February 22, 2011

As you may recall, there is some concern that phytoestrogens – such as the daidzein and genestein found in soy – interfere with thyroid function. Specifically, some evidence (mostly in vitro) suggests that phytoestrogens may inhibit thyroid peroxidase (TPO), the enzyme found on/near the interface of the thyroid cell and the colloid matrix inside the follicle. This enzyme converts iodide into iodine as it exits the cell and enters the colloid, allowing the iodine to bind to thyroglobulin and form T3 and T4. An interesting cross-over randomized controlled trial was published last week that provides some data from humans to add to the mix. Check out the abstract:

J Clin Endocrinol Metab. 2011 Feb 16. [Epub ahead of print]
The Effect of Soy Phytoestrogen Supplementation on Thyroid Status and Cardiovascular Risk Markers in Patients with Subclinical Hypothyroidism: A Randomized, Double-Blind, Crossover Study. Sathyapalan T, Manuchehri AM, Thatcher NJ, Rigby AS, Chapman T, Kilpatrick ES, Atkin SL.
Context: There is concern whether soy phytoestrogens may affect thyroid function. If true, soy phytoestrogens may be expected to have a greater impact in subjects with subclinical hypothyroidism. Objective: The primary aim was to determine the effect of soy phytoestrogen supplementation on thyroid function, with a secondary aim of assessing the effects on cardiovascular risk indices in patients with subclinical hypothyroidism. Design and Setting: We conducted a randomized, double-blind, crossover study in a tertiary care setting. Participants: Sixty patients with subclinical hypothyroidism participated in the study. Intervention: Patients were randomly assigned to either low-dose phytoestrogen (30 g soy protein with 2mg phytoestrogens, representative of a Western diet) or high-dose phytoestrogen (30 g soy protein with 16mgphytoestrogens, representative of a vegetarian diet) supplementation for 8 wk, then crossed over after an 8-wk washout period. Main Outcome Measures: The primary outcome was progression to overt hypothyroidism, with secondary outcome measures of blood pressure, insulin resistance, lipids, and highly sensitive C-reactive protein (hsCRP). Results: Six female patients in the study progressed into overt hypothyroidism with a standardized rate ratio of 3.6 (95% confidence interval, 1.9, 6.2) after 16-mg phytoestrogen supplementation. Both systolic and diastolic blood pressure decreased with 16 mg phytoestrogens, whereas systolic pressure alone decreased with 2mg phytoestrogens. Insulin resistance (homeostasis model assessment of insulin resistance, 3.5 ± 0.09 vs. 2.6 ± 0.08; P < 0.02) and hsCRP (4.9 ± 0.04 vs. 3.9 ± 0.03; P < 0.01) decreased with 16 mg phytoestrogens. Lipid profile remained unchanged. Conclusion: There is a 3-fold increased risk of developing overt hypothyroidism with dietary supplementation of 16 mg soy phytoestrogens with subclinical hypothyroidism. However, 16-mg soy phytoestrogen supplementation significantly reduces the insulin resistance, hsCRP, and blood pressure in these patients.
PMID: 21325465


A few things of interest to herbalists/nutritionists that were not in the abstract:

  • The phytoestrogens in question were composed of 54% genestein, 35% daidzein and 12% glycitein as aglycones
  • The subjects were mostly female (52/60) and the average age was 52.7 +/- 13.8 years.
  • Of the 6 women who developed overt hypothyroidism during the high dose phase, 3 were from the group who completed the high dose in the first phase of the crossover and three completed the high dose in the second phase. All were still on levothyroxine at 6 month follow up, indicating that the hypothyroid situation did not resolve upon discontinuation of the phytoestrogen mix.
  • Despite the above, mean TSH, free T3 and free T4 levels did not differ between groups in either phase of the trial.

Some things that I appreciate about this paper:

  • The researchers did a pretty good job accounting for various external factors. For example, they measured plasma phytoestrogen levels to check compliance and to ensure that the patients were avoiding other dietary phytoestrogens; the authors also did a 24 hour urine collection to measure iodine secretion, to check that patients were iodine-replete.
  • The 8 week washout period was quite generous. Markers returned to baseline during this time, except for the patients who developed hypothyroidism, which did not resolve.
  • The discussion section is strong, and the authors explore a variety of potential issues with the study, including lack of a true placebo.
  • The conclusion is pleasantly nonalarmist, simply stating that it appears that soy phytoestrogen supplementation may hasten hypothyroidism in people who are subclinical to start, and that closer monitoring may be warranted.

A few things that were missing/off:

  • The authors seem to think that ‘vegan’ and ‘vegetarian’ are equivalent
  • The authors also used the term ‘phytoestrogen’ to refer to (primarily) soy phytoestrogens, for the most part without acknowledging that there are many other sources. What about vegans/vegetarians who do not eat soy? These data are likely not relevant for those folks.
  • Along a similar line, I’d also like to see some discussion of the differences between a vegetarian DIET and phytoestrogen supplementation. The soy phytoestrogens may certainly act differently embedded in their natural matrix rather than isolated and added to soy protein alone

Final thoughts

While I’m not a huge fan of soy, particularly not in its more processed forms, there are certainly some potential benefits. Many clients eat a soy-rich diet and some may also be taking supplements that include soy-based phytoestrogens. I agree with the authors that it is worth keeping an eye on thyroid/TSH levels with these folks, particularly given a family history of thyroid disease or the presence of TPO antibodies.

About Camille Freeman, DCN, RH (she/her)

Hi there! I'm a clinical herbalist and nutritionist specializing in fertility and menstrual health. I run the Monday Mentoring community of practice and also offer continuing education programs for practicing herbalists and nutritionists (Check out this year's Deep Dive!). I'm also a former professor with the Maryland University of Integrative Health, where I taught physiology, pathophysiology, and mindful eating for 17 years. 

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