Deficiencies of iron, vitamin B12, and folic acid are the most common nutritional causes of anemia.¹ Although rare, severe deficiencies of several other vitamins and minerals, including vitamin A,^{2 , 3} vitamin B2,⁴ vitamin B6,^{5 , 6} vitamin C,⁷ and copper,^{8 , 9} can also cause anemia by various mechanisms. Rare genetic disorders can cause anemias that may improve with large amounts of supplements such as vitamin B1.^{10 , 11}

Preliminary research shows that supplemental vitamin A improves the likelihood that the measles vaccine will provide protection.¹² Vitamin A has, since the 1920s, been the subject of much research into the prevention and treatment of childhood exanthems, particularly measles.¹³ This nutrient has a critical role in proper immune function, and there is evidence that supplementation with vitamin A reduces the incidence and severity of, and deaths from, childhood measles.^{14 , 15} The World Health Organization (WHO) has therefore recommended that children with signs of deficiency receive supplementation with vitamin A. The recommended amounts are 100,000 IU for children younger than one year and 200,000 IU for children older than one year, immediately upon diagnosis, and repeated once the next day and once in one to four weeks.¹⁶ A controlled trial of African children given vitamin A supplementation according to the WHO’s recommendations found that severity of measles and its long-term consequences were reduced by 82% on day eight, 61% in week six, and 85% six months after the onset.¹⁷

Another controlled trial found that giving approximately 200,000 IU of vitamin A once during measles illness was not adequate to provide any benefit in African children whose vitamin A status was unknown.¹⁸ In a controlled prevention study, Indian children treated with 2,500 mcg (8,333 IU) of vitamin A weekly had fewer measles complications and less than half of the rate of death as compared with children receiving placebo;¹⁹ but in another study, Indian children receiving 200,000 IU of vitamin A every six months did not have a different rate of total infectious illness nor rate of death as compared with children receiving placebo.²⁰

An analysis of 20 controlled trials concluded that vitamin A supplementation reduced deaths from measles respiratory infection by 70%.²¹ While vitamin A deficiency is widespread in developing countries, it has also been reported in the United States and has been linked with more severe cases of measles.²² The American Academy of Pediatrics has recommended supplementation with vitamin A for children between the ages of six months and two years who are hospitalized with measles and its complications. The recommended amount is a single administration of 100,000 IU for children aged 6 to 12 months and 200,000 IU for children older than 1 year, followed by a second administration 24 hours later and a third after four weeks in children who are likely to have vitamin A deficiency.²³

One trial showed that low levels of vitamin A are more prevalent in children with measles than in similar children without measles, with levels rising back to normal several days after the onset of the infection. This observation led the authors of the study to conclude that vitamin A deficiency is a consequence of infection with the measles virus and to recommend supplementation with vitamin A during measles infection even when prior deficiency is not suspected.²⁴ Vitamin A stores have also been shown to be depleted during chicken pox infection,²⁵ and some preliminary data supports its use in treatment of chicken pox. In a controlled trial, in which children without vitamin A deficiency were given either 200,000 IU of vitamin A or placebo one time during chicken pox, the children given vitamin A had shorter duration of illness and fewer severe complications. The researchers then treated the patients’ siblings with vitamin A before chicken pox became evident, and they had an even shorter length of illness.²⁶

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.²⁷ 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,²⁸ and taking pancreatic enzymes helps prevent B12 deficiencies.²⁹

Nutrients useful for maintaining healthy immune function are also applicable for preventing infections. Vitamin A plays an important role in immune system function and helps mucous membranes, including those in the lungs, resist invasion by microorganisms.³⁰ However, most research shows that while vitamin A supplementation helps people prevent or treat infections in developing countries where deficiencies are common,³¹ little to no positive effect, and even slight adverse effects, have resulted from giving vitamin A supplements to people in countries where most people consume adequate amounts of vitamin A.^{32 , 33 , 34 , 35 , 36 , 37 , 38} Moreover, vitamin A supplementation during infections appears beneficial only in certain diseases. An analysis of trials revealed that vitamin A reduces mortality from measles and diarrhea, but not from pneumonia, in children living in developing countries.³⁹ A double-blind trial for vitamin A supplementation in Tanzanian children with pneumonia confirmed its lack of effectiveness for this condition.⁴⁰ In general, parents in the developed world should not give vitamin A supplements to children unless there is a reason to believe vitamin A deficiency is likely, such as the presence of a condition causing malabsorption (e.g., celiac disease). However, the American Academy of Pediatrics recommends that all children with measles should be given high-dose vitamin A for several days.

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%).⁴¹ 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.⁴² 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.⁴³ These results have also been observed in smaller trials.^{44, 45}

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.⁴⁶ 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.⁴⁷ One group of researchers reported that vitamin A (28,500 IU per day) was more effective than beta-carotene in treating people with leukoplakia.⁴⁸ 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.⁴⁹ Women who are or who could become pregnant should not take 100,000 IU of vitamin A per week without medical supervision.

Measles appears to increase the body’s need for vitamin A.^{50 , 51} Studies in developing countries have shown that measles infection is more frequent and severe in people with low vitamin A blood levels,^{52 , 53} and preliminary research suggests this may also be true in the developed world.^{54 , 55 , 56} Repeatedly in controlled trials, preventive supplementation with vitamin A, at oral doses of up to 400,000 IU per day, reduced the risk of death in children with measles living in developing countries.^{57 , 58 , 59} Whether vitamin A supplementation would help people with measles in developed countries, where deficiency is uncommon, is less clear.⁶⁰ However, the American Academy of Pediatrics recommends that all children with measles be given a short course of high-dose vitamin A. Two controlled studies of urban South African⁶¹ and Japanese⁶² children hospitalized with severe measles showed that supplementation with 100,000 to 400,000 IU of vitamin A resulted in faster recoveries, fewer complications, and fewer pneumonia-related deaths. An older study in England found one ounce per day of cod liver oil (containing about 40,000 IU of vitamin A, plus vitamin D and omega-3 fatty acids) reduced measles-related deaths in children hospitalized with severe cases of the disease.⁶³ Such large doses of vitamin A should only be taken under a doctor’s supervision.

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.

In one study, six people with diet-treated celiac disease had abnormal dark-adaptation tests (indicative of “night blindness”), even though some were taking a multivitamin that contained vitamin A. Some of these people showed an improvement in dark adaptation after receiving larger amounts of vitamin A, either orally or by injection.⁶⁴ People with celiac disease should discuss the possibility of vitamin A deficiency with a healthcare practitioner before taking vitamin A 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.⁶⁵ 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.⁶⁶

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.⁶⁷ 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.⁶⁸ One population study found that eating a diet high in beta-carotene is associated with a lower rate of nonfatal heart attacks.⁶⁹ However, beta-carotene supplementation may not offer the same protection provided by foods that contain beta-carotene. Most,^{70 , 71} but not all, trials⁷² have found that supplemental beta-carotene is not associated with a reduced risk of heart attacks.

Vitamin A plays an important role in immune system function and helps mucous membranes, including those in the lungs, resist invasion by microorganisms.⁷³ However, most research shows that while vitamin A supplementation helps people prevent or treat infections in developing countries where deficiencies are common,⁷⁴ little to no positive effect, and even slight adverse effects, have resulted from giving vitamin A supplements to people in countries where most people consume adequate amounts of vitamin A.^{75, 76, 77, 78, 79, 80, 81} Moreover, vitamin A supplementation during infections appears beneficial only in certain diseases. An analysis of trials revealed that vitamin A reduces mortality from measles and diarrhea, but not from pneumonia, in children living in developing countries.⁸² A double-blind trial of vitamin A supplementation in Tanzanian children with pneumonia confirmed its lack of effectiveness for this condition.⁸³ In general, parents in the developed world should not give vitamin A supplements to children unless there is a reason to believe vitamin A deficiency is likely, such as the presence of a condition causing malabsorption (e.g., celiac disease). However, the American Academy of Pediatrics recommends that all children with measles be given short-term supplementation with high-dose vitamin A in cases of hospitalization, malnutrition, and other special circumstances determined by a doctor.⁸⁴

A combination of antioxidants vitamin A, vitamin C, and vitamin E significantly improved immune cell number and activity compared with placebo in a group of hospitalized elderly people.⁸⁵ Daily intake of a 1,000 mg vitamin C plus 200 IU vitamin E for four months improved several measures of immune function in a preliminary study.⁸⁶ To what extent immune-boosting combinations of antioxidants actually reduce the risk of infection remains unknown.

In a study of women with menorrhagia who took 25,000 IU of vitamin A twice per day for 15 days, 93% showed significant improvement and 58% had a complete normalization of menstrual blood loss.⁸⁷ However, women who are or could become pregnant should not supplement with more than 10,000 IU (3,000 mcg) per day of vitamin A.

Vitamin A is needed to heal the linings (called mucous membranes) of the stomach and intestines. In one controlled trial, vitamin A supplementation facilitated healing in a small group of people with stomach ulcer.⁸⁸ The amount used in that study (150,000 IU per day) can be toxic and may also cause birth defects. Such a high dose should not be taken by a pregnant woman, by a woman who could become pregnant, or by anyone else without careful supervision from a doctor. Objective evidence of ulcer healing from taking vitamin A has been reported by the same research group.⁸⁹ The effect of lower amounts of vitamin A has not been studied in people with peptic ulcer.

Vitamin A has a critical role in proper immune function, and evidence suggests that supplementing with it reduces the incidence and severity of, and deaths from, childhood measles.^{90 , 91} The World Health Organization (WHO) has therefore recommended that children with signs of deficiency receive supplementation with vitamin A. The recommended amounts are 100,000 IU for children younger than one year and 200,000 IU for children older than one year, immediately upon diagnosis, and repeated once the next day and once in one to four weeks.⁹² A controlled trial of African children given vitamin A supplementation according to the WHO’s recommendations found that severity of measles and its long-term consequences were reduced by 82% on day eight, 61% in week six, and 85% six months after the onset.⁹³

Another controlled trial found that giving approximately 200,000 IU of vitamin A once during measles illness was not adequate to provide any benefit in African children whose vitamin A status was unknown.⁹⁴ In a controlled prevention study, Indian children treated with 2,500 mcg (8,333 IU) of vitamin A weekly had fewer measles complications and less than half of the rate of death as compared with children receiving placebo;⁹⁵ but in another study, Indian children receiving 200,000 IU of vitamin A every six months did not have a different rate of total infectious illness nor rate of death as compared with children receiving placebo.⁹⁶

An analysis of 20 controlled trials concluded that vitamin A supplementation reduced deaths from measles respiratory infection by 70%.⁹⁷ While vitamin A deficiency is widespread in developing countries, it has also been reported in the United States and has been linked with more severe cases of measles.⁹⁸ The American Academy of Pediatrics has recommended supplementation with vitamin A for children between the ages of six months and two years who are hospitalized with measles and its complications. The recommended amount is a single administration of 100,000 IU for children aged 6 to 12 months and 200,000 IU for children older than 1 year, followed by a second administration 24 hours later and a third after four weeks in children who are likely to have vitamin A deficiency.⁹⁹

One trial showed that low levels of vitamin A are more prevalent in children with measles than in similar children without measles, with levels rising back to normal several days after the onset of the infection. This observation led the authors of the study to conclude that vitamin A deficiency is a consequence of infection with the measles virus and to recommend supplementation with vitamin A during measles infection even when prior deficiency is not suspected.¹⁰⁰ Vitamin A stores have also been shown to be depleted during chicken pox infection,¹⁰¹ and some preliminary data supports its use in treatment of chicken pox. In a controlled trial, in which children without vitamin A deficiency were given either 200,000 IU of vitamin A or placebo one time during chicken pox, the children given vitamin A had shorter duration of illness and fewer severe complications. The researchers then treated the patients’ siblings with vitamin A before chicken pox became evident, and they had an even shorter length of illness.¹⁰²

Vitamin A plays a central role in wound healing,¹⁰³ but the effect of supplemental vitamin A in people who have suffered a minor injury and are not vitamin A-deficient remains unclear. Vitamin A supplements have been shown to improve healing in animal studies,¹⁰⁴ and may be especially useful in a topical ointment for skin injuries in people taking corticosteroid medications.¹⁰⁵ Although there are no studies in humans, some doctors recommend 25,000 IU of vitamin A per day, beginning two weeks prior to surgery and continuing for four weeks after surgery.

Women with a low intake of vitamin A have an increased risk of cervical dysplasia.¹⁰⁶ However, there is little research on the use of vitamin A as a treatment for cervical dysplasia.

Large quantities of vitamin A—such as 300,000 IU per day for females and 400,000–500,000 IU per day for males—have been used successfully to treat severe acne.¹⁰⁷ However, unlike the long-lasting benefits of the synthetic prescription version of vitamin A (isotretinoin as Accutane), the acne typically returns several months after natural vitamin A is discontinued. In addition, the large amounts of vitamin A needed to control acne can be toxic and should be used only under careful medical supervision.

Although the incidence of B-complex deficiencies is known to be high in alcoholics, the incidence of other vitamin deficiencies remains less clear.¹⁰⁸ 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,¹⁰⁹ potential problems accompany the use of either vitamin A or beta-carotene in correcting the deficiency induced by alcoholism.¹¹⁰ 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.¹¹¹ Some doctors recommend 1 to 3 grams per day of vitamin C.

Vitamin A deficiency has been reported in people with chronic conjunctivitis.¹¹² It is unknown whether vitamin A supplementation can prevent conjunctivitis or help people who already have the condition.

Vitamin A is needed for the growth and repair of cells that line both the small and large intestine.¹¹³ At least two case reports describe people with Crohn’s disease who have responded to vitamin A supplementation.^{114, 115} However, in one trial, vitamin A supplementation failed to maintain remission of the disease.¹¹⁶ Therefore, although some doctors recommend 50,000 IU per day for adults with Crohn’s disease, this approach remains unproven. An amount this high should never be taken without qualified guidance, nor should it be given to a woman who is or could become pregnant.

It is known vitamin A supplements support immune function and prevent infections. This is true, however, only under some circumstances. Vitamin A supplementation can also increase the risk of infections, according to the findings of a double-blind trial.¹¹⁷ In a study of African children between six months and five years old, a 44% reduction in the risk of severe diarrhea was seen in those children given four 100,000–200,000 IU supplements of vitamin A (the lower amount for those less than a year old) during an eight-month period. On further investigation, the researchers discovered that the reduction in diarrhea occurred only in children who were very malnourished. For children who were not starving, vitamin A supplementation actually increased the risk of diarrhea compared with the placebo group. The vitamin A-supplemented children also had a 67% increased risk of coughing and rapid breathing, and signs of further lung infection, although this problem did not appear in children infected with the AIDS virus. These findings should be of concern to American parents, whose children are not usually infected with HIV or severely malnourished. Such relatively healthy children fared poorly in the African trial in terms of both the risk of diarrhea and the risk of continued lung problems. Vitamin A provided no benefit to the well-nourished kids. Therefore, it makes sense not to give vitamin A supplements to children unless there is a special reason to do so, such as the presence of a condition causing malabsorption (e.g., celiac disease).

Zinc and vitamin A, nutrients that aid in healing, are commonly used to help people with peptic ulcers. For example, the ulcers of people taking 50 mg of zinc three times per day healed three times faster than those of people who took placebo.¹¹⁸ Since some types of gastritis can progress to peptic ulcer, it is possible that taking it may be useful. Nevertheless, the research does not yet show that zinc specifically helps people with gastritis. The amount of zinc used in this study is very high compared with what most people take (15–40 mg per day). Even at these lower levels, it is necessary to take 1–3 mg of copper per day to avoid a zinc-induced copper deficiency.

Blood levels of vitamin A are lower in people with goiter than in similar people without goiter.^{119 , 120} The same relationship has been found for vitamin E and goiter.¹²¹ 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.¹²² No studies have been done to investigate this benefit in humans.

Vitamin A deficiency appears to be very common in people with HIV infection. Low blood levels of vitamin A are associated with greater disease severity¹²³ and increased transmission of the virus from a pregnant mother to her infant.¹²⁴ However, in preliminary ¹²⁵ and double-blind^{126, 127} trials, supplementation with vitamin A failed to reduce the overall mother-to-child transmission of HIV. HIV-positive women who took 5,000 IU per day of vitamin A (as retinyl palmitate) and 50,000 IU per day of beta-carotene during the third trimester (13 weeks) of pregnancy, plus an additional single amount of 200,000 IU of vitamin A at delivery, had the same rate of transmission of HIV to their infants as those who did not take the supplement. However, lower rates of illness have been observed in the children of HIV-positive mothers when the children were supplemented with 50,000–200,000 IU of vitamin A every two to three months.¹²⁸

Little research has explored whether vitamin A supplements are helpful at halting disease progression. HIV-positive children given two consecutive oral supplements of vitamin A (200,000 IU in a gelcap) in the two days following influenza vaccinations had a modest but significant decrease in viral load.¹²⁹ In one trial, giving people an extremely high (300,000 IU) amount of vitamin A one time only did not improve short-term measures of immunity in women with HIV.¹³⁰

People with hypothyroidism have been shown to have an impaired ability to convert beta-carotene to vitamin A.^{131 , 132} For this reason, some doctors suggest taking supplemental vitamin A (approximately 5,000–10,000 IU per day) if they are not consuming adequate amounts in their diet.

Vitamin A plays an important role in wound healing,¹³³ and one animal study suggests that vitamin A deficiency might contribute to poor recovery after surgery.¹³⁴ Vitamin A may be particularly beneficial to post-surgical patients who are using corticosteroid medications. These medications typically slow wound healing, and a number of animal studies have found that both topical and oral vitamin A reverse this effect; however, vitamin A does not change healing time in animals not given corticosteroids.^{135, 136, 137} Similar results have been reported for topical vitamin A in some human cases, and these researchers suggest a topical preparation containing 200,000 IU of vitamin A per ounce for improved surgical wound healing in patients using corticosteroids after surgery.¹³⁸ Topical vitamin A may also reduce scarring in patients taking corticosteroids.¹³⁹

Very high amounts of vitamin A—100,000 IU per day or more—have reduced symptoms of PMS,^{140 , 141} but such an amount can cause serious side effects with long-term use. Women who are or who could become pregnant should not supplement with more than 10,000 IU (3,000 mcg) per day of vitamin A. Other people should not take more than 25,000 IU per day without the supervision of their doctor. As yet, no trials have explored the effects of these safer amounts of vitamin A in women suffering from PMS.

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.^{142, 143, 144, 145, 146, 147} Low blood levels of vitamin E in particular have been associated with higher numbers of diseased cells in children¹⁴⁸ and with greater frequency of symptoms in adults.¹⁴⁹ 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.¹⁵⁰

Vitamin A deficiency increases the risk of many infections. Although much of the promising research with vitamin A supplements and infections has focused on measles,¹⁵⁴ vitamin A is also thought to be helpful in other infections. Some doctors recommend that people with urinary tract infections take vitamin A. A typical amount recommended to correct a deficiency is 10,000 to 25,000 IU per day.

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.¹⁵⁵ 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.^{156, 157, 158}

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.^{159 , 160 , 161 , 162 , 163}

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.¹⁶⁴ 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.¹⁶⁵ 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.¹⁶⁶

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.¹⁶⁷ 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.¹⁶⁸ Similarly, in a controlled trial, a combination of selenium, copper, and vitamins was found to be ineffective.¹⁶⁹

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.^{170 , 171}

Antioxidants may protect the skin from sunburn due to free radical–producing ultraviolet rays.¹⁷² 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.^{173, 174, 175}

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.^{176 , 177 , 178 , 179 , 180}

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.¹⁸¹ 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.¹⁸² 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.¹⁸³

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.¹⁸⁴ 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.¹⁸⁵ Similarly, in a controlled trial, a combination of selenium, copper, and vitamins was found to be ineffective.¹⁸⁶

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.^{187 , 188}