Impact Factor 3.675

The 2nd most cited open-access journal in Endocrinology & Metabolism

Mini Review ARTICLE

Front. Endocrinol., 31 July 2012 | https://doi.org/10.3389/fendo.2012.00094

Update on genistein and thyroid: an overall message of safety

Herbert Marini1 †, Francesca Polito1 †, Elena B. Adamo1 †, Alessandra Bitto2, Francesco Squadrito2 and Salvatore Benvenga3,4,5*
  • 1 Section of Physiology and Human Nutrition, Department of Biochemical, Physiological and Nutritional Sciences, University of Messina, Messina, Italy
  • 2 Section of Pharmacology, Department of Clinical and Experimental Medicine and Pharmacology, University of Messina, Messina, Italy
  • 3 Section of Endocrinology, Department of Clinical and Experimental Medicine and Pharmacology, University of Messina, Messina, Italy
  • 4 Master on Childhood, Adolescent and Women’s Endocrine Health, University of Messina, Messina, Italy
  • 5 Interdepartmental Program of Molecular and Clinical Endocrinology, and Women’s Endocrine Health, University Hospital of Messina, Messina, Italy

Genistein aglycone, one of the soy isoflavones, has been reported to be beneficial in the treatment of menopausal vasomotor symptoms, osteoporosis, and cardiovascular diseases, as well as in a variety of cancers. However, issues of potential harm on thyroid function resulting from soy isoflavones consumption have been raised. Much of the evidence for the goitrogenic effects of isoflavones is derived from experimental in vitro and in vivo studies. Goitrogenic effects were also noted in infants fed non-iodine-fortified, soy-based formula, a problem that was easily solved with iodine fortification. Recent studies suggest that genistein shows a good profile of safety on the thyroid although definitive conclusions have not reached. The aim of this brief review is to summarize and better clarify the effects of genistein on human thyroid health.

Genistein (4′,5,7-trihydroxyflavone) is a phytoestrogen belonging to the class of soy isoflavones, a sub-class of flavonoids that have received great attention for their potential on human health benefits. Many epidemiological studies suggest that high dietary intake of soy is associated with lower incidence rates of certain forms of cancers (Setchell, 1998; Messina and Messina, 2010). Indeed, Asian women, whose diet is rich in isoflavones, have a low incidence of breast cancer as well as of other hormone-associated problems, such as osteoporosis and menopausal symptoms (Somekawa et al., 2001: Messina et al., 2004). Of the soy isoflavones, genistein ranks first in terms of mass of experimental and clinical studies performed. Genistein aglycone is an isoflavone found at low concentrations in soybeans but at high concentrations in certain soy-derived food. In contrast, genistin, the glucoside form of the aglycone genistein, is much more abundant in the unprocessed soybean. Structurally, genistein closely resembles 17β-estradiol (Figure 1), and indeed it binds to the estrogen receptors (ERs), the stronger affinity being for the ERβ isoform (Kuiper et al., 1998). Acting as a natural selective ER modulator, genistein exerts its estrogen agonist or antagonist action in a tissue- and dose-dependent manner (Setchell, 2001). Moreover, several in vitro and in vivo studies show that genistein aglycone has antineoplastic effects which stem from multiple actions: (a) modulation of cell growth and proliferation throughout tyrosine kinases and topoisomerase II inhibition, (b) stimulation of the immune system, (c) antiangiogenic effects, and (d) potent antioxidant capacity (Polkowski and Mazurek, 2000). Additionally, the anticancer property of genistein may be likely due to DNA methylation and/or chromatin modification (Li and Tollefsbol, 2010).

FIGURE 1
www.frontiersin.org

FIGURE 1. Chemical structure of genistein and estradiol.

Recently, clinical trials have been conducted to evaluate the benefit of genistein aglycone as a cure for menopausal vasomotor symptoms, osteoporosis, and cardiovascular disease. Specifically, administration of 54 mg/day genistein aglycone to postmenopausal women with low bone mass results in positive (beneficial) changes in vasomotor symptoms, bone mineral density and markers of bone turnover, and some predictors of cardiovascular risk without harmful estrogenic activity in the breast and uterus (Atteritano et al., 2007; Marini et al., 2007, 2008, 2010; D’Anna et al., 2009). In those studies, administration of pure genistein avoided possible interferences by other isoflavones and resulted in documented and stable increases of the isoflavone’s serum level. The promising safety profile of genistein aglycone may be a direct consequence of its greater affinity for the ERβ, which is particularly abundant in both the trabecular bone during the mineralization phase and the artery endothelial tissue, than ERα, which is more represented in the reproductive tissues (Nilsson and Gustafsson, 2011).

It is known that estrogens exert several effects on thyroid follicular cells, in that they modulate their cell cycle progression, proliferation, and function, thus potentially contributing to the pathogenesis of thyroid hyperplasia and even thyroid cancer. These effects are mediated by the binding to ERs as well as through distinct non-genomic molecular pathways (Ben-Rafael et al., 1987; Santin and Furlanetto, 2011). However, the expression of ERs in normal and neoplastic human thyroid tissues remains controversial probably because of inter-study differences in the methods used to quantify their expression. Another controversy of major concern is the different action of ERα and ERβ in neoplastic thyroid (Chen et al., 2008; Santin and Furlanetto, 2011).

Thyroid hormones regulate several metabolic processes and are crucial for normal growth, development, and maturation of the central nervous system, the cardiovascular system, and the skeleton in mammals. Decreased thyroid hormones synthesis and action results in impaired neuro-cognitive function and increased risk for cardiovascular diseases (Biondi and Cooper, 2008), thus impacting negatively on human health.

Experimental Studies

Studies on the relationship between soybean intake and thyroid function have started about 80 years ago (Divi et al., 1997; Fitzpatrick, 2000; Doerge and Chang, 2002; Doerge and Sheehan, 2002); they suggest that consumption of soy and, specifically soy isoflavones as genistein, is goitrogenic and alters thyroid function.

The goitrogenic effects of genistein seem to derive from a direct interaction of this isoflavone with key pathways involved in thyroid hormones synthesis, metabolism, and thyroid hormone transport proteins (Radović, 2006). In vitro and in vivo studies showed that genistein is a potent inhibitor of thyroid peroxidase (TPO), a key enzyme in thyroid hormone synthesis (Divi and Doerge, 1996; Divi et al., 1997; Chang and Doerge, 2000; Doerge and Sheehan, 2002). Indeed, TPO catalyzes the iodination of thyroglobulin and oxidative coupling of diiodothyronine resulting in the thyroid hormone formation. Thus, inhibition of TPO leads to a reduction of thyroid hormones levels, with a subsequent increment of TSH release, that, in turn, provides a strong growth stimulus to the thyroid gland. Moreover, genistein also affects the metabolism of thyroid hormones and iodide re-utilization by inhibition of sulfotransferase enzymes (Ebmeier and Anderson, 2004).

Divi et al. (1997) demonstrated that the TPO-catalyzed iodination of tyrosine inhibited by genistein is dose-dependent; this effect reverses when sufficient amounts of iodide are added to incubation mixtures. Similar inhibition was observed in rat microsomal TPO and in rats feeding a diet fortified with different doses of genistein, but no changes were observed in blood sera levels of thyroid hormone or TSH (Chang and Doerge, 2000). Genistein is also known as a potent, dose-dependent, inhibitor of tyrosine kinase (Ravindranath et al., 2004), as well as thyroid hormone deiodination mediated by 5′-iodothyronine deiodinase (Mori et al., 1996; White et al., 2004).

Using preparations of liver enzymes, Ferreira et al. (2002) found that flavonoids other than genistein inhibited 5′-iodothyronine deiodinase. Indeed, in vivo experiments with the synthetic flavonoid EMD 21388 (Schröder-van der Elst et al, 1991), which inhibits thyroid hormone binding to plasma transthyretin, show a reduction of T3 content in tissues that express type II 5′-iodothyronine deiodinase.

More recently, Sosić-Jurjević et al. (2010) showed that a subcutaneous injection of 10 mg/kg of genistein or daidzein can disturb the pituitary-thyroid axis, causing hypothyroidism in orchidectomized middle-aged rats.

However, overall in vitro and in vivo data from animal studies are not easily to compare with data from human studies, as demonstrated by a recent paper (Setchell et al., 2011).

Human Studies

In humans, early studies showed that feeding infants with soy milk caused goiter in those with inadequate iodine intake even if this effect was reverted by iodine supplementation (Chorazy et al., 1995; Jabbar et al., 1997). Moreover, of 530 children aged 6–15 years living in iodine-deficient areas of India and consuming large amounts of flavonoids, almost all were goitrous (Brahmbhatt et al., 2000). This enormous rate of thyroid enlargement led the authors to conclude that goiter was due to the combined effect of iodine deficiency and flavonoid excess in their diet (Brahmbhatt et al., 2000).

A more recent human trial reports the effects of short-term soy consumption on thyroid parameters in relation with isoflavone levels in male and female healthy subjects (Hampl et al., 2008). After 7 days of soy consumption, levels of both genistein and daidzein were increased. The statistically significant relationships found at the end of soy consumption were: (i) between basal levels of daidzein and thyrotropin, (ii) between daidzein and antithyroglobulin in males, and (iii) between daidzein and free thyroxine in females. Genistein lacked any correlation with the above thyroid parameters. These results agree with a previous research in 268 children (Milerová et al., 2006). The authors investigated whether serum levels of genistein and daidzein were correlated with thyroid hormone function. This study showed only a modest association between isoflavones serum levels and parameters of thyroid function, such as free thyroxine, thyroglobulin antibodies, and thyroid volume.

It is well known that thyroid diseases are most common in women, especially during perimenopause and menopause, perhaps as consequence of an altered balance between estrogens and progesterone. Accordingly, the effects of genistein on thyroid function were also analyzed in postmenopausal women. Results from a 3-month study in postmenopausal women consuming an isoflavone-rich diet (containing 58% of total genistein) showed no significant effect of isoflavones on serum levels of thyroid hormones (Duncan et al., 1999).

Bruce et al. (2003) investigated thyroid function in 38 iodine-repleted postmenopausal women at baseline and after 90 and 180 days following supplementation with 90 mg (aglycone weight) of total isoflavones/day. Thyroid parameters did not differ between the placebo and the treatment arm.

In a 16-week duration study, 77 postmenopausal women were randomized to receive cow’s milk and a placebo supplement, soy milk and placebo supplement, or cow’s milk and isoflavone supplement (Ryan-Borchers et al., 2008). The results of this study are congruent with those of Bruce et al. (2003) and provide evidence that the levels of isoflavone intake do not adversely affect thyroid function, as indicated by serum TSH levels that remained within the normal range following the intervention period in all women; cognitive functioning in healthy postmenopausal women was also unaffected. A more recent clinical trial in postmenopausal women evaluated the effects of 3-year administration of pure genistein aglycone (54 mg/day) on thyroid-related markers (Bitto et al., 2010). Specifically, changes in thyroid hormone receptors expression, serum levels of thyroid hormones, and thyroid antibodies were assessed. The results showed that daily consumption of genistein aglycone did not modify circulating FT4, FT3, and TSH levels or thyroid antibodies. Furthermore, genistein aglycone administration over 3 years did not affect the expression of thyroid hormone receptors in peripheral blood mononuclear cells, thus confirming that genistein appears not to alter thyroid function in postmenopausal women.

A 12-week duration randomized, double-blind and placebo-controlled trial in 43 oophorectomized Indian women, evaluated the effect of 75 mg/day soy isoflavones (genistein and genistin 25%; daidzein and daidzin 15%) on serum levels FT3, FT4, TSH, TBG, and anti-TPO antibodies (Mittal et al., 2011). The only variation found was a modest decrease in serum FT3.

Finally, a recent study in men with localized prostate cancer addressed the safety of genistein in the male gender (Lazarevic et al., 2011). Genistein was administered at the dose of 30 mg/day for 3–6 weeks prior to prostatectomy, and thyroid hormones levels were measured as secondary outcome. Serum levels of thyroid hormones remained statistically unchanged.

Conclusion

Overall, there is a scarcity of information about the effect of pure isoflavones, such as genistein, on thyroid safety in humans. Results of intervention trials are not easily comparable because the researchers have used (i) mixed isoflavones or isoflavone and protein mixtures with different dosage regimens, soy foods or supplements as the active treatment; (ii) the quality and amount of genistein varied widely in all of these previous studies; and (iii) the trials were of different duration. Although the overall evidence suggests that isoflavone genistein does not affect adversely thyroid function in euthyroid, iodine-replete individuals, further studies are warranted to better define the relationship between genistein and thyroid.

Infants and women deserve particular attention in order to assess the safety of genistein and/or other isoflavones on thyroid function, also considering that thyroid disorders are age- and gender-related.

Conflict of Interest Statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

References

Atteritano, M., Marini, H., Minutoli, L., Polito, F., Bitto, A., Altavilla, D., Mazzaferro, S., D’Anna, R., Cannata, M. L., Gaudio, A., Frisina, A., Frisina, N., Corrado, F., Cancellieri, F., Lubrano, C., Bonaiuto, M., Adamo, E. B., and Squadrito, F. (2007). Effects of the phytoestrogen genistein on some predictors of cardiovascular risk in osteopenic, postmenopausal women: a two-year randomized, double-blind, placebo-controlled study. J. Clin. Endocrinol. Metab. 92, 3068–3075.

Pubmed Abstract | Pubmed Full Text | CrossRef Full Text

Ben-Rafael, Z., Struass, J. F. III, Arendash-Durand, B., Mastroianni, L. Jr., and Flickinger, G. L. (1987). Changes in thyroid function tests and sex hormone binding globulin associated with treatment by gonadotropin. Fertil. Steril. 48, 318–320.

Pubmed Abstract | Pubmed Full Text

Biondi, B., and Cooper, D. S. (2008). The clinical significance of subclinical thyroid dysfunction. Endocr. Rev. 29, 76–131.

Pubmed Abstract | Pubmed Full Text | CrossRef Full Text

Bitto, A., Polito, F., Atteritano, M., Altavilla, D., Mazzaferro, S., Marini, H., Adamo, E. B., D’Anna, R., Granese, R., Corrado, F., Russo, S., Minutoli, L., and Squadrito, F. (2010). Genistein aglycone does not affect thyroid function: results from a three-year, randomized, double-blind, placebo-controlled trial. J. Clin. Endocrinol. Metab. 95, 3067–3072.

Pubmed Abstract | Pubmed Full Text | CrossRef Full Text

Brahmbhatt, S., Brahmbhatt, R. M., and Boyages, S. C. (2000). Thyroid ultrasound is the best prevalence indicator for assessment of iodine deficiency disorders: a study in rural/tribal schoolchildren from Gujarat (Western India). Eur. J. Endocrinol. 143, 37–46.

Pubmed Abstract | Pubmed Full Text | CrossRef Full Text

Bruce, B., Messina, M., and Spiller, G. A. (2003). Isoflavone supplements do not affect thyroid function in iodine-replete postmenopausal women. J. Med. Food 6, 309–316.

Pubmed Abstract | Pubmed Full Text | CrossRef Full Text

Chang, H. C., and Doerge, D. R. (2000). Dietary genistein inactivates rat thyroid peroxidase in vivo without an apparent hypothyroid effect. Toxicol. Appl. Pharmacol. 168, 244–252.

Pubmed Abstract | Pubmed Full Text | CrossRef Full Text

Chen, G. G., Vlantis, A. C., Zeng, Q., and van Hasselt, C. A. (2008). Regulation of cell growth by estrogen signaling and potential targets in thyroid cancer. Curr. Cancer Drug Targets 8, 367–377.

Pubmed Abstract | Pubmed Full Text | CrossRef Full Text

Chorazy, P. A., Himelhoch, S., Hopwood, N. J., Greger, N. G., and Postellon, D. C. (1995). Persistent hypothyroidism in an infant receiving a soy formula: case report and review of the literature. Pediatrics 96, 148–150.

Pubmed Abstract | Pubmed Full Text

D’Anna, R., Cannata, M. L., Marini, H., Atteritano, M., Cancellieri, F., Corrado, F., Triolo, O., Rizzo, P., Russo, S., Gaudio, A., Frisina, N., Bitto, A., Polito, F., Minutoli, L., Altavilla, D., Adamo, E. B., and Squadrito F. (2009). Effects of the phytoestrogen genistein on hot flushes, endometrium, and vaginal epithelium in postmenopausal women: a 2-year randomized, double-blind, placebocontrolled study. Menopause 16, 301–306.

Pubmed Abstract | Pubmed Full Text | CrossRef Full Text

Divi, R. L., Chang, H. C., and Doerge, D. R. (1997). Anti-thyroid isoflavones from soybean: isolation, characterization, and mechanisms of action. Biochem. Pharmacol. 54, 1087–1096.

Pubmed Abstract | Pubmed Full Text | CrossRef Full Text

Divi, R. L., and Doerge, D. R. (1996). Inhibition of thyroid peroxidase by dietary flavonoids. Chem. Res. Toxicol. 9, 16–23.

Pubmed Abstract | Pubmed Full Text | CrossRef Full Text

Doerge, D. R., and Chang, H. C. (2002). Inactivation of thyroid peroxidase by soy isoflavones, in vitro and in vivo. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci. 777, 269–279.

Pubmed Abstract | Pubmed Full Text | CrossRef Full Text

Doerge, D. R., and Sheehan, D. M. (2002). Goitrogenic and estrogenic activity of soy isoflavones. Environ. Health Perspect. 110, 349–353.

Pubmed Abstract | Pubmed Full Text | CrossRef Full Text

Duncan, A. M., Underhill, K. E., Xu, X., Lavalleur, J., Phipps, W. R., and Kurzer, M. S. (1999). Modest hormonal effects of soy isoflavones in postmenopausal women. J. Clin. Endocrinol. Metab. 84, 3479–3484. Erratum in: J. Clin. Endocrinol. Metab. (2000) 85, 448.

Pubmed Abstract | Pubmed Full Text | CrossRef Full Text

Ebmeier, C. C., and Anderson, R. J. (2004). Human thyroid phenol sulfotransferase enzymes 1A1 and 1A3: activities in normal and diseased thyroid glands, and inhibition by thyroid hormones and phytoestrogens. J. Clin. Endocrinol. Metab. 89, 5597–5605.

Pubmed Abstract | Pubmed Full Text | CrossRef Full Text

Ferreira, A. C., Lisboa, P. C., Oliveira, K. J., Lima, L. P., Barros, I. A., and Carvalho, D. P. (2002). Inhibition of thyroid type 1 deiodinase activity by flavonoids. Food Chem. Toxicol. 40, 913–917.

Pubmed Abstract | Pubmed Full Text | CrossRef Full Text

Fitzpatrick, M. (2000). Soy formulas and the effects of isoflavones on the thyroid. N. Z. Med. J. 113, 24–26.

Pubmed Abstract | Pubmed Full Text

Hampl, R., Ostatnikova, D., Celec, P., Putz, Z., Lapcík, O., and Matucha, P. (2008). Short-term effect of soy consumption on thyroid hormone levels and correlation with phytoestrogen level in healthy subjects. Endocr. Regul. 42, 53–61.

Pubmed Abstract | Pubmed Full Text

Jabbar, M. A., Larrea, J., and Shaw, R. A. (1997). Abnormal thyroid function tests in infants with congenital hypothyroidism: the influence of soy-based formula. J. Am. Coll. Nutr. 16, 280–282.

Pubmed Abstract | Pubmed Full Text

Kuiper, G. G., Lemmen, J. G., Carlsson, B., Corton, J. C., Safe, S. H., van der Saag, P. T., van der Burg, B., and Gustafsson, J. A. (1998). Interaction of estrogenic chemicals and phytoestrogens with estrogen receptor beta. Endocrinology 139, 4252–4263.

Pubmed Abstract | Pubmed Full Text | CrossRef Full Text

Lazarevic, B., Boezelijn, G., Diep, L. M., Kvernrod, K., Ogren, O., Ramberg, H., Moen, A., Wessel, N., Berg, R. E., Egge-Jacobsen, W., Hammarstrom, C., Svindland, A., Kucuk, O., Saatcioglu, F., Taskèn, K. A., and Karlsen, S. J. (2011). Efficacy and safety of short-term genistein intervention in patients with localized prostate cancer prior to radical prostatectomy: a randomized, placebo-controlled, double-blind phase 2 clinical trial. Nutr. Cancer 63, 889–898.

Pubmed Abstract | Pubmed Full Text | CrossRef Full Text

Li, Y., and Tollefsbol, T. O. (2010). Impact on DNA methylation in cancer prevention and therapy by bioactive dietary components. Curr. Med. Chem. 17, 2141–2151.

Pubmed Abstract | Pubmed Full Text | CrossRef Full Text

Marini, H., Bitto, A., Altavilla, D., Burnett, B. P., Polito, F., Di Stefano, V., Minutoli, L., Atteritano, M., Levy, R. M., D’Anna, R., Frisina, N., Mazzaferro, S., Cancellieri, F., Cannata, M. L., Corrado, F., Frisina, A., Adamo, V., Lubrano, C., Sansotta, C., Marini, R., Adamo, E. B., and Squadrito, F. (2008). Breast safety and efficacy of genistein aglycone for postmenopausal bone loss: a follow-up study. J. Clin. Endocrinol. Metab. 93, 4787–4796.

Pubmed Abstract | Pubmed Full Text | CrossRef Full Text

Marini, H., Bitto, A., Altavilla, D., Burnett, B. P., Polito, F., Di Stefano, V., Minutoli, L., Atteritano, M., Levy, R. M., Frisina, N., Mazzaferro, S., Frisina, A., D’Anna, R., Cancellieri, F., Cannata, M. L., Corrado, F., Lubrano, C., Marini, R., Adamo, E. B., and Squadrito, F. (2010). Efficacy of genistein aglycone on some cardiovascular risk factors and homocysteine levels: a follow-up study. Nutr. Metab. Cardiovasc. Dis. 20, 332–340.

Pubmed Abstract | Pubmed Full Text | CrossRef Full Text

Marini, H., Minutoli, L., Polito, F., Bitto, A., Altavilla, D., Atteritano, M., Gaudio, A., Mazzaferro, S., Frisina, A., Frisina, N., Lubrano, C., Bonaiuto, M., D’Anna, R., Cannata, M. L., Corrado, F., Adamo, E. B., Wilson, S., and Squadrito, F. (2007). Effects of the phytoestrogen genistein on bone metabolism in osteopenic postmenopausal women: a randomized trial. Ann. Intern. Med. 146, 839–847.

Pubmed Abstract | Pubmed Full Text

Messina, M., Ho, S., and Alekel, D. L. (2004). Skeletal benefits of soy isoflavones: a review of the clinical trial and epidemiologic data. Curr. Opin. Clin. Nutr. Metab. Care 7, 649–658.

Pubmed Abstract | Pubmed Full Text | CrossRef Full Text

Messina, M., and Messina, V. (2010). The role of soy in vegetarian diets. Nutrients 2, 855–888.

Pubmed Abstract | Pubmed Full Text | CrossRef Full Text

Milerová, J., Cerovská, J., Zamrazil, V., Bílek, R., Lapcík, O., and Hampl, R. (2006). Actual levels of soy phytoestrogens in children correlate with thyroid laboratory parameters. Clin. Chem. Lab. Med. 44, 171–174.

Pubmed Abstract | Pubmed Full Text | CrossRef Full Text

Mittal, N., Hota, D., Dutta, P., Bhansali, A., Suri, V., Aggarwal, N., Marwah, R. K., and Chakrabarti, A. (2011). Evaluation of effect of isoflavone on thyroid economy & autoimmunity in oophorectomised women: a randomised, double-blind, placebo-controlled trial. Indian J. Med. Res. 133, 633–640.

Pubmed Abstract | Pubmed Full Text

Mori, K., Stone, S., Braverman, L. E., and Devito, W. J. (1996). Involvement of tyrosine phosphorylation in the regulation of 5′-deiodinases in FRTL-5 rat thyroid cells and rat astrocytes. Endocrinology 137, 1313–1318.

Pubmed Abstract | Pubmed Full Text | CrossRef Full Text

Nilsson, S., and Gustafsson, J. Å. (2011). Estrogen receptors: therapies targeted to receptor subtypes. Clin. Pharmacol. Ther. 89, 44–55.

Pubmed Abstract | Pubmed Full Text | CrossRef Full Text

Polkowski, K., and Mazurek, A. P. (2000). Biological properties of genistein. A review of in vitro and in vivo data. Acta Pol. Pharm. 57, 135–155.

Pubmed Abstract | Pubmed Full Text

Radović, B., Mentrup, B., and Köhrle, J. (2006). Genistein and other soya isoflavones are potent ligands for transthyretin in serum and cerebrospinal fluid. Br. J. Nutr. 95, 1171–1176.

Pubmed Abstract | Pubmed Full Text | CrossRef Full Text

Ravindranath, M. H., Muthugounder, S., Presser, N., and Viswanathan, S. (2004). Anticancer therapeutic potential of soy isoflavone, genistein. Adv. Exp. Med. Biol. 546, 121–165.

Pubmed Abstract | Pubmed Full Text

Ryan-Borchers, T., Chew, B., Park, J. S., McGuire, M., Fournier, L., and Beerman, K. (2008). Effects of dietary and supplemental forms of isoflavones on thyroid function in healthy postmenopausal women. Top. Clin. Nutr. 23, 13–22.

Santin, A. P., and Furlanetto, T. W. (2011). Role of estrogen in thyroid function and growth regulation. J. Thyroid Res. 2011, 875125.

Pubmed Abstract | Pubmed Full Text | CrossRef Full Text

Schröder-van der Elst, J. P., van der Heide, D., and Köhrle, J. (1991). In vivo effects of flavonoid EMD 21388 on thyroid hormone secretion and metabolism in rats. Am. J. Physiol. 261(Pt 1), E227–E232.

Pubmed Abstract | Pubmed Full Text

Setchell, K. D. (1998). Phytoestrogens: the biochemistry, physiology, and implications for human health of soy isoflavones. Am. J. Clin. Nutr. 68, 1333S–1346S.

Pubmed Abstract | Pubmed Full Text

Setchell, K. D. (2001). Soy isoflavones-benefits and risks from nature’s selective estrogen receptor modulators (SERMs). J. Am. Coll. Nutr. 20, 354S–362S.

Pubmed Abstract | Pubmed Full Text

Setchell, K. D., Brown, N. M., Zhao, X., Lindley, S. L., Heubi, J. E., King, E. C., and Messina, M. J. (2011). Soy isoflavone phase II metabolism differs between rodents and humans: implications for the effect on breast cancer risk. Am. J. Clin. Nutr. 94, 1284–1294.

Pubmed Abstract | Pubmed Full Text | CrossRef Full Text

Somekawa, Y., Chiguchi, M., Ishibashi, T., and Aso, T. (2001). Soy intake related to menopausal symptoms, serum lipids, and bone mineral density in postmenopausal Japanese women. Obstet. Gynecol. 97, 109–115.

Pubmed Abstract | Pubmed Full Text | CrossRef Full Text

Sosić-Jurjević, B., Filipović, B., Ajdzanović, V., Savin, S., Nestorović, N., Milosević, V., and Sekulić, M. (2010). Suppressive effects of genistein and daidzein on pituitary–thyroid axis in orchidectomized middle-aged rats. Exp. Biol. Med. 235, 590–598.

Pubmed Abstract | Pubmed Full Text | CrossRef Full Text

White, H. L., Freeman, L. M., Mahony, O., Graham, P. A., Hao, Q., and Court, M. H. (2004). Effect of dietary soy on serum thyroid hormone concentrations in healthy adult cats. Am. J. Vet. Res. 65, 586–591.

Pubmed Abstract | Pubmed Full Text | CrossRef Full Text

Keywords: genistein, isoflavones, soy, safety, thyroid

Citation: Marini H, Polito F, Adamo EB, Bitto A, Squadrito F and Benvenga S (2012) Update on genistein and thyroid: an overall message of safety. Front. Endocrin. 3:94. doi: 10.3389/fendo.2012.00094

Received: 10 February 2012; Paper pending published: 12 April 2012;
Accepted: 16 July 2012; Published online: 31 July 2012.

Edited by:

Rossella Elisei, University of Pisa, Italy

Reviewed by:

Rossella Elisei, University of Pisa, Italy
Tania M. Ortiga-Carvalho, Universidade Federal do RIo de Janeiro, Brazil

Copyright: © 2012 Marini, Polito, Adamo, Bitto, Squadrito and Benvenga. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in other forums, provided the original authors and source are credited and subject to any copyright notices concerning any third-party graphics etc.

*Correspondence: Salvatore Benvenga, Department of Clinical and Experimental Medicine and Pharmacology, Section of Endocrinology, Azienda Ospedaliera Universitaria Policlinico “G. Martino”, Pad. H 4th Floor, Via C. Valeria, Gazzi, 98125 Messina, Italy. e-mail: s.benvenga@me.nettuno.it

Herbert Marini, Francesca Polito, and Elena B. Adamo have contributed equally to this work.