Preformed
vitamin A (
all-trans-retinol and its
esters) and
provitamin A (
beta-carotene) are essential dietary nutrients that provide a source of
retinol. Both
retinyl esters and
beta-carotene are metabolized to
retinol. The
retinol-binding proteins on binding
retinol provide a means for solubilizing
retinol for delivery to target tissues and for regulating
retinol plasma concentrations. Oxidation of
retinol provides
retinal, which is essential for vision, and
retinoic acid, a
transcription factor ligand that has important roles in regulating genes involved in cell morphogenesis, differentiation, and proliferation. The observations that
vitamin A can produce cell and tissue changes similar to those found during neoplastic transformation and that
vitamin supplementation can reverse this process indicated a potential role for
vitamin A in
cancer prevention. Thus far, correlative epidemiological studies on
vitamin A use and
cancer prevention have produced mixed results, as this review indicates. Apparently, in populations deficient in
vitamin A (caused by an inadequate diet or tobacco use), supplementation programs appear to be effective in reducing
cancer incidence. In groups already having sufficient dietary or supplemental
vitamin A,
cancer prevention by added
vitamin A may not be particularly effective. The most likely reason for the low efficacy in the latter groups is that feedback mechanisms that increase
retinol storage in the liver limit
retinol plasma levels; whereas, supplementation at higher doses causes toxicity. In addition to serving as a metabolic source of
retinol,
beta-carotene, along with other dietary
carotenoids, function as
antioxidants that can prevent
carcinogenesis by decreasing the levels of the
free-radicals that cause DNA damage.