Friday, July 17, 2009

Natural Compounds for Estrogen Metabolism Support

Recall from the last post that we looked at how the liver plays a vital role in metabolizing estrogens. I left you with the thought that those important pathways which so often go awry can be modified with specific compounds from nature. “Although the estrogen receptor is required for a cell to respond to an estrogenic stimulus, the nature and extent of that response are determined by the proteins, pathways, and processes with which the receptor interacts.” Connections and Regulation of the Human Estrogen Receptor, Dean McDonnell and John D. Norris

This means that factors other than the presence or absence of estrogen influence the response of the estrogen receptor and the cell. These factors are what make up the chemical environment in and around the cell, and can be impacted by nutritional factors. The way estrogen receptors create chemical messengers that relate to other receptors is called “cross-talk,” and it would make sense that this “cross-talk” is influenced by nutrient status.

We’ll look at a few of the natural compounds in this post that positively affect estrogen metabolism.

Indole-3-CarbinolIt has been demonstrated convincingly that Indole-3-Carbinol (I3C) from cruciferous vegetables increases the healthful 2-OHE estrogen pathway and decreases the harmful 4-/16-OHE estrogens.

“Indole-3-carbinol (I3C), a compound occuring naturally in cruciferous vegetables, exhibits a potent antitumor activity via its regulation of estrogen activity and metabolism... These results further suggest that antitumor activities of I3C are associated not only with its regulation of estrogen activity and metabolism, but also its modulation of ER transcription activity.” J Nutri 130:2927-2931(2000)

“It has been shown that it induces CyP450 1A1, increasing 2-hydroxylation of estrogens, leading to the protective 2-OHE1, and also decreases CyP 1B1 sharply, inhibiting 4-hydroxylation of estradiol, thereby decreasing the formation of the carcinogenic 4-OHE1. …it has also been shown to be effective against HPV-mediated tumors in human patients.” Ann Ny Acad Sci889:204-213(1999)

“These results indicate that anti-invasion and antimigration activities of I3C occur via estrogen-independent and estrogen-dependent pathways. …current finding is the first demonstration that I3C can activate the function of invasion suppressor molecules associated with the suppression of invasion and migration in breast cancer cells. Thus, clinical application of I3C may contribute to the potential benefit for suppression of breast cancer invasion and metastasis.” J Mol Med78:155-165(2000)

Supplementation with I3C has shown promise in the literature:

  • Supplementation with concentrate (400 mg/d) promotes 2-Hydroxylation and improves 2-OH:16-OH ratio. Michnovicz JJ, et al, J Natl Cancer Inst, 89(10):718-20, 1997.
  • May also reduce 4-Hydroxylation. Bradlow HL, et al, Ann NY Acad Sci, 889:204-13, 1999.
  • 300-400mg/d promises to be a chemopreventive agent. Wong et al., J Cell Biochem Suppl 1997;28-29:111

I3C has also shown to positively influence gene expression! Recall that estrogen metabolism occurs in specific liver pathways. The CYP450 1A1 pathway forms 2-OH, and the single nucleotide polymorphism (SNP) Msp 1 impairs 1A1 function. I3C, however, improves estrogen metabolism even in the presence of the polymorphism! Bartsch et al., Carcinogenesis 1999;20(12):2209, Taioli et al., Cancer Detection and Prev1999;23(3):232

The CYP450 1B1 pathway, however, forms the 16-OH hormone, and the SNP V432L increases the function of the 1B1 pathway. I3C inhibits 1B1 even in the presence of the SNP! Bradlow et al., Ann NY Acad Sci 1999;889:204

We’ll look at more natural compounds for healthy estrogen metabolism in the posts following.


Related Formula: Meta I3C