Perspective: Observational studies involving low soy intake populations have limited ability for providing insight into the health effects of soybean isoflavones.

Isoflavones are naturally occurring plant compounds found in uniquely high amounts in soybeans and foods made from this legume. These soybean constituents have been proposed to exert several health benefits and as such they have been the subject of an enormous amount of research. This research includes randomized controlled trials (RCTs) and epidemiologic investigations. Although statistically significant associations between isoflavone intake and a wide range of health outcomes have been identified in cohorts involving low isoflavone intake populations, we suggest that these associations are unlikely to have a causal basis because exposure is too low for isoflavones to exert physiological effects. In cohorts involving predominantly non-Asian, non-vegetarian populations, the highest isoflavone intake category is typically ≤3 mg/d, an amount of isoflavones provided by approximately 30 ml (2 tablespoons) of soymilk made from whole soybeans. In comparison, mean isoflavone intake in the upper intake categories in observational studies involving high isoflavone intake populations is typically ≥50 mg/d. In RCTs, intervention doses of isoflavones typically range from between 40 and 100 mg/d. Health professionals advising patients and clients about soy food and isoflavone intake need to be aware of the limitations of epidemiologic research involving low isoflavone intake populations. Intake recommendations are best based on the results of RCTs using clinically relevant doses of isoflavones and epidemiologic studies involving populations for whom soy foods are a habitual part of the diet.