Life Extension Magazine®

Issue: Mar 1997

Role Of Soy In Medicine Part 2

More medical advances with soy foods and their phytochemical extracts such as genistein in part II of our exclusive report from Belgium.










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Conference In Brussels, Belgium
Palais des Congress - Sept. 15-17, 1996

By Candy Ostman

image Brussels, Belgium was the site of the 2nd International Symposium on the Role of Soy in Preventing and Treating Chronic Disease. Over a thousand people from every corner of the globe gathered in the beautiful "Palais des Congress". The Palais is a beautiful building with a water fountain in front, and a spacious, modern theater inside where the lectures were held. Downstairs, in the "Leopold 11 Room", were the exhibits and poster sessions. For those of you who couldn't be there, we present a reasonable facsimilie.

Part I of our exclusive report appeared in the February, 1996 issue of Life Extension Magazine.

Here is part II:

SEPT. 17, 1996
SOY AND CANCER
(Animal Studies)
Prevention of Precancerous Colonic Lesions in Rats by Soy Flakes, Soy Flour, Genistein and Calcium
By Maurice Bennink, Ph.D.,
Michigan State University, East Lansing, MI

Dr. Bennink designed a study to determine the prophylactic abilities of different soy products (e.g., soy flakes and soy flour) to prevent colon carcinogenesis in laboratory rats. He found that in the genistein fed rats, there was a 40% reduction in ACF (Aberrant Crypt Foci- which are precancerous lesions of the colon), and a 35% reduction of ACF in the soy flour fed rats. Both soy flakes and soy flour were shown to be effective in reducing these precancerous lesions.

Soy Protein Isolates and Genistein: Effects on Initiation, Promotion and Progression of Colon Cancer
By Daniel D. Gallaher, Ph.D.,
Department of Food Science and Nutrition,
University of Minnesota,
St. Paul, MN
(Ed. Note: Soy Protein Isolates are proteins separated out from the carbohydrate and fat portion of soy beans).

In numerous studies, Dr. Gallaher found that Soy Protein Isolates containing a high amount of genistein, and casein-based diets containing a high amount of genistein, significantly reduce ACF. In one study, rats were fed soy protein during the different stages of cancer (initiation, promotion and progression). The conclusion was that soy protein and genistein helped stop cancer during the initiation and promotion phases, but had little effect on the cancer that had reached the progression phase. He found that aged soy protein isolates (stored for two years) were not effective. Seeking to understand why, Dr. Gallaher took fresh soy protein isolate and "aged" it by subjecting it to heat and humidity. When used in experiments, it caused increased carcinogenesis. These experiments demonstrate the importance of using fresh Soy Protein Isolates, stored at the proper temperature and humidity.

Effects of Dietary Soy Protein Isolates (SPI), Genistein and 1,4 Phenylenebis (Methylene) Selenocyanate
(P-XCS) on the Levels of 7,12-Dimethyl-Benz[A] Anthracene (DMBA)-DNA Binding in Mammary Glands of Female CD Rats
By Pramod Upadhyaya, Ph.D.,
American Health Foundation, Valhalla, NY

Dr. Upadhyaya has found that a diet supplemented with Soy Protein Isolate (10%) genistein (111ppm) or selenium in certain forms can prevent breast cancer in laboratory rats. There are data that suggest simultaneous administration of one or more chemopreventive agents (such as genistein and selenium) may be a very effective way of preventing cancer. In lab tests using both genistein and selenium at the same time, it was found they were more effective in the prevention of cancer in mammary tissues than when either agent was used alone.

Genistein Suppresses Chemically-Induced Mammary Cancer
By Coral A. Lamartiniere, Ph.D.,
Department of Pharmacology and Toxicology,
University of Alabama at Birmingham, Birmingham, AL

Breast cancer is the most common cancer in women, and the second leading cause of cancer death among females. Asian women, however have a lower rate of breast cancer, presumably because their traditional diet contains a lot of soy products. In fact, Asian women who migrate to the West and abandon their traditional diet of soy, have a higher incidence of breast cancer.

Dr. Lamartiniere and her associates devised a study to see if prepubertal oral administration of genistein resulted in a decreased incidence of mammary cancer in laboratory rats. The results showed that genistein did lower the incidence and numbers of mammary tumors when administered early. In addition, animals who were treated prepubertally with genistein had longer estrus phases in the estrus cycle and also showed a slight decrease in fertility. Dr. Lamartiniere concluded that the protective qualities of genistein were related to the fact that it caused early gland development and cell differentiation, without toxicity to the endocrine and reproductive system.

Paradoxical Effects of the Soy Phytoestrogen, Genistein on Growth of Human Breast Cancer Cells In Vitro and In Vivo
By William G. Helferich, Ph.D.,
Department of Food Science & Human Nutrition,
Michigan State University,
E. Lansing, MI

Dr. Helferich found that low doses of genistein stimulate estrogen-dependent human breast cancer cells in vitro, but that high concentrations of genistein inhibit growth of both estrogen- dependent and estrogen-independent human breast cancer cells. He found that genistein can block cell proliferation at high concentrations in vitro, even though these effects were not observed in vivo.

Soy Isoflavone Extract Suppresses Fumonisin B1-Promoted Rat Hepatocarcinogenesis
By Suzanne Hendrich, Ph.D.,
Food Science and Nutrition,
Iowa State University, Ames, IA

In previous studies, Dr. Hendrich observed that soy isoflavone extract significantly suppresses early stages of chemically-induced hepatocarcinogenesis (liver cancer) in rats. In studies using four groups of 10-day old female rats, she showed that endogenous hepatic prostaglandin levels were suppressed by 15% over the control group with isoflavone extract feeding alone (note: prostaglandins are biochemicals which can induce inflammation). Dr. Hendrich concludes that isoflavone extract is clearly antihepatotoxic, and its prostaglandin suppression mechanism provides the anticarcinogenic effect of soy isoflavones. Dr. Hendrich points out that soy isoflavones are capable of being toxic only in extremely high doses and appear to be most effective in the early stages of cancer.

Dietary Soy in the Prevention of Prostate Cancer in Animal Models
By Risto Santti, Ph.D.,
Institute of Biomedicine and Medicity Research Laboratory,
University of Turku, Turku, Finland

Dr. Santti's studies confirm that soy has significant cancer-preventive qualities. Soy has definitely been proven to be a powerful anticarcinogen in prostate carcinogenesis in animal models. Dr. Santti hypothesizes that this anticarcinogenic property may be explained by the ability of soy-derived phytoestrogens (isoflavonoids) to antagonize (especially in young animals) the action of more potent endogenous estrogens which intiate and promote carcinogenesis. Dr. Santti's findings show that soy has antiestrogenic action. There is no evidence to show that this action occurs in more mature animals, indicating that the neonatal period may be more affected by antiestrogenic actions of soy.

SOYBEAN
ANTICANCER MECHANISMS

The Bowman-Birk Inhibitor From Soybeans as an Anticarcinogenic Agent
By Ann R. Kennedy, Ph.D.,
University of Pennsylvania School of Medicine, Philadelphia, PA

Dr. Kennedy points to the fact that previous research has shown that certain protease inhibitors are extremely effective in preventing and suppressing carcinogenesis, particularly in animal model systems. Dr. Kennedy and her associates have been successful in developing a protease inhibitor derived from soy, known as the Bowman-Birk inhibitor (BBI). BBI has been shown to be a very effective cancer preventative agent. It has been shown to be particularly effective in suppressing carcinogenesis in several animal models, in addition to several organ systems and tissue types. In fact BBI has achieved Investigational New Drug status and will hopefully be available commercially in the next few years. According to Dr. Kennedy, BBI and its concentrate has been shown to be effective at every stage of cancer, with few side effects. She suggests that the use of BBI with chemotherapy may decrease hair loss associated with that type of treatment.

BBI-The Trypsin- and Chymo-Trypsin-Inhibitor From Soybeans: Friend or Foe?
By Yehudith Birk, Ph.D.,
Hebrew University of Jerusalem,
Institute of Biochemistry,
Food Science and Nutrition,
Rehovot, Israel

Dr. Birk describes in very technical detail the make-up of the Bowman-Birk Inhibitor. In addition to BBI and soy's ability to protect against carcinogenesis, they have also been shown to counteract nephrotoxicity induced by the antibiotic drug Gentamicin, while not affecting its antimicrobial activity.

Anticarcinogenic Properties of Plant Saponins
By A. Venket Rao, Ph.D., Department of Nutritional Sciences, University of Toronto, Toronto, Ontario, Canada

Many diseases, including cancer and cardiovascular disease, are related to diet. Plant foods contain many beneficial properties like macro-nutrients, dietary fiber and phytochemicals. Saponins are one such group of phytochemicals that have many beneficial properties. One major source of saponins is soybeans. Saponins are claimed to have profound hypocholesterolemic (cholesterol-lowering), immunostimulatory and anticarcinogenic properties. The anticarcinogenic mechanisms of saponins appear to relate to their antioxidant effects. They also exhibit cytotoxicity towards cancer cells, regulation of cell proliferation properties, and a stimulatory effect on the immune system.

Genistein Can Induce MCF-7 Breast Cancer Carcinoma Cell Differentiation or Death, Depending on the Dose
By Andreas I. Constantinou, Ph.D.,
Department of Surgical Oncology,
University of Illinois at Chicago, Chicago, IL

Dr. Constantinou studied the effects of genistein on mammary carcinogenesis. He found that genistein was able to cause cell death in the MCF-7 breast cancer carcinoma cell. Dr. Constantinou's data indicates that genistein, at relatively low concentrations, may interfere with carcinogenesis by promoting mammary cell maturation.

Mechanisms of Action of the Soy Isoflavone Genistein at the Cellular Level
By Stephen Barnes, Ph.D.,
Department of Pharmacology & Toxicology,
University of Alabama at Birmingham, AL

Dr. Barnes has found that genistein inhibits proliferation of both normal and cancer cells. One of the mechanisms of action is genistein's ability to interfere with epidermal growth factor (EGF)-induced tyrosine phosphorylation of the EGF receptor. Dr. Barnes believes that genistein resembles the estrogen agonist, Tamoxifen, in its chemical nature. Other proposed mechanisms of action are genistein's ability to inhibit DNA topisomerase II activity, the regulation of cell cycle checkpoints, and its anti-angiogenic (blood vessel growth) and antioxidant effects.

SEPTEMBER 18

SOY CONSUMPTION AND CANCER RISK
(Human Studies)

Evaluation of Soy Protein in Risk Reduction for Colon Cancer and Cardiovascular Disease:
Preliminary Results

By Maurice R. Bennink, Ph.D.,
Michigan State University,
East Lansing, MI

In a preliminary study involving a population of patients with previously confirmed adenomatous colon polyps or colon cancer, it was determined that soy protein could reduce indicators of risk for colon cancer and cardiovascular disease. The subjects consumed a soy supplement for one year. Most patients had a reduction in total cholesterol, due mostly to lower LDL cholesterol. HDL cholesterol levels did not change. Thyroid function remained relatively unchanged, as well. The cancer results of the study will be reported at a later date, according to Dr. Bennink.

The Effects of Soy Supplementation on Epithelial Proliferation in the Normal Human Breast
By Danielle F. McMicheal-Phillips, Ph.D.,
Department of Epithelial Biology, Paterson Institute for Cancer Research,
Christie Hospital NHS Trust,
Manchester, England

Dr. McMicheal-Phillips sought to ascertain the effects of soy on normal human breast tissue. In her study, short-term ingestion of soy stimulate breast tissue proliferation (most likely due to soy's estrogen agonist properties).

Tofu and Risk of Breast Cancer In Asian-Americans
By Anna Wu, Ph.D., Department of Preventative Medicine,
University of Southern California, Los Angeles, CA

Dr. Wu's study looked at women who migrated to the U.S. from Asia and the effects of a reduced intake of Tofu and other soy products. She determined that there is a definite increase in breast cancer rates among Asian women who have migrated to the U.S. The intake of Tofu in Asian women, according to Dr. Wu, is more than twice as high as the intake among Asian-American women. Correspondingly breast cancer rates are higher for Asian-American women. This association remained after adjustment of selected dietary factors, as well as other factors. Total caloric intake, total fat intake, and certain other factors were not taken into account in this study.

The Association Of Dietary Phytoestrogens With the Risk For Endometrial Cancer
By Jean Hankin, M.S. Cancer Research Center of Hawaii,
U. of Hawaii, Honolulu, HI

Ms. Hankin participated in a study to determine the role of dietary phytoestrogens, particularly tofu, in endometrial cancer. The study involved 341 women of different ethnic backgrounds who were diagnosed with some form of endometrial cancer.

The study found that total caloric intake was definitely related to the incidence of endometrial cancers. There appeared to be no positive correlation between endometrial cancer and the amount of protein and fat ingested as long as total calories were kept at a reasonable level. Dietary fiber had a positive effect on the women in the study. The data suggests that women on a diet rich in soy and fiber could be at a reduced risk for endometrial cancer.

A Double-Blind, Clinical Trial of the Effects of Soy Protein on Risk Parameters for Prostate Cancer
By Stephen Barnes, Ph.D.,
Department of Pathology and Pharmacology & Toxicology,
University of Alabama at Birmingham, AL

A number of studies suggest that soy-based foods are related to a reduction in the rate of prostate cancer. Genistein, a soy isoflavone, inhibits the proliferation of human prostate cancer cells in vitro. In a study involving elderly men who tested positive for the prostate specific antigen (but were without prostate cancer), it was determined that genistein has a positive effect on preventing prostate cancer, even in men who already are at risk. The findings are preliminary, and the study is ongoing.

A Pilot Study of Genistein/Soy Protein Isolate in the Treatment of Hereditary Hemorrhagic Telangiectasia;
Possible Efficacy in HHT-Associated Epistaxis, Gastrointestinal Hemorrhage and Migraine

By Joshua R. Korzenik, M.D. Yale University School of Medicine, New Haven, CT

Hereditary Hemorrhagic Telangiectasia (HHT) is a rare hereditary disease with symptoms including nosebleeds, gastrointestinal bleeding and migraines. The implications of soy protein treatment in disease states such as this are relevant because of soy's overall effect on blood vessels. It was determined that a diet high in genistein was able to decrease the amount of both gastrointestinal bleeding, nosebleeds and, suprisingly, migraines. In the future, soy protein will be looked at specifically for the treatment of migraines, including migraines related to PMS.

HORMONAL EFFECTS OF SOY: PREMENOPAUSAL STUDIES

Metabolic and Hormonal Responses In Elite Female Gymnasts Undergoing Strenuous Training and Supplementation With Supro Brand Isolated Soy Protein
By Valentin Stroescu, Ph.D.,
Institute of Sports Medicine, Bucharest,
and Institute of Endocrinology Bucharest, Romania

Dr. Stroescu and his associates have previously shown that soy protein benefits endurance athletes who compete in kayak-canoeing, rowing and swimming. In the present study, 14 female gymnasts were studied to examine their metabolic-hormonal status while undergoing intense training. They were given soy protein supplementation for a four-month period. Metabolic tests included measurements of serum hemoglobin, protein, serum fats, urea, calcium, magnesium, creatinine, hepatic enzymes, immunoglobulins and urinary mucoproteins. Serum levels of thyroid, T3 and T4 were also measured, as well as estradiol, progesterone, prolactin, testosterone and urinary 17-ketosteroid levels. Results showed that all participants experienced a slight increase in lean body mass. There was also a slight increase in prolactin and T4 and a decrease in alkaline phosphatase. These preliminary findings suggest that with daily supplementation of soy protein during times of strenuous exercise and training, there is lower metabolic-hormonal stress on the body.

Hormonal Effects of Isoflavones in Humans
By Aedin Cassidy, Ph.D.,
Centre for Nutrition and Food Safety,
School of Biological Sciences Guildford, Surrey, England

Fifteen premenopausal, and six postmenopausal women, plus six middle-aged men, were examined to judge the effects of soy protein on different hormones in the body. In the premenopausal women, the soy protein diet had the effect of lengthening the follicular stage of the menstrual cycle and causing a delay in peak progesterone concentrations. Mid-cycle surges of LH and FSH were also suppressed. Total cholesterol levels were significantly reduced in these women as well. In the postmenopausal women, LH levels were also significantly reduced, but there was no change in FSH levels. In the men, the soy protein had no effect on LH and FSH.

The researchers could not reach definite conclusions, however, as the complete dietary habits of all of the participants could not be monitored. (The premenopausal women were monitored 24 hours per day for three months). The researchers did conclude, however, that under controlled conditions, isoflavones are biologically active in premenopausal women and appear to act as weak estrogens.

Reductions in Steroid and Gastrointestinal Hormone Levels in Men and Premenopausal Women with Soya Consumption For One Month By Lee-Jane Lu, Ph.D.,
Department of Preventative Medicine and Community Health,
University of Texas Medical Branch, Galveston, TX

Studies show that soybean consumption can reduce the rate of breast, prostate and colon cancer. Dr. Lu's group sought to understand the mechanisms of the beneficial effect. It was hypothesized that soybean consumption affects hormones which regulate the growth of neoplastic cells. Both males and females were given 12 ounces of soy milk with each meal, for one month. Results of this study showed that in female participants, mean serum levels of estradiol were reduced by 60%, while in men levels of androstanediol glucuronide (a metabolite of dihydrotestosterone) were decreased by 13%.

POSTMENOPAUSAL STUDIES

Effects of Mammalian and Plant Estrogens On Mammary Glands And Uteri Of Macaques By Delores Foth, M.D.
Ernst-Moritz-Arndt University,
Greifswald, Germany,
and Department of Comparative Medicine,
Bowman Gray School Of Medicine Of Wake Forest University, Winston-Salem, NC

Isoflavone-enriched soy isolate was viewed as a possible alternative to synthetic estradiol. Surgically postmenopausal female macaques were treated with either estradiol or soy isoflavones. The doses were roughly equivalent to the consumption of 1 mg/woman/day for estradiol, and 148mg/woman/day of soy isoflavones. Estradiol induced endometrial thickening and epithelial proliferation in mammary gland, whereas soy isoflavone did not.

Dietary Flour Supplementation Decreases Post-Menopausal Hot Flushes:
Effect of Soy and Wheat
By Alice Murkies, M.S.,
Brighton Medical Clinic, Australia

The estrogen-like action of soy flour containing the isoflavone daidzin and wheat flour containing the less potent enterlactones were compared. The goal was to reduce hot flushes, a problem that up to 85% of all postmenopausal women experience. Using 58 postmenopausal women experiencing at least 14 hot flushes a week, Ms. Murkies showed that soy flour reduced the incidence of hot flushes by up to 40% within a six week period. The wheat flour had some effect on the occurrence of hot flushes in the women, however the results were not as dramatic nor as rapid. The amount of soy flour used to achieve these results was 45 grams per day.

The Potential Use of Dietary Soy Supplementation As A Post-Menopausal Hormone Replacement Therapy
By Gregory L Burke, M.D.
Bowman Gray School of Medicine of Wake Forest University, Winston-Salem, NC

According to Dr. Burke, it is a known fact that traditional hormone replacement therapy, using powerful hormones like estradiol, has been able to reduce the incidence of cardiovascular disease and osteoporosis, in addition to controlling vasomotor symptoms in postmenopausal women. However, there are some profound drawbacks, including increased risk for breast and endometrial cancer. Alternatives to HRT-such as soy isoflavones-have potential, especially for the 85% of postmenopausal American women who do not use HormoneReplacement Therapy.

In a short-term study conducted by Dr. Burke and his associates, slight improvements in menopausal symptoms and an improvement in "health-related quality of life" was observed in those women who consumed a soy protein isolate supplement. Also noted were improvements in lipids/lipoproteins and blood pressure levels in these same women.

More significantly, soy supplementation appeared to have some of the benefits of the HRT, with none of the adverse side effects.

Effect of A Dietary Soy Bar On Menopausal Symptoms
By Margo Woods, D.Sc.,
Health Nutrition Unit,
Tufts U. School of Medicine,
Boston MS
Asian women who consume a largely soy-based diet are far less likely to experience hot flashes than American women. Dr. Woods conducted a study on the effects of soy on hot flashes in menopausal women.

Menopausal women complaining of hot flashes were given two dietary soy bars per day, containing a total of 40 mg of phytoestrogens. The study lasted 11 weeks. Although there was a great variation in the number of hot flash episodes in the women studied, all women reported at least some reduction in hot flashes on a daily basis.

Hormonal Effect of Isoflavones
By John Anthony Eden, M.D.
Royal Hospital for Women,
Paddington, Australia

Dr. Eden conducted a study on the benefits of soy in relation to menopausal symptoms in women, particularly hot flashes. The study is still underway, but Dr. Eden reported that 160 mg. of soy isoflavones per day decreased the average number of hot flashes from 6.7 to 3.4. Amelioration of other menopausal symptoms was also noted.




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