How many isoflavones per day

Doerge Doerge, D. Toxicology and Applied Pharmacology, 2 , Genistein crosses over the placenta of rats and may reach the fetal brain; in these animals, this phenomenon occurs with maternal serum concentrations very similar to those observed in humans who consume soy-based foods and dietary supplements.

Toxicological and exposure assessment of rats treated with genistein have demonstrated chronic adverse effects such as an increased incidence of breast fibroadenoma or carcinoma and accelerated reproductive senescence. A particularly relevant fact is that the diet of some babies exclusively consists of infant soy formula.

Vandenplas et al. Safety of soya-based infant formulas in children. British Journal of Nutrition, 8 , Soy infant formula: is it that bad? Acta Paediatrica Oslo, Norway : , 2 , The circulating isoflavone concentrations of these babies overlap those detected in rats fed high genistein doses which exhibited the adverse effects mentioned above.

The small margin of exposure between the doses of genistein that produce demonstrable adverse effects in experimental animal models and in formula-fed babies suggests that the possibility of adverse effects should be considered, but studies in humans are necessary.

Johnson et al. Effects of soy protein-based formula in full-term infants. American Family Physician, 77 1 , Soy, phyto-oestrogens and male reproductive function: a review.

International Journal of Andrology, 33 2 , It is relevant to assert that beneficial effects of soy have been reported even with its early use in infant formulas. Donovan et al. Soy formula and isoflavones and the developing intestine. Nutrition Reviews, 67 Suppl. In another study, Vandenplas et al. They observed that, despite the high quantities of phytates and aluminum in the soy formulas, the anthropometric patterns of the infants were similar to those of infants fed standard formulas, as also were their concentrations of hemoglobin, serum proteins, zinc and calcium, and the bone mineral content.

Although genistein and daidzein concentrations were higher in children fed soy formula, no evidence of a negative effect on reproductive or endocrine function was detected. In addition, the immunological evaluations and the neurocognitive parameters were similar in all groups. In view of the controversial results presented, some studies Zeiger et al. The Journal of Pediatrics, 5 , These formulas present some differences in their composition when compared to formulas based on cow's milk Kemp, Kemp, A.

Hypoallergenic formula prescribing practices in Australia. Journal of Paediatrics and Child Health, 42 4 , They have more protein 2. The National Toxicology Program of the US Department of Health and Human Services concluded that the possibility of long-term or discrete adverse events on human development or reproduction cannot be ruled out. Although events of this nature have not been described after more than 40 years of using soy protein-based formulas in the United States, this subject has never been properly studied McCarver et al.

Birth Defects Research. Part B, Developmental and Reproductive Toxicology, 92 5 , Soy food consumption and breast cancer. Maturitas, 76 2 , This is due to the main bioactive component of soy, isoflavone, which is considered a phytohormone that acts both to present estrogenic effect and to inhibit this activity Franke et al.

Absorption, distribution, metabolism, and excretion of isoflavonoids after soy intake. Archives of Biochemistry and Biophysics, , Impact of soy foods on the development of breast cancer and the prognosis of breast cancer patients. Forschende Komplementarmedizin, 23 2 , This is relevant if considered the role of estrogen in the development, progression and treatment of some breast cancers.

Several investigators have observed that soy has an anti-cancer effect and that isoflavone has antiestrogen properties, thus having a protective effect against estrogen-sensitive cancers Douglas et al.

Soy and its isoflavones: the truth behind the science in breast cancer. Anti-cancer Agents in Medicinal Chemistry, 13 8 , Soy isoflavones, estrogen therapy, and breast cancer risk: analysis and commentary. Nutrition Journal, 7 1 , The fact that this protective effect seems to be always more evident among Asian women has not been explained, but it is speculated that this may be due to factors such as the microbiota, an early beginning of soy consumption, a high intake, and its use in less processed foods Kim, Kim, J.

Protective effects of Asian dietary items on cancers - soy and ginseng. Asian Pacific Journal of Cancer Prevention, 9 4 , Factors to consider in the association between soy isoflavone intake and breast cancer risk. Journal of Epidemiology, 20 2 , Biomedical applications of soy protein: a brief overview. Journal of Biomedical Materials Research. Part A, 2 , Soy isoflavones and human health: breast cancer and puberty timing.

Revista Medica de Chile, 4 , Nagata Nagata, Nagata, C. Other factors in addition to the amount consumed seem to modify the association between soy isoflavone intake and breast cancer risk, among them the form and source, time of exposure, status of estrogen receptors, and production and hormonal profile of the persons Nagata et al.

Soy intake and breast cancer risk: an evaluation based on a systematic review of epidemiologic evidence among the Japanese population. Japanese Journal of Clinical Oncology, 44 3 , Although, theoretically, the estrogenic effect of isoflavone represents a risk for estrogen-sensitive neoplasias, this aspect has not been confirmed. Studies have demonstrated that isoflavone consumption does not change the markers of cancer risk such as density assessed by mammography and cell proliferation.

According to Messina a Messina, M. In Wu et al. Epidemiology of soy exposures and breast cancer risk. British Journal of Cancer, 98 1 , Finally, there was no conclusion about whether habitual soy intake or short-term soy supplementation influences the levels of circulating hormones or the mammographic density. In a review article, Hilakivi-Clarke et al. Is soy consumption good or bad for the breast? The Journal of Nutrition, 12 , ss. The authors also observed that moderate consumption of a diet containing genistein did not increase the risk of breast cancer recurrence in western women and, finally, Asian survivors of breast cancer had a better prognosis of the disease when they continued to consume soy-rich diets.

Cumulative exposure to high quantities of estrogen is a known risk factor for breast cancer, with early puberty, late menopause and hormone replacement therapy being part of this situation. Valladares et al. Soy isoflavones consumption and risk of breast cancer incidence or recurrence: a meta-analysis of prospective studies. Breast Cancer Research and Treatment, 2 , Soy isoflavone consumption was also inversely associated with the risk of breast cancer recurrence.

Stratified analyses have suggested that menopausal status may have an important modifying effect on these associations and were unable to identify a dose-response relationship. In a meta-analysis study Chen et al. Association between soy isoflavone intake and breast cancer risk for pre- and post-menopausal women: a meta-analysis of epidemiological studies. PLoS One, 9 2 , e However, in western pre or postmenopausal women there was no evidence suggesting an association between soy isoflavone intake and breast cancer.

Soy products in the management of breast cancer. In addition, they reported that soy does not interfere with the action of tamoxifen or anastrozole, the drugs used for treatment. The studies analyzed also permitted the conclusion that women with polymorphisms that increase the risk of breast cancer may benefit from the consumption of high doses of isoflavones.

Nagata et al. In a review of cohort studies Eakin et al. The Journal of Family Practice, 64 10 , According to Varinska et al. Soy and breast cancer: focus on angiogenesis.

International Journal of Molecular Sciences, 16 5 , Genistein inhibits enzymes such as tyrosine kinase, DNA topoisomerase II, 5-alpha-reductase, galectin, histidine-protein kinase and cyclin-dependent kinases, all of them involved in cell replication. In addition, genistein has a potent inhibitory effect on angiogenesis, which is considered to be one of the fundamental elements for tumor growth, invasive capacity and metastatic potential.

In a meta-analysis Myung et al. Soy intake and risk of endocrine-related gynaecological cancer: a meta-analysis. BJOG, 13 , Zhang et al. Soy intake is associated with lower endometrial cancer risk: a systematic review and meta-analysis of observational studies.

Medicine, 94 50 , e According to Jian Jian, L. Soy, isoflavones, and prostate cancer. In a review study of , van Die et al. Soy and soy isoflavones in prostate cancer: a systematic review and meta-analysis of randomized controlled trials. Applegate et al. Soy consumption and the risk of prostate cancer: an updated systematic review and meta-analysis.

Nutrients, 10 1 , Influence of isoflavone intake and equol-producing intestinal flora on prostate cancer risk. Asian Pacific Journal of Cancer Prevention, 14 1 , Mahmoud et al. Soy isoflavones and prostate cancer: a review of molecular mechanisms. In addition, they described other effects at the molecular level such as antioxidant defense, DNA repair, inhibition of angiogenesis and metastasis, potentiating of chemotherapeutic and radiotherapeutic agents, and estrogen antagonism. In a meta-analysis study Yu et al.

Soy isoflavone consumption and colorectal cancer risk: a systematic review and meta-analysis. Scientific Reports, 6 1 , The effect was more significant with the consumption of soy-based foods rather than isoflavone alone among Asian people.

Other properties of isoflavones not related to the action of a phytohormone e. In a review study conducted on , participants and 13, patients with gastrointestinal cancer Tse et al. Soy and isoflavone consumption and risk of gastrointestinal cancer: a systematic review and meta-analysis. European Journal of Nutrition, 55 1 , However, when the analysis was carried out in relation to the intake of isoflavone, a significant overall reduction of risk to develop cancer of the digestive tract was observed, particularly regarding colorectal cancer.

Soy isoflavones sensitize cancer cells to radiotherapy. In view of its numerous components isoflavones, saponins, protein substances, lecithin and flavonoids , soy has been extensively studied in terms of its effects on the cardiovascular system Imai, Imai, S.

Soybean and processed soy foods ingredients, and their role in cardiometabolic risk prevention. The mortality rates due to cardiovascular disease are lower in Asian countries than in western countries, a characteristic believed to be linked to the consumption of soy as a basic food for the population Gil-Izquierdo et al.

Soy isoflavones and cardiovascular disease epidemiological, clinical and -omics perspectives. Current Pharmaceutical Biotechnology, 13 5 , Soy protein effects on serum lipoproteins: a quality assessment and meta-analysis of randomized, controlled studies. Journal of the American College of Nutrition, 30 2 , You can see that two to three servings per day keeps you within the range of soy studied. While Peterson is a fan of whole soy, she is leery of isolated soy protein since it is so concentrated.

Peterson refers to one small study without a control group that included young healthy males. The study found that two scoops of pure soy protein powder 56 grams decreased blood testosterone levels by 19 percent after four weeks.

T levels increased within two weeks of skipping the protein powder. However, the protective benefits of soy were only observed in Asian women, while Western women appeared to experience little benefit Based on these studies, a proportion of women eating soy-rich diets may benefit from a lower risk of breast cancer.

Still, more studies are needed to determine which women may benefit the most. Soy-rich diets may also help lower the risk of other types of cancer. On the other hand, men eating soy-rich diets may benefit from a lower risk of prostate cancer Soy-rich diets may improve heart health and lower blood pressure, blood sugar, and cholesterol levels. They may also improve fertility, reduce symptoms of menopause, and protect against certain cancers.

However, more research is needed. Soybeans and foods derived from them have been part of the human diet for centuries. Nevertheless, some people worry about including soy in their diet due to the following areas of concern:. Keep in mind that while these concerns are common, few of them are supported by sound science.

Moreover, when negative effects have been observed, they often followed the consumption of very large amounts of soy. For instance, men who reported experiencing feminizing effects from soy consumed amounts up to 9 times larger than the average intake of men with soy-rich diets.

Although possible, it would be difficult for most people to eat that much soy each day The concerns above are commonly cited when it comes to soy. Generally, few are supported by strong science, and more research is needed to confirm the remaining.

Generally, the less processed a soy food is, the more vitamins, minerals, and beneficial compounds it may contain. On the other hand, the more processed a soy food is, the more salt, sugar, fat, and unnecessary additives and fillers it likely contains.

Minimally processed soy foods may also offer benefits beyond those associated with their nutrient content. For instance, they appear more effective at reducing blood sugar or cholesterol levels than processed soy-based foods or supplements 13 , In addition, fermented soy foods, such as soy sauce, tempeh , miso, and natto, are often considered more beneficial than non-fermented soy products. Cooking, sprouting, and soaking are additional preparation techniques that can help reduce the antinutrient content of soy foods and enhance their digestibility 60 , 61 , 62 , Minimally processed soy foods, such as soybeans, tofu, tempeh, edamame, and unsweetened soy milks and yogurts, are considered superior to highly processed ones.

Fermented soy foods may offer additional benefits. Soybeans are rich in nutrients and beneficial plant compounds. Although diets rich in soy or soy-containing products appear safe and potentially beneficial, the long-term safety of very high supplemental doses of soy isoflavones is not yet known. Yet, longer-term studies are needed to evaluate the safety of isoflavones.

The safety of high intakes of soy isoflavones and other phytoestrogens for breast cancer survivors is an area of concern among scientists and clinicians. A few large prospective cohort studies have examined the association between soy isoflavone intake and breast cancer recurrence and survival. In the Shanghai Breast Cancer Survival Study that followed 5, female breast cancer survivors for a median of 3.

A subgroup analysis showed that the inverse association between soy isoflavone intake and recurrence was significant only among women taking the anticancer drug, tamoxifen. No inverse association was reported between soy isoflavone intake and the risks of all-cause and breast cancer-specific mortality Nevertheless, there is not enough evidence to discourage breast cancer survivors from consuming soy foods in moderation , Infant formula made from soy protein isolate has been commercially available since the mids Soy protein-based formulas are especially indicated for infants with galactosemia and hereditary lactase deficiency, but they have no proven value in the prevention or management of infantile colic and fussiness Since infants fed soy-based formulas are exposed to relatively high levels of isoflavones , which they can absorb and metabolize , concern has been raised regarding potential long-term effects on anthropometric growth, bone health, as well as reproductive, endocrine , and immune functions , In addition to the AAP review , a recent systematic review and meta-analysis of data published between and found no clinical concerns regarding nutritional adequacy, sexual development, thyroid disease, immune function, and neurodevelopment in infants fed soy protein-fed formulas In addition, the results of three observational studies suggested no adverse effects of soy protein-based formula on the neurodevelopment of children Two of these observational studies of low-to-moderate quality also reported associations between soy protein-based formula intake and marginal adverse events, including early menarche , and increased duration of menstrual bleeding Finally, no adverse health effects have been associated with the presence of phytates and aluminum in soy protein-based formulas fed to full-term infants reviewed in Nonetheless, if current evidence shows a safety profile for use of soy protein-based formulas in term infants, they are not designed or recommended for preterm infants Also, recent preliminary findings suggesting potential links between consumption of soy protein-based formulas and adverse effects in autistic children deserve further investigation , Exposure to isoflavones including at levels above typical Asian dietary intakes has not been shown to affect either the concentrations of estrogen and testosterone, or the quality of sperm and semen , Thorough reviews of the literature found no basis for concern but emphasized the need for long-term, large scale comprehensive human studies , In cell culture and animal studies, soy isoflavones have been found to inhibit the activity of thyroid peroxidase, an enzyme required for thyroid hormone synthesis , However, high intakes of soy isoflavones do not appear to increase the risk of hypothyroidism as long as dietary iodine consumption is adequate Since the addition of iodine to soy-based formulas in the s, there have been no further reports of hypothyroidism in soy formula-fed infants Several clinical trials , mostly in women with sufficient iodine intakes, have not found increased consumption of soy isoflavones to result in clinically significant changes in circulating thyroid hormone concentrations To date, studies have not examined the effect of an isoflavone-rich diet on fetal development or pregnancy outcomes in humans, and the safety of isoflavone supplements during pregnancy has not been established.

Fermented soy foods contain highly variable amounts of the biologically active amine, tyramine, which is catabolized in the body by monoamine oxidase enzyme MAO and excreted in the urine. The ingestion of very high amount of tyramine may saturate the detoxification system and lead to clinical symptoms of intoxication.

Because individuals taking MAO inhibitors MAOIs; phenelzine, tranylcypromine are at greater risk of adverse effects, they should avoid consuming fermented soy products , Because colonic bacteria play an important role in the metabolism of soy isoflavones, antibiotic therapy could decrease their biological activity Some evidence from animal studies suggested that high intakes of soy isoflavones, particularly genistein, could interfere with the antitumor effects of tamoxifen Nolvadex Yet, a recent pooled analysis of three prospective cohort studies found that the risk of recurrence in breast cancer survivors was reduced to a greater extent with soy isoflavone intake in tamoxifen users than in nonusers see Safety for breast cancer survivors Nonetheless, until more is known about potential interactions in humans, those taking tamoxifen or other selective estrogen receptor modulators SERMs to treat or prevent breast cancer should be cautious and seek medical advice regarding the use of soy protein supplements or isoflavone extracts High intakes of soy protein may interfere with the efficacy of the anticoagulant medication warfarin.

INR values returned to therapeutic levels two weeks after discontinuing soy milk. The amount of levothyroxine required for adequate thyroid hormone replacement has been found to increase in infants with congenital hypothyroidism fed soy formula , Taking levothyroxine at the same time as a soy protein supplement also increased the levothyroxine dose required for adequate thyroid hormone replacement in an adult with hypothyroidism Regular consumption of a diet high in soy — rather than supplementation with isoflavone extracts or isoflavone containing isolated soy protein — may help lower fasting glucose concentrations It is unknown whether individuals taking antidiabetic agents might be at risk of hypoglycemia if they follow a soy-based meal replacement plan rather than a diet plan recommended by the American Diabetes Association Originally written in by: Jane Higdon, Ph.

Updated in January by: Jane Higdon, Ph. Updated in December by: Victoria J. Drake, Ph. Updated in August by: Barbara Delage, Ph. Reviewed in October by: Alison M. Duncan, Ph. Lampe JW. Isoflavonoid and lignan phytoestrogens as dietary biomarkers. J Nutr. Absorption, distribution, metabolism, and excretion of isoflavonoids after soy intake. Arch Biochem Biophys. Acute benefits of the microbial-derived isoflavone metabolite equol on arterial stiffness in men prospectively recruited according to equol producer phenotype: a double-blind randomized controlled trial.

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