Beta-carotene as a dietary supplement

• DEFINITION: Natural substance promoted as a dietary supplement for specific health benefits.
• PRINCIPAL PROPOSED USE: Nutritional vitamin A
• OTHER PROPOSED USES: Alcoholism, cataract prevention, depression, enhancing mental function, epilepsy, exercise-induced asthma, female infertility, headaches, heartburn, human immunodeficiency virus support, macular degeneration prevention, male infertility, osteoarthritis, Parkinson’s disease, photosensitivity, psoriasis, rheumatoid arthritis, schizophrenia, sunburn prevention
• PROBABLY INEFFECTIVE USES: Cancer prevention, diabetes, heart disease prevention

Overview

All the significant positive evidence for beta-carotene applies to beta-carotene from food sources, not supplements. Beta-carotene belongs to a family of natural chemicals known as carotenoids. Widely found in plants, carotenoids (along with another group of chemicals, bioflavonoids) give color to fruits, vegetables, and other plants.

Beta-carotene is a particularly important carotenoid from a nutritional standpoint because the body easily transforms it into vitamin A. While vitamin A supplements themselves can be toxic when taken to excess, it is believed (although not proven) that the body will make only as much vitamin A out of beta-carotene as it needs. Assuming this is true, this built-in safety feature makes beta-carotene the best way for a person to get vitamin A.

Beta-carotene is also often recommended because it is an antioxidant, like vitamin E and vitamin C. In observational studies, a high intake of carotenoids from food has been associated with reduced risk of various illnesses (including heart disease and cancer). However, observational studies are inherently unreliable. In intervention trials, beta-carotene supplements have not been found to offer any benefits. When taken in high doses for a long period of time, beta-carotene supplements might slightly increase the risk of heart disease and some forms of cancer.

Requirements and Sources

Although beta-carotene is not a required nutrient, vitamin A is essential for health, and beta-carotene is converted into vitamin A in the body. The exact conversion factor varies with the circumstances. In general, two micrograms (mcg) of beta-carotene in supplement form is thought to be equivalent to one mcg of vitamin A. Plant sterols, used to treat high cholesterol, may impair absorption of beta-carotene.

Dark green and orange-yellow vegetables are good sources of beta-carotene. These include carrots, sweet potatoes, squash, spinach, romaine lettuce, broccoli, cantaloupe, apricots, squash, and green peppers.

Therapeutic Dosages

It has not been determined whether it is advisable to take doses of beta-carotene supplements much higher than the recommended allowance for nutritional purposes, which is about 1.5 to 1.8 milligrams (mg) daily in adults. Rather than taking doses higher than this, people should probably increase their intake of fresh fruits and vegetables.

Therapeutic Uses

There are no well-documented therapeutic uses of beta-carotene beyond supplying nutritional doses of vitamin A. Numerous observational studies have found that a high intake of foods rich in carotenoids is associated with a lower incidence of lung cancer, other forms of cancer, and heart disease. However, beta-carotene supplements have not been found to help prevent these conditions. When all major beta-carotene studies are statistically combined through a process called meta-analysis, some evidence suggests that long-term usage of beta-carotene at high doses might increase the overall death rate for unclear reasons.

Similarly, observational evidence links high dietary intake of carotenoids to a lower incidence or slowed progression of cataracts, macular degeneration, and osteoarthritis, but again, there is no reliable evidence that beta-carotene supplements are helpful for these conditions. In fact, a twelve-year study of more than twenty-two thousand male physicians failed to find that beta-carotene had any effect on the incidence of macular degeneration.

Preliminary evidence raised hopes that beta-carotene supplements might increase or preserve immune function or decrease symptoms among people with human immunodeficiency virus (HIV) infection. However, other studies found no benefit, and some evidence hints that too much beta-carotene might be harmful.

Beta-carotene supplements may be helpful for protecting the skin from sunburn, particularly in people with extreme sensitivity to the sun, but the evidence regarding this potential use is somewhat contradictory. One double-blind trial found that faithful daily use of sunscreen was more effective at preventing sun damage to the skin than oral beta-carotene plus sunscreen used as needed.

One preliminary study found evidence that beta-carotene might be helpful for cystic fibrosis by helping prevent lung infections. Another preliminary study suggests that beta-carotene might help prevent exercise-induced asthma. Weak evidence culled from a large double-blind, placebo-controlled study hints that using beta-carotene over many years might enhance mental function.

Some research indicated beta-carotene supplementation may improve symptoms of the connective tissue disorder called scleroderma, but scientific studies failed to support this theory. Limited research indicates that the mouth sores associated with oral leukoplakia may improve with beta-carotene.

Beta-carotene has been proposed as a treatment for alcoholism, asthma, depression, epilepsy, headaches, heartburn, male infertility, female infertility, Parkinson’s disease, psoriasis, rheumatoid arthritis, and schizophrenia, but there is little to no evidence that it works. There is some evidence that beta-carotene is not effective for cervical dysplasia or intermittent claudication.

Scientific Evidence

Cancer prevention. The story of beta-carotene and cancer prevention is full of apparent contradictions. In the early 1980s, the cumulative results of many studies suggested that people who eat a lot of fruits and vegetables are significantly less likely to get cancer. A close look at the data pointed to carotenoids as the active ingredients in fruits and vegetables. It appeared that a high intake of dietary carotene might significantly reduce the risk of lung, bladder, breast, esophageal, and stomach cancers.

However, observational studies cannot prove cause and effect. It is always possible that people who consume a lot of carotenoids in their diet are different in other ways—they might exercise more or have healthier lifestyles in other regards.

This is not a purely theoretical issue. For example, based primarily on observational studies, hormone replacement therapy was promoted as a heart-protective treatment for postmenopausal women. However, when placebo-controlled studies were performed, hormone replacement therapy was shown to slightly increase the risk of heart disease. One possible explanation for this discrepancy is that the benefits of hormone replacement therapy were because women who used it tended to belong to a higher socioeconomic class than those who did not. (For a variety of reasons, some of which are unknown, higher income is associated with improved health.)

Something similar appears to be the case with beta-carotene. Although persons who consume foods high in beta-carotene appear to obtain some protection from heart disease and cancer, when researchers gave beta-carotene supplements to study participants, there was no protective effect. Most studies enrolled people in high-risk groups, such as smokers, because it is easier to see results when researchers look at people who are more likely to develop cancer.

The anticancer bubble burst for beta-carotene in 1994 when the results of the Alpha-Tocopherol, Beta-Carotene (ATBC) study became available. These results showed that beta-carotene supplements did not prevent lung cancer but increased the risk of getting it by 18 percent. This trial followed 29,133 male smokers in Finland who took supplements of about fifty international units (IU) of vitamin E (alpha-tocopherol), 20 mg of beta-carotene (more than ten times the amount necessary to provide the daily requirement of vitamin A), both, or placebo daily for five to eight years. (In contrast to the results for beta-carotene, vitamin E was found to reduce the risk of cancer, especially prostate cancer.)

In January 1996, researchers monitoring the Beta-Carotene and Retinol Efficacy Trial (CARET) confirmed the prior bad news with more of their own: the beta-carotene group had 46 percent more cases of lung cancer deaths. This study involved smokers, former smokers, and workers exposed to asbestos. Alarmed, the National Cancer Institute ended the $42 million CARET trial twenty-one months before it was planned to end.

At about the same time, the twelve-year Physicians’ Health Study of twenty-two thousand male physicians found that 50 mg of beta-carotene (about twenty-five times the amount necessary to provide the daily requirement of vitamin A) taken every other day had no effect, good or bad, on the risk of cancer or heart disease. In this study, 11 percent of the participants were smokers, and 39 percent were former smokers.

Similarly, another study of beta-carotene supplements failed to find any effect on the risk of cancer in women. Also, in a final indictment of beta-carotene’s safety and effectiveness, researchers who combined the results of twelve placebo-controlled trials investigating the association between antioxidant supplementation and cancer found that beta-carotene use was associated with increased cancer among smokers. However, the story does not end there. In yet another careful analysis of four randomized trials involving 109,394 smokers and former smokers, researchers found that smokers who consumed between 20 and 30 mg of beta-carotene were at a significantly greater risk of developing lung cancer. There was no such risk among former smokers. A similar meta-analysis of eight studies with more than 167,141 individuals reported beta-carotene supplementation was associated with an increased risk of developing lung cancer, particularly in individuals who worked with asbestos and those who smoked. However, the dose and longevity of use had no impact on the risk of lung cancer, indicating the supplement likely does not affect lung cancer risk.

There are several possible explanations for these contradictory findings. As noted above, it is possible that intake of carotenoids as such is unrelated to cancer and that some unrelated factor common to individuals with a high carotene diet is the cause of the benefits seen in observational trials.

Another possibility is that beta-carotene alone is not effective, and the other carotenoids found in fruits and vegetables may be more important for preventing cancer than beta-carotene. One researcher has suggested that taking beta-carotene supplements depletes the body of these other beneficial carotenoids and thereby causes a harmful effect. In support of this theory, a large study found that consumption of fruits and vegetables is generally associated with lower lung cancer risk, but when beta-carotene is taken, this preventive effect disappears.

Heart disease prevention. The situation with beta-carotene and heart disease is rather similar to that of beta-carotene and cancer. Numerous studies suggest that carotenoids as a whole can help prevent heart disease. However, isolated beta-carotene may not help prevent heart disease and could actually increase a person’s risk.

The same double-blind intervention trial involving 29,133 Finnish male smokers (mentioned under the discussion of cancer and beta-carotene) found 11 percent more deaths from heart disease and 15 to 20 percent more strokes in those participants taking beta-carotene supplements.

Similar poor results with beta-carotene were seen in another large, double-blind study of smokers. Beta-carotene supplementation was also found to increase the incidence of angina in smokers.

Osteoarthritis. A high dietary intake of beta-carotene is associated with a significantly slower progression of osteoarthritis, according to a study in which researchers followed 640 individuals over eight to ten years. However, as with heart disease and cancer, it is not known if beta-carotene is responsible for this effect.

HIV support. One small, double-blind study suggested that beta-carotene supplements might raise white blood cell count in people with HIV. However, two subsequent, larger controlled trials found no significant differences between those taking beta-carotene or placebo in white blood cell count, CD4+ count, or other measures of immune function.

Evidence from observational studies suggests that higher intakes of vitamin A or beta-carotene may be helpful; however, caution is in order regarding dosage. Researchers generally linked higher intake of vitamin A or beta-carotene to lower risk of AIDS and lower death rates, with an important exception: people with the highest intake of either nutrient (more than 11,179 IU daily of beta-carotene or more than 20,268 IU daily of vitamin A) did worse than those who took somewhat less.

Macular degeneration and cataracts. Despite promising results from observational studies, intervention trials of beta-carotene for these eye conditions have generally not shown benefit. Beta-carotene proved ineffective for preventing cataracts in one large study, and in another large study, beta-carotene supplements combined with vitamins E and C failed to prevent either macular degeneration or cataracts. On a more positive note, one large study found that beta-carotene supplements helped prevent cataracts in study participants who smoked; nonetheless, no benefit was seen in the group as a whole.

Cervical dysplasia. According to a two-year, double-blind, placebo-controlled study of 141 women with mild cervical dysplasia (a precancerous condition of the cervix), beta-carotene, taken at a dosage of 30 mg daily along with 500 mg of vitamin C, does not help to reverse the dysplasia. Negative results were seen in other trials of beta-carotene as well. All oral antioxidant supplements like beta-carotene have shown mixed results in treating or preventing cervical cancer, dysplasia, and intraepithelial neoplasia (CIN). These inconclusive results generally indicate a lack of support for their use.

Intermittent claudication. A double-blind, placebo-controlled trial of 1,484 individuals with intermittent claudication found no benefit from beta-carotene (20 mg daily), vitamin E (50 mg daily), or a combination.

Diabetes. In a very large study involving more than twenty-nine thousand male smokers, researchers failed to find benefits from beta-carotene (20 mg daily), alpha-tocopherol (50 IU daily), or the two taken together for the prevention of type 2 diabetes over five to eight years.

Safety Issues

At recommended dosages, beta-carotene is believed to be very safe. The only side effects reported from beta-carotene overdose are diarrhea and a yellowish tinge to the hands and feet. These symptoms disappear once a person stops taking beta-carotene or reduces the dose.

However, long-term use of beta-carotene supplements, especially at doses considerably above the amount necessary to supply adequate vitamin A, might slightly increase the risk of heart disease and certain forms of cancer and raise the overall death rate. A large study following 77,126 adults over age fifty suggested that long-term use of beta-carotene, lutein, or retinol supplements may increase lung cancer risk. Long-term supplement use was determined by subjects’ memory of the previous ten years, so the results of this study should be interpreted with some caution. If the risk of long-term supplementation is a concern, one solution would be to eat plenty of fresh fruits and vegetables to obtain beta-carotene. In addition, some evidence suggests that beta-carotene supplements might cause alcoholic liver disease to develop more rapidly in individuals who abuse alcohol.

Bibliography

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