The inflammatory response to injury and infection, although an essential part of immune function, carries the risk of severe tissue depletion and immunosuppression. These outcomes increase morbidity and delay recovery. Evidence is accumulating that single-nucleotide polymorphisms in the genes controlling pro-inflammatory cytokine production adversely influence the response. Immunonutrition provides a means of modulating the inflammatory response to injury and infection, and thereby improves clinical outcome. n-3 Polyunsaturated fatty acids (n-3 PUFA), glutamine, arginine, S amino acids and nucleotides are important components of immunonutrient mixes. While animal model studies suggest that all these components may exert a beneficial effect in patients, the number of large randomized placebo-controlled trials utilizing immunonutrition is fairly limited and the observed effects are relatively small. Meta-analyses suggest that while immunonutrition may not reduce mortality rates, a reduction in hospital length of stay, decreased requirements for ventilation and lower infection rates are achieved by this mode of nutrition. The present paper discusses some underlying reasons for the difficulty in demonstrating the clinical efficacy of immunonutrition. Paramount among these reasons is the antioxidant status and genetic background of the patient. A number of studies suggest that there is an inverse relationship between inflammation and T-cell function. Immuno-enhancive effects have been shown in a number of studies in which n-3 PUFA, glutamine and N-acetyl cysteine have been employed. All these nutrients may exert their effects by suppressing inflammation; n-3 PUFA by direct suppression of the process and glutamine and N-acetyl cysteine by acting indirectly on antioxidant status. Glutamine and nucleotides exert a direct effect on lymphocyte proliferation. Preliminary data suggests that not all genotypes are equally sensitive to the effects of immunonutrition. When further studies have been conducted to discern the precise interaction between each individual's genotype of relevance to the response to injury and infection, and immunonutrients, the level of precision in the application of immunonutrition will undoubtedly improve.

The high mortality rate associated with human infections caused by Escherichia coli strains of the serotype O157:H7 has brought to public attention the importance of ruminants as reservoirs of food-borne pathogens. In addition to established examples such as salmonella, campylobacter and listeria, recent evidence is emerging of the role of food in the transmission of Helicobacter pylori and Mycobacterium paratuberculosis. Food-borne pathogens harboured by ruminants are spread through shedding in the faeces and subsequent faecal contamination of raw food. Ruminant shedding appears to be affected by diet and, of particular concern, may be increased during fasting regimens imposed during transport to the slaughterhouse. The survival of food-borne pathogens in the ruminant gut is affected by many factors including microbe–microbe interactions, interactions involving plant metabolites and the presence of inhibitory end-product metabolites such as short-chain fatty acids. The potential importance of digesta flow and bacterial detachment in shedding of food-borne pathogens is discussed. Experimental procedures with dangerous pathogens have constraints, particularly in animal experimentation. This situation may be overcome by the use of rumen-simulating fermentors. One such system which, like the natural rumen, has a different turnover rate for solid and liquid digesta, was found to maintain rumen-like variables over an 11 d period. This system may prove useful for the study of dietary effects on food-borne pathogens.

It is thought that nutrition during pregnancy plays a key role in the well-being of the mother and the newborn infant, and further influences health during childhood and adulthood. Pregnancy is a time of increased nutritional requirements, but many of these requirements will be met by adaptive physiological changes that occur during gestation, with little need to alter maternal dietary intake. A modest increment of food which provides 0.8 MJ/d (above prepregnant requirements) during the third trimester is considered adequate to meet the needs of fetal and maternal growth, and to satisfy the small increase in requirements of many macro- and micronutrients. However, requirements for vitamin D and folic acid increase substantially, and should be met primarily by supplementation. Food selection may also be altered to avoid a range of food-borne diseases and toxic constituents. There are a number of psycho-social reasons why pregnancy might be considered a good time for promoting changes in dietary behaviour for the health of the wider family. However, pregnancy may be a bad time to promote dietary change if it is perceived to involve slimming, if nutritional requirements are greatest before pregnancy, or if dietary changes made are harmful. There is little evidence to support educational interventions as successful at changing dietary behaviour during pregnancy. Pregnancy may be best viewed as an opportunity for maintaining good dietary selections and for building knowledge for future action, and should not be seen as the only opportunity for promoting dietary change within the life course.

Energy balance can affect the risk for hormone-related cancers by altering sex hormone levels. Energy intake and expenditure are difficult to measure in epidemiological studies, but a chronic excess of intake relative to expenditure leads to a high BMI, which can be accurately measured. In premenopausal women obesity has little effect on the serum concentration of oestradiol, but causes an increase in the frequency of anovular menstrual cycles and thus a reduction in progesterone levels; these changes lead to a large increase in the risk for endometrial cancer, but little change, or a small decrease, in the risk for breast cancer. In post-menopausal women oestradiol levels are not regulated by negative feedback, and obesity causes an increase in the serum concentration of bioavailable oestradiol; this factor causes increases in the risk for both endometrial cancer and breast cancer. The development of ovarian cancer appears to be related more strongly to the frequency of ovulation than to direct effects of circulating levels of sex hormones, and BMI is not clearly associated with the risk for ovarian cancer. In men, increasing BMI has little effect on bioavailable androgen levels, and any effect of obesity on prostate cancer risk is small.

Nutritional advice from doctors and other health workers is held in high regard by the general public. It is important, therefore, to ensure that the advice given is sound and safe. Historically, the training in nutrition for the health professions has been piecemeal and selective. As a first step in the development of national standards, a core curriculum on nutrition for health professionals was developed as part of the National Nutrition Task Force. Designed for undergraduates, the curriculum sought to provide a standard for training which would ensure safe practice. The curriculum, which has been accepted by all undergraduate medical schools, identifies eighteen bullet points covering: the principles of nutritional science; public health nutrition; clinical nutrition and nutritional support. Postgraduate training for doctors is the responsibility of the Royal Colleges, who have formed an Intercollegiate Group on nutrition. This group has developed an intercollegiate foundation course in nutrition which lasts for 1 week and is offered at different centres around the country. Using the Intercollegiate Course as a base, individual Colleges are exploring how they might best develop the next level of training by identifying the educational needs for nutrition in different sub-specialities. There is some discussion as to whether it is timely to develop a defined clinical speciality in human nutrition. Within these developments, nutritionists and dietitians are identified as a resource to be called upon by other health professionals, and therefore it is important that in their own training they are suitably equipped to take on this challenge.

Nutrition support for patients in hospital has become an essential form of therapy. Total parenteral nutrition (TPN) was the preferred way of giving nutrition to hospital patients for many years but enteral nutrition (EN) is now the preferred route. EN is believed to promote gut function and prevent translocation of intestinal bacteria, thus reducing the incidence of sepsis in critically ill patients. In consequence, the use of TPN has been discouraged as a dangerous form of therapy. Critical review of the data suggests that in the human subject TPN does not cause mucosal atrophy or increase translocation of bacteria through the small intestine. However, overfeeding, which is easy with TPN, can explain the results of studies which have shown that TPN increases sepsis. Furthermore, the risks of TPN-induced complications have been exaggerated. When there is risk of malnutrition and EN is not tolerated, or there is gut failure, TPN is an equally effective and safe alternative.

Recent theories propose that a Western lifestyle may increase cancer risk through alterations in the metabolism of insulin and insulin-like growth factors (IGF; McKeown-Eyssen, 1994; Giovannucci, 1995; Kaaks, 1996; Werner & LeRoith, 1996). Insulin regulates energy metabolism, and increases the bioactivity of IGF-I, by enhancing its synthesis, and by decreasing several of its binding proteins (IGFBP; IGFBP-1 and -2). Insulin and IGF-I both stimulate anabolic processes as a function of available energy and elementary substrates (e.g. amino acids). The anabolic signals by insulin or IGF-I can promote tumour development by inhibiting apoptosis, and by stimulating cell proliferation. Furthermore, both insulin and IGF-I stimulate the synthesis of sex steroids, and inhibit the synthesis of sex hormone-binding globulin (SHBG), a binding protein that regulates the bioavailability of circulating sex steroids to tissues. The present paper reviews epidemiological findings relating the risk of cancers of the colo-rectum, pancreas, breast, endometrium and prostate to body size (obesity, height) and physical activity, and discusses the relationships between obesity and physical activity and plasma levels of insulin, IGF-I and IGFBP. Subsequent sections review epidemiological findings relating cancer risk to indices of chronic hyperinsulinaemia, and to plasma levels of IGF-I and IGFBP. Conclusions are that chronic hyperinsulinaemia may be a cause of cancers of the colon, pancreas and endometrium, and also possibly of the breast. On the other hand, elevated plasma IGF-I, as total concentrations or relative to levels of IGFBP-3, appears to be related to an increased risk of prostate cancer, breast cancer in young women, and possibly colo-rectal cancer. For cancers of the endometrium, breast and prostate, these findings are discussed in the context of relationships between insulin and IGF-I and levels of bioavailable sex steroids.

A substantial and robust body of epidemiological evidence indicates that prenatal dietary experience may be a factor determining cardiovascular disease risk. Retrospective cohort studies indicate that low birth weight and disproportion at birth are powerful predictors of later disease risk. This prenatal influence on non-communicable disease in later life has been termed programming. Maternal nutritional status has been proposed to be the major programming influence on the developing fetus. The evidence from epidemiological studies of nutrition, fetal development and birth outcome is, however, often weak and inconclusive. The validity of the nutritional programming concept is highly dependent on experimental studies in animals. The feeding of low-protein diets in rat pregnancy results in perturbations in fetal growth and dimensions at birth. The offspring of rats fed low-protein diets exhibit a number of metabolic and physiological disturbances, and are consistently found to have high blood pressure from early postnatal life. This experimental model has been used to explore potential mechanisms of programming through which maternal diet may programme the cardiovascular function of the fetus. Indications from this work are that fetal exposure to maternally-derived glucocorticoids plays a key role in the programming mechanism. Secondary to this activity, the fetal hypothalamic–pituitary–adrenal axis may stimulate renin–angiotensin system activity, resulting in increased vascular resistance and hypertension.

Evidence is accumulating that high levels of physical activity are associated with a reduced risk of some cancers. This evidence is most consistent for colon cancer, which is reduced by 40–50 % among the most active individuals, compared with the least active. The effect is evident in men and women, and appears to be independent of important confounding factors. However, there may be important interactions with body fatness; a high BMI has been reported to be associated with an increased risk of colon cancer in sedentary men but not in physically-active men. Whilst the evidence on breast cancer is less consistent, case–control studies typically suggest a reduction of 25–30 % among the most active women, although several studies have found no effect. Potential mechanisms include systemic influences and others relevant only to site-specific cancers. One unifying hypothesis is that physical inactivity reduces insulin sensitivity, leading to a growth-promotional environment which may facilitate neoplasia. The non-specific immune system may be improved by physical activity, possibly through the summative effects of repeated exercise bouts. Regular exercise, even at a recreational level, probably reduces exposure to oestrogen and thus decreases the risk of breast cancer. Increased colonic peristalsis, and thus reduced bowel transit time, might partly explain the lower risk of colon cancer in active people. Physical activity emerges as one of the few modifiable risk factors for some cancers and, as such, justifies further study.

Predisposition to poor skeletal health resulting in osteoporotic fracture is a major public health problem, the future economical impact of which is likely to be phenomenal. Two mechanisms principally determine adult bone health: (1) maximum attainment of peak bone mass (PBM); (2) the rate of bone loss with advancing age. Both aspects are regulated by a combination of endogenous and exogenous factors, and although genetic influences are believed to account for up to 75 % of the variation in bone mass, there is still room for modifiable factors to play a vital role. Weight-bearing physical activity is beneficial to the skeleton, but clarification of the exact type, intensity and duration required for optimum bone mass is needed. Excessive levels of exercise, which result in amenorrhoea, are detrimental to skeletal health. The importance of Ca to bone remains controversial. There is evidence that Ca is effective in reducing late post-menopausal bone loss, but more research is required on the long-term benefit of increased Ca intake on PBM attainment. Vitamin D ‘insufficiency’ appears to be widespread amongst population groups and is an area of considerable public health concern. The role of other micronutrients on bone metabolism remains to be fully quantified, but data from a combination of experimental, clinical and observational studies suggest a positive link between alkaline-forming foods and indices of bone health. The influence of nutrient–gene interactions on the skeleton requires further elucidation, but it may be useful in the future to target nutrition advice at those individuals who are genetically susceptible to osteoporosis.

The physiological processes that underlie the reproductive cycle impose considerable metabolisable protein (MP) demands on a female, especially during the periparturient period. When MP supply falls short of MP demand (i.e. MP becomes scarce), certain, if not all, bodily functions are expected to be penalised. It has been proposed that partitioning of scarce MP is prioritised to reproductive rather than to immune functions. In other words, at times of MP scarcity, the penalty on expression of immunity would be expected to be greater than that on reproduction. This hypothesis forms a nutritional basis for the occurrence of periparturient breakdown of immunity to parasites (BIP), which can be observed in many host–parasite systems. In the present review we explore this nutritional basis, using periparturient sheep infected with the abomasal nematode Teladorsagia circumcincta as an example, and attempt to quantify its occurrence. Evidence supporting the nutritional basis of periparturient BIP is reviewed, covering experiments in which nutrient supply (from both exogenous and endogenous sources) and/or nutrient demand were manipulated. Quantitatively, MP requirements for expression of immunity to T. circumcincta were estimated to be about 1 g/kg metabolic body weight (body weight0·75) per d, approximately 5 % of the maximum MP requirements of periparturient sheep. The major component of this requirement was assumed to be for replenishing irreversible plasma protein losses into the gastrointestinal tract. Although confirmation of this estimate is required, such estimates may be used to improve the known MP requirements of periparturient animals, enabling the extent and the consequences of periparturient BIP to be minimised.

Research into the metabolic role of glutamine in trauma and sepsis brings evidence to suggest a conditional deficiency occurs because increased and altered tissue demands exceed endogenous production. Such a deficiency has functional implications, and the restorative provision of parenteral glutamine has been shown to offer improved clinical outcomes in a variety of conditions. In the critically-ill it is associated with improvements in immune function, and improved survival from infection leading to an overall improved outcome.

The modern dairy cow has been selectively bred to produce large amounts of milk. Partly as a result, food consumption is considerably less than milk energy output in early lactation. It is only at 2 months or more postpartum that intake increases to the point where positive energy balance is regained, the initial production being achieved by a substantial mobilisation of body reserves. These reserves are laid down before parturition, but it is certainly not the case that the pregnant cow will accumulate adipose tissue recklessly; in the last third of pregnancy well-fed cows in good body condition exhibit reduced, not increased, appetite. There is a fine balancing act to perform. Excessive body condition at parturition quickly leads to metabolic problems such as ketosis, but cows who subsequently become too thin have increased risk of metabolic diseases such as mastitis and lameness. The biological mechanisms regulating output of milk are reasonably well understood, those controlling appetite less well so, and there has been little attempt at systematic integration of the two. The transition from pregnancy to lactation represents a major challenge to homeostasis, made more complicated in multiparous cows by the fact that much of gestation is concurrent with lactation. Herein lies the potential for nutritionally-entrained flexibility. In the wild, concurrent pregnancy and lactation only occur when nutritional conditions are favourable. If conditions are poor, rebreeding will be delayed and lactation will continue, at an energetically-sustainable level, for much longer than its ‘normal’ duration. In this way the twin energetic burdens of pregnancy and lactation are separated, and extremes are avoided. Given the increasing public concern about stresses suffered by intensively-managed dairy cows, this case may be one where commercial dairying could learn useful lessons from nature.

Selection in commercial populations on aspects of output, such as for growth rate in poultry, against fatness and for growth rate in pigs, and for milk yield in cows, has had very large effects on such outputs over the past 50 years. Partly because of the cost of recording intake, there has been little or no selection for food intake or feeding behaviour. In order to predict the effects of such past, and future, selection on intake it is necessary to have some suitable theoretical framework. Intake needs to be predicted in order to make rational feeding and environmental decisions. The idea that an animal will eat ‘to meet its requirements’ has proved useful and continues to be fruitful. An important part of the idea is that the animal (genotype) can be described in a way that is sufficient for the accurate prediction of its outputs over time. Such descriptions can be combined with a set of nutritional constants to calculate requirements. There appears to have been no change in the nutritional constants under selection for output. Under such selection it is simplest to assume that changes in intake follow from the changes in output rates, so that intake changes become entirely predictable. It is suggested that other ways that have been proposed for predicting intake cannot be successful in predicting the effects of selection. Feeding behaviour is seen as being the means that the animal uses to attain its intake rather than being the means by which that intake can be predicted. Thus, the organisation of feeding behaviour can be used to predict neither intake nor the effects of selection on it.

Currently ‘accepted’ treatments for bone disease utilise drugs that inhibit osteoclastic bone resorption; these lead to a reduction in subsequent bone loss and thence, indirectly, to an increase in bone mass and fewer fractures. Three classes of compounds currently form the mainstay of therapy for osteoporosis: oestrogens (hormone-replacement therapy), ‘selective oestrogen receptor modulators’ and the bisphosphonates. Problems of patient compliance, real or theoretical long-term toxicological risks and the lack of bone anabolic agents of clinical utility suggest that there is a need for the development of further novel osteoclast resorption inhibitors. Recent biological and genetic findings in the area of bone cell function have led to the identification of new drug targets. These drugs include agents that (directly or indirectly): inhibit osteoclast adhesion to bone matrix; modify osteoclast differentiation; act on the proton pump and hence affect extracellullar acidification; antagonise extracellular enzymes that are involved in bone matrix protein degradation. Particular emphasis is placed in the present review on the evaluation of antagonists of αvβ3 integrin-mediated cell adhesion for use in bone disease. The wealth of new agents being developed suggests that resorption inhibition will be the best treatment for osteoporosis in the short to medium term, with the long-term aim still being toward developing anabolic drugs or cell therapeutics.

Ca nutritional requirements and bone Ca turnover can be assessed using numerous techniques. Among these techniques are bone mass measurements, tracer kinetic studies, bone histomorphometry and biochemical studies. Stable-isotope-based kinetic studies offer unique advantages in their ability to assess both Ca absorption and turnover. This approach is safe and readily applicable to subjects of all ages. Ca is essential for growth and maintenance of bone mineral throughout life. During pregnancy, increased intestinal absorption of Ca by the mother provides much of the Ca supplied to the fetus. During infancy, Ca supplied in human milk is primarily derived from maternal bone stores, which are quickly replenished during and after weaning. Early childhood is a time of relatively slow bone growth, with a rapid increase occurring during puberty. Recent kinetic studies demonstrate an increase in both Ca absorption and bone Ca deposition associated with early puberty. Bone Ca deposition reaches a maximum in females shortly before menarche. At that time the bone Ca deposition rate is approximately five times that of adulthood. The decline in bone Ca deposition rate is gradual after menarche. Ca absorption from the diet shows a gradual decline in adulthood as well. Ca supplementation, in the presence of adequate vitamin D, is effective in enhancing bone mineral content in childhood and in helping to maintain bone mineral content in adults. Maintaining adequate Ca nutriture throughout life may be necessary to minimize the risk of bone-loss disorders.

The hypothalamus is a major regulatory centre involved in the control of many important physiological axes. One of these axes is the regulation of ingestive behaviour. Recent work using a combination of genetic-mutant mouse models together with targeted gene deletions has contributed much to our understanding of how neural pathways of the hypothalamus are involved in the regulation of energy balance in animals. These pathways are also relevant to human energy homeostasis, as mutations in key genes are correlated with obesity. Many of the genes identified mediate the effects of leptin, and are therefore primarily involved in sensing and responding to peripheral signals. In seasonal animals, such as the Siberian hamster (Phodopus sungorus), there is evidence for a higher level of regulation. The systems involved regulate body weight around an apparent 'set-point' through the action of photoperiod via the neurohormone, melatonin. The ability to manipulate energy balance through photoperiod (and melatonin) in the seasonal-animal model offers novel opportunities to identify further fundamental aspects of the control mechanisms involved in the central control of energy homeostasis and body weight.

Certain dietary risk factors for physical ill health are also risk factors for depression and cognitive impairment. Although cholesterol lowering has been suggested to increase vulnerability to depression, there is better support for an alternative hypothesis that intake of n-3 long-chain polyunsaturated fatty acids can affect mood (and aggression). Possible mechanisms for such effects include modification of neuronal cell membrane fluidity and consequent impact on neurotransmitter function. Stronger evidence exists concerning a role for diet in influencing cognitive impairment and cognitive decline in older age, in particular through its impact on vascular disease. For example, cognitive impairment is associated with atherosclerosis, type 2 diabetes and hypertension, and findings from a broad range of studies show significant relationships between cognitive function and intakes of various nutrients, including long-chain polyunsaturated fatty acids, antioxidant vitamins, and folate and vitamin B12. Further support is provided by data on nutrient status and cognitive function. Almost all this evidence, however, comes from epidemiological and correlational studies. Given the problem of separating cause and effect from such evidence, and the fact that cognitive impairment and cognitive decline (and depression) are very likely to be significant factors contributing to the consumption of a poor diet, greater emphasis should now be placed on conducting intervention studies. An efficient approach to this problem could be to include assessments of mood and cognitive function as outcome measures in studies designed primarily to investigate the impact of dietary interventions on markers of physical health.

The purpose of the present paper is to review recent theoretical developments in food intake modelling applied to animal science and ecology. The models are divided into those that have been developed for intensive agricultural systems, and those which consider more extensive systems and natural systems. For the most part the present paper discusses models that predict the food intake of herbivores. The mechanisms of each model are discussed, along with a brief mention of the experimental support for the most popular models. We include a discussion of models that approach the study of food intake behaviour from an evolutionary perspective, and suggest that lifetime models are especially useful when food intake carries an intrinsic cost. These long timescale evolutionary models contrast with the more common food intake models, whose timescale is usually much shorter. We conclude that the ‘eating to requirements’ model highlights an important food intake mechanism that provides an accurate predictive tool for intensive agricultural systems. The mechanisms of food intake regulation in extensive systems are less certain, and closer links between the ideas of animal science and ecology will be helpful for improving our understanding of food intake regulation.