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Questions and Answers About Beta Carotene Chemoprevention Trials 

1. What is a chemoprevention trial?

A chemoprevention trial is a type of clinical trial, which is a research study conducted 

with people. In a cancer chemoprevention trial, natural or laboratory-made substances 

are tested to see if they prevent cancer. The people who participate in such a study are 

healthy or are at risk of developing cancer, or in some studies, people who have been 

diagnosed with cancer and are at risk of developing a second cancer. 

2. What is the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Trial?

The Alpha-Tocopherol, Beta-Carotene Cancer Prevention Trial or ATBC Trial was 

conducted by the National Cancer Institute (NCI) in collaboration with the National 

Public Health Institute of Finland. The purpose of the study was to see if certain vitamin 

supplements would prevent lung and other cancers in a group of 29,133 male smokers in 

Finland. The 50- to 69-year-old participants took a pill containing either 

50 milligrams (mg) alpha tocopherol (a form of vitamin E), 20 mg beta carotene 

(a precursor of vitamin A), both, or a placebo (inactive pill that looks like the vitamin) 

daily for five to eight years. 

3. What is the Beta Carotene and Retinol Efficacy Trial or CARET?

The Beta Carotene and Retinol Efficacy Trial or CARET is a large NCI-funded 

chemoprevention trial that is being conducted in six areas in the United States. The 

purpose of the study was to see if the combination of beta carotene and vitamin A (a 

retinol) supplements would prevent lung and other cancers in men and women ages 50 to 

69 who are smokers or former smokers, and men ages 45 to 69 who have been exposed to 

asbestos. The 18,314 participants stopped taking the supplements prior to the completion 

of the trial.

4. What is the Physicians’ Health Study?

The Physicians’ Health Study is a chemoprevention trial with 22,071 U.S. male 

physicians, of which only 11 percent smoked. The purpose of the study was to test 

whether a beta carotene supplement reduced the risk of cancer and heart disease as well 

as whether low-dose aspirin reduced the risk of heart disease. The aspirin component 
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was stopped in early 1988 due to a 44 percent reduction in risk of first heart attack among 

those taking aspirin. The beta carotene component ended December 31, 1995, after more 

than 12 years of study. 

5. What did these trials show?

In the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Trial, 18 percent more lung 

cancers were diagnosed and 8 percent more overall deaths occurred in study participants 

taking beta carotene. In CARET, after an average of four years of receiving supplements, 

28 percent more lung cancers were diagnosed and 17 percent more deaths occurred in 

participants taking beta carotene and vitamin A than in those taking placebos. Neither of 

these studies showed a benefit from taking supplements. 

Because the interim results of CARET were similar to the ATBC study, the intervention 

was stopped 21 months early. Both of these studies involved people who were 

specifically invited to participate because of their high risk for developing lung cancer. 

The Physician’s Health Study was completed at the end of 1995 and showed no benefit or 

harm in people taking beta carotene supplements for more than 12 years. 

6. Why did CARET stop early?

The study itself was not stopped, but the participants were told to stop taking the beta 

carotene and vitamin A or placebos. The Safety and Endpoints Monitoring Committee 

for CARET and an ad hoc committee assembled by NCI saw that the interim results 

clearly showed no benefit from the supplements and also showed there was a possibility 

that they were harming participants. CARET investigators made the decision to stop the 

intervention, but they will follow the study group for five more years to determine the 

long-term effects of the intervention. 

The intervention was halted on January 11, 1996, by the CARET investigators. 

Letters were mailed to participants by January 13 and a public announcement made on 

January 18. 

7. Who were the participants in CARET?

The study had two groups: 14,254 current and former smokers with a long history of 

smoking, and 4,060 asbestos-exposed individuals. 

The smokers and former smokers included 14,254 men and women ages 50 to 69 who 

were current smokers or were smokers who had quit within six years of enrolling in the 

study. Smokers and former smokers must have had a smoking history of at least 20 pack 

years (one pack per day for 20 years or two packs for 10 years, etc.). These participants 

were 56 percent male (7,965) and 44 percent female (6,289), and had an average of 50 

pack years of smoking. About 34 percent were former smokers when they joined the 

study. All participants were counseled to quit smoking at their visits to the study centers. 
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The asbestos-exposed participants were 4,060 men ages 45 to 69 who had been exposed 

to asbestos while at work. These participants had to have extensive occupational asbestos 

exposure beginning at least 15 years prior to enrollment, determined by either a chest 

X-ray that showed asbestos exposure, or employment for more than five years in trades 

that carry a high risk of exposure to asbestos (plumbers and pipe fitters, steam fitters, 

shipyard boilermakers, non-shipyard boilermakers, shipyard electricians, shipscalers, 

insulators, plasterboard workers, or sheet metal workers). In addition, they had to be 

either current smokers or had to have quit smoking within the last 15 years. 

8. What is beta carotene?

 

Beta carotene, which is found in plants, is a precursor of vitamin A. The body converts 

beta carotene to vitamin A. It occurs mainly in fruits and vegetables that are deep yellow, 

orange, or dark green in color, such as carrots, squash, yams, peaches, apricots, spinach, 

collard or mustard greens, and broccoli. It is an antioxidant, a compound that may 

prevent cancer-causing substances from damaging DNA. Epidemiologic studies have 

linked high intake of foods rich in beta carotene and high serum levels of the 

micronutrient to a reduced risk of cancer, particularly lung cancer. 

9. What is vitamin A?

Vitamin A is a vitamin, a substance found in foods that is necessary for human health. 

Vitamin A is found in liver, various dairy products with fat, such as milk, cheese, butter 

and ice cream, and in fatty fish such as herring, sardines, and tuna. It can also be found 

in the liver oils of shark, cod, and halibut. Vitamin A is known to play a part in cell 

differentiation, a process by which cells “mature.” Differentiation helps prevent 

inappropriate growth, such as the uncontrolled cell growth that is seen in cancer. Many 

studies in animals show that vitamin A and similar compounds decrease the incidence of 

cancer. 

10. Should Americans who smoke avoid taking beta carotene? 

The NCI has never made recommendations as to whether Americans should take 

supplements. The best advice for smokers who want to reduce their risk of lung cancer is 

still the most direct: stop smoking. The results from CARET and the ATBC Trial 

suggest that smokers should avoid taking beta carotene supplements. 

11. Should Americans who don't smoke take beta carotene supplements?

The results of the Physicians’ Health Study showed no benefit or harm to nonsmokers 

who took beta carotene every other day for 12 years. The results from CARET and the 

ATBC Study do not provide information about the effects of beta carotene supplements 

on non-smokers. 
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NCI does not make recommendations as to whether Americans should take supplements. 

For those who wish to reduce their risk of cancer, NCI advises that it is prudent to adopt a 

low-fat diet containing plenty of fruits, vegetables, and grains. 

12. Should Americans stop eating five fruits and vegetables daily (5-A-Day)?

No. 5-A-Day remains a good idea. In both the ATBC Study and CARET, participants 

with the highest levels of beta carotene in their blood, measured before the study began, 

went on to have fewer lung cancers. These results are consistent with the possibility that 

a different compound or compounds in foods that have high levels of beta carotene may 

be responsible for the protective effect of dietary beta carotene seen in epidemiologic 

studies. Because these are studies of pills, not food intake, NCI stresses that the study 

results do not change the results of studies that show that eating a variety of fruits and 

vegetables each day remains a good way to reduce the risk of some cancers. 

13. What other chemoprevention studies are under way with beta carotene?

The NCI has a number of different agents under study, including calcium, fiber, 

tamoxifen, and others. Only one large-scale study including beta carotene (the Women’s 

Health Study) was ongoing when CARET stopped its intervention, and the beta carotene 

portion of that study has been halted. Principal investigators of smaller or shorter-term 

studies including beta carotene were alerted and advised to consider the results of these 

studies in making decisions about the studies they are conducting. 

In the Women's Health Study, sponsored by the National Institutes of Health, 40,000 

apparently healthy women health professionals ages 45 and older were being assigned at 

random to 50 mg beta carotene, 600 IU vitamin E, 100 mg aspirin, and/or placebos every 

other day. The beta carotene portion of this trial was dropped. The trial, which began in 

1992, will show the balance of benefits and risks of these agents on cancer and 

cardiovascular disease. 

# # # 

Sources of National Cancer Institute Information

Cancer Information Service

 Toll-free: 1–800–4–CANCER (1–800–422–6237) 

 TTY (for deaf and hard of hearing callers): 1–800–332–8615 

NCI Online 

Internet

Use http://cancer.gov to reach the NCI’s Web site. 
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LiveHelp 

Cancer Information Specialists offer online assistance through the LiveHelp link on the 

NCI’s Web site. 

This fact sheet was reviewed on 6/27/97