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A Key Nutrient for Healthy Estrogen Metabolism
By Donald Brown, ND

Estrogen refers to a group of chemically similar hormones knows as "estrogenic" hormones. While men have them too, the primary focus is on the role they play in women's health. Estrogenic hormones (estrone, estradiol, and estriol) are uniquely responsible for the growth and development of female sexual characteristics and reproduction. These hormones control the growth of the uterine lining during the first part of the menstrual cycle and regulate other metabolic processes, including bone growth and cholesterol levels.

Over the past couple of decades, focus has been on the role that estrogen may play in some health conditions commonly affecting women. Known as "Estrogen Dominance," this disorder occurs when women have an imbalance in estrogen production and metabolism that can lead to increased risk of premenstrual syndrome, breast tenderness during their menstrual cycle, endometriosis, uterine fibroids, and cervical dysplasia. While managing a healthy balance of estrogen production is critical, perhaps more critical is how a woman actually metabolizes estrogenic hormones. Unhealthy estrogen metabolism not only contributes to the conditions listed above but may also increase risk of breast cancer.

Estrogenic hormones such as estradiol and estrone are metabolized by enzymes to metabolites that are eventually excreted in the urine or bile. Let's take a look at each of these metabolites and view them through the "good," "bad," or "ugly" prism.

2-hydroxyestrodiol/2-hydroxyestrone ("The Good") – This metabolite (2-OHE) has wonderful health-promoting benefits. It acts as a powerful antioxidant, helps regulate fat cell metabolism, and has beneficial effects for the cardiovascular system. It may also reduce risk of breast cancer.


16-hydroxyestrone ("The Bad [sort of]") – While healthy levels of 16-OHE are needed for bone health, higher levels (particularly in relation to 2-OHE levels) may be associated with increased risk of obesity, autoimmune diseases such as lupus, and breast cancer.

4-hydroxyestrodiol/4-hydroxyestrone ("The Ugly") – This one is Mr. Hyde to 2-OHE's Dr. Jekyll. 4-OHE generates powerful free radicals and can cause cell harm by damaging DNA. It is associated with increased autoimmune disease as well as heart disease. It may also increase risk of uterine fibroids and breast and uterine cancer.

Typically, estrogen metabolites are measured as a ratio of 2-OHE/16-OHE with that ratio in favor of 2-OHE.

Diindolylmethane (DIM) is a phytonutrient found primarily in cruciferous vegetables such as cabbage, broccoli, bok choy, Brussels sprouts, kale, and mustard greens. It's not an estrogenic compound and doesn't influence estrogen levels. However, it has been shown to influence estrogen metabolism by shifting metabolism to the 2-OHE pathway.1 We'll look at that in more detail later on. What is important to note is that for many women, diet alone may not deliver the recommended amount of DIM needed to influence estrogen metabolism. The other one is that DIM, when taken in supplement form is often poorly absorbed.

The absorption issue was solved a number of years ago with the creation of a patented microencapsulated form of DIM known as Bio-Response DIM™ Complex. This creation of Michael Zeligs, MD, is the only DIM supplement shown to increase blood levels of DIM and positively influence 2-OHE/16- OHE ratio. In fact, it's the only DIM supplement used in clinical studies.

Bio-Response DIM has been shown to dose-dependently increase the ratio of 2-OHE/16-OHE. In a 30-day study, postmenopausal women with a history of early stage breast cancer taking 108 mg of Bio-Response DIM had a significant rise in 2-OHE levels compared to women taking a placebo, as well as a 47% increase in the 2-OHE/16-OHE ratio.2

The ingredient has also been found to reduce cyclical breast pain and tenderness. In a three-month, placebocontrolled study, women taking 240 mg per day of Bio-Response DIM had significant reduction in both the monthly duration and severity of breast pain.3 This study also shows a favorable increase in the 2-OHE/16-OHE ratio.

Recommended Use and Precautions
For daily use aimed at influencing healthy estrogen metabolism, I recommend that women take 100 mg of Bio-Response DIM. For women suffering from cyclical breast tenderness and PMS, it's probably a good idea to double that dose. Women who are pregnant or lactating should not take DIM. It should also be avoided in individuals with known allergies to cruciferous vegetables.

References
1. Pharmacol Res 2007;55:224-36.
2. Nutr Cancer 2004;50:161-7.
3. JANA 2005;8:5-15.


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