Isoflavone Research Initiative

The safety of application and the benefits of isoflavones for postmenopausal women were the focus of a symposium organised by the CRN (Council for Responsible Nutrition), which took place on the 13th and 14th of May 2009 in Milan (Italy) under active participation of the EFSA (European Food Safety Authority).

The concerns of the German BfR, which are reflected in a mandate of the EFSA for the safety assessment of isoflavones, referred not only to the connection between isoflavones and cancer, but also to the safety at the thyroid gland (Anon. 2007). Again based on animal trials the BfR had voiced concerns that soy isoflavones might further deteriorate the thyroidal turnover in hypothyreotic women. As 6-10 % of postmenopausal women have an iodine deficiency and therefore a hypothyreosis, the intake of isoflavones should lead to clinically observed adverse effects. This is, however, not the case, as was reported by Prof. Francesco Squadrito of the University of Messina (Italy) (Squadrito 2009).

In experiments with iodine deficient rats high doses of isoflavones inhibit the function of the thyroid peroxidase (Doerge et al. 2002). It is, however, questionable whether these effects can be transferred to humans. In the contrary a review from the year 2006 evaluated data from measurements of thyroidal parameters in clinical trials, but did not find a significant effect of isoflavones on the thyroidal gland (Doerge et al. 2002). In the meantime new clinical data has been published on these aspects (Dillingham et al. 2007; Khaodhiar et al. 2008; Romualdi et al. 2008; Teas et al. 2009), and in all case the intake of isoflavones had either no or only modest effects on the levels of thyroidal hormones.

The working group of Squadrito has performed a double-blind, placebo controlled trial with the administration of a daily dose of 54 mg of genistein. Meanwhile the published data covers three years of exposure (Marini et al. 2008). In this study, which focused on questions of bone health, not only the thyroidal hormones (T3, T4 and TSH) were measured, but also the influence of genistein on the receptors of thyroidal hormones, and the activation of genes of thyroidal turnover (Marini et al. 2008). The examinations made clear that isoflavones do not increase the risk of a clinically relevant hypothyreosis. Iodine deficiency is, however, a known risk factor for hypothyreosis. Especially in menopausal women a sufficient supply of iodine should be encouraged, independent of the ingestion of soy products.

Concluding his presentation Squadrito pointed out that with the results of the third study year there are now sufficient long-term data to disprove the concerns about a negative effect of isoflavones on thyroidal turnover (Marini et al. 2008). The published studies involved also patients with borderline thyroidal function, but did not yield any hint on corresponding adverse effects. Squadrito did therefore not see a reason for concern regarding the connection between isoflavones and thyroidal gland.

Further reports from the Milan 2009 Soy Safety Symposium:

1. Plant “hormones”: Guilty by association with estrogens? International Symposium in Milan on the safety and efficacy of soy

2. Facts Related to Bioavailability

3. Lack of relevance of animal models for an extrapolation of risks of isoflavones

4. Isoflavones protect „menopausal” mice from breast cancer

5. Breast cancer risk is increased by synthetic gestagens

6. Breast tissue density remains unaltered with soy 

7. Clinical studies demonstrate safety of soy in the breast

8. Study in more than 5,000 breast cancer patients: First positive tendencies with soy!

9. No effects of isoflavones on the endometrium

10. Isoflavones also safe at the thyroid gland

11. Backgrounds on Menopausal Hot Flushes

12. Clinical safety of isoflavone-containing preparations

13. Clinical effects of isoflavones against menopausal hot flushes

References

Anon. (2007). Isolierte Isoflavone in Nahrungsergänzungsmitteln und bilanzierten Diäten. Gesundheitliche Bewertung des BfR vom 30 11 2007.

Dillingham BL, McVeigh BL, Lampe JW and Duncan AM (2007). Soy protein isolates of varied isoflavone content do not influence serum thyroid hormones in healthy young men. Thyroid 17(2):131-137.

Doerge DR and Chang HC (2002). Inactivation of thyroid peroxidase by soy isoflavones, in vitro and in vivo. J Chromatogr B Analyt Technol Biomed Life Sci 777(1-2):269-279.

Khaodhiar L, Ricciotti HA, Li L, Pan W, Schickel M, Zhou J and Blackburn GL (2008). Daidzein-rich isoflavone aglycones are potentially effective in reducing hot flashes in menopausal women. Menopause 15(1):125-132.

Marini H, Bitto A, Altavilla D, Burnett BP, Polito F, Di Stefano, V, Minutoli L, Atteritano M, Levy RM, D'Anna R, Frisina N, Mazzaferro S, Cancellieri F, Cannata ML, Corrado F, Frisina A, Adamo V, Lubrano C, Sansotta C, Marini R, Adamo EB and Squadrito F (2008). Breast Safety and efficacy of genistein aglycone for post-menopausal bone loss: A follow-up study. J Clin Endocrinol Metab 93(12):7487-7496.

Romualdi D, Costantini B, Campagna G, Lanzone A and Guido M (2008). Is there a role for soy isoflavones in the therapeutic approach to polycystic ovary syndrome? Results from a pilot study. Fertil Steril 90(5):1826-1833.

Squadrito F (2009). Effects of isoflavones on thyroid function. Symposium on Evaluating the Efficacy and Safety of Isoflavones for Postmenopausal Women, 13-14 May. Milan (Italy): Council for Responsible Nutrition.

Teas J, Hurley TG, Hebert JR, Franke AA, Sepkovic DW and Kurzer MS (2009). Dietary seaweed modifies estrogen and phytoestrogen metabolism in healthy postmenopausal women. J Nutr 139(5):939-944.