Brain development is a complex interactive process in which early disruptive events can have long-lasting effects on later functional adaptation. It is a process that is dependent on the timely orchestration of external and internal inputs through sophisticated intra- and intercellular signalling pathways. Long-chain polyunsaturated fatty acids (LCPUFA), specifically arachidonic acid and docosahexaenoic acid (DHA), accrue rapidly in the grey matter of the brain during development, and brain fatty acid (FA) composition reflects dietary availability. Membrane lipid components can influence signal transduction cascades in various ways, which in the case of LCPUFA include the important regulatory functions mediated by the eicosanoids, and extend to long-term regulation through effects on gene transcription. Our work indicates that FA imbalance as well as specific FA deficiencies can affect development adversely, including the ability to respond to environmental stimulation. For example, although the impaired water-maze performance of mice fed a saturated-fat diet improved in response to early environmental enrichment, the brains of these animals showed less complex patterns of dendritic branching. Dietary n-3 FA deficiency influences specific neurotransmitter systems, particularly the dopamine systems of the frontal cortex. We showed that dietary deficiency of n-3 FA impaired the performance of rats on delayed matching-to-place in the water maze, a task of the type associated with prefrontal dopamine function. We did not, however, find an association over a wider range of brain DHA levels and performance on this task. Some, but not all, studies of human infants suggest that dietary DHA may play a role in cognitive development as well as in some neurodevelopmental disorders; this possibility has important implications for population health.

The purpose of the present paper is to review the evidence in favour of food-based strategies to meet the challenges of micronutrient malnutrition in the developing world. Increasing dietary diversification is the most important factor in providing a wide range of micronutrients, and to achieve this objective in a development context requires an adequate supply, access and consumption of a variety of foods. Diets in developing countries generally lack many nutrients, including energy (inadequate amounts of food), so that strategies need to also emphasize an increase in total food intake, in addition to a greater variety. Agricultural and food policies tend to be oriented to primary agricultural productions, but they could also be formulated to promote and support home gardens and small livestock production for the explicit purpose of increasing the household consumption of micronutrient-rich foods. The adoption of ‘desirable’ dietary patterns for nutrition improvement, e.g. appropriately formulated to meet micronutrient needs, could be used in the formulation of agricultural policies and programmes. This process could be achieved through support for integrated farming systems oriented to assuring household food security, but also based on a variety of foods that will meet total dietary (including micronutrient) needs. Thus, availability of energy-rich staples, animal and/or fish as major sources of protein, and vitamin-, mineral- and phytonutrient-rich fruit and vegetables could constitute the types of production envisaged. The cultivation of edible indigenous plants as additional sources of micronutrients could also be added. The low bioavailability of some key micronutrients from foods, such as Fe, are substantially enhanced with the right food combinations and with appropriate food processing and preparation techniques. Simple appropriate technology for the preservation of micronutrientrich foods would need further development and promotion for their year-round availability. Linking community development policies to national programmes for the alleviation of hunger and malnutrition, with an emphasis on increasing the variety of foods consumed, is probably the best strategy for improving micronutrient malnutrition sustainably.

Vitamin A is necessary for normal differentiation of epithelial tissues, the visual process and reproduction, and is vital for the optimal maintenance and functioning of the innate and adaptive immune system. Vitamin A deficiency is one of the most profuse nutritional deficiencies worldwide. It is associated with increased susceptibility to infectious diseases in both man and animal models. Vitamin A also has a role as an anti-inflammatory agent. Supplementation with vitamin A has been found to be beneficial in a number of inflammatory conditions, including skin disorders such as acne vulgaris, broncho-pulmonary dysplasia and some forms of precancerous and cancer states. The present review suggests that vitamin A deficiency induces inflammation and aggravates existing inflammatory states. Supplementation with vitamin A in selected cases could ameliorate inflammation. The two main mechanisms which appear to be involved in the prevention of disease are the effects of vitamin A on the immune system and the effect on epithelial integrity.

Since the discovery of the protein product of the ob/ob gene, leptin, knowledge of the neurochemical pathways involved in the regulation of feeding has increased enormously. Our understanding of the mechanisms regulating food intake in man has also progressed greatly over a similar time span. Previous research into the regulation of food intake has largely proceeded through a reductionist approach, defining ever-smaller components of these mechanisms. This research strategy has been very productive and instructive, and has yielded a great deal of information on the specific putative components linking energy status and food intake. However, to fully understand the regulation of feeding it is important that these components are systematically reconstructed to investigate relevant interactions. In the present review recent data relating to interactions between systems proposed to be involved in feeding regulation will be highlighted. The review will be directed predominantly (but not exclusively) towards the regulation of human feeding.

Epidemiological studies of human populations show that poor growth in utero predisposes an individual to the later development of type 2 (non-insulin-dependent) diabetes mellitus and hypertension in adulthood. This phenomenon is not confined to man; feeding pregnant rats diets moderately deficient in protein has a similar effect, programming the adult blood pressure and glucose metabolism of the offspring. A restriction in the amino acid supply was thought to cause poor fetal growth. However, recent experiments have shown that this is not the case and instead have implicated the metabolism of the S-containing amino acids. Many semi-synthetic experimental diets contain an imbalance in S-containing amino acids, forcing the animal to synthesise a sizeable part of its cysteine requirement from methionine. Unfortunately, when the diet is low in protein, the oxidation of amino acids is reduced, perturbing methionine metabolism and increasing levels of homocysteine. It is this interaction between protein content and composition of the diet which influences neonatal viability and may also determine the long-term health of the offspring. An excess of homocysteine is known to affect levels of two of the main mediators of cellular methylation reactions, S-adenosyl methionine and methylene tetrahydrofolate. S-adenosyl methionine is the methyl donor for the methylation of newly-synthesised DNA, regulating chromatin assembly and gene expression. The balance between S-adenosyl methionine and the methylated derivatives of folic acid may be critical for the development of differentiating cells and the long-term regulation of gene expression.

Human food intake is driven by necessity. We eat to live, but as Brillat-Savarin and others have noted throughout history, in affluent societies eating is a pleasure and becomes more than a means to an end.Eating signifies lifestyle choice and it has considerable meaning in our society beyond the acquisition of essential energy and nutrients. Thus, it is that the study of human food intake, particularly food choice, in contrast to food intake in other animals, tends to be skewed towards measures of behavioural, social and environmental influences rather than on precise physiological processes reflecting metabolism and nutrient partitioning. The dichotomy between physiological and psychological measures is a false one, since all behaviours are necessarily expressed through physiological systems. However, in the field of human food intake research the dichotomy refers to the divergent strands of interest in either psychological or physiological processes underlying intake and appetite. The present review considers both psychological and physiological measures in promoting our understanding of the human appetite system. The overall conclusion is that the burgeoning interest in identifying appetite suppressant drugs to combat obesity and in genotyping alongside behavioural phenotyping will close the gap between psychological and physiological perspectives on human food intake.

Micronutrient deficiencies occur frequently in refugee and displaced populations. These deficiency diseases include, in addition to the most common Fe and vitamin A deficiencies, scurvy (vitamin C deficiency), pellagra (niacin and/or tryptophan deficiency) and beriberi (thiamin deficiency), which are not seen frequently in non-emergency-affected populations. The main causes of the outbreaks have been inadequate food rations given to populations dependent on food aid. There is no universal solution to the problem of micronutrient deficiencies, and not all interventions to prevent the deficiency diseases are feasible in every emergency setting. The preferred way of preventing these micronutrient deficiencies would be by securing dietary diversification through the provision of vegetables, fruit and pulses, which may not be a feasible strategy, especially in the initial phase of a relief operation. The one basic emergency strategy has been to include a fortified blended cereal in the ration of all food-aid-dependent populations (United Nations High Commissioner for Refugees/World Food Programme, 1997). In situations where the emergency-affected population has access to markets, recommendations have been to increase the general ration to encourage the sale and/or barter of a portion of the ration in exchange for locally-available fruit and vegetables (World Health Organization, 1999a, b, 2000). Promotion of home gardens as well as promotion of local trading are recommended longer-term options aiming at the self-sufficiency of emergency-affected households. The provision of fortified blended foods in the general ration has successfully prevented and controlled micronutrient deficiencies in various emergency settings. However, the strategy of relying only on fortified blended foods to prevent micronutrient deficiencies should be reviewed in the light of recurring evidence that provision of adequate supplies of these foods is often problematic. Donor policies on the bartering or exchange of food aid should also be clarified. Furthermore, the establishment of micronutrient surveillance systems, including standardized micronutrient deficiency diagnostic criteria, are vital for the control of micronutrient deficiency diseases.

As a rule, children and most adults eat what they like and leave the rest. They like and consume foods high in fat and sugar. Parental behaviour shapes food acceptance, and early exposure to fruit and vegetables or to foods high in energy, sugar and fat is related to children's liking for, and consumption of, these foods. Some parents are imposing child-feeding practices that control what and how much children eat. However, over-control can be counter-productive, teaching children to dislike the very foods we want them to consume, and generally undermining self-regulation abilities. The external environment is also important, with concerns expressed about food advertising to children and girls dieting for an ideal thin body shape. Up to one-quarter of young adolescent girls report dieting to lose weight, their motivation driven by weight and shape dissatisfaction. For some, dieting and vegetarianism are intertwined and both legitimised as healthy eating. For others, striving for nutritional autonomy, the choice of less-healthy foods is not just because of their taste, but an act of parental defiance and peer solidarity. The determinants of what children choose to eat are complex, and the balance changes as children get older. A better understanding is crucial to informing how we might modify nutritional behaviour. Adults occupy a central position in this process, suggesting that children should be neither the only focus of nutritional interventions nor expected to solve the nutritional problems with which adults around them are continuing to fail.

The modification of ageing by nutritional intervention is well recognised. Post-weaning diet restriction is the only widely reproducible method to slow ageing, but the effects of prenatal and preweaning diet restriction have been less well characterised. There is some evidence that diet restriction instituted in utero or shortly after birth may have an opposite effect and be associated with increased ageing, and recent work suggests that it may shorten lifespan. Interest in this area has been rekindled by the growing body of epidemiological evidence showing that a number of age-related diseases are associated with poor growth and inadequate nutrition in early life. The relevance of this association to structural and functional ageing changes in different systems is now being considered. Work on musculo-skeletal ageing has demonstrated that loss of muscle strength and bone mass is greater in individuals who did not grow well in early life, and a range of studies suggests that maternal, developmental and nutritional factors are important. The underlying mechanisms remain speculative, and it remains to be determined whether they are system-specific or universal throughout the body. A new cohort of subjects aged between 60 and 70 years is being established to investigate how genetic factors interact with growth and nutritional influences to programme musculo-skeletal ageing in later life.

Many experiments have shown that foraging animals are sensitive to the riskiness, or variance, associated with alternative food sources. For example, when offered a choice of a constant feeding option that always offers three seeds, and a risky option that offers either no seeds or six seeds with equal probability, most animals tested will be either risk-averse or risk-prone, preferring either the fixed or variable option respectively. Whether animals are risk-averse or risk-prone appears to depend on a range of factors, including the energetic status of the forager, the type of variance associated with the feeding options and even the number of feeding options between which the animal is choosing. These behavioural phenomena have attracted much theoretical interest, and a range of different explanations have been suggested, some based on a consideration of the psychological mechanisms involved in decision making, and others on a consideration of the Darwinian fitness consequences of risk-averse or risk-prone behaviour for the forager. A brief review of the recent literature on risk-sensitive foraging will be presented, focusing on results from the two experimental systems with which I have been involved: wild rufous hummingbirds (Selasphorus rufus) foraging on artificial flowers; European starlings (Sturnus vulgaris) foraging in operant boxes in the laboratory. It will be argued that to understand the foraging decisions of animals account needs to be taken of both the psychological mechanisms underlying decision-making and the fitness consequences of different decisions for the forager.

When talented, motivated and highly trained athletes meet for competition the margin between victory and defeat is usually small. When everything else is equal, nutrition can make the difference between winning and losing. Although the primary concern of many athletes is to supplement the diet with protein, vitamins and minerals, and a range of more exotic compounds, key dietary issues are often neglected. Athletes must establish their nutritional goals, and must also be able to translate them into dietary strategies that will meet these goals. Athletes are often concerned with dietary manipulations in the period around competition, but the main role of nutrition may be to support consistent intensive training which will lead to improved performance. Meeting energy demand and maintaining body mass and body fat at appropriate levels are key goals. An adequate intake of carbohydrate is crucial for maintaining muscle glycogen stores during hard training, but the types of food and the timing of intake are also important. Protein ingestion may stimulate muscle protein synthesis in the post-exercise period, promoting the process of adaptation in the muscles. Restoration of fluid and electrolyte balance after exercise is essential. If energy intake is high and a varied diet is consumed, supplementation of the diet with vitamins and minerals is not warranted, unless a specific deficiency is identified. Specific strategies before competition may be necessary, but this requirement depends on the demands of the sport. Generally, it is important to ensure high pre-competition glycogen stores and to maintain fluid balance. There is limited evidence to support the use of dietary supplements, but some, including perhaps creatine and caffeine, may be beneficial.

Present-day human eating behaviour in industrialised society is characterised by the consumption of high-energy-density diets and often unstructured feeding patterns, largely uncoupled from seasonal cycles of food availability. Broadly similar patterns of feeding are found among advantaged groups in economically-emerging and developing nations. Such patterns of feeding are consistent with the evolutionary ecological understanding of feeding behaviour of hominids ancestral to humans, in that human feeding adaptations are likely to have arisen in the context of resource seasonality in which diet choice for energy-dense and palatable foods would have been selected by way of foraging strategies for the maximisation of energy intake. One hallmark trait of human feeding behaviour, complex control of food availability, emerged with Homo erectus (19 × 106-200 000 years ago), who carried out this process by either increased meat eating or by cooking, or both. Another key trait of human eating behaviour is the symbolic use of food, which emerged with modern Homo sapiens (100 000 years ago to the present) between 25 000 and 12 000 years ago. From this and subsequent social and economic transformations, including the origins of agriculture, humans have come to use food in increasingly elaborate symbolic ways, such that human eating has become increasingly structured socially and culturally in many different ways.

Dietary changes can be difficult to effect both at an individual and at a population level, and even when changes do occur they are often far slower and less pronounced than might be expected. Three possible reason for this situation will be considered: the complexity of food choice and competing influences, attitudinal ambivalence and optimistic bias. Food choice is influenced by a large number of factors, not only health considerations, and therefore it is not surprising that interventions based primarily on health concerns have been ineffective. Another concern is that people do not always have clear-cut attitudes, but rather can be ambivalent about foods and about healthy eating, and this factor might impact on the translation of beliets and attitudes into behaviour. A third possible reason is optimistic bias, where individuals believe themselves to be at less risk from various hazards than is the average person. This effect has been demonstrated for nutritional risks, and this factor might lead people to take less note of health education messages. The stages-of-change model from health psychology has been proposed as a method for improving the effectiveness of behaviour change interventions. However, there are a number of problems in transferring such a model from smoking, where it was originally developed, to dietary behaviours, including the lack of clear-cut specific behaviours and behaviour change targets in the dietary field.

The present paper presents a non-technical overview of contemporary developments in food supply, as seen from the standpoint of economic adjustment. The historical concerns over availability and price of food have now passed in the UK, and agriculture is no longer dominantly driven by the supply-side forces of new farming technology and the stimulus of support policies. As a now demand-driven sector of the economy, it is the developing diversity of consumer food preferences that will increasingly determine the adjustment path of agricultural production. Those demands seek distinctive elements of food value, many of which are entirely created and delivered by industries beyond the farm gate. However, many of the quality characteristics of food that consumers increasingly seek are associated explicitly with what takes place on farms and how crop and livestock husbandry is conducted. In responding to these demand preferences many farmers will shift from being merely raw material producers to becoming genuine producers of food, or capturing more of the final value of the products consumed. As a result a dual structure within farming will develop, with a ‘quality agriculture’ becoming increasingly differentiated from a ‘commodity agriculture’ as two distinct strategies for farm business survival.

A wide variety of plant-derived compounds, including the polyphenolic flavonoids, is present in the human diet or is consumed for medicinal reasons. Epidemiological and animal studies tend to suggest a protective effect of flavonoids against cardiovascular diseases and some types of cancer. Although flavonoids have been studied for about 50 years, the cellular mechanisms involved in their biological activity are still largely unknown. Antioxidant properties of the flavonoids have been postulated as a mechanism for putative protective effect against cardiovascular disease. Nevertheless, these properties alone are not sufficient to explain the anti-carcinogenic potential of these polyphenols. The mechanisms by which the molecules interact with cells or are absorbed by them are very important for determining the intracellular concentration and distribution of the metabolites to internal organs. With the exception of the cells lining the gastrointestinal tract, all other cells in the body are only exposed to flavonoid metabolites and degradation products. No previous studies have addressed this aspect of cellular exposure, except for some methylated metabolites. Within the last decade, reports on flavonoid activities have been largely associated with enzyme inhibition and anti-proliferative activity. From our recent work on the human colon cancer cell line HT29 and comparison with published studies, structure–function relationships demonstrate that antioxidant, enzyme inhibitor or anti-proliferative activities are dependent on particular structure motifs. The present review also presents a summary of mechanistic data on a few selected compounds.

Both jurisdictions of Ireland have high rates of chronic degenerative diseases, particularly of the cardiovascular system, and Irish migrants have worse health profiles, often lasting at least two generations. The influence of socio-demographic variation over the life course, and what role diet plays, has not been well researched in epidemiological terms. There is a long history of an unusual Irish diet. Estimated dietary fat intake (% total energy intake) in 1863 was only 9, but had reached 30 in 1948 and 34 in 1999. Conversely, carbohydrate intake has fallen steadily over 150 years. From 1948 onwards household budget survey data illustrate patterns of increasing urbanisation and socio-economic gradients in food availability. The National Survey of Lifestyles, Attitudes and Nutrition, (n 6539, 622 % response rate) provides clear evidence of inverse social-class gradients in intake of fruit and vegetables and dairy products and in reported patterns of healthy eating. Median carbohydrate and vitamin C levels are higher among social classes 1-2 and mean saturated fat intake is lower. International comparisons indicate a continuing, if narrowing, north-south gradient across Europe. Data from the Boston-Ireland study suggest a crossover in both dietary intake patterns and risk of heart disease in Ireland and the USA in the 1970s. Contemporary comparative data of middle-aged Irish and American women demonstrate patterns of diet intake and inactivity consistent with the modern epidemic of obesity and non-insulin-dependent diabetes. Thus, dietary variations within and between countries and over time are consistent with chronic disease patterns in contemporary Ireland.

The search for the causes of CHD has been guided by a `destructive' model, which proposes that influences acting in adult life, such as smoking, obesity or high saturated fat intakes, lead to an acceleration of age-related destructive processes, including a rise in blood pressure and the formation of atheroma. One explanation for the failure of the model to account for, or indeed to prevent rising epidemics of CHD, is that individuals are heterogeneous in their responses to such influences. This heterogeneity in response is linked to different paths of early growth. The recent discovery that individuals who develop CHD grew differently from other individuals during fetal life and in childhood has led to a new `developmental' model for the disease. Reduced fetal growth followed by poor growth in infancy leads to an increased risk of development of CHD, and its associated conditions, stroke, hypertension and impaired glucose tolerance. These effects are compounded by accelerated weight gain, which may represent 'compensatory growth' in childhood.

De novo lipogenesis is the biological process by which C2 precursors of acetyl-CoA are synthesized into fatty acids. In human subjects consuming diets higher in fat (>30 % energy), lipogenesis is down regulated and extremely low; typically < 10 % of the fatty acids secreted by the liver. This percentage will increase when dietary fat is reduced and replaced by carbohydrate, although the extent of carbohydrate-induced lipogenesis is dependent on the type of carbohydrate (monosaccharide v. polysaccharide) and the form in which the carbohydrate is fed (liquid meals, solid less-processed food). Clearly, massive overconsumption of carbohydrate can also increase lipogenesis. A second related phenomenon that occurs when dietary fat is reduced is hypertriacylglycerolaemia. This rise in blood triacylglycerol concentration could be due to increased de novo lipogenesis or to reduced clearance of lipid from the blood. The present paper will review the metabolic mechanisms leading to the elevations in blood triacylglycerol concentration that occur with dietary fat reduction. Studies considered will be those investigating fatty acid synthesis in subjects chronically fed low-fat high-carbohydrate diets and studies in which data were obtained in both the fasted and fed states. Also summarized will be data from subjects who had consumed diets of different carbohydrate types, as well as the most recent data from postprandial studies investigating factors that affect the magnitude of the rise in blood lipids following a meal. Given the changing availability of carbohydrate in the food supply, it will be important to understand how the balance of fat and carbohydrate in the diet influences lipogenesis, and the relative contribution of the process of de novo lipogenesis to the escalating incidence of obesity observed around the world.

Members of the nuclear steroid hormone superfamily mediate essential physiological functions. Steroid hormone receptors (SHR) act directly on DNA, regulate the synthesis of their target genes and are usually activated by ligand binding. Both endogenous and exogenous compounds and their metabolites may act as activators of SHR and disruptors of endocrine, cellular and lipid homeostasis. The endogenous ligands are generally steroids such as 17β-oestradiol, androgens, progesterone and pregnenolone. The exogenous compounds are usually delivered through the diet and include non-steroidal ligands. Examples of such ligands include isoflavanoids or phyto-oestrogens, and food contaminants such as exogenous oestrogens from hormone-treated cattle, pesticides, polychlorinated biphenyls and plasticisers. Certain drugs are also ligands; so nuclear receptors are also important drug targets for intervention in disease processes. The present review summarises recent reports on ligand-activated SHR that describe the selective regulation of a tightly-controlled cross-talking network involving exchange of ligands, and the control of major classes of cytochrome P450 (CYP) isoforms which metabolise many bioactive exogenous compounds. Many CYP have broad substrate activity and appear to be integrated into a coordinated metabolic pathway, such that whilst some receptors are ligand specific, other sensors may have a broader specificity and low ligand affinity to monitor aggregate levels of inducers. They can then trigger production of metabolising enzymes to defend against possible toxic nutrients and xenobiotic compounds. The influence of dietary intakes of nutrients and non-nutrients on the human oestrogen receptors (α and β), the aryl hydrocarbon receptor, the pregnane X receptor, the constitutive androstane receptor, and the peroxisome proliferator-activated receptors (α and γ), can be examined by utilising computer-generated molecular models of the ligand–receptor interaction, based on information generated from crystallographic data and sequence homology. In relation to experimental and observed data, molecular modelling can provide a scientifically sound perspective on the potential risk and benefits to human health from dietary exposure to hormone-mimicking chemicals, providing a useful tool in drug development and in a situation of considerable public concern.

Crohn’s disease is a modern Western disease characterised by transmural inflammation of the gastrointestinal tract. It is of unknown aetiology, but evidence suggests that it results from a combination of genetic predisposition and environmental factors. Bacterial-sized microparticles (0·1–1·0 µm) are potent adjuvants in model antigen-mediated immune responses and are increasingly associated with disease. Microparticles of TiO2 and aluminosilicate accumulate in macrophages of human gut-associated lymphoid tissue where the earliest signs of lesions in Crohn’s disease are observed. Dietary microparticles are of endogenous or exogenous origin. Endogenous microparticles dominate and are calcium phosphate (most probably hydroxyapatite), which precipitates in the lumen of the mid-distal gastrointestinal tract due to secretion of Ca and phosphate in the succus entericus. Exogenous dietary microparticles are contaminants (soil and/or dust) and food additives. TiO2, for example, is a food colourant, and aluminosilicates are anti-caking agents, although some aluminosilicates occur as natural contaminants. Food additives alone account for ingestion of approximately 1012 particles/person per d. Possible mechanisms for the role of exogenous and endogenous dietary microparticles in promoting toleragenic or immune responses of gastrointestinal mucosal phagocytosis are discussed. In a double-blind randomised pilot study we have shown that a diet low in Ca and exogenous microparticles appears to alleviate the symptoms of ileal Crohn’s disease, with a significant (P = 0·002) improvement in the Crohn’s disease activity index. A multi-centre trial and further mechanistic studies at the cellular level are underway.