Dietary isoflavones may protect against prostate cancer in Japanese men

We examined associations between nutritional and other lifestyle factors and the prevalence of prostate cancer in a case-control study of Japanese men. Two hundred patients and 200 age-matched controls (+/-5 y) were selected from 3 geographic areas of Japan. BMI, physical activity, occupation, family history of prostate cancer, and medical history were not associated with prostate cancer risk. Isoflavones and their aglycones (genistein and daidzein) were significantly associated with decreased risk. The odds ratio for the highest category (> or = 89.9 mg/d) compared with the lowest category (<30.5 mg/d) of isoflavone intake was 0.42 (95% CI = 0.24-0.72) and the linear trend was significant (P < 0.01). PUFA, (n-6) fatty acids, and magnesium were significantly associated with decreased risk but not after adjustment for isoflavone intake. Isoflavone intake was correlated with the intake of PUFA (r = 0.68, P < 0.001), (n-6) fatty acids (r = 0.69, P < 0.001), and magnesium (r = 0.56, P < 0.001), because soy products contain high levels of these nutrients. On the other hand, isoflavone significantly decreased the risk of prostate cancer regardless of adjustment by PUFA, (n-6) fatty acids or magnesium. In conclusion, our findings indicate that isoflavones might be an effective dietary protective factor against prostate cancer in Japanese men.     

Dietary soy and soy isoflavones have gender-specific effects on plasma lipids and isoflavones in golden Syrian f(1)b hybrid hamsters

The specific components of soy responsible for its beneficial effects on plasma lipids are unknown. Golden Syrian F(1)B Hybrid hamsters (75 male, 74 female) were evaluated for the effect of dietary soy and soy isoflavones on plasma lipids. They were fed the following diets for 16 wk: casein/lactalbumin (C/L), soy protein with isoflavones [Soy(+)], soy protein with isoflavones removed [Soy(-)], Soy(-) plus isoflavone extract (IF), and C/L + IF. At necropsy, plasma total cholesterol, HDL cholesterol (HDLC), LDL + VLDL cholesterol (LDL + VLDLC), isoflavones, and uterine and accessory gland weights were measured. Male hamsters fed the three soy-containing diets had lower LDL + VLDLC concentrations than those fed the two C/L diets (P < 0.01), and those fed Soy(-) + IF did not differ from those fed Soy(+). In females, diet did not affect plasma LDL + VLDLC concentration. Females fed Soy(+) or Soy(-) had higher HDLC (P < 0.05) than those fed C/L. HDLC was not affected by diet in males. Due to higher equol production (P < 0.01), males had greater plasma isoflavone concentrations (P < 0.01) than females. There was a positive association between plasma total isoflavones and LDL + VLDLC (r = 0.65, P < 0.05) in females. These data suggest gender differences in plasma lipid and isoflavone responses to soy- based diets in Syrian F(1)B Hybrid hamsters, which offer an opportunity to explore effects of sex hormones on isoflavone metabolism and the effects of isoflavones on lipid metabolism.     

Dietary soy protein isolate and isoflavones modulate hepatic thyroid hormone receptors in rats

Thyroid hormone receptors (TRs) are regulators of many genes involved in cholesterol and lipid metabolism. The purpose of this study was to examine the effect of soy protein isolate (SPI) and isoflavones on hepatic TRs in rats. In Expt. 1, Sprague-Dawley rats were fed diets containing either casein or alcohol-washed SPI with or without isoflavone supplementation (5-1250 mg/kg diet) for 70, 190, and 310 d. The offspring (F1) were fed the same diets as their parents (F0). In Expt. 2, Sprague-Dawley rats were fed diets containing casein or casein plus isoflavones (50-400 mg/kg diet) for 120 d. The mRNA and protein contents of the hepatic TRs were measured by semiquantitative RT-PCR and Western blot, respectively. TRalpha1, TRalpha2, and TRbeta2 contents were not affected by SPI. However, the content of the 52-kDa TRbeta1 protein, the major isoform present in the liver, was markedly increased by dietary SPI in both sexes of F0 and F1 compared with casein. The supplemental isoflavones had no effect on TRbeta1, whereas the high doses of isoflavones (250 and 1250 mg/kg diet) reduced the hepatic TRalpha1 protein content in F1 male rats on d 28. SPI had no effect on total T3 and T4 levels. However, higher dose of supplemental isoflavones markedly increased T4 level in female rats. Overall, this study demonstrates for the first time that SPI upregulates hepatic TRbeta1 expression, and that isoflavones reduce the hepatic TRalpha1 level in young male rats. The SPI-induced TRbeta1 may play a role in mediating the hypocholesterolemic and lipid-lowering actions of soy protein.     

Lycopene and soy isoflavones in the treatment of prostate cancer

Dietary intake of lycopene and soy has been associated with a lower risk of prostate cancer. In vitro studies with lycopene and genistein, a soy isoflavone, have shown induction of apoptosis and inhibition of cell growth in androgen-sensitive (LNCaP) and androgen-independent (PC3 and VeCaP) prostate cancer cell lines. In a previous Phase II clinical trial in prostate cancer patients, we observed prostate-specific antigen (PSA) stabilization with soy isoflavone intake. In this Phase II clinical trial, we investigated the efficacy of lycopene alone or in combination with soy isoflavones on serum PSA levels in men with prostate cancer. To be eligible for the study, men with prostate cancer had to have rising serum PSA following local therapy or while on hormone therapy. Study population included 71 eligible patients who had 3 successive rising PSA levels or a minimum PSA of 10 ng/ml at 2 successive evaluations prior to starting therapy. Subjects were randomly assigned to receive a tomato extract capsule containing 15 mg of lycopene alone (n = 38) or together with a capsule containing 40 mg of a soy isoflavone mixture (n = 33) twice daily orally for a maximum of 6 mo. One patient on the lycopene arm did not receive therapy due to his inability to ingest the study pill. There was no decline in serum PSA in either group qualifying for a partial or complete response. However, 35 of 37 (95%) evaluable patients in the lycopene group and 22 of 33 (67%) evaluable patients in the lycopene plus soy isoflavone group achieved stable disease described as stabilization in serum PSA level. The data suggest that lycopene and soy isoflavones have activity in prostate cancer patients with PSA relapse disease and may delay progression of both hormone-refractory and hormone-sensitive prostate cancer. However, there may not be an additive effect between the 2 compounds when taken together. Future studies are warranted to further investigate the efficacy of lycopene and soy isoflavones in prostate cancer as well as the mechanism of potential negative interaction between them.     

Dietary soy isoflavones and bone mineral density: results from the study of women's health across the nation

Isoflavones are naturally occurring selective estrogen receptor modulators, with potential bone protective effects. To study the relation between soy isoflavone intake and bone mineral density (BMD), the authors analyzed baseline data from the Study of Women's Health Across the Nation, a US community-based cohort study of women aged 42-52 years. Their 1996-1997 analysis included African-American (n = 497), Caucasian (n = 1,003), Chinese (n = 200), and Japanese (n = 227) participants. Genistein and daidzein intakes were highly correlated (r = 0.98); therefore, analyses were conducted by using genistein. Median intakes of genistein (measured in micrograms/day) by African Americans and Caucasians were too low to pursue relational analyses further. For Chinese and Japanese women, median genistein intakes were 3,511 and 7,151 microg/day, respectively. Ethnic-specific, linear models were used to predict BMD as a function of energy-adjusted tertile of intake, controlled for relevant covariates. For Chinese women, no association between genistein and BMD was found. Premenopausal, but not perimenopausal, Japanese women whose intakes were greater had higher spine and femoral neck BMD. Adjusted mean spinal BMD of those in the highest tertile of intake was 7.7% greater than that of women in the lowest tertile (p = 0.02); femoral neck BMD was 12% greater in the highest versus the lowest tertile (p < 0.0001).     

Dietary oligofructose and inulin protect mice from enteric and systemic pathogens and tumor inducers

Prebiotics induce changes in the population and metabolic characteristics of the gastrointestinal bacteria, modulate enteric and systemic immune functions, and provide laboratory rodents with resistance to carcinogens that promote colorectal cancer. There is less known about protection from other challenges. Therefore, mice of the B6C3F1 strain were fed for 6 wk a control diet with 100 g/kg cellulose or one of two experimental diets with the cellulose replaced entirely by the nondigestible oligosaccharides (NDO) oligofructose and inulin. From each diet, 25 mice were challenged by a promoter of colorectal cancer (1,2-dimethylhydrazine), B16F10 tumor cells, the enteric pathogen Candida albicans (enterically), or were infected systemically with Listeria monocytogenes or Salmonella typhimurium. The incidences of aberrant crypt foci in the distal colon after exposure to dimethylhdrazine for mice fed inulin (53%) and oligofructose (54%) were lower than in control mice (76%; P < 0.05), but the fructans did not reduce the incidence of lung tumors after injection of the B16F10 tumor cells. Mice fed the diets with fructans had 50% lower densities of C. albicans in the small intestine (P < 0.05). A systemic infection with L. monocytogenes caused nearly 30% mortality among control mice, but none of the mice fed inulin died, with survival intermediate for mice fed oligofructose. Mortality was higher for the systemic infection of S. typhimurium (>80% for control mice), but fewer of the mice fed inulin died (60%; P < 0.05), with mice fed oligofructose again intermediate. The mechanistic basis for the increased resistance provided by dietary NDO was not elucidated, but the findings are consistent with enhanced immune functions in response to changes in the composition and metabolic characteristics of the bacteria resident in the gastrointestinal tract.     

Combined effects of soy isoflavone and lecithin on bone loss in ovariectomized mice

BACKGROUND/OBJECTIVESIsoflavones (ISFs) are effective in preventing bone loss, but not effective enough to prevent osteoporosis. Mixtures of soy ISF and lecithin (LCT) were prepared and characterized in an attempt to improve the bone loss.MATERIALS/METHODSThe daidzein (DZ) and genistein (GN) solubility in soy ISF were measured using liquid chromatography-mass spectrometry. The change in the crystalline characteristics of soy ISF in LCT was evaluated using X-ray diffraction analysis. Pharmacokinetic studies were conducted to evaluate and compare ISF bioavailability. Animal studies with ovariectomized (OVX) mice were carried out to estimate the effects on bone loss. The Student''s t-test was used to evaluate statistical significance.RESULTSThe solubility of DZ and GN in LCT was 125.6 and 9.7 mg/L, respectively, which were approximately 25 and 7 times higher, respectively, than those in water. The bioavailability determined by the area under the curve of DZ for the oral administration (400 mg/kg) of soy ISF alone and the soy ISF-LCT mixture was 13.19 and 16.09 µg·h/mL, respectively. The bone mineral density of OVX mice given soy ISF-LCT mixtures at ISF doses of 60 and 100 mg/kg daily was 0.189 ± 0.020 and 0.194 ± 0.010 g/mm³, respectively, whereas that of mice given 100 mg/kg soy ISF was 0.172 ± 0.028 g/mm³. The number of osteoclasts per bone perimeter was reduced by the simultaneous administration of soy ISF and LCT.CONCLUSIONSThe effect of preventing bone loss and osteoclast formation by ingesting soy ISF and LCT at the same time was superior to soy ISF alone as the bioavailability of ISF may have been improved by the emulsification and solvation of LCT. These results suggest the possibility of using the combination of soy ISF and LCT to prevent osteoporosis.     

Dietary soy isoflavones increase insulin secretion and prevent the development of diabetic cataracts in streptozotocin-induced diabetic rats

Soy isoflavone–containing diets have been reported to be beneficial in diabetes. This present study investigated the hypoglycemic effects of isoflavones in streptozotocin (STZ)-induced diabetes. Diabetes was induced in male Sprague-Dawley rats by intraperitoneal injection of 100 mg/kg STZ. Diabetic rats were then randomly divided into 3 groups and received a special diet supplemented with casein (control), low-isoflavone soy (LIS) protein, and high-isoflavone soy protein (HIS) for 8 weeks. Compared with the control or LIS groups, those rats on the HIS diet had significantly increased body weight and serum insulin levels and reduced serum glucose and methylglyoxal levels. Serum glutathione levels were also increased in rats given the HIS diet compared with those in the control or LIS (P < .01). Serum high-density lipoprotein cholesterol level was significantly higher in HIS-fed rats than that of the control or LIS rats (P < .05). More importantly, the death rate and incidence of cataracts in the diabetic rats were markedly decreased in the HIS group. In conclusion, ingestion of high-isoflavone soy protein not only lowers glucose levels but also reduces the incidence of cataracts in diabetic rats. The beneficial effects of soy isoflavones are attributed to increased insulin secretion, a better glycemic control, and antioxidant protection.     

Absorption in humans of isoflavones from soy and red clover is similar

The absorption of isoflavones varies substantially among individuals. It is unknown whether isoflavone absorption differs between those originating from soy and those from red clover, which contain different mixtures of isoflavones. Because both soy and red clover are increasingly used in foods and supplements, these issues were studied in 14 subjects in a single-blind, randomized, placebo-controlled, crossover trial. Soybean isoflavone glycosides and red clover isoflavone aglycones were incorporated into a breakfast cereal and eaten daily for 2 wk each, separated by a 2-wk control or washout period. The 24-h excretions of isoflavones in urine were measured; approximately 25% of each isoflavone was recovered in urine, suggesting that similar amounts were absorbed irrespective of their glycoside/aglycone nature or the differing compositions of their sources (daidzein and genistein in soy and formononetin and biochanin in red clover). Although interindividual variability was high, there was less intraindividual variability; the amounts excreted when subjects consumed the two sources of isoflavone were correlated (r = 0.69; P = 0.007).     

Dietary iron promotes azoxymethane-induced colon tumors in mice

There is accumulating evidence that high levels of dietary iron may play a role in colon carcinogenesis. We used a mouse model to investigate the impact of elevated dietary iron on incidence of aberrant crypt foci (ACF; a preneoplastic lesion) on tumor formation and on induction of oxidative stress. A/J mice were injected intraperitoneally, once a week for 6 weeks, with the colonotropic carcinogen, azoxymethane (AOM) or saline (vehicle controls). Following AOM or saline treatments, mice were placed on diets of high (3,000 ppm) and low (30 ppm) iron. Mice in each treatment group were sacrificed at 6 and 10 weeks following the final injection with AOM or saline. Colons were removed for subsequent histopathological analysis, which revealed average increases of 4.6 +- 1.3 vs. 10.4 +- 2.5 total tumors at 6 weeks and 30.75 +- 2.7 vs. 41.5 +- 4.4 total tumors at 10 weeks per AOM-treated mouse on low- and high-iron diets, respectively. There were no significant differences in incidence of ACF attributable to iron, although there was a trend toward greater crypt multiplicity per focus in mice on high-iron diets. Notably, no tumors were observed in mice receiving vehicle control injections in place of carcinogen, regardless of the level of dietary iron. These data suggest that iron exerts its effect at the stage of tumor promotion, but is not sufficient to initiate tumor formation. To learn more about mechanisms by which iron promotes tumor growth, colons were assayed for several biomarkers of oxidative stress [BOS; total F2-isoprostanes (F2-IsoPs), 15-F2t-isoprostanes (8-IsoPGF2s), Isofurans (IsoFs), and 8-hydroxyguanosines (8-OH[d]Gs)], as well as iron absorption, programmed cell death, and cellular proliferation. Elevated PCNA and TUNEL staining of the colon epithelium revealed hyperproliferative and apoptotic responses to iron, while no significant differences between iron groups were observed in each of the BOS that were assayed. Our results suggest that, following carcinogen exposure, elevated dietary iron promotes the growth of tumors with altered cellular homeostasis through a mechanism that is independent of oxidative stress.     

Dietary fat and colon cancer: animal models

During the past 15 years, human and animal model studies performed in our laboratory indicate that dietary fat plays an important role in the etiology of colon cancer. The effect of dietary fat during the stages of initiation and postinitiation of colon carcinogenesis depends on not only the amount of fat but also the type of fat and its fatty acid composition. Studies conducted in animal models have shown that high intake of dietary corn oil, beef fat, safflower oil, and lard increases colon carcinogenesis, whereas diets high in olive oil, coconut oil, and fish oil are without enhancing effect. The mechanisms by which various types of fat increase colon carcinogenesis are not fully understood; however, in most instances, the high-fat diet seems to enhance colon carcinogenesis through its elevation of agents that act as promoters of tumor development.     

Effects of soy oligosaccharides on plasma and cecal isoflavones,and cecal enzyme activities in mice

This paper studies the effects of soy oligosaccharides on plasma and cecal isoflavones and floral enzyme activities in adult mice. The isoflavones used in this experiment were daidzein and genistein. Male 6-wk-old mice were fed a soy oligosaccharide-isoflavone (SOI) diet or cellulose-isoflavone (CEI) diet for 10 d. Plasma and cecal isoflavones were analyzed by HPLC, and cecal bacterial beta-glucosidase and beta-glucuronidase activities were also measured. The plasma genistein concentration was significantly higher in the SOI diet group than in the CEI diet group, but no significant difference was observed in plasma daidzein concentration between the two dietary groups. The total amount of cecal isoflavones existing as aglycone were significantly greater in the SOI diet group than in the CEI diet group, and both cecal beta-glucosidase and beta-glucuronidase activities were significantly higher in the SOI diet group than in the CEI diet group. These results indicate that soy oligosaccharides have an impact on the metabolic activity of intestinal microflora, plasma concentrations of isoflavones, and amount of isoflavones in the intestine. The present study suggests that ingestion of soy oligosaccharides may influence the effect of dietary isoflavones on the host.     

Intake of soy foods and soy isoflavones by rural adult women in China

This study evaluated the intake of soy foods and soy isoflavones by rural adult women and potential determinant factors. Soy food consumption and information on age, education and medical history were collected on 1,188 subjects in Gansu Province and Hebei Province, China using a food frequency questionnaire to gather data on food intake over the past year. Weight and height were simultaneously measured. The results showed that 1139 (95.9%) rural women consumed soy foods in the past year. The average intake of soy foods and isoflavones was 38.7 +/- 58.2 (median = 23.5) g/d and 17.7 +/- 26.6 (median= 8.9) mg/d, respectively. Tofu accounted for the most contribution to their intake. The soy isoflavone intake ranged between 0-35 mg/day in 89.2% of subjects. Gansu women had higher intakes of soy foods and isoflavones than Henbei women (P< 0.05). Women aged 41-50 years consumed less soy foods and isoflavones than the 20-30-year olds and 31-40 year olds(P < 0.05). The intake of soy foods (P< 0.01) and isoflavones (P< 0.01) by women who experienced secondary education or above was significantly higher than illiterate women. Women without a medical history had a higher soy isoflavone intake than women with a medical history, but the difference was not statistically significant. These results suggest that the intake of soy isoflavones by Chinese rural adult women was much higher than women in Western countries. The distribution of intake was skewed to the right and varied among women in regard to region, age group and education level.     

Dietary soy protein maintains some indices of bone mineral density and bone formation in aged ovariectomized rats

Hormone replacement therapy (HRT) has been used to prevent osteoporosis in postmenopausal women. However, HRT may increase the incidence of some cancers and has other side effects. There is considerable interest in dietary alternatives that include the consumption of soy and isoflavones derived from soy. The purpose of this study was to determine the effects of dietary soy protein on bone density, formation and resorption in cortical and cancellous bone in aged, ovariectomized rats. Specific emphasis was placed on indices of bone formation. Rats were assigned to the following groups: baseline; sham surgery + casein diet; sham + soy protein diet; ovariectomy (Ovx) + casein diet; Ovx + soy protein diet. The diets were fed for 3 mo. The Ovx Soy group had a greater bone mineral density (BMD) than the Ovx Casein group. There was a trend (P < 0.10) for greater periosteal bone formation rates in the Sham Soy compared with the Sham Casein group. In the Ovx Soy group, indices of endocortical bone formation were greater than those of the Ovx Casein group. There were no significant differences in resorption indices or endochondral growth (bone elongation) rates with soy in either the Sham or Ovx groups. In cancellous bone, the double-labeled surface and bone formation rates were greater in the Ovx Soy group than in the Ovx Casein group. These results show that dietary soy had a beneficial effect on the preservation of BMD associated with estrogen deficiency bone loss in aged rats. These data also show that at the tissue level, soy functions in a manner different from estrogen by increasing or sustaining elevated bone formation rates after ovariectomy.     

Dietary fiber and colon cancer: animal model studies

Support for a protective role for certain dietary fibers in the etiology of colon cancer has come from nutritional epidemiologic studies. Recommendations to increase consumption of fiber-containing food and decrease the intake of dietary fat should form the basis of a diet that is unlikely to do harm, and may have the potential for reducing the development of colon cancer, in humans. Studies examining the role of dietary fiber as an inhibitor of colon cancer in animal models appear to have provided some conflicting results, due mostly to differences in the nature and amount of carcinogen used to induce colon tumors, variation in the composition of the experimental diets, and relative difference in food intake by animals, to cite a few of the methodological problems. However, overall, the feeding of wheat bran appears to inhibit color tumor development to a greater degree than do other dietary sources of fiber.     

Dietary patterns and colon cancer in western New York

Seven dietary patterns were identified among control subjects in the Western New York Diet Study (1975–1986) by application of principal components analysis to data from a 95‐itemfood frequency interview. The results of case‐control analyses of colon cancer risk for these patterns are presented. Cases were matched with neighborhood controls on the bases of age and sex; 205 colon case‐control male and 223 female pairs were obtained. The dietary patterns and intakes of energy, total fat, and dietary fiber were examined with logistic regression for their individual contributions to risk. In males, three of these dietary patterns were associated positively with fat and energy consumption; they elevated risk for colon cancer and accounted for more risk than did the specific nutrients. Control for energy and fat intakes allowed the protective influences of additional dietary patterns to be expressed. No patterns elevated risk in women; two patterns were protective for colon cancer. Controlling for energy and fat intake enhanced the protection afforded by one of these patterns but had no influence on that of the other. Measures of foods rather than single nutrients may be more inclusive of dietary exposures to risk as well as being related more directly to underlying health behaviors. Therefore they may be better able to account for risk in diseases with multiple causation.