The present review will concentrate on the development of the gut-associated lymphoid tissue and the role of early nutrition in promoting immune function. The intestine is the largest immune organ in the body, and as such is the location for the majority of lymphocytes and other immune effector cells. The intestine is exposed to vast quantities of dietary and microbial antigens, and is the most common portal of entry for pathogens, some of which are potentially lethal. The development of normal immune function of the intestine is therefore vital for survival, and is dependent on appropriate antigen exposure and processing, and also an intact intestinal barrier. In early life innate mechanisms of defence are probably more important than active or adaptive mechanisms in responding to an infectious challenge, since the healthy neonate is immunologically naïve (has not seen antigen) and has not acquired immunological memory. During this period maternal colostrum and milk can significantly augment resistance to enteric infections. The mechanisms of enhancing disease resistance are thought to be passive, involving a direct supply of anti-microbial factors, and active, by promoting the development of specific immune function. A tolerance response to dietary and non-invasive antigens is generally induced in the gut. However, it must also be able to mount an adequate immune response to ensure clearance of foreign antigens. It is now recognized that regulation of tolerance and active immune responses is critical to health, and failure to regulate these responses can lead to recurrent infections, inflammatory diseases and allergies. The education of the immune system in early life is thought to be critical in minimizing the occurrence of these immune-based disorders. During this phase of development maternal milk provides signals to the immune system that generate appropriate response and memory. One factor that has been proposed to contribute to the increase in the incidence of immune-based disorders, e.g. atopic diseases in Western countries, is thought to be the increased prevalence of formula-feeding.

The impact of physical inactivity on health is well accepted throughout the medical and health service community. However, the case has largely been established through epidemiological studies with adults. Substantial attention has been paid to the activity levels of children and adolescents, largely because of changing lifestyles that have threatened the opportunity to be active and also introduced attractive sedentary alternatives such as playing computer games. The research evidence that children have become less active to the point where it is seriously damaging their current and future health has been difficult to establish. This situation is due to difficulties in establishing sensitive health risk markers, and also with the assessment of the different elements of physical activity which in children and adolescents is a complex profile of social behaviours. Self report of activity is unreliable with young children, and objective measures are required that are cheap and effective with large samples and that are capable of measuring levels, volume and patterns of physical activity. Accelerometry in combination with diaries offers the best current solution for most activity–health relationships, and for informing intervention need and design.

The rapidly rising prevalence of obesity, worldwide, has prompted re-evaluations of the definitions and diagnostic criteria, and of the extent of the burden it contributes to health care services. Although categorized arbitrarily for epidemiological purposes according to BMI > 25 kg/m2 (‘overweight’) and BMI > 30 kg/m2 (‘obese’), the disease itself (ICD code E.66) is the process of excess fat accumulation. It leads to multiple organ-specific pathological consequences, particularly if there is a tendency to intra-abdominal fat accumulation. The simplest field method to identify obesity and risk of medical problems is the waist circumference, and this method has found a special role in health promotion. Risks begin with waist > 80 cm (women) or > 94 cm (men). As a broad generalization, obesity produces few symptoms below the age of 40 years, but then several symptoms often develop; tiredness, breathlessness, back pain, arthritis, sweatiness, poor sleeping, depression and menstrual disorders all being common. The symptoms are often attributed to diseases in other body systems. Metabolic diseases like diabetes, hyperlipidaemia and, hypertension develop later, but the mean BMI at diagnosis of diabetes is 28 kg/m2. Ultimately, obesity increases the likelihood of myocardial infarction, stroke and several major cancers, but its biggest impact on health, especially in the elderly, is probably the multiplicity of effects on other body systems. The greatest challenge for public health is to develop effective preventive measures, recognizing that BMI > 25 kg/m2 before the age of 20 years is a very strong predictor of obesity and ill health in adulthood.

Dietary assessment of individual fatty acid intake is difficult due to a number of limitations. Information regarding the type, quantity and brand-name of fat used in cooking and at the table is required. In addition, margarine manufacturers may change the component oils used for reasons of cost, which changes the fatty acid composition of their products from season-to-season. Independent markers of fatty acid intake are required, therefore, to compensate for these limitations. Adipose tissue concentrations have been used as a measure of habitual intake of fatty acid groups and individual fatty acids in numerous studies. Saturated (SFA) and monounsaturated fatty acids (MUFA) are generally poorly correlated with adipose tissue concentrations, which can be explained partly by endogenous synthesis. In general, adipose tissue concentrations of exogenously-produced fatty acids (n-3 and n-6 polyunsaturated fatty acids (PUFA)) are well correlated with estimates of habitual intake. Correlations between dietary trans unsaturated fatty acids (TUFA) and adipose tissue concentrations vary between countries, which may be due to differences in dietary sources. Correlations may be affected by differences in bioavailability or selective retention of fatty acids in certain tissue lipids.

Essential fatty acids (EFA) are structural components of all tissues and are indispensable for cell membrane synthesis; the brain, retina and other neural tissues are particularly rich in long-chain polyunsaturated fatty acids (LCPUFA). These fatty acids serve as specific precursors for eicosanoids that regulate numerous cell and organ functions. Results from animal and recent human studies support the essential nature of n-3 EFA in addition to the well-established role of n-6 EFA for human subjects, particularly in early life. The most significant effects relate to neural development and maturation of sensory systems. Recent studies using stable-isotope-labelled tracers demonstrate that even preterm infants are able to form arachidonic acid (AA) and docosahexaenoic acid (DHA), but that synthesis is extremely low. Intracellular fatty acids or their metabolites regulate transcriptional activation of gene expression during adipocyte differentiation, and retinal and nervous system development. Regulation of gene expression by LCPUFA occurs at the transcriptional level and is mediated by nuclear transcription factors activated by fatty acids. These nuclear receptors are part of the steroid hormone receptor family. Two types of polyunsaturated fatty acid responsive transcription factors have been characterized, the peroxisome proliferator-activated receptor (PPAR) and the hepatic nuclear factor 4α. DHA also has significant effects on photoreceptor membranes involved in the signal transduction process, rhodopsin activation, and rod and cone development. Comprehensive clinical studies have shown that dietary supplementation with marine oil or single-cell oils, sources of LCPUFA, results in increased blood levels of DHA and AA, as well as an associated improvement in visual function in formula-fed premature infants to match that of human milk-fed infant. Recent clinical trials convincingly support LCPUFA supplementation of preterm infant formulations and possibly term formula to mimic human milk composition.

Obesity is defined as an excess accumulation of body fat. To measure fat in the body accurately is difficult, and no method is easily available for routine clinical use. Traditionally, overweight and obesity have been evaluated by anthropometric measurement of weight-for-height. More recently, BMI has been used. The normal range is 19–24·9 kg/m2, overweight is 25–29·9 kg/m2, and obesity ≥ 30 kg/m2. Not only is the total amount of fat an individual carries important, but also where the fat is distributed in the body. Fat in a central or upper body (android) distribution is most related to health risk. The most accurate way to measure central obesity is by magnetic resonance imaging or computer-assisted tomography scanning, but this approach is too expensive for routine use. Simple anthropometric measurements can be used, such as waist circumference. A waist circumference of greater than 1020 mm in men and 880 mm in women is a risk factor for insulin resistance, diabetes mellitus and cardiovascular disease. There is a clear genetic predisposition for obesity. The genetic contribution to obesity is between 25 and 40 % of the individual differences in BMI. For the overwhelming majority of individuals, the genetic predisposition will not be defined by one gene, but by multiple genes. Eventually, classification of obesity may be done by genetic means, but this approach will require more knowledge.

The aetiology and treatment of obesity have been fraught with disappointment for researchers, because the mechanisms that control fuel homeostasis and adiposity are incompletely understood. It is assumed that regulatory processes match the dietary fuel supply with energy requirements in order to maintain a stable body mass and adiposity. In this context several theories have been proposed to explain the laws of thermodynamics describing the conservation and transformation of energy in living organisms. In the light of new evidence it can now be hypothesized that the control of body weight and composition depends on an axis with three interrelated and self-controlled components: (1) food intake; (2) nutrient turnover and thermogenesis; (3) body fat stores. Complex feedback mechanisms underlie all these components. The major factors involved in obesity seem to be dietary and physical activity habits. These factors are affected by susceptibility genes that in turn may influence energy expenditure, fuel metabolism, muscle fibre function and appetite or food preferences. However, the increasing rates of obesity cannot be explained exclusively by changes in the gene pool, although genetic variants that were previously ‘silent’ are now being triggered by the high availability of energy- and fat-dense foods, and by the increasingly sedentary lifestyle of modern societies. The study of factors such as genetics and lifestyle implicated in weight gain and obesity is crucial for predictions about the future impact of the global epidemic of obesity, and provides a unique opportunity for the implementation of preventive action.

The present paper reviews the research of the authors and their colleagues over the past 20 years to provide improved nutritional and anthropometric guidelines for the assessment of lactational adequacy and for when the weaning process might be initiated. The nutritional guidelines are based on revised dietary energy requirements. The basic assumption is that since breast milk is a well-balanced food, if energy needs are satisfied so will those for essential nutrients. Energy requirements for young babies have been derived from the application of the doubly-labelled-water technique. This approach indicated that 460 kJ (110 kcal)/kg per d at 1 month and 397 and 355 kJ (95 and 85 kcal)/kg per d at 3 and 6 months respectively would be satisfactory for a nutrient content of high bioavailability. Translated into a breast-milk intake of 850 ml/d the latter would cover the dietary energy needs of the average child growing along the 50th centile until at least 4 months, but the typical child from many developing countries following the 25th centile until 6 months. The importance of revised growth reference values for infancy, equally crucial for assessing lactational adequacy, is also reviewed. In contrast with the shapes of earlier reference patterns, growth trajectories are different when babies are fed in accordance with modern paediatric advice. Mothers and health professionals using the older growth charts to assess the progress of a baby can be misled into assuming that the weaning process needs to be introduced sooner than necessary. Examples of this situation within the context of a developing country are provided.

Alcohol (ethanol; EtOH) provides fuel energy to the body (29·7 kJ (7·1 kcal)/g, 23·4 kJ (5·6 kcal)/ml), as do other macronutrients, but no associated essential nutrients. The thermogenic effect of EtOH (on average 15 % of its metabolizable value) is much greater than that of the main substrates utilized by the body, i.e. fat and carbohydrates (CHO), suggesting a lower net efficiency of energy utilization for EtOH than for fat and CHO. EtOH cannot be stored in the body and is toxic, so that there is an obligatory continuous oxidation of EtOH and it becomes the priority fuel to be metabolized. In contrast to CHO, its rate of oxidation does not depend on the dose ingested. As with CHO intake, it engenders a shift in postprandial substrate utilization (decrease in fat oxidation), but by a non-insulin-mediated mechanism. A limited amount of EtOH can be converted to fatty acids by hepatic de novo lipogenesis (as occurs with high levels of CHO feeding) from acetate production, which inhibits lipolysis in peripheral tissues. There is no evidence that EtOH consumed under normoenergetic conditions (i.e. isoenergetically replacing CHO or fat) leads to greater body fat storage than fat or CHO. However, there is still a lack of experimental studies on the influence of EtOH on the level of spontaneous physical activity in man. This effect may well depend on the dose of EtOH consumed as well as other intrinsic factors.

The increasing worldwide prevalence of obesity suggests that there is a chronic positive energy balance. This situation implies poor coupling between energy intake and energy expenditure, but the contribution of each of these factors remains unclear. Epidemiological data suggests that physical activity has a role in the prevention of weight gain, although there is little evidence that it has a beneficial role in weight loss. High-fat diets have also been implicated, evidence from a variety of sources suggests that diets high in fat undermine appetite regulatory mechanisms. There has been much research to investigate the coupling between energy expenditure and energy intake in the short term in an attempt to elucidate some of the mechanisms involved. However, mechanisms regulating appetite are very complex, and it is currently unclear at which points physical activity and diet may have an influence.

The importance of cultural and behavioural factors in children’s nutrition, particularly with regard to feeding, has been recognized only recently. The combination of evidence regarding the importance of caregiving behaviour for good nutrition, and improved strategies for measuring behaviour have led to a renewed interest in care. The UNICEF conceptual framework suggests that care, in addition to food security and health care services, are critical for children’s survival, growth and development. The present paper focuses on the care practice of complementary feeding, specifically behavioural factors such as parental interaction patterns, feeding style and adaptation of feeding to the child’s motor abilities (self-feeding or feeding by others). Three kinds of feeding styles (Birch & Fisher, 1995) are identified: controlling; laissez-faire; responsive. Probable effects of each feeding style on nutrient intake are described. A number of studies of feeding behaviour have suggested that the laissez-faire style is most frequently observed among families and communities with a higher prevalence of malnourished children. Nutrition interventions that have been able to show significant effects on outcomes, such as the Hearth Model in Vietnam (Sternin et al. 1997), have usually incorporated behavioural components in their intervention. At this time, there have been no tests of the efficacy of behavioural interventions to improve feeding practices. Research is needed to understand behavioural factors in complementary feeding, and to identify and test intervention strategies designed to improve nutrient intake of young children. Finally, the paper concludes with a discussion of how nutrition programmes might change if care were incorporated.

Vitamin A (VA) deficiency compromises antibody responses to T-cell-dependent antigens such as tetanus toxoid, but this effect can be reversed through administration of retinol or retinoic acid (RA). To test whether RA and polyriboinosinioc : polyribocytidylic acid (PIC), a known inducer of several forms of interferon (IFN), can cooperate to increase specific immunoglobulin (Ig)G and IgM production during VA deficiency, rats and mice were made VA-deficient, immunized with TT and treated with all-trans-RA, PIC or their combination. VA-deficient rats produced low primary and secondary anti-tetanus IgG responses (VA-deficient controls v. VA-sufficient controls P < 0·001), although total IgG was slightly elevated when compared with VA-sufficient control rats. Although RA administered alone elevated antibody production during VA deficiency to control levels, RA combined with PIC synergistically enhanced these responses (RA and PIC group v. all other groups P < 0·0001). In contrast, Balb/c mice maintained on a VA-deficient diet and immunized in a similar fashion showed no impairment in antigen-specific IgG levels, but treatment with a combination of RA and PIC still evoked an additive enhancement in antigen-specific antibody production. Additionally, RA and PIC administration to VA-sufficient mice resulted in elevated antibody responses, suggesting that this combination should be evaluated further for its immuno-stimulatory effects.

Despite widespread interest in body-weight control, the prevalence of obesity continues to rise worldwide. Current public health advice for obesity prevention is clearly failing. The present paper examines the appropriateness of current public health advice for body-weight control, i.e. to reduce consumption of fatty foods, to reduce consumption of sugar and to avoid snacking between meals. An increase in carbohydrate : fat ratio should improve body-weight control, as high-carbohydrate low-fat diets are less likely to lead to overeating, and if overeating does occur, less of the excess energy is likely to be stored as fat. However, it is suggested that for the long-term prevention of weight gain, advice to increase consumption of carbohydrate-rich foods may be more effective than advice which focuses on reducing consumption of fatty food. Moreover, in view of the inverse relationship between fat and sugar intakes, sugar may have a positive role to play in body-weight control in facilitating an increase in carbohydrate : fat ratio. Snacking for most individuals appears not to adversely affect body-weight control, and for some it may improve control. This situation may exist because frequent eating helps appetite control, thus preventing overeating at meals, and as snacks overall tend to be higher in carbohydrate and lower in fat than meals, frequent eating may be a strategy for increasing carbohydrate : fat ratio. It is also suggested that eating ‘little and often’ may be a more compatible pattern of eating for a physically-active lifestyle than eating large meals. Perhaps the most appropriate advice on food intake that would work synergistically with concurrent advice to increase physical activity is to eat more carbohydrate, and to eat frequently.

Knowledge of energy expenditure is especially important in disease, and may in fact help in the understanding of the pathophysiology of wasting associated with disease. Energy requirements in a clinical setting are often ‘prescribed’ by health professionals, either directly through enteral or parenteral feeding, or perhaps controlled through a hospital diet. Studies initially suggested an increase in energy expenditure, and thus energy requirements, as a direct result of an increase in basal metabolic rate often seen in disease. However, many problems exist in the measurement of BMR in a disease situation, due to the effects of drugs, clinical practice, feeding or possibly anxiety either as a cause of the disease or the measurement itself. These problems could in themselves contribute to the rise in metabolism seen in disease. More recently, however, with the use of tracer techniques such as doubly-labelled water and the bicarbonate–urea method, more accurate estimates of energy expenditure, and thus energy requirements, have been made. Some such measurements have in fact shown that even with an elevated BMR, free-living total energy expenditure can in fact be reduced in many disease situations, suggesting a reduced rather than an increased energy requirement. The present review investigates measurements of total energy expenditure in disease to explore the hypothesis that energy expenditure in disease, even with an elevated BMR, can in fact be reduced due to a concurrent reduction in physical activity.

Although failure to thrive (FTT) is generally thought to be a nutritional problem, dietary intake in children with FTT has been little researched. We describe two community-based studies of dietary intake and eating behaviour in FTT. The first study of ninety-seven children with FTT identified by population screening found that only a minority of case children were associated with neglect, organic illness or deprivation, even though dietary information suggested an underlying nutritional cause in the majority. Limited case-control data suggested significantly delayed weaning and less liking for food in general among the case children. The second study found diminished appetite, delayed progression onto solid foods and fewer foods eaten by forty-four children referred with FTT compared with forty-five controls, but was unable to detect a significant difference in energy intake, even allowing for varying body composition and other confounding variables. This study also revealed the bias introduced by recruiting case children by referral rather than screening, and that despite rigorous matching procedures the controls were not representative of the general population. These studies suggest a wide range of differences in eating behaviour and feeding patterns between children with FTT and controls, but suggest that measurements of nutrient totals may not be robust. Studies of FTT based on referred children can be misleading, as can comparison with controls, unless allowance can be made for important confounding social variables.

Inadequate nutrition is the main cause of low productivity by ruminants in sub-Saharan Africa. The primary feed resources in the region include natural pasture and crop residues that have tough texture, poor digestibility and are deficient in nutrients. These deficiencies can be corrected by supplementation with high-density feeds such as oilseed cakes and proteins of animal origin. However, protein sources such as oilseed cakes are beyond the economic reach of most farmers, while the incidence of bovine spongiform encephalopathy in Western intensive animal production may be thought to argue against the use of animal proteins. Local tree legumes have been investigated as potential supplements for ruminants because of their beneficial effect of increasing metabolizable energy intake, N intake and feed efficiency, and improving animal performance. However, our work has suggested that some plant materials may have a nutritional value beyond simply their nutrient content, i.e. as rumen-manipulating agents. The foliage of some tree legumes has been shown to be selectively toxic to rumen protozoa. Rumen protozoa ingest and digest bacteria and fungi, degrading their cellular protein to NH3. Microbial protein turnover due to protozoal predation in the rumen may result in the net microbial protein outflow being less than half the total protein synthesized. Results from in vivo experiments have clearly shown that duodenal flow of both undegraded dietary and bacterial protein is generally increased by defaunation. However, no practical method has been developed to date to eliminate protozoa. Anti-protozoal plants may be promising, safe, natural defaunating agents.

Inheriting genetic risk factors for multiple sclerosis (MS) is not sufficient to cause this demyelinating disease of the central nervous system; exposure to environmental risk factors is also required. MS may be preventable if these unidentified environmental factors can be avoided. MS prevalence increases with decreasing solar radiation, suggesting that sunlight may be protective in MS. Since the vitamin D endocrine system is exquisitely responsive to sunlight, and MS prevalence is highest where environmental supplies of vitamin D are lowest, we have proposed that the hormone, 1,25-dihydroxycholecalciferol (1,25-(OH)2D3), may protect genetically-susceptible individuals from developing MS. Evidence consistent with this hypothesis comes not only from geographic studies, but also genetic and biological studies. Over-representation of the vitamin D receptor gene b allele was found in Japanese MS patients, suggesting it may confer MS susceptibility. Fish oil is an excellent vitamin D source, and diets rich in fish may lower MS prevalence or severity. Vitamin D deficiency afflicts most MS patients, as demonstrated by their low bone mass and high fracture rates. However, the clearest evidence that vitamin D may be a natural inhibitor of MS comes from experiments with experimental autoimmune encephalomyelitis (EAE), a model of MS. Treatment of mice with 1,25-(OH)2D3 completely inhibited EAE induction and progression. The hormone stimulated the synthesis of two anti-encephalitogenic cytokines, interleukin 4 and transforming growth factor β-1, and influenced inflammatory cell trafficking or apoptosis. If vitamin D is a natural inhibitor of MS, providing supplemental vitamin D to individuals who are at risk for MS would be advisable.

Adipose tissue performs complex metabolic and endocrine functions. Among the endocrine products produced by adipose tissue are tumour necrosis factor α, interleukin 6, acylation-stimulating protein and leptin. The present review will focus primarily on mechanisms regulating leptin production and leptin action, and the implications of this regulation in the control of energy balance. Leptin acts in the central nervous system where it interacts with a number of hypothalamic neuropeptide systems to regulate feeding behaviour and energy expenditure. The presence of extreme obesity in animals and human subjects with mutations of the leptin gene or the leptin receptor demonstrates that normal leptin production and action are critical for maintaining energy balance. Insulin is the major regulator of leptin production by adipose tissue. Insulin infusions increase circulating leptin concentrations in human subjects. Plasma leptin levels are markedly decreased in insulin-deficient diabetic rodents, and the low leptin levels contribute to diabetic hyperphagia. Based on in vitro studies, the effect of insulin to stimulate leptin production appears to involve increased glucose metabolism. Blockade of glucose transport or glycolysis inhibits leptin expression and secretion in isolated adipocytes. Evidence suggests that anaerobic metabolism of glucose to lactate does not stimulate leptin production. Alterations in insulin-mediated glucose metabolism in adipose tissue are likely to mediate the effects of energy restriction to decrease, and refeeding to increase, circulating leptin levels. Changes in glucose metabolism may also explain the observation that high-fat meals lower 24 h circulating leptin levels relative to high-carbohydrate meals in human subjects, suggesting a mechanism that may contribute to the effects that high-fat diets have in promoting increased energy intake, weight gain and obesity. The decreased circulating leptin observed during energy restriction is related to increased sensations of hunger in human subjects. Thus, decreases in leptin during energy-restricted weight-loss regimens may contribute to the strong propensity for weight regain. A better understanding of the precise mechanisms regulating leptin production and leptin action may lead to new approaches for managing obesity.