Beta-carotene produces sustained remissions in patients with oral leukoplakia: results of a multicenter prospective trial

Arch Otolaryngol Head Neck Surg. 1999 Dec;125(12):1305-10. doi: 10.1001/archotol.125.12.1305.


Background: Beta-Carotene has been reported to produce regressions in patients with oral leukoplakia, a premalignant lesion. However, previous studies have all been of short duration, with clinical response as the end point.

Objective: To evaluate the duration of response and the need for maintenance therapy in subjects who respond to beta-carotene.

Methods: In this multicenter, double-blind, placebo-controlled trial, subjects were given beta-carotene, 60 mg/d, for 6 months. At 6 months, responders were randomized to continue beta-carotene or placebo therapy for 12 additional months.

Results: Fifty-four subjects were enrolled in the trial, with 50 being evaluable. At 6 months, 26 subjects (52%) had a clinical response. Twenty-three of the 26 responders completed the second, randomized phase. Only 2 (18%) of 11 in the beta-carotene arm and 2 (17%) of 12 in the placebo arm relapsed. Baseline biopsies were performed in all patients, with dysplasia being present in 19 (38%) of the 50 evaluable patients. A second biopsy was obtained at 6 months in 23 subjects who consented to this procedure. There was improvement of at least 1 grade of dysplasia in 9 (39%), with no change in 14 (61%). Nutritional intake was assessed using food frequency questionnaires. There was no change in carotenoid intake during the trial. Responders had a lower intake of dietary fiber, fruits, folate, and vitamin E supplements than did nonresponders. Beta-carotene levels were measured in plasma and oral cavity cells. Marked increases occurred during the 6-month induction. However, baseline levels were not restored in subjects taking placebo for 6 to 9 months after discontinuation of beta-carotene therapy.

Conclusions: The activity of beta-carotene in patients with oral leukoplakia was confirmed. The responses produced were durable for 1 year.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aged
  • Alcohol Drinking
  • Antioxidants / therapeutic use*
  • Diet
  • Double-Blind Method
  • Female
  • Humans
  • Leukoplakia, Oral / drug therapy*
  • Leukoplakia, Oral / pathology
  • Male
  • Middle Aged
  • Remission Induction
  • Smoking
  • Treatment Outcome
  • beta Carotene / blood
  • beta Carotene / therapeutic use*


  • Antioxidants
  • beta Carotene