A review of the clinical effects of phytoestrogens

Obstetrics and Gynecology (USA), 1996, 87/5 II SUPPL. (897-904)

Objective: To review the sources, metabolism, potencies, and clinical effects of phytoestrogens on humans. Data Sources: The MEDLINE data base for the years 1980-1995 and reference lists of published articles were searched for relevant English-language articles concerning phytoestrogens, soy products, and diets with high-phytoestrogen content. Methods of Study Selection: We identified 861 articles as being relevant. Human cell line studies, human epidemiologic studies (case-control or cohort), randomized trials, and review articles were included. Animal studies regarding phytoestrogens were included when no human data were available concerning an important clinical area. Tabulation, Integration, and Results: Included were studies containing information considered pertinent to clinical practice in the areas of growth and development, menopause, cancer, and cardiovascular disease. When findings varied, those presented in this study reflect consensus. All studies concurred that phytoestrogens are biologically active in humans or animals. These compounds inhibit the growth of different cancer cell lines in cell culture and animal models. Human epidemiologic evidence supports the hypothesis that phytoestrogens inhibit cancer formation and growth in humans. Foods containing phytoestrogens reduce cholesterol levels in humans, and cell line, animal, and human data show benefit in treating osteoporosis. Conclusion: This review suggests that phytoestrogens are among the dietary factors affording protection against cancer and heart disease in vegetarians. With this epidemiologic and cell line evidence, intervention studies are now an appropriate consideration to assess the clinical effects of phytoestrogens because of the potentially important health benefits associated with the consumption of foods containing these compounds.

Eating to beat breast cancer: Potential role for soy supplements

Annals of Oncology (Netherlands), 1997, 8/3 (223-225)

Background: The study reviews the anticancer properties of natural isoflavones which occur in especially high concentration in soybeans. It considers the suitability of soybean products for clinical trials aiming to reduce the progression of breast cancer. Methods: Evidence is reviewed that plant isoflavones such as genistein show cytostatic activity against human mammary cancer cell lines in vitro and can also suppress carcinogen-induced mammary cancer in young and mature rats. Results: Plant isoflavones are converted in the bowel to compounds with potential antioestrogenic and antioxidative properties. These compounds show cytostatic activity for both oestrogen receptor-positive and negative human mammary cancer cell lines, and also inhibit growth and progress of the rat mammary cancer model. The high content of soybean products in the diet of Asian women has been postulated as one reason for their relatively low breast cancer incidence. Conclusion: Preclinical studies suggest that soybean products be given priority for clinical trials in breast cancer protection. A pilot study could test soy protein supplements as longterm adjuvant dietary treatment after primary surgery for early breast cancer, looking for a decrease in the risk of recurrence or of second primary tumours.

Estrogenic and antiproliferative properties of genistein and other flavonoids in human breast cancer cells in vitro

Nutrition and Cancer (USA), 1997, 27/1 (31-40)

Experimental and epidemiologic studies support the view that soyfoods prevent cancer as well as diseases and symptoms associated with estrogen deficiency. Recent research suggests that the isoflavonoid genistein, a phytoestrogen found in abundance in soyfoods, may be one of the principal molecular components responsible for these health benefits. In this study we investigated the effects of a broad physiologically relevant concentration range of genistein on estrogen receptor (ER) binding, induction of the estrogen-regulated antigen pS2, and cell proliferation rate cells grown in vitro. Dose response to genistein was compared with that of estradiol, tamoxifen, and several other structurally similar iso- and bioflavonoids (e.g., equol, kaempferol, and quercetin). Our results revealed that genistein has potent estrogen agonist and cell growth- inhibitory actions over a physiologically achievable concentration range (10 nM-20 microM). Other flavonoids over the same concentration range were good estrogen agonists and poor cell growth inhibitors (equol) or poor estrogen agonists and potent growth inhibitors (kaempferol and quercetin). The growth- inhibitory actions of flavonoids were distinctly different from those of triphenyl antiestrogens like tamoxifen. In summary, our results reveal that genistein is unique among the flavonoids tested, in that it has potent estrogen agonist and cell growth-inhibitory actions over a physiologically relevant concentration range.

Epidemiology of soy and cancer: perspectives and directions.

J Nutr (UNITED STATES) Mar 1995, 125 (3 Suppl)

Previous epidemiologic studies of the effects of soy protein on cancer risk have been limited by small variations in soy intake, inability to separate soy from other dietary variables and difficulties inherent in relating dietary intake to the development of cancer several decades later. As a result, although existing data suggest that soy protein may be protective for cancer risk, results are overall inconclusive. There is also evidence that soy products may affect risk factors for cancer, such as endogenous hormone levels. Preliminary data from our group indicate that young Adventist women who are vegetarians with high soy intake and a lower risk of breast cancer may have higher levels of an adrenal androgen, dehydroepiandrosterone sulfate. Other groups have noted that soy protein may be associated with alterations in the regulation and binding of ovarian hormones. Additional studies examining effects of soy protein on risk factors for cancer would help, not only in delineating mechanisms of cancer development, but also in designing dietary programs aimed at cancer prevention. (34 Refs.)

Dietary soy protein and estrogen replacement therapy improve cardiovascular risk factors and decrease aortic cholesteryl ester content in ovariectomized cynomolgus monkeys

Metabolism: Clinical and Experimental (USA), 1997, 46/6 (698-705)

Estrogen replacement therapy (ERT) decreases the progression of coronary artery atherosclerosis in monkeys. Dietary soy protein also retards the progression of atherosclerosis relative to animal proteins such as casein. Soy protein contains weakly estrogenic compounds called isoflavones or phytoestrogens that may be responsible for the cardioprotective effects. This study was designed as a 2 x 2 factorial to determine the magnitude of soy protein's effects on cardiovascular risk factors relative to casein and lactalbumin, with or without estradiol treatment. Ovariectomized female monkeys were randomized to four treatment groups based on past dietary cholesterol consumption, their origin, end past reproductive history, end studied for 7 months. The animals were divided into (1) a group fed casein end lactalbumin as the protein source (n = 14), (2) a group fed casein and lactalbumin as the protein source = 13), (3) a group fed soybean protein isolate as the protein source (n = 11), and (4) a group fed soybean protein isolate as the protein source plus E2 (n = 10). Soy protein compared with casein consumption resulted in a significant improvement in plasma lipid and lipoprotein concentrations, e significant improvement in insulin sensitivity and glucose effectiveness as determined by minimal-model analyses, and a decrease in arterial lipid peroxidation, E2- treated monkeys had a significant reduction in fasting insulin levels and insulin to glucose ratios, total body weight, and amounts of abdominal fat, and had smaller low-density lipoprotein (LDL) particles. In addition. E2 treatment resulted in a significant reduction (P = .001) in aortic cholesteryl ester content. A similar trend (P = .14) was found for soy protein compared with casein. There also was a significant interaction (P = .02) with soy and E2, such that animals consuming soy protein + E2 had the least arterial cholesteryl ester content. These results suggest that both ERT and dietary soybean protein have beneficial effects on cardiovascular risk factors. Interestingly, the two treatments affected different risk factors and together resulted in the greatest reduction in arterial cholesterol content. Further studies are needed to determine the active component of the soy protein and to assess its long-term effects on the cardiovascular system and other organ systems (such as the bones and reproductive system).

Soy isoflavones enhance coronary vascular reactivity in atherosclerotic female macaques

Fertility and Sterility (USA), 1997, 67/1 (148-154)

Objective: To examine the effects of soy phytoestrogens on coronary vascular reactivity in atherosclerotic male and female rhesus monkeys. Design: A prospective, randomized, blinded, controlled study. Setting: Comparative Medicine Clinical Research Center of an academic medical center. Patient(s): Twenty-two young adult rhesus monkeys with pre-existing diet- induced atherosclerosis. Intervention(s): Monkeys were fed soy-based diets for 6 months identical in composition, except that the isoflavones were extracted from one (low-isoflavone) and intact in the other (high- isoflavone). Quantitative coronary angiography was performed at the end of the study period. Females in the low-isoflavone group underwent a second angiography after an acute IV dose of genistein. Main Outcome Measure(s): Percent change in diameter of the proximal left circumflex coronary artery in response to intracoronary acetylcholine and nitroglycerin, compared with control diameter. Result(s): Arteries from males constricted in response to acetylcholine. Arteries from females in the low-isoflavone group constricted (-6.2% + 2.8%, mean plus or minus SEM), whereas arteries from females in the high- isoflavone group dilated (6.4% plus or minus 1.2%, mean plus or minus SEM). Intravenous administration of genistein caused dilation in the previously constricting low-isoflavone females (3.39% plus or minus 2.8%). Conclusion(s): Like mammalian estrogens, dietary soy isoflavones enhance the dilator response to acetylcholine of atherosclerotic arteries in female monkeys.

Soybean isoflavones improve cardiovascular risk factors without affecting the reproductive system of peripubertal rhesus monkeys

Journal of Nutrition (USA), 1996, 126/1 (43-50)

Although the beneficial effects of dietary soybean protein compared with animal proteins on plasma lipids, lipoproteins and atherosclerosis have been known for about 50 years, it has been uncertain whether these effects are due to its amino acid concentrations or other components in soybeans. To assess the effect of soybean protein's alcohol-extractable components (including the isoflavonic phytoestrogens genistein and daidzein) on plasma lipid and lipoprotein concentrations and to este fed 27 peripubertal male and female rhesus monkeys moderately atherogenic diets in which the source of dietary protein was a soy isolate (20% by weight), either containing phytoestrogens (also termed isoflavones) or with the phytoestrogens removed by alcohol extraction. The study was a crossover design with each period lasting for 6 mo. The phytoestrogen-intact soy protein (compared with the alcohol-extracted soy protein) had favorable effects on plasma lipid and lipoprotein concentrations, specifically by significantly reducing LDL + VLDL cholesterol concentrations in both males and females (similar30-40% lower), significantly increasing high density lipoprotein cholesterol (HDLC) concentrations for females (similar15% higher) and significantly lowering total plasma cholesterol (TPC):HDLC ratios (similar20% lower for males and 50% lower for females). The phytoestrogens had no adverse effects on the reproductive systems of either the males or females, as evaluated by reproductive hormone concentrations and organ weights at necropsy. Thus, the isoflavones in soy protein improve cardiovascular disease risk factors without apparent deleterious effects on the reproductive system of peripubertal rhesus monkeys.

Comparison between dietary soybean protein and casein of the inhibiting effect on atherogenesis in the thoracic aorta of hypercholesterolemic (ExHC) rats treated with experimental hypervitamin D.

Biosci Biotechnol Biochem (JAPAN) Mar 1997, 61 (3) p514-9

Atherosclerotic lesions of the thoracic aorta were induced in exogenously hypercholesterolemic (ExHC) rats by treating initially with hypervitamin D2 and subsequently feeding on hypercholesterolemic diets for 180 days. Dietary soybean protein, in comparison with casein, substantially decreased the degree of atherosclerotic lesions, which was evaluated by intimal thickening, although with a similar topographical distribution. The casein-fed rats tended to maintain a high concentration of serum cholesterol, particularly in triacylglycerol-rich lipoproteins. The concentrations of apo A-I and TBARS in the serum was comparable between the dietary protein groups. The data suggest that dietary soybean protein, compared to casein, produced lipoproteins which were less atherosclerotic by partitioning cholesterol in the triacylglycerol-poor lipoproteins.

Soy isoflavones enhance coronary vascular reactivity in atherosclerotic female macaques.

Fertil Steril (UNITED STATES) Jan 1997, 67 (1) p148-54

OBJECTIVE: To examine the effects of soy phytoestrogens on coronary vascular reactivity in atherosclerotic male and female rhesus monkeys. DESIGN: A prospective, randomized, blinded, controlled study. SETTING:Comparative Medicine Clinical Research Center of an academic medical center. PATIENT(S): Twenty-two young adult rhesus monkeys with pre-existing diet-induced atherosclerosis. INTERVENTION(S): Monkeys were fed soy-based diets for 6 months identical in composition, except that the isoflavones were extracted from one flow-isoflavone) and intact in the other (high-isoflavone). Quantitative coronary angiography was performed at the end of the study period. Females in the low-isoflavone group under went a second angiography after an acute IV dose of genistein. MAIN OUTCOME MEASURE(S): Percent change in diameter of the proximal left circumflex coronary artery in response to intracoronary acetylcholine and nitroglycerin, compared with control diameter. RESULT(S): Arteries from males constricted in response to acetylcholine. Arteries from females in the low-isoflavone group constricted (-6.2% +/- 2.8%, mean +/- SEM), whereas arteries from females in the high-isoflavone group dilated (6.4% +/- 1.2%, mean +/- SEM). Intravenous administration of genistein caused dilation in the previously constricting low-isoflavone females (3.3% +/- 2.8%). CONCLUSION(S): Like mammalian estrogens, dietary soy isoflavones enhance the dilator response to acetylcholine of atherosclerotic arteries in female monkeys.

Protease inhibitors and carcinogenesis

Cancer Investigation (USA), 1996, 14/6 (597-608)

This brief review article deals with the subject of anticarcinogenic activity of protease inhibitors (PI). Three basic premises are made: (1) Although PI are prevalent constituents of dietary staples such as soy products, which have been epidemiologically associated with reduced cancer incidences at multiple target sites, they are unlikely to be the active anticarcinogenic entities. Cooked soy products, which are devoid of PI activity, are equally as effective at reducing cancer development as raw soy products. Isoflavones are likely to represent major chemopreventive agents in soy, although other constituents may well contribute. (2) Although supplementation of diets with PI (natural or synthetic), or direct topical administration, results in lower cancer incidences in many experimental models in vivo, this effect appears to be indirect. Dietary PI are, in general, poorly absorbed from the GI tract, and never reach target organs in any measureable quantity. The most attractive hypothesis is that dietary PI could induce synthesis and distribution of endogenous PI (acute-phase reactants), which have widespread effects on cell growth and behavior. Effects of topical administration of PI also encompass prominent anti-inflammatory effects. (3) A spectrum of PI inhibit in vitro transformation induced by a variety of carcinogenic agents. Their effects can be grouped into three basic categories, affecting: (a) signal transduction pathways; (b) DNA repair processes; and (c) nuclear proteases. I suggest that the nuclear multicatalytic protease activity, in particular the chymotrypsin-like activity, represents an important cellular target for which considerable anecdotal support can be garnered.

Vegetable, fruit, and grain consumption to colorectal adenomatous polyps

American Journal of Epidemiology (USA), 1996, 144/11 (1015-1025)

Previous studies suggest that colorectal cancer risk decreases with higher intake of vegetables, fruits, and grains. Few studies, however, have examined these factors in relation to occurrence of colorectal polyps. The authors used case-control data from 488 matched pairs to evaluate associations of vegetables, fruits, and grains with polyps. Subjects were southern Californians aged 50-74 years who had a sigmoidoscopy in 1991-1993. Diet in the year before sigmoidoscopy was measured with a food frequency questionnaire. Frequent consumption of vegetables, fruits, and grains was associated with decreased polyp prevalence. Specifically, the adjusted odds ratio comparing the highest with the lowest quintile of intake for vegetables was 0.47 (95% confidence interval (CI) 0.29-0.76), for fruits was 0.65 (95% CI 0.40-1.05), and for grains was 0.55 (95% CI 0.33-0.91). The authors also found inverse associations for high carotenoid vegetables, cruciferae, high vitamin C fruits, garlic, and tofu (or soybeans). After further adjusting for potentially anticarcinogenic constituents of these foods, high carotenoid vegetables, cruciferous vegetables, garlic, and tofu (or soybeans) remained inversely associated with polyps. These findings support the hypothesis that high intake of vegetables, fruits, or grains decreases the risk of polyps and suggest that any protective effects might reflect nmeasured constituents in these foods.

Tofu and risk of breast cancer in Asian-Americans

Cancer Letters (Ireland), 1997, 114/1-2 (313-314)

Breast cancer rates among Asian-Americans are lower than those of US whites but considerably higher than rates prevailing in Asia. It is suspected that migration to the US brings about a change in endocrine function among Asian women, although reasons for this change remain obscure. The high intake of soy in Asia and its reduced intake among Asian-Americans has been suggested to partly explain the increase of breast cancer rates in Asian- Americans. We conducted a population-based case-control study of breast cancer among Chinese-, Japanese-, and Filipino-American women in Los Angeles County MSA, San Francisco Oakland MSA, and Oahu, Hawaii. Using a common questionnaire which assessed frequency of intake of some 90 food items, 597 Asian-American women (70% of those eligible) diagnosed with incident, primary breast cancer during 1983-1987 and 966 population-based controls (75% of those eligible) were interviewed. Controls were matched to casesthnicity, and area of residence. This analysis compares usual adult intake of soy (estimated primarily from tofu intake) among breast cancer cases and control women. After adjustment for age, ethnicity and study area, intake of tofu was more than twice as high among Asian-American women born in Asia (62 times per year) compared to those born in the US (30 times per year). Among migrants, intake of tofu decreased with years of residence in the US. Risk of breast cancer decreased with increasing frequency of intake of tofu after adjustment for age, study area, ethnicity, and migration history; the adjusted OR associated with each additional serving per week was 0.85 (95% CI = 0.74-0.99). The protective effect of high tofu intake was observed in pre- and postmenopausal women. This association remained after adjustment for selected dietary factors and menstrual and reproductive factors. However, this study was not designed specifically to investigate the role of soy intake and our assessment of soy intake may be incomplete. We cannot discount the possibility that soy intake is a marker of other protective aspects of Asian diet and/or Asian lifestyle.

Estrogenic activity of natural and synthetic estrogens in human breast cancer cells in culture

Environmental Health Perspectives (USA), 1997, 105/SUPPL. 3 (637-645)

We investigated the estrogenic activity of various environmental pollutants (xenobiotics), in particular the xenoestrogen o,p-DDT, and compared their effects with those of endogenous estrogens, phytoestrogens, and mycoestrogens on estrogen receptor binding capacity, induction of estrogen end products, and activation of cell proliferation in estrogen-sensitive human breast cancer cells in monolayer culture. We also quantified the levels of phytoestrogens in extracts of some common foods,herbs, and spices acid in human saliva following consumption of a high phytoestrogen food source (soy milk) to compare phytoestrogen abundance and bioavailability relative to the reported xenoestrogen burden in humans. Results show that natural endogenous estrogens, phytoestrogens, mycoestrogens, and xenoestrogens bind estrogen receptor (ER) in intact cells, but demonstrate marked differences in their ability to induce end products of estrogen action and to regulate cell proliferation. All of the different classes of estrogens stimulated cell proliferation at concentrations that half-saturated ER, but only some classes were able to induce estrogen-regulated end products. Genistein, a common phytoestrogen found in soy foods, differed from the xenoestrogen DDT in its effects on cell proliferation and ability to induce estrogen-regulated end products. Moreover, we found that many of the foods, herbs, and spices commonly consumed by humans contain significant amounts of phytoestrogens, and consumption of soy milk, a phytoestrogen-rich food, markedly increases the levels of phytoestrogens in saliva. In conclusion, our in vitro results predict that a diet high in phytoestrogens would significantly reduce the binding of weak xenoestrogens to ER in target tissues in vivo.

Isolation of isoflavones from soy-based fermentations of the erythromycin-producing bacterium Saccharopolyspora erythraea

Applied Microbiology and Biotechnology (Germany), 1997, 47/4 (398-404)

A search for an abundant and economical source of isoflavones, particularly genistein, led to the discovery that the erythromycin-producing organism Saccharopolyspora erythraea also produces this promising new cancer-prevention agent. Erythromycin fermentation is a large-scale, soybean-based process used world-wide for the commercial production of this medically important antibiotic. Results from this study indicate that genistein (the glucoside form of genistein), which is added to the fermentation in the soybean media, was converted to genistein through the action of a beta-glucosidase produced bv the organism. Genistein was co-extracted with erythromycin from the fermentation broth, then separated from erythromycin during the second step of the purification process for the production of erythromycin.

Phyto-oestrogens and Western diseases

Annals of Medicine (United Kingdom), 1997, 29/2 (95-120)

Incidences of breast, colorectal and prostate cancer are high in the Western world compared to countries in Asia. We have postulated that the Western diet compared to the semivegetarian diet in some Asian countries may alter hormone production, metabolism or action at the cellular level by some biochemical mechanisms. Our interest has been focused on two groups of hormone-like diphenolic phyto-oestrogens of dietary origin, the lignans and isoflavonoids abundant in plasma of subjects living in areas with low cancer incidence. The precursors of the biologically active compounds detected in man are found in soybean products, whole-grain cereal food, seeds, and berries. The plant lignan and isoflavonoid glycosides are converted by intestinal bacteria to hormone-like compounds. The weakly oestrogenic diphenols formed influence sex-hormone production, metabolism and biological activity, intracellular enzymes, protein synthesis, growth factor action, malignant cell proliferation, differentiation, cell adhesion and angiogenesis in such a way as to make them strong candidates for a role as natural cancer-protective compounds. Their effect on some of the most important steroid biosynthetic enzymes may result in beneficial modulation of hormone concentrations and action in the cells preventing development of cancer. Owing to their oemen and may to some degree inhibit osteoporosis, but alone they may be insufficient for complete protection. Soy intake prevents oxidation of the low-density lipoproteins in vitro when isolated from soy-treated individuals and affect favourably plasma lipid concentrations. Animal experiments provide evidence suggesting that both lignans and isoflavonoids may prevent the development of cancer as well as atherosclerosis. However, in some of these experiments it has not been possible to separate the phyto-oestrogen effect from the effect of other components in the food. The isoflavonoids and lignans may play a significant inhibitory role in cancer development particularly in the promotional phase of the disease, but recent evidence points also to a role In the initiation stage of carcinogenesis. At present, however, no definite recommendations can be made as to the dietary amounts needed for prevention of disease. This review deals with all the above-mentioned aspects of phyto-oestrogens.

Eating to beat breast cancer: Potential role for soy supplements

Annals of Oncology (Netherlands), 1997, 8/3 (223-225)

Background: The study reviews the anticancer properties of natural isoflavones which occur in especially high concentration in soybeans. It considers the suitability of soybean products for clinical trials aiming to reduce the progression of breast cancer. Methods: Evidence is reviewed that plant isoflavones such as genistein show cytostatic activity against human mammary cancer cell lines in vitro and can also suppress carcinogen-induced mammary cancer in young and mature rats. Results: Plant isoflavones are converted in the bowel to compounds with potential antioestrogenic and antioxidative properties. These compounds show cytostatic activity for both oestrogen receptor-positive and negative human mammary cancer cell lines, and also inhibit growth and progress of the rat mammary cancer model. The high content of soybean products in the diet of Asian women has been postulated as one reason for their relatively low breast cancer incidence. Conclusion: Preclinical studies suggest that soybean products be given priority for clinical trials in breast cancer protection. A pilot study could test soy protein supplements as longterm adjuvant dietary treatment after primary surgery for early breast cancer, looking for a decrease in the risk of recurrence or of second primary tumours.

Inhibition of N-methyl-N-nitrosourea-induced mammary tumors in rats by the soybean isoflavones

Anticancer Research (Greece), 1996, 16/6 A (3293-3298)

Soy-based diets, rich in the isoflavones genistein and daidzein, are thought to protect against breast and prostate cancer. Soy-based diets, rich in the isoflavones genistein and daidzein, are thought to protect against breast and prostate cancer. We used the N-methyl-N-nitrosourea (MNU)-induced mammary carcinogenesis animal model to test the effectiveness of these two isoflavones as chemopreventive agents. Each isoflavone was injected daily into 35-day-old rats for six months while we monitored the animals' body weight and mammary tumor appearance. Genistein was effective in reducing tumor multiplicity, but it reduced tumor incidence only marginally. Daidzein was less effective in reducing both tumor incidence and multiplicity. To investigate genistein's mechanism of action we determined the topoisomerase II (topo II) activity and detected the phosphotyrosine-containing peptides in the extracts of mammary tissues isolated from control and isoflavone-treated animals. Mammary tumors contained over 60-fold higher topo II enzymatic activity than the mammary glands. Similarly, more tyrosine phosphopeptides were detectable in mammary tumors than in mammary glands. Tissue samples from genistein treated animals contained similar topo II and protein tyrosine kinase (PTK) activities as the control group. These data suggest that mammary tumorigenesis is accompanied by an extensive increase in topo II and PTK activities. The mechanism of chemoprevention by genistein, however, is independent of topo II or PTK inhibition.

In vitro hormonal effects of soybean isoflavones.

J Nutr; 125(3 Suppl):751S-756S 1995

Isoflavones exhibit a multitude of biological effects that influence cell growth and regulation, and, thus, may have potential value in the prevention and treatment of cancer. Isoflavones are weak estrogens and can function both as estrogen agonists and antagonists depending on the hormonal milieu and the target tissue and species under investigation. Genistein, one of the two primary isoflavones in soybeans, has attracted much attention from the research community, not only because of its potential antiestrogenic effects, but because it inhibits several key enzymes thought to be involved in carcinogenesis. Although still speculative, greater dietary incorporation of soybean products, because of the high concentration of isoflavones, may be a safe and effective means of reducing cancer risk.

Soy fiber delays disease onset and prolongs survival in experimental Clostridium difficile ileocecitis

Frankel W.L.; Choi D.M.; Zhang W.; Roth J.A.; Don S.H.; Afonso J.J.; Lee
F.- H.; Klurfeld D.M.; Rombeau J.L.
Harrison Department of Surgery, University of Pennsylvania Hospital, 34th
and Spruce Street, Philadelphia, PA 19104 USA
J. PARENTER. ENTER. NUTR. (USA) , 1994, 18/1 (55-61)

Clostridium difficile colitis is a disabling complication in critically ill patients who commonly receive broad-spectrum antibiotics and liquid diets. To date, there is no experimental model specifically designed to investigate the effects of liquid diets on this type of colitis. The addition of fiber to liquid diets normalizes gut structure and improves absorptive function in selected conditions of intestinal dysfunction. The purposes of this study were the following: (1) to develop a reproducible model to examine the interaction of acute C difficile-induced colitis and liquid diets, (2) to determine whether the addition of soy fiber to a liquid diet improves disease, and (3) to investigate possible mechanisms of fiber-mediated disease improvement. Syrian hamsters were pair-fed with either a polymeric liquid diet or the same diet with 1.4% soy fiber for 10 days. Animals were given either clindamycin and C difficile (to produce ileocecitis), or equivalent volumes of saline. Mean survival time and systematic stool examinations for C difficile toxin positivity, liquidity, and percent water were performed to determine the effect of soy fiber on disease. Survival time was prolonged by 34% (p < .05), and C difficile toxin positivity and stool liquidity were significantly reduced (p < .05) with fiber. Additional animals were studied to determine possible mechanisms for improved survival in fiber-supplemented animals. Cecal histology, colonic water absorption, cecal microflora, and gastric to anus transit time were measured in these animals. Colonic water absorption and gastric to anus transit time were significantly increased (p < .05) and decreased (p < .05) with fiber, respectively. A hamster model of C difficile ileocecitis has been designed to investigate the effects of liquid diets. Fiber supplementation prolongs survival in this model due in part to a delay in onset of C difficile infection and improved colonic water absorption.