Protein oxidation can be perceived as essential for the control of intracellular signalling and gene expression on the one hand, but in contrast, a potentially cytotoxic hazard of aerobic life. Reduction and oxidation of thiol groups on specific cysteine residues can act as critical molecular switches, in modulating response to growth factors, apoptotic and inflammatory stimuli to name a few. Such oxidative reactions are likely to be transient and represent low levels of oxidative modification to a protein. Sustained oxidative stress conditions through absence of essential dietary antioxidant or low activity of endogenous enzyme scavengers can cause irreversible damage and loss of function. Such modifications are believed to be important in many diseases associated with ageing. Therefore, it has been postulated that diet may exert an influence on the steady state of protein oxidation and thus offer potential health benefits through preservation of normal protein function. In the present paper, the current evidence from in vivo studies on the effects of dietary antioxidants and oxidants on protein oxidation will be evaluated, and needs for future research will be highlighted.

Epidemiological evidence consistently shows that diets high in fresh fruit and vegetables significantly lower cancer risk. Given the postulated role of oxidative DNA damage in carcinogenesis, the assumption has been made that it is the antioxidant properties of food constituents, such as vitamin C, E and carotenoids, which confer protection. However, epidemiological studies with specific antioxidants, either singly or in combination, have not, on the whole, supported this hypothesis. In contrast, studies examining the in vitro effect of antioxidants upon oxidative DNA damage have generally been supportive, in terms of preventing damage induction. The same, however, cannot be said for the in vivo intervention studies where overall the results have been equivocal. Nevertheless, recent work has suggested that some dietary antioxidants may confer protective properties through a novel mechanism, unrelated to their conventional free-radical scavenging abilities. Upregulation of antioxidant defence, xenobiotic metabolism, or DNA-repair genes may all limit cellular damage and hence promote maintenance of cell integrity. However, until further work has clarified whether dietary supplementation with antioxidants confers a reduced risk of cancer and the mechanism by which this effect is exerted, the recommendation for a diet rich in fruit and vegetables remains valid empirically.

Fetal macronutrient requirements for oxidative metabolism and growth are met by placental transport of glucose, amino acids, and, to a lesser extent that varies with species, fatty acids. It is becoming possible to relate the maternal–fetal transport kinetics of these molecules in vivo to the expression and distribution of specific transporters among placental cell types and subcellular membrane fractions. This is most true for glucose transport, although apparent inconsistencies among data on the roles and relative importance of the predominant placenta glucose transporters, GLUT-1 and GLUT-3, remain to be resolved. The quantity of macronutrients transferred to the fetus from the maternal bloodstream is greatly influenced by placental metabolism, which results in net consumption of large amounts of glucose and, to a lesser extent, amino acids. The pattern of fetal nutrient supply is also altered considerably by placental conversion of glucose to lactate and, in some species, fructose, and extensive transamination of amino acids. Placental capacity for transport of glucose and amino acids increases with fetal demand as gestation advances through expansion of the exchange surface area and increased expression of specific transport molecules. In late pregnancy, transport capacity is closely related to placental size and can be modified by maternal nutrition. Preliminary evidence suggests that placental expression and function of specific transport proteins are influenced by extracellular concentrations of nutrients and endocrine factors, but, in general, the humoral regulation of placental capacity for nutrient transport is poorly understood. Consequences of normal and abnormal development of placental transport functions for fetal growth, especially during late gestation, and, possibly, for fetal programming of postnatal disorders, are discussed.

Domestic ruminants are used to exploit many vegetation resources that would otherwise be unproductive. For maximal effectiveness, there is a need to understand underlying mechanisms controlling animal performance, including seasonal variations in appetite and food intake. Potentially useful experimental approaches, recent findings and aspects for future study are discussed. Seasonal variation in intake is expressed through changes in the pattern of meals (duration, frequency, inter-meal interval and ingestion rate). These changes are signalled through alterations in both structure and function of the gastrointestinal tract and physiological signals. Studies suggest that multiple, interactive signals are involved, including hormones such as cholecystokinin, insulin, leptin and triiodothyronine. However, baseline concentrations in the peripheral circulation are not appropriate measurements of some of these hormones since there can be seasonal differences in postprandial profiles or changes in rate of dilution in the bloodstream or in the rate of degradation in the liver. Interactions between these circulating signals, liver function and neural signals to the brain need clarification. Systemic nutritional signals also act directly in the brain where they are integrated with seasonal photoperiod (melatonin) signalling within the hypothalamus. Melatonin target sites critical to appetite regulation have still to be identified, but leptin receptors and downstream neuropeptides have been localised within the ovine hypothalamus. These orexigenic and anorexigenic ‘compensatory’ pathways are sensitive to imposed changes in nutritional status but, with the exception perhaps of cocaine- and amphetamine-regulated transcript, do not appear to drive seasonal ‘anticipatory’ changes in intake. Mechanisms underlying seasonal changes in hypothalamic sensitivity to nutritional feedback clearly deserve further study.

Growth hormone (GH) is an endocrine regulator of glucose and lipid metabolism as well as body growth. GH levels are decreased and a unique pulsatile secretory pattern becomes obvious after puberty particularly in males. Coincidentally with this, males tend to deposit body fat. Experimental and clinical evidence has accumulated that obesity is associated with a decrease in GH levels. A strain of transgenic rats has been generated with severe obesity but normal nose-to-tail length, which has low circulating GH levels without pulsatility (human growth hormone (hGH) transgenic rats). The present review mainly focuses on recent and current work analysing the relationship between the occurrence of obesity and low GH levels and/or the absence of GH pulsatility in this transgenic animal model. This model has elevated blood glucose, non-esterified fatty acid, insulin and leptin levels associated with hyperphagia, suggesting that these rats also carry insulin- and leptin-resistant characteristics. hGH transgenic rats were subjected to a pair-feeding treatment to normalize food intake and chronic GH replacement to normalize GH levels. While the pair-feeding for 8 weeks successfully suppressed body-weight gain, the fat pad : body weight ratio remained very similar to freely-eating control hGH transgenic rats, which indicates the hyperphagia is not the sole contributor to the excess fat accumulation in this model. However, continuous elevation of peripheral hGH levels (approximately 2-fold) for 8 weeks by means of a slow-release vehicle resulted in a significant decrease in the fat mass : body weight ratios by 30 %. This GH treatment altered neither food intake nor body-weight gain. Thus, two characteristic phenotypes observed in the hGH transgenic rats, hyperphagia and obesity, seem to be closely related to GH levels and GH secretory pattern. This relationship might be working in the regulation of changes in seasonal body composition in wild animals.

Following identification of essential micronutrients, there has been a continuum of research aimed at revealing their absorption, transport, utilization as cofactors, and excretion and secretion. Among those cases that have received our attention are vitamin B6, riboflavin, biotin, lipoate, ascorbate, and certain metal ions. Circulatory transport and cellular uptake of the water-soluble vitamins exhibit relative specificity and facilitated mechanisms at physiological concentrations. Isolation of enzymes and metabolites from micro–organisms and mammals has provided information on pathways involved in cofactor formation and metabolism. Kinases catalysing phosphorylation of B6 and riboflavin have a preference for Zn2+ in stereospecific chelates with adenosine triphosphate. The synthetase for flavin adenine dinucleotide prefers Mg2+. The flavin mononucleotide-dependent oxidase that converts the 5′–phosphates of pyridoxine and of pyridoxamine to pyridoxal phosphate is a connection between B6 and riboflavin and is a primary control point for conversion of B6 to its coenzyme. Sequencing and cloning of a side–chain oxidase for riboflavin was achieved. Details on binding and function have been delineated for some cofactor systems, especially in several flavoproteins. There is both photochemical oxidation and oxidative catabolism of B6 and riboflavin. Both biotin and lipoate undergo oxidation of their acid side chains with redox cleavage of the rings. Applications from our findings include the development of affinity absorbents, enhanced drug delivery, delineation of residues in biopolymer modification, pathogen photoinactivation in blood components, and input into human dietary recommendations. Ongoing and future research in the cofactor arena can be expected to add to this panoply. At the molecular level, the way in which the same cofactor can participate in diverse catalytic reactions resides in interactions with surrounding enzyme structures that must be determined case by case. At the level of human intake, more knowledge is desirable for making micronutrient recommendations based on biochemical indicators, especially for the span between infancy and adulthood.

Mechanistic models of microbial metabolism in the rumen aim at an improved understanding and integration for research purposes or at an improved prediction for practical purposes. The standard way of representing such models is the rate : state formalism. The system is defined by a number of state variables and a set of differential equations describe the change of the state variables with time. Three different types of solution to these dynamic models are distinguished, and examples of these solutions are described to illustrate the applications and contributions of dynamic modelling in the study of the rumen microbial ecosystem. Type I solutions are obtained when the system is in steady state and the differential equations are solved by setting the differentials to zero. An application of the type I solution is the indirect approach to quantifying the fibrolytic anaerobic fungi in the rumen. The solutions of the model describing the alternate life cycle of rumen fungi, with its free-swimming dispersal and particle-attached stages, appear to be consistent with ruminal and faecal observations. Type II solutions are obtained when the system is not in steady state but the differential equations can be integrated analytically. An application of this type of solution is the quantification of the growth and growth yield in batch cultures. Such models help to quantify the degradation of substrates in the rumen and to elucidate the interactions between groups of rumen micro-organisms. Type III solutions are obtained when the system is not in steady state and when the differential equations have to be solved numerically. Applications of the type III solutions are the rumen simulation models that describe substrate degradation, endproduct formation and microbial metabolism in an integrated manner. To illustrate this type III solution, a model of lactic acid metabolism in the rumen is defined, and its contribution to understanding of the paths and rates of lactic acid disappearance described. It is essential that the models are based on sound mathematical and biological principles. However, the various applications described in the paper show that models need not necessarily be complex and very detailed to contribute to better understanding.

The present paper provides a comprehensive review of the literature pertaining to the impact of alcohol intake on cardiovascular disease. Both cross-sectional and prospective studies have disclosed a negative association between moderate intake of alcoholic beverages and cardiovascular disease. The relationship appears to be present for both wine, beer and spirits. Effects of alcohol itself and also the role of different cardio-protective substances in alcoholic beverages are discussed. Alcohol has been suggested to beneficially affect the blood lipid profile, as it increases plasma HDL-cholesterol level. Furthermore, it may inhibit thrombogenesis by reducing thromboxan formation and decreasing the plasma level of fibrinogen. However, high blood concentrations of alcohol may impair fibrinolysis by increasing plasma plasminogen activator inhibitor-1 level. This action could contribute to explaining the ‘U’-shaped association between alcohol intake and cardiac events. Alcohol seems to promote abdominal fat distribution, but the importance of this effect in non-obese individuals is uncertain. Wine in particular, but also beer, contains polyphenols which act as antioxidants. Their action could maintain the integrity of the endothelial function by reducing the formation of superoxide. Moreover, these antioxidants may protect against LDL oxidation and modulate the macrophage attack on the endothelium. Although the cardio-protective effect of alcohol can hardly be addressed in healthy individuals by intervention studies with hard end points, there are many observational and experimental findings indicating that moderate alcohol drinking possesses properties preventive of cardiovascular disease.

The present review focuses on the specific effects of nutrients on the development of the immune system in early life. There is a big gap regarding the specific mechanisms that regulate immunity at the intestinal level and their impact in the systemic immune function. For this reason, during the last few years there has been great interest in ascertaining the mechanisms that regulate the intestinal immune function, as well as to understand how specific nutrients interact with the gut-associated lymphoid tissue. We have reviewed this topic with special emphasis on how human milk, and its components, influence the early development of intestinal immunity in breast-fed infants compared with formula-fed infants. Interactions between nutrients and intestinal microbiota have also been reviewed. Some micronutrients such as nucleotides and gangliosides, which are present in human milk and also in most foods, are able to influence immune functionality at very low concentrations. The specific action of these micronutrients on some parameters of immunity, as well as their potential mechanisms of action, have been considered in detail. However, there are limited data on how other specific nutrients, namely protein and non-protein N-containing compounds, lipids, carbohydrates, and others, such as minerals, vitamins, fibre, non-nutritional dietary compounds (flavonoids, carotenoids, phyto-oestrogens, etc), influence immunity. In the present review we have provided data regarding the potential effects of these compounds on the immune response in early life. The increasing use of functional foods by the public to improve their general health and prevent the incidence of chronic diseases has become a major area of interest within the nutrition community. Of the many functional foods available, probiotics have been most studied in infancy and childhood, particularly with regard to the prevention of allergic diseases. Infant formulae and fermented milks containing large quantities of probiotics are produced and consumed by Europeans and in other industrialized countries. In the present review we cover the clinical effects of probiotics in preventing disease during early life, as well as the potential mechanisms of interaction between probiotics and the gastrointestinal tract.

Beef and its products are an important source of nutrition in many human societies. Methods of production vary and include the use of hormonal compounds (‘hormones’) to increase growth and lean tissue with reduced fat deposition in cattle. The hormonal compounds are naturally occurring in animals or are synthetically produced xenobiotics and have oestrogenic (oestradiol-17β and its esters; zeranol), androgenic (testosterone and esters; trenbolone acetate) or progestogenic (progesterone; melengestrol acetate) activity. The use of hormones as production aids is permitted in North American countries but is no longer allowed in the European Union (EU), which also prohibits the importation of beef and its products derived from hormone-treated cattle. These actions have resulted in a trade dispute between the two trading blocs. The major concern for EU authorities is the possibility of adverse effects on human consumers of residues of hormones and metabolites. Methods used to assess possible adverse effects are typical of those used by international agencies to assess acceptability of chemicals in human food. These include analysis of quantities present in the context of known biological activity and digestive, absorptive, post-absorptive and excretory processes. Particular considerations include the low quantities of hormonal compounds consumed in meat products and their relationships to endogenous production particularly in prepubertal children, enterohepatic inactivation, cellular receptor- and non-receptor-mediated effects and potential for interference with growth, development and physiological function in consumers. There is particular concern about the role of oestradiol-17β as a carcinogen in certain tissues. Now subject to a ‘permanent’ EU ban, current evidence suggests that certain catechol metabolites may induce free-radical damage of DNA in cell and laboratory animal test systems. Classical oestrogen-receptor mediation is considered to stimulate proliferation in cells maintaining receptivity. Mathematical models describing quantitative relationships between consumption of small amounts of oestrogens in meat in addition to greater concentrations from endogenous production, chemical stoichiometry at cellular level and human pathology have not been developed. Such an approach will be necessary to establish ‘molecular materiality’ of the additional hormone intake as a component of relative risk assessment. The other hormones, although generally less well researched, are similarly subject to a range of tests to determine potentially adverse effects. The resulting limited international consensus relates to the application of the ‘precautionary principle’ and non-acceptance by the European Commission of the recommendations of the Codex Alimentarius Commission, which determined that meat from cattle, hormone-treated according to good practice, was safe for human consumers. The present review considers the hormone issue in the context of current international social methodology and regulation, recent advances in knowledge of biological activity of hormones and current status of science-based evaluation of food safety and risk for human consumers.

Acute and chronic alcohol (ethanol) intake and subsequent withdrawal exert major effects on tryptophan (Trp) metabolism and disposition in human subjects and experimental animals. In rats, activity of the rate-limiting enzyme of Trp degradation, liver Trp pyrrolase (TP), is enhanced by acute, but inhibited after chronic, ethanol administration, then enhanced during withdrawal. These changes lead to alterations in brain serotonin synthesis and turnover mediated by corresponding changes in circulating Trp availability to the brain. A low brain-serotonin concentration characterizes the alcohol-preferring C57BL/6J mouse strain and many alcohol-preferring rat lines. In this mouse strain, liver TP enhancement causes the serotonin decrease. In man, acute ethanol intake inhibits brain serotonin synthesis by activating liver TP. This may explain alcohol-induced depression, aggression and loss of control in susceptible individuals. Chronic alcohol intake in dependent subjects may be associated with liver TP inhibition and a consequent enhancement of brain serotonin synthesis, whereas subsequent withdrawal may induce the opposite effects. The excitotoxic Trp metabolite quinolinate may play a role in the behavioural disturbances of the alcohol-withdrawal syndrome. Some abstinent alcoholics may have a central serotonin deficiency, which they correct by liver TP inhibition through drinking. Further studies of the Trp and serotonin metabolic status in long-term abstinence in general and in relation to personality characteristics, alcoholism typology and genetic factors in particular may yield important information which should facilitate the development of more effective screening, and preventative and therapeutic strategies in this area of mental health.

Cats have obligatory requirements for dietary nutrients that are not essential for other mammals. The present review relates these idiosyncratic nutritional requirements to activities of enzymes involved in the metabolic pathways of these nutrients. The high protein requirement of cats is a consequence of the lack of regulation of the aminotransferases of dispensable N metabolism and of the urea cycle enzymes. The dietary requirements for taurine and arginine are consequences of low activities of two enzymes in the pathways of synthesis that have a negative multiplicative effect on the rate of synthesis. Cats have obligatory dietary requirements for vitamin D and niacin which are the result of high activities of enzymes that catabolise precursors of these vitamins to other compounds. The dietary requirement for pre-formed vitamin A appears to result from deletion of enzymes required for cleavage and oxidation of carotenoids. The n-3 polyunsaturated fatty acids (PUFA) requirements have not been defined but low activities of desaturase enzymes indicate that cats may have a dietary need for pre-formed PUFA in addition to those needed by other animals to maintain normal plasma concentrations. The nutrient requirements of domestic cats support the thesis that their idiosyncratic requirements arose from evolutionary pressures arising from a rigorous diet of animal tissue. These pressures may have favoured energy conservation through deletion of redundant enzymes and modification of enzyme activities to result in metabolites more suited to the cat's metabolism. However, this retrospective viewpoint allows only recognition of association rather than cause and effect.

The present review examines the importance of choline in dairy cow nutrition. Choline is an essential nutrient for mammals when excess methionine and folate are not available in the diet. The requirement for choline can be met by dietary choline and by transmethylation reactions. Two types of functions for choline are known: functions of choline per se; functions as a methyl donor. The two principal methyl donors in animal metabolism are betaine, a metabolite of choline, and S-adenosyl-methionine, a metabolite of methionine. Choline and methionine are interchangeable with regard to their methyl group-furnishing functions. In adult ruminants, choline is extensively degraded in the rumen; for this reason dietary choline contributes insignificantly to the choline body pool and methyl group metabolism is generally conservative with a relatively low rate of methyl catabolism and an elevated rate of de novo synthesis of methyl groups via the tetrahydrofolate system. In dairy ruminants, the dietary availability of choline is still low, but the output of methylated compounds in milk is high, and precursors from the tetrahydrofolate pathway are limiting, especially at the onset of lactation. Therefore choline may be a limiting nutrient for milk production in high-yielding dairy cows.

The impact of nutritional variation, within populations not overtly malnourished, on cognitive function and arousal is considered. The emphasis is on susceptibility to acute effects of meals and glucose loads, and chronic effects of dieting, on mental performance, and effects of cholesterol and vitamin levels on cognitive impairment. New developments in understanding dietary influences on neurohormonal systems, and their implications for cognition and affect, allow reinterpretation of both earlier and recent findings. Evidence for a detrimental effect of omitting a meal on cognitive performance remains equivocal: from the outset, idiosyncrasy has prevailed. Yet, for young and nutritionally vulnerable children, breakfast is more likely to benefit than hinder performance. For nutrient composition, despite inconsistencies, some cautious predictions can be made. Acutely, carbohydrate-rich–protein-poor meals can be sedating and anxiolytic; by comparison, protein-rich meals may be arousing, improving reaction time but also increasing unfocused vigilance. Fat-rich meals can lead to a decline in alertness, especially where they differ from habitual fat intake. These acute effects may vary with time of day and nutritional status. Chronically, protein-rich diets have been associated with decreased positive and increased negative affect relative to carbohydrate-rich diets. Probable mechanisms include diet-induced changes in monoamine, especially serotoninergic neurotransmitter activity, and functioning of the hypothalamic pituitary adrenal axis. Effects are interpreted in the context of individual traits and susceptibility to challenging, even stressful, tests of performance. Preoccupation with dieting may impair cognition by interfering with working memory capacity, independently of nutritional status. The change in cognitive performance after administration of glucose, and other foods, may depend on the level of sympathetic activation, glucocorticoid secretion, and pancreatic β-cell function, rather than simple fuelling of neural activity. Thus, outcomes can be predicted by vulnerability in coping with stressful challenges, interacting with nutritional history and neuroendocrine status. Functioning of such systems may be susceptible to dietary influences on neural membrane fluidity, and vitamin-dependent cerebrovascular health, with cognitive vulnerability increasing with age.

There are several enteric bacterial diseases and conditions of pigs that require control to prevent overt disease, to reduce morbidity and mortality, and to improve the efficiency of production. Traditionally, veterinarians, feed manufacturers and producers have relied upon antibiotics and minerals (for example, ZnO, CuSO4) in diets for a large part of this control. However, recent trends, particularly in Europe, are to reduce antimicrobial use and seek alternative or replacement strategies for controlling enteric bacterial diseases. The majority of these strategies rely on ‘nutrition’, taken in its broadest sense, to reduce the susceptibility of pigs to these diseases. Evidence to date suggests that specific dietary interventions, for example feeding very highly-digestible diets based on cooked white rice, can reduce the proliferation of a number of specific enteric bacterial infections, such as post-weaning colibacillosis. No simple and universal way to reduce susceptibility to pathogens in the gastrointestinal tract has been identified, and the underlying basis for many of the reported positive effects of ‘nutrition’ on controlling enteric infections lacks robust, scientific understanding. This makes it difficult to recommend dietary guidelines to prevent or reduce enteric bacterial diseases. Furthermore, some diseases, such as porcine intestinal spirochaetosis caused by Brachyspira pilosicoli, are sometimes associated with other pathogens (co-infections). In such cases, each pathogen might have different nutrient requirements, ecological niches and patterns of metabolism for which a variety of dietary interventions are needed to ameliorate the disease. Greater understanding of how ‘nutrition’ influences gut epithelial biology and immunobiology, and their interactions with both commensal and pathogenic bacteria, holds promise as a means of tackling enteric disease without antimicrobial agents. In addition, it is important to consider the overall system (i.e. management, housing, welfare) of pig production in the context of controlling enteric bacterial diseases.

The present review provides an investigation into the food choice decisions made by individuals in relation to fruit and vegetable consumption. A comprehensive body of evidence now exists concerning the protective effect of fruit and vegetables against a number of diseases, particularly cardiovascular disease and certain forms of cancer. Current UK recommendations are to increase intakes of fruit and vegetables to 400 g/person per d. In the main body of the review the factors that affect food choice decisions of adults in relation to fruit and vegetable consumption are studied, following a suggested framework of food choice. Factors covered include sensory appeal, familiarity and habit, social interactions, cost, availability, time constraints, personal ideology, media and advertising and health. The content of the review shows just how complex the food choice process can be. Health promotion techniques can be better targeted towards certain groups of individuals, all holding similar sets of values, when making food choice decisions. Food choice, in relation to fruit and vegetable intake, needs to be studied in more depth, in order to provide effective nutrition education programmes, in particular the sets of priorities that different sub-groups of the population consider when making food choice decisions.

Abstract Strong epidemiological data exists implicating anthropometric risk factors in breast cancer aetiology. In premenopausal women the risk of breast cancer increases with increased height, yet decreases with increasing weight and BMI. Although the evidence is not strong, a counter-intuitive positive relationship between central adiposity and premenopausal breast cancer risk is emerging. In post-menopausal women an increased risk in breast cancer has been found for all anthropometric measures: height, weight, BMI, measures of central adiposity (waist:hip ratio and waist circumference) and weight gain, with breast size being a possible additional risk factor. Weight loss as a strategy for reducing breast cancer risk seems to offer a viable prophylaxis in obese post-menopausal women, although data are limited. The evidence for anthropometric measures in relation to breast cancer risk is consistently stronger for post-menopausal women compared with premenopausal women and seems to be dependent on age. A number of possible biological mechanisms have been offered to explain the link between breast cancer risk and anthropometric measures. It has been hypothesised that obesity, especially central fat deposits, linked to insulin resistance, increases circulating hormones such as oestrogens, androgens, insulin, insulin-like growth factor-1 (IGF-1), and decreased levels of hormone-binding proteins such as steroid hormone-binding globulin and IGF-1 binding protein-1. Thus there are resulting increased concentrations of bioavailable sex hormones, which have been linked to increased breast cancer risk. As obesity is an important modifiable risk factor, which has been linked to increased post-menopausal breast cancer, public health recommendations to maintain ideal weight throughout life are warranted.