Beta-Carotene: The Controversy Continues

Alternative Medicine Review, Dec, 2000 by Lyn Patrick

The study was conducted for five years. At the conclusion the group taking 50 mcg selenium, 30 mg [Alpha]-tocopherol, and 15 mg [Beta]-carotene, when compared to the other intervention groups and placebo, had a reduction in cancer risk of 13 percent, primarily due to a decrease in the incidence of gastric cancer.

Comparisons of these trials are useful even though they involved different treatment protocols, patient populations, and endpoints (Table 3).

Table 3: Comparisons of Intervention Trials with Beta-Carotene and Other Antioxidants.

Study                PHS[62]                    ATBC[60]

treatment            * Aspirin 325 mg           * [Alpha]-tocopherol
                                                  (50 mg)
                     * [Beta]-carotene 50 mg    * [Beta]-carotene
                       q other day                (20 mg)
                                                * combination
                     * combination              * placebo
                     * placebo

% former plus        50%                        100%
current smokers
at initiation

Plasma [Beta]-       1.2                        3.0
carotene levels
after intervention
(micrograms/ml)

Study                CARET[61]

treatment            (*) retinol (25,000 IU)
                         plus it-carotene
                         (30 mg)
                     (*) placebo

% former plus        80%
current smokers
at initiation

Plasma [Beta]-       2.1
carotene levels
after intervention
(micrograms/ml)

Study                Linxian[63]

treatment            (*) [Beta]-carotene (15 mg)
                     (*) selenium (50 mcg)
                     (*) [Alpha] tocopherol
                     (30 mg)

% former plus        30%
current smokers
at initiation

Plasma [Beta]-       0.86
carotene levels
after intervention
(micrograms/ml)

The Linxian study used the smallest dosage of [Beta]-carotene (15 mg) and resulted in the lowest mean level of plasma [Beta]-carotene (0.86 mcg/mL). The incidence of lung cancer was reduced by 55 percent although, because there were only 31 total deaths from lung cancer in the study, the statistical power of lung cancer incidence was low.[63] The number of patients in this trial who were "ever smokers" (current or former smokers) was 30 percent, compared to 50 percent in the PHS trial, 100 percent in the ATBC trial, and 80 percent in the CARET trial.[60-63]

The ATBC study, providing 20 mg [Beta]-carotene/day, resulted in the highest mean plasma levels of 3.0 mcg/mL, a level 18-times higher than the mean baseline. Higher plasma levels of [Beta]-carotene in this study, however, had no relationship, positive or negative, to lung cancer incidence.[60] In all three intervention studies where the incidence of smoking was highest (ATBC, PHS, CARET), the overall mortality and the incidence of cancer were inversely correlated with the baseline levels of [Beta]-carotene, independent of treatment protocol.[1] The implications of the ATBC and CARET studies -- that [Beta]-carotene acts as a cocarcinogen -- have been criticized because the smokers in the studies had been smoking for many years (36-pack-year history was the average in the ATBC study) prior to study entry. The critical stages of initiation and promotion of tumors, stages that antioxidants have been shown to inhibit,[64] may have already been bypassed at the initiation of the trials.[1]