Conditioned food aversion is a powerful experimental tool to modify animal diets. We have also investigated it as a potential management tool to prevent livestock from grazing poisonous plants such as tall larkspur (Delphinium barbeyi), white locoweed (Oxytropis sericea) and ponderosa pine (Pinus ponderosa) on western US rangelands. The following principles pertain to increasing the strength and longevity of aversions: mature animals retain aversions better than young animals; novelty of the plant is important, although aversions can be created to familiar plants; LiCl is the most effective emetic, and the optimum dose for cattle is 200 mg/kg body weight; averted animals should be grazed separately from non-averted animals to avoid the influence of social facilitation which can rapidly extinguish aversions. Social facilitation is the most important factor preventing widespread application of aversive conditioning. When averted animals see other animals eat the target food they will sample it, and if there is no adverse reaction they will continue eating and extinguish the aversion. However, if averted animals can be grazed separately, aversions will persist. Aversive conditioning may provide an effective management tool to prevent animals from eating palatable poisonous plants that cause major economic loss.

Beef and dairy products suffer from a negative health image, related to the nature of their lipid fraction. Rumen lipid metabolism involves the presence of saturated lipids in ruminant tissues. Lipolysis, fatty acid biohydrogenation and formation of microbial fatty acids in the rumen and their effects on rumen outflow of fatty acids are discussed. Special emphasis is given to the formation of trans-fatty acids and the possibilities of decreasing biohydrogenation. Small differences in intestinal digestibilities of fatty acids are mentioned, followed by a discussion on transfer of absorbed fatty acids into milk and adipose tissue lipids. The preferential retention of polyunsaturated fatty acids as well as the balance between synthesis and incorporation of fatty acids in tissues is described. Dietary means for the modification of milk fat are listed, with special emphasis on the possibilities for enrichment in polyunsaturated fatty acids and the presence of conjugated linoleic acids. A description of the nature and development of fat depots in beef cattle is followed by a discussion of breed, conformation and feed effects on adipose tissue distribution and fatty acid composition. Special emphasis is given to the very lean Belgian Blue double-muscled breed. The review ends with a consideration of the limits to the modification of ruminant fats, involving considerations of consumer acceptance as well as animal welfare and environmental effects.

Placental weight is a primary factor determining size at birth in many species. In sheep, placental weight peaks at approximately mid-gestation, with structural remodelling occurring over the second half of pregnancy to meet the increasing nutritional demands of the growing fetus. Numerous factors influence placental growth and development in sheep, and many workers (see Kelly, 1992) have investigated the role of maternal nutrition as a regulator of placental and fetal size. We have studied the effects of feeding ewes approximately 50 % of their recommended energy requirements during early to mid-pregnancy on fetal and placental indices measured at mid-gestation (i.e. 80 d) and close to term (i.e. 145 d). Maternal nutrient restriction is associated with a reduction in placental weight at 80 d, but an increase in placental weight at 145 d of gestation, compared with ewes fed adequately in early pregnancy. No significant effect on fetal weight was observed at either 80 or 145 d gestation, although differences in body dimensions and the insulin-like growth factor-1 axis were found in lambs from nutrient-restricted ewes delivered close to term. Maternal nutrition during pregnancy plays a pivotal role in the regulation of fetal and placental development in sheep, and therefore has the potential to influence both short- and longer-term health outcomes.

The immune system is highly reliant on accurate cell–cell communication for optimal function, and any damage to the signalling systems involved will result in an impaired immune responsiveness. Oxidant-mediated tissue injury is a particular hazard to the immune system, since phagocytic cells produce reactive oxygen species as part of the body's defence against infection. Adequate amounts of neutralizing antioxidants are required, therefore, to prevent damage to the immune cells themselves. Many antioxidants can be obtained directly from the diet (e.g. ascorbic acid, α-tocopherol, carotenoids and polyphenolic flavonoids) or require micronutrients as integral components (e.g. Se in the metalloenzyme glutathione peroxidase (EC 1.11.1.9)). Numerous epidemiological studies have found strong associations between diets rich in antioxidant nutrients and a reduced incidence of cancer, and it has been suggested that a boost to the body's immune system by antioxidants might, at least in part, account for this. Although more striking effects have been observed in the elderly, there is also evidence that antioxidant nutrients can modify cell-mediated immune responses in younger individuals. Indeed, it might be essential to have an adequate intake of antioxidant nutrients from an early age in order to help prevent the development of, or at least delay the onset of, several degenerative disorders. The present paper will review the effects of specific nutrients on immune function in young to middle-aged human subjects, focusing on the antioxidant vitamins C and E, and on Se. A further review, dealing more specifically with the effects of carotenoids on human immune function, will be presented at a forthcoming meeting of the Nutrition Society.

Vitamin A is the generic term for a variety of fat-soluble substances including retinol, retinyl palmitate and the provitamin A carotenoids such as all-trans-β-carotene. Vitamin A is commonly known as the anti-infective vitamin and has an essential role in vision and cellular differentiation, the latter providing a unique core mechanism helping to explain the influence of vitamin A on epithelial barriers. Alterations in the epithelial lining of vital organs occur early in deficiency, suggesting a potentially important role for the barrier function. Vitamin A deficiency (VAD) is most commonly recognized in the eye. The conjunctival-impression cytology test detects the presence of larger irregular keratinized cells and the absence of mucous-secreting goblet cells, indicative of VAD. The method is simple, quick and sensitive in populations where VAD is present. In the respiratory tract, observational studies all show an association with VAD, although vitamin A supplementation studies appear to have little effect on respiratory disease. Organ-specific targeting may improve success rates. The dual-sugar intestinal-permeability test allows the effect of vitamin A supplementation to be monitored on the gastrointestinal tract. Two vitamin A supplementation studies were carried out recently in Orissa State, India. Healthy infants of weaning age were administered orally eight weekly doses of 5.0 mg retinol equivalents and hospitalized infants received one large oral dose 60 mg retinol equivalents in the form of retinyl palmitate. Improvements in gut integrity and haematological status were observed in both studies. In summary, the response of the eye to vitamin A supplementation is well established; the present review highlights some of the more recent observations examining the effects of vitamin A.

To determine the functions of retinoic acid receptors RAR and RXR, we have systematically knocked-out their genes by homologous recombination in the embryonic stem cells and generated null-mutant mice. This approach has allowed us to perform a genetic dissection of the retinoic acid signalling pathway.

Protein-energy undernutrition, or the possibility of its development, has been documented to occur frequently in surgical patients admitted to hospital. Nutritional status is known to deteriorate over the course of the hospital stay, with poor awareness by medical and nursing staff as to the deleterious effects of impaired nutritional status on clinical outcome and hospital costs. While there is no consensus on the best method for assessment of the nutritional status of surgical patients pre-operatively, there are a number of techniques available. These techniques can be divided into two types, those suitable for screening for nutrition risk on admission to hospital and those used to fully assess nutritional status. Both techniques have their limitations, but if used correctly, and their limitations recognized, should identify the appropriate degree of nutritional intervention for an individual patient in a timely and cost-effective manner. The techniques currently available for nutritional screening and nutritional assessment are reviewed, and their applicability to the Irish setting are discussed in the present paper.

The present article reviews immune ageing and its relationship with nutritional ageing, with a particular insight into the influences of disease on both ageing processes. Immune ageing can be described primarily as the progressive appearance of immune dysregulations, mainly acquired immunity (mature: immature, naive: memory T lymphocyte subset decreases) leading to gradual increases in T-helper 2: T-helper 1 cells. This change is due initially to decreased thymic function, and later to accumulative antigen pressure over the lifespan. In contrast, innate immunity (macrophage functions) is preserved during the ageing process and in the elderly this leads to macrophage–lymphocyte dysequilibrium, which is particularly critical during on-going disease. Indeed, any disease induces long-lasting acute-phase reactions in aged patients and leads to body nutritional reserve (mainly protein) losses. Episodes of disease in the aged patient progressively deplete body nutritional reserves and lead to protein–energy malnutrition, undernutrition-associated immunodeficiency, and finally cachexia. Undernutrition is a common symptom in the elderly; protein-energy malnutrition is found in more than 50 % of hospitalized elderly patients and in most elderly diseased subjects. In addition, micronutrient deficit or low levels are common in home-living self-sufficient apparently-healthy elderly subjects. All these nutritional deficits induce decreased immune responses, and micronutrient deficits are now thought to be partly responsible for the decreased immune responses (immune ageing?) observed in the apparently-healthy elderly. Indeed, several studies have shown that micronutrient supplements induce increased immune responses in the healthy elderly. The progression of infectious diseases depends on immune responses and on nutritional status before the onset of illness in aged subjects. In addition, recovery depends on the intensity of acute-phase responses in the undernourished elderly. In fact, chronic acute-phase responses, commonly associated with diseases in aged patients, lead to progressive lowering of metabolic responses in the undernourished elderly. This can be quantified by increased production of free radicals during treatment and these increases may explain the difficulty in successfully treating aged patients. Nutritive therapy in order to improve metabolic processes and also to maintain body reserves should be considered as a necessary adjuvant therapy in the treatment of elderly patients.

Immunonutrition generally refers to the effect of the provision of specific nutrients on the immune system. These nutrients typically have immunoenhancing properties, and recent advances in nutrition support involve studies designed to exploit the desirable biological properties of these nutrients. The term immunonutrition strictly implies that we are focusing on the effect of certain nutrients on aspects of the immune system. However, in reality immunonutrition also refers to studies that not only examine the function of lymphocytes and leucocytes, but which also study the influence of key nutrients on the acute-phase response, the inflammatory response and on gastrointestinal structure and function. The interest, therefore, is on the impact of immunonutrition on all aspects of host defence mechanisms in response to a catabolic stress. Major surgery evokes an acute-phase response, a transient immunosuppression and alterations in gastrointestinal function. Normal function is usually restored after a few days; however, in a subgroup of patients homeostasis may be lost and development of the systemic inflammatory response syndrome (SIRS) ensues. Results of recent clinical trials suggest that provision of immunomodulatory nutrients, including glutamine, arginine, n-3 polyunsaturated fatty acids and dietary nucleotides, may promote restoration of normal tissue function post-operatively and prevent the occurrence of SIRS.

The reduced contribution of physical activity to daily energy expenditure and the accessibility to high-fat foods have put an excessive burden on energy balance, resulting in an increase in the prevalence of obesity throughout the world. In this context, fat gain can be seen as a natural adaptation to deal with a fattening lifestyle, since the hormonal adaptations that accompany fat gain favour the readjustment of energy expenditure to energy intake. Intense physical activity would also seem to facilitate the regulation of energy balance, since it increases the energy cost of exercise, increases post-exercise energy expenditure and the potential of skeletal muscles to utilize lipids, and also favours a decrease in post-exercise intake. Moreover, the effects of intense exercise seem to be mediated by an activation of sympathetic nervous system activity that seems to be specific to skeletal muscle. It is also important to manipulate macronutrient composition in order to reduce fat intake, because unhealthy food habits can favour overfeeding and thus overcome the energy deficit caused by regular physical activity. Under free-living conditions, the combination of vigorous activity and healthy food practices can amount to a substantial weight loss which is comparable with that of other non-surgical approaches to treat obesity.

Our initial observations, in epidemiological studies, linking indices of poor early (fetal and infant) growth to the subsequent development of poor glucose tolerance and the insulin resistance syndrome in adult life, have been confirmed in studies in a wide variety of populations around the world. These findings led us 5 years ago to propose the ‘thrifty phenotype’ hypothesis. Tests of this hypothesis in an animal model in which the pregnant and/or lactating rat dams are fed on an isoenergetic diet containing just under half the normal protein content are consistent with the ideas put forward. They have also allowed us to refine the hypothesis in the light of the new data as follows: (1) the growth of the fetus (and possibly infant) is quantitatively and qualitatively altered by its nutritional environment (which may include maternal diet-dependent changes in maternal hormones); (2) these changes serve to select between the growth rates of different tissues according to priorities which differ between males and females (nutritional thrift) and to alter organ function to constitute a thrifty offspring adapted to survival in poor nutritional circumstances (thrifty phenotype); (3) an individual so constituted suffers adverse consequences in adult life if he/she experiences good or supranormal nutrition; (4) both poor insulin secretion and insulin resistance can result from these adaptive processes; (5) the adverse consequences include loss of glucose tolerance and hypertension. The precise outcome of growth retardation during early life may vary according to the type and timing of the factors responsible for the retardation. It remains to be determined to what extent these potentially adverse effects can be delayed or prevented by a suitable postnatal diet. Experiments in animal models are largely consistent with the concepts proposed from human epidemiological studies. They show that the metabolism of the liver, muscle and adipose tissue may be programmed by maternal nutrition during gestation and lactation. The combination of early growth restriction and subsequent adult obesity reproduced in the rat are the main features of the insulin resistance syndrome.

While many experimental studies have shown a protective effect of vitamin C in age-related cataract, other studies have revealed contrasting roles for this nutrient. Oxidative damage in the lens can be prevented by vitamin C. However, a pro-oxidant effect of vitamin C through H2O2 generation has been suggested. Vitamin C has also been shown to play a role in protein glycation, which is observed in cataract formation. A protective effect of dietary energy restriction appears to be inversely related to plasma vitamin C levels in rodents. Moreover, conclusions from human epidemiological and intervention studies are not uniform. The available evidence suggests that maintenance of sufficient plasma vitamin C is needed to prevent oxidative damage in the lens. More research will be needed in order to confirm the relative importance of the different roles of vitamin C in the eye lens.

There is an increasing interest in the relationship between nutrition and lung health. Epidemiological studies suggest that dietary habits may have an influence on lung function and the tendency to common lung diseases such as asthma, chronic obstructive pulmonary disease (COPD) and lung cancer. In particular, a diet rich in fresh fruit and fish has been associated with a salutary effect on lung health. End-stage COPD is associated with a state of nutritional depletion which is refractory to conventional nutritional supplementation. In contrast, malnutrition associated with cystic fibrosis is amenable to nutritional therapy, which has been shown to improve prognosis in this disease.

It is intuitive that an energy deficit induced by exercise induces an automatic increased drive for food (hunger and energy intake). However, the absence of a compensatory increase in energy intake (EI) in response to an exercise-induced increase in energy expenditure (EE) is now well documented. Thus, there is a weak coupling between exercise-induced increases in EE and EI. One paradox related to the phenomenon of a weak coupling between the exercise-induced EE and EI is the observation of a positive relationship between physical activity and food intake in the long-term free-living situation (i.e. tight coupling between EE and EI). It is possible, therefore, that a period of transition (uncoupling) occurs in the short-term, before a steady-state (coupling) condition is achieved. It is likely that a combination of physiological and behavioural adaptations occur in order to achieve a tight coupling between EE and EI. The precise physiological and behavioural changes that take place to obtain a new equilibrium (i.e. coupling between EE and EI) are still undetermined. The expectation that exercise-induced increases in EE should drive up hunger and food intake tends to be based on the concept of a strong coupling between physiology and behaviour. However, because of the individual's strong volitional control over eating behaviour, the psychological influences on the appetite response to exercise should not be undervalued. The psychological position of the individual (e.g. dietary restraint, food-related cognitions, reasons for exercising) could have a very strong influence on the food intake response to exercise. Misjudgements concerning the energy value of the food (EI) relative to the energy value of the exercise (EE) could be one possibility why exercise fails to be a successful method of weight loss for some individuals.

Fatty acid synthase (EC 2.3.1.85) is an enzyme involved in the lipogenic pathway allowing fatty acid synthesis from glucose. Glucose up-regulates the transcription of the fatty acid synthase gene in both adipocytes and hepatocytes, with insulin having only an indirect role. The signal metabolite could be glucose-6-phosphate rather than glucose itself. The glucose response element of the fatty acid synthase gene has not yet been precisely identified, although a −2 kb region of the fatty acid synthase promoter is sufficient to confer nutritional responsiveness to a reporter gene. ADD1/SREBP1, a b-HLH-LZ transcription factor belonging to the sterol regulatory element-binding protein family might be involved in the transduction of the glucose effect. Finally, the stimulatory effect of glucose on the expression of the fatty acid synthase gene is inhibited by the activation of AMP-activated protein kinase. Interestingly enough, AMP-activated protein kinase is structurally and functionally related to the yeast SNF1 protein kinase complex which is essential for the transcriptional activation of glucose-repressed genes in Saccharomyces cerevisiae.

Magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) are being increasingly used for investigations of human muscle physiology. While MRI reveals the morphology of muscles in great detail (e.g. for the determination of muscle volumes), MRS provides information on the chemical composition of the tissue. Depending on the observed nucleus, MRS allows the monitoring of high-energy phosphates (31P MRS), glycogen (13C MRS), or intramyocellular lipids (1H MRS), to give only a few examples. The observation of intramyocellular lipids (IMCL) by means of 1H MRS is non-invasive and, therefore, can be repeated many times and with a high temporal resolution. MRS has the potential to replace the biopsy for the monitoring of IMCL levels; however, the biopsy still has the advantage that other methods such as those used in molecular biology can be applied to the sample. The present study describes variations in the IMCL levels (expressed in mmol/kg wet weight and ml/100 ml) in three different muscles before and after (0, 1, 2, and 5 d) marathon runs for a well-trained individual who followed two different recovery protocols varying mainly in the diet. It was shown that the repletion of IMCL levels is strongly dependent on the diet post exercise. The monitoring of IMCL levels by means of 1H MRS is extremely promising, but several methodological limitations and pitfalls need to be considered, and these are addressed in the present review.

In mammals, the plasma concentration of amino acids is affected by nutritional or pathological conditions. For example, an alteration in the amino acid profile has been reported when there is a deficiency of any one or more of the essential amino acids, a dietary imbalance of amino acids, or an insufficient intake of protein. We examined the role of amino acid limitation in regulating mammalian gene expression. Depletion of arginine, cystine and all essential amino acids leads to induction of insulin-like growth factor-binding protein-1 (IGFBP-1) mRNA and protein expression in a dose-dependent manner. Moreover, exposure of HepG2 cells to amino acids at a concentration reproducing the amino acid concentration found in portal blood of rats fed on a low-protein diet leads to a significantly higher (P < 0·0002) expression of IGFBP-1. Using CCAAT/enhancer-binding protein homologous protein (CHOP) induction by leucine deprivation as a model, we have characterized the molecular mechanisms involved in the regulation of gene expression by amino acids. We have shown that leucine limitation leads to induction of CHOP mRNA and protein. Elevated mRNA levels result from both an increase in the rate of CHOP transcription and an increase in mRNA stability. We have characterized two elements of the CHOP gene that are essential to the transcriptional activation produced by an amino acid limitation. These findings demonstrate that an amino acid limitation, as occurs during dietary protein deficiency, can induce gene expression. Thus, amino acids by themselves can play, in concert with hormones, an important role in the control of gene expression.

Reduced physical activity commonly occurs in patients with disease or chronic disabilities, in the elderly, and in certain patients with obesity. Surprisingly, information on the effect of inactivity on energy homeostasis is scarce and often difficult to interpret. In models of reduced physical activity, such as space flights, bed-rest and confinement, subjects frequently lose weight (<5 %), predominantly in the form of fat-free mass. In some cases this is compensated by an increase in fat mass, which means that changes in weight are poor indicators of energy balance. The extent to which spontaneous reduction in energy intake (in most studies energy intake is fixed) compensates or overcompensates for the reduction in energy expenditure (mainly physical activity and to a small extent in BMR, typically <6 %) is largely underexamined. Preliminary observations suggesting that there is a preferential selection of low-energy-dense foods (low in fat) require confirmation under carefully controlled experimental conditions. It is concluded that a comprehensive and systematic evaluation is needed to address the effects and relevance of various degrees of physical inactivity to energy homeostasis, in relation to disease and space medicine.

The epidemiological evidence for a relationship between diet and indicators of asthma and chronic obstructive pulmonary disease (COPD) is evaluated. The review focuses on the intake of Na, n−3 fatty acids, and antioxidant vitamins as well as fruit and vegetables. Experimental studies suggest that a high-Na diet has a small adverse effect on airway reactivity in asthma patients. However, observational studies provide no clear evidence that high Na intake has adverse effects on airway reactivity or asthma symptoms in open populations. n−3 Polyunsaturated fatty acids, which are present in fish oils, are metabolized into less broncho-constricting and inflammatory mediators than n−6 polyunsaturated fatty acids. Studies in the general adult population suggest that a high fish intake has a beneficial effect on lung function, but the relationship with respiratory symptoms and clinically-manifest asthma or COPD is less evident. Also, experimental studies in asthma patients have not demonstrated an improvement in asthma severity after supplementation with fish oil. Several studies showed a beneficial association between fruit and vegetable intake and lung function, but the relationship with respiratory symptoms and the clinically-manifest disease was less convincing. A similar pattern was found for vitamin C in relation to indicators of asthma and COPD, but there are still conflicting results with respect to vitamin E and β-carotene. In conclusion, the epidemiological evidence for a beneficial effect on indicators of asthma and COPD of eating fish, fruit and vegetables is increasing. However, the effectiveness of dietary supplementation in open-population samples is often not demonstrated. Several unresolved questions are raised, which should be addressed in future studies on the relationship between diet and respiratory disease.