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Induction of estradiol metabolism by dietary indole-3-carbinol in humans
1Rockefeller University, New York, NY.
Abstract:
Dietary indoles in cruciferous vegetables induce cytochrome P450 enzymes and have prevented tumors in various animal models. Because estradiol metabolism is also cytochrome P450 mediated and linked to breast cancer risk, indoles may similarly reduce estrogen-responsive tumors in humans. We examined several indoles in female Sprague-Dawley rats for induction of hepatic estradiol 2-hydroxylation. The most potent inducer, indole-3-carbinol, was administered to humans (500 mg daily for 1 wk). It significantly increased the extent (mean +/- SEM) of estradiol 2-hydroxylation from 29.3% +/- 2.1% to 45.6% +/- 2.1% (P less than .001). These results indicate that indole-3-carbinol strongly influences estradiol metabolism in humans and may provide a new chemopreventive approach to estrogen-dependent diseases.
Insights
Dietary indoles, like indole-3-carbinol found in cruciferous vegetables, can alter estradiol metabolism. This suggests a potential new strategy for preventing estrogen-dependent diseases and cancers.
Area of Science:
- Biochemistry
- Oncology
- Nutritional Science
Background:
- Dietary indoles from cruciferous vegetables are known to induce cytochrome P450 enzymes.
- These enzymes play a crucial role in metabolizing estradiol, a hormone linked to breast cancer risk.
- Indoles show potential for preventing tumors in animal models, suggesting a similar effect on estrogen-responsive cancers.
Purpose of the Study:
- To investigate the effect of dietary indoles on hepatic estradiol 2-hydroxylation.
- To determine if indole-3-carbinol can alter estradiol metabolism in humans.
- To explore the potential of indole-3-carbinol as a chemopreventive agent for estrogen-dependent diseases.
Main Methods:
- Several indoles were tested in female Sprague-Dawley rats to assess their ability to induce hepatic estradiol 2-hydroxylation.
- The most potent indole, indole-3-carbinol, was administered to human participants at a dosage of 500 mg daily for one week.
- Estradiol 2-hydroxylation levels were measured before and after indole-3-carbinol administration in humans.
Main Results:
- Indole-3-carbinol was identified as the most potent inducer of hepatic estradiol 2-hydroxylation in rats.
- In human participants, indole-3-carbinol significantly increased estradiol 2-hydroxylation from 29.3% +/- 2.1% to 45.6% +/- 2.1% (P < .001).
- These findings demonstrate a strong influence of indole-3-carbinol on human estradiol metabolism.
Conclusions:
- Indole-3-carbinol significantly enhances estradiol 2-hydroxylation in humans.
- This modulation of estradiol metabolism suggests indole-3-carbinol may offer a novel chemopreventive approach.
- Further research into indole-3-carbinol could lead to new strategies for managing estrogen-dependent diseases and reducing cancer risk.
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