Soy is a unique food that is widely studied for its estrogenic and anti-estrogenic effects on the body. Studies may seem to present conflicting conclusions about soy, but this is largely due to the wide variation in how soy is studied. Results of recent population studies suggest that soy has either a beneficial or neutral effect on various health conditions. Soy is a nutrient-dense source of protein that can safely be consumed several times a week, and probably more often, and is likely to provide health benefits—especially when eaten as an alternative to red and processed meat.

Soy is exalted as a health food by some, with claims of taming hot flashes, warding off osteoporosis, and protecting against hormonal cancers like breast and prostate.

At the same time, soy is shunned by others for fear that it may cause breast cancer, thyroid problems, and dementia, though these claims have not been substantiated.

Whether published in a popular press article or a well-designed clinical study, some debate about soy remains. As a species within the legume family, nutrition scientists often label soy as a food with potential for significant health benefits. However, due to contrary research that suggests possible negative effects of soy in certain situations, there has been a hesitancy to wholeheartedly promote soy.

Part of the uncertainty is due to the intricacy of soy’s effects on the body. Soy is unique in that it contains a high concentration of isoflavones, a type of plant estrogen (phytoestrogen) that is similar in function to human estrogen but with much weaker effects. Soy isoflavones can bind to estrogen receptors in the body and cause either weak estrogenic or anti-estrogenic activity. The two major soy isoflavones are called genistein and daidzein. Soy isoflavones and soy protein appear to have different actions in the body based on the following factors:

• Type of study  Is it being examined in a study with animals or humans? Soy may be metabolized differently in animals, so the outcomes of animal studies may not be applicable to humans.
• Hormone levels  Because soy can have estrogenic properties, its effects can vary depending on the existing level of hormones in the body. Premenopausal women have much higher circulating levels of estradiol—the major form of estrogen in the human body—than postmenopausal women. In this context soy may act like an anti-estrogen, but among postmenopausal women soy may act more like an estrogen. Also, women with breast cancer are classified into hormone type—either hormone positive (ER+/PR+) or hormone negative (ER-/PR-) breast cancer—and these tumors respond differently to estrogens.
• Type of soy  What type of soy is being studied: Whole soy foods such as tofu and soybeans, processed versions like soy protein powders, or soy-based veggie burgers? Fermented or unfermented soy foods? If supplements are used, do they contain isoflavones or soy protein?

Thus, there are many factors that make it difficult to construct blanket statements about the health effects of soy. 

Aside from their isoflavone content, soy foods are rich in nutrients including B vitamins, fiber, potassium, magnesium, and high-quality protein. Unlike some plant proteins, soy protein is considered a complete protein, containing all nine essential amino acids that the body cannot make which must be obtained from the diet. Soy foods are also classified as fermented or unfermented (see table with examples, below). Fermented means that the soy food has been cultured with beneficial bacteria, yeast, or mold. Some believe that fermenting soy improves its digestibility and absorption in the body, as this process partially breaks down soy’s sugar and protein molecules.

Heart Disease

Soy protein took center stage after research showed that it might lower levels of harmful cholesterol. A 1995 meta-analysis of 38 controlled clinical trials showed that eating approximately 50 grams of soy protein a day (no small amount as this translates to 1½ pounds of tofu or eight 8-ounce glasses of soy milk!) in place of animal protein reduced harmful LDL cholesterol by 12.9 percent. [1] Such reductions, if sustained over time, could mean a greater than 20% lower risk of heart attack, stroke, or other forms of cardiovascular disease. In response to this finding, in 1999 the Food and Drug Administration (FDA) allowed companies to claim that diets low in saturated fat and cholesterol that also contain soy “may reduce the risk of heart disease.” [2]

However, a number of studies since have tempered that finding. [3] According to a comprehensive update of soy research by the nutrition committee of the American Heart Association (AHA) published in 2000, eating 50 grams of soy per day lowered LDL by only about 3%. [3] In October 2017, after review of additional scientific studies since the health claim was authorized, the FDA proposed a rule to revoke the claim because numerous studies presented inconsistent findings on the relationship between soy protein and heart disease. [4] Some of these inconsistencies may have resulted because soy was compared with a variety of alternative foods.

Even though soy protein may have only a small direct effect on cholesterol, soy may still benefit the heart in other ways. An epidemiological study following three large cohorts of American men and women who did not have cardiovascular disease at the start of the study found that those who ate the highest amounts of tofu and isoflavones from soy foods, compared with those who ate the least, had an 18% and 13% lower risk, respectively, of developing heart disease. [5] The benefit of tofu was stronger in premenopausal women and postmenopausal women not using hormone therapy.

Soy foods are generally good for the heart and blood vessels because they provide polyunsaturated fat, fiber, vitamins, and minerals, and are low in saturated fat. Replacing red meat with plant proteins including soy foods, beans, and nuts was associated with a 14% lower risk of heart disease, as found in the Health Professionals Follow-up Study, a large long-term epidemiological study of more than 43,000 men. [6] Another large cohort of more than 500,000 Chinese adults with no previous cardiovascular disease found that those with the highest intakes of soy (4+ days a week) compared with those who never ate soy had a 25% lower risk of deaths from heart attack. [7]

Hot Flashes

Hormone replacement therapy has traditionally been used as an effective treatment for hot flashes and other unpleasant symptoms that accompany menopause, but its long-term use has raised concerns of an increased risk of some diseases including breast cancer and stroke. Soy has been a popular alternative treatment but not clearly supported by research; in theory the potential estrogenic effects of soy isoflavones could help to tame hot flashes by giving an estrogen-like boost during a time of dwindling estrogen levels.

In many Far East Asian countries where soy is eaten daily, women have lower rates of menopausal symptoms, although research is conflicting as to whether soy is a primary contributor. [8] Reports suggest that about 70–80% of U.S. women of menopausal and perimenopausal age experience hot flashes, in comparison with 10–20% of Far Eastern Asian women. [9] Further, the average blood concentration of the isoflavone genistein in Asian women who regularly consume soy is about 12 times higher than that of U.S. women. [9]

Yet several meta-analyses and carefully controlled clinical studies have not found strong evidence of a link. [10,11] An AHA review in 2006 concluded that it was unlikely that soy isoflavones exert enough estrogenic activity to have an important impact on hot flashes and other symptoms of menopause. [3] A JAMA review the same year found highly conflicting results with soy isoflavone extracts and stated that the overall evidence did not support its benefit in relieving hot flashes. [12]

In another review of 43 randomized controlled trials have examined the effects of phytoestrogens on hot flashes and night sweats in perimenopausal and postmenopausal women. Four trials found that extracts of 30 mg or greater of genistein consistently reduced the frequency of hot flashes. Other trials that used dietary soy or soy extracts suggested a reduced frequency and severity of hot flashes and night sweats when compared with placebo, but these trials were small with a possible strong placebo effect. [8] No adverse effects were noted from the soy treatments when followed for up to two years, but the authors did not feel overall there was strong and consistent evidence for a benefit of soy.

Another meta-analysis of 16 studies found that soy isoflavone supplements had a small and gradual effect in weakening menopausal hot flashes compared with estradiol (human estrogen). However, authors noted weaknesses in the analysis due to a small number of participants and high variability in study design. [9]

A more recent review of randomized trials found that some studies showed benefit of soy supplements on hot flashes; the therapeutic dosage ranged from 40-70 mg of isoflavones daily. [13] The authors also observed that the presence of equol (a protective substance made from the breakdown of isoflavones that only some women can produce) may be needed for isoflavones to effectively reduce hot flashes. Despite these results, the study authors did not offer a confident conclusion on the use of isoflavone supplements due to variations in study design and length; differences in the types and dosages of supplements; and the small sample sizes and high drop-out rates.

This area needs further research as questions remain about a possible benefit of soy. Results are conflicting, potentially due to variation in the types of soy preparations used, the quantities given, and for how long they are used.

Breast Cancer

Phytoestrogens don’t always mimic estrogen. In some tissues and in some people, they may block the action of estrogen. If soy’s estrogen-blocking action occurs in the breast, then eating soy could, in theory, reduce the risk of breast cancer because estrogen stimulates the growth and multiplication of breast and breast cancer cells. Studies so far have not provided a clear answer. Some have shown a benefit with soy consumption and breast cancer while others show no association. [14-17] It appears that the effects of soy may vary depending on menopausal status, the age at which soy is consumed, and type of breast cancer.

In animal and cell studies, high dosages of isoflavone or isolated soy protein extracts tend to stimulate breast cancer growth. [18,19] However, studies that observe people consuming soy foods over time show either a protective or neutral effect. Women from Asian countries appear to receive greater protective benefit from breast cancer with high soy intakes than American and European women, but this may simply be a difference in the amount of soy consumed. [20,21] Asian women may have higher levels of equol, a substance metabolized from the isoflavone daidzein by bacterial flora in the intestines. [22] Equol is believed to block potentially negative effects of human estrogen, but not all women possess the bacteria needed to create equol. [23] It is estimated that 30-50% of all humans are able to produce equol. [24] Eating soy foods starting at an early age (such as those found in many traditional Far East Asian diets) may be why women from some countries find greater benefit from soy foods than others. [19] However, the overall evidence on equol and cancer risk is unsettled. [25]

The Shanghai Women’s Health Study which followed 73,223 Chinese women for more than 7 years has been the largest and most detailed study of soy and breast cancer risk in a population with high soy consumption. [26] In this study, women who ate the most soy had a 59% lower risk of premenopausal breast cancer compared with those who ate the lowest amounts of soy. There was no association with postmenopausal breast cancer. Risk was 43% lower when soy was eaten during adolescence. Seven years later, the study authors published a follow-up analysis from the same cohort over 13 years to evaluate any association between soy foods and specific types of breast cancer defined by hormone receptors and by menopausal status (Estrogen [ER] +/-; Progesterone [PR] +/-). [27] Key highlights of the study:

• A 22% lower risk of breast cancer when comparing the highest to lowest intakes of soy during adulthood.
• A 28% lower risk of hormone positive (ER+, PR+) breast cancer in postmenopausal women.
• A 54% lower risk of hormone negative (ER-, PR-) breast cancer in premenopausal women.
• A 47% lower risk of premenopausal breast cancer when comparing high to low intakes of soy during adolescence and adulthood.

The Breast Cancer Family Registry was a prospective study following 6,235 women for 9 years diagnosed with breast cancer and living in the U.S. and Canada; intake of soy isoflavones was examined in relation to deaths from all causes. [28] Key highlights of the study:

• Women who ate the highest amounts of soy isoflavones had a 21% lower risk of death compared with women with the lowest intakes.
• Women who had ER-/PR- tumors and who were not receiving tamoxifen appeared to receive greatest benefit from the higher soy isoflavone intakes. However, isoflavone intake did not have a negative impact on women who were receiving tamoxifen or who had ER+/PR+ tumors.
• Of all ethnicities, Asian American women tended to have the highest isoflavone intakes at about 6 mg daily, but this amount was still much lower than women living in Asian countries who eat closer to 46 mg daily. The authors noted that American women appeared to benefit from eating smaller amounts of soy.

Another prospective study followed 1,954 American women who were breast cancer survivors for six years. [29] Key highlights of the study:

• Among postmenopausal women treated with tamoxifen, breast cancer recurrence was 60% lower when comparing the highest to the lowest daidzein (a specific type of soy isoflavone) No benefit was observed in women who had never used tamoxifen.
• Recurrence was lower with increasing isoflavone intake among women with tumors that were ER+/PR+ but not ER-/PR-.
• The most frequent sources of soy foods were not whole or minimally processed soy foods, but rather soy sauce, breakfast or diet drinks, tofu, diet bars, and soy protein isolate powder. The mean amount of isoflavones in the “high” category was about 19 mg daidzein and 27 mg genistein daily—a modest amount compared with Asian populations.
• The authors concluded that soy isoflavones eaten at levels comparable to those in Asian populations may reduce the risk of cancer recurrence in women receiving tamoxifen therapy and does not appear to interfere with tamoxifen efficacy. However, the findings need to be confirmed because they were mainly in subgroups and could be due to chance.

Prospective studies also find soy foods to be protective from breast cancer deaths:

• A cohort study of 1,460 Chinese women who were early-stage breast cancer survivors looked at dietary soy isoflavone intakes at baseline and after the breast cancer diagnosis, over a four-year period. [30] Higher soy intakes at baseline were associated with a 66% lower risk of deaths from any cause and a 64% lower risk of deaths from breast cancer. Higher soy intakes after diagnosis were associated with a 64% and 51% lower risk of deaths, from any cause and from breast cancer, respectively. The effects were greater in women who were premenopausal, had ER-/PR- tumors, and were taking tamoxifen.
• A meta-analysis of prospective cohort studies found a 12% reduction in breast cancer deaths with each 5 gram per day increase in soy protein intake. [31]

However, randomized controlled trials do not show an effect of soy foods on risk factors for breast cancer:

• A review of randomized controlled trials (RCTs) looked at isoflavone intakes ranging from 36-235 mg/day from food or supplements, taken from 1 month to 3 years, and breast cancer risk (as measured by breast density, changes in estrogen, and bloodwork) in healthy women. [32] The eighteen RCTs included both pre- and postmenopausal participants. No changes in breast cancer risk factors were found with isoflavone intakes. The authors noted limitations in their analysis in that there were wide variations in numbers of participants and the doses and duration of treatments, which made drawing firm conclusions difficult. Most importantly, these studies did not examine actual incidence of breast cancer.

Prostate Cancer

The incidence of prostate cancer is highest in Western countries and lowest in Asian countries, where soy foods are a regular part of the daily diet. In addition, observational studies have found an increased risk of prostate cancer in Chinese and Japanese men who move to Western countries and adopt a Western diet, but not in those who continue eating a traditional diet. [33] Soy isoflavones, specifically genistein and daidzein, are incorporated in prostate tissue and may act as weak estrogens and inhibit the development of prostate cancer. [34]

In a meta-analysis of 30 case-control and cohort studies from the U.S., Europe, Japan, and China, intakes of total soy foods, genistein, daidzein, and unfermented soy foods were associated with a lower risk of prostate cancer. [34]

A review of eight randomized controlled trials examined the effects of soy in men with or at risk of developing prostate cancer. Two of these studies found that isoflavone supplements or dietary soy protein reduced the risk of prostate cancer in men at high risk of developing the disease. However, none of the studies found a significant effect on prostate specific antigen (PSA) levels, a protein produced by the prostate gland that is used to detect prostate cancer. There were no adverse effects reported with soy supplementation. The authors discussed limitations of the review including the small number of participants, the short duration of studies (less than one year), and variation in dosages and types of soy given. [33]

A small randomized controlled trial in 2021 examined if soy protein supplements could slow down or reverse rising PSA levels in men who had previously been diagnosed and treated for prostate cancer, but who had a recurrence (as evidenced by rising PSA levels). The study found that even though the soy protein supplements increased blood levels of genistein, there was no effect of the supplement versus placebo on PSA levels when given for 6-8 months. [35]

Memory and Cognitive Function

Fermented soy foods commonly eaten in East Asian diets, including natto, tempeh, soy paste, and soy sauce, contain isoflavones and also bacteria that might have benefits for neurological disorders including cognitive decline, Alzheimer’s disease (AD), and Parkinson’s disease (PD). Soy’s antioxidant and anti-inflammatory effects may reduce the oxidative stresses associated with AD and PD. [36] Animal studies have suggest that soy compounds can weaken the progression of AD and prevent nerve cell death. They also find that soy can reduce inflammation and excess free radical production in the brain. AD has been associated with decreased levels of beneficial anti-inflammatory bacteria while harboring increased levels of proinflammatory bacteria.  Fermented soy foods are produced with beneficial bacteria like Lactobacilli, Bifidobacteria, and Bacillus species that produce butyrate, a short-chain fatty acid that regulates immune function and is being investigated for its protective effects on the brain.

Long-term low levels of estrogen the occur in menopausal women can reduce the number of estrogen receptors in the brain that are necessary for specific cognitive functions like memory and learning. [37] The soy isoflavone, daidzein, has been hypothesized to reduce decline in cognitive function or disease processes related to cognition and behavior. Thus, the possibility has been raised that eating soy foods might help prevent age-related memory loss or decline in thinking skills. [38]

Studies in humans, however, are not conclusive on soy’s effects on the brain:

• Trials have yielded contradictory results, with some showing a benefit with soy isoflavone supplementation [39, 40] and others showing no benefit. [41-43] A review of 13 randomized controlled trials found that in about half of the studies, isoflavone supplementation had a beneficial effect on cognition in older men and women compared with controls, including improvements in attention, information-processing speed, and memory. However the results overall were mixed, with other studies not demonstrating a benefit. This may have been due to differing dosages given or the types of cognition tests used. [37]

One large study in men found a detrimental effect on cognitive function. In a prospective cohort study of more than 3,700 Japanese-American men living in Hawaii, those with the highest intakes of tofu (eaten almost daily) at midlife ages had greater cognitive impairment and brain atrophy in late life compared with men with the lowest tofu intakes (almost never eaten). [44] However, the actual number of men eating very high amounts of tofu was small, and past dietary information was collected by relying on the participants’ memory, some of whom may have already experienced cognitive decline. Because of this, the researchers stated that the findings were too preliminary to make recommendations. [45]

Thyroid

A meta-analysis of 18 randomized controlled trials found that although soy supplements raised thyroid stimulating hormone levels slightly, they did not have any effect on actual thyroid hormone production. [46] However, another study found that soy may interfere with thyroid hormone medication used to treat hypothyroidism. In one randomized double-blinded trial, 60 patients with a mild form of hypothyroidism (called subclinical hypothyroidism) were given low or high-dose phytoestrogen supplements (both also contained 30 grams of soy protein), the amount that might be obtained from a vegetarian diet. [47] Risk of developing clinical hypothyroidism was increased in the higher phytoestrogen group (no effect in the lower phytoestrogen group). The authors suggested that female vegetarian patients with subclinical hypothyroidism may need more careful monitoring of thyroid function. However, the authors also found a benefit on of reduced cardiovascular risk factors in the high phytoestrogen group, with a significant reduction in insulin resistance, inflammatory markers, and blood pressure. The effect of soy on thyroid function needs further examination.

References