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.

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.

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.

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.

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.

At its most fundamental, cancer is a genetic disease resulting from inherited or acquired mutations in tumour suppressor genes and proto-oncogenes. Environmental factors, including ingested food components, interact with genetic inheritance to determine individual cancer risk. There is growing evidence that the immune system exerts selective pressure during neoplastic development. Tumour cells that evade this immunosurveillance because they are non-antigenic or because they defend themselves successfully against immune attack have a survival advantage. Effective chemopreventative agents will include dietary components that enhance the immune system’s ability to identify transformed cells and to target them for apoptosis.

Numerous case–control and prospective studies have identified elevated plasma homocysteine as a strong independent risk factor for cerebovascular, cardiovascular and peripheral vascular disease. Homocysteine is formed as a result of the breakdown of the dietary amino acid methionine. Once formed, homocysteine is either remethylated to methionine, or undergoes a trans-sulfuration reaction to form cysteine. The re-methylation of homocysteine to methionine is dependent on three B-vitamins, i.e. riboflavin, vitamin B12 and folate. The second pathway of homocysteine metabolism is the trans-sulfuration pathway which requires both vitamin B6 and riboflavin for its activity. Thus, up to four B-vitamins are required for intracellular homocysteine metabolism. Many studies have noted strong inverse relationships between homocysteine levels and the status of both vitamin B12 and folate. However, the relationship between vitamin B6 status and homocysteine is still uncertain. Similarly, numerous intervention studies have demonstrated effective lowering of homocysteine levels as a result of folate and vitamin B12 supplementation, while the homocysteine-lowering ability of vitamin B6 is unclear. Even though riboflavin plays a crucial role in both the trans-sulfuration and remethylation pathways of homocysteine metabolism, the relationship between riboflavin status and homocysteine levels has not been investigated. The exact mechanism that explains the vascular toxicity of elevated homocysteine levels is unknown at present, studies indicate that it is both atherogenic and thrombogenic. To date, no randomized clinical trial has demonstrated that lowering of homocysteine levels is beneficial in terms of reducing the prevalence of vascular disease. It is probable, however, that optimal B-vitamin status is important in the prevention of vascular disease.

Taste preferences, food choices and eating habits all change with age. The transition from childhood to adolescence and adult life is associated with reduced sweet taste preferences, lower sugars consumption and reduced energy density of the diet. Ageing is associated with elevated acceptance of bitter tastes, elevated preferences for vegetables and salad greens, and increased consumption of whole grains, vegetables and fruit. The age-associated drop in energy intakes is achieved through a reduction in the weight and volume of food consumed, as well as a reduction in the overall energy density of the diet. Energy density drops from a peak of 5 kJ (1.2 kcal)/g in adolescence and early adult life to a low of 3.1 kJ (0.75 kcal)/g for adult women aged 45–54 years. Older adults, particularly women, consume less fat and saturated fat and more fibre and vitamin C, suggesting a shift in consumption from snacks, sweets and desserts towards grains, vegetables and fruit. These changes in food preferences and eating habits are associated, on a population level, with a decline in preferences for sweet taste and with increased acceptance of bitter tastes. At present there are no data to show a causal relationship between age-related changes in sensory function and the selection of a more bulky energy-dilute diet. However, it is a plausible hypothesis that sensory factors mediate adjustments in energy density of foods at different life stages.

The application of a lifespan perspective in human biology in recent years has shown that a number of early environmental factors influencing human growth and development have long-term biological or psycho-social consequences. Human growth is characterized by prolonged infancy, an extended childhood phase and high rates of growth during the adolescent growth spurt. It is unlikely that these characteristics would have evolved without having advantages, and curtailments have the potential for disadvantage. The present paper examines the evidence for long-term physiological and economic consequences of growth retardation in children and adolescents. The emphasis is the biological and economic imperatives of survival, subsistence, reproduction and production rather than aspects of metabolic competence. Many of the consequences of growth retardation are determined by the direct effect on body size, but many other consequences arise from the conditions that cause the growth retardation. Catch up of retarded growth can occur, but does not usually do so because of the continued presence of the retarding agents. Basal metabolism and physical work capacity are usually commensurate with the size of the individual; mechanical efficiency of physical work is unchanged, but falls in activity levels may occur along with a reduction in the pace of activity. Growth retardation in childhood is associated with a higher disease and mortality risk in adulthood, with decreased productivity and employment and promotion prospects. Studies are showing that relative deprivation and the accumulation of socially patterned exposures are important in some societies. Height and growth retardation have proved invaluable in reflecting these factors, but the next generation of studies may require more discriminating indices.

The ‘fetal origins’ hypothesis (Barker, 1995) would predict that the rising epidemic of diabetes and CHD in India would be due to poor intrauterine growth of the Indian babies. While this explanation may be valid to an extent, the higher prevalence of these disorders in urban compared with rural India (where birth weights are lower) would suggest a significant role for postnatal factors. In a cohort of 477 children born in the King Edward Memorial Hospital, Pune, we found that at 8 years of age current obesity strongly predicted insulin resistance. When this effect was allowed for, low birth weight was significantly associated with insulin-resistance variables and other cardiovascular risk factors. Children who were born small but had grown heavy (or tall) were the most insulin resistant and had the highest levels of cardiovascular risk factors. Accelerated growth in relation to mid parental height was similarly predictive. Poor intrauterine growth also predicted higher central adiposity at 8 years of age. We have also studied maternal nutrition and fetal growth in six villages near Pune. A newborn Indian baby is small (2650 g, SD score (SDS) –1.6 compared with an average white Caucasian baby born in the UK) and ‘thin’ (ponderal index 2.45 kg/m3, SDS –1.2), but has preserved its subcutaneous fat (subscapular skinfold thickness SDS –0.6). The thinness of the Indian babies is due to poor muscle and small abdominal viscera. We have proposed this composition as the ‘thrifty phenotype’ (Hales & Barker, 1992) of Indian babies. Maternal size and intake of certain food groups during pregnancy were important determinants of the baby’s phenotype. Thus, the small Indian babies are programmed to deposit fat from their intrauterine life. Exaggeration of this tendency in later life is associated with insulin-resistance syndrome. Control of the insulin-resistance epidemic in India might depend on improved intrauterine development and prevention of childhood obesity.

It has been proposed that there are critical periods during childhood that influence the development of obesity, including gestation and early infancy, the period of adiposity rebound that occurs between ages 5 and 7 years, and adolescence. Despite an extensive literature, there is to date only modest evidence for most of the factors such as nutrition, physical activity and other behavioural factors that are suspected as playing a role in the development of obesity. A recent review of this evidence (Parsons et al. 1999) showed, however, a consistent relationship between socio-economic status (SES) of origin and adult obesity, whereby those from lower SES backgrounds were fatter subsequently in adulthood. This association appeared to apply to both men and women, a finding that contrasts with the trends observed in cross-sectional studies, of an association with SES for women only. There are several potential explanations for the SES of origin–adult obesity relationship. SES of origin may be confounded by parental body size; studies to date provide insufficient evidence of an independent association with SES after allowing for parental body size. Alternatively, environment in early life (for which SES of origin is a proxy measure) may have a long-term impact on obesity later in adulthood, through one or more of several processes. Three major potential explanations can be identified: (1) nutrition in infancy and childhood, either over- or undernutrition, followed subsequently by overnutrition; (2) psychological factors, possibly involving emotional deprivation in childhood; (3) cultural or social norms regarding dietary restraint and attitudes to fatness that may be acquired during childhood.

Allergic diseases are a common cause of illness in most industrialized countries. Diet during early childhood is an important determinant of the development of allergy, particularly in high-risk infants who have a parental history of atopy. Maternal avoidance of highly-allergenic foods during pregnancy and lactation, prolonged exclusive breast-feeding, the use of a hydrolysed milk formula, and delayed introduction of dairy products, eggs, fish, nuts and soyabean are associated with a lower incidence of allergic symptoms and signs. These beneficial effects are observed for as long as 18 years of age. Similarly, nutrition and physical growth are important factors that influence immunocompetence and morbidity due to infections. Small-for-gestational age low-birth-weight infants show prolonged impairment of cell-mediated immunity, antibody responses and phagocyte function. Recent studies indicate the beneficial effect of moderate amounts of Zn given in the first 6 months of life. Thus, diet and nutrition in early life are crucial for the development of allergic and infectious disease throughout childhood and into adulthood.

When children and adolescents are the target population in dietary surveys many different respondent and observer considerations surface. The cognitive abilities required to self-report food intake include an adequately developed concept of time, a good memory and attention span, and a knowledge of the names of foods. From the age of 8 years there is a rapid increase in the ability of children to self-report food intake. However, while cognitive abilities should be fully developed by adolescence, issues of motivation and body image may hinder willingness to report. Ten validation studies of energy intake data have demonstrated that mis-reporting, usually in the direction of under-reporting, is likely. Patterns of under-reporting vary with age, and are influenced by weight status and the dietary survey method used. Furthermore, evidence for the existence of subject-specific responding in dietary assessment challenges the assumption that repeated measurements of dietary intake will eventually obtain valid data. Unfortunately, the ability to detect mis-reporters, by comparison with presumed energy requirements, is limited unless detailed activity information is available to allow the energy intake of each subject to be evaluated individually. In addition, high variability in nutrient intakes implies that, if intakes are valid, prolonged dietary recording will be required to rank children correctly for distribution analysis. Future research should focus on refining dietary survey methods to make them more sensitive to different ages and cognitive abilities. The development of improved techniques for identification of mis-reporters and investigation of the issue of differential reporting of foods should also be given priority.

The number of US children who are overweight has more than doubled over the last decade. This change has broadened the focus of dietary guidance for children to address nutrient overconsumption and physical activity patterns. Total fat consumption expressed as a percentage of energy intake has decreased among US children. However, this decrease is largely the result of increased total energy intake in the form of carbohydrates and not necessarily due to decreased fat consumption. The majority of children aged 5–17 years are not meeting recommendations for Ca intakes. Much of this deficit is attributed to changing beverage consumption patterns, characterized by declining milk intakes and substantial increases in soft-drink consumption. On average, US children are not eating the recommended amounts of fruits and vegetables. US adolescents become less active as they get older, and one-quarter of all US children watch 4 h television each day, which is positively associated with increased BMI and skinfold thickness. There is an urgent need in the USA for effective prevention strategies aimed at helping children grow up with healthful eating and physical activity habits to achieve optimal health.

Ca is the major mineral in bone, and 99 % of the Ca in the body resides in the skeleton. Skeletal mass is a determinant of risk of fracture in childhood as well as adulthood. Over 40 % of adult peak bone mass is acquired during adolescence. This period is when lifestyle choices, including ensuring adequate dietary Ca, regular weight-bearing exercise and avoiding hormonal insufficiency, are especially important. Current Ca intakes for adolescent females are woefully inadequate.

One in three children in Britain lives in poverty (households whose income was less than 50 % average earnings). Low income is associated with poor nutrition at all stages of life, from lower rates of breast-feeding to higher intakes of saturated fatty acids and lower intakes of antioxidant nutrients. Moreover, there is increasing evidence that poor nutrition in childhood is associated with both short-term and long-term adverse consequences such as poorer immune status, higher caries rates and poorer cognitive function and learning ability. These problems arise primarily because parents do not have enough money to spend on food, not because money is being spent unwisely. Policy options to improve the dietary health of poor children include: giving more money to the parents by increasing Income Support (social security) payments, providing food stamps or vouchers, and using food budget standards to inform the levels of income needed to purchase an adequate diet; feeding children directly at school (not only at lunchtime but also at breakfast or homework clubs), by providing free fruit at school, and by increasing entitlement to free food amongst children living in households with low incomes; improving access to a healthy and affordable diet by first identifying ‘food deserts’ and then considering with retailers and local planners how best to provide food in an economical and sustainable way. The value of using food budget standards is illustrated with data relating expenditure on food to growth in children from ‘at-risk’ families (on low income, overcrowded, headed by a lone parent or with four or more children under 16 years of age) living in a poor area in London. Lower levels of expenditure are strongly associated with poorer growth and health, independent of factors such as birth weight, mother’s height, or risk score. The present paper provides evidence that supports the need to review Government legislation in light of nutrition-related inequalities in the health of children.

Since the 19th century there have been clearly documented secular trends to increasing adult height in most European countries, with current rates of 10–30 mm / decade. Over the same period menarcheal age has also fallen steeply, but has now stabilized at approximately 13 years and may be rising again. Height trends tend to be greater in childhood than in adulthood due to the associated advance in maturation, but no trends are apparent before the age of 2 years. In particular, birth-weight trends are small and different in shape from height trends. The adult height trend matches that at age 2 years, so that the increment in adult height has already been achieved by age 2 years. To try to identify factors relating to the secular trend, increased height gain in late infancy is hypothesized to be equivalent to a reduction in stunting, and stunting is thought to be caused by impaired growth in the long bones of the leg in later infancy. Leg growth may be regulated by the expression of growth-hormone receptors on the growth plates, which it is hypothesized are susceptible to the interaction between concurrent nutrition and the nominal growth rate set during pregnancy. The timing of menarche is also likely to be determined by some growth factor operating near the time of birth, which also affects later weight, but not height.

The acquisition of increased adipose tissue mass in man occurs during prolonged periods of positive energy balance. Normally, energy homeostasis in children and adults is regulated strictly and the energy stores are kept within the defined age-dependent physiological range. Susceptibility to definitive increases in the level of energy balance during times of reduced energy consumption or increased energy intake, leading to changes in body composition and/or changes in relative body weight, seems to be genetically determined. Although at present much information on the regulation of energy homeostasis and related unfavourable factors exists from animal studies, knowledge of the regulation of energy balance in human subjects is still insufficient. Some evidence on relevant factors involved in the regulation of energy balance in man has been obtained from epidemiological data, as well as from studies of patients with rare monogenetic forms of obesity. In the present article a special focus will be put on the regulation of body energy stores at the level of the adipose tissue, with emphasis on the regulation of human adipocyte differentiation. In addition to the currently intensive scientific interest in the central regulation of energy homeostasis in man, there is sufficient evidence to support the idea that the acquisition of an increased adipose tissue mass is also dependent on the susceptibility of pre-adipocytes to proliferate, to differentiate or to enter into apoptosis.