What is a natural aromatase inhibitor?
A natural aromatase inhibitor is any naturally occurring chemical compound that can block the activity of the aromatase enzyme, which is responsible for the aromatization reaction that converts androgens into estrogens. Although there are no known chemicals produced by the body that focus exclusively on aromatase inhibition, several multifunctional substances can have this effect.
One of them is melatonin, commonly known as “the sleep hormone” due to its crucial role in sleep regulation. Melatonin can potentially block aromatase activity in glioma cells, which are cancerous cells originating in the brain and spinal cord. Reportedly, it can suppress aromatase activity in C6 cells and downregulate the expression of this enzyme by reducing the steady-state levels of aromatase mRNA.1
Another natural aromatase suppressor is calcitriol, the active form of vitamin D produced by the body when exposed to sunlight, particularly ultraviolet B (UVB) rays. However, its mechanism of action mainly involves inhibiting aromatase expression rather than its activity.2
Androgen hormones, converted into estrogens through the aromatase-catalyzed reaction, can also potentially inhibit this enzyme. Androgens can bind to the active site of aromatase, occupying the space where the conversion to estrogen normally occurs. This steroid-protein interaction is the mechanism behind steroid-based synthetic aromatase inhibitor drugs, such as the FDA-approved exemestane.
Additionally, androgens may inhibit aromatase gene expression by reducing the activity of steroidogenic factor 1 (SF-1), which is crucial for this process. Elevated levels of androgens can also reduce the stimulation of aromatase in the gonads, the primary reproductive organs, by suppressing the release of gonadotropin-releasing hormone (GnRH) from the hypothalamus and luteinizing hormone (LH) from the pituitary gland.
Aromatase inhibitor foods and nutrients
Some plant-based foods and mushrooms contain substances that may inhibit aromatase, although their effectiveness can vary in different contexts and may require further scientific research.
For example, lignans, found in whole grains, sesame seeds, and flaxseeds, are phytoestrogens that are converted by intestinal bacteria into enterolignans. These metabolites can bind to estrogen receptors, exerting weak estrogenic effects, which may help reduce some symptoms associated with low estrogen levels. However, they can also inhibit the aromatase enzyme and compete with more potent endogenous estrogen, reducing its ability to bind to estrogen receptors in hormone-sensitive (HR+) breast cancer cells.
Flavonoids are another group of nutrients found in natural foods that can have varying inhibitory effects on aromatase. Known for their antioxidant properties, compounds like chrysin, apigenin, and 7-hydroxyflavone can potentially compete with natural substrates and inhibit aromatase activity.3
Indole-3-carbinol (I3C), found in broccoli, Brussels sprouts, and cabbage, is converted into diindolylmethane (DIM) in the stomach. DIM is believed to promote the formation of less active estrogens and downregulate aromatase gene expression.
Grape seed extract (GSE) has gained particular attention for its potential as a natural aromatase inhibitor. Procyanidin dimers and resveratrol, polyphenolic compounds found in GSE, can reportedly interfere with aromatase function and suppress its mRNA expression. Resveratrol, also found in some berries and red wine, can potentially interact with estrogen receptors in HR+ cancer cells.4
An aromatase inhibitor supplement
The potential inhibitory effects on aromatase imposed by certain nutrients present in natural foods have led to the development of aromatase inhibitor supplements and estrogen blockers.
Some manufacturers market nutritional products, such as flaxseed oil, which are already included in some diets, specifically as aromatase inhibitors. Others focus on pure compounds or extracts from plants and mushrooms. Resveratrol, I3C, DIM, and chrysin are particularly popular supplements of this type.
The use of these supplements should align with the recommendations of a healthcare provider who is familiar with the patient’s overall health, treatment plan, and any hormonal imbalances. While emerging research suggests potential benefits of natural aromatase inhibitors, more clinical trials involving humans are needed to better understand how these natural inhibitors function and interact with synthetic drugs in the body.5 Additionally, food supplements are not sufficiently regulated in some countries, which raises concerns about marketing products with inaccurate ingredient information or unfounded health claims.
References:
- Gonzalez A et al. “Inhibitory effects of pharmacological doses of melatonin on aromatase activity and expression in rat glioma cells.” British Journal of Cancer. 2007. 97:755-760.
https://www.nature.com/articles/6603935.pdf - Villaggio B et al. “Vitamin D modulates aromatase expression in human macrophages and downregulates proinflammatory cytokine production via ERK/MAPK signaling.” Annals of the Rheumatic Diseases. 2012.
https://ard.bmj.com/content/annrheumdis/71/Suppl_1/A75.2.full.pdf - Sanderson TJ et al. “Induction and Inhibition of Aromatase (CYP19) Activity by Natural and Synthetic Flavonoid Compounds in H295R Human Adrenocortical Carcinoma Cells.” Toxicological Sciences. 2004. 82(1): 70-79.
https://academic.oup.com/toxsci/article-abstract/82/1/70/1651726?redirectedFrom=fulltext - Kijima I et al. “Grape Seed Extract Is an Aromatase Inhibitor and a Suppressor of Aromatase Expression.” Cancer Research. 2006. 66(11): 5960-5967.
https://aacrjournals.org/cancerres/article/66/11/5960/525648/Grape-Seed-Extract-Is-an-Aromatase-Inhibitor-and-a - Khan SI et al. “Potential utility of natural products as regulators of breast cancer-associated aromatase promoters.” Reproductive Biology and Endocrinology. 2011. 9(91).
https://rbej.biomedcentral.com/articles/10.1186/1477-7827-9-91