Thyroid Function and Soy: The Good, the Bad and the Not-so-ugly!

Source: Bruce B, et al. Isoflavone supplements do not affect thyroid function in iodine-replete postmenopausal women. J Med Food 2003; 6:309-316.

Abstract: Despite the safety review conducted by the U.S. Food and Drug Administration in the process of awarding a health claim for the cholesterol-lowering properties of soy protein, concerns about the possible goitrogenic effects of soybean isoflavones persist. Concerns are based primarily on in vitro research, animal studies, and older reports of goiter in infants fed soy formula not fortified with iodine. In a randomized, double-blind, placebo-controlled study, the authors investigated the effect on thyroid function of a daily supplement containing 90 mg/d (aglycone weight) of total isoflavones vs. placebo in 38 postmenopausal women, ages 64-83 years, who were not on hormone replacement therapy. Serum thyroid-stimulating hormone (TSH), thyroxine (T4), and triiodothyronine (T3) were measured at baseline and after 90 and 180 days. In the supplement group, at baseline and six months, TSH (micro U/mL), T4 (nM), and T3 (nM) levels (mean ± SE) were 3.00 ± 0.44, 149.00 ± 5.04, and 1.53 ± 0.13, respectively, and 3.49 ± 0.52, 154.52 ± 2.09, and 1.78 ± 0.12, respectively. In the control group, levels at baseline and at six months were 3.35 ± 0.51, 145.39 ± 6.69, and 1.55 ± 0.18, respectively, and 3.63 ± 0.57, 153.77 ± 6.64, and 1.75 ± 0.10, respectively. Intragroup differences for all three measures were statistically indistinguishable at six months, and levels were similar between the isoflavone supplement and placebo groups at each measurement. These results indicate that in this group of healthy iodine-replete subjects, soy isoflavones do not adversely affect thyroid function.

Comments by Mary Hardy, MD

In 1999, the U.S. Food and Drug Administration designated soy protein as a heart-healthy food because of its positive effects on lipids1 (The Good). However, persistent concerns have been raised about the negative effect of soy isoflavones on thyroid function (The Bad). A recent clinical trial has provided evidence that these concerns are not clinically significant (The Not-so-ugly) and that deserves to be considered in more detail, given the large number of women with decreased thyroid function and the increasing use of soy foods and supplements.

In vitro studies have shown that genistein and daidzein, the two principle isoflavones in soy, interfere with enzymatic reactions catalyzed by thyroid peroxidase (TPO) that are essential to the production of thyroid hormone.2 In animal studies, inhibitory effects on TPO are demonstrated by soy isoflavones in a dose-dependent fashion, and goiter is more common in rats fed a soy diet, especially if they are iodine-deficient.3 However, effects on other aspects of thyroid function, such as thyroid hormone levels and weight of the gland, were not affected.

Early concerns were raised regarding soy and thyroid function in humans, when a cluster of cases of goiter was reported in infants fed soy formula exclusively. This problem was addressed by adding iodine to formulas and no cases since have been reported.4 However, a study of hypercholesterolemic women reactivated concern.5 These women were fed 40 g of soy with either high (90 mg) or low (56 mg) doses of isoflavones per day for six months. Lipids, steroid hormone levels, and thyroid hormone levels were measured at three and six months. Small effects on thyroid hormone were measured, but the clinical effects of these changes were not known.

To address these persistent concerns, Bruce and her colleagues performed a randomized, double-blind, placebo-controlled trial of the effects of 90 mg/d of isoflavones on thyroid function in postmenopausal women.4 Women were recruited from an ongoing study examining the effect of soy isoflavones on bone density. For this nested study, women must not have a history of breast cancer and currently could not be taking hormone replacement. To ensure an adequate level of iodine, all subjects were given a multivitamin with 150 mcg/d of iodine. Women currently taking thyroid medication were allowed to enroll in the trial; presumably, their conditions were stable before entry into the study. All but one of the recruited women were Caucasian.

After randomization, 42 women were given either an undistinguishable placebo or an isoflavone supplement. This intervention was unusually well-characterized in the article. Each tablet contained 50 mg of isoflavones (30 mg aglycone by weight) in the ratios of 1.3:1.0:0.3 for the glycosides genistin, daidzin, and glycitin. The saponin, protein, and fat content also were reported. This dose was chosen to represent a higher daily dose of isoflavones than was consumed even in the typical Asian diet and is equivalent to approximately 9-12 ounces of tofu. Subjects were instructed to limit soy-containing foods to one serving per week. Blood for thyroid function was drawn at three and six months.

Of the initial 42 subjects, 38 completed the trial. Withdrawals were not related to adverse reactions to the intervention. At six months, there were no statistical differences between groups based on serum levels on TSH, T4, and T3. Isoflavone levels were similar between groups demonstrating equivalent compliance with the study protocol.

This trial is very significant in addressing the lingering concerns regarding the effect of soy isoflavones on thyroid function. As long as women have a normal iodine level, which is easy to ensure with supplementation if dietary sources are not adequate, there should be no concern about clinically significant effects on thyroid hormone levels or function. Happily, we can encourage our patients to use heart-healthy soy foods and supplements without concern for their thyroids.

Dr. Hardy, Associate Director, UCLA Center for Dietary Supplement Research: Botanicals Medical Director, Cedars-Sinai Integrative Medicine Program Los Angeles CA, is on the Editorial Advisory Board of Alternative Therapies in Women’s Health.

References

1. Henkel J. Soy: Health claims for soy protein, questions about other complaints. FDA Consumer May-June 2000. U.S. Food and Drug Administration. Available at: www.fda.gov/fdac/features/2000/300_soy.html. Accessed Feb. 4, 2005.

2. Divi RL, et al. Anti-thyroid isoflavones from soybean: Isolation, characterization, and mechanisms of action. Biochem Pharmacol 1997;54:1087-1096.

3. Doerge DR, Sheehan DM. Goitrogenic and estrogenic activity of soy isoflavones. Environ Health Perspect 2002;110(Suppl 3):349-353.

4. Bruce B, et al. Isoflavone supplements do not affect thyroid function in iodine-replete postmenopausal women. J Med Food 2003;6:309-316.

5. Persky VW, et al. Effect of soy protein on endogenous hormones in postmenopausal women. Am J Clin Nutr 2002;75:145-153. Erratum in: Am J Clin Nutr 2002; 76:695.