1: Biofactors 2000;12(1-4):209-15 
Isoflavonoids and chronic disease: mechanisms of action. Barnes S, Boersma B, Patel R, Kirk M, Darley-Usmar VM, Kim H, Xu J. Department of Pathology, University of Alabama at Birmingham, 35294, USA. Soy and its isoflavones are associated with a reduced risk of chronic disease. The mechanisms of action of isoflavones include their roles as weak estrogens, inhibitors of tyrosine kinase-dependent signal transduction processes and as cellular antioxidants. Although estrogen receptor beta binds genistein with an affinity close to that of 17beta-estradiol, it remains to be determined whether it is a mediator of genistein's activity in vivo. Genistein's inhibition of protein tyrosine kinases is not limited to direct effect on these kinases, but may result from alteration in kinase expression. Genistein is not a particularly good scavanger of cellular oxidants; however, it reacts vigorously with the prooxidant hypochlorous acid, produced by neutrophils as part of the inflammatory response. The chlorinated isoflavones may have altered biochemical and biological effects compared to their parent compounds and may provide increased protection against inflammatory disease. 
Publication Types:
Review
Review, tutorial 
PMID: 11216488 [PubMed - indexed for MEDLINE]
2: Baillieres Clin Endocrinol Metab 1998 Dec;12(4):559-79 
Phytoestrogens and breast cancer.
Barnes S. 
Department of Pharmacology and Toxicology, University of Alabama at Birmingham, USA. 
Phytoestrogens are paradoxical. Because of their structural similarity to the physiological oestrogens, they have been assumed to increase the risk of breast cancer. However, nations where the largest amounts of phytoestrogens are consumed in the diet have the lowest incidence of and rate of death from breast cancer. Although these epidemiological observations do not prove that phytoestrogens have anti-cancer properties, many preclinical experiments support this concept. Some indicate that early life exposure to phytoestrogens may be critical for breast cancer prevention. Clinical studies to define the effect of phytoestrogens on breast cancer recurrence are underway. The recent discovery of a second class of oestrogen receptors, with a differential distribution among the tissues, may enable an explanation of the phytoestrogen paradox. These receptors have opened a way of utilizing phytoestrogens in the treatment of oestrogen-sensitive chronic diseases such as atherosclerosis and osteoporosis. 
Publication Types:
Review
Review, academic 
PMID: 10384813 [PubMed - indexed for MEDLINE]
3: Am J Clin Nutr 1998 Dec;68(6 Suppl):1486S-1491S 
Chemical modification of isoflavones in soyfoods during cooking and processing. 
Coward L, Smith M, Kirk M, Barnes S. 
Department of Pharmacology & Toxicology and the Comprehensive Cancer Center Mass Spectrometry Shared Facility, University of Alabama at Birmingham, 35294, USA. 
The principal chemical forms of isoflavones in soybean are their 6''-O-malonyl-beta-glucoside (6OMalGlc) conjugates. Experiments were carried out to determine the best conditions for extraction of isoflavones from soyfoods and the effects of commercial processing procedures and of cooking on isoflavone concentrations and composition. Hot alcohol extraction of ground soybeans deesterified 6OMalGlc conjugates. Although room temperature extraction slowed the conversion, extraction at 4 degrees C for 2-4 h led to the highest yield of 6OMalGlc conjugates and the lowest proportion of beta-glucoside conjugates. Analysis of soyfood products by reversed-phase HPLC-mass spectrometry revealed that defatted soy flour that had not been heat treated consisted mostly of 6OMalGlc conjugates; in contrast, toasted soy flour contained large amounts of 6''-O-acetyl-beta-glucoside conjugates, formed by heat-induced decarboxylation of the malonate group to acetate. Soymilk and tofu consisted almost entirely of beta-glucoside conjugates; low-fat versions of these products were markedly depleted in isoflavones. Alcohol-washed soy-protein concentrates contained few isoflavones. Isolated soy protein and textured vegetable protein consisted of a mixture of all 3 types of isoflavone conjugates. Baking or frying of textured vegetable protein at 190 degrees C and baking of soy flour in cookies did not alter total isoflavone content, but there was a steady increase in beta-glucoside conjugates at the expense of 6OMalGlc conjugates. The chemical form of isoflavones in foods should be taken into consideration when evaluating their availability for absorption from the diet. 
PMID: 9848521 [PubMed - indexed for MEDLINE]
4: Breast Cancer Res Treat 1997 Nov-Dec;46(2-3):169-79 
The chemopreventive properties of soy isoflavonoids in animal models of breast cancer. 
Barnes S. 
Department of Pharmacology & Toxicology, University of Alabama at Birmingham 35294, USA. Stephen.Barnes@radonc.uab.edu Genistein (5,7,4'-trihydroxyisoflavone), one of two major isoflavonoids in soy, has anti-proliferative effects on mitogen-stimulated cell growth of human breast cancer cells in culture and is a candidate for use in the prevention of breast cancer. Soy protein preparations containing isoflavonoid conjugates have chemopreventive activity in carcinogen-induced rat models of breast cancer. Recent experiments in these models with purified genistein have revealed that the timing of the exposure of rats to this isoflavonoid is critical. Rats treated neonatally or prepuberally with genistein have a longer latency before the appearance of 7,12-dimethylbenz[a]anthracene-induced mammary tumors and a marked reduction in tumor number. The mechanism of genistein's preventive action is in part dependent on its estrogenic activity, which causes a more rapid differentiation of the cells of the mammary gland, and analogous to the effects of an early pregnancy. Rats administered genistein after 35 days of age have smaller alterations in breast cancer risk, with a maximum reduction in mammary tumor number of 27%. In ovariectomized nude mice, dietary genistein increases cell proliferation of human breast cancer MCF-7 cell xenografts compared with a control diet. This estrogen-like effect of genistein is not observed in non-ovariectomized rats. Future studies on the anticancer potential of soy isoflavonoids should examine their interaction with other phytochemical components of soybeans and exploit newly developed animal models of breast cancer in which specific genes have been activated or inactivated. 
Publication Types:
Review
Review, tutorial 
PMID: 9478272 [PubMed - indexed for MEDLINE]
5: Proc Soc Exp Biol Med 1998 Mar;217(3):386-92 
Evolution of the health benefits of soy isoflavones. Barnes S. Department of Pharmacology and Toxicology, University of Alabama at Birmingham, 35294, USA. Stephen.Barnes@pharmtox.uab.edu Soy is a unique dietary source of the isoflavones, genistein and daidzein. It has been part of the Southeast Asian diet for nearly five millenia, whereas consumption of soy in the United States and Western Europe has been limited to the 20th century. Heavy consumption of soy in Southeast Asian populations is associated with reduction in the rates of certain cancers and cardiovascular disease. Recent experimental evidence suggests that phytochemicals in soy are responsible for its beneficial effects, which may also include prevention of osteoporosis, a hereditary chronic nose bleed syndrome, and autoimmune diseases. Exposure of soy formula-fed infants to the potential estrogenizing effects of the isoflavones is limited by the first pass effect of the liver following the uptake of isoflavones from the gut. Several mechanisms of action of isoflavones have been proposed-both through estrogen-dependent and estrogen-independent pathways. 
PMID: 9492352 [PubMed - indexed for MEDLINE]
6: Cell Growth Differ 1996 Oct;7(10):1345-51 
Genistein inhibits both estrogen and growth factor-stimulated proliferation of human breast cancer cells. Peterson G, Barnes S. Department of Pharmacology and Toxicology, University of Alabama at Birmingham 35294, USA. 
Genistein is a naturally occurring dietary protein tyrosine kinase (PTK) inhibitor that is hypothesized to be responsible for the lower rate of breast cancer observed in Asian women consuming soy. Although genistein is a potent in vitro PTK inhibitor, its mechanism of action in vivo is not known. In vivo, breast cancer growth is regulated by estrogens and peptide growth factors, such as epidermal growth factor (EGF), the receptor of which has intrinsic PTK activity. Therefore, genistein may block mammary epithelial cell growth by interfering with signal transduction events stimulated by estradiol or growth factors. The effect of genistein, related isoflavones, and other tyrosine kinase inhibitors on fetal bovine serum-, estradiol-, and EGF-stimulated cell growth and signal transduction pathways was examined in five human breast cancer cell lines. Genistein inhibited the growth of these cells by each of the growth stimuli with IC50 values ranging from 2.6 to over 20 micrograms/ml. Growth inhibition by genistein was cytostatic and reversible at IC50 concentrations. Related isoflavones were less potent growth inhibitors than genistein, whereas the synthetic PTK inhibitor tyrphostin A25 was an equally potent growth inhibitor. The mechanism of genistein growth inhibition in human breast cancer cells did not depend on the presence of functional estrogen receptor signaling pathways or on inhibition of EGF-receptor PTK activity. Furthermore, genistein (< or = 20 micrograms/ml) did not decrease constitutive or EGF-induced tyrosine phosphorylation as determined by Western blotting with antiphosphotyrosine antibodies. These data suggest that although genistein inhibits the growth of breast cancer cells in culture, it does so without gross inhibition of PTK activity. PMID: 8891338 [PubMed - indexed for MEDLINE] 
7: Adv Exp Med Biol 1996;401:87-100 Soy isoflavonoids and cancer prevention. Underlying biochemical and pharmacological issues. 
Barnes S, Sfakianos J, Coward L, Kirk M. Departments of Pharmacology and Toxicology, University of Alabama at Birmingham 35294, USA. The isoflavonoids in soy, genistein and daidzein, have been proposed to contribute an important part of the anti-cancer effect of soy. Although there have been many interesting studies on the effects of isoflavones on biochemical targets in tissue culture experiments, in most cases the concentrations used by investigators have exceeded 10 microM. However, based on simple pharmacokinetic calculations involving daily intake of isoflavones, absorption from the gut, distribution to peripheral tissues, and excretion, it is unlikely that blood isoflavone concentrations even in high soy consumers could be greater than 1-5 microM. Experiments designed to evaluate these pharmacological principles were carried out in anesthetized rats with indwelling biliary catheters and in human volunteers consuming soy beverages. The data from these experiments indicate that genistein is efficiently absorbed from the gut, taken up by the liver and excreted in the bile as its 7-O-beta-glucuronide. Re-infused genistein 
7-O-beta-glucuronide was also well absorbed from the gut, although this occurred in the distal small intestine. In human subjects fed a soy beverage for a period of two weeks, plasma levels of genistein and daidzein, determined by HPLC-mass spectrometry, ranged from 0.55-0.86 microM, mostly as glucuronide and sulfate conjugates. In summary, genistein is well absorbed from the small intestine and undergoes an enterohepatic circulation. Although the plasma genistein levels achievable with soy food feeding are unlikely to be sufficient to inhibit the growth of mature, established breast cancer cells by chemotherapeutic-like mechanisms, these levels are sufficient to regulate the proliferation of epithelial cells in the breast and thereby may cause a chemopreventive effect. 
Publication Types:
Clinical trial 
PMID: 8886128 [PubMed - indexed for MEDLINE]
8: J Nutr 1995 Mar;125(3 Suppl):777S-783S 
Effect of genistein on in vitro and in vivo models of cancer. Barnes S. Department of Pharmacology, University of Alabama at Birmingham 35294. In two-thirds of studies on the effect of genistein-containing soy materials in animal models of cancer, the risk of cancer (incidence, latency or tumor number) was significantly reduced. In addition, purified genistein delayed mammary tumor appearance in association with increased cell differentiation in mammary tissue in rats treated with 7, 12-dimethylbenz[a]anthracene when administered neonatally, inhibited phorbol ester-induced H2O2 production in a model of skin cancer, and inhibited aberrant crypt formation in a model of colonic cancer. In in vitro models, genistein inhibited the proliferation of human tumor cell lines in culture with a wide variation in IC50 values (2.6-79 mumol/L, or 1-30 micrograms/mL). In only a few cases was the IC50 below 13.2 mumol/L (5 micrograms/mL), the presumed upper limit for the serum genistein concentration in those on a high soy diet. In future studies, greater emphasis should be placed on the effect of genistein on nontransformed, normal cell lines from the tissues where cancer can occur rather than established tumor cell lines. Similarly, the effect of genistein on the progression and/or promotion of cancer may be more clearly examined using nontransformed cell lines transfected with specific oncogenes thought to be activated during oncogenesis. Publication Types: 
Review
Review, tutorial 
PMID: 7884564 [PubMed - indexed for MEDLINE]
9: J Cell Biochem Suppl 1995;22:181-7 
Rationale for the use of genistein-containing soy matrices in chemoprevention trials for breast and prostate cancer. Barnes S, Peterson TG, Coward L. 
Department of Pharmacology, University of Alabama at Birmingham 35294, USA. 
Pharmacologists have realized that tyrosine kinase inhibitors (TKI) have potential as anti-cancer agents, both in prevention and therapy protocols. Nonetheless, concern about the risk of toxicity caused by synthetic TKIs restricted their development as chemoprevention agents. However, a naturally occurring TKI (the isoflavone genistein) in soy was discovered in 1987. The concentration of genistein in most soy food materials ranges from 1-2 mg/g. Oriental populations, who have low rates of breast and prostate cancer, consume 
20-80 mg of genistein/day, almost entirely derived from soy, whereas the dietary intake of genistein in the US is only 1-3 mg/day. Chronic use of genistein as a chemopreventive agent has an advantage over synthetic TKIs because it is naturally found in soy foods. It could be delivered either in a purified state as a pill (to high-risk, motivated patient groups), or in the form of soy foods or soy-containing foods. Delivery of genistein in soy foods is more economically viable ($1.50 for a daily dose of 50 mg) than purified material ($5/day) and would require no prior approval by the FDA. Accordingly, investigators at several different sites have begun or are planning chemoprevention trials using a soy beverage product based on SUPRO, an isolated soy protein manufactured by Protein Technologies International of St. Louis, MO. These investigators are examining the effect of the soy beverage on surrogate intermediate endpoint biomarkers (SIEBs) in patients at risk for breast and colon cancer, defining potential SIEBs in patients at risk for prostate cancer, and determining whether the soy beverage reduces the incidence of cancer recurrence.(ABSTRACT TRUNCATED AT 250 WORDS) 
PMID: 8538197 [PubMed - indexed for MEDLINE]
10: Proc Soc Exp Biol Med 1995 Jan;208(1):124-30 
Antioxidant and antipromotional effects of the soybean isoflavone genistein. 
Wei H, Bowen R, Cai Q, Barnes S, Wang Y. Department of Environmental Health Sciences, University of Alabama at Birmingham 
35294. 
Antioxidant and antipromotional effects of the soybean isoflavone genistein have been studied in HL-60 cells and the mouse skin tumorigenesis model. Effects of structure-related flavone/isoflavones on hydrogen peroxide (H2O2) production by 
12-O-tetradecanoylphorbol-13-acetate (TPA)-activated HL-60 cells and superoxide anion (O2-) generation by xanthine/xanthine oxidase were compared. Of tested isoflavones, genistein is the most potent inhibitor among TPA-induced H2O2 formation by (dimethyl sulfoxide) DMSO-differentiated HL-60 cells, daidzein is second, and apigenin and biochanin A show little effect. In contrast, genistein, apigenin, and prunectin are equally potent in inhibiting O2- generation by xanthine/xanthine oxidase, with daidzein showing a moderate inhibitory effect and biochanin A exhibiting no effect. These results suggest that the antioxidant properties of isoflavones are structurally related and the hydroxy group at Position 4' is crucial in both systems. Dietary administration of 250 ppm genistein for 30 days significantly enhances the activities of antioxidant enzymes in the skin and small intestine of mice. Further studies show that genistein significantly inhibits TPA-induced proto-oncogene expression (c-fos) in mouse skin in a dose-dependent manner. In a two-stage skin carcinogenesis study, low levels of genistein (1 and 5 mumol) significantly prolong tumor latency and decrease tumor multiplicity by approximately 50%. We conclude that genistein's antioxidant properties and antiproliferative effects may be responsible for its anticarcinogenic effect. Its high content in soybeans and relatively high bioavailability favor genistein as a promising candidate for the prevention of human cancers. PMID: 7892286 [PubMed - indexed for MEDLINE] 
11: Adv Exp Med Biol 1994;354:135-47 Potential role of dietary isoflavones in the prevention of cancer. Barnes S, Peterson G, Grubbs C, Setchell K. Department of Biochemistry, University of Alabama at Birmingham 35294. PMID: 8067282 [PubMed - indexed for MEDLINE] 
12: Nutr Cancer 1994;21(2):113-31 Soy intake and cancer risk: a review of the in vitro and in vivo data. Messina MJ, Persky V, Setchell KD, Barnes S. National Cancer Institute, National Institutes of Health, Bethesda, MD. International variations in cancer rates have been attributed, at least in part, to differences in dietary intake. Recently, it has been suggested that consumption of soyfoods may contribute to the relatively low rates of breast, colon, and prostate cancers in countries such as China and Japan. Soybeans contain a number of anticarcinogens, and a recent National Cancer Institute workshop recommended that the role of soyfoods in cancer prevention be investigated. In this review, the hypothesis that soy intake reduces cancer risk is considered by examining relevant in vitro, animal, and epidemiological data. Soybeans are a unique dietary source of the isoflavone genistein, which possesses weak estrogenic activity and has been shown to act in animal models as an antiestrogen. Genistein is also a specific inhibitor of protein tyrosine kinases; it also inhibits DNA topoisomerases and other critical enzymes involved in signal transduction. In vitro, genistein suppresses the growth of a wide range of cancer cells, with IC50 values ranging from 5 to 40 microM (1-10 micrograms/ml). Of the 26 animal studies of experimental carcinogenesis in which diets containing soy or soybean isoflavones were employed, 17 (65%) reported protective effects. No studies reported soy intake increased tumor development. The epidemiological data are also inconsistent, although consumption of nonfermented soy products, such as soymilk and tofu, tended to be either protective or not associated with cancer risk; however, no consistent pattern was evident with the fermented soy products, such as miso. Protective effects were observed for both hormone- and nonhormone-related cancers. While a definitive statement that soy reduces cancer risk cannot be made at this time, there is sufficient evidence of a protective effect to warrant continued investigation. Publication Types: 
Review
Review, academic 
PMID: 8058523 [PubMed - indexed for MEDLINE] 
3: Cancer Lett 1995 Apr 14;90(2):149-55 
Decreased plasma levels of cholecystokinin in healthy males after chronic ingestion of a heat-treated soya product. Lu LJ, Anderson KE, Gomez G, Nealon WH. 
Department of Preventive Medicine and Community Health, University of Texas Medical Branch, Galveston 77555, USA. Administration of raw soya containing a trypsin inhibitor stimulated excessive release of cholecystokinin (CCK) which led to pancreatic hypertrophy, hyperplasia and cancer in the rats (Booth et al. (1964) Proc. Soc. Exp. Biol. Med., 116, 1067). More postprandial CCK release in healthy humans was observed after ingestion of a single dose of raw soya than heat-treated soya (Calam et al. (1989) Br. J. Nutr., 58, 175). The effect of chronic ingestion of a heat-treated soya product on postprandial CCK release was investigated in six healthy adult males after ingestion of a 36-oz. portion of soymilk daily for 1 month and at 2-3 months after termination of soymilk ingestion. Subjects fasted for 15 h, ingested Lipomul (1.5 g/kg) and provided blood at timed intervals for CCK analysis. The results show that 1-month ingestion of soymilk decreased the magnitude of Lipomul-induced postprandial CCK release in plasma of all six subjects by 5-60% (P < 0.05) compared to those obtained at 2-3 months after the withdrawal from soymilk ingestion. Plasma pancreatic polypeptide (PP) levels were similarly decreased in five of the six subjects by 19-67% (P = 0.03) in line with the regulation of PP by CCK. Thus, prolonged exposure of humans to a heat-treated soya inhibited slightly meal-induced CCK release in contrast to that found in rats after raw soya diets. PMID: 7736450 [PubMed - indexed for MEDLINE] 
4: J Nutr 1995 Mar;125(3 Suppl):744S-750S Possible adverse effects of soybean anticarcinogens. Liener IE. 
Department of Biochemistry, University of Minnesota, St. Paul 55108. For soybeans to serve as a good source of protein for feeding animals as well as humans, a certain amount of heat treatment or some other form of processing must be applied. This is because there are present in soybeans certain heat-labile factors that exert an adverse effect on the nutritional value of the protein. The so-called protease inhibitors have received the most attention in this regard and have been shown to exert their antinutritional effect in the short term by causing pancreatic hypertrophy and hyperplasia in the rat, the underlying cause for an inhibition of growth in these animals. The prolonged feeding of raw soy flour or an enriched trypsin inhibitor fraction from soybeans to rats results in the development of hyperplastic and neoplastic nodules of the pancreas, including carcinomas. It should be emphasized that all of these adverse effects are seen when protease inhibitors are present in relatively high concentrations in the diet and may be completely unrelated to the anticarcinogenic effects seen at low concentrations of the Bowman-Birk inhibitor. Brief mention is also made of any possible adverse effects that may result from the presence of phytic acid and saponins in soybeans. 
Publication Types:
Review
Review, tutorial 
PMID: 7884560 [PubMed - indexed for MEDLINE]
5: J Nutr 1995 Mar;125(3 Suppl):733S-743S 
Comment in:
 J Nutr. 1996 Feb;126(2):582-5 
The evidence for soybean products as cancer preventive agents. Kennedy AR. 
Department of Radiation Oncology, University of Pennsylvania School of Medicine, Philadelphia 19104. 
There is much evidence suggesting that compounds present in soybeans can prevent cancer in many different organ systems. The evidence for specific soybean-derived compounds having a suppressive effect on carcinogenesis in animal model systems is limited, however. There is evidence that the following isolated soybean derived products suppress carcinogenesis in vivo: a protease inhibitor, the Bowman-Birk inhibitor, inositol hexaphosphate (phytic acid) and the sterol beta-sitosterol. Other compounds that may be able to suppress carcinogenesis in animals are the soybean isoflavones. Soybean compounds reported to have other types of anticarcinogenic activity include soybean trypsin inhibitor, saponins and genistein. There is much evidence to suggest that diets containing large amounts of soybean products are associated with overall low cancer mortality rates, particularly for cancers of the colon, breast and prostate. It is believed that supplementation of human diets with certain soybean products shown to suppress carcinogenesis in animals could markedly reduce human cancer mortality rates. Publication Types: 
Review
Review, tutorial 
PMID: 7884559 [PubMed - indexed for MEDLINE]
6: Nutr Cancer 1993;19(3):281-302 
Preparation and production of a cancer chemopreventive agent, Bowman-Birk inhibitor concentrate. 
Kennedy AR, Szuhaj BF, Newberne PM, Billings PC. Department of Radiation Oncology, University of Pennsylvania School of Medicine, Philadelphia 
19104. 
We describe our studies to produce an extract of soybeans with anticarcinogenic activity that we believe will be useful as a human cancer chemopreventive agent for several different organs. The anticarcinogenic activity of the extract is thought to be due to chymotrypsin inhibitor activity, which is due to the Bowman-Birk protease inhibitor (BBI) present in the extract, termed BBI concentrate (BBIC). We describe the contents of BBIC, the ability of BBIC to inhibit malignant transformation in vitro in terms of its chymotrypsin inhibitor activity, and the results of long-term toxicity studies in which mice and rats were exposed to high levels of BBIC for long periods of time. PMID: 8346077 [PubMed - indexed for MEDLINE] 
4: Biochem Pharmacol 1997 Nov 15;54(10):1087-96 
Anti-thyroid isoflavones from soybean: isolation, characterization, and mechanisms of action. 
Divi RL, Chang HC, Doerge DR. 
National Center for Toxicological Research, Jefferson, AR 72079, USA. The soybean has been implicated in diet-induced goiter by many studies. The extensive consumption of soy products in infant formulas and in vegetarian diets makes it essential to define the goitrogenic potential. In this report, it was observed that an acidic methanolic extract of soybeans contains compounds that inhibit thyroid peroxidase- (TPO) catalyzed reactions essential to thyroid hormone synthesis. [...] Genistein also inhibited thyroxine synthesis using iodinated casein or human goiter thyroglobulin as substrates for the coupling reaction. Incubation of either isoflavone with TPO in the presence of H2O2 caused irreversible inactivation of the enzyme; 
*** however, the presence of iodide ion in the incubations completely abolished the inactivation.*** 
5: J Am Coll Nutr 1997 Jun;16(3):280-2 
Abnormal thyroid function tests in infants with congenital hypothyroidism: the influence of soy-based formula. Jabbar MA, Larrea J, Shaw RA. 
Department of Pediatrics, Hurley Medical Center, Flint, Michigan 48503, USA. 
OBJECTIVE: To assess the etiology of hyperthyroxinemia or 
hyperthyrotropinemia in infants with congenital hypothyroidism who are on replacement therapy with 
L-thyroxine. 
*** Neither the hyperthyroxinemia nor hyperthyrotropinemia in these infants was associated with any adverse behavioral-developmental consequence.*** 
  CONCLUSION: When initiating soy-formula feeding in infants with congenital hypothyroidism, the L-thyroxine dose should be increased because of significant reduction in intestinal absorption: conversely, when soy feeding is discontinued, the L-thyroxine dose should be decreased. PMID: 9176836 [PubMed - indexed for MEDLINE] 
1: Toxicol Appl Pharmacol 2000 Nov 1;168(3):244-52 Dietary genistein inactivates rat thyroid peroxidase in vivo without an apparent hypothyroid effect. Chang HC, Doerge DR. 
Division of Biochemical Toxicology, Jefferson, Arkansas 72079, USA. Biological effects of genistein are currently under investigation by the National Toxicology Program because of widespread and increasing soy consumption by humans and evidence for modulation of endocrine function. *** These findings suggest that, even though substantial amounts of TPO activity are lost concomitant to soy isoflavone consumption by normal rats, the remaining enzymatic activity is sufficient to maintain thyroid homeostasis in the absence of additional 
perturbations.*** 
PMID: 11042097 [PubMed - indexed for MEDLINE]