Soy protein isolate is not recommended for breast cancer
Soy protein isolate is produced by removing most of the fats and carbohydrates from defatted soy flour (soy flour is made by grinding soybeans into a powder). Soybeans have a protein content of approximately 40%, whereas soy protein isolate has a protein content of 90% or higher. Depending on processing, soy protein isolates vary widely in concentrations of genistein and other soy isoflavones. Soy protein concentrate is a product similar to soy protein isolate which is produced by removing the water soluble carbohydrates from defatted soy flour. Soy protein concentrate has a protein content of approximately 70% and also contains some carbohydrate, ash and oil. Textured soy protein is made by forming a dough from defatted soy flour plus water, extruding it through a die, and drying it. The extrusion process alters the structure of the soy protein, resulting in a meat like texture. Textured soy protein contains approximately 50% soy protein. It is used as a meat replacement (e.g., in veggie burgers). Unlike soy protein isolate and soy protein concentrate, textured soy protein is a good source of fiber and soy isoflavones.This web page focuses on soy protein isolate, which is a component of many processed foods, including baked foods, breakfast cereals, processed meat products, soy-based infant formulas, and some protein shakes and protein bars. Soybean oil and soy protein isolate in processed foods are the primarily forms of soy consumed by many U.S. residents. Separate web pages cover soybeans, soybean oil, soybean paste and tofu. We attempt to untangle the conflicting findings regarding breast cancer risk and soybean isoflavones in the genistein and daidzein web page.
Soy protein has been shown to improve glycemic control in diabetic postmenopausal women and to improve insulin sensitivity in female ovariectomized monkeys as well as in male monkeys. Dietary intake of soy protein isolate has been found to reduce circulating insulin levels in rats. Dietary soy has also been found to reduce atherosclerotic plaque development in male monkeys. Several studies have found that rats with carcinogen-induced colon cancer that were fed soy protein isolate had reduced tumor incidence compared to control diets. The reduction in colon tumor incidence in soy protein isolate-fed rats was found to be associated with reduced circulating insulin and leptin in one study. One population study of soy consumption and thyroid cancer risk conducted in the San Francisco Bay Area found that consumption of traditional and nontraditional soy-based foods were associated with reduced risk of thyroid cancer. However, consumption of "Western" foods with added soy flour or soy protein did not affect thyroid cancer risk. Soy protein isolate consumption has been found to have potentially beneficial impact on prostate cancer progression in some studies.
Estrogen is antiresorptive on the skeleton. Hence, the lower estrogen levels associated with menopause typically result in bone loss. Diets supplemented with soy isoflavones or isoflavone-rich soy protein isolate have not been found to prevent bone resorption in postmenopausal women. However, in a study comparing the effects of diets with casein, soy protein isolate, whey protein hydrolysate and rice protein isolate on bone in intact growing female rats and in ovariectomized rats showing signs of sex steroid deficiency-induced bone loss, soy protein isolate was found to have the greatest positive effects in both intact and ovariectomized rats. Soy protein isolate increased serum bone formation markers but suppressed bone resorption markers. It is possible that consumption of soy protein isolate low in soy isoflavones may improve postmenopausal bone health but more studies are required to determine whether this is the case.
Breast cancer-related effects of consuming soy protein isolate
Evidence concerning the impact of soy protein isolate on breast cancer risk consists of animal studies and human experiments. Population studies concerning any possible association between soy protein isolate and risk of breast cancer are not available, which is especially unfortunate since experimental studies have produced conflicting findings.
A diet containing an isoflavone-poor soy protein concentrate was found to inhibit breast tumor progression more effectively than isoflavone-rich soy protein diets in Her2/neu transgenic mice. The same diet also reduced lung metastases compared to isoflavone-rich soy protein diets. The results indicated that it was not the phytoestrogens in soy (such as genistein or daidzein) that were responsible for its anti-cancer properties.
Feeding soy protein isolate to female rats has been shown in several studies to decrease carcinogen-induced mammary tumor incidence. The female offspring of the rats in one of these studies were found to have smaller mammary fat cells, lower abdominal fat mass and lower overall body weight. Another study found that while rats fed a soy protein isolate diet had a lower tumor incidence than rats fed a control diet, the tumors had more invasive characteristics. The authors ascribed the increased invasiveness to a higher ratio of progesterone receptor A to progesterone receptor B in the soy protein isolate group, accompanied by increased levels of HER-2/neu oncogene. Still another study found that soy protein isolate stimulated estrogen positive breast tumor growth and increased uterus weight in ovariectomized mice. Yet another study found that a high soy protein diet increased mitosis (leading to cell division) in the mammary glands of rats. The change in proliferation was associated with increased estrogen receptor α (ERα) and decreased estrogen receptor β (ERβ) expression.
A one-year, 1996 study of the effects of soy protein isolate consumption in women that measured changes in nipple aspirate fluid and plasma hormones, cholesterol and triglycerides found that prolonged consumption of soy protein isolate with a defined level of genistein had little effect on postmenopausal women. However, a stimulatory effect on the breasts of the premenopausal women was observed, characterized by increased secretion of breast fluid, the appearance of hyperplastic epithelial breast cells, and increased levels of plasma estradiol. The authors note that these findings did not support their a priori hypothesis that soy protein isolate consumption would be protective against breast cancer.
Additional comments
The U.S. Food and Drug Administration is in the process of investigating the levels of furan in soy protein isolate and other foods. Furan, which has been found in soy protein isolate, is a toxin which is a possible human carcinogen (furan is carcinogenic in rats and mice) and has been found as a byproduct of heat treatment during processing of various foods.
Selected studies
Early Soy Exposure via Maternal Diet Regulates Rat Mammary Epithelial Differentiation by Paracrine Signaling from Stromal Adipocytes Journal of Nutrition, May 2009The present study was designed to evaluate the contributions of soy protein isolate versus casein in the maternal diet to the mammary tissues of weanling rats. Diet may influence changes in the early differentiation of the mammary gland that could possibly lead to reduced breast cancer risk. The differences in breast cancer rates between Asian and Western women has been attributed in part to high Asian soy food consumption. In the study, genome-wide profiling of mammary tissues of weanling rats exposed to soy protein isolate or control casein (milk protein) via maternal diet was performed to evaluate the impact of very early exposure on mammary gene expression. Of the identified 18 upregulated and 39 downregulated genes with soy protein isolate relative to casein, a subset was found to be associated with smaller mammary adipocyte (fat cell) size, suggesting stromal adipocyte-specific genomic effects. Female offspring of the rats fed soy protein isolate were found to have a tendency to have fewer terminal end buds and had significantly lower abdominal fat mass and overall body weight. Further testing found that in differentiated 3T3-L1 adipocytes, genistein reduced fatty acid synthase and stearoyl-CoA desaturase and increased hydroxysteroid 11-β dehydrogenase 1 expression. The authors conclude that soy-associated components influence mammary epithelial differentiation by targeting mammary adipocytes, with important implications for the prevention of breast cancer associated with obesity and obesity-related diseases.
Isoflavones in urine, saliva, and blood of infants: data from a pilot study on the estrogenic activity of soy formula Journal of Exposure Science & Environmental Epidemiology, February 2009
The current study was designed to examine infants' exposure to isoflavones from different feeding methods. The study included 166 full-term infants between birth and one year of age that were divided into soy formula, cow's milk formula, or breast milk groups according to their feeding histories. A total of 361 saliva, 381 urine, and 88 blood samples were obtained during 382 visits. It was found that daidzein and genistein were undetectable in most blood or saliva samples from the infants fed breast milk or cow's milk formula. Equol was detectable only in a few urine samples. Urinary concentrations of genistein and daidzein were found to be approximately 500 times higher in the soy formula-fed infants than in the cow's milk formula-fed infants. However, the authors did not find significant correlations between phytoestrogen concentrations and the levels of certain hormones in the infants on soy formula. The authors comment that whether phytoestrogens in soy formula are biologically active in infants is still an open question.
A comparison of the effects of soya isoflavonoids and fish oil on cell proliferation, apoptosis and the expression of oestrogen receptors α and β in the mammary gland and colon of the rat British Journal of Nutrition, December 2008
The current study investigated the impact of soybean-derived isoflavonoids and omega-3 fatty acids from fish oil on apoptosis, proliferation and estrogen receptor (ER) expression in the colon and mammary glands of laboratory rats. Female rats were fed diets high in omega-3 fatty acids (80 g/kg diet) or soy protein (765 mg/kg diet isoflavones) for two weeks, then sacrificed in advance of removal of their colons and mammary glands. Cell proliferation and apoptosis were assessed and ERα and ERβ expression were measured in colon tissue and mammary glands. Fish oil was found to significantly increase apoptosis and decrease mitosis in both types of tissue. These effects were associated with a decrease in the expression of both ERα and ERβ. Soy was found to have no effect on apoptosis in either tissue, but did reduce mitosis in the colon while increasing it in the mammary gland. The changes in proliferation were associated with contrasting changes in ER expression: fish oil significantly decreased both ERα and ERβ, whereas soy increased ERα and decreased ERβ. The authors conclude that the results may provide a mechanism by which omega-3 acids could reduce cancer risk. The interpretation of the results in relation to soy consumption and breast cancer risk requires further investigation.
Reduced mammary tumor progression in a transgenic mouse model fed an isoflavone-poor soy protein concentrate Molecular Nutrition & Food Research, October 2008
The present study was designed to examine the effects of soy-based diets in Her2/neu transgenic mice. Soy isoflavones and protein components (e.g., protease inhibitors and the lunasin peptide) have been proposed as potential agents reducing cancer incidence. Neu overexpressing female mice were divided into groups and fed one of the following diets for 20 weeks: (1) a soy- and isoflavone-free diet (control); (2) 4RF21 laboratory mouse diet which is soy-based, and thus isoflavone-rich (isoflavone-rich); (3) AIN-76-based semisynthetic diet with a soy protein isolate (soy protein isolate); or (4) an isoflavone-poor soy protein concentrate (isoflavone-poor soy protein) as protein source. The mice were then sacrificed and tumors removed for examination. Mammary tumor weights were found not to differ in rats fed soy protein isolate or isoflavone-rich diets versus the control diet. In contrast, mice fed isoflavone-poor soy protein were found to have reduced tumor progression versus the control and isoflavone-rich groups (p < 0.05). Notably, isoflavone-poor soy protein fed mice had lower bromo-2'-deoxyuridine (a marker of cell proliferation) incorporated into breast tumor cells compared to the isoflavone-rich and soy protein isolate fed animals (p < 0.02). Lung metastases were found in 80% of the control fed mice, 70% of mice fed isoflavone-rich or soy protein isolate diets, but only in 50% of the isoflavone-poor soy protein fed mice. These results indicate that a diet containing an isoflavone-poor soy protein concentrate may inhibit breast tumor progression and metastasis development.
Enhanced Progesterone Receptor A expression by dietary soy in a hormone-dependent (NMU) model of rat mammary carcinogenesis: implications for tumor progression Proceedings of American Association for Cancer Research (AACR), Volume 47, 2006
The current study was designed to examine serum progesterone levels and progesterone receptor expression in normal mammary glands and corresponding mammary tumors in rats fed a soy protein isolate or casein diet (control diet). Previously, the authors showed that lifetime exposure of Sprague-Dawley rats to a diet made with soy protein isolate as the only protein source protected against chemically-induced mammary tumorigenesis, relative to the control (casein) diet. However, in the soy protein isolate-fed rats that developed tumors, there was a higher proportion of tumors with infiltrating ductal carcinoma (IDC) than with ductal carcinoma in situ (DCIS), compared to the tumors of the casein-fed rats. This suggests potential unfavorable effects of soy components on tumor progression. The present study focused on progesterone. An inverse associated between serum progesterone levels and breast cancer risk has been reported in premenopausal women. Also, the breast tissue of women consuming dietary soy supplements has been reported to have increased progesterone receptor (PR) expression, whereas the breast tissue of women on soy-based diets has been found to be decreased. In the study, the expression of progesterone receptor A (PR-A) and progesterone receptor B (PR-B) isoforms in pathologically normal mammary glands and corresponding mammary tumors (IDC and DCIS) were evaluated. In addition, the serum progesterone levels of rats fed soy protein isolate or casein and exposed to the carcinogen N-nitroso-N-methylurea (NMU) were examined. PR-A levels were found to be higher in normal mammary glands in the soy protein isolate-fed rats than in the casein group, while PR-B levels did not differ with diet. The ratio of PR-A/PR-B was four-fold higher in the soy protein isolate relative to the casein group in normal mammary glands, but was not different in tumor tissues. The increased PR-A/PR-B ratio in the soy protein isolate group was accompanied by increased levels of HER-2/neu oncogene, whose up-regulated expression is reported in invasive breast cancers. Serum progesterone levels were found to be significantly lower (P<0.01) in tumor-bearing rats fed soy protein isolate than those fed casein, while no differences (P=0.259) were observed for serum estrogen. The authors comment that since breast cancer patients with mammary PR-A greater than PR-B expression have been found to be less responsive to endocrine therapy than those with higher PR-B expression, the finding of increased expression of PR-A with dietary soy in rats with NMU-induced tumors may have important implications for women with benign or malignant breast cancer consuming soy-based diets.
Soy processing influences growth of estrogen-dependent breast cancer tumors Carcinogenesis, May 2004
The current study was designed to investigate the ability of various soy products containing genistin (the glycoside form of genistein) to affect the growth of MCF-7 breast cancer cells transplanted into ovariectomized mice. Soybean-based products consumed in Asian countries are minimally processed whereas in the U.S. many soy foods and soy ingredients are highly processed. The soy products investigated included soy flour, two crude extracts of soy (soy molasses and Novasoy®), a mixture of isoflavones, and genistin in pure form. Each of the soy flour products was added to the mouse diet in a manner designed to provide equivalent amounts of genistein equivalents. Tumors in the negative control animal group regressed throughout the study while the tumors in the soy flour-fed animals remained basically the same size (neither grew nor regressed). However, in mice consuming soy molasses, Novasoy®, mixed isoflavones or genistin alone, tumor growth was found to be stimulated compared to animals consuming a control diet devoid of soy. These dietary treatments also resulted in increased cellular proliferation. In further testing, changes in mRNA expression of gene targets (estrogen responsiveness, cell cycle progression, apoptosis and aromatase activity) in tumors induced by the different diets were evaluated. The relative expression of pS2, progesterone receptor and cyclin D1 was higher in animals consuming the Novasoy®, mixed isoflavones and genistin. Bcl2 mRNA expression was low in most of the dietary treatment groups compared to positive (estradiol implant) controls. Aromatase expression was not altered in any of the treatment groups. The authors conclude that the degree of soy flour processing impacts the estrogenicity of products containing a constant amount of genistein. The findings suggest that for postmenopausal women with estrogen-dependent breast cancer, consumption of foods containing soy flour is more advisable than consuming isoflavones in more purified forms.
Developmental Effects and Health Aspects of Soy Protein Isolate, Casein, and Whey in Male and Female Rats International Journal of Toxicology, May 2001
The present study was designed to evaluate the effects of diets containing mainly casein, soy protein isolate, or whey as protein sources by means of short-term, long-term, and multigenerational studies in rats. Soy protein isolate, casein and whey all are used as the major proteins in the infant formulas sold in the U.S. Concerns have developed over soy-based infant formula, in part because of the potential impact of phytoestrogens during important periods of infant development. The current study found only minor differences in body weight gain profiles in the casein-, soy protein isolate- and whey-fed rats and the three groups of rats did not differ in development, organ weights, hepatic metabolism of testosterone, or reproductive performance. However, some endocrine-related processes varied between the rats fed different diets. The soy protein isolate diet was found to accelerated puberty in female rats ( p <.05), whereas whey delayed puberty in both males and females, compared to casein ( p <.05). Male rats fed soy protein isolate were found to have normal serum testosterone levels, but female rats fed the same diet had reduced serum 17 β-estradiol concentrations and a blunted 17 β-estradiol response to ovariectomy, compared to rats fed casein or whey (p <.05). Female rats fed soy protein isolate or whey or treated with genistein were found to have reduced incidence of carcinogen-induced mammary tumors ( p <.05) compared to casein fed rats. Whey reduced tumor incidence by as much as 50%. The findings suggest certain gender-specific differences in development and endocrine responses among rats fed diets containing a single protein source. Whether similar effects occur in human infants fed single-source protein formula is unknown, however no such effects have been reported U.S. infants fed formula containing these proteins. The authors conclude that the long-term health consequence implications of early diet exposure to soy protein isolate and whey, such as reduced breast cancer incidence, are likely to be very positive.
