Whole Body Health Sale

SOY PROTEIN



Table of Contents
image Effects of soya consumption for one month on steroid hormones in premenopausal women: implications for breast cancer risk reduction
image Isoflavonoids in soy drinks and availability in human body fluids.
image Programming against breast cancer with genistein, a component of soy.
image Induction of maturation of breast cancer cells by genistein.
image Estrogenic and anti-estrogenic actions of genistein in human breast cancer cell growth mediated through the polyamine pathway.
image Inhibition of human prostate cancer cell proliferation by genistein.
image Dietary soy protein and estrogen replacement therapy improve cardiovascular risk factors and decrease aortic cholesteryl ester content in ovariectomized cynomolgus monkeys.
image Soy isoflavones improve systemic arterial compliance but not plasma lipids in menopausal and perimenopausal women
image Modulation of age-related hyperparathyroidism and senile bone loss in Fischer rats by soy protein and food restriction
image Dietary Soy Protein
image Soy protein, thyroid regulation and cholesterol metabolism
image Overview of proposed mechanisms for the hypocholesterolemic effect of soy
image Endocrinological response to soy protein and fiber in mildly hypercholesterolemic men
image Response of hormones modulating plasma cholesterol to dietary casein or soy protein in minipigs
image Dietary protein effects on cholesterol and lipoprotein concentrations: A review
image Comparison of dietary casein or soy protein effects on plasma lipids and hormone concentrations in the gerbil (Meriones unguiculatus)
image Hypolipidemic effect of casein vs. soy protein in the hyperlipidemic hypothyroid chick model
image An extract of soy flour influences serum cholesterol and thyroid hormones in rats and hamsters
image Soy protein concentrate and isolated soy protein similarly lower blood serum cholesterol but differently affect thyroid hormones in hamsters
image Soy protein, thyroid regulation and cholesterol metabolism
image Soy and rye diets inhibit the development of Dunning R3327 prostatic adenocarcinoma in rats
image Effects of soya consumption for one month on steroid hormones in premenopausal women: Implications for breast cancer risk reduction
image Influence of isoflavones in soy protein isolates on development of induced prostate-related cancers in L-W rats
image A simplified method to quantify isoflavones in commercial soybean diets and human urine after legume consumption
image Rapid HPLC analysis of dietary phytoestrogens from legumes and from human urine
image Soy intake and cancer risk: A review of the in vitro and in vivo data
image Phytoestrogens are partial estrogen agonists in the adult male mouse
image Pathogenesis and treatment of liver fibrosis in alcoholics: 1996 update.
image Dietary soybean protein prevents bone loss in an ovariectomized rat model of osteoporosis
image 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.
image Dietary soy protein and estrogen replacement therapy improve cardiovascular risk factors and decrease aortic cholesteryl ester content in ovariectomized cynomolgus monkeys
image Effects of soya consumption for one month on steroid hormones in premenopausal women: Implications for breast cancer risk reduction
image Epidemiology of soy and cancer: Perspectives and directions
image Effects of hormonal therapies and dietary soy phytoestrogens on vaginal cytology in surgically postmenopausal macaques
image A review of the clinical effects of phytoestrogens
image Dietary flour supplementation decreases post-menopausal hot flushes: Effect of soy and wheat
image Soy and experimental cancer: Animal studies
image Soy protein concentrate and isolated soy protein similarly lower blood serum cholesterol but differently affect thyroid hormones in hamsters.
image Cholesterol-lowering effect of soyabean lecithin in normolipidaemic rats by stimulation of biliary lipid secretion.
image Biological effects of isoflavones in young women: Importance of the chemical composition of soyabean products
image Overview of proposed mechanisms for the hypocholesterolemic effect of soy
image Biological effects of a diet of soy protein rich in isoflavones on the menstrual cycle of premenopausal women
image A review of the clinical effects of phytoestrogens
image Eating to beat breast cancer: Potential role for soy supplements
image Estrogenic and antiproliferative properties of genistein and other flavonoids in human breast cancer cells in vitro
image Epidemiology of soy and cancer: perspectives and directions.
image Dietary soy protein and estrogen replacement therapy improve cardiovascular risk factors and decrease aortic cholesteryl ester content in ovariectomized cynomolgus monkeys
image Soy isoflavones enhance coronary vascular reactivity in atherosclerotic female macaques
image Soybean isoflavones improve cardiovascular risk factors without affecting the reproductive system of peripubertal rhesus monkeys
image 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.
image Soy isoflavones enhance coronary vascular reactivity in atherosclerotic female macaques.
image Protease inhibitors and carcinogenesis
image Vegetable, fruit, and grain consumption to colorectal adenomatous polyps
image Tofu and risk of breast cancer in Asian-Americans
image Estrogenic activity of natural and synthetic estrogens in human breast cancer cells in culture
image Isolation of isoflavones from soy-based fermentations of the erythromycin-producing bacterium Saccharopolyspora erythraea
image Phyto-oestrogens and Western diseases
image Eating to beat breast cancer: Potential role for soy supplements
image Inhibition of N-methyl-N-nitrosourea-induced mammary tumors in rats by the soybean isoflavones
image In vitro hormonal effects of soybean isoflavones.
image Soy fiber delays disease onset and prolongs survival in experimental Clostridium difficile ileocecitis

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Effects of soya consumption for one month on steroid hormones in premenopausal women: implications for breast cancer risk reduction

Lu LJ; Anderson KE; Grady JJ; Nagamani M Department of Preventive Medicine and Community Health, University of Texas Medical Branch, Galveston, TE 77555, USA. Cancer Epidemiol Biomarkers Prev (U.S.) Jan 1996, 5 (1) p63-70,

Soybean consumption is associated with reduced rates of breast, prostate, and colon cancer, which is possibly related to the presence of isoflavones that are weakly estrogenic and anticarcinogenic. We examined the effects of soya consumption on circulating steroid hormones in six healthy females 22-29 years of age. Starting within 6 days after the onset of menses, the subjects ingested a 12-oz portion of soymilk with each of three meals daily for 1 month on a metabolic unit. Daily isoflavone intakes were approximately 100 mg of daidzein (mostly as daidzin) and approximately 100 mg of genistein (mostly as genistin). Serum 17 beta-estradiol levels on cycle days 5-7, 12-14, and 20-22 decreased by 31% (P = 0.09), 81% (P = 0.03), and 49% (P = 0.02), respectively, during soya feeding. Decreases persisted for two or three menstrual cycles after withdrawal from soya feeding. The luteal phase progesterone levels decreased by 35% during soya feeding (P = 0.002). Dehydroepiandrosterone sulfate levels decreased progressively during soya feeding by 14-30% (P = 0.03). Menstrual cycle length was 28.3 +/- 1.9 days before soymilk feeding, increased to 31.8 +/- 5.1 days during the month of soymilk feeding (P = 0.06), remained increased at 32.7 +/- 8.4 days (P = 0.11) at one cycle after termination of soymilk feeding, and returned to pre-soya diet levels five to six cycles later. These results suggest that consumption of soya diets containing phytoestrogens may reduce circulating ovarian steroids and adrenal androgens and increase menstrual cycle length. Such effects may account at least in part for the decreased risk of breast cancer that has been associated with legume consumption.



Isoflavonoids in soy drinks and availability in human body fluids.

Franke, A.A., Custer, L.J., Tanaka, Y., and Maskarinec G. Cancer Research Center of Hawaii.

Increasing evidence suggests that soy consumption and/or soy isoflavones might protect against various cancers and against other chronic diseases such as osteoporosis and cardiovascular disorders. Epidemiologic studies concerned with the accurate assessment of the role of soy and isoflavones to prevent cancer require fast, reliable and affordable techniques to measure exposure favorably, through non-invasive protocols using biochemical markers. Therefore, we developed a rapid and accurate procedure to extract soy specific isoflavones from foods and from human plasma, urine, saliva and breast milk followed by selective HPLC quantitation using diode-array and electrochemical detection. Soy drinks known to be the main source of soy exposure in Western societies were found to contain isoflavones predominantly (70-90%) as their malonyl and glucoside conjugates. Total daidzein, genistein and glycitein levels varied between 90 and 370 mg/kg, 140 and 620 mg/kg, and 50 and 140 mg/kg, respectively. Similarly, up to fivefold inter-individual differences of isoflavone levels, in human fluids were observed after exposure to a given single soy serving. Isoflavonoid levels in plasma and other body fluids were found to be significantly correlated within an individual, suggesting that non-invasive protocols can be used in future epidemiologic studies evaluating the health benefits of soy foods and/or soy isoflavones.



Programming against breast cancer with genistein, a component of soy.

Lamartiniere, C.A., Cotroneo, M.S., and Murril, W.B. Department of Pharmacology and Toxicology, University of Alabama at Birmingham, Birmingham, AL.

Breast cancer is the most common cancer in females and is the second leading cause of cancer death among women. Yet, Asian women consuming a traditional diet high in soy products have a low incidence of breast cancer. Asians who emigrate to the United States and adopt a Western diet lose this protection. Using the imethylbenz(a) anthracene-mammary cancer rat model, we have investigated the potential of genistein, a phytoestrogen component of soy, to protect against the development of mammary cancer. Our results demonstrated that prepubertal genistein treatment resulted in decreased incidence and number of tumors per rat. Mammary whole mount analysis showed that genistein treatment resulted in mammary glands of adult rats developing fewer terminal end buds and more lobules. Cell proliferation studies with bromodeoxyuridine (BrdU) showed that terminal end buds from mammary glands of 50-day-old females treated with genistein had significantly fewer cells in S-phase of the cell cycle. In vivo mechanistic studies revealed that genistein and estrogen modulated tyrosine phosphorylation of the EGF-receptor. We conclude that genistein exerts its action via the estrogen receptor mechanism, that in turn sets in motion a cascade of down stream events to result in gland differentiation and less susceptibility for mammary cancer..



Induction of maturation of breast cancer cells by genistein.

Constantinou, A.l., Krygier, A., Mehta, R.R., and Murley, J.S., University of Illinois at Chicago, College of Medicine, Department of Surgical Oncology

Recent studies on animal models of mammary carcinogenesis identified the soybean isoflavone genistein as a chemopreventive agent. The objective of the present study is to determine if soybean isoflavones can be applied in the prevention of human breast carcinogenesis. Human adenocarcinoma cells that are either estrogen receptor-positive (ER+, such as MCF-7) or ER-negative ( ER-, such as MDA-MB-468) was used as our model system. Treatment of these cells with genistein Various concentrations resulted in cell growth inhibition, which was accompanied by the expression of maturation markers. Maturation was monitored by the induction of intra-cytoplasmic casein and lipids and the membrane protein l-CAM. Optimal expression of these maturation markers was after nine days of treatment with 30 micromolars of genistein. Both ER+ and ER- cells became differentiated in response to genistein treatments, suggesting that the anti-estrogenic function of genistein is unrelated to the mechanism of cell differentiation. Daidzein, the other major isoflavone component of soy, did not induce differentiation in either MCF-7 or MDA-MB-468 cells. To explore the potential applications of this observation, we used the nude mouse xenograft model of carcinogenesis. Treatment of either cell line with genistein before implantation into nude mice diminished the cells' tumorigenic potential. These data suggest that initiation of the differentiation program provides a protective effect against tumor growth in mice xenografts.



Estrogenic and anti-estrogenic actions of genistein in human breast cancer cell growth mediated through the polyamine pathway.

Balabhadrapargruni, S., Thomas, T., and Thomas, T.J. Rutgers University, New Brunswick, N.J.

Epidemiological and clinical studies suggest potential chemopreventive effects for the phytoestrogen genistein (GEN) against breast cancer. Proliferation of estrogen receptor positive MCF-7 breast cancer calls was determined after treatment with GEN (4, 5, 7-trihydroxyisoflavone). Thymidine incorporation assay, indicated that GEN significantly increased DNA synthesis at 10 micromolars compared to controls. In contrast, there was a 50% reduction in DNA synthesis at 25 micromolars, indicating an anti-estrogenic role for this drug. To elucidate the mechanism by which GEN exhibits the dose-dependent estrogenic or anti-estrogenic actions, its influence on enzymes of polyamine metabolism; ornithine decarboxylase (ODC), S-adenosylmethionine decarboxylase (SAMDC) and Spermidine/spermine-N-acetyltransterase (SSAT) was studied. Polyamines are cellular cations involved in cell proliferation and differentiation and their levels are regulated by estradiol in MCF-7 cells. GEN significantly increased ODC and SAMDC activity at 10 micromolars concentration. At growth inhibitory concentrations of GEN, however, these enzymes were inhibited. There was also a dose-dependent increase in SSAT levels with GEN treatment. These results indicate that a possible mechanism for GEN action might involve a polyamine pathway, eliciting growth promotive and suppressive effects depending on the concentration of the drug.



Inhibition of human prostate cancer cell proliferation by genistein.

Bosland, M.C.,Davies, J.A. and Voermans. C., Depts. Environm. Med. & Urology. NYU Medical Center, New York, N.Y.

Prostate cancer risk is low in countries with a high soy intake, and the soy phytoestrogen genistein inhibits prostate cancer cell proliferation. Our aims were to confirm prostate cancer cell growth inhibition and to explore possible mechanisms. We used androgen receptor (AR) and estrogen receptor positive LNCaP cells, AR- and ER- DU-145 cells, and AR- but possibly ER+ PC-3 cells. 24 hours after plating vehicle or genistein (12.5, 25, 37.5 ~g/ml) were added. At this time and after 24, 48 or 72 hours, the number of viable cells was counted by hemocytometer and dye exclusion. Cells were also harvested for flow cytometry, DNA laddering and TUNEL analysis. Genistein was no1 cytotoxic, but inhibited growth of PC-3 cells dose-relatedly, and abolished growth of LNCaP and DU-145 cells at all doses. Genistein induced apoptosis in LNCaP cells, but not in PC-3 and DU-145 cells (flow cytometry). The highest dose caused 20% of cells in apoptosis after 24 furs, but there was no apoptosis in the vehicle control. This was confirmed by DNA laddering and TUNEL analysis. Genistein caused a partial cell cycle arrest in PC-3 (shift to G0/G1) and DU-145 cells (shift to G2/M), but not in LNCaP cells. Thus, genistein inhibits human prostate cancer cell proliferation by various mechanisms, regardless of their AR/ER status.



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

Wagner JD Cefalu WT Anthony MS Litwak KN Zhang L Clarkson TB, Metabolism (1997 Jun) 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, and past reproductive history, and studied for 7 months.

The animals were divided into (1) a group fed casein and lactalbumin as the protein source (n = 14), (2) a group fed casein and lactalbumin as the protein source plus 17 beta-estradiol (E2) (n = 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, a 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 improve systemic arterial compliance but not plasma lipids in menopausal and perimenopausal women

Nestel PJ Yamashita T Sasahara T Pomeroy S Dart A Komesaroff P Owen A Abbey M. Arterioscler Thromb Vasc Biol (1997 Dec) 17(12):3392-8

The possibility that the heightened cardiovascular risk associated with the menopause, which is said to be ameliorated by soybeans, can be reduced with soy isoflavones was tested in 21 women. Although several were perimenopausal, all have been included. A placebo-controlled crossover trial tested the effects of 80 mg daily of isoflavones (45 mg genistein) over 5- to 10-week periods. Systemic arterial compliance (arterial elasticity), which declined with age in this group, improved 26% (P < .001) compared with placebo. Arterial pressure and plasma lipids were unaffected. The vasodilatory capacity of the microcirculation was measured in nine women; high acetylcholine-mediated dilation in the forearm vasculature was similar with active and placebo treatments. LDL oxidizability measured in vitro was unchanged. Thus, one important measure of arterial health, systemic arterial compliance, was significantly improved in perimenopausal and menopausal women taking soy isoflavones to about the same extent as is achieved with conventional hormone replacement therapy.



Modulation of age-related hyperparathyroidism and senile bone loss in Fischer rats by soy protein and food restriction

Kalu DN Masoro EJ Yu BP Hardin RR Hollis BW. Endocrinology (1988 May) 122(5):1847-54

Studies were carried out to explore the influence of soy protein and food restriction on age-related changes in serum PTH and bone. Three groups of male Fischer 344 rats were studied from 6 weeks of age. Group A rats were fed ad libitum diet A, which has casein as the protein source. Group B rats were fed diet B (with casein as protein source) at 60% of the mean ad libitum food intake. Group C rats were fed ad libitum diet C, which has soy protein as the protein source. Serum PTH, measured with an intact N- terminal-specific RIA, and immunoreactive calcitonin increased progressively with aging. The increase was markedly suppressed by food restriction, and in the case of PTH by the soy protein diet as well. Serum creatinine started to increase after 18 months of age, and both dietary regimens of groups 2 and 3 retarded the increase. Aging was associated with a fall in serum 25-hydroxyvitamin D, and loss of bone occurred during the terminal part of life in the ad libitum-fed animals. These were prevented by food restriction, while the soy protein diet delayed the onset of bone loss.

We conclude from these findings and other data from this study that in the male F344 rats 1) an age-related increase in serum PTH precedes an age-related increase in serum creatinine concentration; 2) an age-related decline in renal function probably contributes to age-related hyperparathyroidism, which, in turn, contributes to senile bone loss; 3) food restriction inhibits age-related hyperparathyroidism and senile bone loss; and 4) on the basis of the data from rats fed a soy protein-containing diet, a decline in renal function and progressive hyper parathyroidism are not inevitable consequences of aging in the ad libitum fed rats.



Dietary Soy Protein

Forsythe WA 3rd J Nutr (1995 Mar) 125(3 Suppl):619S-623S

The effects of dietary protein on plasma cholesterol concentrations are well documented: animal proteins (casein) are hypercholesterolemic compared with plant proteins (soy protein). Although this effect of protein source on plasma cholesterol has been shown in many species, the mechanism is not completely understood. This paper reviews the relationship between dietary protein source and plasma thyroxine concentration. The basic premise is that feeding soy protein lowers plasma cholesterol concentration by causing an increase in plasma thyroxine concentrations. The metabolic changes involving cholesterol that occur when soy protein is fed are discussed. These changes are consistent with changes induced by elevating thyroxine. Data are presented from animal studies showing that feeding soy protein to laboratory animals consistently elevates plasma thyroxine concentrations. Furthermore, this elevation in plasma thyroxine concentrations precedes the change in plasma cholesterol concentrations: a necessary requirement for hypothesizing a causative effect. Possible mechanisms as to how a dietary protein source affects plasma thyroxine are also presented.



Soy protein, thyroid regulation and cholesterol metabolism

Journal of Nutrition (USA), 1995, 125/3 SUPPL.

The effects of dietary protein on plasma cholesterol concentrations are well documented: animal proteins (casein) are hypercholesterolemic compared with plant proteins (soy protein). Although this effect of protein source on plasma cholesterol has been shown in many species, the mechanism is not completely understood. This paper reviews the relationship between dietary protein source and plasma thyroxine concentration. The basic premise is that feeding soy protein lowers plasma cholesterol concentration by causing an increase in plasma thyroxine concentrations. The metabolic changes involving cholesterol that occur when soy protein is fed are discussed. These changes are consistent with changes induced by elevating thyroxine. Data are presented from animal studies showing that feeding soy protein to laboratory animals consistently elevates plasma thyroxine concentrations. Furthermore, this elevation in plasma thyroxine concentrations precedes the change in plasma cholesterol concentrations: a necessary requirement for hypothesizing a causative effect. Possible mechanisms as to how a dietary protein source affects plasma thyroxine are also presented.



Overview of proposed mechanisms for the hypocholesterolemic effect of soy

Journal of Nutrition (USA), 1995, 125/3 SUPPL.

A large body of literature indicates that protein from soybeans reduces blood cholesterol concentrations in experimental animals as well as in humans. The mechanism and component of soy responsible has not been established fully. Some suggest that when soy protein is fed, cholesterol absorption and/or bile acid reabsorption is impaired. This is observed in some animal species, such as rabbits and rats, but not in humans nor when amino acids replace intact soy protein. Others propose that changes in endocrine status, such as alteration in insulin:glucagon ratio and thyroid hormone concentrations, are responsible. The metabolic changes that have been observed on soy protein feeding in a variety of animal models, and in some cases humans, include increased cholesterol synthesis, increased bile acid synthesis (or fecal bile acid excretion), increased apolipoprotein B or E receptor activity and decreased hepatic lipoprotein secretion and cholesterol content, which are associated with an increased clearance of cholesterol from the blood. One hypothesis suggests amino acid composition or proportionality of soy causes changes in cholesterol metabolism (possibly via the endocrine system). Others have proposed that nonprotein components (such as saponins, fiber, phytic acid, minerals and the isoflavones) associated with soy protein affect cholesterol metabolism either directly or indirectly.



Endocrinological response to soy protein and fiber in mildly hypercholesterolemic men

NUTR. RES. (USA), 1993, 13/8 (873-884)

Soy protein and soy fiber may affect hormones involved in cholesterol metabolism. Therefore, plasma insulin, total thyroxine (T4), free thyroxine index (FTI), triiodothyronine (T3), and thyroid stimulating hormone (TSH) were measured in 17 hypercholesterolemic men consuming baked products containing 50 g/d of protein and 20 g/d of fiber from either soy flour (SF), soy protein isolate (ISP)/soy fiber (ISP/SCF), ISP/cellulose (ISP/Cell), or nonfat dry milk/cellulose (NFDM/Cell). A latin square design was used and included all four dietary treatments, each lasting four weeks. Hormones were analyzed at the end of each experimental period and after an initial baseline period of 10 days. Although the mean values of T4 showed an increase in all treatments relative to baseline, significant differences (p&lt0.05) occurred only between the ISP groups and baseline. A similar pattern was observed with FTI (p&lt0.01). Mean insulin concentrations significantly increased (p&lt0.05) when subjects were fed SF compared to the ISP/SCF treatment. No effects were seen with either T3 or TSH. Results are consistent with the findings of animal studies, as well as human studies investigating T3/T4 influences on lipid metabolism, and suggest that the mechanism for the hypocholesterolemic effect of soy protein is via a T4-mediation.



Response of hormones modulating plasma cholesterol to dietary casein or soy protein in minipigs

J. NUTR. (USA), 1990, 120/11 (1387-1392)

To elucidate the mechanism mediating the effect of dietary casein or soy protein on serum cholesterol concentrations we followed the endocrine response to the intake of these dietary proteins. The hormones analyzed were those known to modulate serum cholesterol concentration. A 7-wk crossover nutrition study was performed with six adult Gottingen minipigs consuming semisynthetic diets based on either 20 wt% casein or soy isolate. At d 42 and 49, concentrations of six hormones were determined in 22 blood samples taken over the whole day. There were no significant differences in insulin, glucagon, the insulin/glucagon ratio, hydrocortisone or triiodothyronine among dietary groups. In the late postprandial phase (5 h after the meal and later) there were significantly higher growth hormone concentrations in soy-fed animals. At all times of the day, total and free thyroxine concentrations were higher after soy feeding than after casein feeding. On average, total and free thyroxine concentrations were 34 and 26% higher with soy protein feeding than with casein feeding. Our data agree with other reports of protein-dependent changes of thyroid hormones and may explain why different dietary proteins have different effects on serum cholesterol levels in sensitive species.



Dietary protein effects on cholesterol and lipoprotein concentrations: A review

J. AM. COLL. NUTR. (USA), 1986, 5/6 (533-549)

Different dietary proteins exert different effects on plasma cholesterol concentrations. Animal studies have shown that animal proteins, most notably casein, increase plasma total cholesterol concentrations compared with vegetable proteins, such as soy. Soy protein has been shown to be hypocholesterolemic in rats, swine, primates, and rabbits. Epidemiologic studies have disclosed that vegetarians have lower mean plasma cholesterol cocnentrations than populations consuming diets of mixed proteins, but it is unclear whether this effect results specifically from the animal or vegetable nature of the protein. In human clinical experiments, substituting soy protein for mixed protein reduces plasma total cholesterol concentration in hypercholesterolemic subjects, but it causes only a small, nonsignificant change in persons with normal plasma cholesterol concentrations. The mechanism responsible for the effects of different proteins on plasma cholesterol concentrations has not been established. One hypothesis suggests that animal proteins, which have a greater content of phosphorylated amino acids than vegetable proteins, interfere with bile acid reabsorption. Another hypothesis suggests that the amino acid content of the protein affects cholesterol absorption, tissue storage, synthesis, and excretion. The dietary protein may also alter cholesterol metabolism by affecting plasma hormone concentrations, either postprandially or over weeks to months. Among the hormones thought to be affected by dietary protein source are insulin, and thyroid hormones. Gastrointestinal hormones, such as gastrointestinal inhibitory polypeptide, may also be affected by dietary protein.



Comparison of dietary casein or soy protein effects on plasma lipids and hormone concentrations in the gerbil (Meriones unguiculatus)

J. NUTR. (USA), 1986, 116/7 (1165-1171)

The effects of dietary animal protein (casein) or soy protein (soy isolate) on plasma lipids and hormones were investigated in the gerbil. Diets, fed to male gerbils (initial weight, 60 g) for 4 wk, contained either 18% casein or soy isolate as the protein source. The dietary fat sources were lard (16%) and safflower oil (1%). The cholesterol content of the diet was 0.1%. Plasma total cholesterol concentrations were lower in gerbils fed the soy protein diet (159 mg/dl) than in the gerbils fed the casein diet (190 mg/dl). Absolute HDL-cholesterol concentrations were unaffected by the protein source, but LDL-cholesterol concentrations were lower in the soy-fed gerbils. Thus, the ratio of LDL to HDL cholesterol was lower in the soy-fed gerbils (0.42) compared with the casein-fed gerbils (0.70). Plasma insulin levels were higher in the soy-fed gerbils as were plasma thyroxine and thyroid-stimulating hormone levels. The results indicate that the gerbils can be used to study dietary effects on cholesterol parameters. These data also suggest that changes in plasma thyroxine levels may in part account for the hypocholesterolemic effect of soy protein.



Hypolipidemic effect of casein vs. soy protein in the hyperlipidemic hypothyroid chick model

NUTR. REP. INT. (USA), 1980, 21/4 (497-503)

White Leghorn cockerels were made hypothyroid by propylthiouracil (PTU) administration for one week to induce hyperlipidemia. The hypolipidemic effect of soy and casein protein was determined when the dietary protein level was either 40 or 62%. All chicks administered PTU became hypothyroid as judged by thyroid and liver enlargement. Both soy and casein at each level of administration had a significant hypocholesterolemic and hypotriglyceridemic effect. Whereas soy significantly decresed hepatic triglycerides, casein had no effect. Hypothyroidism decreased both hepatic and biliary cholesterol concentrations. Bile acids concentration seems to decrease only in hypothyroid chicks given PTU in mash. We feel that soy might be a better protein supplement than casein for its hypolipidemic effect because it also decreases liver triglycerides.



An extract of soy flour influences serum cholesterol and thyroid hormones in rats and hamsters

Journal of Nutrition (USA), 1996, 126/12 (3046-3053)

The effects of an ethanol-acetone extract from soy flour on serum lipids and thyroid hormones were studied in rats and hamsters. In Study 1, male Sprague-Dawley rats were fed diets containing protein from ethanol- acetone extracted isolated soy protein (ISP-), nonextracted ISP (ISP), casein (casein-), or casein to which 0.36 mg ethanol-acetone extract/g protein was added (casein+). Rats fed either ISP-containing diet had lower serum total cholesterol concentrations compared with those fed either casein diet (P < 0.05). Lower serum LDL-cholesterol concentrations were present in rats fed either ISP-containing diet and in those fed casein+ compared with those fed casein- (P < 0.05). Adding the extract to casein (casein+) produced higher serum thyroxine concentration and free thyroxine indices compared with all other groups (P < 0.05). In Study 2, male Golden Syrian hamsters were fed experimental diets containing protein from ISP, ISP with added ethanol-acetone extract (0.36 mg extract/g protein; ISP+), casein-, casein+ (0.36 mg extract/g protein), or casein with twice the level of extract (0.72 mg/g protein; casein++). Lower serum total cholesterol and LDL (LDL + VLDL + IDL) cholesterol concentrations were observed in hamsters fed ISP, ISP+ or casein+ compared with those fed casein (P < 0.05). Addition of the extract at higher levels to casein (casein++) did not lower serum lipids relative to those fed casein-. Serum thyroxine concentration and the free thyroxine index were greater in both ISP groups as well as in hamsters fed casein++ compared with those fed casein or casein+ (P < 0.05). In conclusion, both studies show that protein from soybeans decreases serum total and LDL cholesterol while the effects on thyroxine are different in rats and hamsters. It is also apparent that the ethanol-acetone extract of soy flour produces changes in serum cholesterol, particularly in the LDL fraction in both species.



Soy protein concentrate and isolated soy protein similarly lower blood serum cholesterol but differently affect thyroid hormones in hamsters

Journal of Nutrition (USA), 1996, 126/8 (2007-2011)

There is a wide variation in the hypocholesterolemic response to ingestion of soy protein in humans. One possible explanation is that the different soy protein preparations used contain different spectra of biologically active components. This could affect a number of indices including thyroid hormone status. An increased level of thyroxine has been proposed as an underlying mechanism of the hypocholesterolemic effect of soy protein. The objective of this study was to determine if serum cholesterol and thyroid hormone concentrations differed because of feeding soy protein from different sources. Twenty-nine male weanling golden Syrian hamsters were fed rations containing 25 g/100 g protein from either isolated soy protein (ISP), soy protein concentrate (SPC) or casein for 35 d. Serum total cholesterol concentrations were lower in hamsters fed ISP and SPC compared with those fed casein (P < 0.05). No differences in cholesterol concentrations were observed in lipoprotein fractions. Serum thyroxine and free thyroxine were greater only in hamsters fed ISP than in those fed casein (P < 0.05), whereas triiodothyronine concentrations were higher in casein-fed than in SPC-fed hamsters (P < 0.05). Results indicate that protein from ISP and SPC are both effective in lowering blood cholesterol concentrations, whereas only ISP increases thyroxine concentrations. Therefore, it appears unlikely that modulation of thyroid hormone status is responsible for the cholesterol-lowering effect of soy protein.



Soy protein, thyroid regulation and cholesterol metabolism

Journal of Nutrition (USA), 1995, 125/3 SUPPL. (619S-623S)

The effects of dietary protein on plasma cholesterol concentrations are well documented: animal proteins (casein) are hypercholesterolemic compared with plant proteins (soy protein). Although this effect of protein source on plasma cholesterol has been shown in many species, the mechanism is not completely understood. This paper reviews the relationship between dietary protein source and plasma thyroxine concentration. The basic premise is that feeding soy protein lowers plasma cholesterol concentration by causing an increase in plasma thyroxine concentrations. The metabolic changes involving cholesterol that occur when soy protein is fed are discussed. These changes are consistent with changes induced by elevating thyroxine. Data are presented from animal studies showing that feeding soy protein to laboratory animals consistently elevates plasma thyroxine concentrations. Furthermore, this elevation in plasma thyroxine concentrations precedes the change in plasma cholesterol concentrations: a necessary requirement for hypothesizing a causative effect. Possible mechanisms as to how a dietary protein source affects plasma thyroxine are also presented.



Soy and rye diets inhibit the development of Dunning R3327 prostatic adenocarcinoma in rats

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

Two experiments were conducted to investigate the effect of soy and rye on the development of Dunning R3327 prostatic adenocarcinoma in rats.



Effects of soya consumption for one month on steroid hormones in premenopausal women: Implications for breast cancer risk reduction

Cancer Epidemiology Biomarkers and Prevention (USA), 1996, 5/1 (63-70)

Soybean consumption is associated with reduced rates of breast, prostate, and colon cancer, which is possibly related to the presence of isoflavones that are weakly estrogenic and anticarcinogenic. We examined the effects of soya consumption on circulating steroid hormones in six healthy females 22- 29 years of age. Starting within 6 days after the onset of menses, the subjects ingested a 12-oz portion of soymilk with each of three meals daily for 1 month on a metabolic unit. Daily isoflavone intakes were similar100 mg of daidzein (mostly as daidzin) and similar100 mg of genistein (mostly as genistin). Serum 17beta-estradiol levels on cycle days 5-7, 12-14, and 20-22 decreased by 31% (P = 0.09), 81% (P = 0.03), and 49% (P = 0.02), respectively, during soya feeding. Decreases persisted for two to three menstrual cycles after withdrawal from soya feeding. The luteal phase progesterone levels decreased by 35% during soya feeding (P = 0.002). Dehydroepiandrosterone sulfate levels decreased progressively during soya feeding by 14-30% (P = 0.03). Menstrual cycle length was 28.3 plus or minus 1.9 days before soymilk feeding, increased to 31.8 plus or minus 5.1 days during the month of soymilk feeding (P = 0.06), remained increased at 32.7 plus or minus 8.4 days (P = 0. 11) at one cycle after termination of soymilk feeding, and returned to pre-soya diet levels five to six cycles later. These results suggest that consumption of soya diets containing phytoestrogens may reduce circulating ovarian steroids and adrenal androgens and increase menstrual cycle length. Such effects may account at least in part for the decreased risk of breast cancer that has been associated with legume consumption.



Influence of isoflavones in soy protein isolates on development of induced prostate-related cancers in L-W rats

Nutrition and Cancer (USA), 1997, 28/1 (41-45)

Lobund-Wistar (L-W) rats are inherently susceptible to spontaneous and induced metastasizing adenocarcinomas in the prostate-seminal vesicle (P-SV) complex. L-W rats were fed soy protein isolates containing high isoflavones (genistein and daidzein) or low isoflavones to determine their effects on development of induced P-SV tumors in two stages of the tumorigenic process. In rats fed the high-isoflavone-supplemented soy diet before initiation by methylnitrosourea (MNU), the incidence of induced prostate-related cancer was reduced and the disease-free period was prolonged by 27% compared with rats fed the same diet but low in isoflavones. Rats fed the same diets, started after MNU, manifested suggestive but less consistent results than those noted above. The incidence rates were of marginal significance, suggesting that the high intensity of the active induced disease may not represent the character of the slower-growing spontaneous (natural) disease. The delay of disease onset is of clinical significance.



A simplified method to quantify isoflavones in commercial soybean diets and human urine after legume consumption

Cancer Epidemiology Biomarkers and Prevention (USA), 1995, 4/5 (497-503)

Reliable and economical quantification of micronutrients in diets and humans is a critical component of successful epidemiological studies to establish relationships between dietary constituents and chronic disease. Legumes are one of the major dietary components consumed by populations worldwide. Consumption of legumes is thought to play a major role in lowering breast and prostate cancer risk. In this study, a simplified method that uses solid-phase extraction and gas chromatography was developed to measure isoflavones at levels down to 10 microg/5 ml. With the use of this method, 12.5 g miso (a soybean paste), 12 ounces Isomil, and 12 ounces soymilk had daidzin/daidzein levels of 2, 5, and 12.4 mg, respectively, and genistin/genistein levels of 3, 6.5, and 13.7 mg, respectively. In these products, most of the isoflavones were present as glucosides. With the same method, urinary levels of isoflavones in six 15-17-year-old subjects were determined after soymilk ingestion. Each subject was placed on unrestricted nonsoya diets, and three 12-ounce portions of soymilk were given at 12-h intervals. Males excreted 15.02 plus or minus 2.74 (SD) mg of daidzein glucuronides/sulfates (mean recovery, 40.4 plus or minus 7.4% (SD)) by 24 h after the third soymilk ingestion, whereas females excreted 25.56 plus or minus 5.10 mg (68.7 plus or minus 13.7%) of daidzein conjugates, which was more than males (P = 0.02). Males and females excreted 7.73 plus or minus 1.95 mg and 9.11 plus or minus 0.84 mg of genistein glucuronides/sulfates (20% recovery of genistin intake), respectively, in the urine. Most of the isoflavones were excreted within 24 h after ingestion. The relative urinary levels of daidzein to genistein excreted were significantly (P < 0.05) higher in females than males after the third ingestion. The observed sex difference requires more study since two of the females are siblings. Thus, the method described can be used to measure isoflavones in soya products and urinary excretion after soya ingestion.



Rapid HPLC analysis of dietary phytoestrogens from legumes and from human urine

PROC. SOC. EXP. BIOL. MED. (USA), 1995, 208/1 (18-26)

Due to growing evidence suggesting that phytoestrogens might protect against various cancers, particularly against breast and prostate cancer, it is important to measure the exposure of populations to these compounds by determining levels in food and in human tissue or body fluids to assess the possible cancer protective properties of these agents. Therefore, we developed a simple and fast procedure to extract and simultaneously hydrolyze phytoestrogens and their conjugates from food items, and present a fast and selective high-performance liquid chromatography (HPLC) method for precise determinations of the most common dietary phytoestrogens genistein, biochanin-A, daidzein, formononetin, and coumestrol using flavone as internal standard. For the first time HPLC was applied to measure these phytoestrogens and their most abundant metabolites equol and O-desmethyl-angotensin from human urine. The proposed methodology has been evaluated for losses due to thermal degradation during extraction and hydrolysis and due to sample handling during the entire work-up including solid phase extraction, and values are given for inter- and intra-assay variability. We present isoflavonoid levels of most common peas and beans used in 'western' and 'eastern' diets and compare isoflavonoid and coumestrol levels of raw, canned, and cooked foods which can be used in future epidemiological studies. We also determined human urinary levels with our methodology comparing values before and after soybean intake.



Soy intake and cancer risk: A review of the in vitro and in vivo data

NUTR. CANCER (USA), 1994, 21/2 (113-131)

International variations in cancer rates have been attributed, at least in part, to differences in dietary intake. Recently, it has been suggested that consumption of soyfoods may contribute to the relatively low rates of breast, colon, and prostate cancers in countries such as China and Japan. Soybeans contain a number of anticarcinogens, and a recent National Cancer Institute workshop recommended that the role of soyfoods in cancer prevention be investigated. In this review, the hypothesis that soy intake reduces cancer risk is considered by examining relevant in vitro, animal, and epidemiological data. Soybeans are a unique dietary source of the isoflavone genistein, which possesses weak estrogenic activity and has been shown to act in animal models as an antiestrogen. Genistein is also a specific inhibitor of protein tyrosine kinases; it also inhibits DNA topoisomerases and other critical enzymes involved in signal transduction. In vitro, genistein suppresses the growth of a wide range of cancer cells, with IC50 values ranging from 5 to 40 microM (1-10 microg/ml). Of the 26 animal studies of experimental carcinogenesis in which diets containing soy or soybean isoflavones were employed, 17 (65%) reported protective effects. No studies reported soy intake increased tumor development. The epidemiological data are also inconsistent, although consumption of nonfermented soy products, such as soymilk and tofu, tended to be either protective or not associated with cancer risk; however, no consistent pattern was evident with the fermented soy products, such as miso. Protective effects were observed for both hormone- and nonhormone-related cancers. While a definitive statement that soy reduces cancer risk cannot be made at this time, there is sufficient evidence of a protective effect to warrant continued investigation.



Phytoestrogens are partial estrogen agonists in the adult male mouse

Environmental Health Perspectives (USA), 1995, 103/SUPPL. 7

The intake, as well as serum and urinary concentrations, of phytoestrogens is high in countries where incidence of prostate cancer is low, suggesting a chemopreventive role for phytoestrogens. Their significance could be explained by the ability to antagonize the action of more potent endogenous estrogens in initiation or promotion of tumor formation. We have studied estrogenicity and antiestrogenicity of dietary soy and two phyloestrogens, coumestrol and daidzein, in our neoDES mouse model for the study of prostatic neoplasia. Soy was chosen because it is rich in phytoestrogens, is widely used in Oriental diets, and has antiestrogenic and anticarcinogenic properties in the neoDES mouse when given from fertilization onward. In short-term tests with adult animals, no evidence for estrogenicity or antiestrogenicity (capability to antagonize the action of 17beta-estradiol) of soy was found when development of epithelial metaplasia and expression of c-fos protooncogene in prostate were used as end points of estrogen action. Estrogenic activity of coumestrol and daidzein on c-fos expression was subtle. Coumestrol, either given alone or in combination with 17beta-estradiol, had no effect on development of epithelial metaplasia. These marginal or missing effects in adult males could be interpreted by assuming that the neonatal period is more critical for estrogenic or antiestrogenic action of soy and phytoestrogens. Once initiated, estrogen-related lesions would develop spontaneously. Alternatively, the chemopreventive action of soy is not due to antiestrogenicity of soy-derived phytoestrogens.



Pathogenesis and treatment of liver fibrosis in alcoholics: 1996 update.

Lieber CS
Section of Liver Disease, Bronx VA Medical Center, Mount Sinai School of Medicine, New York, N.Y., USA.
Dig Dis (SWITZERLAND) Jan-Apr 1997, 15 (1-2) p42-66

Fibrosis is a common end stage for most chronic liver diseases. It results from an imbalance between collagen production and degradation. One promising approach for prevention and treatment is the stimulation of collagenolytic processes. In nonhuman primates it was found that polyenylphosphatidylcholine (PPC), extracted from soybeans, protects against alcohol-induced fibrosis and cirrhosis and prevents the associated hepatic phosphatidylcholine (PC) depletion by increasing 18:2-containing PC species; it also attenuates the transformation of lipocytes into collagen-producing transitional cells. Furthermore, it increases collagen breakdown, as shown in cultured lipocytes enriched with pure dilinoleoyl PC (18:2-18:2 PC), the main PC species present in the extract, which may be the active ingredient. Since PC appears to promote the breakdown of collagen, there is reasonable hope that this treatment may affect not only the progression of the disease, but may also reverse preexisting fibrosis, as demonstrated for CCl4-induced cirrhosis in the rat. Therefore, PPC may be useful for the management of fibrosis of alcoholic and nonalcoholic etiologies as well. S-Adenosylmethionine opposes CCl4-induced fibrosis and can affect some of the consequences of the ethanol-induced oxidative stress in experimental animals and in man. Anti-inflammatory medications (corticosteroids, colchicine) are also being used and agents that interfere with collagen synthesis, such as inhibitors of prolyl-4-hydroxylase and antioxidants, are being tested. (175 Refs.)



Dietary soybean protein prevents bone loss in an ovariectomized rat model of osteoporosis.

The purpose of this study was to examine whether soybean protein isolate prevents bone loss induced by ovarian hormone deficiency. Thirty-two 95-d- old Sprague-Dawley rats were randomly assigned to four treatment groups (sham-operated (sham); ovariectomized (ovx); ovx + soybean; ovx + 17beta- estradiol (E2)) and killed after 30 d. Rats in the sham, ovx and ovx + 17beta- estradiol groups were fed a casein-based diet, and the soybean group was fed soybean protein isolate instead of casein; the diets were otherwise comparable. Rats in the ovx group had significantly lower densities of the right femur (P < 0.001) and the fourth lumbar vertebra (P < 0.05) than rats in the sham group. These lower bone densities were not observed in animals receiving 17beta-estradiol or fed soybean. The ovx group also had significantly (P < 0.01) greater serum concentrations of 1,25-dihydroxycholecalciferol than the other three groups. Our findings suggest that dietary soybean protein is effective in preventing bone loss due to ovarian hormone deficiency. Because serum activities of both alkaline phosphatase and tartrate-resistant acid phosphatase were significantly greater in the ovx group and in the ovx + soybean group but not in the group receiving 17beta-estradiol, compared with sham animals, this confirms that ovariectomy enhances and 17beta-estradiol suppresses the rate of bone turnover. Despite the higher rate of bone turnover in the soybean-fed animals, the vertebral and femoral bone densities of these rats were significantly greater than those of rats in the ovx group, suggesting that formation exceeded resorption. Further studies are needed to clarify whether this protective effect on bone is due to the protein itself or to the presence of isoflavones in soybean protein.



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.

Sakono M; Fukuyama T; Ni WH; Nagao K; Ju HR; Sato M; Sakata N; Iwamoto H; Imaizumi K
Department of Food Science and Technology, Faculty of Agriculture, Kyushu University, Fukuoka, Japan.
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.



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 plus 17 beta-estradiol(E2) (n = 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).



Effects of soya consumption for one month on steroid hormones in premenopausal women: Implications for breast cancer risk reduction

Cancer Epidemiology Biomarkers and Prevention (USA), 1996, 5/1 (63-70)

Soybean consumption is associated with reduced rates of breast, prostate, and colon cancer, which is possibly related to the presence of isoflavones that are weakly estrogenic and anticarcinogenic. We examined the effects of soya consumption on circulating steroid hormones in six healthy females 22- 29 years of age. Starting within 6 days after the onset of menses, the subjects ingested a 12-oz portion of soymilk with each of three meals daily for 1 month on a metabolic unit. Daily isoflavone intakes were similar100 mg of daidzein (mostly as daidzin) and similar100 mg of genistein (mostly as genistin). Serum 17beta-estradiol levels on cycle days 5-7, 12-14, and 20-22 decreased by 31% (P = 0.09), 81% (P = 0.03), and 49% (P = 0.02), respectively, during soya feeding. Decreases persisted for two to three menstrual cycles after withdrawal from soya feeding. The luteal phase progesterone levels decreased by 35% during soya feeding (P = 0.002). Dehydroepiandrosterone sulfate levels decreased progressively during soya feeding by 14-30% (P = 0.03). Menstrual cycle length was 28.3 plus or minus 1.9 days before soymilk feeding, increased to 31.8 plus or minus 5.1 days during the month of soymilk feeding (P = 0.06), remained increased at 32.7 plus or minus 8.4 days (P = 0. 11) at one cycle after termination of soymilk feeding, and returned to pre-soya diet levels five to six cycles later. These results suggest that consumption of soya diets containing phytoestrogens may reduce circulating ovarian steroids and adrenal androgens and increase menstrual cycle length. Such effects may account at least in part for the decreased risk of breast cancer that has been associated with legume consumption.



Epidemiology of soy and cancer: Perspectives and directions

Journal of Nutrition (USA), 1995, 125/3 SUPPL. (709S-712S)

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.



Effects of hormonal therapies and dietary soy phytoestrogens on vaginal cytology in surgically postmenopausal macaques

Fertility and Sterility (USA), 1996, 65/5 (1031-1035)

Objective: To evaluate the effects of conjugated equine estrogens, medroxyprogesterone acetate (MPA), conjugated equine estrogens combined with MPA, tamoxifen, and soybean estrogens on vaginal cytology in surgically postmenopausal cynomolgus macaques (Macaca fascicularis). Design: Randomized long-term experimental trial. Setting: Cytologic samples were taken from animals in two long-term randomized studies of the effects of hormonal and dietary effects on atherosclerosis. Patients: Surgically postmenopausal cynomolgus macaques. Interventions: Conjugated equine estrogens, MPA, conjugated equine estrogens combined with MPA, tamoxifen, and soybean estrogens were given via the diet, at doses scaled from those given to women. Main Outcome Measure: Vaginal cytologic maturation index. Results: Conjugated equine estrogens elicited a marked maturation effect, which was antagonized partially by the addition of MPA. Tamoxifen produced a lesser estrogenic response. The cytologic pattern in animals given soybean estrogens or MPA alone did not differ from that of controls. Conclusion: Soybean estrogens at the doses given do not exert an estrogenic effect on the vagina of macaques. Conjugated equine estrogens are potent inducers of vaginal keratinization in this model; tamoxifen has a lesser effect. Medroxyprogesterone acetate partially antagonizes the effects of conjugated equine estrogens, and has no effect when given alone. The results support the possibility that soybean estrogens may be a 'tissue-selective' estrogen with minimal effects on the reproductive tract.



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.



Dietary flour supplementation decreases post-menopausal hot flushes: Effect of soy and wheat

Maturitas (Ireland), 1995, 21/3 (189-195)

Plants contain compounds with oestrogen-like action called phytoestrogens. Soy contains daidzin, a potent phytoestrogen, and wheat flour contains less potent enterolactones. We aimed to show in 58 postmenopausal women (age 54, range 30-70 years) with at least 14 hot flushes per week, that their daily diet supplemented with soy flour (n = 28) could reduce flushes compared with wheat flour (n = 30) over 12 weeks when randomised and double blind. Hot flushes significantly decreased in the soy and wheat flour groups (40% and 25% reduction, respectively < 0.001 for both) with a significant rapid response in the soy flour group in 6 weeks (P < 0.001) that continued. Menopausal symptom score decreased significantly in both groups (P < 0.05). Urinary daidzein excretion confirmed compliance. Vaginal cell maturation, plasma lipids and urinary calcium remained unchanged. Serum FSH decreased and urinary hydroxyproline increased in the wheat flour group.



Soy and experimental cancer: Animal studies

Journal of Nutrition (USA), 1995, 125/3 SUPPL.

Studies are reviewed that report consumption of soy protein diets inhibits the growth of various tumors in rats. The inhibitory effect has been attributed to the phytoestrogens (genistein and diadzein) or protein kinase inhibitor in soy protein products. Recent studies indicate that additional factors in soy protein products may also contribute to the inhibition of tumorigenesis, namely the deficiency of the essential amino acid methionine. Metastatic growth to the lungs of a primary rhabdomyosarcoma tumor was inhibited by feeding a soy protein diet. The effect was reversed by methionine fortification of the diet. Carcinogen-induced mammary tumor development was inhibited during the promotional phase in rats fed soy protein isolate diet and reversed with a methionine-supplemented diet. Additional studies demonstrated that after excision of the primary mammary tumor, growth of additional tumors was inhibited when the diet was changed from casein to soy protein isolate. Histopathologic evaluation of the mammary tumors revealed more benign fibroadenomas and lower-grade adenocarcinomas in the soy protein group. Before carcinogen administration (at 7 weeks of age), ornithine decarboxylase activity and polyamine concentrations in the rat mammary epithelium were significantly lower in the soy protein group. These data suggest an inhibitory effect on mammary epithelial growth in the soy-protein-fed group.



Soy protein concentrate and isolated soy protein similarly lower blood serum cholesterol but differently affect thyroid hormones in hamsters.

J Nutr (UNITED STATES) Aug 1996, 126 (8) p2007-11

There is a wide variation in the hypocholesterolemic response to ingestion of soy protein in humans. One possible explanation is that the different soy protein preparations used contain different spectra of biologically active components. This could affect a number of indices including thyroid hormone status. An increased level of thyroxine has been proposed as an underlying mechanism of the hypocholesterolemic effect of soy protein. The objective of this study was to determine if serum cholesterol and thyroid hormone concentrations differed because of feeding soy protein from different sources. Twenty-nine male weanling golden Syrian hamsters were fed rations containing 25 g/100 g protein from either isolated soy protein (ISP), soy protein concentrate (SPC) or casein for 35 d. Serum total cholesterol concentrations were lower in hamsters fed ISP and SPC compared with those fed casein (P < 0.05). No differences in cholesterol concentrations were observed in lipoprotein fractions. Serum thyroxine and free thyroxine were greater only in hamsters fed ISP than in those fed casein (P < 0.05), whereas triiodothyronine concentrations were higher in casein-fed than in SPC-fed hamsters (P < 0.05). Results indicate that protein from ISP and SPC are both effective in lowering blood cholesterol concentrations, whereas only ISP increases thyroxine concentrations. Therefore, it appears unlikely that modulation of thyroid hormone status is responsible for the cholesterol-lowering effect of soy protein.



Cholesterol-lowering effect of soyabean lecithin in normolipidaemic rats by stimulation of biliary lipid secretion.

Br J Nutr (ENGLAND) Mar 1996, 75 (3) p471-8

The purpose of the present study was to assess the role of the liver in the plasma-cholesterol-lowering effect of soyabean lecithin. Normolipidaemic rats were fed on lecithin-enriched or control diets with the same amount of protein. The lecithin diets contained 200 g/kg high-fat commercial semi-purified soyabean lecithin (230 g/kg total lipids as soyabean phosphatidylcholine) or 200 g/kg high-fat purified soyabean lecithin (930 g/kg total lipids as soyabean phosphatidylcholine). The control diets were a lowfat diet (40 g fat/kg) and a high-fat triacylglycerol-rich diet (200 g fat/kg). The high-fat diets were isoenergetic. The cholesterol-lowering effect of the lecithin-enriched diets was associated with significantly lower levels of plasma total- and HDL-cholesterol and significantly higher levels of bile phosphatidylcholine (PC), bile salts and cholesterol. These findings suggest that the liver plays a major role in the reduction of plasma cholesterol, the increased biliary lipid being provided by both HDL and the hepatic microsomal pools of PC and cholesterol.



Biological effects of isoflavones in young women: Importance of the chemical composition of soyabean products

British Journal of Nutrition (United Kingdom), 1995, 74/4 (587-601)

To examine the hormonal effects of isoflavones, of which soyabean is a rich source, fifteen healthy non-vegetarian premenopausal women were studied over 9 months. They lived in a metabolic suite for between 4 and 6 months where their diet and activity levels were kept constant and their hormonal status was measured over two or three menstrual cycles. During one (control) menstrual cycle a normal but constant diet containing no soyabean products was fed. Then, over a second complete cycle six subjects consumed a similar diet into which 60 g textured vegetable protein (TVP)/d, containing 45 mg conjugated isoflavones, had been incorporated. Three participants had 50 g miso (a fermented soyabean paste), containing 25 mg unconjugated isoflavones, added daily to their diet over a menstrual cycle, and six others consumed 28 g TVP/d, containing 23 mg conjugated isoflavones. Five participants completed a third diet period where they were randomly assigned to consume either the control diet over a cycle, or a similar diet incorporating 60 g of a soyabean product which had had the isoflavones chemically extracted (Arcon F). Follicular phase length was significantly (P < 0.01) increased and peak progesterone concentrations were delayed with 60 g TVP but no effects were observed with Arcon F. The increase in menstrual cycle length did not reach statistical significance in the three subjects who ate 50 g miso/d, but peak progesterone levels were significantly (P < 0.05) delayed. Mid-cycle peaks of luteinizing hormone (LH) and follicle stimulating hormone CFSH) were suppressed with 45 mg conjugated isoflavones as 60 g TVP (P < 0.05 and P < 0.01 respectively). No other changes in sex-steroid hormone levels were observed on any of the other diets. A significant reduction in total cholesterol was found with 45 mg conjugated isoflavones (P < 0.05), but not with 23 mg conjugated isoflavone-free Arcon F. There was no effect of menstrual cycle phase on transit time.



Overview of proposed mechanisms for the hypocholesterolemic effect of soy

Journal of Nutrition (USA), 1995, 125/3 SUPPL. (606S-611S)

A large body of literature indicates that protein from soybeans reduces blood cholesterol concentrations in experimental animals as well as in humans. The mechanism and component of soy responsible has not been established fully. Some suggest that when soy protein is fed, cholesterol absorption and/or bile acid reabsorption is impaired. This is observed in some animal species, such as rabbits and rats, but not in humans nor when amino acids replace intact soy protein. Others propose that changes in endocrine status, such as alteration in insulin:glucagon ratio and thyroid hormone concentrations, are responsible. The metabolic changes that have been observed on soy protein feeding in a variety of animal models, and in some cases humans, include increased cholesterol synthesis, increased bile acid synthesis (or fecal bile acid excretion), increased apolipoprotein B or E receptor activity and decreased hepatic lipoprotein secretion and cholesterol content, which are associated with an increased clearance of cholesterol from the blood. One hypothesis suggests amino acid composition or proportionality of soy causes changes in cholesterol metabolism (possibly via the endocrine system). Others have proposed that nonprotein components (such as saponins, fiber, phytic acid, minerals and the isoflavones) associated with soy protein affect cholesterol metabolism either directly or indirectly.



Biological effects of a diet of soy protein rich in isoflavones on the menstrual cycle of premenopausal women

AM. J. CLIN. NUTR. (USA), 1994, 60/3 (333-340)

The influence of a diet containing soy protein on the hormonal status and regulation of the menstrual cycle was examined in six premenopausal women with regular ovulatory cycles. Soy protein (60 g containing 45 mg isoflavones) given daily for 1 mo significantly (P < 0.01) increased follicular phase length and/or delayed menstruation. Midcycle surges of luteinizing hormone and follicle-stimulating hormone were significantly suppressed during dietary intervention with soy protein. Plasma estradiol concentrations increased in the follicular phase and cholesterol concentrations decreased 9.6%. Similar responses occur with tamoxifen, an antiestrogen undergoing clinical trial as a prophylactic agent in women at high risk for breast cancer. These effects are presumed to be due to nonsteroidal estrogens of the isoflavone class, which behave as partial estrogen agonists/antagonists. The responses to soy protein are potentially beneficial with respect to risk factors for breast cancer and may in part explain the low incidence of breast cancer and its correlation with a high soy intake in Japanese and Chinese women.