Isoflavone Research Initiative

The most recent findings on soy and isoflavones were presented in Washington DC on the occasion of the 9^th International Symposium on the Role of Soy in Health Promotion and Chronic Disease Prevention and Treatment (October 16-19, 2010). A major part of the topics was dedicated to safety and health benefits in menopausal women, and to the issue of soy and breast cancer.

Dr. Stephen L. Atkin (Hull York Medical School, University of Hull, UK) addressed the question of potential thyroid adverse effects of soy preparations (Atkins et al. 2010). If such an adverse effect truly exists, it should have a greater impact in subjects with subclinical hypothyroidism, especially with respect to an increased cardiovascular risk (Hak et al. 2000). Soy has been linked to potential hypothyroidism through animal experiments showing such effects in iodine-depleted rats (Doerge et al. 2002). It has also been suspected to be responsible for infant goitre in an older case report (Hydovitz 1960).

Atkin included 60 patients with subclinical hypothyroidism into a randomized clinical double-blind trial, where patients received a diet containing 30 g of soy protein daily. In one group the soy protein contained 16 mg of isoflavones (90 % in the form of glycosides), in the control group the isoflavones were depleted to 2 mg. After 8 weeks of supplementation a wash-out period of 8 weeks, followed by the second 8-week-supplementation on the alternative study arm was made. The primary outcome measure was the progression to overt hypothyroidism. In addition, markers of cardiovascular disease were measured, such as blood pressure, HOMA-IR and CRP.

Six patients progressed into overt hypothyroidism with a standardised rate ratio of 3.6 (95 % CI -1.9 to 6.2) with 16 mg isoflavones, but no deterioration in thyroid function was observed in the other patients. However, no changes in thyroidal hormones T4 and TSH were detected. In accordance to previous observations, systolic blood pressure (140.7±2.4 vs. 133.6±2.8 mm Hg, p < 0.01) and diastolic blood pressure (76.7±1.8 vs. 72.1±1.4 mm Hg, p < 0.02) decreased with the 16 mg of isoflavones, whereas with the 2 mg dose only the systolic blood pressure was marginally decreased. HOMA-IR (3.5±0.99 vs. 2.6±0.08, p < 0.02) and CRP (4.9±0.04 vs. 3.9±0.03, p < 0.01 decreased with 16 mg isoflavones. The lipid profile remained unchanged.

According to this study the risk of developing overt hypothyroidism is threefold increased with dietary supplementation of 30 g of soy protein daily, containing (among other constituents) 16 mg of isoflavones. However, the same diet positively influences parameters of cardiovascular health.

Similar results were found in a second trial where patients were supplemented with 30 g of soy protein containing 66 mg of isoflavones, and 30 g of isoflavone-depleted protein. In this second study, 5 women progressed to overt hypothyroidism in the SPI(+)-group, whereas 2 patients progressed in the SPI(-)-group. Again, blood pressure was improved with SPI(+), but remained uninfluenced with SPI(-).

Conclusions for the issue “Soy and the thyroid gland”

The potential risk of progression into overt hypothyroidism was in fact observed with the dietary supplementation of soy protein, but the hypothesis of potential increase of cardiovascular risk factors was refuted. In addition, the correlation with the isoflavones is not clearly given, as depletion of soy protein by alcohol-washing would also remove other, non-isoflavone constituents.

In earlier studies dedicated to the issue no effect of isoflavone-containing preparations on the thyroid gland was found (Dillingham et al. 2007; Khaodhiar et al. 2008; Marini et al. 2008; Romualdi et al. 2008; Teas et al. 2009). The new findings are therefore in contrast with the clinical experience, and especially the rather high progression rate of subclinical to overt hypothyroidism must be re-examined in further trials. An important point raised in the discussion may be that the patients of Atkin’s study were iodine-deficient and did not receive proper supplementation to make up for this dietary deficiency. In such cases the obvious measure should be to mend the iodine deficiency first before conclusions about the safety of soy or its isoflavones are drawn: in an earlier study it was already demonstrated that the adverse effect does not occur in iodine-repleted postmenopausal women (Bruce et al. 2003).

References

Atkins SL, Sathyapalan P and Thatcher NJ (2010). The effect of soy phytoestrogen supplementation on thyroid status and cardiovascular risk markers in patients with subclinical hypothroidism: A randomized double-blind crossover study. 9^th International Symposium on the Role of Soy in Health Promotion and Chronic Disease Prevention and Treatment, Washington DC, 16-19 October.

Bruce B, Messina M and Spiller GA (2003). Isoflavone supplements do not affect thyroid function in iodine-replete postmenopausal women. J Med Food 6(4):309-316.

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.

Hak AE, Pols HA, Visser TJ, Drexhage HA, Hofman A and Witteman JC (2000). Subclinical hypothyroidism is an independent risk factor for atherosclerosis and myocardial infarction in elderly women: the Rotterdam Study. Ann Intern Med 132(4):270-278.

Hydovitz JD (1960). Occurrence of goiter in an infant on a soy diet. N Engl J Med 262:351-353.

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.

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.