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Phytoestrogens & Isoflavones: The good, the bad, the controversy!

Phytoestrogens & Isoflavones: The good, the bad, the controversy!

Article by Don Goldberg

On the Willner Window Radio Program, airing December 27th, we reported on the conflicting information regarding the intake of phytoestrogen containing foods and supplements by individuals with hormone related cancers.

References, and abstracts of the studies mentioned are provided below, so that the topic can be discussed with your health professional.


Dietary estrogens have little effect on cancer risk
Mon, Dec 21 2009, By Rachael Myers Lowe

NEW YORK (Reuters Health) - Dietary "phytoestrogens" -- plant substances that have weak estrogen-like activity -- have little impact on the risks of developing hormone-sensitive cancers like breast and prostate cancer or colorectal cancers, new research suggests.

In a large study of some 25,000 British adults, researchers failed to find any "significant" differences in cancer risk related to dietary intake of these compounds.

Phytoestrogens are found in a wide range of foods including dairy products, soy foods, cereals, fruits, vegetables, nuts, seeds, coffee and tea. Previous studies have suggested dietary phytoestrogen intake is associated with increased breast cancer risk and reduced colorectal cancer risk in women. The results from earlier studies were hampered, however, by limited data about phytoestrogen content in food.

No previous research has examined the association between phytoestrogen intake and prostate cancer risk.

In the current study, reported in the American Journal of Clinical Nutrition, researchers assigned phytoestrogen values to nearly 11,000 foods following chemical analyses. For the first time, phytoestrogen values were assigned to animal products.

Unlike plants, which themselves contain phytoestrogens, phytoestrogens are generated by the digestion of animal products like meat and dairy products by microbes in the gut, the researchers explain.

Phytoestrogen consumption was estimated for cancer-free adult participants in the European Prospective Investigation into Cancer and Nutrition - Norfolk (EPIC-Norfolk). EPIC-Norfolk participants, recruited between 1993 and 1997, filled out a diet diary for a week and provided information about age, height, weight, smoking, aspirin use, menopausal status, and family history of cancer among other things.

Cancers that developed within 12 months of study recruitment were identified from a cancer registry totaling 244 breast cancers, 221 colorectal cancers, and 204 prostate cancers. The diets and other relevant information from those who developed cancer were compared to information from other participants (controls) who did not develop cancer.

While acknowledging more study is needed, the authors concluded that there is "little evidence" that phytoestrogen intake is "associated with subsequent risk of breast or prostate cancer."

However, phytoestrogens found in eggs and dairy products "may influence the risk of prostate cancer and colon cancer in women," they report.

The associations are weak and without further study do not warrant changes in diet, lead investigator Heather Ward, of the MRC Center for Nutrition and Cancer in the Department of Public Health and Primary Care at Strangeways Research Laboratory in Cambridge, England, told Reuters Health.

"The results of the present study do not suggest that anyone should alter their phytoestrogen intake, in part because the majority of the associations between phytoestrogen intake and cancer risk were not significant," the doctoral candidate wrote in an email.

"It is worth noting that phytoestrogen intake within an Asian-style diet is more than ten-fold greater than in Western diets, without evidence of an increase in cancer risk," she added.

Because phytoestrogen consumption is on the rise in Britain, the authors urge further monitoring because "the relation between phytoestrogen and cancer may change over time."

SOURCE: American Journal of Clinical Nutrition, December 2009.        

The same story, reported by Decision News media:

Soy may slash breast cancer mortality: Study
By Stephen Daniells,

Increased intakes of soy and soy products may reduce the risk of death and breast cancer recurrence, says a new study in the Journal of the American Medical Association.

Women with the highest intake of soy protein had a 29 per cent lower risk of death, and a 32 per cent lower risk of breast cancer recurrence compared to patients with the lowest intake of soy protein, according to findings from a study with Chinese breast cancer survivors.

The study adds to an ever-growing body of science supporting the role of soy, and the isoflavones it contains, with improved breast health.

Soy isoflavones are naturally occurring oestrogen-like compounds, and supplements are currently marketed as a way of reducing symptoms of the menopause and offer an alternative to hormone replacement therapy.

Conflicting reports however have clouded the picture about the beneficial effects of soy isoflavones, with some studies indicating that breast cancer cells in mice were stimulated by the isoflavones. Population studies have shown that women with a high-soy diet generally have lower rates of breast cancer.

“Soy foods are rich in isoflavones, a major group of phytoestrogens that have been hypothesized to reduce the risk of breast cancer. However, the oestrogen-like effect of isoflavones and the potential interaction between isoflavones and tamoxifen have led to concern about soy food consumption among breast cancer patients,” wrote the authors, led by Xiao Ou Shu, M.D., Ph.D., of Vanderbilt University Medical Center.

The researchers analysed data from the Shanghai Breast Cancer Survival Study, a large, population-based study of 5,042 female breast cancer survivors aged between 20 and 75 in China.

After about four years of follow-up, 44 total deaths and 534 recurrences were documented. Soy food intake, as measured by either soy protein or soy isoflavone intake, was inversely associated with mortality and recurrence, said the researchers.

The researchers noted significant reductions in both mortality and breast cancer recurrence with increasing soy protein intake, up to a level of 11 grams per day. After this point, no additional benefits were observed.

“We did not find that risk estimates associated with soy isoflavone intake were stronger than risk estimates associated with soy protein intake,” they stated.

“The inverse association was evident among women with either oestrogen receptor–positive or –negative breast cancer and was present in both users and nonusers of tamoxifen,” they continued.

“In summary, in this population-based prospective study, we found that soy food intake is safe and was associated with lower mortality and recurrence among breast cancer patients… This study suggests that moderate soy food intake is safe and potentially beneficial for women with breast cancer,” they concluded.

Source: Journal of the American Medical Association
Volume 302, Issue 22, Pages 2437-2443
“Soy Food Intake and Breast Cancer Survival”
Authors: X.O. Shu, Y. Zheng, H. Cai, K. Gu, Z. Chen, W. Zheng, W. Lu

© 2000/2009 - Decision News Media SAS - All right reserved

Soy Intake May Modify Risk of Breast Cancer.
Date: 10/6/2009
Source: Cancer Epidemiology, Biomarkers and Prevention

Breast cancer is a cancer that forms in tissues of the breast, usually the ducts (tubes that carry milk to the nipple) and lobules (glands that make milk). It occurs in both men and women, although male breast cancer is rare. There are different types of breast cancer, with different stages (spread), aggressiveness and genetic makeup. Treatment includes surgery, drugs (hormone therapy and chemotherapy) and radiation. The incidence of breast cancer has been increasing steadily for decades. Today breast cancer rates have escalated to the point where women's lifetime risk of developing breast cancer is 1 in 8. In the year 2002, the American Cancer Society estimated that nearly 203,500 women will be diagnosed with breast cancer and approximately 39,600 women will die from the disease. This means that approximately every two and a half minutes a woman in the United States is diagnosed with breast cancer and that approximately every thirteen minutes, a woman dies from this disease. Breast cancer has become the second largest cause of cancer death in women, after skin cancer, and the leading cause of death for women between the ages of 35 and 54.

Risk factors for breast cancer:
    • Being female
    • Increasing age
    • Personal history of breast cancer
    • Family history of breast cancer
    • Inherited genes
    • Radiation exposure
    • Being overweight or obese after menopause
    • Beginning menopause after age 55
    • Postmenopausal hormone therapy
    • Lack of physical activity
    • Drinking alcohol

Soy Isoflavones are a dietary supplement derived from soybeans containing phytoestrogens. These weak estrogens are chemically similar in structure to naturally produced estrogen hormones. Isoflavones are found in soy foods both with and without a sugar molecule attached. The two primary isoflavones in soybeans are daidzein and genistein and their respective glucosides, genistein and daidzein. Soy foods typically contain more genistein than daidzein, although this ratio varies among the different soy products. In cultures where soy products are consumed in abundance, women's health problems, certain cancers, and cardiovascular disease are reported to be less prevalent.

A study published in the journal Cancer Epidemiology, Biomarkers & Prevention investigated the role soy consumption plays in reducing the risk of breast cancer. Researchers enrolled 430 Asian-American women ages 20 to 55 years. They studied the usual adult soy intake and measured urinary concentrations of 15 estrogens and estrogen metabolites (EM) by using liquid chromatography-tandem mass spectrometry. The results suggested that regular soy consumption is associated with increased levels of EM. These observed variations in estrogen metabolism may decrease the risk of breast cancer.1

1 Fuhrman BJ, Pfeiffer R, Xu X, et al. Soy Intake is Associated with Increased 2-Hydroxylation and Decreased 16{alpha}-Hydroxylation of Estrogens in Asian-American Women. Cancer Epidemiol Biomarkers Prev. Sep2009

Study Finds Soy Safe for Men
2009/07/20 - United Soybean Board  


A new study published by the American Society for Reproductive Medicine finds that soyfoods and soy isoflavone supplements have no significant effect on male reproductive hormone levels in men. The literature review indicates that soy does not decrease testosterone levels.

Led by Jill M. Hamilton-Reeves, PhD, RD, of St. Catherine's University, St. Paul, Minnesota, researchers assessed the effects of soy protein and soy isoflavones on measurements of male reproductive hormones. Findings, just published online in Fertility and Sterility, a publication of the American Society for Reproductive Medicine, demonstrate no significant effect of soy protein or soy isoflavone intake on circulating levels of testosterone, sex hormone-binding globulin or free testosterone in men.

The comprehensive meta-analysis examined the existing scientific literature including all clinical studies examining soy's effect on male reproductive hormones published before July 1, 2008. Fifteen placebo-controlled treatment groups with baseline and ending measures were analyzed. Thirty-two reports involving 36 treatment groups were also assessed in simpler statistical models. Studies published after July 1, 2008, which were not included in the meta-analysis, support the conclusions of the meta-analysis.

Reproductive endocrinologist William R. Phipps, MD, of the University of Rochester Medical Center, a co-author of the analysis stated, "As a high-quality source of protein that is relatively low in saturated fat, soy can be an important part of a heart-healthy diet and may contribute to a decreased risk of coronary heart disease." He noted that some men have been reluctant to consume soyfoods due to concerns about estrogen-like effects of soy isoflavones, often referred to as phytoestrogens. But according to Phipps, "it is important for the public to understand that there is no clinical evidence to support these ideas. After conducting a comprehensive review of the existing literature, we found no indication that soy significantly alters male sex hormone levels."

Men can benefit from soyfood consumption as a means to meet daily protein requirements and at the same time possibly also reducing their risk of heart disease.

Citing the research study, Lisa Kelly, MPH, RD, of the United Soybean Board, added, "Soy is often praised for the positive role it can play in the diets of women. But, years of clinical research have shown that men stand to benefit from soy, too. I encourage men to incorporate soyfoods into a balanced and varied diet and talk to their healthcare provider about their own unique nutritional needs."

About the United Soybean Board

The United Soybean Board is comprised of 68 farmer-directors who oversee the investments of the soybean checkoff on behalf of all U.S. soybean farmers. For more information on the health benefits of soy and simple recipe suggestions to help add soy to your diet, please visit USB's

Editor's note: To request a copy of the complete report, please email Diana Steeble at Editors of health professional-oriented publications may also wish to refer readers to USB's article for health professionals on this research study, available here.  

Soy Supplementation Enhances Cognitive Function in Men.
Date: 7/21/2009
Source: British Journal of Nutrition

Cognitive function is the term used to describe a person's state of consciousness (alertness and orientation), memory, and attention span. A mental status examination (MSE) is a standard test used by healthcare professionals to measure a patient's overall mental health. Evaluating a patient's cognitive function includes, first of all, measuring their level of alertness and orientation. Awareness and thinking depend on organized thoughts, personal experiences, emotions, and mental processes, each existing in a special region of the brain. Self-awareness requires sensing this personal stream of thought and emotional experiences. When a person cannot maintain a logical sequence of thoughts, and when this goes along with not being able to pay attention and being disoriented, this describes confusion.

Scientists classify soy isoflavones from the plant Glycine max as phytoestrogens. Phyto is a Greek root word meaning plant, so phytoestrogens are plant-based compounds that have estrogen-like activity. Because they are structurally similar to estrogens, isoflavones exert weak estrogenic activity. Because of their estrogen-like effects, isoflavones have been studied for a wide spectrum of health benefits. Soybeans and soy foods like tofu are the best dietary source of isoflavones. However, many soy protein concentrates and soy products processed with alcohol may not contain isoflavones. A synthetically derived form of isoflavones, known as ipriflavone, is also available.

Researchers reported that men receiving daily supplements of soy isoflavones performed significantly better in tests of their working memory. The 12-week double-blind, placebo-controlled cross-over trial, published in the British Journal of Nutrition, included 34 healthy men. The men were assigned to receive either a daily dose of 116 mg soy isoflavones, providing 68 mg daidzein, 12 mg genistein, and 36 mg glycitin, or placebo for 6 weeks. They were subsequently crossed-over to the other intervention for the following 6 weeks. The results revealed that men who received the isoflavones required 18 percent fewer attempts to correctly complete the tasks, committed 23 percent fewer errors and achieved the tasks in 17 percent less time than they did during the placebo phase. Although soy isoflavones appeared to improve spatial working memory in men, it  had no apparent effect on either auditory or episodic memory, executive function, or visual-spatial processing. The improvements were seen in cognitive processes which appear dependent on estrogen activation.1  

1 Thorp AA, Sinn N, Buckley JD, et al. Soya isoflavone supplementation enhances spatial working memory in men. Br J Nutr. 2009.

Evidence mounts for soy's menopause benefits
By Stephen Daniells, 09-Apr-2009
Related topics: Soy-based ingredients, Cardiovascular health, Women's health

Soy isoflavones in the aglycone form may reduce cholesterol, improve antioxidative properties of the liver, and prevent degeneration of the vaginal wall, suggests a new study with rats.

The animal study, published in the online open access journal Nutrition & Metabolism, adds to previous science about the benefits of soy isoflavones for reducing the symptoms of the menopause.

"These ovariectomised animals are a good model for study of the menopause as the loss of oestrogen from the ovaries mimics the natural reduction in oestrogen seen in menopausal women,” explained lead researcher Robin Chiou from the National Chiayi University in Taiwan.

“SAI (soy aglycons of isoflavone) itself has weak oestrogenic properties and we've shown here that menopause-related syndromes can be prevented or improved by dietary supplementation with the compounds it contains,” he added.

Isoflavones are well known phytoestrogens - active substances derived from plants that have a weak oestrogen-like action.

Isoflavones from soy have been shown to provide a number of health benefits, including the promotion of heart health and the maintenance of bone health in post-menopausal women.

They have also been studied for their role in cancer prevention and slowing down the ageing process in peri-menopausal women, and have proved to be a popular alternative to hormone replacement therapy for those wishing to control menopause symptoms without resorting to drugs.

Study details

The researchers divided 30 ovariectomised Sprague-Dawley rats were distributed into three groups: control group; a low SAI group (0.0135 per cent SAI in the diet, equivalent to 80 mg per day for a 60 kg-human), and a high dose SAI group (0.027 per cent SAI). A further 10 rats acted as the negative controls and did not have their ovaries removed.

The soybean supplement contained 80 per cent soy bean flour, 4.5 per cent daidzein, 14.5 per cent genistein, and about 1.0 per cent other isoflavones, (Glory Biotech Co., Taiwan).

After three months, the researchers found that the ovariectomised animals gained more weight than the negative control animals. Animals fed the soy isoflavones had higher blood levels of isoflavones, said the researchers, and significantly lower LDL-cholesterol levels, and higher HDL-cholesterol levels.

"It is generally agreed that the higher HDL and the lower LDL concentrations are of benefit in chemoprevention of cardiovascular diseases. Our findings support the indication that soybean consumption may prevent coronary heart disease,” said Chiou.

Furthermore, liver antioxidative activities were increased, as evidenced by decreased values of TBARS (thiobarbituric acid-reactive substance). Finally, the decline in the lining of the vagina observed for the ovariectomised control group was “noticeably improved by dietary supplementation with SAI”, said the researchers.

Importance for supplements

“The observations that dietary SAI supplementation in performance of estrogenic effectiveness in improvement of serum biochemical attributes, enhancement of liver antioxidative capacities and protection of vaginal epithelium are of importance from the viewpoint of healthcare and development of dietary supplements,” wrote the researchers.

“Apparently, diets supplemented with soy aglycons of isoflavone have conferred health benefits to the ovariectomised rats. This further supports the effectiveness that menopausal-related syndromes could be prevented or improved by dietary supplementation with soy aglycons of isoflavone,” they concluded.

Source: Nutrition & Metabolism
2009, 6
“Supplementary health benefits of soy aglycons of isoflavone by improvement of serum biochemical attributes, enhancement of liver antioxidative capacities and protection of vaginal epithelium of ovariectomized rats”
Authors: T.-F. Lien, Y.-L. Hsu, D.-Y. Lo, R.Y.-Y. Chiou

© 2000/2009 - Decision News Media SAS