The Effect of High Dose Isoflavone Supplementation on Serum Reverse T in Euthyroid Men With Type 2 Diabetes and Post-menopausal Women.

The health benefits of soy are widely reported but there are queries on the effect of soy isoflavones on thyroid function and the underlying mechanism of action. We examined the effect of soy isoflavones on reverse tri-iodothyronine (or 3,3',5'-tri-iodothyronine; rT) in two studies comprising 400 patients: 200 men (study 1; 3 months) and 200 post-menopausal women (study 2; 6 months) who were randomized to consume 15 g soy protein with 66 mg of isoflavones (SPI) daily, or 15 g soy protein alone without isoflavones (SP) daily. SPI supplementation increased rT serum concentration in both men 0.41 (0.12) vs. 0.45 (0.14) nmol/L and women 0.33 (0.12) vs. 0.37 (0.09) nmol/L at 3 months compared to SP that was not seen at 6 months. Thyroid stimulating hormone (TSH) serum concentrations increased while free thyroxine (fT) concentrations decreased with 3 months of SPI compared to SP supplementation for both men and women. rT correlated with TSH in both studies ( = 0.03) but not with either fT or fT. fT levels did not differ between the SPI and SP preparations. Soy isoflavones transiently increased rT3 levels within 3 months though reverted to baseline at 6 months. The mechanism for this would be either rT3 degrading deiodinase 1 and/or deiodinase 2 activities are transiently inhibited at 3 months, or inhibition of deiodinase 3, which generates rT3 from T4 is induced at 6 months. These changes were mirrored in the TSH concentrations, suggesting that short-term high dose isoflavone transiently impairs thyroid function in the first 3 months and may impact on general health during this period. ISRCTN 90604927; ISRCTN34051237.