Findings from observational studies in the 1980s led researchers to wonder whether supplements of beta carotene and vitamin A (also called retinol) might reduce the incidence of cancer, particularly lung cancer. The body converts beta carotene, which is found in plants, to vitamin A, and vitamin A is known to play a part in preventing the uncontrolled growth of cells. The phase III Beta Carotene and Retinol Efficacy Trial (CARET) was designed to test whether supplements of these nutrients could prevent lung cancer in people at high risk for the disease.

CARET was a clinical trial because it was both experimental and prospective. It was experimental in that it was studying the effects of an intervention – in this case, vitamin supplements. And it was prospective in that researchers tracked the health of participants forward in time, after they enrolled in the trial.

The multicenter trial was both controlled and randomized. Between 1983 and 1994, 18,314 men and women who were smokers, former smokers, or workers exposed to asbestos were randomly assigned to one of two groups: the control group received dummy pills (placebos) each day; the intervention group received daily supplements of beta carotene and vitamin A.

The trial was also double-blinded, meaning neither participants nor their doctors knew who was taking the supplements and who was taking the dummy pills.

In January 1996, researchers reported that a preliminary analysis found 28 percent more lung cancer cases and 17 percent more lung cancer deaths in the intervention group than in the placebo group. In other words, there was “clear evidence of no benefit and substantial evidence of possible harm” with regard to the supplements.

Though researchers had planned to continue the experiment for another two years, the trial had progressed far enough and had enrolled enough participants for these early findings to be statistically significant. Researchers immediately told participants to stop taking both the supplements and the placebos, but kept following the participants' health for the next several years. The initial findings were subsequently published in the November 6, 1996, issue of the Journal of the National Cancer Institute. (See the journal abstract of the study.)

The CARET results confirmed the findings of an earlier phase III, randomized, controlled clinical trial, the Alpha-Tocopherol and Beta Carotene (ATBC) trial, published in 1994 (follow-up data were published in 2003; see the journal abstract). The ATBC trial, conducted in Finland, involved more than 29,000 male smokers. Participants taking beta carotene supplements experienced 16 percent more cases of lung cancer than those taking either a vitamin A supplement or a placebo.

On the strength of the ATBC and CARET findings, current medical consensus is that taking beta carotene supplements does not help to prevent lung cancer, and may in fact be harmful.

Glossary Terms

A group of minerals that take the form of tiny fibers. Asbestos has been used as insulation against heat and fire in buildings. Loose asbestos fibers breathed into the lungs can cause several serious diseases, including lung cancer and malignant mesothelioma (cancer found in the lining of the lungs, chest, or abdomen). Asbestos that is swallowed may cause cancer of the gastrointestinal tract.

A substance found in yellow and orange fruits and vegetables and in dark green, leafy vegetables. The body can make vitamin A from beta carotene. Beta carotene is being studied in the prevention of some types of cancer. It is a type of antioxidant.

In a clinical trial, the group that does not receive the new treatment being studied. This group is compared to the group that receives the new treatment, to see if the new treatment works.

A clinical study that includes a comparison (control) group. The comparison group receives a placebo, another treatment, or no treatment at all.

A clinical trial in which the medical staff, the patient, and the people who analyze the results do not know the specific type of treatment the patient receives until after the clinical trial is over.

In clinical trials, refers to a drug (including a new drug, dose, combination, or route of administration) or procedure that has undergone basic laboratory testing and received approval from the U.S. Food and Drug Administration (FDA) to be tested in human subjects. A drug or procedure may be approved by the FDA for use in one disease or condition, but be considered experimental in other diseases or conditions. Also called investigational.

A clinical trial that is carried out at more than one medical institution.

A type of study in which individuals are observed or certain outcomes are measured. No attempt is made to affect the outcome (for example, no treatment is given).

A study to compare the results of people taking a new treatment with the results of people taking the standard treatment (for example, which group has better survival rates or fewer side effects). In most cases, studies move into phase III only after a treatment seems to work in phases I and II. Phase III trials may include hundreds of people.

An inactive substance or treatment that looks the same as, and is given the same way as, an active drug or treatment being tested. The effects of the active drug or treatment are compared to the effects of the placebo.

In medicine, a study or clinical trial in which participants are identified and then followed forward in time.

A study in which the participants are assigned by chance to separate groups that compare different treatments; neither the researchers nor the participants can choose which group. Using chance to assign people to groups means that the groups will be similar and that the treatments they receive can be compared objectively. At the time of the trial, it is not known which treatment is best. It is the patient's choice to be in a randomized trial.

Describes a mathematical measure of difference between groups. The difference is said to be statistically significant if it is greater than what might be expected to happen by chance alone. Also called significant.

A nutrient that the body needs in small amounts to function and stay healthy. Vitamin A helps in vision, bone growth, reproduction, growth of epithelium (cells that line the internal and external surfaces of the body), and fighting infections. It is fat-soluble (can dissolve in fats and oils). Vitamin A is found in liver, egg yolks, and whole milk dairy products from animals and in fish oils. It can also be made in the body from a substance found in some fruits and vegetables, such as cantaloupes, carrots, spinach, and sweet potatoes. Vitamin A is being studied in the prevention and treatment of some types of cancer. Also called retinol.