3,3′-Diindolylmethane Modulates Estrogen Metabolism in Patients with Thyroid Proliferative Disease: A Pilot Study

Abstract

Background: The incidence of thyroid cancer is four to five times higher in women than in men, suggesting a role for estrogen (E 2 ) in the pathogenesis of thyroid proliferative disease (TPD) that comprises cancer and goiter. The objective of this study was to investigate the antiestrogenic activity of 3,3 0 -diindolylmethane (DIM), a bioactive compound derived from cruciferous vegetables, in patients with TPD. Methods: In this limited phase I clinical trial study, patients found to have TPD were administered 300 mg of DIM per day for 14 days. Patients subsequently underwent a total or partial thyroidectomy, and tissue, urine, and serum samples were collected. Pre-and post-DIM serum and urine samples were analyzed for DIM levels as well as estrogen metabolites. DIM levels were also determined in thyroid tissue samples. Results: DIM was detectable in thyroid tissue, serum, and urine of patients after 14 days of supplementation. Urine analyses revealed that DIM modulated estrogen metabolism in patients with TPD. There was an increase in the ratio of 2-hydroxyestrones (C-2) to 16a-hydroxyestrone (C-16), consistent with antiestrogenic activity that results in more of C-2 product compared with C-16. Conclusion: Our data suggest that DIM enhances estrogen metabolism in TPD patients and can potentially serve as an antiestrogenic dietary supplement to help reduce the risk of developing TPD. The fact that DIM is detected in thyroid tissue implicates that it can manifest its antiestrogenic activity in situ to modulate TPD.

The effect of oral 3,3′-diindolylmethane supplementation on the 2:16α-OHE ratio in BRCA1 mutation carriers

“…Larger studies with well-timed sample collection are needed to confirm these findings. There is epidemiologic evidence, albeit not entirely conclusive, suggesting that a higher 2:16a-OHE ratio is associated with a reduced risk of breast cancer in both preand post-menopausal women [27,[33][34][35][36]. Results from three distinct groups evaluating a cancer-predictive role of estrogen metabolite levels among high-risk women have been inconclusive, possibly as a result of differing definitions of high-risk [10,25,37].…”

“…It is of interest to see if the effect of DIM would have been more pronounced with a greater sample size and timed sample collection. In addition, perhaps the dose and duration of DIM (i.e., 300 mg/day for 4-6 weeks) were not sufficient; however, this is unlikely given that this was based on previously published studies demonstrating a significant effect on estrogen metabolism [27,[33][34][35] as well as BRCA1 mRNA expression [31]. Furthermore, there were a few adverse effects reported and this dose was generally welltolerated by our participants which is consistent with previously published studies using Rx Balance BioResponse DIM [27,33].…”

Chemopreventive properties of 3,3′-diindolylmethane in breast cancer: evidence from experimental and human studies

“…78 The bioavailability and plasma levels of DIM following oral doses of BR-DIM have been published previously in placebocontrolled human studies. [78][79][80] Thus far, most clinical research on DIM is based on the consumption of cruciferous vegetables, but current clinical trials are examining the effects of DIM, specifically the BR-DIM formulation, on breast cancer risk.…”

Phase Ib placebo-controlled, tissue biomarker trial of diindolylmethane (BR-DIMNG) in patients with prostate cancer who are undergoing prostatectomy

“…For instance, Rajoria et al (2011) studied patients with thyroid proliferative disease in whom detectable levels of DIM were identified in thyroid tissue following administration of 300 mg DIM/day for 14 days. This is the minimum duration of DIM administration utilized in our study design, and yet we did not identify detectable DIM levels in prostate tissue in the majority of our patients.…”