April 2020 Issue
Soyfoods & Thyroid Health
By KC Wright, MS, RDN, LD
Vol. 22, No. 4, P. 28
Are Clients’ and Patients’ Concerns Justified?
Over the past several decades, consumption of soyfoods in the United States has increased, largely due to the legume’s potential health benefits and the increase in people following plant-based diets. According to the Soyfoods Association of North America, the US retail soyfoods industry rose from $1 billion in 1996 to $4.5 billion in 2013, with dramatic growth following the 1999 FDA approval of a health claim linking soy with heart disease reduction.
Beyond fresh soybeans (edamame), dried soybeans, tofu, soymilk, miso, soy sauce, soybean oil, meat alternatives, and more, the soy industry also has promoted the development of soy supplements and fortification of foods with soy.1
Soyfoods have been rigorously investigated for their role in chronic disease prevention and treatment. There’s evidence that they help reduce risk of coronary heart disease, breast cancer, and prostate cancer. Soy also has been shown to help alleviate menopausal symptoms, reduce depressive symptoms, improve skin health, and positively affect renal function.
Despite all the potential nutritional attributes of soyfoods, there has been much consumer concern about their interference with thyroid health, especially among individuals whose thyroid function already is compromised. “It’s a huge concern I hear from my patients,” says Stephanie L. Lee, MD, PhD, associate chief of the section of endocrinology, nutrition and diabetes at Boston Medical Center.
The two main components of soy responsible for its proposed health benefits are soy protein and soy isoflavones. US daily per capita soy protein consumption averages less than 2 g, just a fraction of the 60 to 85 g total protein typically consumed.2 For reference, a cup of soymilk contains 8 g protein (the same as cow’s milk.)
Soy protein contributes negligible amounts of isoflavones to American diets not only because the amount of soy protein consumed is small but also as a result of processing; the concentration of isoflavones in isolated soy protein used in the food industry is low. Estimated US per capita intake of isoflavones is less than 2.5 mg, compared with one cup of soymilk made from whole soybeans that contains about 25 mg isoflavones.2
In addition to providing high-quality protein, soybean’s isoflavones are phytoestrogens—plant-derived compounds with estrogenic activity. The compounds genistein and daidzein account for the majority of isoflavone content. According to Angela M. Leung, MD, an assistant professor of medicine at the UCLA David Geffen School of Medicine and an endocrinologist at both UCLA and the VA Greater Los Angeles Healthcare System, “Genistein and daidzein can interfere with the thyroid’s ability to produce thyroid hormone but can be potentially reversed by supplemental iodine.”
Much of the research on soyfoods and thyroid health has been done in animal studies, including one dating back to 1933 where rats fed raw soybeans had markedly enlarged thyroids.3 In the 1960s, case reports of infants developing hypothyroidism in response to the consumption of soy infant formula were addressed when the formula began to be fortified with iodine, a vital constituent of thyroid hormones.4,5
“The concern of soy intake on thyroid health is different for infants and children vs adults,” Leung says. “In early development, the thyroid gland is still immature, and thus even small insults to adequate thyroid hormone production may be enough to have clinically significant effects. Historically, soy-based infant formula did not universally contain iodine, thus there had been reported cases of soy formula–induced hypothyroidism. Currently, iodine is a required component of infant formula, thus this is no longer a concern.”
But the issue of soyfoods having a potential effect on thyroid health emerged again in 1999 during the approval process of a health claim for soybeans and coronary heart disease. FDA researchers raised concerns about the possibility of soybean isoflavones inducing goitrogens, substances that disrupt the production of thyroid hormones by interfering with iodine uptake in the thyroid gland.6,7
To understand how soy may affect thyroid health, it’s important to review iodine’s role and basic thyroid gland function. Iodine is an essential trace mineral naturally found in seawater, kelp, dairy, and grains, and fortified in salt.8 Only thyroid cells can absorb iodine, as the thyroid gland functions to take up the mineral and convert it into thyroxine, the major hormone secreted by the thyroid gland.
Thyroxine is also called T4 because it contains four iodine atoms. To be effective, T4 loses an iodine atom to convert to triiodothyronine (T3), which is unbound and able to enter and affect body tissues, including the brain.9 These hormones regulate many key biochemical processes (including protein synthesis and enzyme activity). They’re critical determinants of metabolism and are required for normal development in both fetuses and infants. Thyroid function is regulated by thyroid-stimulating hormone (TSH) secreted by the pituitary gland, which triggers the thyroid to take up iodine.
Without adequate iodine, TSH levels remain high, leading to goiter—an enlargement of the thyroid gland, reflecting the body’s failed attempt to sequester iodine from circulation. Thus, hypothyroidism ensues, with an occurrence rate of approximately 5 out of 100 people.10
Most cases of hypothyroidism are caused by an underactive thyroid gland and are relatively mild. Though hypothyroidism can’t be cured, the condition can be controlled with a prescribed synthetic thyroid medication. For maximum effectiveness, the medication should be taken on an empty stomach, at least three hours after eating food and at least 30 to 60 minutes before consuming food.11
Soy-Thyroid Research Debate
The ongoing debate among the research community about soy consumption and thyroid health has been long and controversial. In vitro studies have demonstrated that soy inhibits thyroid peroxidase (TPO), an enzyme involved in the synthesis of T3 and T4.7 There also has been much speculation that, for certain population subgroups, soyfoods and isoflavones may adversely affect thyroid function in susceptible individuals by interfering with the absorption of synthetic thyroid hormone.
As mentioned, the goitrogens in soy interfere with the uptake of iodine in the thyroid and can exacerbate iodine deficiency.8 Yet in a 2006 narrative review that evaluated 14 clinical trials, the authors concluded that neither soy nor isoflavones affect thyroid function in euthyroid individuals.12 The review authors acknowledged that more research needs to be conducted to address two issues: whether soy has any effect on patients with a compromised thyroid function, and whether the legume is detrimental to thyroid health in patients whose iodine intake may be inadequate.
Research later addressed the iodine issue in a 2012 study on menopausal women taking phytoestrogen dietary supplements. Subjects with adequate iodine intake weren’t at risk of developing any thyroid gland disorders.13
To determine soy’s effect on those with a compromised thyroid function, a randomized, double-blinded, crossover study of 60 patients with subclinical hypothyroidism were randomly assigned to take either a low-dose phytoestrogen supplement—30 g soy protein with 2 mg phytoestrogen (representative of a Western diet)—or a high-dose phytoestrogen supplement—30 g soy protein with 16 mg phytoestrogen (representative of a vegetarian diet).14
Results showed a three-fold increased risk of developing overt hypothyroidism with the high-dose supplement. Data also suggest that the risk of developing overt hypothyroidism was much higher in females. The authors suggested that this subgroup of people with subclinical hypothyroidism may need more careful monitoring of thyroid function.14 Lee agrees: “Only in this one category of subclinical hypothyroidism should people be concerned” about high soy intake. “The vast majority of people should have no problems at all (with thyroid function) consuming soy,” she says.
More recently, this same research group published results from another double-blinded crossover study that examined the effect of a pharmacologic dose of soy phytoestrogens on thyroid function in subjects with subclinical hypothyroidism. Forty-four patients were randomly assigned to receive either 66 mg phytoestrogens with 30 g soy protein or 0 mg phytoestrogens with 30 g soy protein. Results showed that the 66-mg pharmacologic dose of soy phytoestrogens didn’t change thyroid function in patients with subclinical hypothyroidism.15
Seventh-day Adventists, whose doctrine encourages followers to eat a plant-based diet when feasible, have been a demographic that has proven to be a good resource for epidemiologic data.16 Many Seventh-day Adventists who follow a vegan diet consume an average of 8 to 12 g soy protein daily.
One observational study examined the relationship between soy consumption and thyroid function among Seventh-day Adventists.17 Approximately one-half of the study cohort of 800 men and women aged 30 and older were vegetarians. None of the study subjects were on thyroid medication. Over a six-month period, subjects completed six 24-hour diet recalls that were compared with blood levels of TSH.
Researchers found that subjects who ate just under two servings of soyfoods daily, compared with those who didn’t eat any soy, were four times more likely to have a high TSH. These findings were evident only among female subjects; there was no association found in men. Higher TSH levels were found in women who followed either a vegan or lacto-ovo vegetarian diet. The women in the group eating the most soy averaged about 11 g per day, or about two servings.
According to Serena Tonstad, MD, PhD, an endocrinologist from the University of Oslo and the lead author of the study, women appear to have a higher risk of developing thyroid problems, especially with age.18 This study didn’t look at levels of T4 or T3 thyroid hormones.
More recently published, a systematic review and meta-analysis of 18 randomized controlled trials investigated the link between soy or soy product consumption and thyroid function via the measurement of thyroid hormone levels. The studies intervened primarily with soy protein or isoflavone supplements with doses ranging from 40 to 200 mg per day. Results showed there was a modest yet significant increase in TSH as a result of soy protein and/or isoflavone supplementation. However, the analysis found no effects of the intervention on the two primary thyroid hormones, free T4 and free T3, suggesting that, clinically, this may not be significant. The authors concluded that, overall, soy supplementation has no effect on thyroid hormones.19 “In adults, most studies have shown that soy intake does not appear to adversely affect thyroid hormone production, although there are some limited data suggesting impacts to the thyroid axis in basic and animal studies,” Leung says.
Counseling Cues for RDs
According to Lee, there’s “lots of hearsay, but not a lot of good science” demonstrating that soyfoods are detrimental to thyroid health. RDs can address consumer confusion about soyfoods by explaining that conflicting outcomes in nutrition research can be attributed to variables such as the difference between animal and human studies, as well as the type of soyfood being tested, be it fresh soybeans or soy protein isolates.
The Nutrition Source at the Harvard School of Public Health, an online research and academic resource for consumers and professionals, also emphasizes this point: “Soy is a unique food that is widely studied for its estrogenic and antiestrogenic effects on the body. Studies may seem to present conflicting conclusions about soy, but this is largely due to the wide variation in how soy is studied. Results of recent population studies suggest that soy has either a beneficial or neutral effect on various health conditions. Soy is a nutrient-dense source of protein that can safely be consumed several times a week and is likely to provide health benefits—especially when eaten as an alternative to red and processed meat.”20
Despite lingering concerns over soy’s effects on thyroid health, RDs can discuss how soyfoods can be part of a balanced diet. Soyfoods contain high-quality protein, comprising all nine essential amino acids. Soyfoods also are rich in B vitamins, fiber, potassium, and magnesium. Adults with hypothyroidism also can consume soyfoods without any detrimental effects.
Although soy has been shown to inhibit the absorption of synthetic thyroid hormone replacement medication, RDs should remind patients to consume all food, including soyfood, at least three hours before or one hour after taking the medication.21
Individuals who consume soyfoods regularly and have subclinical hypothyroidism, as determined by a high TSH level, and/or those whose iodine intake is marginal, must be counseled on ways to achieve adequate iodine intake. In fact, all individuals—independent of soy intake—should consume adequate food sources of iodine, including kelp, dairy, grains, and iodized salt. (See “Update on Iodine” in the December 2018 issue of Today’s Dietitian.)
As evident from the research, women—especially women older than 60—along with those who follow a strict high-soy, vegetarian, or vegan diet with subclinical hypothyroidism, may need additional monitoring for irregularities in thyroid hormone levels.
Finally, as with any food recommendations, it’s best to obtain soy from whole food sources—before they’ve been highly processed with the addition of substances (eg, sodium, modifiers, preservatives) or the removal of beneficial nutrients (eg, fiber, isoflavones) that change the nutrient density of the food. Industrial processing separates the oil and protein from the soybean for soybean oil and isolated soy protein. And, Lee says, “isolated soy protein has very little isoflavones.”
Edamame is the least processed source of soy and can be found fresh seasonally or frozen in the shell or shelled. When edamame is aerated to remove moisture, the result is dried soybeans. Tofu is made from dried soybeans that are ground in water, heated, and coagulated with minerals such as calcium or magnesium salt. The curds are then pressed into a block and may or may not be seasoned with flavorings. Soymilk, a stable emulsion of protein, water, and oil, is made by soaking and grinding soybeans before filtering out particulates.
Eating a couple of servings of any of these minimally processed soyfoods on a regular basis can be part of a healthful diet for most people.
— KC Wright, MS, RDN, LD, divides her time between being a research dietitian at Dartmouth-Hitchcock Medical Center and maintaining a nutrition communications practice. She advocates for good food and sustainable food systems at www.wildberrycommunications.com.
1. US Department of Health & Human Services. Dietary Guidelines for Americans 2015–2020: Eighth Edition. http://health.gov/dietaryguidelines/2015/guidelines/. Published January 7, 2016.
2. Messina M. Soybeans and the U.S. food supply. Soy Nutrition Institute website. https://thesoynutritioninstitute.com/soybeans-and-the-u-s-food-supply/. Updated May 4, 2016. Accessed December 27, 2019.
3. McCarrison R. The goitrogenic action of soy-bean and ground-nut. Indian J Med Res. 1933;21:179-181.
4. Shepard TH, Pyne GE, Kirschvink JF, McLean M. Soybean goiter — report of three cases. N Engl J Med. 1960;262:1099-1103.
5. Van Wyk JJ, Arnold MB, Wynn J, Pepper F. The effects of a soybean product on thyroid function in humans. Pediatrics. 1959;24:752-760.
6. Food labeling: health claims; soy protein and coronary heart disease. Food and Drug Administration, HHS. Final rule. Fed Regist. 1999;64(206):57700-57733.
7. Divi RL, Chang HC, Doerge DR. Anti-thyroid isoflavones from soybean: isolation, characterization, and mechanisms of action. Biochem Pharmacol. 1997;54(10):1087-1096.
8. Iodine: fact sheet for health professionals. National Institutes of Health, Office of Dietary Supplements website. https://ods.od.nih.gov/factsheets/Iodine-HealthProfessional/. Updated July 9, 2019. Accessed December 27, 2019.
9. Thyroid abbreviations & definitions. American Thyroid Association website. https://www.thyroid.org/patient-thyroid-information/abbreviations-definitions/. Accessed December 27, 2019.
10. Hypothyroidism (underactive thyroid). National Institute of Diabetes and Digestive and Kidney Diseases website. https://www.niddk.nih.gov/health-information/endocrine-diseases/hypothyroidism#common. Updated August 2016. Accessed December 27, 2019.
11. AbbVie Inc. Synthroid® (levothyroxine sodium) tablets. https://www.rxabbvie.com/pdf/synthroid.pdf. Updated November 2018. Accessed December 27, 2019.
12. Messina M, Redmond G. Effects of soy protein and soybean isoflavones on thyroid function in healthy adults and hypothyroid patients: a review of the relevant literature. Thyroid. 2006;16(3):249-258.
13. Sosvorová L, Mikšátková P, Bičíková M, Kaňová N, Lapčík O. The presence of monoiodinated derivates of daidzein and genistein in human urine and its effect on thyroid gland function. Food Chem Toxicol. 2012;50(8):2774-2779.
14. Sathyapalan T, Manuchehri AM, Thatcher NJ, et al. The effect of soy phytoestrogen supplementation on thyroid status and cardiovascular risk markers in patients with subclinical hypothyroidism: a randomized, double-blind, crossover study. J Clin Endocrinol Metab. 2011;96(5):1442-1449.
15. Sathyapalan T, Dawson AJ, Rigby AS, Thatcher NJ, Kilpatrick ES, Atkin SL. The effect of phytoestrogen on thyroid in subclinical hypothyroidism: randomized double blind, crossover study. Front Endocrinol (Lausanne). 2018;9:531.
16. Rizzo G, Baroni L. Soy, soy foods and their role in vegetarian diets. Nutrients. 2018;10(1):E43.
17. Tonstad S, Jaceldo-Siegl K, Messina M, Haddad E, Fraser GE. The association between soya consumption and serum thyroid-stimulating hormone concentrations in the Adventist Health Study-2. Public Health Nutr. 2016;19(8):1464-1470.
18. Doheny K. Soy & your thyroid: how much is too much? EndocrineWeb website. https://www.endocrineweb.com/news/thyroid-diseases/54056-soy-your-thyroid-how-much-too-much. Updated March 5, 2019. Accessed December 27, 2019.
19. Otun J, Sahebkar A, Östlundh L, Atkin SL, Sathyapalan T. Systematic review and meta-analysis on the effect of soy on thyroid function. Sci Rep. 2019;9(1):3964.
20. Straight talk about soy. Harvard T.H. Chan School of Public Health, The Nutrition Source website. https://www.hsph.harvard.edu/nutritionsource/soy/. Accessed December 27, 2019.
21. Liwanpo L, Hershman JM. Conditions and drugs interfering with thyroxine absorption. Best Pract Res Clin Endocrinol Metab. 2009;23(6):781-792.