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Resveratrol is a well-known polyphenol found naturally in grapes that is proposed to have several anti-aging benefits. Resveratrol is also noted to have estrogenic properties, meaning that it can potentially activate estrogen receptors. [1]
Given its ostensibly desirable health benefits, it’s perhaps no surprise that resveratrol has gained in popularity as a dietary supplement. In fact, a study of Spanish wine consumers’ preferences for resveratrol-enriched wine identified a willingness to pay a 55% premium for such wine! [2]
Natural compounds which have estrogenic properties are called “phytoestrogens”. In simple terms, a phytoestrogen is any plant or food-based compound that bears a structural or functional relationship to ovarian and placental estrogens that occur in the body. Red wine is especially famous for being one such source of resveratrol (it contains around 1 – 10 milligrams per litre). [3]
The purpose of this article is to give an overview of resveratrol, its mechanisms of action and some of its proposed health benefits as well as explore its potential effects on estrogen levels.
What Does Resveratrol Do?
Resveratrol is a naturally occurring bioactive compound that belongs to the stilbene family. It is obtained from plants in the diet, predominantly from the skin and seeds of grapes, although it has been found in various other kinds of plants and foods such as tea, berries, and peanuts. [4]
Resveratrol was discovered and extracted for the first time by Japanese scientist Takaoka from a white hellebore in 1939. It gained a substantial amount of media coverage much later, in the early 1990s in fact, due to a study nicknamed the Red Wine Paradox or French Paradox. [4]
The study suggested that the comparatively low prevalence of coronary heart disease in the French population was due to their practice of drinking red wine, in spite of the typically high fat intake in the French diet.
The proposed mechanism for this is the antioxidant activity of resveratrol, which blocks the conversion of good fats to bad fats by free radicals. [5]
More recently, resveratrol has garnered enhanced interest due to the work of prominent aging and longevity researcher Dr. David Sinclair. More specifically, it’s been shown in animal studies to activate sirtuins. These are a group of proteins that are critically important for cell aging and involved in processes such as DNA repair and cell metabolism.
Resveratrol activates sirtuin 1 (SIRT1), and has been shown to blunt detrimental aging-associated changes in skeletal muscle and the heart in mice, mainly by restoring autophagy (the orderly degradation and recycling of cellular components). [6]
With all that said, resveratrol is ultimately a plant-based compound that also has other actions in the body. These are important to be aware of if you’re planning to take a resveratrol supplement. Most notably, resveratrol does potentially have some estrogenic activity which we will explore next.
The Relationship Between Resveratrol and Estrogen
Resveratrol is classed as a phytoestrogen, which essentially means that it is a plant-based compound that has a similar chemical structure to human estrogen. [7]
Resveratrol’s similarity to human estrogen gives it the ability to bind and activate estrogen receptors. [7,8]
Resveratrol interacts with these receptors as both an agonist and antagonist. In simple terms, an agonist can be described as a key that opens a lock on a door (the receptor) to produce an effect. On the other hand, an antagonist produces an effect by binding to the receptor, therefore blocking the agonist. [9]
Estrogen plays its essential roles by acting on both estrogen receptor alpha (ERα) and beta (ERβ). This has been shown in a variety of different cell types (breast cancer and bone cells for example). [10,11]
Studies have shown significant overlap of genes involved in inflammation that are influenced by both resveratrol and estrogen, which further demonstrates the similarity of these compound. [10,11]
Does Resveratrol Change Estrogen Levels?
In humans, taking resveratrol as a supplement has no impact on your estrogen levels. Estrogen is produced in the ovaries in women, as well as in the adrenal glands and fat cells in small amounts.
However, resveratrol can act as an estrogen modulator, meaning that it changes how estrogen receptors work and interact with the natural estrogen produced in the body. This interaction is different across organs and tissues.
In some types of cells, resveratrol acts as a “super” agonist. A super agonist is a type of agonist that produces a response greater than the original compound, in this case estrogen.
In other types of cells, however, resveratrol produces an equal or lesser activation than that of estrogen. It can also act as an antagonist at higher concentrations.
For instance, in breast cancer cells, resveratrol has mixed agonist/antagonist effects when estrogen is not present. However, when estrogen is present, resveratrol acts as an anti-estrogen (a substance that stops cells from making or using estrogen).
Antiestrogens can stop some cancer cells from growing and are used to prevent and treat breast cancer. [8]
Health Implications of Resveratrol's Estrogenic Activity
Benefits
Resveratrol is reported to potentially improve therapeutic outcomes in a host of health conditions, such as those typically associated with aging. These include diabetes mellitus, obesity, cancer, cardiovascular diseases, osteoporosis, and Alzheimer’s disease. [12,13]
A study in a mouse model of Alzheimer’s disease showed that resveratrol improved the spatial cognition abilities of the mice. It also found enhanced estrogen levels following administration of resveratrol. [13]
Other studies have observed that resveratrol interferes with the metabolism of estrogen in the liver and intestines, increasing their levels and intensifying its effects. [9]
In women with polycystic ovary syndrome, a condition that can cause insulin resistance and reproductive dysfunction, resveratrol increased insulin sensitivity by 66%. [14]
Early evidence also seems to suggest that resveratrol can help with bone formation, and therefore might serve as an osteoporosis treatment in the future. Its action on bone is also likely due to its direct activation on estrogen receptors. [9]
Risks
The beneficial hormonal actions of resveratrol represent an important avenue for health, but there is also a risk of disruption to the estrogen pathways if taken during certain situations.
For example, some studies have raised concerns about the estrogenic activity of resveratrol, advising that the compound may interfere with oral contraceptives and that women who are pregnant or intend to become pregnant should avoid it as a supplement. [15]
Other research has indicated that resveratrol should not be taken by those under 18 years of age given the lack of data on how it affects their natural development. [16]
There are also suggestions that resveratrol might have detrimental effects in individuals with estrogen-sensitive conditions (e.g., breast, ovarian, uterine cancers) by promoting tumor growth and proliferation. However, these effects depend on the molecular properties of the specific cancer. [17]
Given the low content of resveratrol in food, an increased risk of breast cancer progression in women is only likely to be seen following the continuous consumption of high-dose resveratrol supplements. [18]
Conclusions
In this article, we have discussed the structural similarities between resveratrol and estrogen. Studies in cells and animals have shown that Resveratrol has potential benefits for a wide range of conditions in health and disease.
When it comes to Resvatrol and Estrogen, the relationship is complex and in some cases, it activates Estrogen receptors and in others, blocks Estrogen receptors.
Ultimately, the amount of resveratrol present in food and drink is unlikely to have any significant impact on any estrogen-related aspects of health.
However, the main takeaway from this article is that if you have an estrogen-sensitive disorder such as breast cancer, or a strong family history of the same, then taking high-dose resveratrol in supplement form is best avoided. It is always best to consult with your doctor before taking any supplement.