Clinical Abstracts
With Comments by Adriane Fugh-Berman, MD
Broccoli and CIN
May 2001; Volume 3; 40
Source: Bell MC, et al. Placebo-controlled trial of indole-3-carbinol in the treatment of CIN. Gynecol Oncol 2000;78:123-129.
Design: Randomized, placebo-controlled, trial. Patients and colposcopists were blinded to treatment.
Subjects: Thirty women with cervical intraepithelial neoplasia (CIN I-III) by cervical biopsy. Sixteen women (5 placebo, 11 treated) had CIN II, while 11 (5 placebo and 6 treated) had CIN III. Seven of 10 placebo patients, seven of eight patients receiving 200 mg/d indole-3-carbinol, and eight of nine patients receiving 400 mg/d indole-3-carbinol tested positive for human papilloma virus (HPV).
Treatment: Placebo, 200 mg/d indole-3-carbinol, or 400 mg/d indole-3-carbinol for 12 weeks.
Outcome Measures: Cervical biopsy. Colposcopic examination was performed and urinary 2-hydroxy- estrone/16-alpha-hydroxyestrone ratios obtained at baseline and monthly for three months.
Results: None of the 10 patients in the placebo group had complete regression of CIN (although three of five initially CIN III improved to CIN I). Four of eight patients (three initially CIN II, one initially CIN III) who received 200 mg/d indole-3-carbinol experienced complete regression. Four of nine patients (three initially CIN II, one initially CIN III) in the group receiving 400 mg/d had complete regression. The protective effect calculated as relative risk was 0.50 in the 200 mg group (95% CI 0.25-0.99, P = 0.023) and 0.55 in the 400 mg group (95% CI, 0.31-0.99, P = 0.032). The presence of HPV did not correlate with treatment response. Urinary 2-hydroxy- estrone/16-alpha-hydroxyestrone ratios showed marked individual variability.
Comments: This trial was quite small but is intriguing. Confidence intervals were fairly wide, a function of the small number of subjects in this trial. Results should be confirmed in a larger trial, as CIN II may regress spontaneously (CIN III usually does not). It is interesting that in this series three of five placebo-treated CIN III patients improved to CIN I. Found in vegetables of the cruciferous family (including broccoli, cauliflower, cabbage, and Brussels sprouts), indole-3-carbinol alters estrogen metabolism by up-regulating 2-hydroxylation. In the liver, estradiol is degraded to 2-hydroxyestrone or 16-alpha-hydroxyestrone. 2-hydroxyestrone appears to have anti-estrogenic and anti-proliferative effects, while 16-alpha-hydroxyestrone has proliferative effects in some breast cancer cell lines. A dose of 400 mg indole-3-carbinol is equivalent to about one-third of a head of raw cabbage (400 g) per day. There are no known health risks for incorporating broccoli, cabbage, or other cruciferous vegetables into one’s diet.
May 2001; Volume 3; 40
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