Effect of circulating forms of soy isoflavones on the oxidation of low density lipoprotein

Soy isoflavones are thought to have a cardioprotective effect that is partly mediated by an inhibitory influence on the oxidation of low density lipoprotein (LDL). However, the aglycone forms investigated in many previous studies do not circulate in appreciable quantities because they are metabolised in the gut and liver. We investigated effects of various isoflavone metabolites, including for the first time the sulphated conjugates formed in the liver and the mucosa of the small intestine, on copper-induced LDL oxidation. The parent aglycones inhibited oxidation, although only 5% as well as quercetin. Metabolism increased or decreased their effectiveness. Equol inhibited 2.65-fold better than its parent compound daidzein and 8-hydroxydaidzein, not previously assessed, was 12.5-fold better than daidzein. However, monosulphated conjugates of genistein, daidzein and equol were much less effective and disulphates completely ineffective. Since almost all isoflavones circulate as conjugates, these data suggest that despite the increased potency produced by some metabolic changes, isoflavones may not be effective antioxidants in vivo unless they are deconjugated again.

Savory peptides present in Moromi obtained from soy sauce fermentation of yellow soybean

The presence of savory peptides in moromi has been investigated. Moromi was prepared by fermenting yellow soybean using Aspergillus oryzae as the starter at the first step (mold fermentation) and 20% brine solution at the next step (brine fermentation). The moromi was then ultrafiltered stepwise using membranes with MW cut-offs of 10,000, 3,000, and 500 Da, respectively. The fraction with MW < 500 Da was chromatographed using Sephadex G-25 SF to yield four fractions, 1-4. Analysis of soluble peptides, NaCl content, alpha-amino nitrogen, amino acid composition, peptide profile using CE coupled with DAD, taste profile and free glutamic acid content, were performed for each fraction. Fraction 2 contained a relatively high total glutamic acid content, but a relatively low free glutamic acid content and had the highest umami taste. This fraction also had more peptides containing non-aromatic amino acids than the other fractions. The peptides present in fraction 2 may play a role, at least in part, in its intense umami taste.

Soy isoflavones increase preprandial peptide YY (PYY), but have no effect on ghrelin and body weight in healthy postmenopausal women

Background: Soy isoflavones show structural and functional similarities to estradiol. Available data indicate that estradiol and estradiol-like components may interact with gut "satiety hormones" such as peptide YY (PYY) and ghrelin, and thus influence body weight. In a randomized, double-blind, placebo-controlled, cross-over trial with 34 healthy postmenopausal women (59 ± 6 years, BMI: 24.7 ± 2.8 kg/m2), isoflavone-enriched cereal bars (50 mg isoflavones/day; genistein to daidzein ratio 2:1) or non-isoflavone-enriched control bars were consumed for 8 weeks (wash-out period: 8-weeks). Seventeen of the subjects were classified as equol producers. Plasma concentrations of ghrelin and PYY, as well as energy intake and body weight were measured at baseline and after four and eight weeks of each intervention arm. Results: Body weight increased in both treatment periods (isoflavone: 0.40 ± 0.94 kg, P < 0.001; placebo: 0.66 ± 0.87 kg, P = 0.018), with no significant difference between treatments. No significant differences in energy intake were observed (P = 0.634). PYY significantly increased during isoflavone treatment (51 ± 2 pmol/L vs. 55 ± 2 pmol/L), but not during placebo (52 ± 3 pmol/L vs. 50 ± 2 pmol/L), (P = 0.010 for treatment differences, independent of equol production). Baseline plasma ghrelin was significantly lower in equol producers (110 ± 16 pmol/L) than in equol non-producers (162 ± 17 pmol/L; P = 0.025). Conclusion: Soy isoflavone supplementation for eight weeks did not significantly reduce energy intake or body weight, even though plasma PYY increased during isoflavone treatment. Ghrelin remained unaffected by isoflavone treatment. A larger and more rigorous appetite experiment might detect smaller differences in energy intake after isoflavone consumption. However, the results of the present study do not indicate that increased PYY has a major role in the regulation of body weight, at least in healthy postmenopausal women.

Developing a quantitative approach for determining the in vitro prebiotic potential of dietary oligosaccharides

Prebiotics are nondigestible carbohydrates that beneficially affect the host by selectively stimulating the growth and/or activity of one, or a limited number of, bacteria present in the colon. The selected genera should have the capacity to improve host health (e.g. Bifidobacterium, Lactobacillus). To help identify preferred types, for inclusion into the diet, a quantitative equation [measure of the prebiotic effect (MPE)] is suggested. This will help evaluate, in vitro, the fermentation of dietary carbohydrates and compare their prebiotic effect. Although the approach is not meant to define health values, it is formulated to better inform the choice of prebiotic. It therefore, compares measurements of bacterial changes through the determination of maximum growth rates of predominant groups present in faeces, rate of substrate assimilation and the production of lactic, acetic, propionic and butyric acids. The equation will allow further in vitro comparisons of MPE, leading towards further studies (e.g. in humans) to determine the success of dietary intervention. (C) 2004 Federation of European Microbiological Societies. Published by Elsevier B.V. All rights reserved.

Effect of circulating forms of soy isoflavones on the oxidation of low density lipoprotein

Soy isoflavones are thought to have a cardioprotective effect that is partly mediated by an inhibitory influence on the oxidation of low density lipoprotein (LDL). However, the aglycone forms investigated in many previous studies do not circulate in appreciable quantities because they are metabolised in the gut and liver. We investigated effects of various isoflavone metabolites, including for the first time the sulphated conjugates formed in the liver and the mucosa of the small intestine, on copper-induced LDL oxidation. The parent aglycones inhibited oxidation, although only 5% as well as quercetin. Metabolism increased or decreased their effectiveness. Equol inhibited 2.65-fold better than its parent compound daidzein and 8-hydroxydaidzein, not previously assessed, was 12.5-fold better than daidzein. However, monosulphated conjugates of genistein, daidzein and equol were much less effective and disulphates completely ineffective. Since almost all isoflavones circulate as conjugates, these data suggest that despite the increased potency produced by some metabolic changes, isoflavones may not be effective antioxidants in vivo unless they are deconjugated again.

Effects of high pressure on functional properties of soy protein

Simultaneous measurement of the effects of low soy protein concentration, pH and high pressure treatment at room temperature on solubility, emulsifying properties and rheological properties (loss modulus, G '') of soy protein isolate (SPI) were evaluated. Central composite rotatable designs (2(3)) were employed over two pH ranges (2.66-4.34 and 5.16-6.84) with SPI concentration (0.32-3.68%) and pressure (198-702 MPa) as the other independent variables. The surface responses were obtained for protein solubility, emulsifying activity index (EAI) and G ''. The samples with the highest effect on protein solubility, EAI and G '' values were evaluated, as well, by electrophoresis and free sulphydryl determination. The pH was the main factor that affected protein solubility, with solubility at a maximum at pH < 3 or pH > 6. Increasing SPI concentration and decreasing/increasing the pH away from the isoelectric point both caused a reduction in EAI. Loss modulus (G '') was found to increase with SPI concentration in both pH ranges. (c) 2006 Elsevier Ltd. All rights reserved.

Genistein protects human mammary epithelial cells from benzo(a)pyrene-7,8-dihydrodiol-9,10-epoxide and 4-hydroxy-2-nonenal genotoxicity by modulating the glutathione/glutathione S-transferase system

Epidemiological studies have shown that ingestion of isoflavone-rich soy products is associated with a reduced risk for the development of breast cancer. In the present study, we investigated the hypothesis that genistein modulates the expression of glutathione S-transferases (GSTs) in human breast cells, thus conferring protection towards genotoxic carcinogens which are GST substrates. Our approach was to use human mammary cell lines MCF-10A and MCF-7 as models for non-neoplastic and neoplastic epithelial breast cells, respectively. MCF-10A cells expressed hGSTA1/2, hGSTA4-4, hGSTM1-1 and hGSTP1-1 proteins, but not hGSTM2-2. In contrast, MCF-7 cells only marginally expressed hGSTA1/2, hGSTA4-4 and hGSTM1-1. Concordant to the protein expression, the hGSTA4 and hGSTP1 mRNA expression was higher in the non-neoplastic cell line. Exposure to genistein significantly increased hGSTP1 mRNA (2.3-fold), hGSTP1-1 protein levels (3.1-fold), GST catalytic activity (4.7-fold) and intracellular glutathione concentrations (1.4-fold) in MCF-10A cells, whereas no effects were observed on GST expression or glutathione concentrations in MCF-7 cells. Preincubation of MCF-10A cells with genistein decreased the extent of DNA damage by 4-hydroxy-2-nonenal (150 mu M) and benzo(a)pyrene-7,8-dihydrodiol-9,10-epoxide (50 mu M), compounds readily detoxified by hGSTA4-4 and hGSTP1-1. In conclusion, genistein pretreatment protects non-neoplastic mammary cells from certain carcinogens that are detoxified by GSTs, suggesting that dietary-mediated induction of GSTs may be a mechanism contributing to prevention against genotoxic injury in the aetiology of breast cancer.

UK Food Standards Agency workshop report: the effects of the dietary n-6 : n-3 fatty acid ratio on cardiovascular health

This report summarises a workshop convened by the UK Food Standards Agency (FSA) on 11 September 2006 to review the results of three FSA-funded studies and other recent research on effects of the dietary n-6:n-3 fatty acid ratio on cardiovascular health. The objective of this workshop was to reach a clear conclusion on whether or not it was worth funding any further research in this area. On the basis of this review of the experimental evidence and on theoretical grounds, it was concluded that the n-6:n-3 fatty acid ratio is not a useful concept and that it distracts attention away from increasing absolute intakes of long-chain n-3 fatty acids which have been shown to have beneficial effects on cardiovascular health. Other markers of fatty acid intake, that more closely relate to physiological function, may be more useful.

Biomarkers of the intake of dietary polyphenols: strengths, limitations and application in nutrition research

In order to establish firm evidence for the health effects of dietary polyphenol consumption, it is essential to have quantitative information regarding their dietary intake. The usefulness of the current methods, which rely mainly on the assessment of polyphenol intake using food records and food composition tables, is limited as they fail to assess total intake accurately. This review highlights the problems associated with such methods with regard to polyphenol-intake predictions. We suggest that the development of biological biomarkers, measured in both blood and urine, are essential for making accurate estimates of polyphenol intake. However, the relationship between dietary intakes and nutritional biomarkers are often highly complex. This review identifies the criteria that must be considered in the development of such biomarkers. In addition, we provide an assessment of the limited number of potential biomarkers of polyphenol intake currently available.

Metabolism of dietary phytochemicals: a review of the metabolic forms identified in humans

Dietary derived phytochemicals have been proposed to act as beneficial agents in a multitude of disease states, including cancer, cardiovascular disease and neurodegenerative disorders. However, the biological effect of such compounds will ultimately depend on the cellular effects of their circulating metabolites. The focus of this review is to examine the current knowledge regarding the biotransformation of different classes of phytochemicals in humans. Notably, the data compiled here represents only that obtained from human studies following consumption of phytochemicals in meals or in a dose comparable with normal dietary intake. In addition, we have considered only those studies where more powerful analytical techniques have been used in the characterisation of metabolic forms. We provide clear information regarding the types of metabolites that are likely to be present in humans following oral ingestion. Ultimately this will help identify metabolic forms that should represent the focus of future cellular mechanistic investigations.

Food for thought: the role of dietary flavonoids in enhancing human memory, learning and neuro-cognitive performance

Emerging evidence suggests that dietary-derived flavonoids have the potential to improve human memory and neuro-cognitive performance via their ability to protect vulnerable neurons, enhance existing neuronal function and stimulate neuronal regeneration. Long-term potentiation (LTP) is widely considered to be one of the major mechanisms underlying memory acquisition, consolidation and storage in the brain and is known to be controlled at the molecular level by the activation of a number of neuronal signalling pathways. These pathways include the phosphatidylinositol-3 kinase/protein kinase B/Akt (Akt), protein kinase C, protein kinase A, Ca-calmodulin kinase and mitogen-activated protein kinase pathways. Growing evidence suggests that flavonoids exert effects on LTP, and consequently memory and cognitive performance, through their interactions with these signalling pathways. Of particular interest is the ability of flavonoids to activate the extracellular signal-regulated kinase and the Akt signalling pathways leading to the activation of the cAMP-response element-binding protein, a transcription factor responsible for increasing the expression of a number of neurotrophins important in LTP and long-term memory. One such neurotrophin is brain-derived neurotrophic factor, which is known to be crucial in controlling synapse growth, in promoting an increase in dendritic spine density and in enhancing synaptic receptor density. The present review explores the potential of flavonoids and their metabolite forms to promote memory and learning through their interactions with neuronal signalling pathways pivotal in controlling LTP and memory in human subjects.

Chylomicron particle size and number, factor VII activation and dietary monounsaturated fatty acids

This study evaluated the effects of substituting dietary saturated fatty acids (SFAs) with monounsaturated fatty acids (MUFAs) on postprandial chylomicron (triacylglycerol (TAG), apolipoprotein B-48 (apo B-48) and retinyl ester (RE)), chylomicron particle size and factor VII (FVII) response when subjects were given a standard meal. In a controlled sequential design, 51 healthy young subjects followed an SFA-rich diet (Reference diet) for 8 weeks after which half of the subjects followed a moderate MUFA diet (n = 25) and half followed a high MUFA diet (n = 26) for 16 weeks. Fasting lipoprotein and lipid measurements were evaluated at baseline and at 8-week intervals during the Reference and MUFA diets. In 25 of the subjects (n = 12 moderate MUFA, n = 13 high MUFA), postprandial responses to a standard test meal containing RE and 13 C-tripalmitin were investigated at the end of the Reference and the MUFA diet periods. Although there were no differences in the postprandial lipid markers (TAG, RE, C-13-TAG) on the two diets, the postprandial apo B-48 response (incremental area under the curve (IAUC) was reduced by 21% on the moderate MUFA diet (NS) and by 54% on the high MUFA diet (P < 0.01). The postprandial peak concentrations of apo B-48 were reduced by 33% on the moderate MUFA diet (P < 0.01) and 48% on the high MUFA diet (P < 0.001). Fasting values for factor VII activity (FVIIc), activated factor VII (FVIIa) or factor VII antigen (FVIIag) did not differ significantly when subjects were transferred from Reference to MUFA diets. However, the postprandial increases in coagulation FVII activity (FVIIc) were 18% lower and of activated FVII (FVIIa) were 17% lower on the moderate MUFA diet (NS). Postprandial increases in FVIIc and FVIIa were 50% (P < 0.05) and 29% (P < 0.07) lower on the high MUFA diet and the area under the postprandial FVIIc response curve (AUC) was also lower on the high MUFA diet (P < 0.05). Significantly higher ratios of RE:apo B-48 (P < 0.001) and 13 C-palmitic acid:apo B-48 (P < 0.01) during both MUFA diets suggest that the CMs formed carry larger amounts of dietary lipids per particle, reflecting an adaptation to form larger lipid droplets in the enterocyte when increased amounts of dietary MUFAs are fed. Smaller numbers of larger chylomicrons may explain attenuated activation of factor VII during the postprandial state when the background diet is rich in MUFA. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.

Effect of dietary fish oil on biohydrogenation of fatty acids and milk fatty acid content in cows

Mechanisms underlying milk fat conjugated linoleic acid (CLA) responses to supplements of fish oil were investigated using five lactating cows each fitted with a rumen cannula in a simple experiment consisting of two consecutive 14-day experimental periods. During the first period cows were offered 18 kg dry matter (DM) per day of a basal (B) diet formulated from grass silage and a cereal based-concentrate (0.6 : 0.4; forage : concentrate ratio, on a DM basis) followed by the same diet supplemented with 250 g fish oil per day (FO) in the second period. The flow of non-esterified fatty acids leaving the rumen was measured using the omasal sampling technique in combination with a triple indigestible marker method based on Li-Co-EDTA, Yb-acetate and Cr-mordanted straw. Fish oil decreased DM intake and milk yield, but had no effect on milk constituent content. Milk fat trans-11C(18:1), total trans-C-18:1, cis-9 trans-11 CLA, total CLA, C-18 :2 (n- 6) and total C-18:2 content were increased in response to fish oil from 1.80, 4.51, 0.39, 0. 56, 0.90 and 1.41 to 9.39, 14.39, 1.66, 1.85, 1.25 and 4.00 g/100 g total fatty acids, respectively. Increases in the cis-9, trans-11 isomer accounted for proportionately 0.89 of the CLA response to fish oil. Furthermore, fish oil decreased the flow of C-18:0 (283 and 47 g/day for B and FO, respectively) and increased that of trans-C-18:1 fatty acids entering the omasal canal (38 and 182 g/day). Omasal flows of trans-C-18:1 acids with double bonds in positions from delta-4 to -15 inclusive were enhanced, but the effects were isomer dependent and primarily associated with an increase in trans-11C(18:1) leaving the rumen (17.1 and 121.1 g/day for B and FO, respectively). Fish oil had no effect on total (4.36 and 3.50 g/day) or cis-9, trans-11 CLA (2.86 and 2.08 g/day) entering the omasal canal. Flows of cis-9, trans-11 CLA were lower than the secretion of this isomer in milk. Comparison with the transfer of the trans-9, trans-11 isomer synthesized in the rumen suggested that proportionately 0.66 and 0.97 of cis-9, trans-11 CLA was derived from endogenous conversion of trans-11 C-18:1 in the mammary gland for B and FO, respectively. It is concluded that fish oil enhances milk fat cis-9, trans-11 CLA content in response to increased supply of trans-11 C-18:1 that arises from an inhibition of trans C-18:1 reduction in the rumen.