Phytoestrogens
CATEGORY: Not classified
USED IN: Naturally occurring in whole grains, dried beans, peas, fruits, broccoli, cauliflower, soy; also as concentrated extracts from these foods
Studies leading to concerns about harmful effects of synthetic estrogens must be understood alongside evidence about the effects of plant estrogens (phytoestrogens). Foods such as whole grains, dried beans, peas, fruits, broccoli, cauliflower and especially soy products are rich in phytoestrogens. Although scientific evidence suggests that plant-based estrogens offer nutritional benefits and are associated with healthy diets (Cederroth, 2009), the data are conflicting as to whether the soy-based diets have beneficial, harmful or neutral effects on breast cancer risk (Rice, 2006; Ziegler, 2000).
Some of the disparity in the literature may be related to type of soy product or other phytoestrogen-containing vegetables consumed by individuals. The isoflavones genistein and its metabolite genistin are both natural phytoestrogens found in soy. Both have been shown to increase tumor growth in a variety of different models, but highly processed soy flour that does not contain these isoflavones has no effect. Purified soy-protein isolates are often processed to contain different concentrations of isoflavones, and their influence on mammary tumors is related to the amount of isoflavone, not the total amount of soy protein consumed (Helferich, 2008).
Several epidemiological studies have shown that regular consumption of soy-based products or other vegetables high in phytoestrogens, as part of a normal balanced diet, can exert a protective influence with regard to later development of breast cancer. This effect has been studied extensively in China, where soy intake is a regular part of the cultural diet. There, substantial evidence indicates that higher soy intake in adulthood or in adolescence is associated with a decreased risk of pre-menopausal breast cancer (Lee, 2009). Other studies have found protective effects of soy intake for both pre- and post-menopausal cancer, independent of receptor profile (ER and PR positive or negative) of the tumors (Zhang, 2009). For Chinese women who were previously diagnosed with breast cancer, consumption of soy in its many forms found regularly in a woman’s diet was correlated with decreased recurrence of cancer and longer survival (Shu, 2009).
Looking at Asian-American women living in California and Hawaii, a recent study reported that soy intake during childhood, adolescence and adulthood all were associated with decreased later risk of breast cancer (Korde, 2009). The protective effect of regular dietary soy intake during childhood was the strongest, and it was not mitigated when other variables, like site of birth (Asian countries or United States), degree of continuing Asian lifestyle and cultural practices, reproductive factors or family history of breast cancer, were factored into the analysis. In general, protective effects of dietary soy intake have been found to be strongest in association with childhood and early adolescent intake (Adlercreutz, 2003). One possible explanation for this association is that peri-pubertal exposures to genistein and other phytoestrogens may mimic the protective changes in breast development that are usually observed during the first pregnancy (Messina, 2009; Warri, 2008).
Studies examining phytoestrogen intake and breast cancer risk in non-Asian populations have found more mixed results (Wu, 2008). This may be related to the difference in both amounts and types of phytoestrogens typically eaten as part of the traditional diets found in both the United States and Europe (Mense, 2008). As examples, a recent French study found that consuming non-soy phytoestrogens as part of a woman’s daily diet had a protective effect against post-menopausal breast cancer (Touillaud, 2007), while a British study found no such relationship (Travis, 2008). And a recent multiethnic study conducted in Hawaii demonstrated that the amount of soy in the diet might interact with other phytoestrogens in protecting against breast cancer. For Japanese Americans who had high soy content in their regular diets, there was a strong and significant relationship with non-soy-based phytoestrogens and decreased risk of breast cancer. A similar strong relationship was not found for white women in the study, who tended to eat diets lower in soy content (Goodman, 2009).
Data from studies on laboratory animals and cell culture models have also indicated a complicated story. In several studies, exposures to phytoestrogens have led to increases in mammary tumor proliferation and growth. The soy phytoestrogens genistein and daidzein, as well as their metabolites, cause oxidative DNA damage, a process that is thought to play a role in tumor initiation (Murata, 2004). Other data suggest that these two soy-based phytoestrogens may have opposing effects on the efficacy of the breast cancer drug tamoxifen (Constantinou, 2005; Liu, 2005).
The effects of the phytoestrogens may be related to the particular mixtures of components in the diet (Dip, 2009), and cellular effects may vary depending on concentration and timing. In a recent study examining the effects of different types and concentrations of phytoestrogens on the expression of estrogen-dependent gene activity in human breast cancer cells grown in vitro (MCF-7 cells), low doses of genistein resulted in a pattern of expression that indicated increased cell proliferation, while higher concentrations led to increased apoptosis, or cell death. On the other hand, the phytoestrogen daidzein (found in soy) slightly enhanced cell proliferation in the absence of natural estrogen (a possible model for post-menopausal breast cancer), while resveratrol (found in grapes and red wine) significantly decreased tumor cell proliferation (Sakamoto, 2009). These latter data are consistent with other studies finding anti-carcinogenic effects of resveratrol in several models (Athar, 2009; Garvin, 2006).
Recently, concern has been raised about exposure of newborn babies to soy-based products, primarily through infant formulas. Although one study has shown that feeding only soy formula for the first four months of life was associated with a decrease in later development of breast cancer (Boucher, 2008), animal studies have indicated deleterious effects of neonatal soy exposure on development of the female reproductive system and subsequent fertility (Jefferson, 2009).
