Isoflavone Supplements Are Safe According to the European Food Safety Authority
By Mark Messina, PhD, Executive Director, Soy Nutrition Institute
Soybean isoflavone supplements have no adverse effects on the breast or uterus of postmenopausal women or on thyroid function according to the European Food Safety Authority (EFSA). The organization’s comprehensive report was published in October of 2015. The EFSA is comparable to the US Food and Drug Administration.
EFSA’s conclusion is not surprising given the evidence but is especially welcome given the history behind the report. EFSA undertook their multiyear in-depth evaluation of isoflavones in response to a request in 2008 by the BfR (Bundesininstut für Riskobewertung), which is the German Federal Institute for Risk Assessment in the field of consumer health protection. The initial focus of the EFSA review included isoflavones from foods, supplements and soy infant formula but the EFSA inexplicably decided not to release this report and instead to focus only on isoflavones from supplements.
The EFSA identified 43 human and 62 animal studies that met their inclusion criteria. To be eligible, the human and animal studies had to be at least 12 weeks and 5 days in duration, respectively. Since the evaluation was focused specifically on peri- and postmenopausal women only human studies involving these populations were considered eligible for evaluation. Ovariectomized animals were also included in the review.
The evaluation of breast tissue included 4 epidemiologic studies involving 2,216 women that investigated isoflavone supplements and breast cancer risk, 8 clinical studies involving 741 women that assessed mammographic density and 2 clinical studies involving 75 women that determined histopathological changes. Not included in the formal review because of its short duration was a study published in the Journal of the National Cancer Institute in 2014 that caused quite a stir because the authors found that isoflavone exposure caused changes in gene expression possibly representative of a proliferative effect.1 However, the EFSA noted that the findings of this study were actually consistent with their overall conclusion about the safety of isoflavone supplements because direct measurement of in vivo breast cell proliferation found no changes.
One of the studies cited by EFSA that found no adverse effects on breast tissue intervened with an amount of genistein provided by approximately 15 servings of soyfoods. Genistein is the main isoflavone in soybeans and is the isoflavone that stimulates tumor growth in some rodent models. Thus, even pharmacological doses of isoflavones don’t exert adverse effects. Finally, the EFSA noted that conclusions regarding the safety of isoflavones are consistent with the Women’s Health Initiative Trial which found that estrogen exposure did not increase risk of invasive breast cancer. In fact, estrogen therapy was protective against breast cancer in this study involving 10,000 women.
A total of 11 clinical studies involving 1,501 women that evaluated thyroid-related endpoints were identified. The collective findings from these studies led to the conclusion that isoflavones don’t adversely affect thyroid function. A British study that evaluated the effects of isoflavones on the progression of subclinical hypothyroidism to overt hypothyroidism was excluded from the review because data were not reported separately for men and women.
No epidemiologic studies investigating isoflavone supplements and risk of uterine cancer were identified. Included in the review were 25 clinical studies involving 1,484 women that measured endometrial thickness and 9 studies involving 677 women that assessed histopathological changes. EFSA noted that one study that intervened with high-dose isoflavone supplements provided evidence of a possible estrogenic, but not carcinogenic, effect on the uterus.
EFSA concluded that the existing data do not allow for a single health-based guidance value for isoflavone intake from supplements but that the doses used in the trials, which generally ranged from about 50 to 100 mg/day, can serve as guide.
The EFSA was not charged with evaluating the health benefits of isoflavones from food or supplements. Nevertheless, the EFSA report should allow researchers and health professionals to focus greater attention on the proposed benefits of isoflavones now that concerns about safety have been alleviated, at least with respect to postmenopausal women. In this regard there is solid evidence that isoflavones improve arterial health and alleviate hot flashes in this group.
Soyfoods have also been linked to statistically significant reductions in cancer recurrence and mortality in women who have been treated for breast cancer.2 Likewise, although EFSA found isoflavone supplements do not increase risk of endometrial cancer, epidemiologic data not considered by EFSA show that soyfood intake is actually associated with a decreased risk of developing cancer of the endometrium.3