Optimal health and well-being are now considered the true measures of human development. Integrated strategies for infant, child and adult nutrition are required that take a life-course perspective to achieve life-long health. The major nutrition challenges faced today include: (a) addressing the pending burden of undernutrition (low birth weight, severe wasting, stunting and Zn, retinol, Fe, iodine and folic acid deficits) affecting those individuals living in conditions of poverty and deprivation; (b) preventing nutrition-related chronic diseases (obesity, diabetes, CVD, some forms of cancer and osteoporosis) that, except in sub-Saharan Africa, are the main causes of death and disability globally. This challenge requires a life-course perspective as effective prevention starts before conception and continues at each stage of life. While death is unavoidable, premature death and disability can be postponed by providing the right amount and quality of food and by maintaining an active life; (c) delaying or avoiding, via appropriate nutrition and physical activity interventions, the functional declines associated with advancing age. To help tackle these challenges, it is proposed that the term ‘malnutrition in all its forms’, which encompasses the full spectrum of nutritional disorders, should be used to engender a broader understanding of global nutrition problems. This term may prove particularly helpful when interacting with policy makers and the public. Finally, a greater effort by the UN agencies and private and public development partners is called for to strengthen local, regional and international capacity to support the much needed change in policy and programme activities focusing on all forms of malnutrition with a unified agenda.

Nutrigenetics and personalised nutrition are components of the concept that in the future genotyping will be used as a means of defining dietary recommendations to suit the individual. Over the last two decades there has been an explosion of research in this area, with often conflicting findings reported in the literature. Reviews of the literature in the area of apoE genotype and cardiovascular health, apoA5 genotype and postprandial lipaemia and perilipin and adiposity are used to demonstrate the complexities of genotype–phenotype associations and the aetiology of apparent between-study inconsistencies in the significance and size of effects. Furthermore, genetic research currently often takes a very reductionist approach, examining the interactions between individual genotypes and individual disease biomarkers and how they are modified by isolated dietary components or foods. Each individual possesses potentially hundreds of ‘at-risk’ gene variants and consumes a highly-complex diet. In order for nutrigenetics to become a useful public health tool, there is a great need to use mathematical and bioinformatic tools to develop strategies to examine the combined impact of multiple gene variants on a range of health outcomes and establish how these associations can be modified using combined dietary strategies.

Profound loss of adipose and other tissues is a hallmark of cancer cachexia, a debilitating condition associated with increased morbidity and mortality. Fat loss cannot be attributable to reduced appetite alone as it precedes the onset of anorexia and is much more severe in experimental models of cachexia than in food restriction. Morphological examination has shown marked remodelling of adipose tissue in cancer cachexia. It is characterised by the tissue containing shrunken adipocytes with a major reduction in cell size and increased fibrosis in the tissue matrix. The ultrastructure of ‘slimmed’ adipocytes has revealed severe delipidation and modifications in cell membrane conformation. Although the molecular mechanisms remain to be established, evidence suggests that altered adipocyte metabolism may lead to adipose atrophy in cancer cachexia. Increased lipolysis appears to be a key factor underlying fat loss, while inhibition of adipocyte development and lipid deposition may also contribute. Both tumour and host-derived factors are implicated in adipose atrophy. Zinc-α2-glycoprotein (ZAG), which is overexpressed by certain malignant tumours, has been identified as a novel adipokine. ZAG transcripts and protein expression in adipose tissue are up regulated in cancer cachexia but reduced with adipose tissue expansion in obesity. Studies in vitro demonstrate that recombinant ZAG stimulates lipolysis. ZAG may therefore act locally, as well as systemically, to promote lipid mobilisation in cancer cachexia. Further elucidation of ZAG function in adipose tissue may lead to novel targets for preventing adipose atrophy in malignancy.

Use of the energy balance equation for understanding the causation of obesity is discussed. Its basis on the thermodynamic laws is expressed in mathematical models for body-weight changes. Only a very small net energy surplus per time unit constitutes the energy deposition during weight gain, making measurements of its components difficult. The physical laws provide exact quantitative relationships between energy intake, energy expenditure and deposition of energy, but cannot disentangle the initiating and driving forces of the energy imbalance, which may also be an active storage of fat in adipose tissue. These and various other limitations of the energy balance model warrant cautiousness in using the model in studies of obesity causation. Weight gain may be self-promoting and mathematical feedback models allowing estimation of such effects show that they are realistic. Predisposition and susceptibility should be distinguished, and susceptibility as a modifiable predisposition, the genetic and environmental contribution to predisposition and its usefulness as targets for prevention and treatment are discussed. Current progress in unravelling genetic predisposition, the complex genetically-determined mechanisms, the slower progress in unravelling the environmental influences, the different nature of genetic and environmental influences, the possible pathways of environmental influences and the environmental influences as mediators of genetic effects are addressed. The evidence behind the prevailing concept of the ‘obesogenic’ environment is critically analysed. Finally, particular opportunities for the identification of the causes of the obesity epidemic by detailed analysis of an observed irregular development of the epidemic over long time periods are presented, and evidence for predisposition as a result of postnatal environmental influences is inferred from these studies.

The relationship between glutamine and malignancy can be traced back to the 1950s and the requirement for glutamine for malignant-cell growth in culture. Later studies demonstrated an association between the rate of proliferation of the malignant cells and glutamine usage. The excessive use of glutamine by malignant cells was seen as an opportunity for the development of a treatment using glutamine analogues, but unfortunately excessive toxicity was observed during clinical studies. In animal models glutamine supplementation, initially thought to increase tumour growth, actually causes tumour regression as a result of improved immune clearance of the tumour and appears to reduce the severity of the side effects of chemo- and radiotherapy. This finding led to human studies in both traditional cancer therapy and bone-marrow transplantation, which are reviewed here. Unfortunately, the majority of the studies performed are small and have poor methodological reporting. There is clinical heterogeneity in terms of routes of administration, dosing schedules, chemotherapy regimens and diseases. Studies of glutamine in non-bone-marrow transplantation chemo- and/or radiotherapy treatment suggest a possible trend towards reductions in objective mucositis but no effect on subjective symptoms. There is no evidence for its effect on other clinical outcomes. For bone-marrow transplantation there appears to be some benefit from oral glutamine in reducing mucositis and graft v. host disease, while intravenous glutamine may reduce infections but at the expense of an increased relapse rate. Good-quality studies are required in this area.

The emerging role of adipose tissue as a dynamic endocrine organ with an extent of anatomical and physiological plasticity has generated numerous studies linking early-life events with long-term alterations in adipose tissue structure and function. Coupled with increasing rates of human obesity, which cannot be explained without some genetic component, the role of early programming of adipose tissue may provide an insight into potential mechanisms. The developmental origins of health and disease hypothesis investigates the potential association between a compromised fetal and postnatal environment and later disease, such as obesity and type 2 diabetes, in the offspring. A number of animal models have been developed to examine potential mechanisms that drive these physiological changes, including rodent and large-mammal models that provide mechanistic insights into the epidemiological findings. In utero challenges such as under- or over-provision of nutrients, placental insufficiency and glucocorticoid infusion, as well as postnatal nutritional challenges, can all result in the long-term programming of adipose tissue abundance and function. A range of hormones, enzymes, transcription factors and other metabolic signalling molecules have been implicated in adverse adipose tissue development, including leptin, glucocorticoids, members of the PPAR family, fatty acid-binding proteins and adipokines. The long-term structural and physiological consequences associated with these molecular and cellular changes are less well described. The experimental models, potential mechanisms and regulators of the early programming of adipose tissue in large mammalian species will be summarised in the present review.

The systematic failure to recognise and appropriately treat children with severe malnutrition has been attributed to the elevated case-fatality rates, often as high as 50%, that still prevail in many hospitals in Africa. Children admitted to Kilifi District Hospital, on the coast of Kenya, with severe malnutrition frequently have life-threatening features and complications, many of which are not adequately identified or treated by WHO guidelines. Four main areas have been identified for research: early identification and better supportive care of sepsis; evidence-based fluid management strategies; improved antimicrobial treatment; rational use of nutritional strategies. The present paper focuses on the identification of children with sepsis and on fluid management strategies.

Diabetes mellitus is escalating globally and it is predicted that 200 million individuals worldwide will have diabetes by 2010 and 300 million by 2025. However, there is compelling evidence from many studies that for subjects with impaired fasting glucose or impaired glucose tolerance the presentation of type 2 diabetes can be delayed by lifestyle modification. The aim of the present review is to present a summary of lifestyle modification interventions that have included a dietary component in their overall diabetes prevention programme. Medline, allied health literature and diabetes journals were searched for peer-reviewed literature using the terms ‘diet*’ and ‘diabetes’ and ‘intervention’. Inclusion criteria were: peer-reviewed studies from 1975 to 2008; a sample of at least fifty subjects; a healthy eating and/or physical activity component; prevention of diabetes as a primary goal. Generally, the participants were in a high-risk category for the development of diabetes. Outcomes were evaluated at two points in time (pre- and post-intervention) in terms of knowledge, behaviour change and clinical improvement, which included weight, blood pressure, BMI, body fat, waist circumference, waist:hip ratio and physiological and/or biochemical measures. Findings indicate that the most successful interventions combine individual dietary counselling with an activity component. Further factors predicting success are weight loss achieved, duration and intensity of the intervention and dietary compliance.

The ability to not only replicate but also extend the findings from both historical epidemiological studies and contemporary cohorts of the developmental programming of later disease are critical if the mechanisms by which early diet impacts on later disease are to be fully understood. To date, a plethora of models have been established, with the range including global changes in dietary input, imbalanced diets and diets deficient in single nutrients. Key factors in translating these findings to the human situation are the pronounced differences in the relative growth and development between large and small mammals from the time of conception through pregnancy, lactation and weaning. This disparity is reflected in the very different nutritional requirements between species and the substantial divergence between rodents and large animals in the ontogeny of many of the organ systems that are nutritionally regulated. For example, hypothalamic circuitry is much more developed in species with a long gestation and offspring are born with a mature hypothalamic–pituitary axis in sheep and man compared with mice and rats. Similarly, nephron number is established towards the end of gestation in large mammals compared with the lactational period in rats. These types of differences will impact on the ability of individual and combined nutritional interventions to reset developmental processes, and may be further compounded by the gender of a fetus. The challenge for future work in this exciting and dynamic area of research is to utilise these marked comparative differences to generate imaginative nutritional interventions in order to improve the viability, health and well-being of the offspring.

Anorexia nervosa has the highest mortality rate of any psychiatric condition and its management is complex and multi-faceted, requiring a multidisciplinary team approach. Dietitians are an important part of the multidisciplinary team, offering objective nutritional advice with the aim of helping the patient to develop an improved relationship with food. Refeeding patients with a low body weight requires careful management; nonetheless, refeeding the low-weight patient with anorexia presents many additional complications, largely of a psychological nature. Treatment plans need to consider psychological, physical, behavioural and psycho-social factors relating to anorexia nervosa. Currently, there is no consistent approach and a paucity of evidence to support best practice for weight restoration in this group of patients. Tube feeding is utilised at varying BMI in anorexia nervosa, mainly in an inpatient setting. However, its use should be seen as a last resort and limited to a life-saving intervention. Weight restoration is best managed by an experienced dietitian within a specialist eating disorders team, using normal foods. This approach is ideal for nutrition rehabilitation, promoting skills for eating and normal behaviour and providing a longer-term solution by challenging unhelpful coping strategies from the onset. Dietitians have a unique mix of skills and knowledge in numerous areas including nutrition, physiology, psychology, sociology and behaviour change, which can be applied to support patients with thoughts and behaviours around food, weight and appetite. Further research is required into the effectiveness of dietetic interventions in eating disorders in order to establish an evidence base for best practice.

The hypothesis that early-life growth patterns contribute to non-communicable diseases initially emerged from historical cohort studies, consistently associating low birth weight and infant weight gain with later disease risk. Cohort studies offer crucial life-course data on disease aetiology, but also suffer from important limitations, including the difficulty of adjusting for confounding factors and the challenge of interpreting data on early growth. Prospective randomised trials of infant diet appear to provide evidence in direct contradiction to cohort studies, associating faster early growth with disease risk. The present article attempts to resolve this contradiction on two grounds. First, insufficient attention has been directed to inconsistency of outcomes between cohort studies and prospective trials. Cohort studies can assess actual mortality, whereas prospective trials investigate proxies for disease risk. These proxies are often aspects of phenotype that reflect the ‘normalisation’ of metabolism in response to growth, and not all those displaying normalisation in adolescence and early adulthood may go on to develop disease. Second, a distinction is made between ‘metabolic capacity’, defined as organ development that occurs in early life, and ‘metabolic load’, which is imposed by subsequent growth. Disease risk is predicted to be greatest when there is extreme disparity between metabolic capacity and metabolic load. Whereas cohort studies link disease risk with poor metabolic capacity, prospective trials link it with increased metabolic load. Infancy is a developmental period in which nutrition can affect both metabolic capacity and metabolic load; this factor accounts for reported associations of both slow and fast infant growth with greater disease risk.

Whilst previously type 2 diabetes occurred in older adults, its incidence, together with obesity, has increased rapidly in children. An improved understanding of this disease pathway from a developmental view point is critical. It is likely that subtle changes in dietary patterns over an extended period of time contribute to diabetes, although this type of rationale is largely ignored in animal studies aimed at determining the mechanisms involved. Small-animal studies in which large, and often extreme, changes in the diet are imposed at different stages of the life cycle can have substantial effects on fat mass and/or pancreatic functions. These responses are not representative of the much more gradual changes seen in the human population. An increasing number of studies indicate that it is growth rate per se, rather than the type of dietary intervention that determines pancreatic function during development. Epigenetic mechanisms that regulate insulin secretion by the pancreas can be re-set by more extreme changes in dietary supply in early life. The extent to which these changes may contribute to more subtle modulations in glucose homeostasis that can accompany excess fat growth in childhood remains to be established. For human subjects there is much less information as to whether specific dietary components determine disease onset. Indeed, it is highly likely that genotype has a major influence, although recent data relating early diet to physical activity and the FTO gene indicate the difficulty of establishing the relative contribution of diet and changes in body mass to diabetes.