Impact of dietary supplementation with resistant dextrin (NUTRIOSE®) on satiety, glycaemia, and related endpoints, in healthy adults.

PURPOSE: Resistant dextrin (RD) supplementation has been shown to alter satiety, glycaemia, and body weight, in overweight Chinese men; however, there are limited data on its effects in other demographic groups. Here, we investigated the effects of RD on satiety in healthy adults living in the United Kingdom. METHODS: 20 normal weight and 16 overweight adults completed this randomised controlled cross-over study. Either RD (14 g/day NUTRIOSE® FB06) or maltodextrin control was consumed in mid-morning and mid-afternoon preload beverages over a 28-day treatment period with crossover after a 28-day washout. During 10-h study visits (on days 1, 14, and 28 of each treatment period), satietogenic, glycaemic and anorectic hormonal responses to provided meals were assessed. RESULTS: Chronic supplementation with RD was associated with higher fasted satiety scores at day 14 (P = 0.006) and day 28 (P = 0.040), compared to control. RD also increased satiety after the mid-morning intervention drink, but it was associated with a reduction in post-meal satiety following both the lunch and evening meals (P < 0.01). The glycaemic response to the mid-morning intervention drink (0-30 min) was attenuated following RD supplementation (P < 0.01). Whilst not a primary endpoint we also observed lower systolic blood pressure at day 14 (P = 0.035) and 28 (P = 0.030), compared to day 1, following RD supplementation in the normal weight group. Energy intake and anthropometrics were unaffected. CONCLUSIONS: RD supplementation modified satiety and glycaemic responses in this cohort, further studies are required to determine longer-term effects on body weight control and metabolic markers. CLINICALTRIALS. GOV REGISTRATION: NCT02041975 (22/01/2014).

Metabolic targets of watercress and PEITC in MCF-7 and MCF-10A cells explain differential sensitisation responses to ionising radiation.

PURPOSE: Watercress is a rich source of phytochemicals with anticancer potential, including phenethyl isothiocyanate (PEITC). We examined the potential for watercress extracts and PEITC to increase the DNA damage caused by ionising radiation (IR) in breast cancer cells and to be protective against radiation-induced collateral damage in healthy breast cells. The metabolic events that mediate such responses were explored using metabolic profiling. METHODS: 1H nuclear magnetic resonance spectroscopy-based metabolic profiling was coupled with DNA damage-related assays (cell cycle, Comet assay, viability assays) to profile the comparative effects of watercress and PEITC in MCF-7 breast cancer cells and MCF-10A non-tumorigenic breast cells with and without exposure to IR. RESULTS: Both the watercress extract and PEITC-modulated biosynthetic pathways of lipid and protein synthesis and resulted in changes in cellular bioenergetics. Disruptions to the redox balance occurred with both treatments in the two cell lines, characterised by shifts in the abundance of glutathione. PEITC enhanced the sensitivity of the breast cancer cells to IR increasing the effectiveness of the cancer-killing process. In contrast, watercress-protected non-tumorigenic breast cells from radiation-induced damage. These effects were driven by changes in the cellular content of the antioxidant glutathione following exposure to PEITC and other phytochemicals in watercress. CONCLUSION: These findings support the potential prophylactic impact of watercress during radiotherapy. Extracted compounds from watercress and PEITC differentially modulate cellular metabolism collectively enhancing the therapeutic outcomes of radiotherapy.

Olive Polyphenols and the Metabolic Syndrome.

Here, the effects of consuming polyphenol-rich olive products, including olive leaves, their crude extract, and extra virgin olive oil, on aspects of the metabolic syndrome are reviewed. We have sought to summarize the available scientific evidence from dietary intervention trials demonstrating a role for these phytochemicals in ameliorating aberrant glucose metabolism, high blood pressure and elevated blood lipids, and we discuss the potential mechanisms underpinning these observations. Searches for relevant literature published in English were conducted via PubMed and Science Direct. Based on published dietary intervention studies, there is convincing evidence to show that olive polyphenols, independently of olive lipids, reduce risk factors for metabolic syndrome, in particular by improving blood sugar and blood pressure control, and in reducing low density lipoprotein oxidation. There is more limited evidence to suggest that the consumption of olive polyphenols or related products can reduce body weight and visceral fat or impede weight gain, and similarly there are some limited data suggesting improved lipid profiles. There is some mechanistic data to support observations made in human volunteers, but further work is needed in this area. The consumption of olive polyphenols within the context of a healthy pattern of food intake may, in part, explain the reduced risk of metabolic disease associated with adherence to the Mediterranean diet.

Daidzein, R-(+)equol and S-(-)equol inhibit the invasion of MDA-MB-231 breast cancer cells potentially via the down-regulation of matrix metalloproteinase-2.

PURPOSE: Soy isoflavones may inhibit tumor cell invasion and metastasis via their effects on matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs). The current study investigates the effects of daidzein, R- and S-equol on the invasion of MDA-MB-231 human breast cancer cells and the effects of these compounds on MMP/TIMP expression at the mRNA level. METHODS: The anti-invasive effects of daidzein, R- and S-equol (0, 2.5, 10, 50 µM) on MDA-MB-231 cells were determined using the Matrigel invasion assay following 48-h exposure. Effects on MMP-2, MMP-9, TIMP-1 and TIMP-2 expression were assessed using real-time PCR. Chiral HPLC analysis was used to determine intracellular concentrations of R- and S-equol. RESULTS: The invasive capacity of MDA-MB-231 cells was significantly reduced (by approximately 50-60 %) following treatment with 50 µM daidzein, R- or S-equol. Anti-invasive effects were also observed with R-equol at 2.5 and 10 µM though overall equipotent effects were induced by all compounds. Inhibition of invasion induced by all three compounds at 50 µM was associated with the down-regulation of MMP-2, while none of the compounds tested significantly affected the expression levels of MMP-9, TIMP-1 or TIMP-2 at this concentration. Following exposure to media containing 50 µM R- or S-equol for 48-h intracellular concentrations of R- and S-equol were 4.38 ± 1.17 and 3.22 ± 0.47 nM, respectively. CONCLUSION: Daidzein, R- and S-equol inhibit the invasion of MDA-MB-231 human breast cancer cells in part via the down-regulation of MMP-2 expression, with equipotent effects observed for the parent isoflavone daidzein and the equol enantiomers.

Chickpea (Cicer arietinum) and other plant-derived protease inhibitor concentrates inhibit breast and prostate cancer cell proliferation in vitro.

The soybean-derived protease inhibitor, Bowman-Birk inhibitor (BBI), is currently showing great promise as a novel cancer chemopreventive agent. In contrast to the wealth of research conducted on this compound, the anticancer effects of protease inhibitors isolated from other leguminous sources have received limited attention. In the current study, 7 protease inhibitor concentrates (PICs) were isolated from various leguminous sources (including soybean) and characterized. The effects of PICs on the proliferation of breast and prostate cancer cells were investigated in vitro. Chickpea PIC significantly inhibited the viability of MDA-MB-231 breast cancer and PC-3 and LNCaP prostate cancer cells at all concentrations tested (25-400 µg/ml). In addition, kidney bean (200, 400 µg/ml), soybean (50, 100 µg/ml), and mungbean (100, 200 µg/ml) PICs inhibited LNCaP cell viability. These findings suggest that leguminous PICs may possess similar anticancer properties to that of soybean BBI and deserve further study as possible chemopreventive agents.

Impact of polydextrose on the faecal microbiota: a double-blind, crossover, placebo-controlled feeding study in healthy human subjects.

In this placebo-controlled, double-blind, crossover human feeding study, the effects of polydextrose (PDX; 8 g/d) on the colonic microbial composition, immune parameters, bowel habits and quality of life were investigated. PDX is a complex glucose oligomer used as a sugar replacer. The main goal of the present study was to identify the microbial groups affected by PDX fermentation in the colon. PDX was shown to significantly increase the known butyrate producer Ruminococcus intestinalis and bacteria of the Clostridium clusters I, II and IV. Of the other microbial groups investigated, decreases in the faecal Lactobacillus-Enterococcus group were demonstrated. Denaturing gel gradient electrophoresis analysis showed that bacterial profiles between PDX and placebo treatments were significantly different. PDX was shown to be slowly degraded in the colon, and the fermentation significantly reduced the genotoxicity of the faecal water. PDX also affected bowel habits of the subjects, as less abdominal discomfort was recorded and there was a trend for less hard and more formed stools during PDX consumption. Furthermore, reduced snacking was observed upon PDX consumption. This study demonstrated the impact of PDX on the colonic microbiota and showed some potential for reducing the risk factors that may be associated with colon cancer initiation.

Assessing the in vivo data on low/no-calorie sweeteners and the gut microbiota.

Low/no-calorie sweeteners (LNCS) are continually under the spotlight in terms of their safety and benefits; in 2014 a study was published linking LNCS to an enhanced risk of glucose intolerance through modulation of the gut microbiota. In response, an in-depth review of the literature was undertaken to evaluate the major contributors to potential changes in the gut microbiota and their corresponding sequelae, and to determine if consuming LNCS (e.g., acesulfame K, aspartame, cyclamate, neotame, saccharin, sucralose, steviol glycosides) contributes to changes in the microbiome based on the data reported in human and animal studies. A few rodent studies with saccharin have reported changes in the gut microbiome, but primarily at high doses that bear no relevance to human consumption. This and other studies suggesting an effect of LNCS on the gut microbiota were found to show no evidence of an actual adverse effect on human health. The sum of the data provides clear evidence that changes in the diet unrelated to LNCS consumption are likely the major determinants of change in gut microbiota numbers and phyla, confirming the viewpoint supported by all the major international food safety and health regulatory authorities that LNCS are safe at currently approved levels.

Modelling the role of microbial p-cresol in colorectal genotoxicity.

Background: A greater understanding of mechanisms explaining the interactions between diet and the gut microbiota in colorectal cancer is desirable. Genotoxic microbial metabolites present in the colon may be implicated in carcinogenesis and potentially influenced by diet. Aims: We hypothesised that microbial p-cresol is a colonic genotoxin and set out to model potential exposures in the colon and the effects of these exposures on colonic cells. Methods: Batch culture fermentations with human faecal inoculate were used to determine the synthesis of p-cresol and other metabolites in response to various substrates. The fermentation supernatants were evaluated for genotoxicity and the independent effects of p-cresol on colonic cells were studied in vitro. Results: In batch culture fermentation, supplementary protein increased the synthesis of phenols, indoles and p-cresol, whereas supplementary fructoligosaccharide (FOS) increased the synthesis of short chain fatty acids. The p-cresol was the greatest predictor of genotoxicity against colonocytes in the fermentation supernatants. Spiking fermentation supernatants with exogenous p-cresol further increased DNA damage, and independently p-cresol induced DNA damage in a dose-dependent manner against HT29 and Caco-2 cells and influenced cell cycle kinetics. Conclusions: In the colon p-cresol may reach physiologically significant concentrations which contribute to genotoxic exposures in the intestinal lumen, p-cresol production may be attenuated by substrate, and therefore diet, making it a potential modifiable biomarker of genotoxicity in the colon.

Inhibitory effects of olive oil phenolics on invasion in human colon adenocarcinoma cells in vitro.

Studies in human, animal and cellular systems suggest that phenols from virgin olive oil are capable of inhibiting several stages in carcinogenesis, including metastasis. The invasion cascade comprises cell attachment to extracellular matrix components or basement membrane, degradation of basement membrane by proteolytic enzymes and migration of cells through the modified matrix. In the present study, we investigated the effect of phenolics extracted from virgin olive oil (OVP) and its main constituents: hydroxytyrosol (3,4-dihydroxyphenylethanol), tyrosol (p-hydroxyphenylethanol), pinoresinol and caffeic acid. The effects of these phenolics were tested on the invasion of HT115 human colon carcinoma cells in a Matrigel invasion assay. OVP and its compounds showed different dose-related anti-invasive effects. At 25 microg/ml OVP and equivalent doses of individual compounds, significant anti-invasive effects were seen in the range of 45-55% of control. Importantly, OVP, but not the isolated phenolics, significantly reduced total cell number in the Matrigel invasion assay. There were no significant effects shown on cell viability, indicating the reduction of cell number in the Matrigel invasion assay was not due to cytotoxicity. There were also no significant effects on cell attachment to plastic substrate, indicating the importance of extracellular matrix in modulating the anti-invasive effects of OVP. In conclusion, the results from this study indicate that phenols from virgin olive oil have the ability to inhibit invasion of colon cancer cells and the effects may be mediated at different levels of the invasion cascade.

Watercress supplementation in diet reduces lymphocyte DNA damage and alters blood antioxidant status in healthy adults.

BACKGROUND: Cruciferous vegetable (CV) consumption is associated with a reduced risk of several cancers in epidemiologic studies. OBJECTIVE: The aim of this study was to determine the effects of watercress (a CV) supplementation on biomarkers related to cancer risk in healthy adults. DESIGN: A single-blind, randomized, crossover study was conducted in 30 men and 30 women (30 smokers and 30 nonsmokers) with a mean age of 33 y (range: 19-55 y). The subjects were fed 85 g raw watercress daily for 8 wk in addition to their habitual diet. The effect of supplementation was measured on a range of endpoints, including DNA damage in lymphocytes (with the comet assay), activity of detoxifying enzymes (glutathione peroxidase and superoxide dismutase) in erythrocytes, plasma antioxidants (retinol, ascorbic acid, alpha-tocopherol, lutein, and beta-carotene), plasma total antioxidant status with the use of the ferric reducing ability of plasma assay, and plasma lipid profile. RESULTS: Watercress supplementation (active compared with control phase) was associated with reductions in basal DNA damage (by 17%; P = 0.03), in basal plus oxidative purine DNA damage (by 23.9%; P = 0.002), and in basal DNA damage in response to ex vivo hydrogen peroxide challenge (by 9.4%; P = 0.07). Beneficial changes seen after watercress intervention were greater and more significant in smokers than in nonsmokers. Plasma lutein and beta-carotene increased significantly by 100% and 33% (P < 0.001), respectively, after watercress supplementation. CONCLUSION: The results support the theory that consumption of watercress can be linked to a reduced risk of cancer via decreased damage to DNA and possible modulation of antioxidant status by increasing carotenoid concentrations.

Hypothesis about mechanisms through which nicotine might exert its effect on the interdependence of inflammation and gut barrier function in ulcerative colitis.

Ulcerative colitis (UC) is characterized by impairment of the epithelial barrier and the formation of ulcer-type lesions, which result in local leaks and generalized alterations of mucosal tight junctions. Ultimately, this results in increased basal permeability. Although disruption of the epithelial barrier in the gut is a hallmark of inflammatory bowel disease and intestinal infections, it remains unclear whether barrier breakdown is an initiating event of UC or rather a consequence of an underlying inflammation, evidenced by increased production of proinflammatory cytokines. UC is less common in smokers, suggesting that the nicotine in cigarettes may ameliorate disease severity. The mechanism behind this therapeutic effect is still not fully understood, and indeed it remains unclear if nicotine is the true protective agent in cigarettes. Nicotine is metabolized in the body into a variety of metabolites and can also be degraded to form various breakdown products. It is possible these metabolites or degradation products may be the true protective or curative agents. A greater understanding of the pharmacodynamics and kinetics of nicotine in relation to the immune system and enhanced knowledge of gut permeability defects in UC are required to establish the exact protective nature of nicotine and its metabolites in UC. This review suggests possible hypotheses for the protective mechanism of nicotine in UC, highlighting the relationship between gut permeability and inflammation, and indicates where in the pathogenesis of the disease nicotine may mediate its effect.

Nutritional value of edible seaweeds.

This article presents information on the nutritional aspects of seaweeds in terms of fiber, mineral content, fats and lipids, vitamin contents, and components that have a confirmed and investigated nutritional effect. The nutrient levels of seaweeds are also shown in comparison to currently applicable reference nutrient intakes or guideline daily amounts of nutrients and are contrasted with terrestrial foodstuffs with respect to selected nutrients. For the purpose of comparison, a sample serving size of 8 g dry weight of seaweed is used to illustrate the potential contribution of seaweeds to the diet.

In vitro approaches to assess the effects of açai (Euterpe oleracea) digestion on polyphenol availability and the subsequent impact on the faecal microbiota.

A considerable proportion of dietary plant-polyphenols reach the colon intact; determining the effects of these compounds on colon-health is of interest. We hypothesise that both fibre and plant polyphenols present in açai (Euterpe oleracea) provide prebiotic and anti-genotoxic benefits in the colon. We investigated this hypothesis using a simulated in vitro gastrointestinal digestion of açai pulp, and a subsequent pH-controlled, anaerobic, batch-culture fermentation model reflective of the distal region of the human large intestine. Following in vitro digestion, 49.8% of the total initial polyphenols were available. In mixed-culture fermentations with faecal inoculate, the digested açai pulp precipitated reductions in the numbers of both the Bacteroides-Prevotella spp. and the Clostridium-histolyticum groups, and increased the short-chain fatty acids produced compared to the negative control. The samples retained significant anti-oxidant and anti-genotoxic potential through digestion and fermentation. Dietary intervention studies are needed to prove that consuming açai is beneficial to gut health.

Variability in fecal water genotoxicity, determined using the Comet assay, is independent of endogenous N-nitroso compound formation attributed to red meat consumption.

Red meat consumption causes a dose-dependent increase in fecal apparent total N-nitroso compounds (ATNC). The genotoxic effects of these ATNCs were investigated using two different Comet assay protocols to determine the genotoxicity of fecal water samples. Fecal water samples were obtained from two studies of a total of 21 individuals fed diets containing different amounts of red meat, protein, heme, and iron. The first protocol incubated the samples with HT-29 cells for 5 min at 4 degrees C, whereas the second protocol used a longer exposure time of 30 min and a higher incubation temperature of 37 degrees C. DNA strand breaks were quantified by the tail moment (DNA in the comet tail multiplied by the comet tail length). The results of the two Comet assay protocols were significantly correlated (r = 0.35, P = 0.003), however, only the second protocol resulted in detectable levels of DNA damage. Inter-individual effects were variable and there was no effect on fecal water genotoxicity by diet (P > 0.20), mean transit time (P = 0.588), or weight (P = 0.705). However, there was a highly significant effect of age (P = 0.019). There was no significant correlation between concentrations of ATNCs in fecal homogenates and fecal water genotoxicity (r = 0.04, P = 0.74). ATNC levels were lower in fecal water samples (272 microg/kg) compared to that of fecal homogenate samples (895 microg/kg) (P < 0.0001). Failure to find dietary effects on fecal water genotoxicity may therefore be attributed to individual variability and low levels of ATNCs in fecal water samples.

In vitro antioxidant activity and antigenotoxicity of 5-n-alkylresorcinols.

Incubation with 5-n-alkylresorcinols (chain lengths C15:0, C17:0, C19:0, C21:0, and C23:0) increased the self-protection capacity of HT29 human colon cancer cells against DNA damage induced by hydrogen peroxide and genotoxic fecal water samples using comet assay (single-cell gel electrophoresis assay). The alkylresorcinols did not exert potent antioxidant activity in the FRAP (ferric reduction ability of plasma) and DPPH (2,2-diphenyl-1-picrylhydrazyl) radical assays. However they were able to significantly inhibit copper-mediated oxidation of human LDL (low-density lipoprotein) in vitro, and pentadecylresorcinol at 25 micromol/L increased lag time by 65 min. The results show that alkylresorcinols have antigenotoxic and antioxidant activity under in vitro conditions.

Consumption of a flavonoid-rich açai meal is associated with acute improvements in vascular function and a reduction in total oxidative status in healthy overweight men.

BACKGROUND: Açai (Euterpe oleracea) is a polyphenol-rich fruit marketed as beneficial for health. Experimental data showing improvements in health markers arising from açai consumption in humans is limited. OBJECTIVE: The objective of the present study was to investigate the effect of açai consumption on acute changes in vascular function and on other disease risk markers, including postprandial plasma insulin, glucose, and oxidative stress. DESIGN: Twenty-three healthy male volunteers, aged 30-65 y and with a body mass index (in kg/m2) of 25-30, completed a randomized, controlled, high-fat challenge, double-blind, crossover, acute dietary intervention trial. The volunteers consumed either an açai-based smoothie (AS) or a macronutrient-matched control smoothie (PS) together with a high-fat breakfast meal challenge. The primary endpoint was the assessment of endothelial function in the brachial artery by flow-mediated dilatation (FMD). RESULTS: The acute consumption of an AS containing 694 mg total phenolics improved vascular function, with postprandial increases in FMD from baseline of 1.4% at 2 h compared with 0.4% after consumption of the PS (P = 0.001) and increases at 6 h of 0.8% for the AS compared with -0.3% for the PS (P < 0.001). There was also a significantly lower incremental area under the curve (iAUC) for total peroxide oxidative status after açai consumption relative to the control. No significant changes were observed in blood pressure, heart rate, or postprandial glucose response. However, the first postprandial insulin peak (after breakfast) and the iAUC for insulin were elevated for the AS relative to the PS. CONCLUSIONS: In this acute study in overweight men, açai consumption was associated with improvements in vascular function, which may lower the risk of a cardiovascular event. Future intervention studies, perhaps with a chronic design, in wider populations and with other biomarkers of disease risk are needed to fully elucidate the benefits of açai to health. This trial was registered at clinicaltrials.gov as NCT02292329.

Components of olive oil and chemoprevention of colorectal cancer.

Olive oil contains a vast range of substances such as monounsaturated free fatty acids (e.g., oleic acid), hydrocarbon squalene, tocopherols, aroma components, and phenolic compounds. Higher consumption of olive oil is considered the hallmark of the traditional Mediterranean diet, which has been associated with low incidence and prevalence of cancer, including colorectal cancer. The anticancer properties of olive oil have been attributed to its high levels of monounsaturated fatty acids, squalene, tocopherols, and phenolic compounds. Nevertheless, there is a growing interest in studying the role of olive oil phenolics in carcinogenesis. This review aims to provide an overview of the relationship between olive oil phenolics and colorectal cancer, in particular summarizing the epidemiologic, in vitro, cellular, and animal studies on antioxidant and anticarcinogenic effects of olive oil phenolics.

Modulation of the microbial ecology of the human colon by probiotics, prebiotics and synbiotics to enhance human health: an overview of enabling science and potential applications.

The application of probiotics and prebiotics to the manipulation of the microbial ecology of the human colon has recently seen many scientific advances. The sequencing of probiotic genomes is providing a wealth of new information on the biology of these microorganisms. In addition, we are learning more about the interactions of probiotics with human cells and with pathogenic bacteria. An alternative means of modulating the colonic microbial community is by the use of prebiotic oligosaccharides. Increasing knowledge of the metabolism of prebiotics by probiotics is allowing us to consider specifically targeting such dietary intervention tools at specific population groups and specific disease states.

Influence of 10 wk of soy consumption on plasma concentrations and excretion of isoflavonoids and on gut microflora metabolism in healthy adults.

BACKGROUND: Little information is currently available on the role of the gut microflora in modulating isoflavone bioavailability or on sex differences in isoflavone metabolism and bioavailability. OBJECTIVE: We sought to determine whether chronic soy consumption influences isoflavone bioavailability as judged by plasma isoflavone concentrations and modified gut microflora activities [beta-glucoside hydrolysis and equol and O-desmethylangolensin (O-DMA) production]. We also examined whether sex differences in isoflavone metabolism exist. DESIGN: A randomized, parallel, controlled study design was used to compare a high-soy diet (104 +/- 24 mg total isoflavones/d) with a low-soy diet (0.54 +/- 0.58 mg total isoflavones/d) in 76 healthy young adults for 10 wk. RESULTS: Concentrations of isoflavones and their gut microflora metabolites in the plasma, urine, and feces were significantly higher in the subjects who consumed the high-soy diet than in those who consumed the low-soy diet. Concentrations of O-DMA in plasma and urine were higher in the men than in the women. Fecal bacteria from subjects consuming both diets could convert daidzein to equol ex vivo. Fecal beta-glucosidase activity was significantly higher in the subjects who consumed the high-soy diet than in those who consumed the low-soy diet. CONCLUSIONS: Although interindividual variation in isoflavone metabolism was high, intraindividual variation was low. Only concentrations of O-DMA in plasma and urine appeared to be influenced by sex. Chronic soy consumption does not appear to induce many significant changes to the gut metabolism of isoflavones other than higher beta-glucosidase activity.