Obesity is now a major public health problem in both developed and developing countries. In the UK over 16 % men and 17.5 % women are obese, an increase of more than 100 % since 1980. However, interventions to prevent and treat obesity are hampered by an inadequate understanding of the aetiology of this condition. The present paper considers the current state of knowledge regarding the causes of obesity, including some of the genetic, metabolic, behavioural and environmental factors which influence energy balance. The present paper comprises The Nutrition Society Medal Lecture and focuses in particular on the research carried out at the MRC Dunn Nutrition Centre in Cambridge. It argues that despite decades of intensive research there is relatively little evidence of genetic or metabolic defects to explain the majority of cases of human obesity. Instead we must look to behavioural and/or environmental factors which may be underpinning the current epidemic of obesity.

The present lecture begins with a brief overview of the professional and scientific journey taken by Rudolf Schoenheimer, before turning to a discussion of the power of isotopic tracers in nutrition research. Schoenheimer's remarkable contributions to the study of intermediary metabolism and the turnover of body constituents, based initially on compounds tagged with 2H and later with 15N, spanned a mere decade. It is difficult, however, to overestimate the enormous impact of Schoenheimer's research on the evolution of biological science. After a relative hiatus, following Schoenheimer's death in 1941, in the use of stable nuclides as tracers in metabolism and nutrition, especially in human subjects, there is now an expanded and exciting range of techniques, experimental protocols and stable-isotope tracer compounds that are helping to probe the dynamic aspects of the metabolism of the major energy-yielding substrates, amino acids and other N-containing compounds, vitamins and mineral elements in human subjects. Various aspects of the contemporary applications of these tracers in nutrition research are covered in the present lecture.

New techniques in air-displacement plethysmography seem to have overcome many of the previous problems of poor reproducibility and validity. These have made body-density measurements available to a larger range of individuals, including children, elderly and sick patients who often have difficulties in being submerged underwater in hydrodensitometry systems. The BOD POD air-displacement system (BOD POD body composition system; Life Measurement Instruments, Concord, CA, USA) is more precise than hydrodensitometry, is simple and rapid to operate (approximately 1 min measurements) and the results agree closely with those of hydrodensitometry (e.g. ± 3.4 % for estimation of body fat). Body line scanners employing the principles of three-dimensional photography are potentially able to measure the surface area and volume of the body and its segments even more rapidly (approximately 10s), but the validity of the measurements needs to be established. Advances in i.r. spectroscopy and mathematical modelling for calculating the area under the curve have improved precision for measuring enrichment of 2H2O in studies of water dilution (CV 0.1–0.9 % within the range of 400–1000 μl/1) in saliva, plasma and urine. The technique is rapid and compares closely with mass spectrometry (bias 1 (SD 2) %). Advances in bedside bioelectrical-impedance techniques are making possible potential measurements of skinfold thicknesses and limb muscle mass electronically. Preliminary results suggest that the electronic method is more reproducible (intra- and inter-individual reproducibility for measuring skinfold thicknesses) and associated with less bias (+ 12 %), than anthropometry (+40%). In addition to these selected examples, the ‘mobility’ or transfer of reference methods between centres has made the distinction between reference and bedside or field techniques less distinct than in the past.

Surveys have shown that 20–50 % of hospital admissions suffer from nutritional depletion and that there is failure to recognize its existence and significance. More emphasis must be placed in clinical medicine on identifying subjects who are at high risk of developing disease-related malnutrition. There is a need to screen patients on admission to hospital to identify those at risk of nutrition-related complications. More formal determination of nutritional status should be carried out to define the nutritional status of the patient and to monitor changes in nutritional status during nutritional support. The most frequently used tests of nutritional status include dietary, anthropometric, biochemical and functional indices of nutritional status. It is important, and indeed is the skill of the nutritional care team (particularly the dietitian) to be able to evaluate these measurements, as many of them are affected by non-nutritional factors. There is no consensus on the best method for the accurate assessment of nutritional status. Practical difficulties arise with individual measurements and in their interpretation in the acute setting. The aim of the present paper is to identify the most relevant variables to measure in clinical medicine, and to discuss the limitations of their use in the acute setting.

The present paper explores the problems associated with assessment of nutritional status in the community and reviews the literature related to this subject. The first problem is one of terminology, since a logical first step before assessment is screening, which identifies characteristics known to be associated with dietary or nutritional problems. Its purpose is to differentiate individuals who are at high nutritional risk or have poor nutritional status. There are certain factors which should alert the primary health care team to the fact that nutritional intake may be reduced and that risk of malnutrition is increased. These include disease condition, functional disabilities, inadequate or inappropriate food intake, poor dentition or difficulty swallowing, polypharmacy, alcoholism, depression, poor social circumstances or recent discharge from hospital. Patients suffering from these factors need to be identified so that screening becomes a routine part of their medical treatment. At-risk groups include the elderly, the chronically ill, those with cancer and neurological disorders, post-surgical patients and children with developmental disabilities. In the community, practice and community nurses see the majority of at-risk patients and should carry out screening. A number of screening tools have been developed for community use. Most are aimed at the elderly population, but there are others designed to assess nutritional risk in children with developmental disabilities and the general population. These are reviewed and problems of content and validity identified. Some problems associated with nutritional assessment are also reviewed.

The purpose of the present paper is to outline the current situation in the management of obesity in adults, and to make some suggestions as to how health professionals involved in obesity treatment can best address this growing problem. Dietitians and nutritionists have long been involved in the treatment of obesity, and have a vital role to play in the battle to reverse the increasing prevalence of this major public health problem. However, the current management of obesity is far from ideal. There is evidence to suggest that in general health care, even when there are clearly effective clinical interventions, health professionals may not practise in the best way. Furthermore, some professionals may also hold negative attitudes towards the obese. These are the subject of a systematic review on improving health professionals' practice and organization of care in obesity treatment, the preliminary findings of which will be discussed in the present paper (Harvey et al. 1998a, b). A new approach to obesity is required, encompassing effective treatment and prevention strategies. A greater understanding of the problems faced by the obese individual in attempting to lose weight is also needed, with a range of treatment approaches on offer to acknowledge the heterogeneity of obesity. Those health professionals involved in obesity treatment must consider the impact of dietary advice given in a consultation against the impact of environmental cues that assail the patient as soon as they leave the room. Tackling the obesity epidemic requires action at the individual and population level if we are to see any reduction in prevalence.

An individual's eating behaviour is shaped by factors ranging from economic conditions and cultural practices to biological influences. The physiological system controlling appetite appears to be adapted to solving the problem of an unevenness of food supply across time, and is fairly permissive in its response to undereating and overeating. Consequently, when food is abundant, the diet is energy dense and energy expenditure is low, there is a strong tendency to become obese (i.e. obesity is better viewed as due to a ‘toxic’ environment than to faulty physiological control of appetite). Under such conditions the most common method of avoiding obesity is through the cognitive control of eating. However, dietary restraint and dieting are demanding tasks, and are associated with psychological costs, including significant impairment of cognitive performance. Restraint is also prone to disinhibition, with the result that it can sometimes undermine eating control, even leading to the development of highly disordered eating patterns. In part, these difficulties are due to the self-perpetuating nature of dietary habits: for example, hunger tends to be diminished during strict unbroken dieting, but increased in individuals having a highly variable eating pattern (such as occurs when eating is frequently disinhibited). These features of appetite control provide both barriers and opportunities for changing behaviour. Accordingly, there is a need for future research to focus on the psycho-social factors and the dieting practices predicting successful eating and weight control, with the objective of identifying the actual cognitive and behavioural strategies used by the many dieters and restrained eaters who are able to achieve weight loss and maintain long-term weight stability.

The immunological relationship beween the mammalian fetus and its mother during pregnancy has been considered similar to that between a transplanted allograft and its recipient ever since Medawar (1953) first proposed the concept of the ‘fetus as an allograft’ in the early 1950s. Based on this analogy, it has been assumed that implantation of the fetal placenta in the uterus would be controlled similarly by a maternal immune response mediated by T-cells recognizing paternally-derived alloantigens expressed by the placenta. Surprisingly, recent evidence suggests that implantation might involve predominantly a novel allogeneic recognition system based on natural killer cells rather than T-cells (Loke & King, 1995). The cellular and molecular basis of this local immune interaction between the fetal placenta and maternal uterus is now the focus of intense research interest. Since aberrant implantation can cause a variety of clinical problems, including miscarriage, intrauterine growth retardation and pre-eclampsia, an understanding of the immunological mechanism by which this process is controlled could lead to the development of regimens to improve fetal growth and development.

Recently, there has been much interest in the literature in the role of early nutrition and the health of the individual in adulthood. A majority of infants in the UK are born full term, while preterm infants account for 4–6 % of the total births. Milk feeding practices are divided into three groups: breast, combination (breast-fed with formula as‘top-up) and bottle (formula). In studies conducted by our group and other researchers immune function in full-term and preterm infants has been assessed by monitoring total and specific immunoglobulin E and specific immunoglobulin G levels. Dietary modification by the pregnant mother with a history of allergy in the family has been shown to have a positive effect with respect to allergy outcome and prevention of atopic disease in the infant. However, this dietary modification has to occur before week 22 of pregnancy and continue until the end of lactation to achieve a beneficial outcome to the infant. The stress of mothers restricting their diets may be disadvantageous to the fetus, and therefore any gain due to the dietary restriction may be lost. Researchers have shown that the early introduction of complementary foods and the greater diversity of these foods appeared to result in an increase in the incidence of atopic disease in the infant. In conclusion, in order to reduce the risk in their babies, mothers with a family history of atopic disease should breast-feed for more than 15 weeks and introduce solid foods after 4 months, limiting the variety until at least 6 months.

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.

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.

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.

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.

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.

During late autumn insectivorous bats must deposit a fat store to cover their energy demands throughout the period of hibernation, yet the density of aerial insects by this time has already declined from its peak in midsummer. Krzanowski (1961) suggested that bats are able to deposit a fat store by manipulating their energy expenditure; specifically by selecting cold roosting locations rather than warm roosts, and depressing their body temperatures during the day roosting period. It was hypothesized that these behavioural changes result in very low daily energy demands, and despite reduced food intake the animals are still able to gain body fat. We made several tests of this hypodiesis. First, we explored the thermo-selection behaviour of long-eared bats (Plecotus auritus) in the summer and in the pre-hibernal period. We found that in summer bats preferred temperatures of about 32–35° (about thermoneutral), but in the pre-hibernal period they preferred much colder temperatures of about 10°. Second, using open-flow respirometry we found that in the cold pre-hibernal bats entered torpor for an average of 14 h each day. Compared with bats held at 30° (that did not go torpid), the bats at 7° expended less energy. The extent of saving was sufficient to positively affect their mass balance, despite the fact that bats at lower temperature also had reduced digestive efficiencies. Our findings support the hypothesis that during the pre-hibernal period insectivorous bats manipulate their mass balance primarily by alterations in their energy expenditure, specifically utilizing energy-sparing mechanisms such as torpor.

The purpose of the present paper is to provide an introduction to modelling, particularly mathematical modelling, for nutritional researchers with little or no experience of the modelling process. It aims to outline the function of modelling, and to give some guidance on factors to consider when designing protocols to generate data as part of the modelling process. It is not intended in any way to be a comprehensive guide to mathematical modelling. The paper discusses the uses of modelling, and presents a ‘hydrodynamic analogy’ to compartmental modelling, to explain the process to the non-mathematically-minded and to examine some of the pitfalls to be avoided when using stable-isotope tracers. Examples of the use of modelling in nutrition are presented, including methods for determining absorption, as well as a discussion of possible future avenues for nutritional modelling.

The bioavailability in human subjects of non-nutrient plant factors, including dietary flavonoids and phyto-oestrogens, is of great importance relative to their reported health protective effects. These effects include protection against heart disease, and also in the case of the phyto-oestrogens, hormone-dependent cancers. Epidemiological studies have shown flavonoid intake (mostly quercetin) to be inversely associated with mortality from CHD. Quercetin is a potent antioxidant in vitro, and protection against the oxidative damage to LDL implicated in atherogenesis has been suggested as a possible mechanism. Human subjects can absorb significant amounts of quercetin (particularly in the glucoside form) and it would appear to be sufficiently bioavailable to act as an antioxidant in vivo; however, following our recent study (J O'Reilly, TAB Sanders and H Wiseman, unpublished results), it is currently less clear whether quercetin really can act as an antioxidant in vivo. The isoflavone phyto-oestrogens genistein and daidzein are much less effective antioxidants than quercetin in vitro, however, they are well-absorbed by human subjects and appear to be sufficiently bioavailable to act as antioxidants in vivo. In our recent study (O'Reilly et al. 1998) lower plasma isoprostane concentrations and increased resistance of LDL to oxidation were observed following the high-isoflavone dietary phase compared with the low-isoflavone dietary phase. Considerable inter-individual variation in isoflavone metabolite excretion has been observed, in particular the production of equol (the gut bacterial metabolite of daidzein; a more potent antioxidant and more oestrogenic than daidzein), and this appears to be influenced by habitual diet. Further studies on the bioavailability of these non-nutrient plant factors and related influencing factors are clearly still required.

The absorption of metal ions in the mammalian single-stomached gut is fortunately highly selective, and both luminal and tissue regulation occur. Initially, assimilation of metal ions in an available form is facilitated by the intestinal secretions, chiefly soluble mucus (mucin) that retards hydrolysis of ions such as Cu, Fe and Zn. Metal ions then bind and traverse the mucosally-adherent mucus layer with an efficiency M+ > M2+ > M3+. At the mucosa Fe3+ is probably uniquely reduced to Fe2+, and all divalent cations (including Fe2+) are transported by a membrane protein (such as divalent cation transporter 1) into the cell. This minimizes absorption of toxic trivalent metals (e.g. A13+). Intracellular metal-binding molecules (such as mobilferrin) may be present at the intracellular side of the apical membrane, anchored to a transmembrane protein such as an integrin complex. This mobilferrin would receive the metal ion from divalent cation transporter 1 and, with part of the integrin molecule, transport the metal to the cytosol for safe sequestration in a larger complex such as ferritin or‘paraferritin’. β2-Microglobulin and HFE (previously termed human leucocyte antigen H) may be involved in stabilizing metal mobilferrin-integrin to form this latter complex. Finally, a systemic metal-binding protein such as transferrin may enter the antiluminal (basolateral) side of the cell for binding of the sequestered metal ion and delivery to the circulation. Regulatory proteins, such as HFE, may determine the degree of ion transport from intestinal cells to the circulation. Gradients in pH and perhaps pCa or even pNa could allow the switching of ions between the different transporters throughout this mechanism.

There is growing need for accurate information regarding the bioavailability of carotenoids, both with respect to carotenoids per se and to the vitamin A value of provitamin A carotenoids in foods or supplement preparations. Little quantitative information is currently available, owing primarily to the lack of adequate methods to assess carotenoid bioavailability. Methods applied to xenobiotic drugs are in most cases not useful for carotenoids, many of which circulate in appreciable quantities in human plasma. Reported ranges of carotenoid bioavailability (% dose absorbed) range from 1–99, and variability is generally high both within and between treatments. With the current methods, relative bioavailability is more readily assessed than absolute bioavailability. The most commonly applied methods include measuring the increase in plasma carotenoid concentration following chronic intervention, and use of postprandial chylomicron (PPC) carotenoid or retinyl ester response following a single dose of carotenoid. The advantages and limitations of these approaches, together with examples of each, are discussed. A new PPC approach utilizing extrinsic-stable-isotope-labelled vitamin A (2H4-labelled retinyl acetate) is under development in our laboratory, and examples of its application are presented. The currently available data suggest that oil solutions of carotenoids are more bioavailable than those from food matrices, and heating can improve the bioavailability of carotenoids from some food products. Increased availability of labelled carotenoids and retinoids should aid the development of reliable methods of carotenoid bioavailability assessment. Such data are needed for dietary recommendations, supplement formulation, and design of intervention strategies involving carotenoids.