Straight Talk About Soy

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 little direct effect on cholesterol, soy foods are generally good for the heart and blood vessels if they replace less healthful choices, like red meat, and because they deliver plenty of polyunsaturated fat, fiber, vitamins, and minerals, and are low in saturated fat.

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 carries 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 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. [5] Reports suggest that about 70–80% of U.S. women of menopausal and perimenopausal age experience hot flashes, in comparison with 10–20% of Asian women. [6] Further, the average blood concentration of the isoflavone genistein in Asian women is about 12 times higher than that of U.S. women because of higher soy consumption.

Yet several meta-analyses and carefully controlled clinical studies have not found strong evidence of a link. [7, 8] 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. [9]

A 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. [5] 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, the authors noted weaknesses in the analysis due to a small number of participants and high variability in study design. [6]

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.

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. [3, 10-12] 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. [13, 14] 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. [15] Asian women may have higher levels of equol, a substance metabolized from the isoflavone daidzein by bacterial flora in the intestines. [16] Equol is believed to block potentially negative effects of human estrogen, but not all women possess the bacteria needed to create equol. [17] It is estimated that 30-50% of all humans are able to produce equol. [18] Eating soy foods starting at an early age (such as those found in traditional Asian diets) may be why women from some countries find greater benefit from soy foods than others. [14] However, the overall evidence on equol and cancer risk is mixed in American, European, and Asian women. [19]

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. 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. Risk was 43% lower when soy was eaten during adolescence. [14] 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] +/-). [21] 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% decreased risk of hormone positive (ER+, PR+) breast cancer in postmenopausal women.
• A 54% decreased risk of hormone negative (ER-, PR-) breast cancer in premenopausal women.
• A 47% decreased 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 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. [22] 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. [23] 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.

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. [24] Soy isoflavones, specifically genistein and daidzein, are found to collect in prostate tissue and may act as weak estrogens and exert a protective effect against the development of prostate cancer. [25]

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 significantly associated with a reduced risk of prostate cancer. [25]

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. PSA is 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. [24]

Menopause has been linked with changes in mood and memory impairment. Long‐term low levels of estrogen in women can reduce the number of estrogen receptors in the brain that are necessary for specific cognitive functions like memory and learning. [26] The soy isoflavone, daidzein, has been hypothesized to reduce decline in cognitive function or disease processes related to cognition and behavior. Thus, research has raised the possibility that eating soy foods might help prevent age-related memory loss or decline in thinking skills. [27]

Trials have yielded contradictory results, with some showing a benefit with soy isoflavone supplementation [28, 29] and others showing no benefit. [30-32] 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. [26]

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, the highest intakes of tofu (eaten almost daily) at midlife ages were significantly associated with greater cognitive impairment and brain atrophy in late life compared with men with the lowest tofu intakes (almost never eaten). [33] 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. [34]

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. [35] 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.

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