Soy Isoflavones for Women's Health:
Is Soy a Viable Alternative to
Traditional Estrogen Hormone Replacement?This section is compiled by Frank M. Painter, D.C.
Send all comments or additions to: Frankp@chiro.org
From Nutrition Science News
BY JACK CHALLEMIs soy a viable alternative to traditional estrogen hormone replacement?
In April and May, newspaper headlines were buzzing with news of the latest cancer prevention pills. Two prescription drugs, tamoxifen and raloxifene, were found to reduce the risk of breast cancer. There were drawbacks to the pharmaceuticals, however, as there usually are: Tamoxifen increased the risk of endometrial cancer and pulmonary embolism (blood clots in the lungs), and raloxifene users were more likely to suffer from hot flashes and leg cramps.
Is there a safe and effective alternative for reducing the risk of breast cancer? According to a rapidly growing body of evidence, it may be eating soy foods, which are rich in the phytoestrogen isoflavone. Phytoestrogens are estrogenlike compounds found in plants; they have slight hormonal (and sometimes hormone-blocking) properties without being true steroid hormones. Eaten for more than 5,000 years in Asia, soy appears to reduce the risk of breast and other reproductive-organ cancers--and doesn't have the unwanted side effects or risks of drugs.
In recent years, epidemiologists have focused on soy foods as one of the major dietary differences between Asians and Americans. Asian women eating traditional high-soy diets have a relatively low risk of breast cancer, but their risk increases when they move to the United States and adopt a Western diet. Similarly, Asian men who eat high-soy diets have a low risk of invasive prostate cancer.
"The standard American diet has no phytoestrogens," says Susan Lark, M.D., who specializes in women's health issues in Los Altos, Calif. Of soy and other natural sources of phytoestrogens, she adds, "You have to keep taking these foods to maintain their estrogenlike benefits."
The benefits of soy go beyond reducing long-term cancer risk. Recent studies have found that soy--in the form of either isoflavone-rich protein or pure isoflavone supplements--can reduce menopausal hot flashes and increase bone density in women. Indeed, many menopausal and postmenopausal health problems may result from a lack of isoflavones in the typical American diet.
Stephen Barnes, Ph.D., who researches soy at the University of Alabama, Birmingham, notes the shift in thinking toward soy. "The American diet's much higher fat content compared to the Asian diet was initially considered the most important factor leading to increased cancer risk in Americans--that is, suggesting that fat is cancer-causing," he explains. "A new hypothesis is being examined to determine whether one or more components of the Southeast Asian diet is cancer-preventing." [1]
How Isoflavones Work
During just the past three years, more than 1,000 articles on soy isoflavones--part of the larger group of phytoestrogens--have been published in scientific and medical journals. According to Terrance Graham, Ph.D., of Ohio State University, Columbus, soy plants produce isoflavones in response to environmental stresses. Speaking at the Phytoestrogens Research Methods symposium, held in September 1997 in Tucson, Ariz., he explained that, in addition to their hormonelike roles in cell regulation, isoflavones function as plant antibiotics and antifungal compounds. [2]
Two isoflavones predominant in soy are genistein and daidzein. Soy also contains genistin and daidzin, which are sugar-containing isoflavone molecules. During digestion, intestinal bacteria cleave or cut off the sugar molecules, creating still more genistein and daidzein.
Research suggests that soy isoflavones act in four distinct ways: as estrogens and antiestrogens, as cancer-enzyme inhibitors, as antioxidants and as immune enhancers.
Estrogens and antiestrogens: Isoflavones are considered nonsteroidal estrogens: They are strikingly similar in chemical structure to the estrogen hormones women produce, but they are also different enough not to be full-fledged steroidal hormones.
In the relative absence of true estrogen, isoflavones tend to have an estrogenlike effect. Christine Conrad, co-author with Marcus Laux, N.D., of Natural Woman, Natural Menopause (HarperCollins, 1997), relates that soy isoflavones and other plant estrogens are effective hormone replacements after a hysterectomy. Other researchers have reported the isoflavones are also estrogenic enough to promote bone formation. In fact, the European drug ipriflavone, used to treat osteoporosis, is a synthetic isoflavone; daidzein is one of its metabolites.
The isoflavones also act as antiestrogens--that is, in opposition to estrogen--and many researchers believe this is why they reduce the risk of breast and endometrial cancer. Estrogen signals cells to proliferate, which is why it can be carcinogenic. Genistein, which has only 1/1,000 the hormonal activity of estrogen, attaches to the breast cells' estrogen receptors and by doing so blocks the more potent female hormone from attaching. [3] So in summary, when a woman has little natural estrogen production (post-hysterectomy or postmenopause), isoflavones can attach to open estrogen receptor sites on cells and produce a weak estrogen effect. When there is too much estrogen (during PMS, for example), isoflavones can compete with the natural estrogen for receptor sites, and because their effect is weak in comparison, they blunt the estrogen effect.
Cancer-enzyme inhibitors: Isoflavones also reduce cancer risk by inhibiting the activity of tyrosine kinase, an enzyme that promotes cancer cell growth. [1] Some researchers, including David T. Zava, Ph.D., of the California Public Health Foundation in Berkeley, believe the inhibition of tyrosine kinase is the primary anticancer mechanism of isoflavones. But other researchers have shown that genistein is antiangiogenic. As an antiangiogenic substance, it blocks the growth of blood vessels that tumors need to expand. [4]
Antioxidants: Recent research by Catherine Rice-Evans, Ph.D., co-director of the International Antioxidant Research Center at Guy's Hospital, London, has demonstrated that isoflavones are also powerful antioxidants. Like other antioxidants, they can reduce the long-term risk of cancer by preventing free radical damage to deoxyribonucleic acid (DNA), the complex molecule that contains genes. According to Rice-Evans' research, genistein is the most potent antioxidant among the isoflavones, followed by daidzein. [5]
Genistein may also increase the body's production of superoxide dismutase (SOD), a powerful antioxidant that quenches superoxide radicals. [6] Genistein also seems to function as an SOD mimic, according to results of a cell-culture study at the Mount Sinai School of Medicine, New York. [7]
Immune enhancers: Two recent studies conducted by a team of American and Chinese researchers found that daidzein may reduce the risk of cancer by activating immune cells. In experiments with laboratory mice, researchers found that daidzein, but not genistein, increased the activity of lymphocytes (T cells) and macrophages (a type of white blood cell). [8, 9]
Ease Menopausal Symptoms
In areas outside cancer research, the most immediate and observable effect of supplemental soy isoflavones is the reduction of menopausal hot flashes. In one study, Italian researchers gave 104 women daily servings of either isolated soy protein, containing 76 mg of isoflavones, or a placebo for 12 weeks. Within three weeks, women eating soy averaged a 26 percent reduction in hot flashes. By the end of the study they had a 45 percent reduction in hot flashes. [10]
Other studies have shown similar benefits. Gregory L. Burke, M.D., of the Bowman Gray School of Medicine, Winston-Salem, N.C., gave isoflavone-rich soy supplements to 51 postmenopausal women. The soy lessened menopausal symptoms, lowered blood pressure and resulted in a healthier blood lipoprotein profile. The supplements led to these benefits, Burke noted, without the side effects associated with conventional hormone replacement therapy. [11]
In women, estrogen promotes bone formation, and the postmenopausal decrease in estrogen production increases the risk of osteoporosis. In a study at the University of Illinois, Urbana, John W. Erdman, Ph.D., gave daily soy supplements or a placebo to 60 postmenopausal women. The soy supplements contained either 55.6 or 90 mg of isoflavones. After six months, the women consuming soy isoflavones had significant increases in bone mineral content and density in their lumbar spines, compared with a control group. The researchers did not note any dose-related differences between the supplement groups. [12]
Reduce Heart Disease Risk
Soy isoflavones also appear to reduce cardiovascular disease risk via several distinct mechanisms. Researchers have reported that soy foods lower blood cholesterol levels. In a study of almost 5,000 subjects, a team of scientists from the Gifu University School of Medicine, Japan, reported that high soy intake correlated with low cholesterol levels. [13] When researchers collectively analyzed 38 studies that included 730 human subjects, soy consumption was strongly associated with low cholesterol levels. People who obtained about half their protein from soy had cholesterol levels about 10 percent lower than thosenot eating soy.
Research suggests that soy isoflavones act in four distinct ways: as estrogens and antiestrogens, as cancer-enzyme inhibitors, as antioxidants and as immune enhancers. In addition, soy isoflavones may maintain normal vascular function. At the Bowman Gray School of Medicine, J. Koudy Williams, D.V.M., fed 22 monkeys diets containing soy protein with isoflavones either intact or removed. When Williams stimulated and stressed the monkeys' hearts, animals eating isoflavones maintained normal heart function. Those eating soy without isoflavones developed heart abnormalities. Looking at the big picture of soy and health, Williams observes that "a dietary supplement [of soy] potentially may provide a viable alternative to traditional [estrogen] hormone replacement therapy." [14]
In another study on soy isoflavones and heart disease, other researchers at the Bowman Gray School of Medicine fed monkeys diets with milk protein, isoflavone-containing soy protein or soy protein with most of the isoflavones removed. Animals receiving the soy isoflavones for 14 months had the lowest levels of low-density lipoproteins (LDL) and very-low-density lipoproteins (VLDL), suggesting a protective effect against heart disease. These animals also had the smallest lesions on their arteries. [15]
Cautious Optimism
Do soy isoflavones prevent cancer? Researchers express optimism--along with caution. Population-based studies show a strong association between consumption of soy and other phytoestrogens and a reduced risk of breast and endometrial cancer.
Australian researchers analyzed phytoestrogen levels in the diets, blood and urine of 144 women with newly diagnosed breast cancer, comparing the levels with those of healthy women. Women with high levels of two phytoestrogens, equol and enterolactone, as measured by amounts excreted, were less likely to have developed breast cancer. Equol is formed when intestinal bacteria break down the isoflavone daidzein, and enterolactone is a phytoestrogenic lignan found in soy fiber, whole grains and flaxseed. [16] These compounds are therefore "markers" of isoflavone consumption. A study of Hawaiians found that diets high in soy and fiber were associated with a reduced risk of endometrial cancer. [17]
Furthermore, there's intriguing evidence from animal experiments hinting that early consumption of genistein can reduce the risk of cancer later in life. In an experiment at the University of Alabama, Birmingham, Coral A. Lamartiniere, Ph.D., fed genistein to rats for three days before they entered puberty and later exposed them to a cancer-causing chemical. According to Lamartiniere's report, rats receiving genistein developed half the tumors as rats given a placebo. [18]
Although soy isoflavones look promising in the prevention of breast and endometrial cancers, researchers and clinicians have expressed caution and are reluctant to use the substances in the treatment of active cancer. Although isoflavones may help treat some cancers, the data are inconclusive; hence the hesitation. Charles Simone, M.D., author of Breast Health (Avery, 1995), discourages his breast cancer patients from eating any soy foods because their effect on active cancers is not known. [19] Meanwhile, Tori Hudson, N.D., a professor at the National College of Naturopathic Medicine, Portland, Ore., encourages her cancer patients to eat soy foods but does not ask them to take isoflavone supplements. Herman Adlercreutz, M.D., of the University of Helsinki, Finland, reassuringly points out that there is "no evidence in the literature suggesting that phytoestrogens, present in such amounts in human food that they could have biological effects, stimulate already existing cancer, and there is also no evidence that such phytoestrogens could initiate cancer." [20]
Still, Adlercreutz, one of the world's top soy isoflavone researchers, emphasizes the importance of other phytoestrogens. "Don't forget the lignans," he points out, noting that they are also phytoestrogens, but different from those found in soy. In a similar vein, the University of Alabama's Stephen Barnes believes that a diversity of phytoestrogens, including the lignans, may be more beneficial than any single group. Research on the estrogenic and antioxidant properties of lignans is interesting but limited; most phytoestrogen research has centered on soy. Clinicians and researchers are understandably cautious about recommending isoflavone supplements in the treatment of cancer. Such supplements may help some types of cancers but not others, in part because cancer cells do not behave the way normal cells do.
The picture emerging from all this research is that many Americans appear to be eating a fundamentally unbalanced diet--one lacking in isoflavones, lignans and other natural phytoestrogens found in legumes, fruits, vegetables and whole grains. These people also seem to be paying the price of an increased risk of disease. Restoring phytoestrogen intake--through a good vegetarian diet that includes soy and, under some circumstances, supplements--can lead to a more natural and balanced diet.© 1998 by Jack Challem
Jack Challem is based in Aloha, Ore. He has been writing about vitamin research for more than 20 years and publishes The Nutrition Reporter newsletter.
REFERENCES 1. Barnes S, et al. Rationale for the use of genistein-containing soy matrices in chemoprevention trials for breast and prostate cancer. J Cellular Biochemistry, 1995; 22S:181-7.
2. Graham T. The biosynthesis and distribution of phytoestrogens and their roles in plant defense, signal transduction and cell to cell signalling. Symposium on Phytoestrogen Research Methods; 1997 Sep 21-24;Tucson, Ariz..
3. Zava DT, Duwe G. Estrogenic and antiproliferative properties of genistein and other flavonoids in human breast cancer cells in vitro. Nutrition and Cancer 1997;27:31-40.
4. Fotsis T, et al. Genistein, a dietary ingested isoflavonoid, inhibits cell proliferation and in vitro angiogenesis. J Nutr 1995;125:790S-7S.
5. Ruiz-Larrea MB, et al. Antioxidant activity of phytoestrogenic isoflavones. Free Radical Research 1997;26:63-70.
6. Cai Q, Wei H. Effect of dietary genistein on antioxidant enzyme activities in SENCAR mice. Nutr and Cancer 1996;25:1-7.
7. Wei H, et al. Inhibition of UV light- and Fenton reaction-induced oxidative DNA damage by the soybean isoflavone genistein. Carcinogenesis 1996;17:73-7.
8. Wang W, et al. Individual and combinatory effects of soy isoflavones on the in vitro potentiation of lymphocyte activation. Nutr and Cancer 1997;29:29-34.
9. Zhang R, et al. Enhancement of immune function in mice fed high doses of soy daidzein. Nutr and Cancer 1997;29:24-8.
10. Albertazzi P, et al. The effect of dietary soy supplementation on hot flashes. Obstetrics and Gynecology 1998;91:6-11.
11. Burke GL. The potential use of a dietary soy supplement as a post-menopausal hormone replacement therapy. Second International Symposium on the Role of Soy in Preventing and Treating Chronic Disease; 1996 Sep 15-18; Brussels, Belgium.
12. Erdman JW, et al. Short-term effects of soybean isoflavones on bone in postmenopausal women. Second International Symposium on the Role of Soy in Preventing and Treating Chronic Disease; 1996 Sept 15-18; Brussels, Belgium: 21.
13. Nagata C, et al. Decreased serum total cholesterol concentration is associated with high intake of soy products in Japanese men and women. J Nutr 1998;128:209-13.
14. Honoré EK, et al. Soy isoflavones enhance coronary vascular reactivity in atherosclerotic female macaques. Fertility and Sterility 1997;67:148-54.
15. Anthony MS, et al. Soy protein versus soy phytoestrogens in the prevention of diet-induced coronary artery atherosclerosis of male cynomolgus monkeys. Arteriosclerosis, Thrombosis, and Vascular Biology 1997;17:2524-31.
16. Ingram D, et al. Case-control study of phyto-oestrogens and breast cancer. Lancet 1997;350:990-4.
17. Goodman MT, et al. Association of soy and fiber consumption with the risk of endometrial cancer. Am J Epidemiology 1997;146:294-306.
18. Murrill WB, et al. Prepubertal genistein exposure suppresses mammary cancer and enhances gland differentiation in rats. Carcinogenesis 1996 July;17:1451-7.
19. Simone CB, Breast cancer: nutrition and lifestyle modification to augment oncology care. 26th Annual Nutritional Medicine Today Conference; 1997 Apr 18-20; Toronto, Ontario, Canada.
20. Adlercreutz H, Mazur W. Phytoestrogens and western diseases. Annals of Medicine 1997;29:95-120.
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