The first cases of human Zn deficiency were described in the 1960s in the Middle East. Nevertheless, it was not until 2002 that Zn deficiency was included as a major risk factor in the global burden of disease, and only in 2004 did WHO/UNICEF include Zn supplements in the treatment of acute diarrhoea. Despite this recognition Zn is still not included in the UN micronutrient priority list, an omission that will continue to hinder efforts to reduce child and maternal mortality, combat HIV/AIDS, malaria and other diseases and achieve the UN Millennium Development Goals for improved nutrition in developing countries. Reasons for this omission include a lack of awareness of the importance of Zn in human nutrition, paucity of Zn and phytate food composition values and difficulties in identifying Zn deficiency. Major factors associated with the aetiology of Zn deficiency include dietary inadequacies, disease states inducing excessive losses or impairing utilization and physiological states increasing Zn requirements. To categorize countries according to likely risk of Zn deficiency the International Zinc Nutrition Consultative Group has developed indirect indicators based on the adequacy of Zn in the national food supplies and/or prevalence of childhood growth stunting. For countries identified as at risk confirmation is required through direct measurements of dietary Zn intake and/or serum Zn in a representative sample. Finally, in at risk countries either national or targeted Zn interventions such as supplementation, fortification, dietary diversification or modification, or biofortification should be implemented, where appropriate, by incorporating them into pre-existing micronutrient intervention programmes.

Critically-ill patients experience an extent of hyperinflammation, cellular immune dysfunction, oxidative stress and mitochondrial dysfunction. Supplementation with key nutrients, such as glutamine and antioxidants, is most likely to have a favourable effect on these physiological derangements, leading to an improvement in clinical outcomes. The results of two meta-analyses suggest that glutamine and antioxidants may be associated with improved survival. The purpose of the present paper is to report the background rationale and study protocol for the evaluation of the effect of high-dose glutamine and antioxidant supplementation on mortality in a large-scale randomized trial in 1200 mechanically-ventilated, critically-ill patients. Patients admitted to an intensive care unit (ICU) with clinical evidence of severe organ dysfunction will be randomized to one of four treatments in a 2×2 factorial design: (1) glutamine; (2) antioxidant therapy; (3) glutamine and antioxidant therapy; (4) placebo. The primary outcome for this study is 28 d mortality. The secondary outcomes are duration of stay in ICU, adjudicated diagnosis of infection, multiple organ dysfunction, duration of mechanical ventilation, length of stay in hospital and health-related quality of life at 3 and 6 months. A novel design feature is the combined use of parenteral and enteral study nutrients dissociated from the nutrition support. The therapeutic strategies tested in the randomized trial may lead to less morbidity and improved survival in critically-ill patients. The trial will be conducted in approximately twenty tertiary-care ICU in Canada and the first results are expected in 2009.

Fungi are a good source of digestible proteins and fibre, are low in fat and energy and make a useful contribution to vitamin and mineral intake. In terms of current dietary advice, 80 g fungi represent one portion of vegetables. Dried fungi and concentrated extracts are also used as medicines and dietary supplements. Some species show strong anti-tumour and antioxidant activity by enhancing various immune system functions and lowering cholesterol levels. Nevertheless, there are also some safety concerns. Edible species might be mistaken for poisonous ones, high heavy-metal concentrations in wild edible fungi (WEF) are a known source of chronic poisoning and the consumption of WEF can contribute markedly to the radiocaesium intake of human subjects. Some regions of Europe have a strong WEF tradition, especially eastern Europe. In the UK the consumption of wild fungi is considered of minor importance. Only one-third of adults consume fungi (cultivated species and WEF) throughout the UK; the average intake of fungi in the UK is estimated to be 0.12 kg fresh weight per capita per year. At least eighty-two species of wild fungi are recorded as being consumed in the UK, although certain species (e.g. chanterelle (Cantharellus cibarius), cep (Boletus edulis), oyster mushroom (Pleurotus ostreatus)) are favoured over others. Although WEF are not essential components in the daily diet, they are a nutritionally-valuable addition to the range of vegetables consumed, and their role in helping to avert food shortages in less-favoured areas should be definitely considered.

Body dissatisfaction is commonplace for teenage girls and is associated with dieting and unhealthy weight-control behaviours. The idealisation and pursuit of thinness are seen as the main drivers of body dissatisfaction, with the media prominent in setting thin body ideals. Television and consumer magazine production in the UK are extensive, annually releasing 1×106 h programming and >3000 magazine titles. Their engagement by adolescent girls is high, and in surveys girls identify thin and revealing body images as influential to the appeal of thinness and their pursuit of dieting. Experimental studies show a short-term impact of these images on body dissatisfaction, especially in teenagers who are already concerned about body image. Magazine images appear more influential than television viewing. For many adolescents selecting thin-image media is purposive, permitting comparison of themselves with the models or celebrities featured. Indeed, the impact of the media needs to be understood within a social context, as engagement is often a highly-social process. Media influence is uneven because of differences in its content and manner of communication, and individual differences in vulnerability to its content. Greater social responsibility on the part of the media and better media literacy by children would be beneficial. For those working in adolescent nutrition it is a reminder that adolescent food choice and intake are subject to many competing, contradictory and non-health-related determinants.

Increasing recognition of the importance of the long-chain n−3 PUFA, EPA and DHA, to cardiovascular health, and in the case of DHA to normal neurological development in the fetus and the newborn, has focused greater attention on the dietary supply of these fatty acids. The reason for low intakes of EPA and DHA in most developed countries (0·1–0·5 g/d) is the low consumption of oily fish, the richest dietary source of these fatty acids. An important question is whether dietary intake of the precursor n−3 fatty acid, α-linolenic acid (αLNA), can provide sufficient amounts of tissue EPA and DHA by conversion through the n−3 PUFA elongation–desaturation pathway. αLNA is present in marked amounts in plant sources, including green leafy vegetables and commonly-consumed oils such as rape-seed and soyabean oils, so that increased intake of this fatty acid would be easier to achieve than via increased fish consumption. However, αLNA-feeding studies and stable-isotope studies using αLNA, which have addressed the question of bioconversion of αLNA to EPA and DHA, have concluded that in adult men conversion to EPA is limited (approximately 8%) and conversion to DHA is extremely low (<0·1%). In women fractional conversion to DHA appears to be greater (9%), which may partly be a result of a lower rate of utilisation of αLNA for β-oxidation in women. However, up-regulation of the conversion of EPA to DHA has also been suggested, as a result of the actions of oestrogen on Δ6-desaturase, and may be of particular importance in maintaining adequate provision of DHA in pregnancy. The effect of oestrogen on DHA concentration in pregnant and lactating women awaits confirmation.

Excessive or inappropriate inflammation and immunosuppression are components of the response to surgery, trauma, injury and infection in some individuals and can lead, progressively, to sepsis and septic shock. The hyperinflammation is characterised by the production of inflammatory cytokines, arachidonic acid-derived eicosanoids and other inflammatory mediators, while the immunosuppression is characterised by impairment of antigen presentation and of T-helper lymphocyte type-1 responses. Long-chain n-3 fatty acids from fish oil decrease the production of inflammatory cytokines and eicosanoids. They act both directly (by replacing arachidonic acid as an eicosanoid substrate and by inhibiting arachidonic acid metabolism) and indirectly (by altering the expression of inflammatory genes through effects on transcription factor activation). Thus, long-chain n-3 fatty acids are potentially useful anti-inflammatory agents and may be of benefit in patients at risk of hyperinflammation and sepsis. As a consequence, an emerging application for n-3 fatty acids, in which they may be added to parenteral (or enteral) formulas, is in surgical or critically-ill patients. Parenteral nutrition that includes n-3 fatty acids appears to preserve immune function better than standard formulas and appears to diminish the extent of the inflammatory response. Studies to date are suggestive of clinical benefits from these approaches, especially in patients post surgery, although evidence of clinical benefit in patients with sepsis is emerging.

Plants provide the major part of human food intake. Whilst advances in agronomic characteristics (improved yield and better pest and disease resistance) continue to be a very high priority, there is increasing opportunity to enhance the nutritional value of plant based diets by improving the nutritional quality of staple foods. We now have proof of principle that genetic engineering can be used to produce plant-derived human vaccines. In relation to plant foods for human health, the research challenges include understanding: (1) why certain foods cause adverse reactions in some individuals but not in others; (2) the mechanisms of action of apparently ‘protective’ foods such as fruits and vegetables. There is also a need to develop much more informative and robust methods for measuring dietary exposure to specific plant foods or food constituents, including both recent exposure, for which a metabolomics approach may be particularly helpful, and long-term exposure.

The global epidemic of obesity in children will see a rise in the number of cases of metabolic syndrome, which is a clustering of CVD risk factors, including atherogenic levels of blood lipids, hyperinsulinaemia and raised blood pressure. Rather than excess general fatness (assessed by BMI), more specifically it is excess abdominal fatness, quantified by waist circumference measurement, which is a better measure of risk for these metabolic abnormalities in children of all ages. Insulin resistance, a consequence of excess visceral fat, is understood to be the driving force underpinning the metabolic syndrome. Consequently, assessment of abdominal fatness in children is proving to be more clinically useful. Waist circumference centile charts have now been developed for the UK and other paediatric populations to assist in this process. Furthermore, studies in the UK and elsewhere have shown that abdominal fatness has increased in infants, children and adolescents to a greater extent than overall fatness over the past 10–20 years, suggesting that obesity prevalence may be underestimated when based entirely on BMI. Additionally, ethnic differences in fat distribution have been demonstrated in children, with those from south Asian backgrounds having a greater abdominal distribution compared with Caucasian children and consequently having a much greater risk for type 2 diabetes. The information that can be provided by waist circumference measurement in children, as in adults, together with the recent changes in body fat distribution should provide the impetus for its measurement to be standardised and routinely taken in clinical and epidemiological settings.

The involvement of free radical mechanisms in the pathogenesis of alcoholic liver disease (ALD) is demonstrated by the detection of lipid peroxidation markers in the liver and the serum of patients with alcoholism, as well as by experiments in alcohol-feed rodents that show a relationship between alcohol-induced oxidative stress and the development of liver pathology. Ethanol-induced oxidative stress is the result of the combined impairment of antioxidant defences and the production of reactive oxygen species by the mitochondrial electron transport chain, the alcohol-inducible cytochrome P450 (CYP) 2E1 and activated phagocytes. Furthermore, hydroxyethyl free radicals (HER) are also generated during ethanol metabolism by CYP2E1. The mechanisms by which oxidative stress contributes to alcohol toxicity are still not completely understood. The available evidence indicates that, by favouring mitochondrial permeability transition, oxidative stress promotes hepatocyte necrosis and/or apoptosis and is implicated in the alcohol-induced sensitization of hepatocytes to the pro-apoptotic action of TNF-α. Moreover, oxidative mechanisms can contribute to liver fibrosis, by triggering the release of pro-fibrotic cytokines and collagen gene expression in hepatic stellate cells. Finally, the reactions of HER and lipid peroxidation products with hepatic proteins stimulate both humoral and cellular immune reactions and favour the breaking of self-tolerance during ALD. Thus, immune responses might represent the mechanism by which alcohol-induced oxidative stress contributes to the perpetuation of chronic hepatic inflammation. Together these observations provide a rationale for the possible clinical application of antioxidants in the therapy for ALD.

Neural-tube defects (NTD) are common congenital malformations that can lead to severe disability or even death. Periconceptional supplementation with the B-vitamin folic acid has been demonstrated to prevent 50–70% of NTD cases. Since the identification of the first genetic risk factor of NTD, the C677T single-nucleotide polymorphism (SNP) in the methylenetetrahydrofolate reductase (MTHFR) gene, and the observation that elevated plasma homocysteine levels are associated with NTD, research has focused on genetic variation in genes encoding for enzymes of folate metabolism and the closely-related homocysteine metabolism. In the present review relevant SNP in genes that code for enzymes involved in folate transport and uptake, the folate cycles and homocysteine metabolism are summarised and the importance of these SNP discussed in relation to NTD risk.

A strong and persistent effect of plant-derived foods on the prevention of lifestyle diseases has emerged from observational studies. Several groups of constituents in plants have been identified as potentially health promoting in animal studies, including cholesterol-lowering factors, antioxidants, enzyme inducers, apoptosis inducers etc. In human intervention studies the dose levels achieved tend to be lower than the levels found to be effective in animals and sampling from target organs is often not possible. A controlled dietary human intervention study was performed with forty-three volunteers, providing 600 g fruit and vegetables/d or in the controls a carbohydrate-rich drink to balance energy intake. Surrogate markers of oxidative damage to DNA, protein and lipids, enzymic defence and lipid metabolism were determined in blood and urine. It was found that a high intake of fruit and vegetables tends to increase the stability of lipids towards oxidative damage. Markers of oxidative enzymes indicate a steady increase in glutathione peroxidase (GPX1) activity in erythrocytes during intervention with fruit and vegetables but there is no effect on GPX1 transcription levels in leucocytes. No change occurs in glutathione-conjugating or -reducing enzyme activities in erythrocytes or plasma, and there are no effects on the transcription of genes involved in phase 2 enzyme induction or DNA repair in leucocytes. Fruit and vegetable intake decreases the level of total cholesterol and LDL-cholesterol, but does not affect sex hormones. In conclusion, it has been shown that total cholesterol and LDL-cholesterol, markers of peripheral lipid oxidation, and erythrocyte GPX1 activity are affected by high intakes of fruit and vegetables. This finding provides support for a protective role of dietary fruit and vegetables against CVD.

With the increasing prevalence of childhood obesity, there is an urgent need to identify risk factors that are amenable to preventative action. However, there is a remarkable lack of consistency between studies that have investigated the relationships between measurements of physical activity and energy expenditure and body fatness in children. This disparity could be because energy intake is a more important determinant in preventing obesity. Alternatively, some of the conflicting results could be related to methodological limitations in assessing activity and body composition. Erroneous conclusions may be drawn if physical activity energy expenditure is not adjusted for differences in body composition, or body fat is not appropriately adjusted for body size. For public health purposes it may be more informative to evaluate the amount and intensity of physical activity required to prevent fat-mass gain than to assess energy expended in physical activity. The lack of consensus in the cut-off points applied to define intensity levels is severely hindering comparisons between studies using accelerometers that have examined relationships between activity intensity and body fatness. Thus, it is not currently possible to develop a firm evidence base on which to establish physical activity recommendations until the limitations are addressed and more prospective studies undertaken. In order to turn research into effective prevention strategies a clearer understanding of the psycho-social, behavioural and environmental factors that influence activity is needed, including the interactions between physical activity and other behaviours such as time spent sedentary, sleeping and eating.

Childhood obesity has reached a crisis stage and has become a population health issue. The few traditional systematic reviews that have been done to identify best practice provide little direction for action. The concept of evidence-based practice has been adopted in health care, and in medicine in particular, to determine best practice. Evidence-based medicine has its origins in the scientific method and for many researchers this concept means strict adherence to standards determining internal validity in order to justify a practice as evidence based. Practitioners addressing population health face challenges in identifying criteria for determining evidence, in part because of the nature of population health with its goal of shifting the health of whole populations. As well, the type of evidence provided by more traditional critical appraisal schema is limiting. Expanded approaches in finding and defining evidence have been proposed that use: expert panels; broad and inclusive search and selection strategies; appraisal criteria that incorporate context and generalizability. A recent synthesis of 147 programmes addressing childhood overweight and obesity provides a concrete example of using a broader approach to identify evidence for best practice (Flynn et al.2006). Incorporating evaluation and population health frameworks as criterion components in addition to traditional methodological rigour criteria, this synthesis has identified programmes that provide contextual information that can be used to populate what Swinburn et al. (2005) have described as the ‘promise table’. Using this approach a range in ‘certainty of effectiveness’ and a range in ‘potential for population impact’ are integrated to identify promising strategies. The exercise can provide direction for agencies and practitioners in taking action to address obesity.

Mounting epidemiological evidence indicates an association between the moderate ingestion of alcoholic beverages and higher bone mineral density (v. abstainers). More limited findings provide some evidence for translation of this association into reduced fracture risk, but further studies are required. Here, these data are reviewed and caveats in their assimilation, comparison and interpretation as well as in the use and application of bone health indices are discussed. Whilst it is concluded that evidence is now strong for the moderate alcohol–bone health association, at least in relation to bone mineral density, mechanisms are less clear. Both ethanol and non-ethanol components have been implicated as factors that positively affect bone health in the light of moderate consumption of alcoholic beverages, and four particular areas are discussed. First, recent findings suggest that moderate ethanol consumption acutely inhibits bone resorption, in a non-parathyroid hormone- and non-calcitonin-dependent fashion, which can only partly be attributed to an energy effect. Second, critical review of the literature does not support a role for moderate ethanol consumption affecting oestrogen status and leading to a knock-on effect on bone. Third, Si is present at high levels in certain alcoholic beverages, especially beer, and may have a measurable role in promoting bone formation. Fourth, a large body of work indicates that phytochemicals (e.g. polyphenols) from alcoholic beverages could influence bone health, but human data are lacking. With further work it is hoped to be able to model epidemiological observations and provide a clear pathway between the magnitude of association and the relative contribution of these mechanisms for the major classes of alcoholic beverage.

Many isothiocyanates (ITC), which are available to human subjects mainly through consumption of cruciferous vegetables, demonstrate strong cancer-preventive activity in animal models. Human studies also show an inverse association between consumption of ITC and risk of cancer in several organs. Whereas earlier studies primarily focused on the ability of ITC to inhibit carcinogen-activating enzymes and induce carcinogen-detoxifying enzymes, more recent investigations have shown that ITC inhibit the proliferation of tumour cells both in vitro and in vivo by inducing apoptosis and arresting cell cycle progression. ITC cause acute cellular stress, which may be the initiating event for these effects. These findings shed new light on the mechanism of action of ITC and indicate that ITC may be useful both as cancer-preventive and therapeutic agents. ITC activate caspase 9-mediated apoptosis, apparently resulting from mitochondrial damage, and also activate caspase 8, but the mechanism remains to be defined. Cell cycle arrest caused by ITC occurs mainly in the G2/M phase, and both the G2 and M phases are targetted; critical G2-phase regulators, including cyclin B1, cell division cycle (Cdc) 2 and Cdc25C, are down regulated or inhibited, and tubulin polymerization and spindle assembly are disrupted. Moreover, ITC are metabolized in vivo through the mercapturic acid pathway, giving rise to thiol conjugates (dithiocarbamates). Studies show that these dithiocarbamates are similar to their parent ITC in exerting anti-proliferative activity. Taken together, dietary ITC are highly-promising anti-cancer agents, capable of targetting multiple cellular components that are important for tumour cell survival and proliferation.

Currently, the only treatment for any food hypersensitivity (including food allergy) is the dietary avoidance of the causative allergen, using an elimination diet. In addition to being used for the management of food hypersensitivity, an elimination diet may also be used in the diagnosis of food allergy. Dietary exclusion should be managed by a dietitian or other health professional with nutritional expertise to ensure that the exclusion does not lead to a nutritionally-deficient diet. There are three main types of elimination diets: single-food exclusion; multiple-food exclusion; the ‘few-food’ diet, which requires the avoidance of a large number of allergens and therefore concentrates on the foods that can be included rather than the foods that need to be avoided. Any sort of elimination diet is hard to manage. Thus, as well as ensuring that the diet is nutritionally adequate, it is essential that families are given advice and support relevant to their circumstances to aid them in the day-to-day management of the diet, so that it remains varied and enjoyable for food-allergy sufferers. This approach involves advice about which alternative foods are available, provision of ‘free-from’ recipes and guidance on which nutritional supplements are needed to meet their nutritional needs.

A consensus view of soyabean phyto-oestrogens in clinical interventions in post-menopausal women is presented that is based on data from the EU-funded project Phytohealth. The phyto-oestrogens, primarily genistein and daidzein, were given as soyabean-protein isolates, whole-soyabean foods or extracts, supplements or pure compounds. A comprehensive literature search was conducted with well-defined inclusion or exclusion criteria. For areas for which substantial research exists only placebo-controlled double-blind randomised controlled trials (RCT) conducted on healthy post-menopausal women were included. For emerging areas all available human studies in post-menopausal women were reviewed. In order to make cross comparisons between studies the doses of isoflavones were calculated as aglycone equivalents. There is a suggestion, but no conclusive evidence, that isoflavones from the sources studied so far have a beneficial effect on bone health. The consumption of whole-soyabean foods and soyabean-protein isolates has some beneficial effects on lipid markers of cardiovascular risk. The consumption of isolated isoflavones does not affect blood lipid levels or blood pressure, although it may improve endothelial function. For menopausal symptoms there is currently limited evidence that soyabean-protein isolates, soyabean foods or red-clover (Trifolium pratense L.) extract are effective but soyabean isoflavone extracts may be effective in reducing hot flushes. There are too few RCT studies to reach conclusions on the effects of isoflavones on breast cancer, colon cancer, diabetes or cognitive function. The health benefits of soyabean phyto-oestrogens in healthy post-menopausal women are subtle and even some well-designed studies do not show protective effects. Future studies should focus on high-risk post-menopausal women, especially in the areas of diabetes, CVD, breast cancer and bone health.

In rural Gambia the risk of mainly infection-related mortality is 10-fold higher for adults born in the nutritionally-debilitating ‘hungry’ season, suggesting that immune function may be compromised by events early in life. The current programme of research focuses on the biological mechanisms underlying this hypothesis, exploring early-life environmental influences on immune development and the long-term functional consequences these influences may have. Results obtained to date show that thymus development during infancy is critically sensitive to environmental exposures, with smaller thymuses observed in the hungry season. Measurement of the frequency of T-cell receptor excision circles indicate that thymus function is also sensitive to seasonal influences, with further studies implicating variations in breast-milk IL-7 as a possible mediator of these effects. Studies in adults have shown that size at birth is positively correlated with antibody responses to vaccination with polysaccharide antigens, thus providing evidence for long-term functional deficits. The present paper will review progress made to date within this field of research.

Acetylsalicylic acid (aspirinTM; 2-acetoxybenzoic acid) has been used for >100 years for pain relief and to treat inflammatory conditions and fevers. More recently, regular intake has been associated with decreased incidence of certain cancers, particularly colon cancer. After absorption aspirin is very rapidly hydrolysed to salicylic acid (2-hydroxybenzoic acid). The anti-cancer effects of aspirin may be a result of salicylic acid reducing the transcription of prostaglandin H2-synthase and thereby the synthesis of pro-inflammatory and potentially-neoplastic prostaglandins. Salicylic acid is widely present in plants and functions as a hormonal mediator of the systemic acquired resistance response to pathogen attack and environmental stress. Thus, it is present in a large range of fruit, vegetables, herbs and spices of dietary relevance. Consequently, the recognised effect of consuming fruit and vegetables on lowering risk of colon cancer may be partly attributable to salicylates in plant-based foods. The present review discusses which types of fruit and vegetables are the richest source of salicylates and whether they are sufficiently released from the food matrix to modify the key cellular events associated with the pathogenesis of colon cancer.