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

Antioxidants may protect the skin from sunburn due to free radical–producing ultraviolet rays.¹³ 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.^14,15,16

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.^{17,18,19,20,21}

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.²² 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.²³ 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.²⁴

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.²⁵ 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.²⁶ Similarly, in a controlled trial, a combination of selenium, copper, and vitamins was found to be ineffective.²⁷

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.^28,29

Most,^30,31 but not all,³² 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.³³ Burn victims have also experienced fewer infections after receiving trace mineral supplements in double-blind research.³⁴ These studies suggest that trace minerals may be the most important micronutrients for enhancing immunity and preventing infections in the elderly.

People with RA have been reported to have an impaired antioxidant system, making them more susceptible to free radical damage.³⁵Vitamin 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.³⁶ In a double-blind trial, approximately 1,800 IU per day of vitamin E was found to reduce pain from RA.³⁷ 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.^38,39 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.^40,41