Published March 14 2016
Phytoestrogens are compounds which are derived from plants, and they are found in many different foods. There is a lot of controversy over phytoestrogens, as while there are many studies showing their health benefits, there are also potential risks involved. As a result, there is a great deal of confusion as to whether phytoestrogens are safe to consume, or if they should be avoided. In this article I will discuss both the benefits and risks associated with phytoestrogens, including whether they can be safely consumed in those with thyroid and autoimmune thyroid conditions.
Before I talk about some of the pros and cons of phytoestrogens, I’d like to talk about what phytoestrogens are. As I mentioned in the opening paragraph, phytoestrogens are compounds which are derived from plants, and they have weak estrogenic or antiestrogenic activity (1) [1]. The major groups of phytoestrogens include isoflavones, lignans, and coumestans. Isoflavones are mostly found in soy products, although some other foods have them as well. The most studied isoflavones include genistein and daidzein. Lignans are abundant in flax, although these compounds can be present in other foods as well, such as sesame seeds, grains, and even some fruits and vegetables (2) [2]. For example, brassica vegetables (broccoli, cabbage, etc.) include high levels of lignans (2) [2]. Coumestans are another type of phytoestrogen, and some food sources include split peas, pinto beans, and lima beans.
Which Foods and Herbs Have Phytoestrogens?
There are many different foods and herbs which have phytoestrogens. Here are a few of them:
Soy
Flax
Sesame
Berries
Wine
Grains
Nuts
Cruciferous vegetables
Resveratrol
Quercitin
Milk thistle
Licorice
Red clover
Thyme
Baicalein
Apigenin
Genistein
Curcumin
What Are The Potential Health Benefits of Phytoestrogens?
There are numerous studies which demonstrate the health benefits of phytoestrogens. For example, genistein inhibits the activity of protein tyrosine kinases in numerous tissues including breast cancer cells (3) [3] (4) [4]. By inhibiting these protein tyrosine kinases, genistein can potentially slow the formation of tumors. In addition, genistein can inhibit other DNA replication enzymes associated with the formation of tumors including DNA topoisomerases I and II (5) [5] (6) [6] and matrix metalloprotein (MMP9).
Phytoestrogens are considered to be good antioxidants and anti-inflammatory agents. This is especially true with regards to genistein and resveratrol. For example, one study showed that genistein inhibits pro-inflammatory cytokines in human mast cells (7) [7]. Another study showed that genistein ameliorates cardiac inflammation and oxidative stress (8) [8]. Another study concluded that genistein exerts anti-inflammatory properties affecting granulocytes, monocytes, and lymphocytes (9) [9].
With regards to resveratrol, there are many studies which demonstrate its anti-inflammatory benefits. Resveratrol has been shown to act directly on the immune cells of both innate and adaptive immunity, such as macrophages, lymphocytes, and dendritic cells, and there is very little evidence which suggests that there are any harmful side effects of resveratrol (10) [10]. A randomized, double-blind trial showed that resveratrol supplementation might benefit smokers due to its anti-inflammatory, anti-oxidant, and hypotriglyceridemic affects (11) [11]. Another study showed that resveratrol helps to reduce obesity-related inflammation markers by inhibiting NF-kB activity (12) [12]. I’ve written a blog post on resveratrol in the past entitled “Can Resveratrol Benefit People With Graves’ Disease and Hashimoto’s Thyroiditis? [13]“.
In addition to helping to reduce inflammation and oxidative stress, there is also some evidence that phytoestrogens can benefit people with the following conditions:
Menopausal symptoms. Millions of women in postmenopause take phytoestrogens to help with their symptoms. But the research is conflicting in this area. One systematic review from 2004 concluded that phytoestrogens available as soy foods, soy extracts, and red clover extracts do not improve hot flashes or other menopausal symptoms (13) [14]. Another more recent review (from 2012) concluded that isoflavones don’t relieve menopausal symptoms any better than a placebo, although it did mention that long-term safety studies suggest that women who consume a high amount of isoflavones may have a lower risk of endometrial and ovarian cancer (14) [15]. However, a 2015 meta-analysis and systematic review concluded that phytoestrogens appear to reduce the frequency of hot flashes in menopausal women, without serious side effects (15) [16].
Maintain normal bone density. There is some evidence that consumption of phytoestrogens can help to improve bone density. One double-blind, randomized, placebo-controlled trial looked at the effects of phytoestrogen isoflavones on bone density in women (16) [17]. The results of the study showed that loss of lumbar spine bone mineral content and bone mineral density was significantly lower in the women taking the isoflavone supplement than those taking the placebo (16) [17]. Another randomized, double-blind, placebo-controlled trial involving 389 postmenopausal women with low bone density of the femoral neck showed that twenty-four months of treatment with genistein has positive effects on bone mineral density (17) [18]. Another study showed that high dietary phytoestrogen intake is associated with higher bone mineral density in postmenopausal but not in premenopausal women (18) [19].
Improve cardiovascular health. In 1999 the FDA approved the health claim that consuming soy on a daily basis can reduce the risk of cardiovascular disease (19) [20]. The study mentioned that soy might accomplish this by reducing blood cholesterol levels, but it’s now well known that high cholesterol levels don’t cause heart disease. The truth is that there has been some discrepancy between experimental studies demonstrating the vascular benefits of phytoestrogens and the data from clinical trials (20) [21]. This doesn’t mean that phytoestrogens can’t benefit cardiovascular health, but more research still needs to be done in this area.
Reduce the risk of breast cancer. Breast cancer is the most common malignant neoplasm and the second most common cause of cancer death in women (21) [22]. There is some evidence that phytoestrogens can help reduce the risk of breast cancer, although some are concerned that they can actually increase the risk. What does the evidence show? Well, while the phytoestrogen genistein can inhibit the formation of tumors and reduce the incidence of certain diseases that are dependent upon estrogen, some research has shown that genistein can increase the risk of breast cancer (22) [23] (23) [24]. But overall the evidence seems to be stronger about genistein helping to prevent cancer. A few recent studies have looked at the mechanisms in which genistein can help to prevent breast cancer (24) [25] (25) [26]. Another recent study suggests that the ERα/ERβ ratio is an important factor to consider in breast cancer cells treated with genistein (25), as the study concluded that consuming genistein may be counterproductive in those patients receiving anticancer treatment with a high ERα/ERβ ratio diagnosed breast cancer and it could be harmless or even beneficial in those patients with a lower ERα/ERβ ratio breast cancer cells. Although the focus here has been on genistein, a few studies have shown that resveratrol can also suppress the proliferation of breast cancer cells (26) [27] (27) [28].
What About Flaxseed?
I haven’t spoken much about the benefits of flax. Flaxseed is the richest source of lignans, and the flaxseed lignans have been shown to reduce the risk of hormone-dependent cancers of the breast, uterus, and prostate (28) [29]. One study showed that supplementation with flaxseed alters estrogen metabolism in postmenopausal women to a greater extent than supplementation with an equal amount of soy (29) [30]. This caused increased concentrations of 2-hydroxyestrone, which is considered to be the “good” estrogen metabolite. Another study showed that flax extracts can modify progesterone and possibly estradiol production, while altering estrogen receptor-beta (ERβ) expression (30) [31]. I’ll be talking about the different types of estrogen receptors shortly. Let’s not forget that flaxseed is also an excellent source of the omega 3 fatty acid alpha-linolenic acid (ALA), and is also a good source of fiber.
What Are The Potential Risks Associated With Phytoestrogens?
One main concern of phytoestrogens is that they can bind to the estrogen receptor, and thus some sources classify them as being endocrine disruptors. However, there are a few things you need to understand. First of all, while there is no question that synthetic xenoestrogens such as BPA and BPS disrupt the endocrine system, this isn’t necessarily the case with phytoestrogens.
Another thing you should know is that there are two main types of estrogen receptors, which are estrogen receptor alpha (ERα) and estrogen receptor beta (ERβ). These two forms of estrogen receptors have different tissue expression patterns (31) [32]. ERα and ERβ are encoded by separate genes, ESR1 and ESR2, respectively, found at different chromosomal locations (32) [33]. Selective estrogen receptor modulators such as tamoxifen and raloxifene are examples of compounds that demonstrate tissue-specific estrogenic activity (32) [33]. Tamoxifen, although an estrogen receptor agonist in bone and uterus, is an antagonist in the breast (32) [33].
It seems that most phytoestrogens bind to both ERα and ERβ. However, most have a higher binding affinity for ERβ than ERα (33) [34] (34) [35] (35) [36]. Of these two estrogen receptors, ERα is considered to be the “bad” estrogen receptor, whereas ERβ is the “good” estrogen receptor. Truth to be told, both have important functions in the body, but excess stimulation of the ERα receptors can promote cancer growth, whereas the opposite is true with ERβ. The research shows that ERβ decreases cellular sensitivity to estradiol, which is the most potent estrogen (36) [37]. In addition, ERβ helps to downregulate ERα. In breast cancer ERβ is usually turned off, and phytoestrogens such as genistein, daidzein, and coumestrol have a higher binding affinity for this “good” estrogen receptor (37) [38]. It’s also important to note that while estradiol and estrone have higher binding affinities to ERα, estriol has a higher binding affinity to ERβ (37) [38]. Studies also show that phytoestrogens can increase sex hormone-binding globulin (SHBG) synthesis in postmenopausal women (38) [39] (39) [40] (40) [41], which in turn can affect both estrogen and testosterone levels.
Phytoestrogens In Infants and Children
While phytoestrogens can have some positive health effects in adults, there is a risk of exposure to phytoestrogens in children and infants, and possibly even before birth. One research study found an association between high soy intake during early life and increased breast density, which is a risk factor for breast cancer (41) [42]. A 2008 study consisting of 694 girls in Israel found an increased prevalence of breast buds in 2-year old girls who were fed soy formula as infants (42) [43]. I wasn’t able to find any studies showing a negative correlation between other phytoestrogens (i.e. flax, resveratrol) and children, although I’d still be cautious about giving these to infants and children.
Just about all animal studies have demonstrated that the manipulation of estrogen during specific critical windows of development throughout gestation and early infancy leads to a myriad of adverse health outcomes. This includes malformations in the ovary, uterus, mammary gland and prostate, early puberty, reduced fertility, disrupted brain organization, and reproductive tract cancers (43) [44] (44) [45] (45) [46] (46) [47] (47) [48]. I briefly mentioned soy formula earlier, as this is another possible area of concern, as many infants are raised on soy formula. Infants on soy formula consume approximately 6–9 mg of isoflavones per kg of body weight per day, an amount, when adjusted for body weight, that is up to seven times higher than for adults meeting the FDA soy consumption guideline, or Asians consuming a traditional soy-based diet (0.3–1.2 mg/kg per day) (48) [49] (49) [50].
Other Things To Consider About Phytoestrogens
One thing to keep in mind is that the isoflavone content of certain foods can vary greatly. For example, one study showed that the total isoflavone content of raw soy beans can range from 18 to 562mg/100mg (50) [51]. In addition, one has to consider that different people will absorb and metabolize phytoestrogens differently.
And staying on the topic of soy, I haven’t yet mentioned that most soy is genetically modified. And so if you do consume soy you want to make sure it’s from a non-GMO source. Soy is also a common allergen, and is high in phytates. And while I’m not too concerned about the goitrogenic properties of cruciferous vegetables, there is some concern about the effect soy has on thyroid hormone production (51) [52] (52) [53]. So while eating some organic fermented soy has some health benefits, there are also certain risks as well.
So What’s My Final Verdict On Phytoestrogens?
I think that consuming certain phytoestrogens by adults can be beneficial. Of course cruciferous vegetables are very healthy, as are berries, and others such as flaxseed, curcumin, and resveratrol also can have certain health benefits. Soy is more controversial, as while there are some health benefits of eating organic fermented soy, some people are better off avoiding this due to the reasons I mentioned earlier.
In summary, there is controversy over phytoestrogens, as while there are studies showing numerous health benefits associated with flax, soy, and other phytoestrogens, there are other studies showing some health risks. There is evidence that phytoestrogens can help with menopausal symptoms, bone density, improve cardiovascular health, and can reduce the risk of certain types of cancers. Most phytoestrogens seem to have a greater binding affinity to ERβ, which is considered to be the “good” estrogen receptor. However, more research needs to be conducted, and I would be cautious about giving phytoestrogens to children, especially soy. Speaking of soy, most soy is genetically modified, and soy also is a common allergen, has goitrogenic properties, and is high in phytates. So while organic fermented soy has some health benefits, many people need to be cautious about consuming too much soy.