Soybean meal, a common ingredient in laboratory animal diets, contains variable levels of phytoestrogens. These plant-derived compounds mimic the structure and function of estrogens in mammals and can have an impact on research results.

The main phytoestrogens (and their primary sources) include:

  • isoflavones (mainly genistein and daidzin, which are found in soybean protein),
  • coumestans (mainly coumestrol, which is found in alfalfa), and
  • ligans (found in flax and sunflower).

Read more about the physiological effects and research variations that can occur, if diets contain isoflavones.

Physiological effects of isoflavones

Estrogen receptors affect a wide range of physiological systems, including the cardiovascular, immune, reproductive, endocrine, and central nervous systems. Isoflavones act through the estrogen receptor and also feature estrogen independent mechanisms, such as acting as PPAR agonists, activating the cAMP/PKA pathway and performing antioxidant activities.

Research variations can occur if diets contain isoflavones

Interestingly, isoflavones appear to have a protective effect in animal models, modulating pathological conditions such as cancer, metabolic syndrome, and neurodegeneration. This can decrease the effectiveness of research since the animal models were developed in order to exhibit a specific pathology. Isoflavones may also confound the effects of putative or potential therapeutic compounds.

Dietary isoflavones can affect research in a variety of ways. First, since isoflavones do not illicit a classic dose response, there is no simple absolute threshold for the physiological effects of isoflavones. Some effects have been demonstrated with low levels of phytoestrogens. For example, American investigators found that athymic BALB/c mice who were implanted with prostate cancer cells and fed a diet with 100 ppm genistein exhibited reduced lung metastases. In another study, the proportion of TRAMP mice exhibiting prostate tumors dropped significantly when 100 ppm genistein was added to their diet.

Tissue responses can also differ. For example, Naaz et al., reported that in ovariectomized mice that were fed 300 ppm genistein, uterine weight increased; at the same time, the mice had to be fed 500 ppm in order to decrease adipose tissue. Effects on body weight were only significant when the mice were fed 1500 ppm. Moreover, the magnitude and direction of isoflavone effects varies. Similar levels of dietary genistein (less than 1000 ppm) suppressed or enhanced the action of tamoxifen in models of ectopic breast cancer in the presence of estradiol.

Variation of isoflavone levels in animal feed further complicates matters

Diets which feature typical amounts of soybean meal will contain isoflavone levels ranging from 100-700 ppm. The isoflavone content of soybean meal can fluctuate widely – from two to six fold – due to genetics and growing conditions. Fortunately, steps can be taken to minimize the wide range in the levels of isoflavone. Fixed formulation, or adding the same amount of soybean meal to each diet lot, can help. In addition, sourcing the soybeans from the same region restricts isoflavone variation to twofold.

Laboratory animal diets which contain soybean meal should be avoided if the end point might be affected by dietary isoflavones. Teklad Global Rodent Diets have minimal isoflavones and lead to reliable, repeatable research results. If you would like to know more about the impact of phytoestrogens on research, please chat with our Inotiv nutritionists.

Discover more about dietary phytoestrogens: a source of research variation


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