Prospective cohort and case-control studies suggest an association between low folate intake and increased risk of colo-rectal adenoma and cancer. Some, but not all, animal studies indicate that folate supplementation protects against the development of colo-rectal neoplasms, although supraphysiological folate doses have been shown to enhance tumour growth. Folate is a methyl donor for nucleotide synthesis and biological methylation reactions, including DNA methylation. A low dietary folate intake may increase the risk of colo-rectal neoplasia by inducing genomic DNA hypomethylation, which can affect the expression of proto-oncogenes and tumour suppressor genes associated with the development of cancer. Common polymorphisms in genes involved in the methylation pathway, such as methylenetetrahydrofolate reductase and methionine synthase, have been shown to influence risk of colo-rectal neoplasia, with interactions dependent on folate status and/or alcohol intake, which is known to antagonise methyl group availability. There is some evidence to show that DNA from normal-appearing colo-rectal mucosa in individuals with colo-rectal cancer is hypomethylated. In a case-control study DNA methylation in normal-appearing colo-rectal mucosa has been shown to be lower in individuals with colo-rectal cancer (P=0.08) and colo-rectal adenoma (P=0.009) than in controls free of colo-rectal abnormalities. Human intervention trials to date suggest that supraphysiological doses of folate can reverse DNA hypomethylation in colo-rectal mucosa of individuals with colo-rectal neoplasia. In a double-blind randomised placebo-controlled study folate supplementation at physiological doses has been shown to increase DNA methylation in leucocytes (P=0.05) and colonic mucosa (P=0.09). Further studies are required to confirm these findings in larger populations and to define abnormal ranges of DNA methylation.

Obese individuals are at increased risk from a range of metabolic diseases, including insulin resistance, dyslipidaemia and hypertension. Adipose tissue is an important endocrine organ, secreting a range of inflammatory mediators, including tumour necrosis factor a and interleukin 6. Circulating concentrations of these cytokines are increased in obesity and may contribute to the pathogenesis of metabolic diseases. The present review considers the evidence linking inflammation and obesity-related disease. The data show that an inflammatory phenotype, measured by serum sialic acid concentration, identifies individuals with insulin resistance, dyslipidaemia and hypertension. Serum sialic acid concentration increases progressively in obese individuals with none, one or multiple features of the metabolic syndrome, independent of BMI. Supplementation with long-chain n-3 polyunsaturated fatty acids has shown anti-inflammatory effects in studies of both healthy populations and in models of chronic inflammatory conditions. The effect on insulin sensitivity has been varied, with both positive and negative effects. This variability may relate to the metabolic characteristics of the study population; individuals with high background inflammation may derive greater benefits from n-3 polyunsaturated fatty acid supplements, suggesting a possible interaction between diet and phenotype. Future research is needed to fully evaluate the role of anti-inflammatory strategies in the dietary management of obesity.

Whole grains are important dietary constituents as they provide a plethora of nutrients and protective chemicals that may have synergistic actions in promoting health. Regular consumption of wholegrain foods has been associated with a reduced risk of several chronic diseases such as CHD and certain cancers, although their exact role in disease prevention is not yet fully elucidated. Studies reporting levels of whole grain consumption reveal that those subjects who include higher levels of whole grain foods in their diets also have many other favourable dietary and lifestyle practices. While the actions of these practices and whole grains may not be mutually exclusive, these variables do not appear to explain the reduction in risk of disease observed for high-whole grain consumers. Actual whole grain consumption levels are extremely low and many practical barriers exist to consumer uptake of these foods. Effective communication of the whole grain health message is an important strategy to increase awareness of the importance of whole grains in the diet. Increasing the variety and availability of acceptable wholegrain foods is also important. Whole grain consumption at breakfast can have an important impact on total daily nutrient intakes. This simple dietary modification is potentially relatively easy to achieve and could greatly contribute to increased whole grain intake for many individuals.

Platelets play a substantial role in cardiovascular disease, and for many years there has been a search for dietary components that are able to inhibit platelet function and therefore decrease the risk of cardiovascular disease. Platelets can be inhibited by alcohol, dietary fats and some antioxidants, including a group of compounds, the polyphenols, found in fruits and vegetables. A number of these compounds have been shown to inhibit platelet function both in vitro and in vivo. In the present study the effects of the hydroxycinnamates and the flavonoid quercetin on platelet activation and cell signalling in vitro were investigated. The hydroxycinnamates inhibited platelet function, although not at levels that can be achieved in human plasma by dietary intervention. However, quercetin inhibited platelet aggregation at levels lower than those previously reported. Quercetin was also found to inhibit intracellular Ca mobilisation and whole-cell tyrosine protein phosphorylation in platelets, which are both processes essential for platelet activation. The effect of polyphenols on platelet aggregation in vivo was also investigated. Twenty subjects followed a low-polyphenol diet for 3 d before and also during supplementation. All subjects were supplemented with a polyphenol-rich meal every lunchtime for 5 d. Platelet aggregation and plasma flavonols were measured at baseline and after 5 d of dietary supplementation. Total plasma flavonoids increased significantly after the dietary intervention period (P=0·001). However, no significant changes in ex vivo platelet aggregation were observed. Further investigation of the effects of individual polyphenolic compounds on platelet function, both in vitro and in vivo, is required in order to elucidate their role in the relationship between diet and the risk of cardiovascular disease.

Homocysteine, derived from the demethylation of the ammo acid methionine, is either further catabolised by trans-sulfuration to cysteine or remethylated to methionine. Remethylation to methionine requires the cofactors, folate and vitamin B12. Folate is an effective homocysteine-lowering agent and, thus, homocysteine and folate status are inversely related. Hyperhomocysteinaemia is a strong independent risk factor for venous thromboembolism (VTE) and is associated with adverse pregnancy outcomes such as pre-eclampsia, placental abruption, early pregnancy loss and neural-tube defects. Pregnancy is a risk factor for VTE as a result of prothrombotic changes in levels of haemostatic factors. However, despite this hypercoagulable state, the incidence of pregnancy-associated VTE is relatively low. Hyperhomocysteinaemia is associated with abnormalities in markers of coagulation activation, and recent research suggests that folic acid supplementation, as well as lowering homocysteine, lowers markers of coagulation activation and increases levels of coagulation inhibitors. Tissue factor (TF) is the initiator of blood coagulation in vivo, and homocysteine induces TF expression in vitro. During pregnancy, monocyte TF expression is lower than that in the non-pregnant state, and this lowering of TF may act to counterbalance increases in coagulation activation. Furthermore, despite a high folate requirement, several studies have reported that homocysteine is lower in normal pregnancy than in the non-pregnant state. Although the exact mechanism of homocysteine lowering during pregnancy is unclear, one possible outcome of lower homocysteine may be the protection of women from pregnancy complications and VTE, and thus lower homocysteine may contribute to maintaining homeostasis in haemostasis.

Raised blood pressure (BP) is a major cause of CHD and the leading cause of stroke. Although BP rises with age in most populations, there are remote populations around the world where BP does not rise with age and where the high prevalence of high BP and frank hypertension seen in the UK and other Western countries in the older age-groups is not found. However, when such populations migrate to urban settings, their BPs rise, indicating that the population-wide BP problem is largely environmental in origin. Thus, a substantial body of evidence has accumulated on the importance of dietary factors in BP (Na and alcohol intakes (direct relationship) and K intake (inverse relationship)) as well as body weight (direct relationship). More recently, attention has shifted to other dietary factors that might affect BP. Data from studies of vegetarians (who tend to have lower BP than meat-eating populations) as well as clinical data on the adverse effects of protein intake in patients with renal insufficiency led to the view in Western countries that dietary (animal or total) protein had an adverse effect on BP. By contrast, studies in Japan and China suggested that dietary protein might be protective of high BP and stroke. Recent epidemiological studies have found inverse associations between dietary protein intake and BP, consistent with this view, and supported by some evidence from animal studies. Recent controlled clinical trials of soyabean supplementation have also suggested a BP-lowering effect of protein intake. Results of further large-scale epidemiological studies of protein and BP are awaited.

Dietary protein has several opposing effects on Ca balance and its net effect on bone is not well established. It has long been recognized that increasing protein intake increases urinary Ca excretion. More recently, it has been observed that increasing dietary protein raises the circulating level of insulin-like growth factor-1, a growth factor that promotes osteoblast formation and bone growth. Other effects of protein on the Ca economy have been suggested in some studies, but they are less well established. Several studies have examined associations between protein intake and bone loss and fracture rates. In the original Framingham cohort subjects with lower total and animal protein intakes had greater rates of bone loss from the femoral neck and spine than subjects consuming more protein. In another study higher total (and animal) protein intakes were associated with a reduced incidence of hip fractures in post-menopausal women. In contrast, a high animahplant protein intake has been associated with greater bone loss from the femoral neck and a greater risk of hip fracture in older women. Higher total and higher animal protein intakes have also been associated with increased risk of forearm fracture in younger post-menopausal women. In a recent study it was found that increasing dietary protein was associated with a favourable (positive) change in bone mineral density of the femoral neck and total body in subjects taking supplemental calcium citrate malate with vitamin D, but not in those taking placebo. The possibility that Ca intake may influence the impact of dietary protein on the skeleton warrants further investigation.

Bone growth and turnover results from the coordinated activities of two key cell types. Bone matrix is deposited and mineralised by osteoblasts and it is resorbed by osteoclasts, multinucleate cells that excavate pits on bone surfaces. It has been known since the early 20th century that systemic acidosis causes depletion of the skeleton, an effect assumed to result from physico-chemical dissolution of bone mineral. However, our own work has shown that resorption pit formation by cultured osteoclasts was absolutely dependent on extracellular acidification; these cells are inactive at pH levels above about 7·3 and show maximum stimulation at a pH of about 6·9. Bone resorption is most sensitive to changes in H+ concentration at a pH of about 7·1 (which may be close to the interstitial pH in bone). In this region pH shifts of <0·05 units can cause a doubling or halving of pit formation. In whole-bone cultures, chronic HCO3- acidosis results in similar stimulations of osteoclast-mediated Ca2+ release, with a negligible physico-chemical component. In vivo, severe systemic acidosis (pH change of about –0·05 to –0·20) often results from renal disease; milder chronic acidosis (pH change of about –0·02 to –0·05) can be caused by excessive protein intake, acid feeding, prolonged exercise, ageing, airway diseases or the menopause. Acidosis can also occur locally as a result of inflammation, infection, wounds, tumours or diabetic ischaemia. Cell function, including that of osteoblasts, is normally impaired by acid; the unusual stimulatory effect of acid on osteoclasts may represent a primitive ‘fail-safe’ that evolved with terrestrial vertebrates to correct systemic acidosis by ensuring release of alkaline bone mineral when the lungs and kidneys are unable to remove sufficient H+ equivalent. The present results suggest that even subtle chronic acidosis could be sufficient to cause appreciable bone loss over time.

Body composition in children is of increasing interest within the contexts of childhood obesity, clinical management of patients and nutritional programming as a pathway to adult disease. Energy imbalance appears to be common in many disease states; however, body composition is not routinely measured in patients. Traditionally, clinical interest has focused on growth or nutritional status, whereas more recent studies have quantified fat mass and lean mass. The human body changes in proportions and chemical composition during childhood and adolescence. Most of the weight gain comprises lean mass rather than fat. In general, interest has focused on percentage fat, and less attention has been paid to the way in which lean mass varies within and between individuals. In the general population secular trends in BMI have been widely reported, indicating increasing levels of childhood obesity, which have been linked to reduced physical activity. However, lower activity levels may potentially lead not only to increased fatness, but also to reduced lean mass. This issue merits further investigation. Diseases have multiple effects on body composition and may influence fat-free mass and/or fat mass. In some diseases both components change in the same direction, whereas in other diseases, the changes are contradictory and may be concealed by relatively normal weight. Improved techniques are required for clinical evaluations. Both higher fatness and reduced lean mass may represent pathways to an increased risk of adult disease.

Energy balance can be estimated in tissues, body segments, individual subjects (the focus of the present article), groups of subjects and even societies. Changes in body composition in individual subjects can be translated into changes in the energy content of the body, but this method is limited by the precision of the techniques. The precision for measuring fat and fat-free mass can be as low as 0.5 kg when certain reference techniques are used (hydrodensitometry, air-displacement plethysmography, dual-energy X-ray absorptiometry), and approximately 0.7 kg for changes between two time points. Techniques associated with a measurement error of 0.7 kg for changes in fat and fat-free mass (approximately 18MJ) are of little or no value for calculating energy balance over short periods of time, but they may be of some value over long periods of time (18 MJ over 1 year corresponds to an average daily energy balance of 70 kJ, which is <1% of the normal dietary energy intake). Body composition measurements can also be useful in calculating changes in energy balance when the changes in body weight and composition are large, e.g. >5–10 kg. The same principles can be applied to the assessment of energy balance in body segments using dual-energy X-ray absorptiometry. Energy balance can be obtained over periods as short as a few minutes, e.g. during measurements of BMR. The variability in BMR between individuals of similar age, weight and height and gender is about 7–9%, most of which is of biological origin rather than measurement error, which is about 2%. Measurement of total energy expenditure during starvation (no energy intake) can also be used to estimate energy balance in a whole-body calorimeter, in patients in intensive care units being artificially ventilated and by tracer techniques. The precision of these techniques varies from 1 to 10%. Establishing energy balance by measuring the discrepancy between energy intake and expenditure has to take into consideration the combined validity and reliability of both components. The measurement error for dietary intake may be as low as 2–3% in carefully controlled environments, in which subjects are provided only with certain food items and bomb calorimetry can be undertaken on duplicate samples of the diet. Reliable results can also be obtained in hospitalised patients receiving enteral tube feeding or parenteral nutrition as the only source of nutrition. Unreliability increases to an unknown extent in free-living subjects eating a mixed and varied diet; thus, improved methodology is needed for the study of energy balance.

The current epidemic of human obesity implies that whilst energy balance appears to be regulated, the extent of this regulatory process is being overwhelmed in large numbers of the population by environmental changes. Clearly, the shift towards positive energy balance reflects both alterations in energy intake and decreases in physical activity. Increased energy intake and, in particular, the rising proportion of energy from fat is linked with obesity. However, on a population level reduced levels of activity probably play the predominant role. It is apparent that individual susceptibility to weight gain varies enormously. The factors underlying this susceptibility are an area of intense research interest. Variations in BMR from that predicted appear to be linked to the propensity to gain weight. The genes responsible for this variation may include uncoupling proteins-2 and -3, with a number of studies showing a link with obesity. However, in vivo studies of these proteins have not yet demonstrated a physiological role for them that would explain the link with obesity. Non-exercise activity thermogenesis may also protect from weight gain, but the regulation of this type of thermogenesis is unclear, although the sympathetic nervous system may be important. A profusion of hormones, cytokines and neurotransmitters is involved in regulating energy intake, but whilst mutations in leptin and the melanocortin-3 receptor are responsible for rare monogenic forms of obesity, their wider role in common polygenic obesity is not known. Much current work is directed at examining the interplay between genetic background and environmental factors, in particular diet, that both lead to positive energy balance and seem to make it so hard for many obese subjects to lose weight.

Energy balance is the difference between energy consumed and total energy expended. Over a given period of time it expresses how much the body stores of fat, carbohydrate and protein will change. For the critically-ill patient, who characteristically exhibits raised energy expenditure and proteolysis of skeletal muscle, energy balance information is valuable because underfeeding or overfeeding may compromise recovery. However, there are formidable difficulties in measuring energy balance in these patients. While energy intake can be accurately recorded in the intensive care setting, the measurement of total energy expenditure is problematic. Widely used approaches, such as direct calorimetry or doubly-labelled water, are not applicable to the critically ill patient. Energy balance was determined over periods of 5–10 d in patients in intensive care by measuring changes in the fat, protein and carbohydrate stores of the body. Changes in total body fat were positively correlated with energy balance over the 5 d study periods in patients with severe sepsis (n24, r 0.56, P=0.004) or major trauma (n 24, r 0.70, P<.0001). Fat oxidation occurred in patients whose energy intake was insufficient to achieve energy balance. Changes in body protein were independent of energy balance. These results are consistent with those of other researchers who have estimated total energy requirements from measurements of O2 consumption and CO2 production. In critically-ill patients achievement of positive non-protein energy balance or total energy balance does not prevent negative N balance. Nutritional therapy for these patients may in the future focus on glycaemic control with insulin and specialised supplements rather than on energy balance per se.

The need for an evidence base for human nutrition action is analysed in the context of human rights. Over the last 50 years the twin tracks of development, economical needs based and normative rights based, have come progressively closer in terms of goals and objectives, even if they do maintain different orientations and origins. The international human rights machinery is described, together with those parts that are of relevance to the right to food and nutrition. The role of the State in respecting, protecting and facilitating these rights is further described. The evidence base for the benefit of nutrition interventions during the fetal and infant period to the health and well-being of populations throughout life's course is briefly reviewed, and reasons why such a large body of evidence has not been acted upon are discussed. The power of nutrition is in prevention more than cure, and the prevention of nutritional deficiency is best suited to radical population-wide strategies rather than high-risk strategies targeted at individuals. The population-wide distribution of benefits of nutrition is in congruence with universality of human rights. In the UK much remains to be done to ensure that food and nutrition rights are realised, especially during the critical period of fetal and infant growth. What role the Nutrition Society might play in the realisation of these rights, including the creation of a robust evidence base for nutrition action, is further discussed.

The present paper addresses the emergence and development of Nordic food and nutrition policies, with some reference to the types of nutrition policies characteristic of other North European countries. Nutrition programmes aimed at dietary change have a long history of public responsibility in several Nordic and North European countries. The extent of involvement, the orientation and (indication of) success have, however, varied considerably between countries. First, different types of policies are characterised by their choice of programmes and measures, e.g. information campaigns v. market regulation or catering and public services. Second, the distinctions are associated not only with programmes, but also with the status and validity of nutritional advice and dietary guidelines in public policy making. Third, when focusing on how and on what grounds the governments have developed nutrition policies, it is evident that while more or less the same participants and issues are involved, their roles and relationships may be different. In this case the role and involvement of nutritional expertise and scientific arguments in various countries will be discussed. Finally, nutrition policies may entail conflicts of interest, particularly when health concerns are confronted with food industry and agricultural interests. This situation is quite evident in the question of animal fat. The present paper addresses how these issues have been dealt with quite differently in various countries.