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

Clin Cancer Res. 2005 Mar 15;11(6):2305-11. doi: 10.1158/1078-0432.CCR-04-2074.


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 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.

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 alpha-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 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.

Conclusions: 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.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Aged
  • Alitretinoin
  • Antineoplastic Agents / therapeutic use*
  • Bronchi* / drug effects
  • Bronchi* / metabolism
  • Bronchi* / pathology
  • Cholesterol / blood
  • Chromatography, High Pressure Liquid
  • Double-Blind Method
  • Female
  • Humans
  • Male
  • Middle Aged
  • Placebos
  • Smoking / blood*
  • Treatment Outcome
  • Tretinoin / therapeutic use*
  • Triglycerides / blood
  • alpha-Tocopherol / blood*


  • Antineoplastic Agents
  • Placebos
  • Triglycerides
  • Alitretinoin
  • Tretinoin
  • Cholesterol
  • alpha-Tocopherol