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

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

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

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

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

Fe plays a critical role in the immune system and defence against infection. However, many aspects of the way in which Fe influences these processes at the molecular and cellular level are unclear. The present review summarizes the role of Fe in lymphocyte activation and proliferation, and discusses how Fe is handled by macrophages.

Zn is an essential trace element for all organisms. In human subjects body growth and development is strictly dependent on Zn. The nervous, reproductive and immune systems are particularly influenced by Zn deficiency, as well as by increased levels of Zn. The relationship between Zn and the immune system is complex, since there are four different types of influence associated with Zn. (1) The dietary intake and the resorption of Zn depends on the composition of the diet and also on age and disease status. (2) Zn is a cofactor in more than 300 enzymes influencing various organ functions having a secondary effect on the immune system. (3) Direct effects of Zn on the production, maturation and function of leucocytes. (4) Zn influences the function of immunostimulants used in the experimental systems. Here we summarize all four types of influence on the immune function. Nutritional aspects of Zn, the physiology of Zn, the influence of Zn on enzymes and cellular functions, direct effects of Zn on leucocytes at the cellular and molecular level, Zn-altered function of immunostimulants and the therapeutic use of Zn will be discussed in detail.

Substrates with immune-modulating actions have been identified among both macro- and micronutrients. Currently, the modes of action of individual immune-modulating substrates, and their effects on clinical outcomes, are being examined. At present, some enteral formulas are available for the clinical setting which are enriched with selected immune-modulating nutrients. The purpose of the present paper is to review the scientific rationale of enteral immunonutrition. The major aspects considered are mucosal barrier structure and function, cellular defence function and local or systemic inflammatory response. It is notable that in critical illness the mucosal barrier and cellular defence are impaired and a reinforcement with enteral immunonutrition is desirable, while local or systemic inflammatory response should be down regulated by nutritional interventions. The results available from clinical trials are conflicting. Meta-analyses of recent trials show improvements such as reduced risk of infection, fewer days on a ventilator, and reduced length of intensive care unit and hospital stay. Thus, a grade A recommendation was proclaimed for the clinical use of enteral immune-modulating diets. Improvement in outcome was only seen when critical amounts of the immune-modulating formula were tolerated in patients classified as being malnourished. However, in other patients with severe sepsis, shock and organ failure, no benefit or even disadvantages from immunonutrition were reported. In such severe conditions we hypothesize that systemic inflammation might be undesirably intensified by arginine and unsaturated fatty acids, directly affecting cellular defence and inflammatory response. We therefore recommend that in patients suffering from systemic inflammatory response syndrome great caution should be exercised when immune-enhancing substrates are involved which may aggravate systemic inflammation.

Breast-feeding policy tends to be an emotive issue. International agencies recommend exclusive breast-feeding for 4–6 months followed by continued partial breast-feeding into the second year of life in order to promote infant and child health and minimize the damage caused by the malnutrition–infection cycle. To what extent are these recommendations supported by the experimental evidence? Are they a simplification for emotional reasons or public health purposes? Breast-feeding is believed to benefit infants because breast milk contains the ideal mix of nutrients for infants, because it contains factors which promote development of the infant’s gut and immune system and which prevent pathogen invasion, and because exclusive breast-feeding prevents intake of pathogens in food or water. However, some apparently contradictory evidence exists. First, in environments which are not highly contaminated breast-fed infants tend to growth falter relative to those fed formula. Second, in such environments partial breast-feeding is not associated with significantly increased gut damage relative to exclusive breast-feeding, suggesting that active promotion of gut development by breast-feeding is more important than simple avoidance of pathogens from other foods. Third, many immune factors in breast milk are probably present primarily to protect the mother, not the infant. Finally, breast milk itself may contain bacteria or viruses. This problem has come to the fore with the human immunodeficiency virus epidemic, since it is clear breast-feeding is an important mode of mother-to-child transmission. The present review will examine these challenges to the basis of the international infant feeding recommendations and will suggest that the science does actually support the policy.

Cow’s milk-based infant formulas and cow’s milk consumption in childhood have been suggested to promote the development of type 1 diabetes mellitus and other immune-mediated or neurological diseases. Epidemiological studies in man have led to the hypothesis that introduction of cow’s milk-based infant formula within the first 3 months of life is associated with increased risk of type 1 diabetes mellitus. Furthermore, in animal models of type 1 diabetes mellitus, cow’s milk proteins have been proven to be ‘diabetogenic’. However, the issue seems far from being resolved. Several epidemiological studies and, more importantly, the first prospective trials did not show an association between early exposure to cow’s milk and type 1 diabetes mellitus. In animal models, cow’s milk proteins are modestly and variably diabetogenic, wheat or soyabean proteins in the diet cause higher rates of autoimmune diabetes. In both man and rodents there is increasing evidence that the gut-associated immune system plays a major role in disease development, probably because of disturbed oral tolerance mechanisms. Oral tolerance depends on immunological homeostasis and normal maturation of the gut. These factors are influenced by growth factors and cytokines from breast milk, normal bacterial colonization, infections and diet. All these factors have been proposed as risk factors for type 1 diabetes mellitus. Hence, cow’s milk proteins may provide mimicry epitopes relevant in autoimmunity, as well as destabilizing oral tolerance mechanisms by biologically active peptides. The concept of dietary regulation of autoimmunity does not apply only to cow’s milk protein, but also to other dietary proteins.

Previous work in our laboratory demonstrated that a virus could undergo rapid mutation in a host deficient in Se, leading to a normally avirulent virus acquiring virulence due to genome changes. Once these mutations occur, even a host with adequate Se-nutriture is susceptible to the newly virulent virus. What influence does the deficiency in Se have on the immune response of the host? Infection with myocarditic strains of coxsackievirus induces an inflammatory response in the cardiac tissue. It is this immune response that induces the heart damage, rather than direct viral effects on the heart tissue. Chemokines are chemo-attractant molecules that are secreted during an infection in order to attract immune cells to the site of the injury, and have been found to be important for the development of coxsackievirus-induced myocarditis. We found that a deficiency in Se influences the expression of mRNA for the chemokine monocyte chemo-attractant protein-1, which may have implications for the development of myocarditis in the Se-deficient host. Expression of mRNA for interferon-γ was also greatly decreased in the Se-deficient animal. Thus, a deficiency in Se can have profound effects on the host as well as on the virus itself. How the alteration of the immune response of the Se-deficient animal affects the development of the virulent genotype remains to be answered.

Complex inter-relationships exist between certain micronutrients, immune function and disease resistance in cattle. Several micronutrients have been shown to influence immune responses. The relationship between deficiencies of some micronutrients and disease resistance is less clear. A number of studies have indicated that Cr supplementation may improve cell-mediated and humoral immune response as well as resistance to respiratory infections in stressed cattle. With respiratory-disease challenge models Cr generally does not affect disease resistance. Deficiencies of Cu, Se, vitamin E and Co in cattle reduce the ability of isolated neutrophils to kill yeast and/or bacteria. Cu deficiency reduces antibody production, but cell-mediated immunity is generally not altered. However, Cu deficiency appears to reduce production of interferon and tumour necrosis factor by mononuclear cells. Numerous studies have linked low vitamin E and/or Se status to increased susceptibility of dairy cows to intramammary infections. In contrast to findings in laboratory animals, marginal Zn deficiency does not appear to impair antibody production or lymphocyte responsiveness to mitogen stimulation in ruminants. Co deficiency has been associated with reduced resistance to parasitic infections. It is well documented that vitamin A-deficient animals are more susceptible to various types of infections. β-Carotene, possibly via its antioxidant properties, may affect immune function and disease resistance independent of its role as a precursor of vitamin A.

The immune system works best if the lymphoid cells have a delicately balanced intermediate level of glutathione. Even moderate changes in the intracellular glutathione level have profound effects on lymphocyte functions. Certain functions, such as the DNA synthetic response, are exquisitely sensitive to reactive oxygen intermediates and, therefore, are favoured by high levels of the antioxidant glutathione. Certain signal pathways, in contrast, are enhanced by oxidative conditions and favoured by low intracellular glutathione levels. The available evidence suggests that the lymphocytes from healthy human subjects have, on average, an optimal glutathione level. There is no indication that immunological functions such as resistance to infection or the response to vaccination may be enhanced in healthy human subjects by administration of glutathione or its precursor amino acid cysteine. However, immunological functions in diseases that are associated with a cysteine and glutathione deficiency may be significantly enhanced and potentially restored by cysteine supplementation. This factor has been studied most extensively in the case of human immunodeficiency virus (HIV)-infected patients who were found to experience, on average, a massive loss of S equivalent to a net loss of approximately 4 g cysteine/d. Two randomized placebo-controlled trials have shown that treatment of HIV-infected patients with N-acetyl-cysteine caused in both cases a significant increase in all immunological functions under test, including an almost complete restoration of natural killer cell activity. It remains to be tested whether cysteine supplementation may be useful also in other diseases and conditions that are associated with a low mean plasma cystine level and impaired immunological functions.

Numerous dietary treatments that purport to promote something unique for stimulating weight loss have been published. These treatments include fad diets, diets formulated by various commercial slimming clubs, very-low-energy diets (VLCD) and conventional diets. Fad diets may possibly reduce some weight short-term; however, there is no scientific basis to their long-term use. Commercial slimming clubs may be suitable for some individuals but they need to be properly assessed professionally. There are specific guidelines for the use of VLCD, which are only appropriate for short-term use. There is scientific evidence to suggest that conventional diets can produce both short- and long-term weight loss. A successful weight-loss programme depends on a multidisciplinary team approach. Management strategies should be devised for addressing issues such as goals, monitoring, follow-up, relapse and evaluation. Initial assessments should include medical, laboratory and anthropometric data, fitness level and dietary and behavioural attitudes. These results will form the basis of the treatment plan. Frequent visits to the clinic are fundamental in promoting continuing weight loss during the long-term maintenance stage of treatment. The visits should be made worthwhile for the patient. Realistic and attainable goals for diet, exercise and behaviour modification should be made. The diet should have a novel approach and be tailored to the needs of the patient. It should be adequate nutritionally, low in energy and fat. The overall aim should be to promote lifelong changes in lifestyle, improvement in quality of life and health risks.

Certain developments in the agricultural and food sciences have far-reaching implications for society and the environment, which suggest the need to examine their ethical acceptability as a standard component of technology assessment. Such considerations have led to the emergence of a new academic discipline, food ethics. The present paper describes how ethical theory may be applied to the analysis of the impacts of prospective food biotechnologies to assess potential effects on four 'interest groups', i.e. consumers, producers, treated organisms and the biota (fauna and flora). The principles which structure the framework used, i.e. the ethical matrix, are adapted to the field of agriculture and food from those applied in medical ethics. Use of the ethical matrix is illustrated by applying it to the specific case of bovine somatotrophin, the genetically-engineered protein hormone which is injected into lactating cattle to increase their milk yields. Ethical analysis is seen to depend on a number of critical requirements, i.e. scientific data, non-scientific evidence and predictions, suitably-qualified assessors ('competent moral judges'), the 'world-views' of the assessors and application of the precautionary principle to cope with 'uncertainty'.

Dietary guidelines for health promotion and disease prevention in the USA recommend a consumption pattern based largely on grains, fruit and vegetables, with smaller amounts of meat and dairy foods, and even smaller amounts of foods high in fat and sugar. Such diets are demonstrably health promoting, but following them raises ethical issues related to the role of nutritionists in advising the public about healthful dietary choices, as well as to the role of the food industry in food production and marketing. In the USA a shift towards a more plant-based diet would affect the economic interests of producers of food commodities, food products and meals prepared outside the home; it would also affect the environment, food prices, trade with other countries (developing as well as industrialized) and relationships among the food industry, government agencies (domestic and international) and food and nutrition professionals. In a free-market economy any dietary choice has consequences for food producers. Thus, considerations of ethical dilemmas in choosing healthful diets suggest that food choices are political acts that offer opportunities for all parties concerned to examine the consequences of such choices and ‘vote with forks’.