Caution: Synthetic beta-carotene has been linked to increased risk of lung cancer in smokers. Until more is known, smokers should avoid all beta-carotene supplements.

Beta-carotene is the most widely used supplement in the treatment of leukoplakia. In a clinical trial of betel nut chewers with leukoplakia, supplementation with 150,000 IU of beta-carotene twice per week for six months significantly increased the remission rate compared with placebo (14.8% vs. 3.0%).¹ The effectiveness of beta-carotene for treating leukoplakia was also confirmed in a double-blind trial that used 100,000 IU per day for six months.² In one trial, supplementation with 33, 333 IU of beta-carotene per day, alone or combined with 50 IU of vitamin E, was reported not to reduce the incidence of leukoplakia.³ These results have also been observed in smaller trials.^{4, 5}

Drug therapy with a synthetic, prescription form of vitamin A (known as Accutane, isotretinoin, and 13-cis retinoic acid) has been reported to be more effective than treatment with 50,000 IU per day of beta-carotene.⁶ However, because of the potential toxicity of the vitamin A-like drug, it may be preferable to treat leukoplakia with beta-carotene, which is much safer.

Before the research on beta-carotene was published, vitamin A was used to treat leukoplakia.⁷ One group of researchers reported that vitamin A (28,500 IU per day) was more effective than beta-carotene in treating people with leukoplakia.⁸ Another trial found that the combination of 150,000 IU per week of beta-carotene plus 100,000 IU per week of vitamin A led to a significant increase in remission time compared to beta carotene alone in betel nut chewers.⁹ Women who are or who could become pregnant should not take 100,000 IU of vitamin A per week without medical supervision.

In double-blind trials, synthetic beta-carotene supplementation has led to an increased risk of lung cancer in smokers,^{10 , 11} though not in groups consisting primarily of nonsmokers.¹² Smokers should avoid synthetic beta-carotene supplements, including the relatively small amounts found in many multivitamins.

The researchers who conducted the lung cancer trials have been criticized for not having used the natural form of beta-carotene.¹³ Preliminary evidence suggests that natural beta-carotene supplementation results in better antioxidant activity¹⁴ and anticancer activity in humans¹⁵ than does supplementation with synthetic beta-carotene. Nonetheless, much less is known about natural beta-carotene and questions remain about its potential efficacy.¹⁶ The effect of natural beta-carotene supplementation on lung cancer risk has yet to be studied.

The strong association between increased intake of beta-carotene from food and a reduced risk of lung cancer¹⁷ does not necessarily mean that supplementation with natural beta-carotene supplements would reduce the risk of lung cancer. Dietary beta-carotene may be a marker for diets high in certain fruits and vegetables that contain other anticancer substances that may be responsible for the protective effects. Until more is known, some doctors advise smokers to avoid all forms of beta-carotene supplementation—even natural beta-carotene.

Caution: Synthetic beta-carotene has been linked to increased risk of lung cancer in smokers. Until more is known, smokers should avoid all beta-carotene supplements.

Night blindness may be an early sign of vitamin A deficiency. Such a deficiency may result from diets low in animal foods (the main source of vitamin A), such as eggs, dairy products, organ meats, and some fish. Low intake of fruits and vegetables containing beta-carotene, which the body converts into vitamin A, may also contribute to a vitamin A deficiency. Doctors often recommend 10,000 to 25,000 IU of vitamin A per day to correct a deficiency. Beta-carotene is less effective at correcting vitamin A deficiency than is vitamin A itself, because it is not absorbed as well and is only slowly converted by the body into vitamin A.

Caution: Synthetic beta-carotene has been linked to increased risk of lung cancer in smokers. Until more is known, smokers should avoid all beta-carotene supplements.

Years ago, researchers theorized that beta-carotene in skin might help protect against sensitivity to ultraviolet light from the sun. Large amounts of beta-carotene (up to 300,000 IU per day for at least several months) have allowed people with photosensitivity to stay out in the sun several times longer than they otherwise could tolerate.^{18 , 19 , 20} The protective effect appears to result from beta-carotene’s ability to protect against free-radical damage caused by sunlight.²¹

Caution: Synthetic beta-carotene has been linked to increased risk of lung cancer in smokers. Until more is known, smokers should avoid all beta-carotene supplements.

Some researchers have suggested that asthma attacks triggered by exercise might be caused by free-radical damage caused by the exercise. Beta-carotene is an antioxidant that protects against free-radical damage. Israeli researchers reported that 64 mg per day of natural beta-carotene for one week in a double blind trial protected over half of a group of asthmatics who experienced attacks as a result of exercise.²² More research is needed to confirm this promising finding.

Caution: Synthetic beta-carotene has been linked to increased risk of lung cancer in smokers. Until more is known, smokers should avoid all beta-carotene supplements.

Most,^{23 , 24} but not all,²⁵ 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.²⁶ Burn victims have also experienced fewer infections after receiving trace mineral supplements in double-blind research.²⁷ These studies suggest that trace minerals may be the most important micronutrients for enhancing immunity and preventing infections in the elderly.

Beta-carotene and other carotenoids have increased immune cell numbers and activity in animal and human research, an effect that appears to be separate from their role as precursors to vitamin A.^{28 , 29} Placebo-controlled research has shown positive benefits of beta-carotene supplements in increasing numbers of some white blood cells and enhancing cancer-fighting immune functions in healthy people at 25,000–100,000 IU per day.^{30 , 31}

In double-blind trials in the elderly, supplementation with 40,000–150,000 IU per day of beta-carotene has increased natural killer (NK) cell activity,³² but not several other measures of immunity.³³

Controlled research has found that 50,000 IU per day of beta-carotene boosted immunity in people with colon cancer but in not those with precancerous conditions in the colon.³⁴ Beta-carotene has also prevented immune suppression from ultraviolet light exposure.³⁵ Effects on immunodefiency in HIV-positive people have been inconsistent using beta-carotene.^{36 , 37}

Caution: Synthetic beta-carotene has been linked to increased risk of lung cancer in smokers. Until more is known, smokers should avoid all beta-carotene supplements.

Free radical damage has been linked to pancreatitis in animal and human studies,^{38 , 39 , 40} suggesting that antioxidants might be beneficial for this disease. One controlled study found that chronic pancreatitis patients consumed diets significantly lower in several antioxidants due to problems such as appetite loss and abdominal symptoms.⁴¹ Several controlled studies found lower blood levels of antioxidants, such as selenium, vitamin A, vitamin E, vitamin C, glutathione, and several carotenoids, in patients with both acute and chronic pancreatitis.^{42 , 43 , 44 , 45 , 46 , 47}

There are few controlled trials of antioxidant supplementation to patients with pancreatitis. One small controlled study of acute pancreatitis patients found that sodium selenite at a dose of 500 micrograms (mcg) daily resulted in decreased levels of a marker of free radical activity, and no patient deaths occurred.⁴⁸ In a small double-blind trial including recurrent acute and chronic pancreatitis patients, supplements providing daily doses of 600 mcg selenium, 9,000 IU beta-carotene, 540 mg vitamin C, 270 IU vitamin E, and 2,000 mg methionine significantly reduced pain, normalized several blood measures of antioxidant levels and free radical activity, and prevented acute recurrences of pancreatitis.⁴⁹ These researchers later reported that continuing antioxidant treatment in these patients for up to five years or more significantly reduced the total number of days spent in the hospital and resulted in 78% of patients becoming pain-free and 88% returning to work.⁵⁰ Another double-blind study using similar amounts of selenium, beta-carotene, vitamin C, vitamin E, and methionine as those in the study mentioned above reported significant improvements in pain and overall health in patients with chronic pancreatitis.⁵¹

Caution: Synthetic beta-carotene has been linked to increased risk of lung cancer in smokers. Until more is known, smokers should avoid all beta-carotene supplements.

Antioxidants may protect the skin from sunburn due to free radical–producing ultraviolet rays.⁵² 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.^{53, 54, 55}

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 amounts (180 mg per day) or in smaller amounts (30 mg per day) in combination with topical sunscreen.^{56 , 57 , 58 , 59 , 60}

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.⁶¹ 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.⁶² 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.⁶³

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.⁶⁴ 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.⁶⁵ Similarly, in a controlled trial, a combination of selenium, copper, and vitamins was found to be ineffective.⁶⁶

It should be noted that while protection from sunburn has been demonstrated with several types of orally administered 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.^{67 , 68}

Caution: Synthetic beta-carotene has been linked to increased risk of lung cancer in smokers. Until more is known, smokers should avoid all beta-carotene supplements.

In a double-blind trial, supplementation with beta-carotene in the amount of 50 mg every other day for 18 years appeared to slow the loss of cognitive function in middle-aged healthy males. Short-term supplementation (one year) was not beneficial.⁶⁹

Caution: Synthetic beta-carotene has been linked to increased risk of lung cancer in smokers. Until more is known, smokers should avoid all beta-carotene supplements.

Although the incidence of B-complex deficiencies is known to be high in alcoholics, the incidence of other vitamin deficiencies remains less clear.⁷⁰ 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,⁷¹ potential problems accompany the use of either vitamin A or beta-carotene in correcting the deficiency induced by alcoholism.⁷² 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.⁷³ Some doctors recommend 1 to 3 grams per day of vitamin C.

Caution: Synthetic beta-carotene has been linked to increased risk of lung cancer in smokers. Until more is known, smokers should avoid all beta-carotene supplements.

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.^{74 , 75}

Some,⁷⁶ but not all,⁷⁷ studies have reported that people eating more foods rich in beta-carotene had a lower the risk of developing cataracts. Supplementation with synthetic beta-carotene has not been found to reduce the risk of cataract formation.⁷⁸ It remains unclear whether natural beta-carotene from food or supplements would protect the eye or whether beta-carotene in food is merely a marker for other protective factors in fruits and vegetables high in beta-carotene.

Caution: Synthetic beta-carotene has been linked to increased risk of lung cancer in smokers. Until more is known, smokers should avoid all beta-carotene supplements.

The antioxidant beta-carotene may reduce free radical damage in the stomach,⁷⁹ and eating foods high in beta-carotene has been linked to a decreased risk of developing chronic atrophic gastritis.⁸⁰ Moreover, people with active gastritis have been reported to have low levels of beta-carotene in their stomachs.⁸¹ In a preliminary trial, giving 30,000 IU of beta-carotene per day to people with ulcers or gastritis led to the disappearance of gastric erosions.⁸² In another study, combining vitamin C and beta-carotene also led to improvement in most people with chronic atrophic gastritis.⁸³

Caution: Synthetic beta-carotene has been linked to increased risk of lung cancer in smokers. Until more is known, smokers should avoid all beta-carotene supplements.

Blood levels of the antioxidant nutrients vitamins A, C, and E, and beta-carotene are reported to be lower in people with a history of heart attack, compared with healthy individuals.⁸⁴ The number of free radical molecules is also higher, suggesting a need for antioxidants. Streptokinase, a drug therapy commonly used immediately following a heart attack, enhances the need for antioxidants.⁸⁵

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.⁸⁶ After 28 days, the infarct size of those receiving antioxidants was significantly smaller than the infarct size of the placebo group.

Low levels of beta-carotene in fatty tissue have been linked to an increased incidence of heart attacks, particularly among smokers.⁸⁷ One population study found that eating a diet high in beta-carotene is associated with a lower rate of nonfatal heart attacks.⁸⁸ However, beta-carotene supplementation may not offer the same protection provided by foods that contain beta-carotene. Most,^{89 , 90} but not all, trials⁹¹ have found that supplemental beta-carotene is not associated with a reduced risk of heart attacks.

Caution: Synthetic beta-carotene has been linked to increased risk of lung cancer in smokers. Until more is known, smokers should avoid all beta-carotene supplements.

Beta-carotene levels have been found to be low in HIV-positive people, even in those without symptoms.⁹² However, trials on the effect of beta-carotene supplements have produced conflicting results. In one double-blind trial, supplementing with 300,000 IU per day of beta-carotene significantly increased the number of CD4+ cells in people with HIV infection.⁹³ In a second double-blind study, supplementing with natural mixed carotenoids equivalent to 120,000 IU of beta-carotene per day significantly prolonged survival times in adults with advanced AIDS who were also receiving conventional therapy and a multivitamin.⁹⁴ In another trial, however, 300,000 IU per day of beta-carotene had no effect on CD4+ cell counts or various other measures of immune function in HIV-infected people.⁹⁵

Caution: Synthetic beta-carotene has been linked to increased risk of lung cancer in smokers. Until more is known, smokers should avoid all beta-carotene supplements.

Sunlight triggers oxidative damage in the eye, which in turn can cause macular degeneration.⁹⁶ Animals given antioxidants—which protect against oxidative damage—have a lower risk of this vision problem.⁹⁷ People with high blood levels of antioxidants also have a lower risk.⁹⁸ 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).⁹⁹ People who eat fruits and vegetables high in beta-carotene, another antioxidant, are also at low risk.¹⁰⁰ 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.¹⁰¹ 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.¹⁰²

Caution: Synthetic beta-carotene has been linked to increased risk of lung cancer in smokers. Until more is known, smokers should avoid all beta-carotene supplements.

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.^{103, 104, 105, 106, 107, 108} Low blood levels of vitamin E in particular have been associated with higher numbers of diseased cells in children¹⁰⁹ and with greater frequency of symptoms in adults.¹¹⁰ 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.¹¹¹