Life Extension Magazine November 2013
Enjoy Estrogen’s Multiple Benefits While Guarding Against Potential Risks
By William Faloon
Cruciferous Vegetables Protect Against Tumor-Proliferating Estrogen Metabolites
Scientists have identified compounds in cruciferous vegetables (broccoli, cauliflower, Brussels sprouts, cabbage, kale) that specifically inhibit the formation of dangerous breakdown products of estrogen that promote cancer growth.7,43,44 Cruciferous vegetable compounds also help activate vital enzyme pathways responsible for neutralizing the many carcinogens we are inevitably exposed to each day.7,45-47
One of the best-studied cruciferous vegetable compounds is called indole-3-carbinol (I3C). Women seeking to restore youthful hormone balance should make sure to obtain enough I3C from their diet or by taking standardized supplements. The reason for this is that I3C increases levels of a less potent estrogen metabolite (2-hydroxyestrone) with lower affinity for the estrogen receptor, while reducing levels of an estrogen metabolite that is more potent and binds with greater affinity to the estrogen receptor (16-alpha-hydroxyestrone).43 Higher levels of 16-alpha-hydroxyestrone and lower levels of 2-hydroxyestrone are associated with greater risk of breast and other estrogen-responsive cancers.48,49
To emphasize the critical importance of indole-3-carbinol (I3C), please understand that aging women still produce estrogen. All the estrogen in women’s bodies (both endogenously produced and supplemental) can follow one of two primary metabolic pathways in the body.48 If estrogen is converted to 16-alpha-hydroxyestrone, then the risk of breast and other cancers is increased. If, on the other hand, the estrogen is converted to 2-hydroxyestrone, then the risk for cancer such as that of the breast and cervix is decreased.50,51
I3C can readily be obtained by eating lots of cruciferous vegetables and/or taking I3C in dietary supplement form.
To confirm the theory that certain estrogen metabolites can contribute to cancer, researchers analyzed data gathered from over 10,000 Italian women over more than five years. The objective was to determine how dietary and hormonal factors influence breast cancer risk. They found that among premenopausal women, a higher ratio of 2-hydroxyestrone to 16-hydroxyestrone was associated with protection against breast cancer.50 This same finding has been shown in additional studies of different populations.52,53
The potent estrogen metabolite 16-alpha-hydroxyestrone acts as a breast tumor promoter.54 By contrast, estrogen metabolized via the 2-hydroxyestrone pathway is associated with reduced estrogenic activity in breast tissue.54 Additionally, a conjugated form of this less active estrogen metabolite may help prevent the formation of blood vessels necessary to feed growing cancers, thus helping to arrest tumor growth.55
Cruciferous vegetable compounds (such as I3C) are effective in shifting estrogen metabolism to the more beneficial pathway, thus reducing levels of 16-alpha-hydroxyestrone and increasing levels of 2-hydroxyestrone.43,54
This beneficial modulation of estrogen is associated with reduced risk of breast and other cancers, including cervical and head and neck cancers.50,51,56 Cruciferous vegetable compounds thus play an important role in fighting cancer. To illustrate, research conducted at the University of California at Berkeley documented that I3C in combination with the anti-estrogenic chemotherapeutic agent tamoxifen inhibited the growth of human breast cancer cells by an astounding 95%.56
Interestingly, an assay study performed at the National Cancer Institute determined that I3C was superior to over 80 other natural substances with regard to anti-cancer potential.57
Soy May Reduce Breast Cancer Risk
The controversy over whether people can reduce their risk of cancer by increasing their consumption of soy foods or soy supplements has been hotly debated for many years. In response to the debate, a number of studies were initiated in the 1990s to ascertain soy’s effects on human health.58
The results of these studies have now been released and while ignored by the mainstream media, the startling findings indicate that breast cancer risk can be nearly cut in half if women consume more soy.26,59,60
One recent study showed that postmenopausal women who ate a Western-style diet, high in meats and sweets, had nearly twice the risk of developing estrogen receptor-positive breast cancer, compared with women who ate a traditional Asian diet high in soy and vegetables.26 This and other studies provide evidence that compounds found in soy have a breast cancer-preventive effect.
Isoflavones derived from soy have shown promise in providing natural protection against multiple types of cancer.61-63 Two of the best known soy isoflavones are genistein and daidzein.
Isoflavones exert a number of positive biological effects on the human body, and many practitioners of integrative medicine (and even a small but growing number in mainstream medicine) now believe that consumption of soy and isoflavones can reduce the risk of many chronic diseases, including cancer, heart disease, and osteoporosis.58-65
Studies conducted in Asia found that breast cancer risk was significantly lower among Asian women who consumed large quantities of isoflavones and other soy products, compared with those who consumed less of these healthful nutrients.66 Because animal studies have shown that a diet high in soy and genistein can protect against breast, colon, and skin cancers, it seemed reasonable to think that soy could also help prevent human cancers and, in particular, breast cancer.67 Yet many mainstream medical practitioners remain skeptical that something as simple as soy could have such a profound effect on human health.
Soy isoflavones are correctly classified as selective estrogen receptor modulators.68 Due to their unique molecular structure, soy isoflavones can act as both estrogen receptor agonists and receptor blockers. In fact, elegant biochemical studies have shown that some isoflavones bind to the cancer-protective estrogen beta receptor six-to eight-fold more readily than native estrogen.68 With this ability, soy isoflavones are thought by many to confer the beneficial effects of estrogen without its potentially dangerous side effects, especially in hormonally sensitive tissues found in both the breast and endometrium.68
Numerous studies show the potential benefits to women of incorporating soy in their diets to help prevent breast cancer. A landmark case control study of women in Singapore, involving 200 case subjects and 420 control subjects, found that younger women with the highest consumption of soy-based products had a markedly decreased risk of developing breast cancer.69 Finally, a very large population-based, prospective study of 21,852 Japanese women aged 40-59 found that women with the highest intake of soy isoflavones reduced their risk of breast cancer by up to 54%, compared with women with the lowest intake of soy isoflavones.66
In addition to potentially preventing breast cancer, soy isoflavones are also thought to be effective in warding off other types of cancer that afflict women, including endometrial cancer. A recent case control study reported the effects of soy isoflavones and other phytoestrogens on the risk of developing endometrial cancer.70 The study compared 500 women aged 35-79 who were diagnosed with endometrial cancer between 1996 and 1999 with 470 age- and ethnicity-matched controls. As in studies examining the effects of isoflavones on breast cancer, this study showed that women with a higher intake of soy isoflavones had a significantly lower risk of developing endometrial cancer. Even more interesting was that the levels of isoflavones needed to provide protection against endometrial cancer were found to be much lower than the amount believed necessary to protect against breast cancer (in fact, they were the amounts that could be obtained from a healthy American- style diet).70
A recent 2012 analysis of about 46,000 non-hysterectomized postmenopausal women who were recruited into the Multiethnic Cohort (MEC) Study and provided detailed baseline information on diet and other endometrial cancer risk factors showed a significantly reduced risk of endometrial cancer associated with total isoflavone intake, daidzein intake, and genistein intake.71
As for long-term safety, a recent 2010 clinical study supports supplementation with soy isoflavones. This international study involving postmenopausal women treated for 3 years with a standardized soy isoflavone extract, examined via endometrial biopsy, transvaginal ultrasonography, and mammography, showed an excellent safety profile, with no significant changes in endometrial thickness and no change in mammography. The global safety was rated as either ‘excellent’ or ‘good’ by 99.1% of investigators and 99.0% of patients after 3 years of treatment.72
As another example of long-term safety, a 2011 multicenter 2-year trial involving over 400 postmenopausal women supplemented with soy isoflavones plus calcium and vitamin D showed no increase in endometrial thickness and a reduced rate of breast cancer and endometrial cancer compared with expected population rates for these cancers.73