PLASMA-CONCENTRATIONS OF MICRONUTRIENTS DURING A 9-MONTH CLINICAL-TRIAL OF BETA-CAROTENE IN WOMEN WITH PRECURSOR CERVICAL-CANCER LESIONS

The effects of oral supplementation of a 30-mg dose of beta-carotene o n the plasma levels of carotenoids, tocopherols, and retinol were stud ied sequentially in 69 patients participating in a nine-month randomiz ed placebo controlled trial conducted to examine efficacy of beta-caro tene to induce regression of cervical intraepithelial neoplasia. At ea ch visit (baseline and 1.5, 3, 6, 9, 10.5, and 15 mo), blood samples w ere collected and the levels of six micronutrients were determined by high-performance liquid chromatography. No limitations or changes were introduced in each participant's dietary habits. Cervicovaginal lavag e samples were also obtained at the same visit and assayed for the pre sence of human papillomavirus DNA by Southern blot hybridization and p olymerase chain reaction. In the supplemented group, mean plasma beta- carotene levels were significantly higher (p = 0.0001) than baseline a nd remained markedly elevated for 15 months. In the longitudinal analy sis of the placebo group, there were no variations among individual me an plasma levels of beta-carotene, alpha-carotene, lycopene, retinol, gamma-tocopherol, or alpha-tocopherol, suggesting absence of seasonal or dietary, changes. In the placebo group, cigarette smoking and stero id contraceptive use were significantly associated with low levels of plasma beta-carotene (p = 0.05 and p = 0.012, respectively). However, in contrast in the beta-carotene-supplemented group, steroid contracep tive rue had no influence on the plasma beta-carotene levels. An addit ional noteworthy finding was that beta-carotene supplementation did no t reverse the depletion effect in smokers. There was no association be tween the plasma levels of these six micronutrients in women with cerv ical intraepithelial neoplasia and persistent human papillomavirus inf ection status in the placebo or the supplemented groups. Functional se quential nutrient interactions with each other or with other essential micronutrients and possible longterm toxicity need to be addressed in clinical trials.