9-cis-retinoic acid treatment increases serum concentrations of α-tocopherol in former smokers

Purpose: 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 α-tocopherol. This study was designed to determine whether 9-cis-retinoic acid (9-cis-RA), the most common chemopreventive agent, could alter serum α-tocopherol in former smokers. Because hyperlipidemia is a known side effect of retinoids, we also evaluated the association between serum α-tocopherol and lipids in the same population. Experimental Design: 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 α-tocopherol concentrations were measured by high-performance liquid chromatography and lipid levels by enzymatic assays before treatment and every month during the treatment Results: Of the 149 subjects in the study, 113 completed 3 months of treatment and provided samples for evaluation of serum α-tocopherol. Serum α-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 ≥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. Conclusions: Treatment of former smokers with 9-cis-RA significantly increased their serum α-tocopherol levels, and this could be a benefit. In addition, serum α-tocopherol could serve as a biomarker for 9-cis-RA treatment.