Cruciferous vegetables including broccoli, Brussels sprouts, cauliflower, and kale contain a beneficial phytonutrient known as indole-3-carbinol, which the digestive system naturally breaks down into diindolylmethane (DIM). DIM has become a popular dietary supplement among female patients receiving care from integrative and functional medicine providers. This popularity stems largely from compelling anecdotal evidence of DIM’s ability to support healthier estrogen metabolism and lower total estrogen levels. But how well are these effects of DIM substantiated by scientific research? In reality, there have been few studies offering definitive evidence of the expected changes in the estrogen profile. And the DIM studies that have been published generally look at only a single component of the estrogen profile, not at the entire estrogen profile.

To address this crucial gap in evidence, Precision Analytical recently published the first study providing a detailed analysis of DIM’s effects on the urinary estrogen profile of premenopausal women (Newman & Smeaton, ). This study is unique in that it comprehensively analyzed DIM’s effects on the complete urinary estrogen profile — including parent estrogens, estrogen metabolites, and estrogen metabolite ratios — which was made possible by the dried urinary sampling method used in DUTCH Testing.

Key Findings

In this study, Precision Analytical researchers compared the urinary estrogen profile between two large groups of healthy premenopausal women (a total of 19,294 women), which included women taking DIM or not taking DIM. They found that women taking DIM had significant changes across the urinary estrogen profile compared to women not taking DIM, including:

• Lower levels of each form of estrogen (estradiol, estrone, and estriol)
• Lower levels of total estrogen
• Lower levels of 16-OHE1, an estrogen metabolite that promotes cell proliferation
• Higher levels of 2-hydroxy metabolites (2-OHE1 and 2-OHE2), which are protective estrogen metabolites considered to be less proliferative than the other estrogen metabolites
• Differences in estrogen metabolite ratios, such as an increase in the 2-OHE1/16-OHE1 and 2-OHE1/4-OHE1 ratios

The study was also able to look at urinary estrogen profiles in a smaller subset of premenopausal women before and after initiating DIM treatment. Overall, the key differences there were in the same direction as in the larger group, especially lower estradiol, estrone, and estriol concentrations, as well as lower levels of a proliferative estrogen metabolite (16-OHE1) that may contribute to overall estrogenic burden in the body.

^{Urinary estrogen metabolite before and after values. Shown are values before and after DIM therapy for some of the estrogen metabolites and ratios in the context of the estrogen metabolic pathway.}

One interesting finding worth mentioning relates to a change observed in 4-OHE1, an estrogen metabolite associated with DNA damage and oxidative stress. Women taking DIM showed higher 4-OHE1 levels than women not taking DIM — an effect that may be surprising to some integrative and functional medicine providers who expect DIM to reduce 4-OHE1. However, it should be noted that there was a significant increase in the 2-OHE1/4-OHE1 ratio in women taking DIM compared to those not taking DIM. The 4-OHE1 level is rarely looked at in isolation because its negative impact on long-term health has been studied in relation to 2OHE1, the biologically inert metabolite associated with reduced breast cancer and health risk. The ratio of 2-OHE1 to 4-OHE1 is a better way to assess the potential impact of 4-OHE1, with a higher ratio being associated with lower long-term breast cancer risk. In this study, the significant increase in the 2-OHE1/4-OHE1 ratio in women taking DIM compared to those not taking DIM indicates that, while both the 2-OH pathway and the 4-OH pathway may have increased with DIM, the increase in phase I detox favored the safer 2-OH pathway.

Implications for Clinical Practice

Overall, this study showed that the dried urinary sampling method used in DUTCH Testing effectively captured the key expected changes in the estrogen profiles of women taking DIM — overall lower estrogen concentrations, lower levels of a proliferative estrogen metabolite (16-OHE1), higher levels of protective estrogen metabolites (2-OHE1 and 2-OHE2), and increases in clinically relevant estrogen metabolite ratios (2-OHE1/16-OHE1 and 2-OHE1/4-OHE1). The findings offer a research-based explanation for some of the effects of DIM that providers have long observed in their patients.

In real world clinical practice, this study provides strong support for monitoring the effects of DIM supplementation on urinary estrogen and estrogen metabolites in female patients. Information from urinary estrogen monitoring can enable providers to offer personalized treatment recommendations about any needed adjustments in dietary supplements to ultimately support healthier estrogen metabolism.

Read the full study here.

To learn more about the DUTCH Test and to gain access to more expert clinical education, comprehensive patient reports, and validated and peer-reviewed research, become a DUTCH Provider.