Cu is an essential nutrient for man, but can be toxic if intakes are too high. In sensitive populations, marginal over- or under-exposure can have detrimental effects. Malnourished children, the elderly, and pregnant or lactating females may be susceptible for Cu deficiency. Cu status and exposure in the population can currently not be easily measured, as neither plasma Cu nor plasma cuproenzymes reflect Cu status precisely. Some blood markers (such as ceruloplasmin) indicate severe Cu depletion, but do not inversely respond to Cu excess, and are not suitable to indicate marginal states. A biomarker of Cu is needed that is sensitive to small changes in Cu status, and that responds to Cu excess as well as deficiency. Such a marker will aid in monitoring Cu status in large populations, and will help to avoid chronic health effects (for example, liver damage in chronic toxicity, osteoporosis, loss of collagen stability, or increased susceptibility to infections in deficiency). The advent of high-throughput technologies has enabled us to screen for potential biomarkers in the whole proteome of a cell, not excluding markers that have no direct link to Cu. Further, this screening allows us to search for a whole group of proteins that, in combination, reflect Cu status. The present review emphasises the need to find sensitive biomarkers for Cu, examines potential markers of Cu status already available, and discusses methods to identify a novel suite of biomarkers.

It was the aim of the present study to estimate the intake of heterocyclic aromatic amines (HCA) from meat, which have been associated with cancer risk in several epidemiological studies, of 21 462 subjects who participated in the European Prospective Investigation into Cancer and Nutrition (EPIC) in Heidelberg. This was accomplished by using a detailed dietary questionnaire that assessed meat consumption, cooking methods, and degree of browning of the respective food items. Median total HCA intake from meat was 31 ng/d (mean 69 ng/d), which was lower than results observed in previous studies. 2-Amino-1-methyl-6-phenylimidazo[4,5b]pyridine was the most common HCA in this cohort (median 17; mean 48 ng/d). The present study offers the opportunity of a detailed examination of the associations between meat cooking as well as HCA intake from meat and cancer risk in a prospective way.

Personalised, genotype-based nutrition is a concept that links genotyping with specific nutritional advice in order to improve the prevention of nutrition-associated, chronic diseases. This review describes the current scientific basis of the concept and discusses its problems. There is convincing evidence that variant genes may indeed determine the biological response to nutrients. The effects of single-gene variants on risk or risk factor levels of a complex disease are, however, usually small and sometimes inconsistent. Thus, information on the effects of combinations of relevant gene variants appears to be required in order to improve the predictive precision of the genetic information. Furthermore, very few associations between genotype and response have been tested for causality in human intervention studies, and little is known about potential adverse effects of a genotype-derived intervention. These issues need to be addressed before genotyping can become an acceptable method to guide nutritional recommendations.

Malnutrition, secondary to deficiency in intake of proteins, minerals or vitamins, consistently results in changes in the thymus. This organ undergoes a severe atrophy due to apoptosis-induced thymocyte depletion, particularly affecting the immature CD4+CD8+ cells, as well as a decrease in cell proliferation. This feature is apparently linked to a hormonal imbalance, involving a decrease in leptin and consequent increase in glucocorticoid hormone levels in the serum. The thymic microenvironment is also affected in malnutrition: morphological changes in thymic epithelial cells have been found, together with a decrease of thymic hormone production by these cells. Additionally, intrathymic contents of extracellular proteins, such as fibronectin, laminin and collagens, are increased in thymuses from malnourished children. Taken together, these data clearly point to the notion that the thymus is significantly affected in malnutrition. Similar patterns of thymic changes occur in acute infectious diseases, including a severe atrophy of the organ, mainly due to the apoptosis-related depletion of immature CD4+CD8+ thymocytes. Additionally, thymocyte proliferation is compromised in acutely-infected subjects. The microenvironmental compartment of the thymus is also affected in acute infections, with an increased density of the epithelial network and an increase in the deposition of extracellular matrix. In conclusion, it seems clear that the thymus is targeted in malnutrition as well as in acute infections. These changes are related to the impaired peripheral immune response seen in malnourished and infected individuals. Thus, strategies inducing thymus replenishment should be considered in therapeutic approaches, in both malnutrition and acute infectious diseases.

To investigate the effects of three different conjugated linoleic acid (CLA) preparations containing different ratios of CLA isomers on insulin signalling, fatty acid oxidation and mitochondrial function, Sprague–Dawley rats were fed a high-fat diet either unsupplemented or supplemented with one of three CLA preparations at 1 % of the diet for 8 weeks. The first CLA preparation contained approximately 30 % cis-9, trans-11 (c9, t11)-CLA isomer and 40 % trans-10, cis-12 (t10, c12)-CLA isomer (CLA-mix). The other two preparations were an 80:20 mix (c9, t11-CLA-mix) or a 10:90 mix of two CLA isomers (t10, c12-CLA-mix). Insulin resistance was decreased in all three supplemented groups based on the results of homeostasis model assessment and the revised quantitative insulin-sensitivity check index. The phosphorylation of insulin receptor substrate-1 on serine decreased in the livers of all three supplemented groups, while subsequent Akt phosphorylation increased only in the t10, c12-CLA-mix group. Both the c9, t11-CLA-mix and the t10, c12-CLA-mix increased the expression of hepatic adiponectin receptors R1 and 2, which are thought to enhance insulin sensitivity and fat oxidation. The c9, t11-CLA-mix increased protein and mRNA levels of PPARα, acyl-CoA oxidase and uncoupling protein, which are involved in fatty acid oxidation and energy dissipation. The c9, t11-CLA-mix enhanced mitochondrial function and protection against oxidative stress by increasing the activities of cytochrome c oxidase, manganese-superoxide dismutase, glutathione peroxidase, and glutathione reductase and the level of GSH. In conclusion, all three CLA preparations reduced insulin resistance. Among them, the c9, t11-CLA-mix was the most effective based on the parameters reflecting insulin resistance and fat oxidation, and mitochondrial antioxidative enzyme activity in the liver.

Foods containing plant sterol or stanol esters can be beneficial in lowering LDL-cholesterol concentration, a major risk factor for CVD. The present study examined whether high dietary intake of rapeseed oil (RSO) derived plant sterol and stanol esters is associated with increased levels of these components in brain tissue of homozygous and heterozygous Watanabe rabbits, an animal model for familial hypercholesterolemia. Homozygous animals received either a standard diet, RSO stanol or RSO sterol ester while heterozygous animals were additionally fed with 2 g cholesterol/kg to the respective diet form for 120 d (n 9 for each group). Concentrations of cholesterol, its precursor lathosterol, plant sterols and stanols in brain and additionally in liver and plasma were determined by highly sensitive GC–MS. High-dose intake of RSO derived plant sterols and stanols resulted in increased levels of these components in plasma and liver. In brain a limited uptake of plant sterols and stanols was proven, indicating that these compounds passed the blood–brain barrier and may be retained in the brain tissue of Watanabe rabbits. Plant stanol ester feeding lowered plant sterol levels in brain, liver, and plasma. Cholesterol synthesis in brain, indicated by lathosterol, a local surrogate cholesterol synthesis marker, does not seem to be affected by plant sterol or stanol ester feeding. We conclude that high dose intake of plant sterol and stanol esters in Watanabe rabbits results in elevated concentrations of these components not only in the periphery but also in the central nervous system.

Neonates are particularly susceptible to malnutrition due to their limited reserves of micronutrients and their rapid growth. In the present study, we examined the effect of vitamin C deficiency on markers of oxidative stress in plasma, liver and brain of weanling guinea pigs. Vitamin C deficiency caused rapid and significant depletion of ascorbate (P < 0·001), tocopherols (P < 0·001) and glutathione (P < 0·001), and a decrease in superoxide dismutase activity (P = 0·005) in the liver, while protein oxidation was significantly increased (P = 0·011). No changes in lipid oxidation or oxidatively damaged DNA were observed in this tissue. In the brain, the pattern was markedly different. Of the measured antioxidants, only ascorbate was significantly depleted (P < 0·001), but in contrast to the liver, ascorbate oxidation (P = 0·034), lipid oxidation (P < 0·001), DNA oxidation (P = 0·13) and DNA incision repair (P = 0·014) were all increased, while protein oxidation decreased (P = 0·003). The results show that the selective preservation of brain ascorbate and induction of DNA repair in vitamin C-deficient weanling guinea pigs is not sufficient to prevent oxidative damage. Vitamin C deficiency may therefore be particularly adverse during the neonatal period.

Fe-deficiency anaemia is the most common cause of anaemia in developing countries. In these settings, many chronic infections, including tuberculosis (TB), are highly prevalent. Fe is an essential nutrient for both host and mycobacteria that play a pivotal role in host immunity and mycobacterial growth. A case–control study was performed in a TB-endemic region in Jakarta, Indonesia, among 378 pulmonary TB patients and 436 healthy controls from the same neighbourhood with the same socio-economic status. In a number of these subjects the Fe status could be explored. The distribution of three polymorphisms in the natural resistance-associated macrophage protein gene (NRAMP1) including INT4, D543N and 3′UTR was examined for a possible association with susceptibility to TB. Anaemia (corrected for sex) was present in 63·2 % of active TB compared with 6·8 % of controls, with female patients more often affected. Anaemia was more pronounced in advanced TB as diagnosed by chest radiography. Lower Hb concentrations in TB patients were accompanied by lower plasma Fe concentrations, lower Fe-binding capacity and higher plasma ferritin. After successful TB therapy, Fe parameters improved towards control values and Hb levels normalised, even without Fe supplementation. NRAMP1 gene polymorphisms were not associated with TB susceptibility, TB severity or anaemia. In conclusion, most active TB patients had anaemia, which was probably due to inflammation and not to Fe deficiency since TB treatment without Fe supplementation was sufficient to restore Hb concentration.

One of the challenges in type 2 diabetes treatment is to ensure pancreas functionality with gut peptides such as glucagon-like peptide-1 (GLP-1). We have recently shown that the endogenous GLP-1 production is promoted by dietary non-digestible carbohydrates (oligofructose), the higher GLP-1 secretion could participate in the control of obesity and associated disorders. This experimental study was designed to highlight the mechanisms of endogenous increase of GLP-1 following non-digestible carbohydrate feeding. Male Wistar rats were fed a standard diet (70·4 g/100 g total carbohydrates; controls) or the same diet supplemented with oligofructose (10 g/100 g diet) for 4 weeks. GLP-1-producing L-cells of the colon were quantified by immunohistochemistry. GLP-1 was quantified by ELISA, and proglucagon, neurogenin 3 and NeuroD mRNA were measured in the colon by quantitative RT–PCR. The number of GLP-1-expressing cells was doubled in the proximal colon of oligofructose-treated rats, a phenomenon correlated with the increase in proglucagon mRNA and peptide content in the tissue. Moreover, oligofructose increased the number of enteroendocrine L-cells in the proximal colon by a mechanism involving up-regulation of two differentiation factors: neurogenin 3 and NeuroD. It is the first demonstration that nutrients fermented in the gut may promote L-cell differentiation in the proximal colon, a phenomenon contributing to a higher endogenous GLP-1 production. These results suggest a new mechanism by which dietary fibres may lower food intake and fat mass development.

The interaction between nutrition and infection is a key determinant of human health. Traditionally the interaction has centered on the role of nutrients in defining host defenses and the impact of infection in defining nutritional needs and status. Over the past decades the interaction has expanded its scope to encompass the role of specific nutrients in defining acquired immune function, in the modulation of inflammatory processes and on the virulence of the infectious agent itself. More recently the role of micronutrients and fatty acids on the response of cells and tissues to hypoxic and toxic damage has been recognized suggesting a fourth dimension to the interaction. The list of nutrients affecting infection, immunity, inflammation and cell injury has expanded from traditional protein-energy supply to several vitamins, multiple minerals and more recently specific lipid components of the diet. The promise of nutrition in the defense against infection, inflammation and tissue injury has spawned a thriving pharma-nutritional supplement industry and the development of novel foods that require appropriate evaluation of efficacy, safety and effectiveness relative to costs. Academics need to aware of the ethics and the pitfalls in the interaction with industry; conversely industry has to define its role in the process of bringing new knowledge to useful products. The process needs to be interactive, transparent and clearly place public interest above all other considerations.

Reduced food availability in pregnancy influences fetal growth, obstetric outcomes and offspring health in both developing and developed countries. The objective of the present study was to determine responses to moderate global maternal nutrient restriction (MNR) during pregnancy in baboons (Papio hamadryas) – an established non-human primate model for pregnancy-related research. Starting at 30 d gestation (dG), twelve pregnant baboons received 70 % of food (MNR group) consumed by twenty ad libitum-fed pregnant controls. Maternal body weight, BMI, food intake and physical activity were measured before pregnancy, at 90 dG and at 165 dG (full-term 180 dG). Fetal and placental weights were recorded at the time of Caesarean section (90 and 165 dG). Activity patterns were also evaluated in fourteen non-pregnant female baboons. Behavioural observations were made in five non-pregnant, six control and four MNR animals. Pregnant baboons decreased overall physical activity and energy-expensive behaviours compared with non-pregnant baboons. In the MNR group, maternal weight, weight gain and maternal physical activity were reduced compared with the control animals. MNR decreased placental weight and volume compared with control, while fetal weight and length were unaffected. We conclude that decreased physical activity and increased usage of maternal available body stores play an important role in the maternal response to pregnancy. Also, adaptations in maternal behaviour and energy utilisation protect fetal growth during moderate MNR.

An inverse relationship between Ca intake and BMI has been found in several studies. It has been suggested that Ca affects adipocyte metabolism via suppressing 1,25-dihydroxycholecalciferol (1,25(OH)2-D3) and decreases fat absorption. We studied the effect of Ca and milk proteins (whey and casein) on body weight in C57Bl/6J mice. Male mice, age 9 weeks, were divided into three groups (ten mice per group) receiving modified high-fat (60 % of energy) diets. Two groups received a high-Ca diet (1·8 % calcium carbonate (CaCO3)), with casein or whey protein (18 % of energy), and one group received a low-Ca diet (0·4 % CaCO3) with casein for 21 weeks. Food intake was measured daily and body weight twice per week. Body fat content (by dual-energy X-ray absorptiometry) of all mice and faecal Ca and fat excretion of seven mice/group were measured twice during the study. Final body weight (44·1 (sem 1·1) g) and body fat content (41·6 (sem 0·6) %) were significantly lower (P < 0·05) in the high-Ca whey group than in the low-Ca casein group (48·1 (sem 0·8) g and 44·9 (sem 0·8) %). Body weight and body fat content of the high-Ca casein group did not differ significantly from the low-Ca casein group even though serum 1,25(OH)2-D3 levels were significantly lower (P < 0·001) in both high-Ca groups than in the low-Ca casein group. Thus changes in serum 1,25(OH)2-D3 do not seem to affect body weight in this animal model. There was a significant difference in fat excretion between the high-Ca whey and low-Ca casein groups (3·9 (sem 0·9) % in the high-Ca whey v. 1·4 (sem 0·2) % in the low-Ca casein group; P < 0·05), which may partly explain the effect on body weight.

Most of diurnal time is spent in a postprandial state due to successive meal intakes during the day. As long as the meals contain enough fat, a transient increase in triacylglycerolaemia and a change in lipoprotein pattern occurs. The extent and kinetics of such postprandial changes are highly variable and are modulated by numerous factors. This review focuses on factors affecting postprandial lipoprotein metabolism and genes, their variability and their relationship with intermediate phenotypes and risk of CHD. Postprandial lipoprotein metabolism is modulated by background dietary pattern as well as meal composition (fat amount and type, carbohydrate, protein, fibre, alcohol) and several lifestyle conditions (physical activity, tobacco use), physiological factors (age, gender, menopausal status) and pathological conditions (obesity, insulin resistance, diabetes mellitus). The roles of many genes have been explored in order to establish the possible implications of their variability in lipid metabolism and CHD risk. The postprandial lipid response has been shown to be modified by polymorphisms within the genes for apo A-I, A-IV, A-V, E, B, C-I and C-III, lipoprotein lipase, hepatic lipase, fatty acid binding and transport proteins, microsomal triglyceride transfer protein and scavenger receptor class B type I. Overall, the variability in postprandial response is important and complex, and the interactions between nutrients or dietary or meal compositions and gene variants need further investigation. The extent of present knowledge and needs for future studies are discussed in light of ongoing developments in nutrigenetics.

Plant extracts rich in polyphenols (PERP) could represent interesting alternative antioxidants but their use in ruminants needs further investigation since the antioxidant capacity of PERP could be altered by digestive processes. The aim of the study was to investigate the bioavailability and the antioxidant capacity of four PERP (rosemary; grape; citrus; marigold) in ruminants made highly susceptible to lipoperoxidation by a continuous linseed oil infusion (4 % DM) in the duodenum. The PERP were given, as a single acute dose (10 % DM), directly into the rumen of sheep (n 5) and blood was then collected every 3 h over a period of 30 h. Grape was particularly efficient to enhance the plasma total antioxidant status (P < 0·05). Moreover, many new polyphenols were detected in the plasma and the identification of epicatechin in the grape group suggested that, contrary to monogastrics, ruminants can benefit from the antioxidant effect of polymeric proanthocyanidins. Finally, the four PERP tested, and more especially marigold, significantly reduced plasma susceptibility to liperoxidation (mean increase of lag phase: +5·9 min, P < 0·02; mean reduction of oxidation rate: − 1·7 A234/min, P < 0·01). In conclusion, the digestive processes in ruminants do not inhibit the antioxidant properties of PERP in vivo and are beneficial by improving the biological effect of polymeric proanthocyanidins. Further experiments are now necessary to determine the optimum dose of administration and to characterize the bioactive molecules.

Human milk is a rich source of RNA, free nucleotides (NT) and nucleosides (NS). To determine the uptake of different NS sources by the intestinal epithelium, jejunal explants from suckling piglets were cultured in a medium supplemented with a mixture of NS (adenosine, cytidine, guanosine, inosine, uridine; 10 mg/l each), a mixture of five NT (AMP, CMP, GMP, IMP, UMP; 7 mg/l each) or RNA (60 mg/l), respectively. Aliquots from the media were taken at different times (0·5, 2, 5, 15, 30, 60, 180 min). NS and NT concentrations were analysed in the different supernatants at those periods using solid-phase extraction followed by HPLC. When explants were cultured in the presence of NS the concentration of these compounds, excepting cytidine, rapidly decreased, suggesting that they are efficiently taken up. When explants were incubated in the presence of NT, the total concentration of these compounds decreased while the total concentration of NS increased, suggesting that enterocytes efficiently hydrolyse NT into NS. Likewise, when explants were incubated in the presence of RNA, the total concentration of both NT and NS increased, indicating that intestinal explants are able to hydrolyse RNA to NT and then to NS in the absence of luminal enzymes. In conclusion, the jejunum of piglets at weaning is able to hydrolyse RNA and free NT to NS, and NS, excepting cytidine, are efficiently taken up by the small intestine. These results suggest that the current concentration of NT used to supplement infant formulas should be reconsidered.

Our previous studies have shown that genistein can enhance the insulin-like growth factor (IGF)-1 receptor signalling pathway via an oestrogen receptor (ER) in human breast cancer MCF-7 cells. The present study aims to investigate how genistein regulates IGF-1 receptor expression in human MCF-7 cells. Genistein at 1 μm stimulated the growth of MCF-7 cells and this effect could be completely blocked by the IGF-1 receptor antagonist JB-1, suggesting that IGF-1 receptor is essential for mediating the proliferative effects of genistein in MCF-7 cells. Genistein increased IGF-1 receptor promoter activity. This effect could be completely abolished by co-treatment of MCF-7 cells with ICI 182,780 (10− 6 m). Genistein increased IGF-1 receptor gene expression and this effect could be completely blocked by the IGF-1 receptor antagonist JB-1. Co-treatment of MCF-7 cells with cycloheximide (5 μg/ml) completely blocked the induction of IGF-1 receptor protein and mRNA expression by genistein. The results indicated that the induction of IGF-1 receptor promoter activity by genistein required the action of ER while the stimulatory actions of genistein on IGF-1 receptor expression required the activity of the IGF-1 receptor and de novo protein synthesis. These data provide evidence to support the hypothesis that the inductive effects of genistein on IGF-1 receptor expression require the cross-talk between IGF-1 receptor and the ER-dependent pathways.

In food databases, the specific contents of vitamin D3 and 25-hydroxyvitamin D3 in food have been implemented in the last 10 years. No consensus has yet been established on the relative activity between the components. Therefore, the objective of the present study was to assess the relative activity of 25-hydroxyvitamin D3 compared to vitamin D3. The design was a parallel study in pigs (n 24), which from an age of 12 weeks until slaughter 11 weeks later were fed approximately 55 μg vitamin D/d, as vitamin D3, in a mixture of vitamin D3 and 25-hydroxyvitamin D3, or 25-hydroxyvitamin D3. The end-points measured were plasma 25-hydroxyvitamin D3, and in the liver and loin the content of vitamin D3 and 25-hydroxyvitamin D3. Vitamin D3 and 25-hydroxyvitamin D3 in the feed did not affect 25-hydroxyvitamin D3 in the plasma, liver or loin differently, while a significant effect was shown on vitamin D3 in the liver and loin (P < 0·001). 25-Hydroxyvitamin D3 in the plasma, liver and loin significantly correlates with the sum of vitamin D3 and 25-hydroxyvitamin D3 in the feed (P < 0·05). Therefore, 25-hydroxyvitamin D3 should be regarded as having the same activity as vitamin D3 in food databases. Sole use of 25-hydroxyvitamin D3 as a vitamin D source in pig feed will produce liver and meat with a negligible content of vitamin D3, while an increased content of vitamin D3 in the feed will produce liver and meat with increased content of both vitamin D3 and 25-hydroxyvitamin D3.

Provided that they are scientifically substantiated, nutrition and health (NH) claims linked to food products can help consumers make well-informed food choices. The new European legislation on NH claims made on foods entered into force on 19 January 2007. The law sets out conditions for their use, establishes a system for their scientific evaluation, and will create European lists of authorised claims. An important aspect of this proposed legislation is that it states, in article 5.2, ‘the use of nutrition and health claims shall only be permitted if the average consumer can be expected to understand the beneficial effects expressed in the claim’. The present review examines consumer understanding of NH claims from a consumer science perspective. It focuses on the type of data and information that could be needed to provide evidence that the average consumer adequately understands a particular NH claim. After exploring several different methodologies, it proposes a case-specific approach using a stepwise procedure for assessing consumer understanding of a NH claim.