Most of the investigations for an alternative medicinal treatment on atherosclerosis have been focused on natural or dietary compounds including phytochemicals. So far, few studies regarding anti-atherosclerotic small peptides except for tetrapeptide of Lys-Arg-Glu-Ser have been reported. The present study was, thus, to investigate whether dipeptide Trp-His, which is one of vasodilating small peptides, could reduce atherosclerotic lesions in apo E-deficient mice fed a high-fat diet. The animal study involved a 9-week-successive administration of Trp-His at a dose of 0, 10 or 100 mg/kg per d. After 9-week administration, en face analyses provided the first direct evidence that the atherosclerotic lesion area was significantly reduced by 27 and 38 % for Trp-His dosed at 10 and 100 mg/kg per d, respectively, compared with the control group. Administration of Trp-His did not affect growth parameters such as body weight and feeding efficiency (P>0·1). Total serum cholesterol and HDL-cholesterol as well as lipid profiles in the liver did not differ between the tested groups. Taken together, the anti-atherosclerotic effect of dipeptide Trp-His should be addressed into physiological functions of bioactive peptides, in which the dipeptide may elicit the power by alternative mechanism(s), not by the regulation of lipid metabolism.

Major surgery induces an immuno-inflammatory response accompanied by oxidative stress that may impair cellular function and delay recovery. The objective of the study was to investigate the effect of an enteral supplement, containing glutamine and antioxidants, on circulating levels of immuno-inflammatory markers after major gastrointestinal tract surgery. Patients (n 21) undergoing major gastrointestinal tract surgery were randomised in a single-centre, open-label study. The effects on circulating levels of immuno-inflammatory markers were determined on the day before surgery and on days 1, 3, 5 and 7 after surgery. Major gastrointestinal surgery increased IL-6, TNF receptor 55/60 (TNF-R55) and C-reactive protein (CRP). Surgery reduced human leucocyte antigen-DR (HLA-DR) expression on monocytes. CRP decrease was more pronounced in the first 7 d in the treatment group compared with the control group. In the treatment group, from the moment Module AOX was administered on day 1 after surgery, TNF receptor 75/80 (TNF-R75) level decreased until the third post-operative day and then stabilised, whereas in the control group the TNF-R75 level continued to increase. The results of the present pilot study suggest that enteral nutrition enriched with glutamine and antioxidants possibly moderates the immuno-inflammatory response (CRP, TNF-R75) after surgery.

The Survey of Sugar Intake among Children in Scotland was carried out in May to September 2006. The present study aimed to identify dietary patterns in school-aged children from the survey and investigate associations with socio-economic factors, obesity and physical activity. Habitual diet was assessed using the Scottish Collaborative Group FFQ. Height and weight were measured by trained fieldworkers. A total of 1233 FFQ were available for analysis. Dietary patterns were identified by age (5–11 and 12–17 years) and sex using principal components analysis. Associations between factor scores and socio-economic status, education level of the main food provider, physical activity levels and BMI category (based on UK 1990 charts) were examined. Three dietary patterns were identified in each age and sex group. ‘Healthier’ patterns loading highly for fruit and vegetables were significantly associated with higher socio-economic status and higher education levels of the main food provider whereas more ‘unhealthy’ patterns (‘snacks’ and ‘puddings’) were associated with lower socio-economic status and lower education levels of the main food provider. There was no consistent association between dietary patterns and BMI group or time spent in physical activity. However, inactivity (screen time) was inversely associated with ‘healthier’ patterns in all age and sex groups and positively associated with ‘puddings’ and ‘snacks’ in girls aged 5–11 years. Clear dietary patterns can be identified in school-age children in Scotland, which are consistently related to socio-economic factors and inactivity. This has implications for targeting health promotion at subgroups in terms of lifestyle changes required.

Gut bacteria contribute to energy conservation in man through their ability to ferment unabsorbed carbohydrate. The present study examined the composition of predominant faecal microbiota in obese and non-obese children. The participants (n 28) aged 11–14 years provided fresh faecal samples and completed a dietary survey consisting of 24 h diet recall and a FFQ of commonly used foods taken over the previous 3 months. Faecal bacteria were quantitated by real-time PCR using primers targeted at 16S rDNA. Of the participants, fifteen (seven female) were obese, with median BMI-for-age at the 99th percentile (range 97 to>99) while thirteen participants (seven female) were normal weight, with median BMI-for age being at the 50th percentile (range 1–85). Consumption of energy, carbohydrates, fat and protein was not significantly different between the obese and non-obese participants. There was no significant difference between the two groups in faecal levels of Bacteroides–Prevotella, Bifidobacterium species, Lactobacillus acidophilus group or Eubacterium rectale. Levels of Faecalibacterium prausnitzii were significantly higher in obese children than in non-obese participants (P = 0·0253). We concluded that the finding of increased numbers of F. prausnitzii in the faeces of obese children in south India adds to the growing information on alterations in faecal microbiota in obesity.

It has been demonstrated that intact plasma alkylresorcinols (AR) and urinary AR metabolites could be used as biomarkers of whole-grain intake. Thereafter, we developed the method for the plasma AR metabolites, which is more convenient and requires less sample pretreatment than the analysis of intact plasma AR. The aim of the present study is to evaluate whether AR metabolites measured in plasma, in the same population, could also be considered as useful biomarkers of cereal fibre. Fifty-six women were recruited in a cross-sectional and observational study. Dietary intake (5-d record) and plasma AR metabolites (3,5-dihydroxybenzoic acid, DHBA; 3-(3,5-dihydroxyphenyl)-1-propanoic acid, DHPPA) were measured. The relationship between plasma AR metabolites and cereal fibre intake was examined using partial correlation and stepwise regression. Cereal fibre intake correlated significantly with plasma DHBA (r 0·411; P = 0·002) and DHPPA (r 0·463; P = 0·000) even after adjustment for BMI and age. Thus, plasma AR metabolites correlate with cereal fibre intake as noted with plasma intact AR and urinary AR metabolites. We observed that plasma DHPPA was the independent predictor of cereal fibre intake, explaining 18 % of the variance (adjusted r2 0·176; P = 0·002). In epidemiological screening, it might be easier to obtain and to collect plasma than urine samples. In addition, the plasma AR metabolites half-life seems longer than those of intact plasma AR, and their measurements are more convenient, and faster. Thus, sum of plasma AR metabolites and more specifically plasma DHPPA seems to be good and specific biomarkers of cereal fibre intake.

Zn and DHA have putative neuroprotective effects and these two essential nutrients are known to interact biochemically. We aimed to identify novel protein candidates that are differentially expressed in human neuronal cell line M17 in response to Zn and DHA that would explain the molecular basis of this interaction. Two-dimensional gel electrophoresis and MS were applied to identify major protein expression changes in the protein lysates of human Ml7 neuronal cells that had been grown in the presence and absence of Zn and DHA. Proteomic findings were further investigated using Western immunoblot and real-time PCR analyses. Four protein spots, which had significant differential expression, were identified and selected for in-gel trypsin digestion followed by matrix-assisted laser desorption ionisation MS analysis. The resultant peptide mass fingerprint for each spot allowed their respective identities to be deduced. Two human histone variants H3 and H4 were identified. Both H3 and H4 were downregulated by Zn in the absence of DHA (Zn effect) and upregulated by DHA (DHA effect) in the presence of Zn (physiological condition). These proteomic findings were further supported by Western immunoblot and real-time PCR analyses using H3- and H4-specific monoclonal antibodies and oligonucleotide primers, respectively. We propose that dietary Zn and DHA cause a global effect on gene expression, which is mediated by histones. Such novel information provides possible clues to the molecular basis of neuroprotection by Zn and DHA that may contribute to the future treatment, prevention and management of neurodegenerative diseases such as Alzheimer's disease.

Personal food preferences can either enhance or suppress the development of obesity and the selection and proportion of macronutrients in the diet seem to have a heritable component. In the present study, we therefore focused on dietary composition as a specific trait related to obesity and we determined whether genetic variations in leptin (LEP), LEP receptor (LEPR), adiponectin (ADIPOQ), IL-6 and pro-opiomelanocortin (POMC) underlie specific native food preferences and obesity-related anthropometric parameters. The total of 409 individuals of Czech Caucasian origin were enrolled into the present study and 7 d food records were obtained from the study subjects along with selected anthropometric measurements. In a subset of study subjects, plasma levels of ADIPOQ, LEP and soluble LEPR were measured. Independently of the BMI of the individuals, common variations in LEP and LEPR genes were associated with specific eating patterns, mainly with respect to timing of eating. The LEP+19A/G polymorphism served as an independent predictor for BMI, percentage of body fat and skinfold thickness and significantly affected the time structure of the daily energy intake. The POMC RsaI polymorphism was associated with percentage of body fat. The ADIPOQ 45 T/G polymorphism was associated with the thickness of the subscapular skinfold. The LEPR Gln223Arg polymorphism was associated with multiple parameters, including diastolic blood pressure, meal sizes during the day and plasma ADIPOQ levels. In a separate analysis, soluble leptin receptor (sObR) plasma levels and LEP:sObR ratio were significantly correlated with systolic blood pressure (β = − 0·66, P = 0·002; β = − 1·23, P = 0·02) and sObR plasma levels also served as an independent predictor for diastolic blood pressure (β = − 0·50; P = 0·04). To conclude, we report common allelic variants associated with specific feeding behaviour and obesity-related anthropometric traits. Moreover, we identified allelic variants that significantly influence the time structure of food intake during the day.

Fermentation of dietary fibre by the gut microflora may enhance levels of SCFA, which are potentially chemoprotective against colon cancer. Functional food containing wheat aleurone may prevent cancer by influencing cell cycle and cell death. We investigated effects of fermented wheat aleurone on growth and apoptosis of HT29 cells. Wheat aleurone, flour and bran were digested and fermented in vitro. The resulting fermentation supernatants (fs) were analysed for their major metabolites (SCFA, bile acids and ammonia). HT29 cells were treated for 24–72 h with the fs or synthetic mixtures mimicking the fs in SCFA, butyrate or deoxycholic acid (DCA) contents, and the influence on cell growth was determined. Fs aleurone was used to investigate the modulation of apoptosis and cell cycle. The fermented wheat samples contained two- to threefold higher amounts of SCFA than the faeces control (blank), but reduced levels of bile acids and increased concentrations of ammonia. Fs aleurone and flour equally reduced cell growth of HT29 more effectively than the corresponding blank and the SCFA mixtures. The EC50 (48 h) ranged from 10 % (flour) to 19 % (blank). Markedly after 48 h, fs aleurone (10 %) significantly induced apoptosis and inhibited cell proliferation by arresting the cell cycle in the G0/G1 phase. In conclusion, fermentation of wheat aleurone results in a reduced level of tumour-promoting DCA, but higher levels of potentially chemopreventive SCFA. Fermented wheat aleurone is able to induce apoptosis and to block cell cycle – two essential markers of secondary chemoprevention.

The present study aimed to investigate the role of Zn alone and in the presence of ascorbic acid (AA) and folic acid (FA) in albumin glycation. Glycation was performed by incubations of bovine serum albumin with glucose at 37°C along with Zn, AA or FA separately and Zn+AA or Zn+FA for 150 d. Glycation-mediated modifications were monitored as fluorescence of advanced glycation endproducts, carbonyl formation, β aggregation (thioflavin T and Congo red dyes), albumin-bound Zn, thiol groups and glycated aggregate's toxicity in HepG2 cells. Zn inhibited glycation and β aggregation, probably due to observed higher protein-bound Zn. It also protected protein thiols and increased cell survival. AA and FA enhanced glycation, which was lowered in Zn-co-incubated samples. FA increased albumin-bound Zn and showed maximum cell survival. Although these results warrant further in vivo investigation, the present data help in the understanding of the interplay of Zn with micronutrients in albumin glycation.

We investigated the effects of a high-cholesterol (HC) diet administered long term (25 or 55 weeks) on metabolic disorders including hepatic damage in mice. The mice were fed the HC diet (15 % milk fat, 1·5 % cholesterol and 0·1 % cholic acid, w/w) for 25 or 55 weeks. Body and adipose tissue weights were similar to those of mice fed a control diet. Consumption of the HC diet long term resulted in hypercholesterolaemia, hepatic steatosis and gallstones. In addition, focal nodular hyperplasia (FNH) and mild fibrosis of the liver developed in all mice fed the HC diet for 55 weeks. Plasma levels of monocyte chemoattractant protein (MCP)-1 were elevated, and the level of hepatic platelet-derived growth factor (PDGF)-B protein was increased in mice fed the HC diet compared with those fed the control diet. Thus, it seems likely that the liver fibrosis and FNH caused by the long-term consumption of a HC diet may be partly due to an elevation of plasma MCP-1 and hepatic PDGF expression.

Chronic diseases that are typical of adulthood may originate in intra-uterine life through inadequate fetal development. The present epidemiological cohort study of 506 healthy children aged 5–8 years evaluated the relationship between birth weight and insulin resistance in an age group that has been assessed in few similar studies. Insulin concentration was determined by chemiluminescence and insulin resistance by the homeostasis model assessment (HOMA). Blood glucose, total cholesterol and fractions (LDL cholesterol and HDL cholesterol) and TAG concentrations were determined by automated enzymatic methods. Linear regression analysis investigated the relationship between birth weight (assessed as a continuous variable and in three categories: small for gestational age, SGA; adequate for gestational age and large for gestational age) and the HOMA index, using backward stepwise selection and biological models to explain the causal pathway of the relationship. There were negative associations between birth weight (P < 0·001), SGA (P = 0·027) and the HOMA index, and a positive association between waist circumference (P < 0·001) and the HOMA index. Considering the significant associations between birth weight and waist circumference (P < 0·001) and waist circumference and insulin resistance (P < 0·001), we can probably suspect that lower birth weight is a common cause of higher waist circumference and insulin resistance. In summary, the results of the present study showed increased insulin resistance in apparently healthy, young children, who had lower weight at birth and higher measurements of waist circumference. There is a need to develop public health policies that adopt preventive measures to promote adequate maternal-fetal and child development and enable early diagnosis of metabolic abnormalities.

Polysaccharides are one of the most potent mushroom-derived substances exhibiting anti-inflammatory and immunomodulatory properties. The aims of the present study were to determine whether orally administered glucans from the edible mushroom Pleurotus pulmonarius could attenuate or prevent the development of experimental colitis in mice. Colonic inflammation was induced in mice by treatment with 3·5 % dextran sulfate sodium (DSS) for 18 d. Before or after DSS administration, mice were given hot water solubles (HWS) or mycelium extract (ME) (2 or 20 mg per mouse) daily in their food. Colonic damage was macroscopically and histologically evaluated. Inflammation was assessed by changes in colon length, TNF-α levels released by colonic samples in organ culture and myeloperoxidase (MPO) activity. mRNA levels of pro-inflammatory (IL-1β) and anti-inflammatory (IL-10) cytokines in colonic samples were determined by quantitative real-time RT-PCR. P. pulmonarius glucans attenuated and prevented the development of symptoms associated with DSS-induced colitis. High doses of HWS and ME blocked colon shortening, suppressed MPO activity and improved macroscopic score in all treatment groups. In addition, histological damage from colitis was reduced by HWS and ME at all doses. The tissue levels of TNF-α protein were significantly decreased and correlated with degree of inflammation and macroscopic score. All treatments significantly attenuated the increased DSS-mediated expression levels of IL-1β. We conclude that the different glucan preparations (HWS or ME) harvested from P. pulmonarius when orally administered to DSS-treated mice attenuate the development of colonic inflammation, suggesting putative clinical utility for these extracts in the treatment of colitis.

A new in vitro fermentation model with immobilised infant faecal microbiota simulating the proximal colon of a formula-fed baby was developed and used to test the effects of known prebiotic fructans. Intestinal fermentation, based on a previously developed colonic fermentation model, using a new feeding medium simulating a formula-fed infant ileal chyme, was carried out for seventy-one consecutive days divided into four stabilisation periods intercalated with four prebiotic treatment periods. At the end of the first stabilisation period, total bacterial concentration in colonised beads and in faecal sample was similar, metabolite concentrations returned to stabilisation values after each treatment period. As expected, the four prebiotic treatments significantly increased the bifidobacterial populations, whereas they decreased bacteroides and clostridia. No difference was observed in the prebiotic effect of these substrates selected. The treatments significantly increased total production of SCFA and decreased ammonia compared to stabilisation periods. Long-term stability of the system together with the reproducibility of the known prebiotic effects highlights the potential of the present model to quantify and compare the effects of different substrates in a formula-fed infant microbiota within the same fermentation experiment.

Evidence from observational, animal and human studies supports a role for soya protein and its isoflavones in the improvement of glycaemic control in type 2 diabetes. The objective of the present study was to determine the effect of isoflavone-rich soya protein on markers of glycaemic control in adults with type 2 diabetes. Using a randomised, crossover, double-blind, placebo-controlled design, adults with diet-controlled type 2 diabetes (n 29) consumed soya protein isolate (SPI) and milk protein isolate (MPI) for 57 d each separated by a 4-week washout. Blood was collected on days 1 and 57 of each treatment period for analysis of fasting HbA1C, and fasting and postprandial glucose, insulin and calculated indices of insulin sensitivity and resistance. Urine samples of 24 h were collected at the end of each treatment period for analysis of isoflavones. Urinary isoflavone excretion was significantly greater following consumption of SPI compared with MPI, and 20·7 % of the subjects (n 6) were classified as equol excretors. SPI consumption did not significantly affect fasting or postprandial glucose or insulin, fasting HbA1C, or indices of insulin sensitivity and resistance. These data do not support a role for soya protein in the improvement of glycaemic control in adults with diet-controlled type 2 diabetes and contribute to a limited literature of human studies on the effects of soya protein on the management of type 2 diabetes.

Type 2 diabetes is associated with a higher cardiovascular risk and there has been a growing interest in using dietary intervention to improve lipid profile and glucose control. The present work aims at analysing the effects of the enrichment of a normal diet with β-glucan (3·5 g/d) in free-living type 2 diabetic subjects for 2 months, using a palatable soup. This trial was a parallel, placebo-controlled, double-blinded randomised study performed in fifty-three type 2 diabetic subjects. During a 3-week run-in period, subjects daily consumed a ready meal control soup (without β-glucan). For the following 8 weeks, subjects were randomly assigned to consume daily either a control soup or a β-glucan soup. Changes in lipid profile (total cholesterol (TC), HDL- and LDL-cholesterol (HDLc and LDLc), apo B and TAG) and in glucose control (HbA1c and fasting glucose) were measured. There was no significant alteration in lipid profile in the two groups (TC, HDLc, LDLc and apo B). TAG decreased significantly in the β-glucan group compared with the control group ( − 0·12 (sd 0·38) v. 0·12 (sd 0·44) mmol/l, P = 0·03). HbA1c and fasting glucose were not reduced in any group. A single daily ingestion of 3·5 g β-glucan, as required by official dietary recommendations, for 8 weeks did not change the lipid profile and HbA1c in type 2 diabetic subjects. To improve the metabolic profile of type 2 diabetic subjects in the long term, the quantity, the food vectors and the tolerability of β-glucan products may be re-evaluated.

Diets rich in flavonoids may reduce the risk of developing colorectal cancer. Flavonoids are widely distributed in foods of plant origin, though in the UK tea is the main dietary source. Our objective was to evaluate any independent associations of total dietary and non-tea intake of four flavonoid subclasses and the risk of developing colorectal cancer in a tea-drinking population with a high colorectal cancer incidence. A population-based case–control study (264 cases with histologically confirmed incident colorectal cancer and 408 controls) was carried out. Dietary data gathered by FFQ were used to calculate flavonoid intake. Adjusted OR and 95 % CI were estimated by logistic regression. No linear association between risk of developing colorectal cancer and total dietary flavonol, procyanidin, flavon-3-ol or flavanone intakes was found, but non-tea flavonol intake was inversely associated with colorectal cancer risk (OR 0·6; 95 % CI 0·4, 1·0). Stratification by site of cancer and assessment of individual flavonols showed a reduced risk of developing colon but not rectal cancer with increasing non-tea quercetin intake (OR 0·5; 95 % CI 0·3, 0·8; Ptrend < 0·01). We concluded that flavonols, specifically quercetin, obtained from non-tea components of the diet may be linked with reduced risk of developing colon cancer.

Migration to the UK is associated with higher incidence of stroke in African populations. A low folate status has been associated with increased risk of stroke, likely to be mediated through raised plasma homocysteine concentrations. We conducted a cross-sectional study to compare blood folate and homocysteine concentrations in eighty healthy Ghanaian migrants living in London matched by sex, age and occupation to 160 individuals from an urban population in Accra, Ghana. Folate intake was determined using three 24 h recalls. Fasting blood samples were collected for the determination of serum and erythrocyte folate and plasma homocysteine concentrations and the methylenetetrahydrofolate reductase (MTHFR) 677C → T polymorphism. Reported mean folate intake was 20 % lower in London compared with Accra (P < 0·001). However, serum folate was 44 % higher, erythrocyte folate 30 % higher and plasma homocysteine was 26 % lower in subjects from London compared with those from Accra (P < 0·001). These differences persisted after adjusting for confounders including the MTHFR 677C → T mutation, which was rare in both populations. Although there were no associations between dietary folate intake and blood folates (P>0·05), folic acid supplement use, which was more prevalent in London than Accra (25 and 10 %, respectively, P = 0·004) was associated with erythrocyte folate in both populations (P < 0·01). The main predictors of plasma homocysteine concentrations were erythrocyte folate and male sex (P < 0·001). Findings from the present study suggest that migration from Ghana to the UK results in improvement of biomarkers of folate status despite the fact that reported dietary intake of folate was apparently lower in subjects from London.

Folate deficiency during embryogenesis is an established risk factor for neural tube defects in the fetus. An adequate folate nutritional status is also important for normal fetal growth and brain development. The aim of the present research was to study the association between folic acid use of the mother during pregnancy and child behavioural development. Within a population-based cohort, we prospectively assessed folic acid supplement use during the first trimester by questionnaire. Child behavioural and emotional problems were assessed with the Child Behaviour Checklist at the age of 18 months in 4214 toddlers. Results showed that children of mothers who did not use folic acid supplements in the first trimester had a higher risk of total problems (OR 1·44; 95 % CI 1·12, 1·86). Folic acid supplement use protected both from internalising (OR of no supplement use 1·65; 95 % CI 1·24, 2·19) and externalising problems (OR 1·45; 95 % CI 1·17, 1·80), even when adjusted for maternal characteristics. Birth weight and size of the fetal head did not mediate the association between folic acid use and child behaviour. In conclusion, inadequate use of folic acid supplements during early pregnancy may be associated with a higher risk of behavioural problems in the offspring. Folic acid supplementation in early pregnancy, aimed to prevent neural tube defects, may also reduce mental health problems in children.

Although the inverse association between coffee consumption and risk of diabetes has been reported numerous times, the role of caffeine intake in this association has remained unclear. We evaluated the consumption of coffee and other beverages and food containing caffeine in relation to the incidence of diabetes. The study participants were 5897 men and 7643 women in a community-based cohort in Takayama, Japan. Consumption of coffee, green tea, oolong tea, black tea and chocolate snacks were measured with a semi-quantitative FFQ in 1992. At the follow-up survey in 2002, the development of diabetes and the time of diagnosis were reported. To assess the association, age, smoking status, BMI, physical activity, education in years, alcohol consumption, total energy intake, fat intake and women's menopausal status were adjusted. Among men who consumed one cup per month to six cups per week and among those who consumed one cup per d or more, the associated hazard ratios were 0·69 (95 % CI 0·50, 0·97) and 0·69 (95 % CI 0·49, 0·98) compared with those who drank little to no coffee, with a P value for trend of 0·32. The hazard ratios for women with the same coffee consumption patterns were 1·08 (95 % CI 0·74, 1·60) and 0·70 (95 % CI 0·44, 1·12), with a P value for trend of 0·03. The association between estimated total caffeine intake and risk of diabetes was insignificant both among men and among women. The results imply that coffee consumption decreased the risk of developing diabetes. The protective effect may exist aside from the influence of caffeine intake.