Air is one of our most important natural resources; however, it is also in the front line for receiving environmental pollution. Air quality decreased markedly following the industrial revolution, but it was not until the great London Smog in 1952 that air quality made it onto the political agenda. The introduction of the Clean Air Act in 1956 led to dramatic decreases in black smoke and SO2 concentrations over the next two decades, as domestic and industrial coal-burning activities ceased. However, as these improvements progressed, a new threat to public health was being released into the air in ever-increasing quantities. Rapid motorisation of society from the 1960s onwards has led to the increased release of atmospheric pollutants such as tiny particles (particulate matter of &10 μm in aerodynamic diameter) and oxides of N, and the generation of the secondary pollutant O3. These primary and secondary traffic-related pollutants have all proved to be major risks factors to public health. Recently, oxidative stress has been identified as a unifying feature underlying the toxic actions of these pollutants. Fortunately, the surface of the lung is covered with a thin layer of fluid containing a range of antioxidants that appear to provide the first line of defence against oxidant pollutants. As diet is the only source of antioxidant micronutrients, a plausible link now exists between the sensitivity to air pollution and the quality of the food eaten. However, many questions remain unanswered in relation to inter-individual sensitivity to ambient air pollution, and extent to which this sensitivity is modified by airway antioxidant defences.

Over the last 25 years, the effects of fatty acids on the immune system have been characterized using in vitro, animal and human studies. Advances in fatty acid biochemistry and molecular techniques have recently suggested new mechanisms by which fatty acids could potentially modify immune responses, including modification of the organization of cellular lipids and interaction with nuclear receptors. Possibilities for the clinical applications of n-3 PUFA are now developing. The present review focuses on the hypothesis that the anti-inflammatory properties of n-3 PUFA in the arterial wall may contribute to the protective effects of n-3 PUFA in CVD, as suggested by epidemiological and secondary prevention studies. Studies are just beginning to show that dietary n-3 PUFA can be incorporated into plaque lipid in human subjects, where they may influence the morphology and stability of the atherosclerotic lesion.

Glucose and long-chain fatty acids (LCFA) are two major substrates used by heart and skeletal muscle to support contractile activity. In quiescent cardiac myocytes a substantial portion of the glucose transporter GLUT4 and the putative LCFA transporter fatty acid translocase (FAT)/CD36 are stored in intracellular compartments. Induction of cellular contraction by electrical stimulation results in enhanced uptake of both glucose and LCFA through translocation of GLUT4 and FAT/CD36 respectively to the sarcolemma. The involvement of protein kinase A, AMP-activated protein kinase (AMPK), protein kinase C (PKC) isoforms and the extracellular signal-regulated kinases was evaluated in cardiac myocytes as candidate signalling enzymes involved in recruiting these transporters in response to contraction. The collected evidence excluded the involvement of PKA and implicated an important role for AMPK and for one (or more) PKC isoform(s) in contraction-induced translocation of both GLUT4 and FAT/CD36. The unravelling of further components along this contraction pathway can provide valuable information on the coordinated regulation of the uptake of glucose and of LCFA by an increase in mechanical activity of heart and skeletal muscle.

Fluid and electrolyte balance is often poorly understood and inappropriate prescribing can cause increased post-operative morbidity and mortality. The efficiency of the physiological response to a salt or water deficit, developed through evolution, contrasts with the relatively inefficient mechanism for dealing with salt excess. Saline has a Na+:Cl-of 1:1 and can produce hyperchloraemic acidosis, renal vasoconstriction and reduced glomerular filtration rate. In contrast, the more physiological Hartmann's solution with a Na+:Cl-of 1·18:1 does not cause hyperchloraemia and Na excretion following infusion is more rapid. Salt and water overload causes not only peripheral and pulmonary oedema, but may also produce splanchnic oedema, resulting in ileus or acute intestinal failure. This overload may sometimes be an inevitable consequence of resuscitation, yet it may take 3 weeks to excrete this excess. It is important to avoid unnecessary additional overload by not prescribing excessive maintenance fluids after the need for resuscitation has passed. Most patients require 2–2·5 litres water and 60–100?mmol?Na\d for maintenance in order to prevent a positive fluid balance. This requirement must not be confused with those for resuscitation of the hypovolaemic patient in whom the main aim of fluid therapy is repletion of the intravascular volume. Fluid and electrolyte balance is a vital component of the metabolic care of surgical and critically-ill patients, with important consequences for gastrointestinal function and hence nutrition. It is also of importance when prescribing artificial nutrition and should be given the same careful consideration as other nutritional and pharmacological needs.

Enteral tube feeding is common in both the hospital and community environment; however, patients can suffer alterations in faecal output that can have serious clinical sequelae. Problems associated with accurate characterisation of faecal output and definition of diarrhoea impede the comparison of research studies and prevent standardised assessment of therapeutic interventions in clinical practice. The colonic microflora may protect the patient against diarrhoea by preventing enteropathogenic infection and by producing SCFA that stimulate colonic water absorption. However, studies in healthy volunteers suggest that the composition of the enteral formula may have a negative impact on the microflora and SCFA concentrations. The addition of fructo-oligosaccharides to the enteral formula may partially prevent negative alterations to the microflora, although conclusive data from studies in patients are not yet available. Modification of the microflora with probiotics and prebiotics may hold potential in prophylaxis against diarrhoea during enteral tube feeding.

Malnutrition remains a problem in surgical and critically-ill patients. In surgical patients the incidence of malnutrition ranges from 9 to 44%. Despite this variability there is a consensus that malnutrition worsens during hospital stay. In the intensive care unit (ICU), 43% of the patients are malnourished. Although poor nutrition during hospitalisation may be attributable to many factors, not least inadequacies in hospital catering services, there must also be the question of whether those patients who receive nutritional support are being fed appropriately. Indirect calorimetry is the ‘gold standard’ for determining an individual's energy requirements, but limited time and financial resources preclude the use of this method in everyday clinical practice. Studies in surgical and ICU patient populations have been reviewed to determine the ‘optimal’ energy and protein requirements of these patients. There are only a small number of studies that have attempted to measure energy requirements in the various surgical patient groups. Uncomplicated surgery has been associated with energy requirements of 1·0–1·15×BMR whilst complicated surgery requires 1·25–1·4×BMR in order to meet the patient's needs. Identifying the optimal requirements of ICU patients is far more difficult because of the heterogeneous nature of this population. In general, 5·6 kJ (25 kcal)/kg per d is an acceptable and achievable target intake, but patients with sepsis or trauma may require almost twice as much energy during the acute phase of their illness. The implications of failing to meet and exceeding the requirements of critically-ill patients are also reviewed.

Adverse dietary factors account for approximately 30% of all cancers. Overconsumption of energy is undoubtedly one of the major risk factors, but dietary composition is also very important. In particular, a low consumption of fruits and vegetables appears to double the risk of carcinomas of the lung and alimentary tract. Epidemiological studies suggest that high plasma levels of Se, carotenoids and ascorbic acid are protective against cancer. However, intervention studies with antioxidant nutrients have given mixed results, and it has not been established that the benefits of a high intake of fruits and vegetables are invariably related to the prevention of oxidative DNA damage. Folic acid supplementation appears to protect against colo-rectal neoplasia, probably by preventing mutations associated with the repair of uracil mis-incorporation. However, there are indications from animal studies that exposure to high levels of folic acid at certain stages of development may lead to epigenetic effects that are, as yet, poorly understood. There seems little doubt that micronutrients contribute to the protective effects of plant foods against cancers of the lung and alimentary tract, but it has not been established that these benefits can be achieved using supplements.

Efficient uptake and channelling of long-chain fatty acids (LCFA) are critical cell functions. Evidence is emerging that proteins are important mediators of LCFA-trafficking into cells and various proteins have been suggested to be involved in this process. Amongst these proteins is a family of membrane-associated proteins termed fatty acid transport proteins (FATP). So far six members of this family, designated FATP 1–6, have been characterized. FATP 1, 2 and 6 show a highly-conserved AMP-binding region that participates in the activation of very-long-chain fatty acids (VLCFA) to form their acyl-CoA derivatives. The mechanisms by which FATP mediate LCFA uptake are not well understood, but several studies provide evidence that uptake of LCFA across cellular membranes is closely linked to acyl-CoA synthetase activity. It is proposed that FATP indirectly enhance LCFA uptake by activating VLCFA to their CoA esters, which are required to maintain the typical structure of lipid rafts in cellular membranes. Recent work has shown that the structural integrity of lipid rafts is essential for cellular LCFA uptake. This effect might be exerted by proteins, e.g. caveolin-1 and FAT/CD36, that use lipid rafts as platforms and bind or transport LCFA. The proposed molecular mechanisms await further experimental investigation.

The present review focuses on the B-vitamins, i.e. folate, vitamin B12, vitamin B6 and riboflavin, that are involved in homocysteine metabolism. Homocysteine is a S-containing amino acid and its plasma concentrations can be raised by various constitutive, genetic and lifestyle factors, by inadequate nutrient status and as a result of systemic disease and various drugs. Hyperhomocysteinaemia is a modest independent predictor of CVD and stroke, but causality and the precise pathophysiological mechanism(s) of homocysteine action remain unproven. The predominant nutritional cause of raised plasma homocysteine in most healthy populations is folate insufficiency. Vitamin B12 and, to a lesser extent, vitamin B6 are also effective at lowering plasma homocysteine, especially after homocysteine lowering by folic acid in those individuals presenting with raised plasma homocysteine. However, riboflavin supplementation appears to be effective at lowering plasma homocysteine only in those individuals homozygous for the T allele of the C677 T polymorphism of the methylenetetrahydrofolate reductase (MTHFR) gene. This gene codes for the MTHFR enzyme that produces methyltetrahydrofolate, which, in turn, is a substrate for the remethylation of homocysteine by the vitamin B12-dependent enzyme methionine synthase. Individuals with the MTHFR 677 TT genotype are genetically predisposed to elevated plasma homocysteine, and in most populations have a markedly higher risk of CVD.

At the outset of the research programme into irritable bowel syndrome (IBS) it was perceived that there was a need to develop a symptom-based classification for the patients. Four groups of patients were identified, those with spastic colon syndrome, diarrhoea-predominant spastic colon syndrome, functional diarrhoea and midgut dysmotility. While working with outpatients with IBS it was noted how some of them had suffered symptoms for many years; specifically, a group of patients satisfying the criteria for midgut dysmotility had also suffered from particularly severe and intractable intestinal symptoms. These patients underwent 24 h ambulatory studies of small intestinal motility and the majority were found to have manometric features of chronic idiopathic intestinal pseudo-obstruction (CIIP). To characterise the cause, laparoscopic full-thickness small intestine and colonic biopsies have been obtained in forty-five of the latter group of patients. Of these patients 58% have been found to have complete or partial deficiency of α-actin epitope staining in the inner circular layer of small intestinal smooth muscle. This deficiency is believed to represent an important biomarker rather than the cause of CIIP, since α-actin epitope deficiency has been observed in association with enteric neuropathy and myopathies. In relation to the management of CIIP patients, a multidisciplinary model is proposed incorporating management of co-morbid psychological and psychiatric pathology, abdominal and musculoskeletal pain, fatigue, urological symptoms and nutrition. A six-stage nutritional management plan for these patients is presented.

Indian Asians living in the UK have a 50% higher CHD mortality rate compared with the indigenous Caucasian population, which cannot be attributed to traditional risk factors. Instead, features of the metabolic syndrome, including raised plasma triacylglycerol, reduced HDL-cholesterol (HDL-C) and an increased proportion of small dense LDL particles, together with insulin resistance and central obesity, are prevalent among this population. The present review examines evidence to support the hypothesis that an imbalance in dietary PUFA intake, specifically a higher intake of n-6 PUFA in combination with the lower intake of the long-chain (LC) n-3 PUFA, plays an important role in the prevalence of the metabolic syndrome observed in Indian Asians. Data are presented to illustrate the impact of manipulation of the background n-6 PUFA intake (moderate or high n-6 PUFA) and the subsequent response to supplementation with LC n-3 PUFA on blood lipids and insulin action in a group of Indian Asian volunteers. The results demonstrate that supplementation with LC n-3 PUFA had no impact on insulin action in those subjects consuming either the moderate- or high-n-6 PUFA diet. In the postprandial phase reductions in plasma triacylglycerol concentrations were greater in those consuming the high-n-6 PUFA background diet subsequent to fish oil supplementation. The present study concludes that, contrary to the central hypothesis, the prevalence of metabolic abnormalities in Indian Asians compared with Caucasians may not be attributable to differences in intakes of n-6 and n-3 PUFA.

For most of the last century, researchers have searched for a muscle contraction-induced factor that mediates some of the exercise effects in other tissues such as the liver and the adipose tissue. It has been called the ‘work stimulus’, the ‘work factor’ or the ‘exercise factor’. In the search for such a factor, a cytokine, IL-6, was found to be produced by contracting muscles and released into the blood. It has been demonstrated that IL-6 has many biological roles such as: (1) induction of lipolysis; (2) suppression of TNF production; (3) stimulation of cortisol production. The IL-6 gene is rapidly activated during exercise, and the activation of this gene is further enhanced when muscle glycogen content is low. In addition, carbohydrate supplementation during exercise has been shown to inhibit the release of IL-6 from contracting muscle. Thus, it is suggested that muscle-derived IL-6 fulfils the criteria of an exercise factor and that such classes of cytokines could be termed ‘myokines’.

The somatotrophic axis is the main endocrine system regulating postnatal growth; however, prenatal growth is independent of growth hormone (GH). Fetal development relies on the coordinated actions of a range of hormones, including insulin-like growth factors (IGF), and prolactin (PRL), in the control of differentiation, growth and maturation. In the sheep the abundance peaks for liver IGF-II and PRL receptors occur during late gestation while that for IGF-I receptor occurs at birth. All receptors, with the exception of GH receptor subsequently decrease by age 6 months. It has been proposed that maternal undernutrition during gestation regulates the maturation of the fetal hypothalmic–pituitary–adrenal axis and endocrine sensitivity. Critically, the timing of the nutritional insult may affect the magnitude of reprogramming. Maternal malnutrition during early to mid-gestation (3·2–3·8 MJ/d (60% total metabolisable energy requirements) v. 8·7–9·9 MJ/d (150% total metabolisable energy requirements) between 28 and 80 d of gestation) had no effect on body or liver weight. Nutrient-restricted (NR) fetuses sampled at 80 d (mid-gestation) showed up-regulation of hepatic PRL receptor, but following refeeding the normal gestational rise in PRL and GH receptors did not occur. Hepatic IGF-II receptor was down regulated in NR fetuses at both mid- and late gestation. Conversely, 6-month-old offspring showed no difference in the abundance of either GH receptor or PRL receptor, while IGF-II mRNA was increased. Offspring of ewes malnourished during late gestation (9·1 MJ/d (60% total metabolisable energy requirements) v. 12·7 MJ/d (100% total metabolisable energy requirements) from 110 d of gestation to term) showed reduced abundance of hepatic GH and PRL receptor mRNA. In conclusion, maternal undernutrition during the various stages of gestation reprogrammed the PRL–GH–IGF axis. Nutritional regulation of cytokine receptors may contribute to altered liver function following the onset of GH-dependent growth, which may be important in regulating endocrine adaptations during subsequent periods of nutritional deprivation.

As the 21st century moves forward, it is becoming more and more apparent that the genetic makeup of any individual strongly influences the way they metabolise nutrients. It is very important, therefore, to understand the techniques and technologies used to assess the contribution genes make to the physiology of an individual. Clearly, it is not possible to provide a comprehensive overview, but in the present review an attempt will be made to show, using examples from the authors' research, how these methods have contributed to this understanding. Studies are being undertaken into Fe transport across the placenta, from the mother to the fetus, and the consequences of maternal anaemia on pregnancy outcome. Levels of gene transcript and protein have been measured using Northern and Western blotting respectively. During the course of this work a new protein has been identified using the available human genome database. Following this ‘in silico’ or ‘cyber biology’, techniques such as real-time RT–PCR and RNA interference have been used to examine expression of this gene and its protein. The methods used, briefly how they work and some of their limitations will be explained. The objective of the present review is primarily to give a better perception of how molecular biology can be used in research and to help gain a clearer understanding of some of the techniques used.

Micronutrient malnutrition is widespread throughout the world, with important health and economic consequences. Tools to address this situation include food fortification, supplementation and dietary diversification, each having different and complementary roles. Fortification (mandatory and voluntary) has been practised over several decades in Western countries as well as in developing countries. Iodised salt was introduced in the USA in 1924 to reduce severe I deficiency. In 1938 voluntary enrichment of flours and breads with niacin and Fe was initiated to reduce the incidence of pellagra and Fe-deficiency anaemia respectively. Micronutrient intakes in European countries appear to be generally adequate for most nutrients. However, a number of population subgroups are at higher risk of suboptimal intakes (below the lower reference nutrient intake) for some micronutrients, e.g. folate, Fe, Zn and Ca in children, adolescents and young women. Dietary surveys indicate that fortified foods play a role in mitigating such risks for several important nutrients. The number of foods suited to fortification are considerably limited by several factors, including technological properties (notably moisture, pH and O2 permeability), leading to unacceptable taste and appearance, as well as cost and consumer expectations. In countries in which voluntary fortification is widely practised micronutrient intakes are considerably below tolerable upper intake levels. Concerns about safety are addressed in relation to the potentially increased level or proportion of fortified foods (e.g. following potential EU legislation), for nutrients with relatively low tolerable upper intake levels and where the potential benefit and risks are in different subpopulations (e.g. folic acid). Recent models for assessing these issues are discussed.

Endurance exercise training induces an increase in the respiratory capacity of muscle, resulting in an increased capacity to generate ATP as well as improved efficiency of muscle contraction. Such adaptations are largely the result of a coordinated genetic response that increases mitochondrial proteins, fatty acid oxidation enzymes and the exercise- and insulin-stimulated glucose transporter GLUT4, and shifts the contractile and regulatory proteins to their more efficient isoforms. In recent years a number of the transcriptional regulators involved in this genetic response have been identified and these factors can be classified into two different groups. The first group comprises transcription factors such as nuclear respiratory factors (NRF) 1 and 2 and PPARα that bind DNA in a sequence-specific manner. The second group, referred to as transcriptional co-activators, alter transcription without directly binding to DNA. The PPARγ co-activator (PGC) family of proteins have been identified as the central family of transcriptional co-activators for induction of mitochondrial biogenesis. PGC-1α is activated by exercise, and is sufficient to produce the endurance phenotype through direct interactions with NRF-1 and PPARα, and potentially NRF-2. Furthering the understanding of the activation of PGC proteins following exercise has implications beyond improving athletic performance, including the possibility of providing targets for the treatment of frailty in the elderly, obesity and diseases such as mitochondrial myopathies and diabetes.

Although dietary factors have been extensively studied in many chronic diseases, the role of diet in the epidemiology of rheumatoid arthritis (RA) has received little attention. Fruit and vegetables and dietary antioxidants are thought to play a protective role in the pathogenesis of CVD and some cancers, but few studies have investigated these dietary components in the aetiology of RA. Fish oil supplementation has consistently been shown to have a beneficial effect on the symptoms of established RA, but it is not known whether the PUFA present in fish oils can reduce the risk of developing the disease. There is evidence that RA is less severe in the southern Mediterranean countries, such as Italy and Greece, where oil-rich fish, fruit, vegetables and olive oil are consumed in greater amounts than in many other countries. Overall, the evidence for a role of diet in the aetiology of RA is limited to a small number of observational studies of very different designs. Recently, it was demonstrated that lower intakes of fruit and vegetables and dietary vitamin C are associated with an increased risk of developing inflammatory polyarthritis in a free-living population in Norfolk, UK. These findings provide further evidence for a role of diet in the development of inflammatory arthritis, although the mechanisms involved are uncertain.

There is extensive evidence to show that there is considerable variation in diet and disease patterns in Europe and that many of the dietary patterns are predictive of chronic disease. Increasingly, there is evidence that this dietary effect is mediated by genetic background. The present paper examines the role of polymorphisms within three genes, those responsible for the synthesis of apoE, 5,10-methylenetetrahydrofolate reductase (MTHFR) and PPARγ. There is clear evidence to support the concept that the diet–disease link is moderated by genetic variation. The paper then considers whether this moderating effect will have implications for dietary recommendations. In the formulation of dietary reference values it has long been recognized that these values cannot cover the needs of all individuals. By setting the upper level at the mean value +2 sd, the needs of 97·5% of the population are covered. Setting a hypothetical scenario of a nutrient requirement of 200 mg\d and a polymorphism with an allelic frequency in the general population in the range of 0, 10, 20 and 30% that causes an increased nutrient requirement of 25%, there was no evidence that the traditional approach requires revision. Whilst it is recognized that genetic variability may not influence population goals, genetic variability will have to be taken into account in the clinical nutrition management of disease. To knowingly assign a patient to life-long treatment with a diet that for genetic reasons will have no success is both unethical and uneconomical. Once accepted in clinical nutrition, the diet–gene interaction will filter into the prevention of disease in public health nutrition.

Diet and lifestyle advice for individuals with diabetes has changed dramatically. The changes in nutritional recommendations have largely been in response to advances in the knowledge of the biochemical and physiological mechanisms of impaired glucose metabolism and the micro- and macrovascular complications of diabetes. The most recent guidelines for the nutritional management of diabetes were set out by Diabetes UK in 2003. This consensus-based advice paper builds on the previous evidence-based review papers of the European Association for the Study of Diabetes in 2000 and the American Diabetes Association in 2002. The changes from previous recommendations include a more liberal use of sucrose, in line with healthy eating recommendations for the general population, and allow for greater flexibility in energy derived from carbohydrate and monounsaturated fat. In addition, monounsaturated fats are promoted as the fat of choice and active promotion of carbohydrate foods with a low glycaemic index is encouraged. These guidelines emphasise the practical application of nutritional management of diabetes and the need to provide education and support in a structured way that will facilitate change in diet and lifestyle behaviour. Structured educational programmes have been shown to be effective in reducing the progression to diabetes and also in slowing the onset and progression of the complications of diabetes. These programmes require ongoing intensive input to maintain behavioural change in diet and lifestyle. Considerable energy and resources are required to set up and maintain these educational programmes, but the cost per individual is small compared with the costs of treating the complications of diabetes.

Contractile activity induces mitochondrial biogenesis and increases glucose transport capacity in muscle. There has been much research on the mechanisms responsible for these adaptations. The present paper reviews the evidence, which indicates that the decrease in the levels of high-energy phosphates, leading to activation of AMP kinase (AMPK), and the increase in cytosolic Ca2+, which activates Ca2+/calmodulin-dependent protein kinase (CAMK), are signals that initiate these adaptative responses. Although the events downstream of AMPK and CAMK have not been well characterized, these events lead to activation of various transcription factors, including: nuclear respiratory factors (NRF) 1 and 2, which cause increased expression of proteins of the respiratory chain; PPAR-α, which up regulates the levels of enzymes of β oxidation; mitochondrial transcription factor A, which activates expression of the mitochondrial genome; myocyte-enhancing factor 2A, the transcription factor that regulates GLUT4 expression. The well-orchestrated expression of the multitude of proteins involved in these adaptations is mediated by the rapid activation of PPARγ co-activator (PGC) 1, a protein that binds to various transcription factors to maximize transcriptional activity. Activating AMPK using 5-aminoimidizole-4-carboxamide-1-β-D-riboside (AICAR) and increasing cytoplasmic Ca2+using caffeine, W7 or ionomycin in L6 myotubes increases the concentration of mitochondrial enzymes and GLUT4 and enhances the binding of NRF-1 and NRF-2 to DNA. AICAR and Ca-releasing agents also increase the levels of PGC-1, mitochondrial transcription factor A and myocyte-enhancing factors 2A and 2D. These results are similar to the responses seen in muscle during the adaptation to endurance exercise and show that L6 myotubes are a suitable model for studying the mechanisms by which exercise causes the adaptive responses in muscle mitochondria and glucose transport.