The effects of oral supplementation of a 30-mg dose of
beta-carotene on the plasma levels of
carotenoids,
tocopherols, and
retinol were studied sequentially in 69 patients participating in a nine-month randomized placebo controlled trial conducted to examine efficacy of
beta-carotene to induce regression of
cervical intraepithelial neoplasia. At each visit (baseline and 1.5, 3, 6, 9, 10.5, and 15 mo), blood samples were 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. Cervico-vaginal lavage samples were also obtained at the same visit and assayed for the presence of human papillomavirus
DNA by Southern blot hybridization and polymerase chain reaction. In the supplemented group, mean plasma
beta-carotene levels were significantly higher (p = 0.0001) than baseline and remained markedly elevated for 15 months. In the longitudinal analysis of the placebo group, there were no variations among individual mean 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
steroid 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 contraceptive use had no influence on the plasma
beta-carotene levels. An additional noteworthy finding was that
beta-carotene supplementation did not reverse the depletion effect in smokers. There was no association between the plasma levels of these six
micronutrients in women with
cervical intraepithelial neoplasia and persistent
human papillomavirus infection status in the placebo or the supplemented groups. Functional sequential nutrient interactions with each other or with other essential
micronutrients and possible long-term toxicity need to be addressed in clinical trials.