Osteoporosis is a common disease with a strong genetic component characterised by reduced bone mass and an increased risk of fragility fractures. Twin and family studies have shown that genetic factors contribute to osteoporosis by influencing bone mineral density (BMD), and other phenotypes that are associated with fracture risk, although the heritability of fracture itself is modest. Linkage studies have identified several quantitative trait loci that regulate BMD but most causal genes remain to be identified. In contrast, linkage studies in monogenic bone diseases have been successful in gene identification, and polymorphisms in many of these genes have been found to contribute to the regulation of bone mass in the normal population. Population-based studies have identified polymorphisms in several candidate genes that have been associated with bone mass or osteoporotic fracture, although individually these polymorphisms only account for a small amount of the genetic contribution to BMD regulation. Environmental factors such as diet and physical activity are also important determinants of BMD, and in some cases specific nutrients have been found to interact with genetic polymorphisms to regulate BMD. From a clinical standpoint, advances in knowledge about the genetic basis of osteoporosis are likely to be important in increasing the understanding of the pathophysiology of the disease; providing new genetic markers with which to assess fracture risk and in identifying genes and pathways that form molecular targets for the design of the next generation of drug treatments.

In their current guidelines cardiac societies recommend the consumption of the two n-3 fatty acids EPA and DHA to prevent cardiovascular complications. Cardiovascular events are reduced by EPA and DHA, because they are antiarrhythmic, mitigate the course of atherosclerosis and stabilise plaque. As atherosclerosis is considered an inflammatory disorder a number of studies have investigated the anti-inflammatory mechanisms of EPA and DHA in a cardiovascular context in human dietary intervention studies. Pro-inflammatory cytokines, or cytokines reflecting inflammatory processes, e.g. IL-1β, IL-2, IL-6, TNFα, platelet-derived growth factor (PDGF)-A and -B and monocyte chemoattractant protein-1 (MCP-1), are reduced by ingestion of EPA and DHA by human subjects. Interestingly, C-reactive protein remains largely unaltered. However, in in vitro and animal models, but less so in human subjects, soluble cytokines reflecting interactions between blood cells and the vessel wall, such as intercellular adhesion molecule-1 and vascular cell adhesion molecule-1, are reduced. Moreover, in contrast to common expectations, oxidative stress seems to be reduced after ingestion of EPA and DHA, at least as indicated by measurement of urinary F2 isoprostane excretion. Notably, for PDGF-A and -B and for MCP-1 the reduction has been demonstrated to occur at the gene expression level, which indicates that a deliberate change in diet can alter gene expression quantitatively. The precise underlying mechanism, however, remains to be clarified, but might involve PPAR, NF-κB and/or the eicosanoid system. The same holds true for the mechanisms by which levels of other cytokines are altered by EPA and DHA.

The importance of adipose tissue in health as well as disease has been demonstrated in several studies recently, and it has become appropriate to use the term ‘adipose organ’ when referring to adipose tissue as a whole. The obesity epidemic, with a marked increase in the incidence of the metabolic syndrome leading to diabetes type 2 as well as cardiovascular complications, has stimulated considerable interest in adipose tissue biology. Moreover, several studies in different species have shown that limited energy intake is associated with less inflammation, improved biomarkers of health and a marked increase in longevity. In addition, there is convincing evidence that an optimal amount of adipose tissue is essential for many body functions such as immune response, reproduction and bone quality. Some nutrients and their metabolites are important as energy sources as well as ligands for many transcription factors expressed in adipose tissue, including all energy-providing nutrients both directly and indirectly as well as cholesterol, vitamin E and vitamin D. In particular, fatty acids can be effectively taken up by adipocytes and they can interact with several transcription factors crucial for growth, development and metabolic response, e.g. PPARα, −δ and −γ, sterol regulatory element-binding proteins1 and 2 and liver X receptors α and β). Moreover, glucose is also readily taken up and stored as fatty acids via lipogenesis in adipocytes. It is known that some metabolic signals released as proteins from adipose tissue (adipokines) are important for normal as well as pathological responses to the amount of energy stored in the adipose organ. The future challenge will be to understand the function of adipose tissue in energy homeostasis and the interplay with nutrients in order to be able to give optimal advice for the prevention and treatment of obesity.

Cardiovascular risk is determined by the complex interactions between genetic and environmental factors. The apoE genotype represents the most-widely-studied single nucleotide polymorphism in relation to CVD risk, with >3600 publications cited in PubMed. Although originally described as a mediator of lipoprotein metabolism, the lipoprotein-independent functions of apoE are being increasingly recognised, with limited data available on the potential impact of genotype on these metabolic processes. Furthermore, although meta-analyses suggest that apoE4 carriers may have a 40–50% increased CVD risk, the associations reported in individual studies are highly heterogeneous and it is recognised that environmental factors such as smoking status and dietary fat composition influence genotype–phenotype associations. However, information is often derived from observational studies or small intervention trials in which retrospective genotyping of the cohort results in small group sizes in the rarer E2 and E4 subgroups. Either larger well-standardised intervention trials or smaller trials with prospective recruitment according to apoE genotype are needed to fully establish the impact of diet on genotype–CVD associations and to establish the potential of dietary strategies such as reduced total fat, saturated fat, or increased antioxidant intakes to counteract the increased CVD burden in apoE4 carriers.

The increasing prevalence of the metabolic syndrome in numerous populations throughout the world is currently of major concern, and presents a huge global health problem. The link between low birth weight and the subsequent development of obesity, disrupted glucose homeostasis and hypertension is now well established, and there is extensive evidence supporting these associations in both epidemiological and experimental studies. Alterations in the secretion of, and responses to, the circulating hormones insulin and leptin are likely candidates in terms of disease development. The aim of current research is to define how the central and peripheral pathways in which these signals exert their effects may be disrupted following poor early growth, and how this disruption contributes to the development of metabolic disease. The present review aims to outline the existing evidence whereby alterations in early growth may programme an individual to be at increased risk of the metabolic syndrome. The development of central appetite and expenditure circuits and of peripheral metabolic tissues, are likely to play a key role in the long-term regulation of energy balance.

Epidemiological studies showing a protective effect of diets rich in fruits and vegetables against cancer have focused attention on the possibility that biologically-active plant secondary metabolites exert anti-carcinogenic activity. This huge group of compounds, now collectively termed ‘phytochemicals’, provides much of the flavour and colour of edible plants and the beverages derived from them. Many of these compounds also exert anti-carcinogenic effects in animal models of cancer, and much progress has been made in defining their many biological activities at the molecular level. Such mechanisms include the detoxification and enhanced excretion of carcinogens, the suppression of inflammatory processes such as cyclooxygenase-2 expression, inhibition of mitosis and the induction of apoptosis at various stages in the progression and promotion of cancer. However, much of the research on phytochemicals has been conducted in vitro, with little regard to the bioavailability and metabolism of the compounds studied. Many phytochemicals present in plant foods are poorly absorbed by human subjects, and this fraction usually undergoes metabolism and rapid excretion. Some compounds that do exert anti-carcinogenic effects at realistic doses may contribute to the putative benefits of plant foods such as berries, brassica vegetables and tea, but further research with human subjects is required to fully confirm and quantify such benefits. Chemoprevention using pharmacological doses of isolated compounds, or the development of ‘customised’ vegetables, may prove valuable but such strategies require a full risk–benefit analysis based on a thorough understanding of the long-term biological effects of what are often surprisingly active compounds.

A life-course approach to chronic-disease epidemiology uses a multidisciplinary framework to understand the importance of time and timing in associations between exposures and outcomes at the individual and population levels. Such an approach to chronic diseases is enriched by specification of the particular manner in which timing in relation to physical growth, reproduction, infection, social mobility, behavioural transitions etc. can influence various adult chronic diseases in different ways, and more ambitiously by how these temporal processes are interconnected and manifested in health inequalities within a population and in population-level disease trends. The paper will discuss some historical background to life-course epidemiology and theoretical models of life-course processes, and will review some of the empirical evidence linking life-course processes to CHD, haemorrhagic stroke, stomach cancer and other chronic diseases in adulthood. It will also underscore that a life-course approach offers a way to conceptualize how underlying socio-environmental determinants of health, experienced at different life-course stages, can differentially influence the development of chronic diseases, as mediated through proximal specific biological processes.

The balance of intake of n-6 and n-3 PUFA, and consequently their relative incorporation into immune cells, is important in determining the development and severity of immune and inflammatory responses. Some disorders characterised by exaggerated inflammation and excessive formation of inflammatory markers have become among the most important causes of death and disability in man in modern societies. The recognition that long-chain n-3 PUFA have the potential to inhibit (excessive) inflammatory responses has led to a large number of clinical investigations with these fatty acids in inflammatory conditions as well as in healthy subjects. The present review explores the presence of dose-related effects of long-chain n-3 PUFA supplementation on immune markers and differences between healthy subjects and those with inflammatory conditions, because of the important implications for the transfer of information gained from studies with healthy subjects to patient populations, e.g. for establishing dose levels for specific applications. The effects of long-chain n-3 PUFA supplementation on ex vivo lymphocyte proliferation and cytokine production by lymphocytes and monocytes in healthy subjects have been studied in twenty-seven, twenty-five and forty-six treatment cohorts respectively, at intake levels ranging from 0·2 g EPA+DHA/d to 7·0 g EPA+DHA/d. Most studies, particularly those with the highest quality study design, have found no effects on these immune markers. Significant effects on lymphocyte proliferation are decreased responses in seven of eight cohorts, particularly in older subjects. The direction of the significant changes in cytokine production by lymphocytes is inconsistent and only found at supplementation levels ≥2·0 g EPA+DHA/d. Significant changes in inflammatory cytokine production by monocytes are decreases in their production in all instances. Overall, these studies fail to reveal strong dose–response effects of EPA+DHA on the outcomes measured and suggest that healthy subjects are relatively insensitive to immunomodulation with long-chain n-3 PUFA, even at intake levels that substantially raise their concentrations in phospholipids of immune cells. In patients with inflammatory conditions cytokine concentrations or production are influenced by EPA+DHA supplementation in a relatively large number of studies. Some of these studies suggest that local effects at the site of inflammation might be more pronounced than systemic effects and disease-related markers are more sensitive to the immunomodulatory effects, indicating that the presence of inflamed tissue or ‘sensitised’ immune cells in inflammatory disorders might increase sensitivity to the immunomodulatory effects of long-chain n-3 PUFA. In a substantial number of these studies clinical benefits related to the inflammatory state of the condition have been observed in the absence of significant effects on immune markers of inflammation. This finding suggests that condition-specific clinical end points might be more sensitive markers of modulation by EPA+DHA than cytokines. In general, the direction of immunomodulation in healthy subjects (if any) and in inflammatory conditions is the same, which indicates that studies in healthy subjects are a useful tool to describe the general principles of immunomodulation by n-3 PUFA. However, the extent of the effect might be very different in inflammatory conditions, indicating that studies in healthy subjects are not particularly suitable for establishing dose levels for specific applications in inflammatory conditions. The reviewed studies provide no indications that the immunomodulatory effects of long-chain n-3 PUFA impair immune function or infectious disease resistance. In contrast, in some conditions the immunomodulatory effects of EPA+DHA might improve immune function.

Early weaning of piglets is often accompanied by a severe growth check and diarrhoea. It is well established that this process is multi-factorial and that post-weaning anorexia and undernutrition are major aetiological factors. Gastrointestinal disturbances include alterations in small intestine architecture and enzyme activities. Recent data indicate transiently-increased mucosal permeability, disturbed absorptive–secretory electrolyte balance and altered local inflammatory cytokine patterns after weaning. These responses appear to operate according to two distinct temporal patterns, an acute response followed by a long-lasting adaptation response. Pigs coexist with a diverse and dense commensal microbiota in their gastrointestinal tract. Most of these microbes are beneficial, providing necessary nutrients or protection against harmful pathogens for the host. The microbial colonisation of the porcine intestine begins at birth and follows a rapid succession during the neonatal and weaning period. Following the withdrawal of sow's milk the young piglets are highly susceptible to enteric diseases partly as a result of the altered balance between developing beneficial microbiota and the establishment of intestinal bacterial pathogens. The intestinal immune system of the newborn piglet is poorly developed at birth and undergoes a rapid period of expansion and specialisation that is not achieved before early (commercial) weaning. Here, new insights on the interactions between feed components, the commensal microbiota and the physiology and immunology of the host gastrointestinal tract are highlighted, and some novel dietary strategies are outlined that are focused on improving gut health. Prebiotics and probiotics are clear nutritional options, while convincing evidence is still lacking for other bioactive substances of vegetable origin.

Waterlow's (1981) Sixth Boyd Orr Lecture on a ‘crisis of identity for nutrition’ stimulated the Nutrition Society's drive to professionalisation. Twenty-five years on, the Society begins a new stage; first, towards an independent voluntary regulator, and then towards statutory regulation. It is timely to reflect on progress and identify the remaining challenges. The Society has made impressive progress as a voluntary regulator since 1991 when the Insitute of Biology opened a register in cooperation with the Institute of Food Science and Technology and the Nutrition Society; the present register is 2·75-fold larger. The Society has specialist standards for course accreditation that enable graduates to apply for direct entry to the register, having met standards of competency in nutrition or public health nutrition. A code of ethics and a statement of professional conduct underpin a functioning system for oversight and governance that protects the public, the hallmark of all professions. Registered nutritionists lay easy claim to a unique science basis for their profession. A scheme for continuing professional development (CPD) started in July 2006, 1 year before a sample audit starts to show the link between CPD and re-registration. The scheme will be piloted in the first year. The critical challenge is the issue of identity. Waterlow (1981) stated that professional registration must lead explicitly and formally to a specific vocation, an occupation that provides services that society requires and one that contributes to the well-being and health of all. The present time may be the last and best chance for nutritionists, as nutrition has a higher priority for government in the UK than ever before. The Society has begun to help in strategic public health workforce planning and development; new and still plastic, it is the ideal locus from which a discipline and a profession can emerge. The CPD scheme will work if it helps nutritionists meet their own needs; more mutual cooperation and consensus about real world standards of performance are needed. Nutritionists need to show how they actually contribute to national health and/or wealth. Then, sustained resources can be advocated for and the support of the voting public and legislators secured, without which it will not be possible to get the legal protection that is desirable for the profession.

Cravings are hedonic responses to food, characterised by their intensity and their specificity. Food cravings are extremely common, reported by the majority of young adults. They are closely associated with liking but not synonymous with increased intake. Structured interviews and prospective incident accounts of food cravings have succeeded in revealing a richness of information about their character, their antecedents and their consequences. In addition, laboratory investigations are adding to what is being learned from field and clinical studies. Taking dieting as an example of an assumed influence on food craving, the outcomes of cross-sectional studies are mixed and unconvincing. Prospective and experimental research shows a clearer relationship. Dieting or restrained eating generally increase the likelihood of food craving while fasting makes craving, like hunger, diminish. Attempted restriction or deprivation of a particular food is associated with an increase in craving for the unavailable food. This relationship suggests a variety of underlying cognitive, conditioning and emotional processes, of which ironic cognitive processes, conditioned cue reactivity and dysphoric mood are prominent. Food cravings may also be self-attributions, accounting for why a highly-palatable but self-restricted food is (over-)consumed. Overall, the popularised account of cravings as elicited by specific nutritional need is having to give way to a more subtle and complex appreciation of human eating behaviour.

The prevalence of the metabolic syndrome (MetS), CVD and type 2 diabetes (T2D) is known to be higher in populations from the Indian subcontinent compared with the general UK population. While identification of this increased risk is crucial to allow for effective treatment, there is controversy over the applicability of diagnostic criteria, and particularly measures of adiposity in ethnic minorities. Diagnostic cut-offs for BMI and waist circumference have been largely derived from predominantly white Caucasian populations and, therefore, have been inappropriate and not transferable to Asian groups. Many Asian populations, particularly South Asians, have a higher total and central adiposity for a similar body weight compared with matched Caucasians and greater CVD risk associated with a lower BMI. Although the causes of CVD and T2D are multi-factorial, diet is thought to make a substantial contribution to the development of these diseases. Low dietary intakes and tissue levels of long-chain (LC) n-3 PUFA in South Asian populations have been linked to high-risk abnormalities in the MetS. Conversely, increasing the dietary intake of LC n-3 PUFA in South Asians has proved an effective strategy for correcting such abnormalities as dyslipidaemia in the MetS. Appropriate diagnostic criteria that include a modified definition of adiposity must be in place to facilitate the early detection and thus targeted treatment of increased risk in ethnic minorities.