

Because oxidation damage is believed to play a role in the development of retinopathy, antioxidant nutrients might be protective. One doctor has administered a daily regimen of 500 mcg selenium, 800 IU vitamin E, 10,000 IU vitamin A, and 1,000 mg vitamin C for several years to 20 people with diabetic retinopathy. During that time, 19 of the 20 people showed either improvement or no progression of their retinopathy.³⁰⁰ People who wish to supplement with more than 250 mcg of selenium per day should consult a healthcare practitioner.

People with low blood levels of antioxidants and those who eat few antioxidant-rich fruits and vegetables have been reported to be at high risk for cataracts.^301,302

Low blood levels of vitamin E have been linked to increased risk of forming cataracts.^303,304 Dietary vitamin E intake has not been consistently associated with protection from cataracts.^305,306 Vitamin E supplements have been reported to protect against cataracts in animals³⁰⁷ and people,³⁰⁸ though the evidence remains inconsistent.³⁰⁹ In one trial, people who took vitamin E supplements had less than half the risk of developing cataracts, compared with others in the five-year study.³¹⁰ Doctors typically recommend 400 IU of vitamin E per day as prevention. Smaller amounts (approximately 50 IU per day) have been proven in double-blind research to provide no protection.³¹¹

Based on the personal experience of a doctor who reported his findings,³¹² some physicians recommend vitamin E (400 IU per day) and selenium (50 mcg three times per day). One well-known, nutritionally oriented doctor reports anecdotally that he has had considerable success with this regimen and often sees results in two to six weeks.³¹³

Healthy immune function also requires adequate amounts of vitamin E. Vitamin E deficiency is associated with increased severity of viral infections in mice.^314,315,316 Supplementation with vitamin E during viral infections has been shown to increase immune cell activity³¹⁷ and reduce virus activity³¹⁸ in mice. Research into the effects of vitamin E supplementation on childhood exanthems has not been done.

In a double-blind trial, supplementation with 200 IU of synthetic vitamin E per day was found to reduce several risk factors for kidney stone formation in people with elevated levels of urinary oxalate.³¹⁹

Vitamin E deficiency in animals leads to infertility.³²⁰ In a preliminary human trial, 100–200 IU of vitamin E given daily to both partners of infertile couples led to a significant increase in fertility.³²¹ Vitamin E supplementation may enhance fertility by decreasing free-radical damage to sperm cells. In another preliminary study, men with low fertilization rates in previous attempts at in vitro fertilization were given 200 IU of vitamin E per day for three months.³²² After one month of supplementation, fertilization rates increased significantly, and the amount of oxidative stress on sperm cells decreased. However, the evidence in favor of vitamin E remains preliminary. A review of research on vitamin E for male infertility concluded that there is no justification for its use in treating this condition.³²³ Controlled trials are needed to validate these promising preliminary findings.

In a group of nine people with RLS, 300 IU of vitamin E per day produced complete relief in seven.³²⁴ Doctors who give vitamin E to people with RLS generally recommend at least 400 IU of vitamin E per day, and the full benefits may not become apparent for three months.³²⁵

Use of vitamin C or vitamin E supplements, or both, has been associated with better cognitive function and a reduced risk of certain forms of dementia (not including Alzheimer’s disease).³²⁶ Clinical trials of these antioxidants are needed to confirm the possible benefits suggested by this study.

Most research has demonstrated that strenuous exercise increases production of harmful substances called free radicals, which can damage muscle tissue and result in inflammation and muscle soreness. Exercising in cities or smoggy areas also increases exposure to free radicals. Antioxidants, including vitamin C and vitamin E, neutralize free radicals before they can damage the body, so antioxidants may aid in exercise recovery. Regular exercise increases the efficiency of the antioxidant defense system, potentially reducing the amount of supplemental antioxidants that might otherwise be needed for protection. However, at least theoretically, supplements of antioxidant vitamins may be beneficial for older or untrained people or athletes who are undertaking an especially vigorous training protocol or athletic event.^327,328

Placebo-controlled research, some of it double-blind, has shown that taking 400 to 3,000 mg of vitamin C per day for several days before and after intense exercise may reduce pain and speed up muscle strength recovery.^329,330,331 However, taking vitamin C only after such exercise was not effective in another double-blind study.³³² While some research has reported that vitamin E supplementation in the amount of 800 to 1,200 IU per day reduces biochemical measures of free radical activity and muscle damage caused by strenuous exercise,^333,334,335 several studies have not found such benefits,^{336,337,338,339} and no research has investigated the effect of vitamin E on performance-related measures of strenuous exercise recovery. A combination of 90 mg per day of coenzyme Q10 and a very small amount of vitamin E did not produce any protective effects for marathon runners in one double-blind trial,³⁴⁰ while in another double-blind trial a combination of 50 mg per day of zinc and 3 mg per day of copper significantly reduced evidence of post-exercise free radical activity.³⁴¹

In most well-controlled studies, exercise performance has not been shown to improve following supplementation with vitamin C, unless a deficiency exists, as might occur in athletes with unhealthy or irrational eating patterns.^342,343 Similarly, vitamin E has not benefited exercise performance, ^344,345 except possibly at high altitudes. ^346,347

Most research has demonstrated that strenuous exercise increases production of harmful substances called free radicals, which can damage muscle tissue and result in inflammation and muscle soreness. Exercising in cities or smoggy areas also increases exposure to free radicals. Antioxidants, including vitamin C and vitamin E, neutralize free radicals before they can damage the body, so antioxidants may aid in exercise recovery. Regular exercise increases the efficiency of the antioxidant defense system, potentially reducing the amount of supplemental antioxidants that might otherwise be needed for protection. However, at least theoretically, supplements of antioxidant vitamins may be beneficial for older or untrained people or athletes who are undertaking an especially vigorous training protocol or athletic event.^348,349

Placebo-controlled research, some of it double-blind, has shown that taking 400 to 3,000 mg of vitamin C per day for several days before and after intense exercise may reduce pain and speed up muscle strength recovery.^350,351,352 However, taking vitamin C only after such exercise was not effective in another double-blind study.³⁵³ While some research has reported that vitamin E supplementation in the amount of 800 to 1,200 IU per day reduces biochemical measures of free radical activity and muscle damage caused by strenuous exercise,^354,355,356 several studies have not found such benefits,^{357,358,359,360} and no research has investigated the effect of vitamin E on performance-related measures of strenuous exercise recovery. A combination of 90 mg per day of coenzyme Q10 and a very small amount of vitamin E did not produce any protective effects for marathon runners in one double-blind trial,³⁶¹ while in another double-blind trial a combination of 50 mg per day of zinc and 3 mg per day of copper significantly reduced evidence of post-exercise free radical activity.³⁶²

In most well-controlled studies, exercise performance has not been shown to improve following supplementation with vitamin C, unless a deficiency exists, as might occur in athletes with unhealthy or irrational eating patterns.^363,364 Similarly, vitamin E has not benefited exercise performance, ^365,366 except possibly at high altitudes. ^367,368

Supplementation with vitamin E has been used successfully with people who have yellow nail syndrome in several preliminary reports.^369,370,371 Although topical use of the vitamin has also been reported to be effective,³⁷² taking vitamin E supplements is much easier and less messy. A typical amount is 800 IU per day, with results beginning to appear after several months.