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As you walk the supplement aisle of the market, you may see products that contain soy isoflavones and other phytoestrogens, especially formulas targeted at reducing menopause symptoms. However, many people in the industry have also started to caution against taking these supplements or eating soy and other phytoestrogen-rich foods due to potentially negative impacts on the neuroendocrine system. So, what is the truth?

Researchers began to look at the potential benefits of phytoestrogens due to studies pointing to a reduced risk of breast cancer in Asian populations compared to Western populations. The consumption of soy products was identified as one potential reason, as traditional Asian diets contain isoflavone intakes ranging from 15 – 50 mg per day compared to around 2 mg per day in traditional Western diets.

Decades of research investigated the possibility and found some potential validation to the hypothesis. However, more recent research began to consider whether the same phytoestrogens may have a detrimental impact as endocrine disruptors.

Is there a consensus on whether phytoestrogens and the foods that contain them should be consumed or avoided? Let’s find out.

What Are Phytoestrogens?

Before we dive into the literature, let’s take a moment to get on the same page about what phytoestrogens are: these compounds are found in plant foods whose chemical structure closely resembles that of one form of estrogen—E2 or 17-beta-estradiol—and as such, they can bind to estrogen receptors.

Their ability to bind to the receptors creates antiestrogenic effects, which may have health benefits but may also have risks due to the potential to interfere with normal hormone production and action, thus becoming endocrine disruptors. Many varieties tend to have a higher affinity for ER-beta than ER-alpha receptors, and phytoestrogens have a weaker bond in general compared to E2.

Although many link phytoestrogens to soy and isoflavones, there are several types of phytoestrogens found in a variety of plant foods:

• Coumestans (most common in split peas, pinto beans, lima beans, alfalfa sprouts, and clover sprouts)
• Isoflavones (most common in soy)
  • Biochanin A
  • Daidzein
  • Formononetin
  • Genistein
  • Glycitein
• Lignans (fermented in the microbiome with the precursors commonly found in flaxseeds, whole grains, sesame seeds, legumes, and fruits and vegetables)
  • Enterodiol
  • Enterolactone
• Prenylflavonoids (e.g., hops, beer)

The microbiome may play a significant role in the metabolism and activation of phytoestrogens, and thus, the health benefits because they hydrolyze isoflavone glycosides and break them down to the metabolites humans can use. Equol is one key metabolite of isoflavones produced by gut bacteria, but it is estimated that only about 30% of people are equol producers, likely due to a difference in microbiome makeup. Asian populations and vegetarians have been shown to have a higher frequency of equol producers compared to the general population.

Benefits of Phytoestrogens

There has been a significant amount of research into the potential benefits of phytoestrogens over the past decades, so this is by no means an exhaustive list. Much of the research has focused on benefits for menopause symptoms and chronic disease risk factors associated with a higher risk in menopause, such as osteoporosis and cardiovascular disease.

Menopause Relief

Due to the potential estrogenic effects of phytoestrogens, especially isoflavones, much research has been done on the potential for phytoestrogen consumption or supplementation to reduce menopause symptoms, especially hot flashes. However, the studies have shown mixed results.

One meta-analysis found that, in menopausal women, phytoestrogens led to a significant reduction in hot flashes compared to placebo with no side effect difference to those taking a placebo, although it did not impact other symptoms of menopause based on the Kupperman index, an index that includes 11 symptoms of menopause, including hot flashes. Another meta-analysis found that phytoestrogen supplementation led to improvements in hot flashes and vaginal dryness but not night sweats.

In a recent systematic review on isoflavone supplements in menopausal women, the researchers found taking the supplements reduced hot flashes, attenuated bone mineral density (BMD) loss in the lumbar spine, and demonstrated potential benefits for blood pressure and glycemic control.

Equol may be one reason for the different findings in studies. In one observational study, reduction in vasomotor symptoms of menopause occurred only in equol producers. Those with the highest quartile intake were 76% less likely to have those symptoms compared to the lowest quartile. One randomized, double-blind, placebo-controlled trial used an equol supplement for 12 weeks in menopausal women and found improved mood-related symptoms in equol nonproducers, with those who took 10 mg 3 times having a better outcome. A meta-analysis found a significant benefit to equol supplementation for reducing hot flashes.

Preventing Cardiovascular Disease

Several studies have looked at the benefits of phytoestrogen for reducing the risk of cardiovascular disease. Soy isoflavones have been shown to lower cholesterol, especially in combination with probiotics or prebiotics. Additionally, one study in early menopausal women found that supplementation with 15 g soy protein (containing 66 mg isoflavones) for 6 months compared to supplementing with the same amount of soy protein depleted of isoflavones led to a “27% reduction in 10-year coronary heart disease risk, 37% reduction in myocardial infarction risk, 24% reduction in cardiovascular disease, and 42% reduction in cardiovascular disease death risk,” based on significant reductions in systolic blood pressure and metabolic parameters.

Arterial stiffness is another marker used for cardiovascular health, and phytoestrogens—at least in equol producers—may have some benefit. In one study on men, those who were equol producers experienced an acute benefit to arterial stiffness significantly associated with plasma equol concentrations, while no vascular effect was experienced by the non-equol producers. This change only lasted for less than six hours but, if sustained, could equate to an “11 – 12% reduced risk of cardiovascular disease,” according to the researchers.

Isoflavones and other phytoestrogens may also protect against atherosclerosis. In a double-blind, placebo-controlled study, 500 mg of isoflavonoid-rich herbal preparation for 12 months led to a 1.5-fold inhibition of existing atherosclerotic plaques (27% compared to 41% in the placebo group). Additionally, the group taking the herbal supplement also experienced more improvement in other markers for cardiovascular disease, including a total cholesterol decrease of 6.3% compared to 5.2% in the placebo group and a 7.6% LDL decrease compared to 5.2%.

Although several studies on markers for cardiovascular health have been promising, one small, 6-week, randomized, double-blind, parallel, placebo-controlled trial found no changes in blood pressure in menopausal women supplementing of 80 mg isoflavones. However, the lack of benefit may be because only 3 of the 12 women in the treatment group were equol producers.

Reduction of Cancer Risk

Another promising area of health benefits from phytoestrogens is in prevention of cancer, including breast, prostate, endometrial, and colorectal. However, some of the studies demonstrating a potentially protective effect of soy intake on breast cancer showed an impact only on Asian populations. One systematic review on epidemiological studies of Japanese populations found a protective effect of isoflavones for breast cancer risk.

In prostate cancer, the benefits have been better, with one meta-analysis finding an inverse association between phytoestrogen intake and risk of prostate cancer, especially with high genistein and daidzein intake. The odds ratio in the tier with the highest phytoestrogen consumption was 0.8, and for the highest serum concentration, it was 0.83. Another meta-analysis found that supplementing with soy isoflavones led to a significant reduction in prostate cancer diagnosis in those with an identified risk, although there was no impact on PSA levels or sex steroid endpoints. The authors mentioned that the studies were mostly small samples with a short duration, and more research was necessary.

Additional Potential Benefits

There are additional areas in which researchers are looking at the potential benefit of phytoestrogens.

One area is whether they are beneficial to bone health, especially in postmenopausal women. Some of the research is promising, but it is not yet definitive. One meta-analysis and systematic review found potentially beneficial effects on bone health in menopausal women, but there was no definitive proof, and more research was needed to see whether supplementation with phytoestrogen could help maintain healthy bones during menopause. Another meta-analysis of randomized controlled trials found weak or no impact of soy isoflavones on BMD.

Some studies also point to potential benefits to cognitive function and the prevention of neurodegenerative diseases, including Alzheimer’s disease. However, one randomized controlled trial in patients with Alzheimer’s disease found there were no cognitive benefits to taking 100 mg per day of soy isoflavone supplements for 6 months. Equol producers had a better result, with improved performance in verbal fluency and speeded manual dexterity.

There is also promising research showing potential benefits of phytoestrogens for urinary incontinence and pelvic organ prolapse as well as abdominal aortic aneurysms in men (based on a mouse study).

Some of the health benefits of phytoestrogens may come from their ability to reduce inflammation. In one study, there was an inverse association “between urinary phytoestrogens and serum CRP,” a marker of inflammation. This may be due to antioxidant properties, especially in genistein, daidzein, and equol.

Risks of Phytoestrogens

Although there are plenty of studies pointing to potential benefits of phytoestrogens, studies are emerging that point to possible risks. This has led to some people being hesitant to consume phytoestrogens in food, but is it a valid concern? As with many foods and phytochemicals, there are pros and cons to exposure to phytoestrogens, so let’s see whether the research points to there being more cons than pros.

The main reason for concern surrounding phytoestrogens is the potential to be an endocrine disruptor due to its interference with estrogen from binding with the estrogen receptors. Infants and children may be most at risk because they are still developing. In the studies looking at the endocrine-disrupting potential of phytoestrogens, most of the research has found potential disruption with the thyroid hormone, specifically the possibility it can inhibit thyroid peroxidase and estrogen. Studies on the endocrine-disrupting actions of phytoestrogens have been on animals, although there have been some studies on humans.

The studies demonstrating a potential impact on female reproductive health is mixed. One meta-analysis found no association between endometrial thickness or breast density in those consuming phytoestrogens and those taking a placebo. A small, randomized, double-blind trial with 34 premenopausal women looking at how consumption of 100 mg of isoflavones impacted the ovulatory cycle during one year found no significant differences in the groups.

On the other hand, one meta-analysis found that isoflavone-rich soy products decreased FSH and LH (22% and 24%, respectively) and increased menstrual cycle length by 1.05 days in premenopausal women and increased total circulating estradiol non-significantly in postmenopausal women, although they did not determine whether this was clinically significant. Another study found that while there was no statistically significant difference in 30 outcomes, including several on reproductive health and puberty, in those who had consumed soy formula as a child and those who had cow’s milk formula, the women had a slightly longer duration of menstrual bleeding and had greater discomfort during menstruation in the soy-formula group.

A study on girls in Korea found a positive association between serum isoflavone levels and precocious (or early) puberty, with the prevalence significantly higher in children with serum levels above 30 nmol/l. One study also found a greater risk for early fibroid diagnosis in those who consumed soy formula as infants, with a relative risk of 1.25, although this was based on self-reporting.

Some have also expressed concern that there may be a higher risk of breast and uterine cancer from phytoestrogen intake. One review study found there was no evidence linking a phytoestrogen-rich diet to increased malignant growth in hormone-dependent tissue, such as breast or ovarian. Another systematic review found no association between black cohosh use and increased risk of breast cancer, and there also was not a protective effect.

Another meta-analysis study found a 34% increase in breast cancer risk in those who used cardiac glycosides, a type of phytoestrogen. However, they could not determine whether it was a causal relationship or not based on the data. Another systematic review found a potential reduction of risk in “breast cancer incidence, recurrence, and mortality” with soy consumption “consistent with a traditional Japanese diet” and that soy did not have estrogenic effects.  Although the researchers did state more evidence on the safety of taking high doses of isoflavones was necessary, there was no clear evidence of harm in breast cancer patients.

There may be an impact on body weight in postmenopausal women as well. One meta-analysis found that, in general, there was no association between body weight, BMI, total fat mass, waist and hip circumference, or body fat percentage in those who consumed a phytoestrogen supplementation compared to placebo. There was a small decrease in the waist to hip ratio. However, in subgroup analysis, they found healthy postmenopausal women experienced a modest decrease in body weight, while for those who had preexisting metabolic disorders, there was an association with increased body weight.

The Verdict

The consensus in the literature is still out, with variability in studies making it difficult to create a blanket verdict for all people. Bio-individuality, tolerance of soy, the type of phytoestrogen and food source, microbiome makeup (especially whether one is an equol producer or not), risk factors, and more all play a role in whether or not phytoestrogen-rich food should make it to your dinner table—or whether you should supplement. One small study suggested that consuming small amounts throughout the day could lead to more optimal serum isoflavone content than a higher dose singular product.

Consuming foods rich in phytoestrogens as one aspect of a varied, colorful, plant-based diet most likely will not pose a risk and may impart benefits for many people. Some people may hesitate to consume soy, one of the richest in isoflavones, for reasons beyond the scope of this blog, such as the use of GMO and non-organic farming practices. Supplementation and consuming high levels may provide more benefit, but for some people and situations, it may also come with more risk. Certain populations, especially infants and developing children, are at a higher risk for the endocrine-disrupting potential.

Thus, it is best to discuss your situation, risk factors, and health goals with your doctor, nutritionist, or another healthcare practitioner to see the best way to incorporate phytoestrogens into your diet to get the benefits and reduce the potential risks if it is something you wish to include in your diet.