9-cis-Retinoic Acid Treatment Increases Serum Concentrations of α-Tocopherol in Former Smokers

Abstract

Low serum concentrations of antioxidants may be associated with an increased risk of cancer. Based on the accumulated evidence, we hypothesized that retinoids would elevate serum alpha-tocopherol. This study was designed to determine whether 9-cis-retinoic acid (9-cis-RA), the most common chemopreventive agent, could alter serum alpha-tocopherol in former smokers. Because hyperlipidemia is a known side effect of retinoids, we also evaluated the association between serum alpha-tocopherol and lipids in the same population. Subjects who had stopped smoking at least 12 months before the study were randomly assigned to receive oral 9-cis-RA or placebo daily for 3 months. Clinical information and blood samples were obtained monthly; serum alpha-tocopherol concentrations were measured by high-performance liquid chromatography and lipid levels by enzymatic assays before treatment and every month during the treatment. Of the 149 subjects in the study, 113 completed 3 months of treatment and provided samples for evaluation of serum alpha-tocopherol. Serum alpha-tocopherol levels in the 9-cis-RA group (n = 52) were higher after treatment (r = 0.445, P < 0.01) than before. The incidences of grade > or =2 hypertriglyceridemia and hypercholesterolemia were higher in the 9-cis-RA group than in the placebo group (P = 0.0005 and P = 0.01, respectively), but there were no serious complications related to hyperlipidemia. Treatment of former smokers with 9-cis-RA significantly increased their serum alpha-tocopherol levels, and this could be a benefit. In addition, serum alpha-tocopherol could serve as a biomarker for 9-cis-RA treatment.