Estrogen Detoxification

Estrogen, a sex hormone present in both men and women, but occurs in higher concentrations in women. The body tightly regulates its levels, treating it akin to a toxin during the detoxification and elimination processes (4). Elevated estrogen levels have been linked to breast and uterine cancer in women, underscoring the importance of supporting efficient estrogen detoxification pathways (Aiyer et al, 2010). During Phase 1 detoxification, 17B-Etrodiol is transformed into 4-hydroxy estradiol, a process mediated by the cytochrome P450 family of enzymes, specifically CYP 1A1, CYP1B1, catechol-O-methyltransferase (COMT), UDP-glucuronosyltransferase (UGT), and glutathione S-transferase (GST), all of which play pivotal roles. Notably, both CYP1B1 and 4-OH estradiol are elevated in breast cancer cells (2).

To support impaired estrogen detoxification and rebalance 4-OH, specific dietary and supplemental compounds can be beneficial. Berries, particularly blueberries and black raspberries, are rich in anthocyanins and ellagic acid, which have demonstrated detoxication-supporting and anti-cancer properties by influencing the CYP450 pathway and upregulating proapoptotic mechanisms (5). Other fruits high in ellagic acid, such as pomegranates, grapes, and strawberries, are also recommended for individuals dealing with impaired estrogen metabolism in a Functional Medicine detoxification diet. An intriguing mouse study conducted by Aiyer (2008) revealed significant reductions in breast tumor volume after administering ellagic acid for 2 weeks—75% reduction with ellagic acid (p=0.005), 69% with black raspberry (p=0.005), and 40% with blueberry. This reduction may be attributed to ellagic acid's ability to decrease the levels of enzymes producing harmful estradiol metabolites.

Cruciferous vegetables are another excellent addition to the Functional Medicine detox diet. They actively support estrogen metabolism by rebalancing CY1A1 and CYP1B1 (6). Indole-3-carbinol (I3C) appears to be the key compound responsible for this effect, as it has been shown to suppress tumorigenesis at estrogen-responsive sites through mediation of the CYP450 enzyme pathway, detoxifying estrogen (3).

References:

1. Aiyer, H. S., & Gupta, R. C. (2010). Berries and ellagic acid prevent estrogen-induced mammary tumorigenesis by modulating enzymes of estrogen metabolism. Cancer Prevention Research (Philadelphia, Pa.), 3(6), 727–737. https://doi-org.uws.idm.oclc.org/10.1158/1940-6207.CAPR-09-0260 https://uws.idm.oclc.org/login?url=https://search.ebscohost.com/login.aspx?direct=true&db=mdc&AN=20501861&site=eds-live&scope=sitehttps://aacrjournals.org/cancerpreventionresearch/article/3/6/727/6620/Berries-and-Ellagic-Acid-Prevent-Estrogen-Induced

2. Aiyer, H. S., Srinivasan, C., & Gupta, R. C. (2008). Dietary berries and ellagic acid diminish estrogen-mediated mammary tumorigenesis in ACI rats. Nutrition and Cancer, 60(2), 227–234. https://doi-org.uws.idm.oclc.org/10.1080/01635580701624712https://uws.idm.oclc.org/login?url=https://search.ebscohost.com/login.aspx?direct=true&db=mdc&AN=18444155&site=eds-live&scope=site

3. Horn, T. L., Reichert, M. A., Bliss, R. L., & Malejka-Giganti, D. (2002). Modulations of P450 mRNA in liver and mammary gland and P450 activities and metabolism of estrogen in liver by treatment of rats with indole-3-carbinol. Biochemical Pharmacology, 64(3), 393–404. https://doi-org.uws.idm.oclc.org/10.1016/S0006-2952(02)01190-5. https://uws.idm.oclc.org/login?url=https://search.ebscohost.com/login.aspx?direct=true&db=edselp&AN=S0006295202011905&site=eds-live&scope=site

4. Liehr J. G. (2000). Is estradiol a genotoxic mutagenic carcinogen?. Endocrine reviews, 21(1), 40–54. https://doi.org/10.1210/edrv.21.1.0386 https://pubmed.ncbi.nlm.nih.gov/10696569/

5. Munagala, R., Aqil, F., Vadhanam, M. V., & Gupta, R. C. (2013). MicroRNA ‘signature’ during estrogen-mediated mammary carcinogenesis and its reversal by ellagic acid intervention. Cancer Letters, 339(2), 175–184. https://doi-org.uws.idm.oclc.org/10.1016/j.canlet.2013.06.012 https://uws.idm.oclc.org/login?url=https://search.ebscohost.com/login.aspx?direct=true&db=edselp&AN=S030438351300462X&site=eds-live&scope=site

6. Walters, D. G., Young, P. J., Agus, C., Knize, M. G., Boobis, A. R., Gooderham, N. J., & Lake, B. G. (2004). Cruciferous vegetable consumption alters the metabolism of the dietary carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) in humans. Carcinogenesis, 25(9), 1659–1669. https://doi-org.uws.idm.oclc.org/10.1093/carcin/bgh164 https://uws.idm.oclc.org/login?url=https://search.ebscohost.com/login.aspx?direct=true&db=mdc&AN=15073045&site=eds-live&scope=site