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.^{1 , 2} 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)^{3 , 4 , 5} and anemia caused by kidney dialysis.^{6 , 7}

Vitamin E has been studied as a possible add-on to conventional drug treatment for epilepsy. A double-blind trial found that adding 400 IU per day of vitamin E reduced seizure frequency in children without side effects.⁸ Other preliminary trials^{9, 10} have reported similar results, and, while some preliminary research suggested this effect might also be achieved in adults,¹¹ a double-blind trial found no effect of vitamin E supplementation on adults with epilepsy.¹²

Most,^{13 , 14} but not all,¹⁵ 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.¹⁶ Burn victims have also experienced fewer infections after receiving trace mineral supplements in double-blind research.¹⁷ These studies suggest that trace minerals may be the most important micronutrients for enhancing immunity and preventing infections in the elderly.

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.^{18, 19} Increasing dietary intake of vitamin E was also associated with better blood flow to the legs.²⁰ Some early studies did not find vitamin E useful. Possibly this failure was due to the short duration of the studies,²¹ 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.²² 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.

People with RA have been reported to have an impaired antioxidant system, making them more susceptible to free radical damage.²³ Vitamin 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.²⁴ In a double-blind trial, approximately 1,800 IU per day of vitamin E was found to reduce pain from RA.²⁵ 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.^{26 , 27} 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.^{28 , 29}

Antioxidants may protect the skin from sunburn due to free radical–producing ultraviolet rays.³⁰ 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.^{31, 32, 33}

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.^{34 , 35 , 36 , 37 , 38}

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.³⁹ 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.⁴⁰ 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.⁴¹

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.⁴² 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.⁴³ Similarly, in a controlled trial, a combination of selenium, copper, and vitamins was found to be ineffective.⁴⁴

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.^{45 , 46}

Vitamin E has been found in a number of studies to reduce the severity of TD. In a double-blind trial, people with TD were randomly assigned to receive vitamin E (800 IU per day for two weeks and 1,600 IU per day thereafter) or a placebo. Vitamin E was significantly more effective than placebo in reducing involuntary movements.⁴⁷ An uncontrolled study of 20 people with TD reported that 1,600 IU of vitamin E per day may be the optimal amount;⁴⁸ this large amount should be supervised by a healthcare practitioner. Other studies have also found that vitamin E supplements reduce the severity of TD.^{49, 50, 51} Two studies failed to show a beneficial effect of vitamin E.^{52, 53} However, the people in those studies had been receiving neuroleptics for at least ten years, and research has shown that vitamin E is most effective when started within the first five years of neuroleptic treatment.^{54, 55}

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.⁵⁶ Other preliminary research shows that higher blood levels of vitamin E correlate with better brain functioning in middle-aged and older adults.⁵⁷ 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.⁵⁸ 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.⁵⁹

Low levels of antioxidant vitamins in the blood, particularly vitamin E, are associated with greater rates of angina.⁶⁰ 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.⁶¹ 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.⁶² Those affected by variant angina have been found to have the greatest deficiency of vitamin E compared with other angina patients.⁶³

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.^{64 , 65}

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.^{66 , 67 , 68} However, taking vitamin C only after such exercise was not effective in another double-blind study.⁶⁹ 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,^{70 , 71 , 72} several studies have not found such benefits,^{73 , 74 , 75 , 76} 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,⁷⁷ 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.⁷⁸

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.^{79 , 80} Similarly, vitamin E has not benefited exercise performance, ^{81 , 82} except possibly at high altitudes. ^{83 , 84}

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.⁸⁵ Similar results were reported in another study.⁸⁶

A deficiency in the selenium-containing antioxidant enzyme known as glutathione peroxidase has been reported in DH.^{87 , 88} 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.

Alzheimer’s disease, cataracts, autoimmune diseases, and a general increase in the pace of aging are all seen in people with Down’s syndrome.⁹¹ These associated conditions are similar in that they involve damage to body tissues by free radicals. It is believed that the genetic defect that produces Down’s syndrome increases the need for antioxidants (nutrients that prevent free-radical damage), and several studies of blood and urine biochemistry have shown this to be true.^{92, 93} In a preliminary study, vitamin E protected cells of people with Down’s syndrome from the oxidative damage to which they are most susceptible.⁹⁴ However, blood levels of vitamin C and vitamin E, two antioxidant nutrients, have not been found to be different when compared with those of healthy individuals.^{95, 96} The role of vitamin E and other antioxidants in treating Down’s syndrome needs further exploration.

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.⁹⁷ 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.⁹⁸

In a study of women with pelvic pain presumed to be due to endometriosis, supplementation with vitamin E (1,200 IU per day) and vitamin C (1,000 mg per day) for two months resulted in an improvement of pain in 43% of women, whereas none of the women receiving a placebo reported pain relief.⁹⁹

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.¹⁰⁰

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.¹⁰¹ After 28 days, the infarct size of those receiving antioxidants was significantly smaller than the infarct size of the placebo group.

In a double-blind study of people with high blood pressure, 200 IU of vitamin E per day taken for 27 weeks was significantly more effective than a placebo at reducing both systolic and diastolic blood pressure.¹⁰² This study was done in Iran, and it is not clear whether the results would apply to individuals consuming a Western diet.

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.¹⁰³

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.¹⁰⁴ 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.¹⁰⁵ 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).¹⁰⁶ 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.¹⁰⁷ After 24 weeks, 46% showed some improvement in signs or symptoms of leukoplakia or related conditions and 21% showed microscopic evidence of improvement.

Relatively high blood levels^{108 , 109} and dietary levels¹¹⁰ of vitamin E have been associated with a reduced risk of lung cancer. In a preliminary trial, nonsmokers who took vitamin E supplements had a 45% lower risk of lung cancer compared with nonsmokers who did not supplement with vitamin E.¹¹¹ While a double-blind trial reported that vitamin E supplementation had no effect on lung cancer risk,¹¹² the amount used—approximately 50 IU per day—may have been too low to have a significant effect.

Many years ago, researchers studied the effects of vitamin E supplementation in reducing symptoms of menopause. Most,^{113 , 114 , 115 , 116 , 117} but not all,¹¹⁸ studies found vitamin E to be helpful, and the benefit of vitamin E was confirmed more recently in a double-blind trial.¹¹⁹ 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.

Based on the personal experience of a doctor who reported his findings,¹²⁰ 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.¹²¹

People who have OA 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.¹²² Of the individual antioxidants, only vitamin E has been studied as a supplement in controlled trials. Vitamin E supplementation has reduced symptoms of OA in both single-blind¹²³ and double-blind research.^{124 , 125} 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 OA of the knee, 500 IU per day of vitamin E was no more effective than a placebo.¹²⁶

Some preliminary studies have indicated that high dietary intakes of antioxidant nutrients, especially vitamin E, are associated with a low risk of Parkinson’s disease,^{127 , 128} even though Parkinson’s patients are not deficient in vitamin E.^{129 , 130} The correlation between protection from Parkinson’s and dietary vitamin E may be not be due to the vitamin E itself, however. Legumes (beans and peas) contain relatively high amounts of vitamin E. Independent of their vitamin E content, consumption of legumes has been associated with low risk of Parkinson’s disease.¹³¹ In other words, high vitamin E intake may be a marker for diets high in legumes, and legumes may protect against Parkinson’s disease for reasons unrelated to their vitamin E content.

Interest in the relationship between antioxidants and Parkinson’s disease led to a preliminary trial using high amounts of vitamin C and vitamin E in early Parkinson’s disease¹³² and to a large ten-year controlled trial of high amounts of vitamin E combined with the drug deprenyl.¹³³ In the trial combining vitamins C and E, people with early Parkinson’s disease given 750 mg of vitamin C and 800 IU of vitamin E four times each day (totaling 3,000 mg of vitamin C and 3,200 IU of vitamin E per day) were able to delay the need for drug therapy (i.e., L-dopa or selegiline) by an average of about two and a half years, compared with those not taking the vitamins.¹³⁴ The ten-year controlled trial used 2,000 IU of vitamin E per day found no benefit in slowing or improving the disease.¹³⁵ The difference in the outcomes between these two trials might be due to the inclusion of vitamin C and/or the higher amount of vitamin E used in the successful trial. However, the difference might also be due to a better study design in the trial that found vitamin E to be ineffective.

The amounts of vitamin E used in the above trials were very high, because raising antioxidant levels in brain tissue is quite difficult to achieve.¹³⁶ In fact, some researchers have found that even extremely high intakes of vitamin E (4,000 IU per day) failed to increase brain vitamin E levels.¹³⁷ The difficulty in increasing brain vitamin E levels may explain the poor results of the large, controlled trial.

Although women with PMS do not appear to be deficient in vitamin E,¹³⁸ a double-blind trial reported that 300 IU of vitamin E per day may decrease symptoms of PMS.¹³⁹

Relatively high blood levels of vitamin E have been associated with relatively low levels of hormones linked to prostate cancer.¹⁴⁰ While a relationship between higher blood levels of vitamin E and a reduced risk of prostate cancer has been reported only inconsistently,^{141 , 142} supplemental use of vitamin E¹⁴³ has been associated with a reduced risk of prostate cancer in smokers. In a double-blind trial studying smokers, vitamin E supplementation (50 IU of vitamin E 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.¹⁴⁴ Both findings were statistically significant.¹⁴⁵ 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 did not reduce the incidence of prostate cancer.¹⁴⁶ The effects of vitamin E have yet to be studied in men already diagnosed with prostate cancer.

Free radicals have been implicated in the development and progression of several forms of retinopathy.¹⁴⁷ 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%.^{148, 149} 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.¹⁵⁰ 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.¹⁵¹ 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,¹⁵² 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.¹⁵³ 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.¹⁵⁴ People who wish to supplement with more than 250 mcg of selenium per day should consult a healthcare practitioner.

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.^{155, 156} The topical use of the hormone melatonin has been shown to protect human skin against ultraviolet rays in double-blind research.^{157, 158} 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.¹⁵⁹ Other studies in which topical antioxidants were applied after ultraviolet exposure have found no benefits.^{160, 161}

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.^{162, 163} The topical use of the hormone melatonin has been shown to protect human skin against ultraviolet rays in double-blind research.^{164, 165} 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.¹⁶⁶ Other studies in which topical antioxidants were applied after ultraviolet exposure have found no benefits.^{167, 168}

People with low blood levels of vitamin E are more likely to develop type 1 and type 2 diabetes.^{169 , 170} Vitamin E supplementation has improved glucose tolerance in people with type 2 diabetes in most,^{171 , 172 , 173} but not all,¹⁷⁴ double-blind trials. Vitamin E has also improved glucose tolerance in elderly people without diabetes.^{175 , 176} 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.¹⁷⁷ Animal and preliminary human data indicate that vitamin E supplementation may protect against diabetic retinopathy and nephropathy,^{178 , 179} 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,^{180 , 181 , 182 , 183 , 184} although not all,^{185 , 186 , 187} studies.

In one report, vitamin E was found to impair glucose tolerance in obese patients with diabetes.¹⁸⁸ 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).¹⁸⁹

People with low blood levels of vitamin E are more likely to develop type 1 and type 2 diabetes.^{190 , 191} Vitamin E supplementation has improved glucose tolerance in people with type 2 diabetes in most,^{192 , 193 , 194} but not all,¹⁹⁵ double-blind trials. Vitamin E has also improved glucose tolerance in elderly people without diabetes.^{196 , 197} 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.¹⁹⁸ Animal and preliminary human data indicate that vitamin E supplementation may protect against diabetic retinopathy and nephropathy,^{199 , 200} 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,^{201 , 202 , 203 , 204 , 205} although not all,^{206 , 207 , 208} studies.

In one report, vitamin E was found to impair glucose tolerance in obese patients with diabetes.²⁰⁹ 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).²¹⁰

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.²¹¹ In another study, however, wound healing was inhibited by supplementation with a massive amount of vitamin E (equivalent to about 35,000 IU).²¹² 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,^{213 , 214} and one trial found vitamin E improved the effect of silicon bandages on large scars called keloids.²¹⁵

Supplementation with vitamin E has been used successfully with people who have yellow nail syndrome in several preliminary reports.^{216 , 217 , 218} Although topical use of the vitamin has also been reported to be effective,²¹⁹ 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.

Women with cervical dysplasia may have lower blood levels of beta-carotene and vitamin E^{220 , 221} compared to healthy women.

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).²²² Clinical trials of these antioxidants are needed to confirm the possible benefits suggested by this study.

The daily combination of 3 grams of vitamin C, 3 grams of niacin, 600 mg of vitamin B6, and 600 IU of vitamin E has been used by researchers from the University of Mississippi Medical Center in an attempt to reduce anxiety and depression in alcoholics.²²³ Although the effect of vitamin supplementation was no better than placebo in treating alcohol-associated depression, the vitamins did result in a significant drop in anxiety within three weeks of use. Because of possible side effects, anyone taking such high amounts of niacin and vitamin B6 must do so only under the care of a doctor.

Although the incidence of B-complex deficiencies is known to be high in alcoholics, the incidence of other vitamin deficiencies remains less clear.²²⁴ Nonetheless, deficiencies of vitamin A, vitamin D, vitamin E, and vitamin C are seen in many alcoholics. While some reports have suggested it may be safer for alcoholics to supplement with beta-carotene instead of vitamin A,²²⁵ potential problems accompany the use of either vitamin A or beta-carotene in correcting the deficiency induced by alcoholism.²²⁶ These problems result in part because the combinations of alcohol and vitamin A or alcohol and beta-carotene appear to increase potential damage to the liver. Thus, vitamin A-depleted alcoholics require a doctor’s intervention, including supplementation with vitamin A and beta-carotene accompanied by assessment of liver function. Supplementing with vitamin C, on the other hand, appears to help the body rid itself of alcohol.²²⁷ Some doctors recommend 1 to 3 grams per day of vitamin C.

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.²²⁸ 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.²²⁹ 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.²³⁰ 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.²³¹ 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.

Vitamin E is an antioxidant that serves to protect LDL from oxidative damage²³² and has been linked to prevention of heart disease in double-blind research.²³³ 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.²³⁴ 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.²³⁵

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,²³⁶ although it is not known how much vitamin E is needed to produce that protective effect.

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.^{237 , 238} Therefore, those planning to apply vitamin E to the skin should buy the tocopherol form.

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.^{239 , 240}

Low blood levels of vitamin E have been linked to increased risk of forming cataracts.^{241 , 242} Dietary vitamin E intake has not been consistently associated with protection from cataracts.^{243 , 244} Vitamin E supplements have been reported to protect against cataracts in animals²⁴⁵ and people,²⁴⁶ though the evidence remains inconsistent.²⁴⁷ 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.²⁴⁸ 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.²⁴⁹

Healthy immune function also requires adequate amounts of vitamin E. Vitamin E deficiency is associated with increased severity of viral infections in mice.^{250 , 251 , 252} Supplementation with vitamin E during viral infections has been shown to increase immune cell activity²⁵³ and reduce virus activity²⁵⁴ in mice. Research into the effects of vitamin E supplementation on childhood exanthems has not been done.

The fat malabsorption associated with CF often leads to a deficiency of fat-soluble vitamins. Oral supplementation of these nutrients is considered crucial to maintaining good nutritional status.²⁶⁰ Current recommendations for supplementation are as follows: vitamin A, 5,000 to 10,000 IU/day; vitamin D, 1,000 to 2,000 IU/day; vitamin E, 100 to 300 IU/day; and vitamin K, 5 mg every three days. Of the water-soluble vitamins, only vitamin B12 is poorly absorbed in cystic fibrosis,²⁶¹ and taking pancreatic enzymes helps prevent B12 deficiencies.²⁶²

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.²⁶³ Other studies, however, did not find it useful.²⁶⁴ Overall, there are more positive trials than negative ones,²⁶⁵ 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.

Vitamin E has been studied as a possible add-on to conventional drug treatment for epilepsy. A double-blind trial found that adding 400 IU per day of vitamin E reduced seizure frequency in children without side effects.²⁶⁶ Other preliminary trials^{267, 268} have reported similar results, and, while some preliminary research suggested this effect might also be achieved in adults,²⁶⁹ a double-blind trial found no effect of vitamin E supplementation on adults with epilepsy.²⁷⁰

Vitamin E deficiency in animals leads to infertility.²⁷¹ 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.²⁷²

While several studies report that 200–600 IU of vitamin E per day, taken for several months, reduces symptoms of FBD,^{273 , 274} most double-blind trials have found that vitamin E does not relieve FBD symptoms.^{275 , 276} Nonetheless, many women take 400 IU of vitamin E for three months to see if it helps.

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.²⁷⁷ Double-blind trials are needed to confirm these preliminary observations.

Blood levels of vitamin A are lower in people with goiter than in similar people without goiter.^{278 , 279} The same relationship has been found for vitamin E and goiter.²⁸⁰ Animal research has found that, in iodine-deficient conditions, a supplement combination of vitamin C, vitamin E, and beta-carotene prevented goiter formation (though hypothyroidism was not improved), and vitamin E alone had a similar effect.²⁸¹ No studies have been done to investigate this benefit in humans.

Nutritional supplements recommended by some doctors for prevention and treatment of periodontitis include vitamin C (people with periodontitis are often found to be deficient),²⁸² vitamin E, selenium, zinc, coenzyme Q10, and folic acid.²⁸³ Folic acid has also been shown to reduce the severity of gingivitis when taken as a mouthwash.²⁸⁴

Vitamin E levels have been shown to be low in people with hepatitis,²⁸⁵ as well as in those who later develop liver cancer from long-standing hepatitis.²⁸⁶ Vitamin E levels in the liver may also be decreased in some people with hepatitis.²⁸⁷ In a controlled trial of individuals with hepatitis B, 600 IU of vitamin E per day for nine months resulted in all signs of hepatitis disappearing in five of twelve people.²⁸⁸ In a preliminary trial of adults with hepatitis C, administering 1,200 IU per day of vitamin E for eight weeks appeared to reduce liver damage to some extent.²⁸⁹ In a preliminary trial of people with hepatitis C, 544 IU of vitamin E per day for 24 weeks improved the response to interferon/antioxidant therapy, although the results did not reach statistical significance.²⁹⁰ However, in children with viral hepatitis, daily injections of vitamin E (300 IU) for seven days did not produce any benefit.²⁹¹

In test-tube studies, vitamin E improved the effectiveness of the anti-HIV drug zidovudine (AZT) while reducing its toxicity.²⁹⁸Similarly, animal research suggests that zinc and NAC supplementation may protect against AZT toxicity.²⁹⁹ It is not known whether oral supplementation with these nutrients would have similar effects in people taking AZT.

Research has shown that supplementing with chromium (200 mcg per day)³⁰⁰ or magnesium (340 mg per day)³⁰¹ 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.³⁰² Other nutrients, including vitamin C, vitamin E, zinc, copper, manganese, and vitamin B6, may help control blood sugar levels in diabetics.³⁰³ 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.

Vitamin E, 800–1,350 IU per day, has been shown to increase insulin sensitivity in both healthy³⁰⁴ and hypertensive³⁰⁵ people in double-blind studies. Research is needed to investigate this effect in people with IRS.

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.³⁰⁶

Vitamin E has been shown to decrease damage in cirrhotic livers and may reduce immune abnormalities that contribute to the development of the disease.³⁰⁷ However, a study reported that supplementation of 500 IU per day of vitamin E for one year failed to influence laboratory tests, liver function, survival or hospitalization rates in people with alcoholic cirrhosis.³⁰⁸ Further clinical trials are needed to determine if any benefits may be expected from vitamin E supplementation in people with liver cirrhosis.

Sunlight triggers oxidative damage in the eye, which in turn can cause macular degeneration.³⁰⁹ Animals given antioxidants—which protect against oxidative damage—have a lower risk of this vision problem.³¹⁰ People with high blood levels of antioxidants also have a lower risk.³¹¹ 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).³¹² People who eat fruits and vegetables high in beta-carotene, another antioxidant, are also at low risk.³¹³ 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.³¹⁴ 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.³¹⁵ 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.³¹⁶

Vitamin E deficiency in animals leads to infertility.³¹⁷ 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.³¹⁸ 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.³¹⁹ 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.³²⁰ Controlled trials are needed to validate these promising preliminary findings.

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).³²¹ 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 studies of surgery patients,^{322 , 323} though not all, ³²⁴ 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,³²⁵ but a human study reported disappointing results.³²⁶ Vitamin E taken by mouth may interfere with blood clotting³²⁷; 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.

In a group of nine people with RLS, 300 IU of vitamin E per day produced complete relief in seven.³²⁸ 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.³²⁹

Free radicals have been implicated in the development and progression of several forms of retinopathy.³³⁰ 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%.^{331, 332} 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.³³³ 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.³³⁴ 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,³³⁵ 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.³³⁶ 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.³³⁷ People who wish to supplement with more than 250 mcg of selenium per day should consult a healthcare practitioner.

Some doctors have found vitamin E to be effective for people with postherpetic neuralgia—even those who have had the problem for many years.^{338 , 339} 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;³⁴⁰ however, in the study that produced negative results, vitamin E may not have been used for a long enough period of time.

Antioxidant nutrients protect the body’s cells from oxygen-related damage. Many studies show that sickle cell anemia patients tend to have low blood levels of antioxidants, including carotenoids, vitamin A, vitamin E, and vitamin C, despite adequate intake.^{341, 342, 343, 344, 345, 346} Low blood levels of vitamin E in particular have been associated with higher numbers of diseased cells in children³⁴⁷ and with greater frequency of symptoms in adults.³⁴⁸ A small, preliminary trial reported a 44% decrease in the average number of diseased cells in six sickle cell anemia patients given 450 IU vitamin E per day for up to 35 weeks. This effect was maintained as long as supplementation continued.³⁴⁹

In another preliminary trial, 13 patients with sickle cell anemia were given two supplement combinations for seven to eight months each. The first combination included 109 mg zinc, 153 IU vitamin E, 600 mg vitamin C, and 400 ml (about 14 ounces) of soybean oil containing 11 grams of linoleic acid and 1.5 grams of alpha linolenic acid. The second combination included 140 IU vitamin E, 600 mg vitamin C, and 20 grams of fish oil containing 6 grams of omega-3 fatty acids. Reduction in diseased cells was observed only during the administration of the first protocol. The authors concluded that zinc was the important difference between the two combinations and may be a protector of red blood cell membranes.³⁵⁰

Fish oil alone has also been studied. In a double-blind trial, supplementation with menhaden oil, in the amount of 250 mg per 2.2 pounds of body weight per day for one year, reduced the frequency of severe pain episodes by approximately 45%, compared with placebo.³⁵¹ This treatment may work by correcting an imbalance between omega-3 and omega-6 fatty acids that occurs in people with sickle cell anemia.³⁵²

Antioxidant supplements, including vitamin C and vitamin E, may help prevent exercise-related muscle injuries by neutralizing free radicals produced during strenuous activities.³⁵³ 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.^{354, 355} 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,^{356, 357, 358} but no measurable benefits in exercise recovery have been reported.³⁵⁹ 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.³⁶⁰

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.^{361 , 362}

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.³⁶³ Vitamin E plus aspirin, has been more effective in reducing the risk of strokes and other related events than has aspirin, alone.³⁶⁴ However, most preliminary trials have shown no protective effects from antioxidant supplementation.^{365 , 366 , 367 , 368 , 369 , 370} A large Finnish trial concluded that supplementation with either vitamin E or beta-carotene conferred no protection against stroke in male smokers,³⁷¹ 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.³⁷²

People with high risk for stroke, such as those who have had TIAs or who have a heart condition known as atrial fibrillation,³⁷³ are often given aspirin or anticoagulant medication to reduce blood clotting tendencies. Some natural inhibitors of blood clotting such as garlic,^{374 , 375 , 376} fish oil,³⁷⁷ and vitamin E,^{378 , 379} may have protective effects, but even large amounts of fish oil are known to be less potent than aspirin.³⁸⁰ 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.

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.

Antioxidants may protect the skin from sunburn due to free radical–producing ultraviolet rays.³⁸⁴ 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.^{385, 386, 387}

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.^{388 , 389 , 390 , 391 , 392}

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.³⁹³ 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.³⁹⁴ 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.³⁹⁵

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.³⁹⁶ 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.³⁹⁷ Similarly, in a controlled trial, a combination of selenium, copper, and vitamins was found to be ineffective.³⁹⁸

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.^{399 , 400}