The group of CYP450 enzymes plays crucial roles in drug metabolism and the synthesis of cholesterol, steroids, and other lipids. Among these enzymes, the CYP19A1 enzyme encodes aromatase and plays a pivotal role in estrogen biosynthesis by catalyzing the bioconversion of male hormones to estrogens through aromatase activity. High CYP19A1 expression promotes aromatase activity and is significantly associated with poor overall survival in estrogen receptor-positive breast cancer patients (Jenzer & Sadeghi-Reeves, 2020).
Aromatase is a central topic of ER-positive breast cancer because it has been a primary treatment target for this type of cancer. Therefore, aromatase inhibitors have been the “go-to therapy” for postmenopausal breast cancer patients. Plant aromatase inhibitors extracted from the flavonoid group could be applied as adjuvant or stand-alone therapies for long-term breast cancer prevention. I often recommend functional foods and herbal plants to my clients with breast cancer, estrogen dominance, or poor estrogen metabolism. Here is my understanding of the mechanisms of plant flavonoids as aromatase inhibitors. (Jenzer & Sadeghi-Reeves, 2020):
First, flavonoids compete for the oxygen provided by the heme moiety of aromatase in the aromatase-catalyzed conversion of androgens to estrogens. Therefore, flavonoids may slow the aromatase activity, thus inhibiting estrogen synthesis.
Second, flavonoids may be associated with histone deacetylation. There are three main mechanisms that lead to epigenetic modification of our genomes: methylation, histone modification, and miRNAs. Among the many types of histone modifications, the best-known mechanism for the alteration of histone tails is the process of acetylation. Acetylation occurs when an acetyl group is added to a histone tail, changing how tightly the histone tail is bound to the DNA. As a result, it essentially loosens the connections, making it easier for transcription factors to have access to bind the DNA at that location, thereby turning genes on and increasing the activity of the associated genes. On the other hand, histone tails can also be deacetylated by removing the acetyl group. This causes the histone tails to bind to the DNA tightly again, thereby decreasing gene activity. This may explain why plant flavonoids’ ability to inhibit acetylation can switch genes off, therefore initiating the regulation of repressing cancer genes.
Flavonoids are the most potent natural aromatase inhibitors with anti-estrogenic effects (El-Kersh et al., 2021). In situations with increased aromatase activity associated with the CYP19A1 genetic variant, consuming high flavonoid-containing foods and compounds, such as citrus peel, organic soybeans, green tea, quercetin, and cruciferous vegetables, can be a practical therapeutic approach in slowing the conversion process of androgen to estrogen, resulting in reduced synthesis of estrogen, and thereby lowering the risk of breast cancer (Fatima et al., 2021).
Jenny Noland, MS, CNS, CNGS, CKNS, LDN, MBA
Functional Nutritionist in Eugene, Oregon
Board-Certified Nutrition Specialist
Board-Certified Nutritional Genomics Specialist
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Personalized Nutrition Therapy for Metabolic Dysfunction and Cancer Care
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El-Kersh, D. M., Ezzat, S. M., Salama, M. M., Mahrous, E. A., Attia, Y. M., Ahmed, M. S., & Elmazar, M. M. (2021). Anti-estrogenic and anti-aromatase activities of citrus peels major compounds in breast cancer. Scientific Reports 2021 11:1, 11(1), 1–14. https://doi.org/10.1038/s41598-021-86599-z
Fatima, N., Baqri, S. S. R., Bhattacharya, A., Koney, N. K. K., Husain, K., Abbas, A., & Ansari, R. A. (2021). Role of Flavonoids as Epigenetic Modulators in Cancer Prevention and Therapy. Frontiers in Genetics, 12, 2266. https://doi.org/10.3389/FGENE.2021.758733/BIBTEX
Jenzer, H., & Sadeghi-Reeves, L. (2020). Nutrigenomics-Associated Impacts of Nutrients on Genes and Enzymes With Special Consideration of Aromatase. Frontiers in Nutrition, 7, 37. https://doi.org/10.3389/FNUT.2020.00037