Two important documents resulting from prior workshops and an evidence-based review served as the background to the current workshop. In 2005 the National Institute of Environmental Health Sciences of NIH held 2 workshops, 1 to review the literature to assess whether phytoestrogens could significantly affect hormonal and other endpoints in animals and the other to develop strategies to address problems caused by batch-to-batch variation in estrogenic compounds in animal diets. The workshop results were reported in early 2008 (1
). The key finding of these workshops and report was that research results are often confounded by unanticipated levels of phytoestrogens in laboratory unpurified diets. Even though the protein content of soy-containing animal diets was constant, there was significant batch-to-batch variability in estrogenic content of commercial animal diets and this variability resulted in differences in experimental outcomes. Much of the variability may be eliminated by using phytoestrogen-free diets, such as the AIN 93 semipurified diet, supplemented with a known quantity of phytoestrogens (2
). Although the National Institute of Environmental Health Sciences workshops focused on animal studies, they concluded that it is clear that variation in diet components may also affect clinical studies. Hence, the NIH questioned the quality of data from human studies.
NIH has supported research on soy in its many forms for a range of outcomes. Results of clinical studies have been inconsistent. Questions concerning which forms of soy might be better for studies of specific health outcomes and at what doses led the National Center for Complementary and Alternative Medicine and the Office of Dietary Supplements, both of NIH, to commission an evidence-based review of the literature, “Effects of Soy on Health Outcomes,” through the Agency for Health Care Research and Quality (AHRQ) (4
). The review summarized the formulations of soy products and/or soy food used in clinical trials and the current evidence of the health effects of soy and its constituents on the following health outcomes: cardiovascular disease, menopausal symptoms, endocrine function, cancer, bone health, reproductive health, kidney function, cognitive function, and glucose metabolism. In addition, safety issues and drug interactions associated with using soy were summarized.
The AHRQ evidence-based review, released in 2005 (4
), reported that about three-quarters of the 281 included trials studied soy supplements with the remainder being trials of soy foods. Fifty-seven percent of the soy supplement trials used isolated soy protein with isoflavones, 36% used isoflavones alone, and 6% used soy protein without isoflavones. Textured soy protein was evaluated in 25% of soy foods trials and soy flour was evaluated in another 25%. The remaining 50% evaluated soybeans alone, tofu alone, and other soy foods. Isoflavone and soy protein doses varied widely, from 10 to 18516
mg/d and 14 to 154 g/d, respectively. Only a few studies directly compared doses. In addition, there was a considerable degree of heterogeneity among the studies, including study design, intervention duration, background diet, and controls. A large number of studies suffered from inadequacies of reporting or study design, thereby limiting conclusions.
If clinical studies are to be pursued, then study sponsors, investigators, reviewers, and journal editors need to ensure that the experimental designs are optimal and the studies properly executed. How do we move forward?