Oxidant stress is increasingly becoming an important hypothesis to explain the genesis of several pathologies, including cancer, atherosclerosis and also ageing. Beside a few rare genetic defects, dietary factors are thought to play a key role in the regulation of the production of reactive oxygenated species. An imbalance between nutrients, and in particular those involved in antioxidant status, could explain the onset of an enhanced production of free radicals. We will briefly review information concerning oxidation of lipids and lipoproteins which lead to atherothrombosis. We also present new findings supporting a role for blood platelets in generating oxidant species. New data are also described concerning the role of oxygenated derivatives of cholesterol, oxysterols, in cellular cholesterol efflux and NO production. Also, new developments relating to the influence of direct effects of free radicals on cellular cholesterol homeostasis are presented. Finally, the in vitro effects of butyrate, a natural short-chain fatty acid produced by bacterial fermentation, in the protection against free radical-mediated cytotoxicity are discussed. These data provide information on the mechanisms of dietary antioxidants in preventing oxidant stress.Résumé Au côté des rares cas d’origine génétique, les facteurs nutritionnels (déséquilibres alimentaires, déficience en nutriments antioxydants) jouent des rôles cruciaux dans la modulation de la production d’espèces actives de l’oxygène, conduisant à l’établissement d’un stress oxydant, situation métabolique de plus en plus reconnue comme susceptible d’être à l’origine de nombreuses pathologies comme les cancers, l’athérosclérose et également le vieillissement. Après avoir brièvement rappelé les données concernant l’oxydation des lipides et des lipoprotéines susceptibles de conduire au développement de l’athéro-thrombogenèse, nous présentons des données récentes et originales indiquant que les plaquettes sont en fait capables à l’instar d’autres cellules, de produire des formes actives de l’oxygène susceptibles de modifier les LDL. Des résultats originaux sont également exposés concernant l’effets des oxystérols, produits d’oxydation du cholestérol générés au cours de l’oxydation des LDL ou présents dans l’alimentation, sur deux paramètres importants comme l’efflux du cholestérol cellulaire et la production de monoxyde d’azote. De plus, des données nouvelles relatives à l’effets du stress oxydant et son inhibition par des antioxydants d’origine nutritionnelle sont exposées sur l’homéostasie du cholestérol cellulaire. Enfin, dans ce contexte, les effets potentiellement antiathérogènes d’un acide gras à courte chaîne produit par la fermentation bactérienne, le butyrate, sont décrits sur la protection de cellules en culture vis-à-vis d’un stress oxydant in vitro. Ces éléments contribuent à apporter de nouvelles informations renforçant la notion de fonctionnalité des nutriments dans la protection du stress oxydant en relation avec la pathogenèse.

It is now widely accepted that obesity develops by way of genetic mechanisms conferring specific dispositions which interact with strong environmental pressures. It is also accepted that certain dispositions constitute metabolic risk factors for weight gain. It is less well accepted that certain patterns of behaviour (arising from biological demands or environmental influences) put individuals at risk of developing a positive energy balance and weight gain (behavioural risk factors). Relevant patterns of behaviour include long-lasting habits for selecting and eating particular types of foods. Such habits define two distinct groups characterized as high-fat (HF) and low-fat (LF) phenotypes. These habits are important because of the attention given to dietary macronutrients in body-weight gain and the worldwide epidemic of obesity. Considerable evidence indicates that the total amount of dietary fat consumed remains the most potent food-related risk factor for weight gain. However, although habitual intake of a high-fat diet is a behavioural risk factor for obesity, it does not constitute a biological inevitability. A habitual low-fat diet does seem to protect against the development of obesity, but a high-fat diet does not guarantee that an individual will be obese. Although obesity is much more prevalent among HF than LF, some HF are lean with BMI well within the normal range. The concept of 'different routes to obesity' through a variety of nutritional scenarios can be envisaged, with predisposed individuals varying in their susceptibility to different dietary inputs. In a particular subgroup of individuals (young adult males) HF and LF displayed quite different profiles of appetite control, response to nutrient challenges and physiological measures, including BMR, RQ, heart rate, plasma leptin levels and thermogenic responses to fat and carbohydrate meals. These striking differences suggest that HF and LF can be used as a conceptual tool to investigate the relationship between biology and the environment (diet) in the control of body weight.

The adequacy of plant-based diets in developed and developing countries as sources of protein and amino acids for human subjects of all ages is examined. Protein quantity is shown not to be an issue. Digestibility is identified as a problem for some cereals (millet (Panicum miliaceum) and sorghum (Sorghum sp.)) and generally is poorly understood. Direct measurements of biological value in children are reviewed and scoring is consid-ered. Various existing requirement values for amino acids and especially lysine are reviewed, and it is concluded that stable-isotope studies do not yet provide adequate alternative values to N balance data, which for lysine are robust after recalculation and adjustment. A new maintenance requirement pattern is developed, with higher values than those of Food and Agriculture Organization/World Health Organization/United Nations University (1985) but lower values than the Massachusetts Institute of Technol-ogy pattern (Young et al. 1989). Calculations of age-related amino acid requirements are based on most recent estimates of human growth and maintenance protein requirements, a tissue amino acid pattern and the new maintenance amino acid pattern. These values appear valid when used to score plant proteins, since they indicate values similar to or less than the biological value measured directly in young children. When used to score plant-based diets in India, no marked deficiencies are identified. All regions score > 1 for adults, whilst for children scores range from > 1, (Tamil Nadhu) from 6 months of age to 0.78 (West Bengal), rising to 0.9 in the 2–5 year old, consistent with reports that high-lysine maize supports similar weight and height growth to that of casein. Inadequate amino acid supply is not an issue with most cereal-based diets.

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.

In early epidemiological studies of diet and cancer the stress was on the search for causal factors. Population (ecological) studies tended to show a strong correlation between meat intake, particularly red meat, and the risk of colo-rectal cancer. They also tended to show meat to be strongly inversely correlated with cancers of the stomach and oesophagus and liver. Early case- control studies tended to support the postulated role for red meat in colo-rectal carcinogenesis, although more recent case-control studies, particularly those from Europe, have tended to show no relationship. The cohort studies in general failed to detect any relationship between meat intake and colo-rectal cancer risk. The available evidence points to the intake of protective factors such as vegetables and whole-grain cereals being the main determinants of colo-rectal cancer risk, with meat intake only coincidentally related.

The p53 protein is a multi-function nuclear factor that is activated in response to multiple forms of stress and controls the proliferation, survival, DNA repair and differentiation of cells exposed to potentially genotoxic DNA damage. Loss of p53 function by mutation is a frequent event in human cancer, and is thought to result in the capacity of cells to acquire and accumulate oncogenic mutations during the progression of neoplasia. The p53 protein is a metal-binding transcription factor that is inactivated by metal chelation and by oxidation in vitro. In intact cells, p53 protein activity is crucially dependent on the availability of Zn ions and is impaired by exposure to Cd, a metal which readily substitutes for Zn in a number of transcription factors. Inactivation by Cd suppresses the p53-dependent responses to DNA damage. Overall, these findings indicate that regulation by metals plays an important role in the control of p53, and that perturbation of this control may explain the carcinogenic potential of several metal compounds. Résumé La protéine p53 est un facteur nucléaire multi-fonctionnel qui est activé en réponse à de multiples formes de stress et qui contrôle la prolifération, la survie, la réparation de l’ADN et la différenciation de cellules exposées à des agents génotoxiques. La perte de la fonction de p53 par mutation est un évènement fréquent dans les cancers chez l’homme, et l’on considère que cette inactivation a pour conséquence de rendre la cellule susceptible d’accumuler rapidement des mutations oncogéniques au cours de la progression du cancer. La protéine p53 est un facteur de transcription qui lie les métaux et qui peut être inactivée in vitro par chélation des métaux ainsi que par oxydation. Dans des cellules en culture, l’activité biologique de la p53 dépend de la bio-disponibilité en Zn, et est altérée par l’exposition des cellules au Cd, un métal qui se substitue facilement au Zn dans nombre de facteurs de transcription Zn-dépendants. L’inactivation de p53 par le Cd inhibe les réponses p53-dépendantes suite à la formation de lésions de l’ADN. Globalement, ces données suggèrent que la régulation par les métaux joue un rôle important dans le contrôle de la p53, et que des perturbations de ce contrôle pourraient contribuer à expliquer le potentiel carcinogénique de certains composés métalliques.

We have introduced a framework that enables the identification of the important elements in complex nutritional systems, and the quantification of the interactions among them. These interactions include those among the multiple constituents of the ingesta, as well as between behavioural (ingestive) and physiological (post-ingestive) components of nutritional homeostasis. The resulting descriptions provide a powerful means to generate and test hypotheses concerning the mechanisms, ecology and evolution of nutritional systems. We provide an overview of the key concepts involved in our scheme, and then introduce four examples in which the framework is used to develop and test hypotheses. In the first example we use comparative methods based on a data set of 117 insect species to test a prediction about the relationship between evolving an association with bacterial endosymbionts and the composition of the optimal diet. Second, using two species of locusts (a grass specialist and a generalist), we consider the relationship between an animal's diet breadth and the decision rules employed when feeding on foods containing suboptimal protein: carbohydrate values. Third, we introduce a mathematical model that predicts the dose-response properties of gustatory systems in the context of nutritional homeostasis. Finally, we consider the interaction between tannic acid and macronutrient balance in the diet of locusts.

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.

Ageing (and related diseases) may be described as a process which results from impaired immunological, genetic, neurological or endocrinological functions. Oxidative mechanisms may play an important role in the ageing process. It is important, therefore, to emphasize the relationship between health and nutrition in the elderly, particularly with regard to antioxidant micronutrient requirements. Indeed, accelerated ageing may be related to a deficit in the intakes of antioxidant vitamins (tocopherols, carotenoids and vitamin C) and trace elements (Zn and Se), as well as to an impaired adaptative mechanism against oxidative stress. Physiological modifications occurring during the lifetime and environmental influences are significant factors contributing to the impairment of micronutrient status, and these factors have to be considered when defining the specific requirements of the elderly. For Fe there is no evidence of benefit of supplementation in healthy subjects, but in the present state of knowledge combined supplementation, including Zn, Se, vitamins C and E and carotenoids, could be the best way to prevent accelerated ageing and reduce the risk of several common age-related diseases. Résumé De nombreuses théories (immunologique, génétique et neuroendocrinologique) ont été proposées pour expliquer les processus de vieillissement et les pathologies qui s’y rapportent. Les mécanismes oxydatifs pourraient contribuer à ces processus et plus particulièrement à leur accélération. La théorie radicalaire repose sur une modification avec l’âge du rapport prooxydants ou antioxydants dû à une majoration des processus oxydatifs accompagnés d’une diminution des systèmes de défense subséquentes à une carence en un ou plusieurs micronutriments antioxydants. Les modifications physiologiques qui accompagnent le vieillisement et une alimentation sélective contribuent aux modifications d’apport et d’absorption des micronutriments. Ces altérations sont accentuées lors de pathologies chroniques. Il n’existe pas de réel consensus sur les recommandations d’apports en oligoéléments adaptés au sujet âgé. Néanmoins les études récentes montrent qu’une association zinc, sélénium, vitamines antioxydantes (vitamines A et E et caroténodes) pourrait être le moyen le plus efficace de lutte contre les pathologies du grand âge et également de prévention du vieillissement accéléré.

The nutritional adequacy of plant-based diets is discussed. Energy and protein intakes are similar for plant-based diets compared with those containing meat. Fe and vitamin B12 are the nutrients most likely to be found lacking in such diets. Bioactive substances present in foods of plant origin significantly influence the bioavailability of minerals and requirements for vitamins. Well-balanced vegetarian diets are able to support normal growth and development. It is concluded that meat is an optional rather than an essential constituent of human diets.

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.

Effects of extreme environments on food intake in human subjects are analysed as behavioural and physiological adaptations to annual and circadian rhythms, temperature and altitude. Effects of the environment on food intake through food availability have direct consequences on energy balance and body weight. Different geographical regions show variations in the composition of dietary foods, i.e. the relative proportions of carbohydrate, protein and fat. In developing countries the annual cycle appears to affect body weight through dependence on food availability. In West-European countries this effect appears to depend on physical activity. Energy and macronutrient intakes appear to follow a circadian pattern, with breakfast being relatively high in carbohydrate and dinner being relatively high in fat. In cold conditions, maintaining an adequate food intake is important in sustaining normal physiological responses to cold. Evidence for a possible cold-induced increase in appetite is poor. A condition influencing level of intake is the palatability of the food. High altitude, i.e. hypobaric hypoxia, appears to reduce appetite, energy intake and body mass, irrespective of acute mountain sickness (AMS). Meal size is reduced and meal frequency increased. Under circumstances of AMS, dissociation between appetite and hunger occurs. Thus, spontaneous adaptation to extreme environments requiring increased energy intake occurs first by adaptation of body weight to a new energy balance. In general, prevention of a negative energy balance occurs by learning with respect to food intake. After return to normal, adjustment of energy intake to the original energy balance occurs with restoration of body weight.

Compared with non-vegetarians, Western vegetarians have a lower mean BMI (by about 1 kg/m2), a lower mean plasma total cholesterol concentration (by about 0.5 mmol/l), and a lower mortality from IHD (by about 25 %). They may also have a lower risk for some other diseases such as constipation, diverticular disease, gallstones and appendicitis. No differences in mortality from common cancers have been established. There is no evidence of adverse effects on mortality. Much more information is needed, particularly on other causes of death, other morbidity including osteoporosis, and long-term health in vegans. The evidence available suggests that widespread adoption of a vegetarian diet could prevent approximately 40 000 deaths from IHD in Britain each year.

Large herbivores play a major role in shaping vegetation community dynamics through selective consumption of particular plants and plant communities. An understanding of the factors influencing diet selection at the level of individual bites (‘bite scale’) is important for prediction of the impact of herbivores on vegetation at the habitat scale. Bite-scale diet selection represents an integration of the twin goals of maximizing nutrient intake and minimizing toxin intake. Recent research with ruminants in pen-fed situations has shown that animals are able to make choices between artificial foods that maximize growth and other production variables. The role of post-ingestive feedback as an important mechanism for allowing animals to assess the nutritional quality of particular foods, and so select optimal diets, has been recognized in a number of recent experiments. Our understanding of the role of toxin intake minimization in diet selection decisions is more rudimentary. An important advance in the last decade has been the acknowledgement of the role of post-ingestive feedback and learning as a mechanism for avoidance of dietary toxicity. Further research is required to assess the importance of these processes in relation to free-grazing animals. The extent to which an understanding of bite-scale diet selection can be used to predict habitat utilization is not well understood. At the habitat scale additional factors such as predator avoidance, social constraints, avoidance of parasitism and microclimatic effects have an important influence on foraging decisions. Future research needs to focus on developing a quantitative understanding of such decisions at the habitat scale.

Since discovering fire man has used heat to modify the sensory properties and to preserve foodstuffs. Nutrients are involved in a number of reactions induced by this form of treatment. Some of these reactions are desirable, e.g. the improvement in the digestibility and the attractiveness of a food. Some reactions are undesirable because they lead to considerable nutritional loss or may result in the formation of mutagenic and carcinogenic molecules. The present paper reviews recent studies in which most of the modifications generated by thermal treatments at both the industrial and domestic level are demonstrated. We focus on the processes and the importance of thermal treatments used currently, as well as the necessity for optimization to minimize undesirable effects. Résumé L’homme a toujours recherché les moyens de développer ou modifier les propriétés sensorielles des aliments. Certaines sont souhaitées (amélioration de l’attractivité de l’aliment, meilleure digestibilité), d’autres sont proscrites en raison de la perte de qualité nutritionnelle ou de l’apparition de substances mutagènes et carcinogènes, par exemple. Cet article est une compilation des plus récents travaux sur les modifications générées par les traitements thermiques des aliments, tant au niveau industriel que domestique. Il insiste particulièrement sur les process. En conclusion, l’importance des traitements thermiques est aujourd’hui confirmée, mais il convient de poursuivre l’optimisation des procédés afin de réduire les effets indésirables.

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.

Food choice is influenced by a large number of factors, including social and cultural factors. One method for trying to understand the impact of these factors is through the study of attitudes. Research is described which utilizes social psychological attitude models of attitude-behaviour relationships, in particular the Theory of Planned Behaviour. This approach has shown good prediction of behaviour, but there are a number of possible extensions to this basic model which might improve its utility. One such extension is the inclusion of measures of moral concern, which have been found to be important both for the choice of genetically-modified foods and also for foods to be eaten by others. It has been found to be difficult to effect dietary change, and there are a number of insights from social psychology which might address this difficulty. One is the phenomenon of optimistic bias, where individuals believe themselves to be at less risk from various hazards than the average person. This effect has been demonstrated for nutritional risks, and this might lead individuals to take less note of health education messages. Another concern is that individuals do not always have clear-cut attitudes, but rather can be ambivalent about food and about healthy eating. It is important, therefore, to have measures for this ambivalence, and an understanding of how it might impact on behaviour.

The quantitative evaluation of the allergenicity of food proteins and the clinical tolerance towards antigens are problems the food industry and the clinicians have to face. The allergenicity of a protein depends on multiple factors, including the stability to digestion and the interaction with the intestinal environment. In addition to the possible reduction in allergenicity by technological treatments such as heat and enzymic hydrolysis, the complex interactions existing between the antigens, the intestinal epithelium and the underlying immune system, as well as the individual susceptibility to the sensitizing epitopes, have to be taken into account. Indeed, the intestinal cells are able to take up and process proteins, and possibly to present them directly to mucosal lymphocytes. On the other hand, pathophysiological conditions can modify the interactions between food antigens and the immune system. A large number of methods has been developed to assess the residual antigenicity of food proteins, based on the various immune responses leading to intestinal or extradigestive pathologies. Thus, the difficulty in measuring the residual allergenicity of hypoallergenic formulas is partly due to the physiology of the gastrointestinal tract, since an intricate network of interactions between enterocytes and immune cells governs the development of the immune response to food antigens. RésuméL’évaluation de l’allergénicité des aliments et leur bonne tolérance clinique est une question touchant à la fois les industriels de l’agro-alimentaire et les cliniciens. L’allergénicité d’une protéine dépend de multiples facteurs parmi lesquels la résistance à la digestion, les interactions avec le tractus digestif et les facteurs environnementaux. L’allergénicité d’un produit alimentaire peut être modifiée non seulement par les traitements technologiques industriels, mais aussi par le tractus gastrointestinal. La susceptibilité individuelle aux epitopes peptidiques formés est également un facteur primordial. En effet, les interactions complexes existant entre les antigènes, l’épithelium intestinal et le système immunitaire muqueux peuvent conduirent à des réponses immunitaires différentes selon les individus. De nombreuses méthodes existent pour mesurer l’antigénicité résiduelle des aliments, basées sur la nature des différentes réactions immunitaires anormales conduisant à une pathologie intestinale ou extradigestive. La difficulté de mesurer l’allergénicité résiduelle de formules hypoallergéniques repose donc sur les relations complexes entre les antigènes alimentaires, l’épithelium intestinal et le système immunitaire muqueux.

The prevalence of obesity in children, as in adults, is increasing dramatically. The extent to which this is due to reduced energy expenditure, increased energy intake, or both, is unclear at present. This in part reflects the limitations of existing models of the pre-obese state. In childhood acute lymphoblastic leukaemia (ALL), patients typically gain weight excessively during and after 2 years of therapy, and are at high risk of becoming obese. Previous studies have failed to identify the cause of obesity in these patients. We have tested the hypothesis that excess weight gain in ALL is due to reduced total energy expenditure (TEE), measured using the doubly-labelled water method, and have identified risk factors for excess weight gain in ALL. Pre-obese children with ALL in the dynamic phase of weight gain are less physically active than their peers, with a reduced TEE of approximately 1.2 (95 % CI 0.2, 2.2) MJ/d. While other factors might contribute to excess weight gain, lifestyle (i.e. reduced habitual physical activity) plays a central role in ALL. Several considerations suggest that ALL might be a useful model of the pre-obese state: lifestyle is critical to development of obesity in ALL; ALL is relatively common; approximately 70 % of patients survive; patients are readily accessible during the 2 years of therapy and beyond.