Serum isoflavones and soya food intake in Japanese, Thai and American end-stage renal disease patients on chronic haemodialysis.

BACKGROUND: Soya foods, a staple in several Asian countries, have received increasing attention because of their nutritional properties and their high isoflavone content. We have shown recently abnormal pharmacokinetics of soya isoflavones following acute oral intake, in soya-naive end-stage renal disease (ESRD) patients. No information is available, however, about blood levels of soya isoflavones in ESRD patients with habitual soya intake. Additionally, no information is available about the conjugation profile of these compounds in ESRD patients. METHODS: To assess the relationship between habitual soya intake on blood isoflavone levels in ESRD patients, we recorded dietary soya food intake and analysed circulating levels of soya isoflavones in randomly selected, clinically stable haemodialysis patients from the United States (n = 20), Thailand (n = 17) and Japan (n = 20). Dietary records and three weekly blood samples were collected from each participant. Combined isoflavones and individual genistein, daidzein, glycitein and O-desmethylangolensin (DMA) were analysed in serum by liquid chromatography/mass spectrometry. Lipid phase micronutrients, including tocopherols, carotenoids and retinol were also measured to compare ethnic differences in isoflavones with those of more common lipid soluble antioxidant micronutrients. RESULTS: Soya intake was higher in Japanese than in Thai patients and it was negligible in the US patients. Blood levels of genistein were very elevated and significantly higher in the Japanese patients (1128 +/- 205 nM), as compared with the Thai and US patients (258 +/- 64 and 168 +/- 49 nM, respectively; P < 0.001). The other isoflavones followed the same trend. Daidzein was more concentrated than genistein in the dialysis patients. Robust correlation was present between weekly soya intake and blood isoflavone levels (r = 0.56, P < 0.001). Despite very high total isoflavone concentrations, the levels of unconjugated and sulphated isoflavones in the Japanese patients were comparable to those described in healthy subjects. Compared with the striking difference in isoflavones, more easily accessible dietary antioxidants, including tocopherols, carotenoids and retinol, differed only minimally or not at all in the three groups. CONCLUSIONS: ESRD patients appear to accumulate isoflavones as a function of dietary soya intake, resulting in blood concentrations that are higher than those reported in subjects with preserved kidney function. Even in the presence of very elevated total isoflavone levels, the concentrations of the unconjugated and sulphated fractions are comparable to those of healthy subjects. A discrepancy is noted between accumulation of soya isoflavones and other more common lipid-soluble antioxidant micronutrients.     

Soy protein diet improves endothelial dysfunction in renal transplant patients.

BACKGROUND: Since it has been demonstrated that soy diet can improve endothelial function, in the present study we evaluated the effect of dietary substitution of 25 g of animal proteins with soy proteins on endothelial dysfunction in renal transplant patients. METHODS: In 20 renal transplant patients (55 +/- 11 years, serum creatinine 1.7 +/- 0.6 mg/dl), brachial artery flow mediated dilation (FMD) and endothelium-independent vasodilation (sublingual nitroglycerine, 25 microg) were measured at baseline, after 5 weeks of a soy diet and finally after 5 weeks of soy wash-out. Changes in plasma lipids, markers of oxidative stress (lipid peroxides, LOOH) and inflammation (C-reactive protein), isoflavones (genistein and daidzein), asymmetric dimethyl arginine (ADMA) and L-arginine were also evaluated. RESULTS: At baseline, patients showed a significantly lower FMD as compared with age-matched healthy subjects (3.2 +/- 1.8 vs 6.3 +/- 1.9, respectively; P < 0.001), while response to nitroglycerine was similar. After soy diet, actual protein intake was not changed, cholesterol and lipid peroxides were significantly reduced, and isoflavones were detectable in plasma. Soy diet was associated with a significant improvement in FMD (4.4 +/- 2.0; P = 0.003 vs baseline), while response to nitroglycerine was unchanged. Improvement in FMD was related to L-arginine/ADMA ratio changes, but no significant relation was found to changes in cholesterol, lipid peroxides or genistein and daidzein plasma concentrations. After 5 weeks of soy diet discontinuation, FMD (3.3 +/- 1.7%) returned to baseline values and isoflavones were no longer detectable in plasma. CONCLUSIONS: A soy protein diet for 5 weeks improves endothelial function in renal transplant patients. This effect seems to be strictly dependent on soy intake as it disappears after soy withdrawal and is mediated by an increase in the L-arginine/ADMA ratio, independently of change in lipid profile, oxidative stress or isoflavones.     

Positive effect of dietary soy in ESRD patients with systemic inflammation--correlation between blood levels of the soy isoflavones and the acute-phase reactants.

BACKGROUND: Inflammation is commonly associated with malnutrition and cardiovascular disease in end-stage renal failure patients. Anti-inflammatory properties of the isoflavones, a micronutrient component of soy, have been reported in several experimental models and disease conditions, but never in renal failure. We hypothesized that dietary soy isoflavones correct laboratory evidence of systemic inflammation in haemodialysis (HD) patients with underlying high blood levels of C-reactive protein (CRP). METHODS: End-stage renal disease patients on chronic HD, with elevated CRP (>10.0 mg/l) were enrolled in this pilot study. The subjects were double-blind randomly distributed with 2 : 1 ratio to receive isoflavone-containing soy-based nutritional supplements (soy group) or isoflavone-free milk protein (control group) for 8 weeks. Serum isoflavone, inflammatory markers and nutrition markers were assessed at baseline and at the end of the treatment. RESULTS: Thirty-two subjects were enrolled. Fifteen subjects in the soy group and 10 in the control group completed the study; five dropouts were due to acute illness and two due to food intolerance. After intervention, blood isoflavone levels were 5- to 10-fold higher in the soy group than in the control group [e.g. median genistein (25-75th percentile): 337.9 (175.5-1007) nM in the soy group vs 41.4 (22.9-100.4) nM in the control group; P < 0.001]. However, the isoflavone levels ranged widely in the soy group (e.g. genistein: 33-1868 nM) and, depending on the individual compound, four to seven subjects had end-of-treatment levels that were not different from baseline. Variation from baseline of the individual serum isoflavone levels (Delta-isoflavone) and CRP displayed a strong inverse correlation in the soy group (R = -0.599, P < 0.02). In addition, Delta-isoflavone correlated positively with the variation of albumin (R = 0.522, P = 0.05) and insulin-like growth factor-1 (R = 0.518, P < 0.05). Group levels of CRP were not statistically different after intervention although a trend towards lower levels was noted in the soy group [18.2 (12.7-29.1) mg/l at baseline vs 9.7 (5.2-20.7) mg/l at week 8; NS] but not in the control group [20.6 (9.2-38.5) vs 17.6 (9.1-40.7) mg/l]. CONCLUSION: These data suggest the possibility of beneficial effects of isoflavone-rich soy foods on the inflammatory and nutritional status of HD patients with underlying systemic inflammation.     

Effect of soy protein-rich diet on renal function in young adults with insulin-dependent diabetes mellitus

BACKGROUND: Diabetic nephropathy is the most frequent cause of end-stage renal disease in the Western world. Dietary intake, including protein amount and type, seems to affect the progression of renal disease. This pilot study tested the hypothesis that substituting soy protein for animal protein in the diets of diabetics would help correct glomerular hyperfiltration. METHODS: Twelve young adults (aged 29.9 +/- 2.4 years) with type 1 diabetes mellitus (duration of diabetes 15.1 +/- 2.3 years) and hyperfiltration (glomerular filtration rate, GFR > 120 ml/min/1.73 m2) completed a crossover, dietary intervention trial. After a four-week assessment of baseline characteristics and dietary habits, subjects were assigned to either a control or soy diet for eight weeks after which each subject was crossed over to the alternative diet for another eight-week period. RESULTS: Mean GFR was significantly reduced (p < 0.02) after eight weeks on the soy diet (143 +/- 7.4 ml/min/1.73 m2) compared with baseline (159 +/- 7.7 ml/min/ 1.73 m2) and control diets (161 +/- 10.0 ml/min/1.73 m2). Urinary excretion of the soy isoflavones was significantly higher (p < 0.01) at the end of the soy diet (genistein 1,014.6 +/- 274.1 nmol/h, daidzein 2,645.1 +/- 989.6 nmol/h) compared with baseline (genistein 53.7 +/- 31.1 nmol/h, daidzein 151.1 +/- 74.1 nmol/h) and control diets (genistein 41.1 +/- 13.3 nmol/h, daidzein 127.5 +/- 54.0 nmol/h). The soy diet significantly reduced total and LDL cholesterol by 7% and 9%, respectively. CONCLUSIONS: Implementation of a soy-based diet appears to reduce the GFR and total and LDL cholesterol of young adults with type 1 diabetes and glomerular hyperfiltration, thus affecting positively their clinical profile.     

The effect of isolated soy protein on plasma biomarkers in elderly men with elevated serum prostate specific antigen

PURPOSE: We performed a randomized double-blind crossover pilot study in elderly men with elevated prostate specific antigen (PSA) on the effects of the daily consumption of 2 soy beverages, each containing 20 gm. of isolated soy protein, on the isoflavone concentration in blood and urine, and on the 3 serum biomarkers cholesterol, PSA and the soluble p105 component of the p185erbB-2 proto-oncogene. MATERIALS AND METHODS: A total of 34 men supplemented their diet by consuming 1 of 2 soy protein beverages assigned randomly twice daily for a 6-week period. In a second 6-week period they consumed the other soy protein beverage. The beverage ISP+ provided 42 mg. of genistein and 27 mg. of daidzein daily, whereas the other beverage, ISP-, provided only 2.1 and 1.3 mg. of these isoflavones daily, respectively. Blood and 24-hour urine samples were obtained before the study, at 2-week intervals during the study and 2 weeks after study completion. RESULTS: ISP+ and to a lesser extent ISP- substantially increased the serum concentration and urinary output of the isoflavones and their metabolites. Serum cholesterol was significantly decreased by ISP+ irrespective of the order in which the 2 soy beverages were administered and in apparent correlation with the total isoflavone concentration. There was no significant effect of the soy beverages on serum PSA and p105erbB-2 values. CONCLUSIONS: This study reveals that short-term exposure of elderly men with elevated serum PSA values to soy protein containing isoflavones decreases serum cholesterol but not the serum biomarkers PSA and p105erbB-2.     

Soy Product Intake and Serum Isoflavonoid and Estradiol Concentrations in Relation to Bone Mineral Density in Postmenopausal Japanese Women

To evaluate soy intake and serum concentrations of estradiol and isoflavonoids and their relationship to bone mineral density (BMD) and serum bone-specific alkaline phosphatase (bone ALP) activity, we conducted a cross-sectional study of 87 postmenopausal Japanese women. Soy product and isoflavone intake from soy products and intake of nutrients were assessed with a semiquantitative food-frequency questionnaire. BMD (mg/cm²) was measured by single-energy X-ray absorptiometry at the site of the calcaneus. Serum estradiol (E₂) and the sex hormone-binding globulin (SHBG) were measured by radioimmunoassay. Serum genistein and daidzein concentrations were measured by a high-performance liquid chromatography MS/MS method. A statistically significant correlation was observed between the ratio of E₂ to SHBG and BMD (Spearman r = 0.38, p = 0.0003) after controlling for age, body mass index, smoking status, age at menarche, and intake of vegetable fat, vitamin C and salt. Soy product and isoflavone intake and serum isoflavones were not significantly correlated with BMD after controlling for the covariates. Serum ALP was not significantly correlated with soy product and isoflavone intake, the E₂/SHBG ratio or serum isoflavones. The present study supports the association of BMD with serum estradiol; however, it does not support the association of BMD with soy or isoflavone intake or serum isoflavone levels. Received: 13 August 2001 / Accepted: 30 October 2001     

Modulation of soy isoflavones bioavailability and subsequent effects on bone health in ovariectomized rats: the case for equol

Introduction

Soy products are of particular interest because of their potential health benefits in a range of hormonal conditions, such as osteoporosis, due to their high content in phytoestrogens. Because equol, the main metabolite from soy isoflavones, is thought to be powerful, the present study was designated to evaluate the bone-sparing effects of equol by either providing the molecule through the diet or by eliciting its endogenous production by modulating intestinal microflora by short-chain fructooligosaccharides (sc-FOS) or live microbial (Lactobacillus casei) together with daidzein, its precursor.

Methods

A comparison with daidzein and genistein was also performed. Rats (3 months old) were ovariectomised (OVX) or sham-operated (SH). Ovariectomised rats were randomly assigned to six experimental diets for 3 months: a control diet (OVX), the control diet supplemented with either genistein (G), or daidzein (D), or equol (E) at the level of 10 μg/g body weight/d. The remaining OVX rats were given daidzein at the dose of 10 μg/g body weight/d, simultaneously with short-chain FOS (Actilight®, Beghin-Meiji) (D+FOS) or Lactobacillus casei (Actimel, Danone) (D+L). The SH rats were given the same control diet as OVX.

Results

Genistein, daidzein or equol exhibited a bone sparing effect. Indeed, total femoral bone mineral density (BMD) was significantly enhanced (compared to that of OVX rats), as was the metaphyseal compartment. Bone strength was improved by E consumption, but not by genistein or daidzein given alone. As far as the FOS diet is concerned, the addition of prebiotics significantly raised efficiency of the daidzein protective effect on both femoral BMD and mechanical properties. The effects of lactobacillus were similar, except that the increase in metaphyseal-BMD was not significant.

Conclusion

In conclusion, long-term equol consumption, like genistein and daidzein, in the ovariectomized rat, provides bone sparing effects. Adding indigestible sugars, such as FOS or live microbial as L. casei, in the diet significantly improves daidzein protective effects on the skeleton.     

Soy isoflavonoid equol modulates the growth of benign and malignant prostatic epithelial cells in vitro

BACKGROUND: The dietary consumption of high levels of soy has been linked to reduced risks for prostate cancer (PC) in Asians and vegetarians. In vitro studies have focused on the two most abundant isoflavones in soy, genistein and daidzein. However, daidzein is differentially metabolized by gut microflora in humans, yielding compounds with very different bioactivities and half-lives. Asians are significantly more likely to produce the metabolite equol than Caucasians, suggesting its role in the prevention of PC. We hypothesize that equol is a bioactive metabolite that exerts direct antiproliferative effects on prostatic epithelial cells. METHODS: Benign and malignant prostatic epithelial cells were treated in vitro with equol, genistein, and daidzein by using the range of concentrations found in the prostatic fluids of Asians consuming soy. Growth and cell cycle distribution were analyzed over time. RESULTS: After 9 days of treatment, equol inhibited growth of benign human prostatic epithelial cells (PrEC) by 37% at 10(-6) M and 80% at 10(-5) M. Although genistein also had profound effects, daidzein appeared only one tenth as potent as equol. Equol and daidzein caused an accumulation of cells in G0/G1, whereas genistein arrested cells in G2/M. The isoflavonoids demonstrated differential effects on the established PC cell lines 22Rv1, LNCaP, LAPC-4, PC-3, and DU 145. PC-3 cells showed the greatest resistance. CONCLUSION: Equol is a biologically active metabolite of daidzein that has potent antiproliferative effects on benign and malignant prostatic epithelial cells at concentrations that can be obtained naturally through dietary soy consumption.     

The specific role of isoflavones in reducing prostate cancer risk

AIMS: To evaluate the effectiveness of supplementing a group of early stage prostate cancer patients, with 60 mg of soy isoflavones in producing a change in hormonal and proliferative risk parameters that are implicated in prostate cancer promotion. METHODS: Seventy six eligible prostate cancer patients with a Gleason score of 6 or below, between ages 50 and 80 were admitted and supplemented with soy isoflavones or placebo for a 12 week period and changes in PSA and steroid hormones were analyzed at baseline and post intervention. RESULTS: Fifty-nine patients completed the 12-week intervention. Serum free testosterone was reduced or showed no change in 61% of subjects in the isoflavone group compared to 33% in the placebo group. Serum total PSA decreased or was unchanged in 69% of the subjects in the isoflavone treated group compared to 55% in the placebo group. However, we did not see an increase in SHBG levels. Nineteen percent of subjects receiving soy isoflavones reduced total PSA by two points or more during the intervention period. CONCLUSIONS: These data suggest that supplementing early stage prostate cancer patients with soy isoflavones, even in a study of short duration, altered surrogate markers of proliferation such as serum PSA and free testosterone in a larger number of subjects in the isoflavone supplemented group than the group receiving placebo. The study establishes the need to explore further the effects of prolonged and consistent soy consumption, which could potentially delay onset of histologic disease in this patient population.     

Genistein acutely stimulates insulin secretion in pancreatic beta-cells through a cAMP-dependent protein kinase pathway

Although genistein, a soy isoflavone, has beneficial effects on various tissues, it is unclear whether it plays a role in physiological insulin secretion. Here, we present evidence that genistein increases rapid glucose-stimulated insulin secretion (GSIS) in both insulin-secreting cell lines (INS-1 and MIN6) and mouse pancreatic islets. Genistein elicited a significant effect at a concentration as low as 10 nmol/l with a maximal effect at 5 micromol/l. The effect of genistein on GSIS was not dependent on estrogen receptor and also not related to an inhibition of protein tyrosine kinase (PTK). Consistent with its effect on GSIS, genistein increases intracellular cAMP and activates protein kinase A (PKA) in both cell lines and the islets by a mechanism that does not involve estrogen receptor or PTK. The induced cAMP by genistein, at physiological concentrations, may result primarily from enhanced adenylate cyclase activity. Pharmacological or molecular intervention of PKA activation indicated that the insulinotropic effect of genistein is primarily mediated through PKA. These findings demonstrated that genistein directly acts on pancreatic beta-cells, leading to activation of the cAMP/PKA signaling cascade to exert an insulinotropic effect, thereby providing a novel role of soy isoflavones in the regulation of insulin secretion.     

Serum ionic fluoride levels in haemodialysis and continuous ambulatory peritoneal dialysis patients

High serum fluoride (F-) in patients with chronic renal failure (CRF) and end-stage renal disease (ESRD) is associated with risk of renal osteodystrophy and other bone changes. This study was done to determine F- in normal healthy controls and patients with ESRD on haemodialysis (HD) or peritoneal dialysis (PD). Seventeen healthy controls (12 males, 5 females) and 39 ESRD patients on dialysis (17 males, 22 females) were recruited in the study in a community with 47.4 +/- 3.28 microM/l (range 44-51 microM/l) of F- content in drinking water. Control subjects showed a mean serum F- concentration of 1.08 +/- 0.350 microM/l. Males in control group showed slightly higher F- levels (1.15 +/- 0.334, range 0.55-1.9 microM/l) than females (0.92 +/- 0.370, range 0.6-1.5 microM/l). Mean serum F- concentration did not correlate significantly with age and sex among control subjects, whereas such correlation was observed in patients with ESRD on dialysis. Mean serum F- concentration was significantly higher in patients on dialysis (2.67 +/- 1.09, range 0.8-5.2 microM/l) than normal controls. When grouped according to sex, the mean serum F- concentration in males (3.05 +/- 1.04, range 1.8-5.2 microM/l) was significantly higher than females (2.38 +/- 1.08, range 0.8-5.2 microM/l). When patients were grouped according to age, it was observed that F- concentration was significantly higher in patients with age groups 21-70 (2.86 +/- 1.05) than those with age group 13-20 years (1.42 +/- 0.531). Thus F- concentration correlated with age and sex, being higher in males and above 20 years. Despite appreciable clearance of F- (39-90%) across the peritoneum, patients on CAPD showed higher serum F- concentration than those on HD (3.1 +/- 1.97 vs 2.5 +/- 1.137 microM/l). Of the total 39 patients on dialysis 39% had their serum F- concentration above 3.0 microM/l, posing the risk of renal osteodystrophy.      

Vascular function in patients with end-stage renal disease and/or coronary artery disease: a cardiac magnetic resonance imaging study

Decreased arterial compliance in end-stage renal disease (ESRD) is associated with increased cardiovascular risk. Our aim was to examine aortic compliance in patients with ESRD using cardiac magnetic resonance imaging (MRI) and to compare these with patients with advanced atherosclerotic disease who are known to be at high cardiovascular risk. We examined a total of 83 subjects matched for age: 24 had ESRD and were on dialysis therapy for 3+/-6 years, 24 had severe coronary artery disease (CAD), 11 had both ESRD and CAD (4+/-5 years on dialysis therapy), and 24 healthy subjects with no evidence of CAD. Vascular and cardiac function was assessed using cardiac MRI. Aortic compliance was significantly reduced in patients with CAD compared to control subjects (11.3+/-6.3 ml x 10(-3)/mm Hg vs 15.6+/-6.0 ml x 10(-3)/mm Hg, P=0.009). Patients with ESRD also exhibited significantly reduced aortic compliance compared to healthy controls (12.4+/-5.8 ml x 10(-3)/mm Hg vs 15.6+/-6.0 ml 10(-3)/mm Hg, P=0.012), whereas there was no significant difference in aortic compliance between patients with CAD and ESRD. Even in the absence of symptomatic CAD, patients with ESRD have significantly reduced aortic compliance compared to normal subjects. Patients with ESRD have equivalent aortic compliance to patients with advanced CAD. These findings suggest that a significantly reduced aortic compliance is one of many mechanisms promoting premature cardiovascular events in patients with ESRD compared to age-matched controls from the general population.     

Soy Protein: Its Effects on Intestinal Calcium Transport, Serum Vitamin D, and Insulin-like Growth Factor-I in Ovariectomized Rats

Recent reports indicate that soy protein and its isoflavones exert beneficial effects on bone in ovarian hormone deficiency. These positive effects, in part, may be due to improved intestinal calcium (Ca) absorption. We examined the role of soy protein or its isoflavones on intestinal Ca transport using ovariectomized rats. Rats were fed either a casein- or a soy protein-based diet with normal or depleted isoflavone levels. After 35 days of treatment, rats were exsanguinated and isolated cells from all intestinal segments were used to measure in vitro Ca transport. Ovariectomy significantly decreased the rates of Ca transport in duodenal and colonic cells, which were prevented by soy protein with normal isoflavone content. This enhanced Ca transport by isoflavones present in soy protein appeared to be independent of circulating insulin-like growth factor-I, 25(OH)vitamin D, or l,25(OH)2vitamin D as these variables were unaffected by dietary treatments. The findings of this study imply that soy isoflavones may promote Ca absorption in a manner analogous to that of estrogen but without exerting uterotrophic effect. Further studies are needed to explore the mechanism(s) by which soy protein or its isoflavones promote intestinal Ca absorption in ovarian hormone deficiency.     

Free serum leptin but not bound leptin concentrations are elevated in patients with end-stage renal disease.

BACKGROUND: Leptin is a 16-kDa protein that is thought to be a regulator of food intake and body weight. Although total serum leptin levels have been reported to be elevated in obese and normal weight patients with end-stage renal disease (ESRD), it is not known whether serum-free leptin concentrations are also increased in patients with ESRD with no apparent nutritional problems. Furthermore, there are no data on how different dialysis modes (high-flux haemodiafiltration and low-flux dialysis) influence serum leptin subfractions. METHODS: We measured fasting serum free and bound leptin levels in three groups of male subjects: patients on haemodiafiltration with high flux dialysers (n=11), patients on haemodialysis with low-flux dialysers (n=17) and healthy age (61+/-8 years) and BMI (23.8+/-3.1 kg/m(2)) matched control subjects (n=28). Both leptin components were determined before and after a single dialysis session. RESULTS: Body mass indices were correlated with serum free leptin levels in both patients (r=0.69, P<0.001) and controls (r=0.77, P<0.001). Mean (SD) serum free leptin levels were significantly higher in ESRD patients than in control subjects (91+/-33 vs 41+/- 21 pmol/l; P<0.01). Bound leptin levels did not differ in both groups (0.67+/-0.12 vs 0.56+/-0.11 nmol/l, NS). Elevated serum-free leptin levels in ESRD patients could be reduced by haemodiafiltration with high-flux membranes, but not with low-flux haemodialysis membranes.The former led to a reduction of initial serum free leptin values to 76+/-17% (P<0.01), whereas bound leptin remained unaffected. CONCLUSION: Serum-free leptin levels are elevated in ESRD without any apparent effect on body weight. In contrast, serum bound leptin levels remain stable, thus central feedback regulation via the bound form of the hormone may serve as an alternative explanation in the regulation of food intake and energy expenditure in chronic patients on haemodialysis with no apparent nutritional problems.     

Associations between plasma ghrelin levels and body composition in end-stage renal disease: a longitudinal study.

BACKGROUND: Ghrelin is a newly detected orexigenic gastric hormone that stimulates food intake. Increased levels of ghrelin are often found in disease states associated with wasting. Wasting is a common phenomenon in end-stage renal disease (ESRD) patients in whom elevated ghrelin levels have been reported. However, no data are available on the relationship between body composition and plasma ghrelin levels in this patient group. METHODS: The study population consisted of 108 (71 males) ESRD patients aged 53+/-12 years. Body composition, nutritional status (subjective global assessment), estimated protein intake (nPNA), plasma ghrelin, plasma insulin and serum leptin were evaluated close to the start of dialysis treatment. Twelve healthy subjects (nine males, 44+/-6 years) served as the control group. A longitudinal evaluation of changes in plasma ghrelin and body composition was performed in 52 of the patients after 12 months of dialysis treatment. RESULTS: Markedly elevated plasma ghrelin levels (843+/-485 vs 443+/-302 pg/ml; P<0.01) were observed in ESRD patients compared with controls. Basal plasma ghrelin levels correlated significantly with plasma insulin (R = -0.32; P<0.05), body mass index (R = -0.24; P<0.05), log serum leptin levels (R = -0.23; P<0.05) and truncal fat mass (R = -0.25; P<0.05). The longitudinal analysis of body composition demonstrated that whereas fat mass increased (23.7+/-8.6 to 25.3+/-9.9 kg; P<0.05) and plasma ghrelin levels decreased (855+/-429 to 693+/-408 pg/ml; P<0.05) significantly in peritoneal dialysis patients, no significant changes in either body composition or plasma ghrelin levels were found in patients treated by haemodialysis. CONCLUSION: Markedly elevated plasma ghrelin levels are found in advanced renal failure and correlate with fat mass, plasma insulin and serum leptin levels. Changes in plasma ghrelin during 12 months of peritoneal dialysis treatment are associated with changes in body composition.     

Effect of genistein, a soy isoflavone, on whole body insulin sensitivity and renal damage induced by a high-fructose diet

The study evaluates the effect of genistein, a soy isoflavone, on insulin sensitivity and renal functional and structural injury in rats rendered insulin-resistant by feeding on a high-fructose diet for 60 days. Fructose-fed animals (60 g /100 g) displayed insulin resistance as indicated by the measures of insulin sensitivity [insulin sensitivity index (ISI(0,120)), quantitative insulin check index (QUICKI), and homeostatic model assessment (HOMA)]. Alterations in body weight, kidney weight, urine volume, plasma, and urine electrolytes accompanied by significant increases in plasma and urinary levels of urea, uric acid, creatinine, total protein, and albumin were observed in fructose-fed rats. Oxidative stress in kidney was noted by an elevation in lipid peroxides and a decline in glutathione (GSH). Insulin sensitivity and renal function were improved in fructose-fed rats administered genistein. Histological changes such as fatty infiltration and thickening of glomeruli observed in fructose-fed rats were also ameliorated when genistein was co-administered. The study shows that genistein improves insulin sensitivity and kidney function in a dietary model of insulin resistance. We suggest that genistein may have benefits for patients suffering from kidney disease associated with insulin resistance.     

The role of soy phytoestrogens in prostate cancer

Epidemiological data of phytoestrogens and prostate cancer strongly supports the cancer protective effects of isoflavones found in soy products. Inhibition of cell proliferation via hormone-dependent and hormone-independent mechanisms by soy phytochemicals has been studied extensively in cell culture and animal studies. Herein, we review the current literature on the epidemiology and effects of two soy phytoestrogens, genistein and daidzein, and would stress the need for controlled human trials to assess the true preventive and therapeutic effects of these compounds.     

The correlation between dietary soy phytoestrogens and neuropathic pain behavior in rats after partial denervation.

Soy diets suppress the development of neuropathic pain behavior in rats undergoing partial sciatic nerve ligation (PSL) injury. Phytoestrogens, plant isoflavones and lignans, abundantly found in soy products, have powerful estrogenic properties. Because, in some preparations, steroid estrogens were found to exert antinociception, we examined whether the analgesic effect of dietary soy is mediated by phytoestrogens. Male Wistar rats were fed five different diets containing 8-180 microg of phytoestrogens per gram. These diets were administered 2 wk before and 2 wk after PSL injury. Levels of tactile allodynia and mechanical and heat hyperalgesia of these rats were determined on Days 3, 8, and 14 after PSL injury. Plasma levels of two major phytoestrogens (genistein and daidzein) and two daidzein metabolites (equol and dihydrodaidzein) were assessed on Day 14 postoperatively. We found that the plasma concentration of these phytoestrogens and the levels of allodynia and hyperalgesia varied highly among dietary groups. Average plasma concentrations of phytoestrogens were associated with reduced levels of tactile allodynia and mechanical hyperalgesia, but not with reduced heat allodynia. Low and high plasma phytoestrogen levels were not analgesic in these tests. This report is the first to show that, at certain plasma concentrations, phytoestrogens reduce neuropathic pain in rats. IMPLICATIONS: Dietary soy suppresses neuropathic pain in rats after partial sciatic nerve ligation. Some of the pain-suppression properties of soy can be attributed to phytoestrogens, isoflavones abundantly found in soy products. Average, but not low or high, plasma levels of phytoestrogens are associated with analgesia.     

Effect of dietary soy protein and genistein on disease progression in mice with polycystic kidney disease

The effects of feeding a soy protein isolate or genistein, an isoflavonoid present in soy protein, on cyst development were examined in the DBA/2FG-pcy (pcy) mouse, an accepted animal model of polycystic kidney disease, before the appearance of clinical symptoms. In study 1, 60-day-old male pcy mice were evenly divided into two groups and fed semipurified diets, based on casein or a soy protein isolate (15 g protein/100 g diet) for 90 days. In study 2, the animals were fed a casein-based diet (25 g casein/100 g diet) with or without genistein (0.05 g/100 g diet) for 60 days. In study 1, total kidney weight and kidney weight relative to body weight were significantly reduced (by 24% to 25%) in the animals fed the soy protein-based diet, relative to the casein-fed group, as was kidney water content (by 38%). In addition, mean cyst volume, as measured by morphometry, were lower (by 25%) in kidneys from the soy protein-fed group. No differences were found between these two groups with respect to final body weight, plasma creatinine, and protein content; however, plasma urea values were significantly lower in the soy protein-fed animals. Genistein supplementation of a casein-based diet in study 2 did not reduce the renal enlargement and cyst development associated with progression of polycystic kidney disease. These results suggest that soy protein is effective in retarding cyst development in the pcy mouse and that this beneficial effect may be unrelated to its genistein content.     

The isoflavone genistein inhibits LPS-stimulated TNFalpha, but not IL-6 expression in monocytes from hemodialysis patients and healthy subjects

BACKGROUND: Whole blood and peripheral blood mononuclear cells from hemodialysis (HD) patients show increased production and secretion of inflammatory cytokines. We determined the contribution of blood monocytes to the production of inflammatory cytokines in whole blood from HD patients. METHODS: Whole blood and isolated mononuclear cells from HD patients and healthy control subjects were preincubated with the isoflavone genistein and stimulated with LPS. TNFalpha, IL-6 and IL-10 formation in the whole blood was measured with ELISA and intracellular cytokine formation in CD 14-positive monocytes was determined by flow cytometry. RESULTS: Unstimulated blood levels of TNFalpha, IL-6 and IL-10 were significantly elevated in HD patients compared to controls, but intracellular monocyte content of these cytokines was identical between groups. LPS induced a robust TNFalpha response in both whole blood and monocytes, and TNFalpha formation was 2.3-fold higher in blood from HD patients compared to controls. A similar trend was observed in monocytes. Conversely, LPS stimulation increased IL-6 levels >1000-fold in whole blood, albeit without a noticeable difference between groups. Only minor increases in monocyte IL-6 content were observed. The isoflavone genistein did not inhibit IL-6 formation and did not alter basal TNFalpha levels, but genistein selectively blocked LPS-induced TNFalpha formation in whole blood and monocytes from both groups. CONCLUSION: Intracellular levels of TNFalpha, IL-6 and IL-10 in monocytes are indistinguishable between HD patients and healthy controls. However, monocytes from HD patients are selectively primed for enhanced TNFalpha secretion in response to LPS. The selective inhibition of monocyte TNFalpha production by genistein may explain the anti-inflammatory action of this phytochemical observed in vivo.