Nutrient Support for Estrogen Metabolism

Imbalances in estrogen metabolism, whether caused by genetic or environmental factors are associated with numerous health issues including PMS, cancer (breast and uterine), infertility, endometriosis, depression, anxiety, weight gain, and insomnia. Signs and symptoms of excess estrogen can include:

• Bloating

• Mood swings

• PMS

• Headaches

• Low libido

• Irregular menstrual cycle

• Breast swelling and tenderness

• Depression and/or anxiety

• Uterine fibroids

• Fibrocystic breasts

• Weight gain

• Brain fog

• Fatigue

• Insomnia

Many factors can contribute to excess estrogen including hormonal birth control, xenoestrogen exposure (BPA, phthalates, polychlorinated biphenyls (PCBs), hormones in animal products), excessive stress, chronic alcohol consumption, obesity, low fiber intake, and genetics. Over time, excessive estrogen exposure and/or unfavorable estrogen metabolism can lead to DNA damage and increased breast cancer risk.

Strategies to enhance estrogen metabolism can include increasing intake of cruciferous vegetables, probiotics, fiber, and foods rich in B vitamins, magnesium, and other nutrients, which work primarily by inducing favorable alterations in phase I and II metabolism.

Cruciferous Vegetables

Cruciferous vegetables such as broccoli, Brussels sprouts, cabbage, cauliflower, and collard greens are rich in compounds called glucosinolates. When broken down, glucosinolates form other compounds called isothiocyanates, which have been shown to exert cytoprotective and anti-carcinogenic effects (1). Both human and animal studies have demonstrated these effects and suggest that isothiocyanates may protect against breast cancer by influencing both phase I and phase II metabolism (1). For example, a team of researchers treated rats with 7,12-dimethylbenz[a]anthracene (a polycyclic aromatic hydrocarbon used to induce breast cancer) and found that oral administration of sulforaphane (a common isothiocyanate) effectively inhibited mammary carcinogenesis (1). They also reported elevated activity of cytoprotective enzymes NAD(P)H:quinone oxidoreductase (NQO1), an important phase II enzyme, and heme oxygenase-1 (HO-1) in rat mammary epithelium (1).

Indole-3-carbinol (I3C), another important compound found in cruciferous vegetables has been shown to beneficially affect phase I estrogen metabolism by inducing 2-hydroxylation of estrogens, producing less-harmful estrogen metabolites and decreasing levels of other, more harmful estrogen metabolites such as 16α-hydroxyestrone (2). In other words, I3C helps covert estrogens to weaker, less harmful forms. While I3C is rich in foods like Brussels sprouts and broccoli, it is also available as a supplement in the form of DIM (diindolylmethane), which is a breakdown product of I3C.

Fiber and the Microbiome

Diets high in fiber have been associated with a decreased risk of a number of diseases including breast cancer. An analysis of fiber intake and reproductive function using data from the BioCycle study reported that higher fiber intake was associated with lower circulating levels of estradiol, progesterone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH), providing a possible explanation for the decreased risk of breast cancer often observed with high-fiber diets (3). Dietary fiber, especially insoluble fiber such as flax lignans can beneficially alter estrogen levels by binding to unconjugated estrogens in the GI tract and increasing fecal excretion. Soluble fiber, on the other hand, can also regulate circulating estrogen levels by improving gut flora composition. An unfavorable gut flora composition can lead to estrogen reabsorption, allowing it to be re-metabolized, thus maintaining a healthy microbiome can help prevent this reabsorption. Calcium D-glucarate supplementation has also been shown to reduce estrogen reabsorption, thereby allowing for proper estrogen elimination.

Conjugation Reactions

Estrogen detoxification is also dependent upon phase II conjugation reactions such as methylation, sulfation, glucuronidation, and glutathione conjugation, and focusing on nutrients to support these pathways can aid in favorable estrogen metabolism. For example, methionine, magnesium, betaine, vitamin B6, folate, and vitamin B12 support the methylation of estrogen metabolites, resulting in less harmful and more excretable forms of estrogen. A few common foods that promote methylation include eggs, beef, chicken, liver, lentils, almonds, tuna, turkey, salmon, sweet potatoes, spinach, bananas, Brussels sprouts, asparagus, cauliflower, kale, chickpeas, and brown rice (4). Additionally, sulfur-rich foods such as cabbage, Brussels sprouts, chicken, Brazil nuts, eggs, almonds, spinach, and turkey can promote sulfation, which, like methylation, plays an important role in proper estrogen metabolism (4).

While the above information is only a fraction of the puzzle when it comes to estrogen metabolism, focusing on cruciferous vegetables and foods rich in B vitamins, fiber, and various nutrients needed for phase II metabolism is a great start to supporting the proper metabolism and excretion of estrogen.

If you suffer from hormonal imbalance, consider working with a nutritionist or qualified healthcare professional who can provide a detailed protocol and personalized lifestyle recommendations.

For more on estrogen metabolism: Estrogen Metabolism and Breast Cancer

For biochem nerds: Estrogen Metabolism Pathways

References

1. Cornblatt, B. S., Ye, L., Dinkova-Kostova, A. T., Erb, M., Fahey, J. W., Singh, N. K., Chen, M.-S. A., Stierer, T., Garrett-Mayer, E., Argani, P., Davidson, N. E., Talalay, P., Kensler, T. W., & Visvanathan, K. (2007). Preclinical and clinical evaluation of sulforaphane for chemoprevention in the breast. Carcinogenesis, 28(7), 1485–1490.

2. Michnovicz, J. J., Adlercreutz, H., & Bradlow, H. L. (1997). Changes in levels of urinary estrogen metabolites after oral indole-3-carbinol treatment in humans. Journal of the National Cancer Institute, 10, 718.

3. Gaskins, A. J., Mumford, S. L., Zhang, C., Wactawski-Wende, J., Hovey, K. M., Whitcomb, B. W., Howards, P. P., Perkins, N. J., Yeung, E., Schisterman, E. F., & BioCycle Study Group (2009). Effect of daily fiber intake on reproductive function: the BioCycle Study. The American Journal of Clinical Nutrition, 90(4), 1061–1069.

4. Hodges, R. E., & Minich, D. M. (2015). Modulation of metabolic detoxification pathways using foods and food-derived components: a scientific review with clinical application. Journal of Nutrition and Metabolism.