High protein intake in early childhood is associated with obesity, suggesting possible adverse effects on other cardiometabolic outcomes. However, studies in adults have suggested beneficial effects of protein intake on blood pressure (BP) and lipid profile. Whether dietary protein intake is associated with cardiovascular and metabolic health in children is unclear. Therefore, we aimed to systematically review the evidence on the associations of protein intake with BP, insulin sensitivity and blood lipids in children. We searched the databases Medline, Embase, Cochrane Central and PubMed for interventional and observational studies in healthy children up to the age of 18 years, in which associations of total, animal and/or vegetable protein intake with one or more of the following outcomes were reported: BP; measures of insulin sensitivity; cholesterol levels; or TAG levels. In the search, we identified 6636 abstracts, of which fifty-six studies met all selection criteria. In general, the quality of the included studies was low. Most studies were cross-sectional, and many did not control for potential confounders. No overall associations were observed between protein intake and insulin sensitivity or blood lipids. A few studies suggested an inverse association between dietary protein intake and BP, but evidence was inconclusive. Only four studies examined the effects of vegetable or animal protein intake, but with inconsistent results. In conclusion, the literature, to date provides insufficient evidence for effects of protein intake on BP, insulin sensitivity or blood lipids in children. Future studies could be improved by adequately adjusting for key confounders such as energy intake and obesity.

Knowledge on the role of early nutritional stimuli as triggers of metabolic pathways in fish is extremely scarce. The objective of the present study was to assess the long-term effects of glucose injection in the yolk (early stimulus) on carbohydrate metabolism and gene regulation in zebrafish juveniles challenged with a high-carbohydrate low-protein (HC) diet. Eggs were microinjected at 1 d post-fertilisation (dpf) with either glucose (2 m) or saline solutions. Up to 25 dpf, fish were fed a low-carbohydrate high-protein (LC) control diet, which was followed by a challenge with the HC diet. Survival and growth of 35 dpf juveniles were not affected by injection or the HC diet. Glucose stimulus induced some long-term metabolic changes in the juveniles, as shown by the altered expression of genes involved in glucose metabolism. On glycolysis, the expression levels of hexokinase 1 (HK1) and phosphofructokinase-6 (6PFK) were up-regulated in the visceral and muscle tissues, respectively, of juveniles exposed to the glucose stimulus, indicating a possible improvement in glucose oxidation. On gluconeogenesis, the inhibition of the expression levels of PEPCK in fish injected with glucose suggested lower production of hepatic glucose. Unexpectedly, fructose-1,6-bisphosphatase (FBP) expression was induced and 6PFK expression reduced by glucose stimulus, leaving the possibility of a specific regulation of the FBP–6PFK metabolic cycle. Glucose metabolism in juveniles was estimated using a [14C]glucose tracer; fish previously exposed to the stimulus showed lower retention of [14C]glucose in visceral tissue (but not in muscle tissue) and, accordingly, higher glucose catabolism, in comparison with the saline group. Globally, our data suggest that glucose stimulus at embryo stage has the potential to alter particular steps of glucose metabolism in zebrafish juveniles.

It is hypothesised that during immune system activation, there is a competition for amino acids (AA) between body protein deposition and immune system functioning. The aim of the present study was to quantify the effect of immune system activation on N retention and AA metabolism in growing pigs, depending on dietary protein supply. A total of sixteen barrows received an adequate (Ad) or restricted (Res) amount of dietary protein, and were challenged at day 0 with intravenous complete Freund's adjuvant (CFA). At days − 5, 3 and 8, an irreversible loss rate (ILR) of eight AA was determined. CFA successfully activated the immune system, as indicated by a 2- to 4-fold increase in serum concentrations of acute-phase proteins (APP). Pre-challenge C-reactive protein concentrations were lower (P< 0·05) and pre- and post-challenge albumin tended to be lower in Res-pigs. These findings indicate that a restricted protein supply can limit the acute-phase response. CFA increased urinary N losses (P= 0·04) and tended to reduce N retention in Ad-pigs, but not in Res-pigs (P= 0·07). The ILR for Val was lower (P= 0·05) at day 8 than at day 3 in the post-challenge period. The ILR of most AA, except for Trp, were strongly affected by dietary protein supply and positively correlated with N retention. The correlations between the ILR and APP indices were absent or negative, indicating that changes in AA utilisation for APP synthesis were either not substantial or more likely outweighed by a decrease in muscle protein synthesis during immune system activation in growing pigs.

Acute psychological stress is positively associated with a cold/flu. The present randomised, double-blind, placebo-controlled study examined the effect of three potentially probiotic bacteria on the proportion of healthy days over a 6-week period in academically stressed undergraduate students (n 581) who received Lactobacillus helveticus R0052, Bifidobacterium longum ssp. infantis R0033, Bifidobacterium bifidum R0071 or placebo. On each day, participants recorded the intensity (scale: 0 = not experiencing to 3 = very intense) for nine cold/flu symptoms, and a sum of symptom intensity >6 was designated as a day of cold/flu. B. bifidum resulted in a greater proportion of healthy days than placebo (P≤ 0·05). The percentage of participants reporting ≥ 1 d of cold/flu during the 6-week intervention period was significantly lower with B. bifidum than with placebo (P< 0·05). There were no effects of B. infantis or L. helveticus compared with placebo on either outcome. A predictive model accounted for influential characteristics and their interactions on daily reporting of cold/flu episodes. The proportion of participants reporting a cold on any given day was lower at weeks 2 and 3 with B. bifidum and B. infantis than with placebo for the average level of stress and the most commonly reported number of hours of sleep. Daily intake of bifidobacteria provides benefit related to cold/flu outcomes during acute stress.

Dairy products are rich sources of an array of fatty acids (FA) that have been shown individually and in certain clusters to exert varying effects on cardiovascular health, for which the circulating lipid profile is a powerful biomarker. Whether the profile of these FA is reflected in blood upon short terms of intake, possibly contributing to the lipid-related health impacts of dairy products, remains to be fully established. The objectives of the present study were to assess a recommended dairy product consumption in relation to circulating FA and lipid profiles, and to evaluate certain FA in dairy fat as potential biomarkers of intake. In a free-living, multi-centre, cross-over design, 124 healthy individuals consumed 3 servings/d of commercial dairy (DAIRY; 1 % fat milk, 1·5 % fat yogurt and 34 % fat cheese) or energy-equivalent control (CONTROL; fruit and vegetable juice, cashews and a cookie) products for 4 weeks each, separated by a 4-week washout period. Plasma FA and serum lipid profiles were assessed by standard methods at the end of each dietary phase. After 4 weeks of intake, plasma levels of FA pentadecanoic acid (15 : 0) and heptadecanoic acid (17 : 0) were higher (0·26 v. 0·22 % and 0·42 v. 0·39 % of the total identified FA, respectively) after the DAIRY phase than after the CONTROL phase (P< 0·0001). This was accompanied by a small but significant increase in serum LDL-cholesterol levels after the DAIRY phase compared with the CONTROL phase (+0·08 mmol/l; P= 0·04). In conclusion, intake of 3 servings/d of conventional dairy products may modify certain circulating FA and lipid profiles within 4 weeks, where 15 : 0 and 17 : 0 may be potential short-term biomarkers of intake.

The bran and particularly the aleurone fraction of wheat are high in betaine and other physiological methyl donors, which may exert beneficial physiological effects. We conducted two randomised, controlled, cross-over postprandial studies to assess and compare plasma betaine and other methyl donor-related responses following the consumption of minimally processed bran and aleurone fractions (study A) and aleurone bread (study B). For both studies, standard pharmacokinetic parameters were derived for betaine, choline, folate, dimethylglycine (DMG), total homocysteine and methionine from plasma samples taken at 0, 0·5, 1, 2 and 3 h. In study A (n 14), plasma betaine concentrations were significantly and substantially elevated from 0·5 to 3 h following the consumption of both bran and aleurone compared with the control; however, aleurone gave significantly higher responses than bran. Small, but significant, increases were also observed in DMG measures; however, no significant responses were observed in other analytes. In study B (n 13), plasma betaine concentrations were significantly and substantially higher following consumption of the aleurone bread compared with the control bread; small, but significant, increases were also observed in DMG and folate measures in response to consumption of the aleurone bread; however, no significant responses were observed in other analytes. Peak plasma betaine concentrations, which were 1·7–1·8 times the baseline levels, were attained earlier following the consumption of minimally processed aleurone compared with the aleurone bread (time taken to reach peak concentration 1·2 v. 2·1 h). These results showed that the consumption of minimally processed wheat bran, and particularly the aleurone fraction, yielded substantial postprandial increases in plasma betaine concentrations. Furthermore, these effects appear to be maintained when aleurone was incorporated into bread.

Bioavailability studies are vital to assess the potential impact of bioactive compounds on human health. Although conjugated phenolic metabolites derived from colonic metabolism have been identified in the urine, the quantification and appearance of these compounds in plasma is less well studied. In this regard, it is important to further assess their potential biological activity in vivo. To address this gap, a cross-over intervention study with a mixed fruit purée (blueberry, blackberry, raspberry, strawberry tree fruit and Portuguese crowberry) and a standard polyphenol-free meal was conducted in thirteen volunteers (ten females and three males), who received each test meal once, and plasma metabolites were identified by HPLC–MS/MS. Sulfated compounds were chemically synthesised and used as standards to facilitate quantification. Gallic and caffeic acid conjugates were absorbed rapidly, reaching a maximum concentration between 1 and 2 h. The concentrations of sulfated metabolites resulting from the colonic degradation of more complex polyphenols increased in plasma from 4 h, and pyrogallol sulfate and catechol sulfate reached concentrations ranging from 5 to 20 μm at 6 h. In conclusion, phenolic sulfates reached high concentrations in plasma, as opposed to their undetected parent compounds. These compounds have potential use as biomarkers of polyphenol intake, and their biological activities need to be considered.

Studies on the role of diet in the development of chronic diseases often rely on self-report surveys of dietary intake. Unfortunately, many validity studies have demonstrated that self-reported dietary intake is subject to systematic under-reporting, although the vast majority of such studies have been conducted in industrialised countries. The aim of the present study was to investigate whether or not systematic reporting error exists among the individuals of African ancestry (n 324) in five countries distributed across the Human Development Index (HDI) scale, a UN statistic devised to rank countries on non-income factors plus economic indicators. Using two 24 h dietary recalls to assess energy intake and the doubly labelled water method to assess total energy expenditure, we calculated the difference between these two values ((self-report − expenditure/expenditure) × 100) to identify under-reporting of habitual energy intake in selected communities in Ghana, South Africa, Seychelles, Jamaica and the USA. Under-reporting of habitual energy intake was observed in all the five countries. The South African cohort exhibited the highest mean under-reporting ( − 52·1 % of energy) compared with the cohorts of Ghana ( − 22·5 %), Jamaica ( − 17·9 %), Seychelles ( − 25·0 %) and the USA ( − 18·5 %). BMI was the most consistent predictor of under-reporting compared with other predictors. In conclusion, there is substantial under-reporting of dietary energy intake in populations across the whole range of the HDI, and this systematic reporting error increases according to the BMI of an individual.

The frequency of dining out has rapidly increased; however, the independent associations between dining out, metabolic syndrome risk factors and nutritional status have not been well characterised. The aim of the present study was to investigate the associations between dining out, nutritional intakes and metabolic syndrome risk factors among Korean adults, using data from the 2011 Korean National Health and Nutrition Examination Survey. Frequency of dining out was significantly associated with intake of nutrients such as energy, water, protein, fat, carbohydrate, Ca, Na, vitamin A and carotene. Especially, the result revealed that Korean adults had insufficient Ca intake compared with the Korean reference intake (700 mg). As the frequency of dining out increased, so did energy intake. In addition, individuals who dined out seven or more times per week experienced a 64 % higher likelihood of blood pressure abnormalities, an 88 % higher likelihood of waist circumference abnormalities, and a 32 % higher likelihood of low HDL-cholesterol levels than those who dined out less than once per week. BMI was not associated with the frequency of dining out. Our findings suggest that strategies to modify dining-out behaviour could reduce metabolic syndrome risk factors via improved nutrition.

In the present study, we examined the associations of total carbohydrate intake, dietary glycaemic load (DGL) and white rice intake with metabolic syndrome risk factors by sex in Korean adolescents. For the present cross-sectional study, data from the Fourth Korea National Health and Nutrition Examination Survey (2007–9) were used. A total of 2209 adolescents (n 1164 boys and n 1045 girls) aged 10–18 years with complete anthropometric, biochemical and dietary intake data were included in the study. Dietary intake data were obtained using the 24 h recall method, and total carbohydrate intake, DGL and white rice intake were divided into quartiles by sex. The metabolic syndrome and its risk factors were defined using the International Diabetes Federation criteria for children and adolescents. Fasting insulin levels and insulin resistance were included as the metabolic syndrome risk factors. All statistical analyses considered the complex sampling design effect and appropriate sampling weights. Multivariate linear regression analysis was used to estimate means with their standard errors of the mean for the metabolic syndrome risk factors across the quartiles of total carbohydrate intake, DGL and white rice intake. While high DGL was significantly associated with increased fasting glucose levels in boys, high total carbohydrate intake, DGL and white rice intake were consistently associated with reduced HDL-cholesterol levels in girls. High white rice intake was significantly associated with an increased risk of insulin resistance and the metabolic syndrome in girls but not in boys. Optimising dietary carbohydrate intake with respect to the source or amount is fundamental to preventing and managing metabolic diseases in Asian adolescents.

High dietary Na intake is associated with multiple health risks, making accurate assessment of population dietary Na intake critical. In the present study, reporting accuracy of dietary Na intake was evaluated by 24 h urinary Na excretion using the EPIC-Soft 24 h dietary recall (24-HDR). Participants from a subsample of the European Food Consumption Validation study (n 365; countries: Belgium, Norway and Czech Republic), aged 45–65 years, completed two 24 h urine collections and two 24-HDR. Reporting accuracy was calculated as the ratio of reported Na intake to that estimated from the urinary biomarker. A questionnaire on salt use was completed in order to assess the discretionary use of table and cooking salt. The reporting accuracy of dietary Na intake was assessed using two scenarios: (1) a salt adjustment procedure using data from the salt questionnaire; (2) without salt adjustment. Overall, reporting accuracy improved when data from the salt questionnaire were included. The mean reporting accuracy was 0·67 (95 % CI 0·62, 0·72), 0·73 (95 % CI 0·68, 0·79) and 0·79 (95 % CI 0·74, 0·85) for Belgium, Norway and Czech Republic, respectively. Reporting accuracy decreased with increasing BMI among male subjects in all the three countries. For women from Belgium and Norway, reporting accuracy was highest among those classified as obese (BMI ≥ 30 kg/m2: 0·73, 95 % CI 0·67, 0·81 and 0·81, 95 % CI 0·77, 0·86, respectively). The findings from the present study showed considerable underestimation of dietary Na intake assessed using two 24-HDR. The questionnaire-based salt adjustment procedure improved reporting accuracy by 7–13 %. Further development of both the questionnaire and EPIC-Soft databases (e.g. inclusion of a facet to describe salt content) is necessary to estimate population dietary Na intakes accurately.

The objective of the present study was to investigate the relationship between total and subtypes of bacterial fermented food intake (dairy products, cheese, vegetables and meat) and mortality due to all causes, total cancer and CVD. From the European Prospective Investigation into Cancer and Nutrition-Netherlands cohort, 34 409 Dutch men and women, aged 20–70 years who were free from CVD or cancer at baseline, were included. Baseline intakes of total and subtypes of fermented foods were measured with a validated FFQ. Data on the incidence and causes of death were obtained from the national mortality register. Cox proportional hazards models were used to analyse mortality in relation to the quartiles of fermented food intake. After a mean follow-up of 15 (sd 2·5) years, 2436 deaths occurred (1216 from cancer and 727 from CVD). After adjustment for age, sex, total energy intake, physical activity, education level, hypertension, smoking habit, BMI, and intakes of fruit, vegetables and alcohol, total fermented food intake was not found to be associated with mortality due to all causes (hazard ratio upper v. lowest quartile (HRQ4 v. Q1) 1·00, 95 % CI 0·88, 1·13), cancer (HRQ4 v. Q1 1·02, 95 % CI 0·86, 1·21) or CVD (HRQ4 v. Q1 1·04, 95 % CI 0·83, 1·30). Bacterial fermented foods mainly consisted of fermented dairy foods (78 %) and cheese (16 %). None of the subtypes of fermented foods was consistently related to mortality, except for cheese which was moderately inversely associated with CVD mortality, and particularly stroke mortality (HRQ4 v. Q1 0·59, 95 % CI 0·38, 0·92, Ptrend= 0·046). In conclusion, the present study provides no strong evidence that intake of fermented foods, particularly fermented dairy foods, is associated with mortality.

More than 1·4 billion individuals are overweight or obese worldwide. While complications often require therapeutic intervention, data regarding the impact of obesity on drug disposition are scarce. As the influence of diet-induced obesity on drug transport and metabolic pathways is currently unclear, the objective of the present study was to investigate the effect of high fat feeding for 13 weeks in female Sprague–Dawley rats on the hepatic expression of the nuclear receptors pregnane X receptor (PXR), constitutive androstane receptor (CAR), liver X receptor (LXR) and farnesoid X receptor (FXR) and several of their target genes. We hypothesised that high fat feeding would alter the gene expression of major hepatic transporters through a dysregulation of the expression of the nuclear receptors. The results demonstrated that, along with a significant increase in body fat and weight, a high-fat diet (HFD) induced a significant 2-fold increase in the expression of PXR as well as a 2-, 5- and 2·5-fold increase in the hepatic expression of the PXR target genes Abcc2, Abcb1a and Cyp3a2, respectively (P< 0·05). The expression levels of FXR were significantly increased in rats fed a HFD in addition to the increase in the expression levels of FXR target genes Abcb11 and Abcb4. The expression levels of both LXRα and LXRβ were slightly but significantly increased in rats fed a HFD, and the expression levels of their target genes Abca1 and Abcg5, but not Abcg8, were significantly increased. The expression of the nuclear receptor CAR was not significantly altered between the groups. This suggests that a HFD may induce changes in the hepatobiliary transport and metabolism of endogenous and exogenous compounds.

Exploring changes in children's diet over time and the relationship between these changes and socio-economic status (SES) may help to understand the impact of social inequalities on dietary patterns. The aim of the present study was to describe dietary patterns by applying a cluster analysis to 9301 children participating in the baseline (2–9 years old) and follow-up (4–11 years old) surveys of the Identification and Prevention of Dietary- and Lifestyle-induced Health Effects in Children and Infants Study, and to describe the cluster memberships of these children over time and their association with SES. We applied the K-means clustering algorithm based on the similarities between the relative frequencies of consumption of forty-two food items. The following three consistent clusters were obtained at baseline and follow-up: processed (higher frequency of consumption of snacks and fast food); sweet (higher frequency of consumption of sweet foods and sweetened drinks); healthy (higher frequency of consumption of fruits, vegetables and wholemeal products). Children with higher-educated mothers and fathers and the highest household income were more likely to be allocated to the healthy cluster at baseline and follow-up and less likely to be allocated to the sweet cluster. Migrants were more likely to be allocated to the processed cluster at baseline and follow-up. Applying the cluster analysis to derive dietary patterns at the two time points allowed us to identify groups of children from a lower socio-economic background presenting persistently unhealthier dietary profiles. This finding reflects the need for healthy eating interventions specifically targeting children from lower socio-economic backgrounds.

Beverages are among the first independent product choices that school-aged children will make and unhealthy choices can be a threat to children's health. The present study investigated which beverage attributes shape adults' and children's health perceptions. For this purpose, 100 children (fifty-two boys; mean age 8·8 (sd 1·1) years) and their parents were invited to independently perform a beverage-sorting task. Participants were asked to place twenty commonly consumed soft drinks in a line ranging from ‘unhealthy’ to ‘healthy’. The sorting data were analysed using multidimensional scaling with property fitting and hierarchical clustering. Sugar content (βparents= − 0·78, βchildren= − 0·68; P< 0·001), artificial sweeteners (βparents= − 0·68, βchildren= − 0·66; P< 0·001), fruit content (βparents= 0·33, βchildren= 0·36; P< 0·05) and caffeine content (βparents= − 0·45, βchildren= − 0·46; P< 0·01) were found to be the predictors of parents' and children's health perceptions. Parents' and children's estimates were strongly related (rs 0·70 (sd 0·15)); both groups classified the beverages into similar clusters. However, compared with their parents, children perceived beverages such as fruit juices and grapefruit soda to be healthier. In conclusion, parents' and children's health perceptions were strongly related based on the same relevant attributes for evaluation. However, fruit content was considered a more important criterion by children, which might lead to differences in the health perception between children and their parents. Low fruit content and the belief of beverages being ‘natural’ could positively bias perceptions. Therefore, certain soft drinks such as squashes or fruit lemonades are problematic, and the consumer's awareness of their low nutritional quality should be raised.

The suppression of prolactin production with bromocriptine (BRO) in the last 3 d of lactation reduces milk yield (early weaning) and increases the transfer of leptin through the milk, causing hyperleptinaemia in pups. In adulthood, several changes occur in the offspring as a result of metabolic programming, including overweight, higher visceral fat mass, hypothyroidism, hyperglycaemia, insulin resistance, hyperleptinaemia and central leptin resistance. In the present study, we investigated whether overweight rats programmed by early weaning with maternal BRO treatment have hypothalamic alterations in adulthood. We analysed the expression of neuropeptide Y (NPY), cocaine- and amphetamine-regulated transcript (CART), pro-opiomelanocortin (POMC) and α-melanocyte-stimulating hormone (α-MSH) by immunohistochemistry in the following hypothalamic nuclei: medial and lateral arcuate nucleus (ARC); paraventricular nucleus (PVN); lateral hypothalamus (LH). Additionally, we sought to determine whether these programmed rats exhibited hypothalamic inflammation as indicated by astrogliosis. NPY immunostaining showed a denser NPY-positive fibre network in the ARC and PVN (+82 % in both nuclei) of BRO offspring. Regarding the anorexigenic neuropeptides, no difference was found for CART, POMC and α-MSH. The number of astrocytes was higher in all the nuclei of BRO rats. The fibre density of glial fibrillary acidic protein was also increased in both medial and lateral ARC (6·06-fold increase and 9·13-fold increase, respectively), PVN (5·75-fold increase) and LH (2·68-fold increase) of BRO rats. We suggest that early weaning has a long-term effect on the expression of NPY as a consequence of developmental plasticity, and the presence of astrogliosis indicates hypothalamic inflammation that is closely related to overweight and hyperleptinaemia observed in our model.