The liver plays a unique role in nutrient homeostasis. Its anatomical location makes it ideally suited to control the systemic supply of absorbed nutrients, and it is the primary organ that can both consume and produce substantial amounts of glucose. Moreover, it is the site of a substantial fraction (about 25 %) of the body's protein synthesis, and the liver and other organs of the splanchnic bed play an important role in sparing dietary N by storing ingested amino acids. This hepatic anabolism is under the control of hormonal and nutritional changes that occur during food intake. In particular, the route of nutrient delivery, i.e. oral (or intraportal) v. peripheral venous, appears to impact upon the disposition of the macronutrients and also to affect both hepatic and whole-body nutrient metabolism. Intraportal glucose delivery significantly enhances net hepatic glucose uptake, compared with glucose infusion via a peripheral vein. On the other hand, concomitant intraportal infusion of both glucose and gluconeogenic amino acids significantly decreases net hepatic glucose uptake, compared with infusion of the same mass of glucose by itself. Delivery of amino acids via the portal vein may enhance their hepatic uptake, however. Elevation of circulating lipids under postprandial conditions appears to impair both hepatic and whole-body glucose disposal. Thus, the liver's role in nutrient disposal and metabolism is highly responsive to the route of nutrient delivery, and this is an important consideration in planning nutrition support and optimising anabolism in vulnerable patients.

More than 80 years after the discovery of the essentiality of vitamin E for mammals, the molecular basis of its action is still an enigma. From the eight different forms of vitamin E, only α-tocopherol is retained in the body. This is in part due to the specific selection of RRR-α-tocopherol by the α-tocopherol transfer protein and in part by its low rate of degradation and elimination compared with the other vitamers. Since the tocopherols have comparable antioxidant properties and some tocotrienols are even more effective in scavenging radicals, the antioxidant capacity cannot be the explanation for its essentiality, at least not the only one. In the last decade, a high number of so-called novel functions of almost all forms of vitamin E have been described, including regulation of cellular signalling and gene expression. α-Tocopherol appears to be most involved in gene regulation, whereas γ-tocopherol appears to be highly effective in preventing cancer-related processes. Tocotrienols appear to be effective in amelioration of neurodegeneration. Most of the novel functions of individual forms of vitamin E have been demonstrated in vitro only and require in vivo confirmation. The distinct bioactivities of the various vitamers are discussed, considering their metabolism and the potential functions of metabolites.

Obesity is a chronic disorder caused by an imbalance of the energy metabolism with high associated burdens. Therefore, huge efforts are being currently devoted in studying new types of hypoenergetic diets and their composition, in order to characterise more specific, long-lasting and safe slimming protocols. A number of investigations are trying to determine the specific influence of the macronutrient distribution in energy-restricted diets on the management of excessive body weight. In this context, very-low-energy diets supplying between 1670 and 3350 kJ (400 and 800 kcal)/d have been beneficial in short-term treatments causing a weight loss of 300–500 g/d. Such strategies place more emphasis on energy restriction than on the macronutrient composition of the diet prescription. Weight loss produced by either low-carbohydrate or low-fat moderately energy-restricted diets ranges from 0·5 to 1·0 kg/week, while diets with high or moderately high protein content have also been applied in weight-reducing programmes by inducing losses of 0·2–0·4 kg/week. Other factors that determine weight loss by dieting are sex, age, initial body weight, race, genetics, regional fat deposition, etc, which must be taken into account to explain the variability in the outcomes of different low-energy diets. Therefore, more research is needed about the impact of diets with different fuel substrates and foods on the characteristics of the weight-loss process.

Bread is one of the most widely consumed staple foods worldwide. White-wheat bread, largely consumed in France, is made from highly refined flour, which leads to a low nutrient density. Due to a highly porous structure and gelatinised starch, it is easily broken down during digestion, leading to a rapid increase of glucose released into the bloodstream. Low glycaemic responses are considered favourable to health, especially against a background of diabetes. Literature reports show that selection of raw material is an essential factor in decreasing the glycaemic index (GI) of white bread. There are two means of decreasing the rate of starch degradation: either (i) slowing gastric emptying rate and/or glucose diffusion–absorption through the intestinal mucosa, which can be achieved by incorporating soluble fibre or organic acid in bread, or (ii) limiting starch accessibility to α-amylase by using high-amylose cereal varieties and/or incorporating intact cereal grains. Studies on cereal products show that preservation of the food structure during digestion seems to be a more important GI-reducing factor than the degree of starch crystallinity or the presence of soluble fibre. Thus, we should look to produce bread with a more compact food structure or higher density, which is the case in leavened wholewheat bread or bread with intact cereal grains. The baking process should also be improved to achieve this goal, by using, for example, a reduced kneading time or less yeast than usual.

Dietary lignans are phyto-oestrogens that possibly influence human health. The present review deals with lignan bioavailability, the study of which is crucial to determine to what extent metabolism, absorption and excretion of lignans alter their biological properties. Since intestinal bacteria play a major role in lignan conversion, for instance by producing the enterolignans enterodiol and enterolactone, emphasis is put on data obtained in recent bacteriological studies.

α-Linolenic acid (αLNA; 18: 3n-3) is essential in the human diet, probably because it is the substrate for the synthesis of longer-chain, more unsaturated n-3 fatty acids, principally EPA (20: 5n-3) and DHA (22: 6n-3), which confer important biophysical properties on cell membranes and so are required for tissue function. The extent to which this molecular transformation occurs in man is controversial. The present paper reviews the recent literature on the metabolism of αLNA in man, including the use of dietary αLNA in β-oxidation, recycling of carbon by fatty acid synthesis de novo and conversion to longer-chain PUFA. Sex differences in αLNA metabolism and the possible biological consequences are discussed. Increased consumption of EPA and DHA in fish oil has a number of well-characterised beneficial effects on health. The present paper also reviews the efficacy of increased αLNA consumption in increasing the concentrations of EPA and DHA in blood and cell lipid pools, and the extent to which such dietary interventions might be protective against CVD and inflammation. Although the effects on CVD risk factors and inflammatory markers are variable, where beneficial effects have been reported these are weaker than have been achieved from increasing consumption of EPA+DHA or linoleic acid. Overall, the limited capacity for conversion to longer-chain n-3 fatty acids, and the lack of efficacy in ameliorating CVD risk factors and inflammatory markers in man suggests that increased consumption of αLNA may be of little benefit in altering EPA+DHA status or in improving health outcomes compared with other dietary interventions.

Obesity, physical activity status and circulating levels of sex steroid hormones and growth factor proteins are intrinsically linked to energy balance. Epidemiological studies have previously reported associations between these factors and the risk of hormone-related cancers such as prostate and breast cancer in men and postmenopausal women. An increasing number of intervention studies in ‘at-risk’ populations and cancer survivors are now investigating the effects of lifestyle interventions that promote negative energy balance on circulating levels of sex hormones and growth factor proteins as surrogate markers of cancer risk. Evidence from these studies suggests that lifestyle interventions can improve insulin sensitivity, alter the balance of circulating sex steroid hormones and insulin-like growth factor (IGF) axis proteins (including IGF-1 and the IGF binding proteins 1 and 3) and change the functioning of immune cells in peripheral blood. Such changes could influence the risk of developing hormone-related cancers, as well as having the potential to improve disease-free survival in patients recovering from cancer treatment. However, despite promising results, the methodological quality of most intervention studies has been limited due to small subject numbers, lack of adequate control groups or non-randomised designs and the absence of long-term follow-up measures. More intervention studies with randomised controlled designs, higher numbers of subjects and longer-term follow-up measures are needed to establish which combination of specific dietary and physical activity interventions work best for reducing risk in ‘at-risk’ populations and survivors, optimal dose–response relationships and the magnitude of change in surrogate markers of cancer risk that is required to induce a protective effect.

Human clinical trials have shown that fish oils reduce the risk of a variety of disorders including CVD. Despite this, results have been inconsistent. Fish oils are easily oxidised and some fish oils contain higher than recommended levels of oxidised products, but their effects have not been investigated. Recent evidence indicates that dietary oxidised fats can contribute to the development of atherosclerosis and thrombosis. This review summarises findings from cellular, animal and human trials that have examined the effects of oxidised lipids and their potential to affect health outcomes, and proposes that oxidised products in fish oils may attenuate their beneficial effects. More research is required to determine the magnitude of negative effects of fish oil on health outcomes in clinical trials.

Health and wellbeing are challenged constantly by pathogens. A number of defence mechanisms exist to protect the body from pathogen colonisation and invasion, with an important role to play for the natural intestinal bacterial flora (mainly by bifidobacteria and lactobacilli). The present paper reviews the evidence on the effects of inulin and oligofructose on colonisation and translocation of pathogens and the prevention of intestinal diseases. In vitro experiments have shown that lactic acid-producing bacteria have antagonistic (antibacterial) activity against pathogens partly because of the production of organic acids which are the endproducts of inulin and oligofructose fermentation. In addition, studies with epithelial layers have shown that inulin and oligofructose inhibit pathogen colonisation and that endproducts of their fermentation have the ability to support barrier function. Furthermore, studies in various animal models have shown that inulin and oligofructose accelerate the recovery of beneficial bacteria, slow down pathogen growth, decreasing pathogen colonisation and systemic translocation. Finally, data from human intervention trials either in patients with intestinal disorders or disease, or prone to critical illness, found that inulin and oligofructose restore the balance when the gut microbial community is altered, inhibit the progression of disease or prevent it from relapsing and/or developing. To conclude, the dietary use of inulin and oligofructose offers a promising approach to restore microbial communities and to support barrier function of the epithelia by their prebiotic action. This may offer the host protection against invasion and translocation of pathogens (endogenous and/or exogenous) and in the prevention of gastrointestinal diseases.

A rationale is given for a modelling approach to identify the mechanisms involved in the functioning and metabolic activity of tissues in the wall of the gastrointestinal tract. Maintenance and productive functions are discussed and related to the distinct compartments of the gastrointestinal tract and the metabolic costs involved. Functions identified are: tissue turnover; tissue proliferation; ion transport; nutrient transport; secretions of digestive enzymes, mucus and immunoglobulins; production of immune cells. The major nutrients involved include glucose, amino acids and volatile fatty acids. In vivo measurements of net portal fluxes of these nutrients in pigs and ruminants are evaluated to illustrate the complexity of physiology and metabolic activity of the gastrointestinal tract. Experimental evidence indicates that high, but variable and specific, nutrient costs are involved in the functioning of the gastrointestinal tract.

After birth, development of a normal microbial community occurs gradually, and is affected by factors such as the composition of the maternal gut microbiota, the environment, and the host genome. Diet also has a direct influence, both on composition and activity of this community. This influence begins with the milk, when specific components exert their growth-promoting effect on a beneficial microbiota, thereby suppressing potential pathogens. For example, breast-fed infants compared with formula-fed babies usually have a microbial community dominated by bifidobacteria. When solid food is introduced (weaning), dramatic changes in microbial composition occur, so pathogens can gain access to the disturbed gastrointestinal (GI) ecosystem. However, use of specific dietary components can alter the composition and activity of the microbiota positively. Of all dietary components, fermentable carbohydrates seem to be most promising in terms of promoting proliferation of beneficial bacterial species. Carbohydrate fermentation results in the production of SCFA which are known for their trophic and health-promoting effects. Fermentation of proteins, on the other hand, is often associated with growth of potential pathogens, and results in production of detrimental substances including NH3 and amines. In terms of the GI microbiota, lipids are often associated with the antimicrobial activity of medium-chain fatty acids and their derivatives. The present review aims to provide deeper insights into the composition and development of the neonatal GI microbiota, how this microbiota can be influenced by certain dietary components, and how this might ultimately lead to improvements in host health.

Events such as BSE, foot and mouth disease and avian influenza illustrate the importance of animal health on a global basis. The only practical solution to deal with such problems has usually been mass culling of millions of animals at great effort and expense. Serious consideration needs to be given to nutrition as a practical solution for health maintenance and disease avoidance of animals raised for food. Health or disease derives from a triad of interacting factors; diet–disease agent, diet–host and disease agent–host. Various nutrients and other bioactive feed ingredients, nutricines, directly influence health by inhibiting growth of pathogens or by modulating pathogen virulence. It is possible to transform plant-based feed ingredients to produce vaccines against important diseases and these could be fed directly to animals. Nutrients and nutricines contribute to three major factors important in the diet–host interaction; maintenance of gastrointestinal integrity, support of the immune system and the modulation of oxidative stress. Nutrition-based health is the next challenge in modern animal production and will be important to maintain economic viability and also to satisfy consumer demands in terms of food quality, safety and price. This must be accomplished largely through nutritional strategies making optimum use of both nutrients and nutricines.

The aim of the present review is to synthesise and summarise our recent knowledge on the involvement of cholecystokinin (CCK) and gastrin peptides and their receptors in the control of digestive functions and more generally their role in the field of nutrition in mammals. First, we examined the release of these peptides from the gut, focusing on their molecular forms, the factors regulating their release and the signalling pathways mediating their effects. Second, general physiological effects of CCK and gastrin peptides are described with regard to their specific receptors and the role of CCK on vagal mucosal afferent nerve activities. Local effects of CCK and gastrin in the gut are also reported, including gut development, gastrointestinal motility and control of pancreatic functions through vagal afferent pathways, including NO. Third, some examples of the intervention of the CCK and gastrin peptides are exposed in diseases, taking into account intervention of the classical receptor subtypes (CCK1 and CCK2 receptors) and their heterodimerisation as well as CCK-C receptor subtype. Finally, applications and future challenges are suggested in the nutritional field (performances) and in therapy with regards to the molecular forms or in relation with the type of receptor as well as new techniques to be utilised in detection or in therapy of disease. In conclusion, the present review underlines recent developments in this field: CCK and gastrin peptides and their receptors are the key factor of nutritional aspects; a better understanding of the mechanisms involved may increase the efficiency of the nutritional functions and the treatment of abnormalities under pathological conditions.

The availability of ‘omics’ technologies is transforming scientific approaches to physiological problems from a reductionist viewpoint to that of a holistic viewpoint. This is of profound importance in nutrition, since the integration of multiple systems at the level of gene expression on the synthetic side through to metabolic enzyme activity on the degradative side combine to govern nutrient availability to tissues. Protein activity is central to the process of nutrition from the initial absorption of nutrients via uptake carriers in the gut, through to distribution and transport in the blood, metabolism by degradative enzymes in tissues and excretion through renal tubule exchange proteins. Therefore, the global profiling of the proteome, defined as the entire protein complement of the genome expressed in a particular cell or organ, or in plasma or serum at a particular time, offers the potential for identification of important biomarkers of nutritional state that respond to alterations in diet. The present review considers the published evidence of nutritional modulation of the proteome in vivo which has expanded exponentially over the last 3 years. It highlights some of the challenges faced by researchers using proteomic approaches to understand the interactions of diet with genomic and metabolic–phenotypic variables in normal populations.

The use of exogenous enzymes to improve the nutritional value of poultry diets is a relatively new concept. The technology is rapidly evolving, with new enzymes, enzyme combinations, and novel applications being developed as rapidly as regulatory restrictions will allow. Most researchers in the field of poultry nutrition would consider phytase to be the last significant leap forward in terms of enzyme use in the animal feed industry. However, there is a great deal of ongoing research into the next generation of enzymes with a focus on ingredient quality, predictability of response via least-square models, improvements in food safety, effect of bird age, effect of various side activities and enzyme dose, maximisation of net income and reduction in environmental pollution. It is the purpose of the present review article to summarise the current research in the area of feed enzymes for poultry and to speculate on future applications of enzymes and new enzyme technologies that may be of value to the industry in the coming years.

Abstract:Insulin and amino acids are key factors in regulating protein synthesis. The mechanisms of their action have been widely studied for several years. The insulin signal is mediated by the activation of intracellular kinases such as phosphatidylinositol–3'kinase and the mammalian target of rapamycin (mTOR), affecting the phosphorylation of some major effectors involved in the regulation of translation initiation, i.e. p70 S6 kinase (p70S6K) and the translational repressor eukaryotic initiation factor 4E binding protein (4E-BP1). The amino acid–induced signalling cascade also originates from mTOR and promotes p70S6K and 4E–BP1 activation. However, the mechanisms of regulation are complex and little understood, especially in vivo. Elucidating these mechanisms is important for both fundamental physiology and nutritional applications, i.e. better control of the use of nutrients and optimisation of dietary amino acid supplies in various physiological and physiopathological situations. In comparative physiology, the chicken is an interesting model to gain better understanding of the nutritional regulation of mRNA translation because of the very high rates of muscle growth and protein synthesis, and the unusual features compared with mammals. In the present review we provide an overview of the roles of insulin and amino acids as regulators of protein synthesis in both mammals and avian species.

The cost of psychiatric illness to the UK economy was recently estimated at £77 billion annually. Despite years of research no firm aetiological explanation exists, and with no physiological or biochemical markers diagnosis is made entirely on a behavioural basis. All current pharmacological therapies are associated with serious long-term side effects. Substantial evidence supports the involvement of one-carbon cycle dysregulation in psychiatric illness, but this is not currently used as a basis for diagnosis or treatment. The present paper reviews the evidence for one-carbon cycle dysregulation in schizophrenic, bipolar, depressed and autistic patients. Also presented are novel findings from the field of epigenetics, which demonstrate how the one-carbon cycle-derived methyl donor S-adenosylmethionine influences the expression of key genes in the brain affecting memory, learning, cognition and behaviour, genes whose expression is reduced to varying degrees in these patient groups. Clinical evidence that nutritional supplements can rectify one-carbon cycle activity, and restore normal gene expression, suggests a novel approach to the development of biochemical tests and simple, non-harmful treatments for some psychiatric patients. Conversely, evidence from animal studies highlights the dangers of exposing the unborn fetus to very high dietary levels of folic acid, a one-carbon cycle cofactor. Fetal adaptations to a high-folate environment may interfere with folate metabolism postnatally, with serious consequences for the epigenetic regulation of gene expression. The public health implications of these diverse scenarios indicate an urgent need for further research in this field.

Interest in the health-promoting properties of berry anthocyanins is intensifying; however, findings are primarily based on in vitro characteristics, leaving mechanisms associated with absorption, metabolism and pharmacokinetics largely unexplored. The present review integrates the available anthocyanin literature with that of similar flavonoids or polyphenols in order to form hypotheses regarding absorption, metabolism and clearance in humans. Of the limited available literature regarding the absorption and clearance kinetics of anthocyanins, maximum plasma concentrations are reported anywhere between 1·4 and 592 nmol/l and occur at 0·5–4 h post-consumption (doses; 68–1300 mg). Average urinary excretion is reported between 0·03 and 4 % of the ingested dose, having elimination half-lives of 1·5–3 h. In addition, much is unknown regarding the metabolism of anthocyanins. The most commonly cited conjugation reactions involved in the metabolism of other flavonoids include glucuronidation, methylation and sulfation. It is reasonable to suspect that anthocyanins are metabolised in much the same manner; however, until recently, there was little evidence to suggest that anthocyanins were metabolised to any significant extent. New evidence now suggests that anthocyanins are absorbed and transported in human serum and urine primarily as metabolites, with recent studies documenting as much as 68–80 % of anthocyanins as metabolised derivatives in human urine. Further research is required to resolve mechanisms associated with the absorption, metabolism and clearance of anthocyanins in order to establish their true biological activities and health effects. The presented evidence will hopefully focus future research, refining study design and propagating a more complete understanding of anthocyanins' biological significance in humans.

Based upon recent sales numbers, nutritional supplements play a key role in the lifestyle of a substantial proportion of the population. As well as products such as vitamins or minerals, several precursors of anabolic steroids are marketed as nutritional supplements. Another group of commercially available supplements are products for weight loss based upon herbal formulations originating from Ephedra species. Apart from supplements indicating the presence of these active compounds, numerous non-hormonal nutritional supplements were found that were contaminated with non-labelled anabolic steroids. Stimulating agents other than naturally occurring analogues of ephedrine were detected. A major group using dietary supplements are sportsmen, ranging from amateur level to elite athletes. Besides the possible health risks associated with the use of dietary supplements, athletes should take care not to violate the rules of the World Anti-Doping Agency because athletes remain responsible for substances detected in their biofluids, irrespective of their origin. Several analytical methods have been developed to determine the presence of doping agents as contaminants. The present review attempts to address the issues concerning the use of nutritional supplements and the detection of doping agents as contaminants in dietary supplements.