Triacylglycerols represent the main form of storage for a wide spectrum of fatty acids. Their utilization first involves mobilization from adipose tissue through lipolysis. The release of individual fatty acids from adipose tissue is selective in vitro and in vivo in animal studies and also in human subjects. Generally, fatty acids are more readily mobilized from fat cells when they are short-chain and unsaturated. This selectivity could affect the storage of individual fatty acids in adipose tissue, and their subsequent supply to tissues. The nature of the dietary fats could affect lipid homeostasis and body fat deposition. Dietary fish oil influences adipose tissue development in a site-specific manner as a function of diet and feeding period. A diet high in n-3 polyunsaturated fatty acids (PUFA) results in a preferential partitioning of ingested energy towards oxidation at the expense of storage. Fatty acids are important mediators of gene expression in the liver. Indeed, genes encoding both glycolytic and lipogenic enzymes and key metabolic enzymes involved in fatty acid oxidation are regulated by dietary PUFA. White adipose tissue could also be a target for PUFA control of gene expression. The treatment of pre-adipose cells by fatty acids induces the expression of numerous genes that encode proteins involved in fatty acid metabolism. The mechanisms of PUFA-mediated repression of gene expression in adipocytes seem to be different, at least partly, from those described in liver. Tissue-specific and site-specific factors are possibly involved in the specific effect of PUFA on gene expression, although other mechanisms cannot be excluded.

The present paper reviews current knowledge of the pulmonary cachexia syndrome with reference to chronic obstructive pulmonary disease (COPD). Aspects of incidence, aetiology and management are discussed. Malnutrition occurs in approximately one-quarter to one-third of patients with moderate to severe COPD. Both fat mass and fat-free mass become depleted. Loss of fat-free mass is the more important and appears to be due to a depression of protein synthesis. Weight loss is an independent prognostic indicator of mortality, and is associated with increased morbidity and decreased health-related quality of life. The aetiology of malnutrition in COPD is not well understood. Reduced food intake does not seem to be the primary cause. Resting energy expenditure (REE) is elevated in a proportion of patients and probably contributes to negative energy balance. Measurement of actual REE is helpful when considering the adequacy of nutritional supplementation. The underlying reason for a hypermetabolic state is not known. Although weight-losing COPD patients are not catabolic, nutritional supplementation alone does not appear to reverse the loss of fat-free mass. Strategies involving nutritional supplementation in combination with a second intervention are being explored, and there are some encouraging results using anabolic hormones.

Natural-abundance 13CNMR spectroscopy is a non-invasive technique that enables in vivo assessments of muscle and/or liver glycogen concentrations. Over the last several years, 13C NMR has been developed and used to obtain information about human glycogen metabolism with diet and exercise. Since NMR is non-invasive, more data points are available over a specified time course, dramatically improving the time resolution. This improved time resolution has enabled the documentation of subtleties of muscle glycogen re-synthesis following severe glycogen depletion that were not previously observed. Muscle and liver glycogen concentrations have been tracked in several different human populations under conditions that include: (1) muscle glycogen recovery from intense localized exercise with normal insulin and with insulin suppressed; (2) muscle glycogen recovery in an insulin-resistant population; (3) muscle glycogen depletion during prolonged low-intensity exercise; (4) effect of a mixed meal on postprandial muscle and liver glycogen synthesis. The present review focuses on basic 13C NMR and gives results from selected studies.

During late autumn insectivorous bats must deposit a fat store to cover their energy demands throughout the period of hibernation, yet the density of aerial insects by this time has already declined from its peak in midsummer. Krzanowski (1961) suggested that bats are able to deposit a fat store by manipulating their energy expenditure; specifically by selecting cold roosting locations rather than warm roosts, and depressing their body temperatures during the day roosting period. It was hypothesized that these behavioural changes result in very low daily energy demands, and despite reduced food intake the animals are still able to gain body fat. We made several tests of this hypodiesis. First, we explored the thermo-selection behaviour of long-eared bats (Plecotus auritus) in the summer and in the pre-hibernal period. We found that in summer bats preferred temperatures of about 32–35° (about thermoneutral), but in the pre-hibernal period they preferred much colder temperatures of about 10°. Second, using open-flow respirometry we found that in the cold pre-hibernal bats entered torpor for an average of 14 h each day. Compared with bats held at 30° (that did not go torpid), the bats at 7° expended less energy. The extent of saving was sufficient to positively affect their mass balance, despite the fact that bats at lower temperature also had reduced digestive efficiencies. Our findings support the hypothesis that during the pre-hibernal period insectivorous bats manipulate their mass balance primarily by alterations in their energy expenditure, specifically utilizing energy-sparing mechanisms such as torpor.

The purpose of the present paper is to provide an introduction to modelling, particularly mathematical modelling, for nutritional researchers with little or no experience of the modelling process. It aims to outline the function of modelling, and to give some guidance on factors to consider when designing protocols to generate data as part of the modelling process. It is not intended in any way to be a comprehensive guide to mathematical modelling. The paper discusses the uses of modelling, and presents a ‘hydrodynamic analogy’ to compartmental modelling, to explain the process to the non-mathematically-minded and to examine some of the pitfalls to be avoided when using stable-isotope tracers. Examples of the use of modelling in nutrition are presented, including methods for determining absorption, as well as a discussion of possible future avenues for nutritional modelling.

31P magnetic resonance spectroscopy (MRS) offers a unique non-invasive window on energy metabolism in skeletal muscle, with possibilities for longitudinal studies and of obtaining important bioenergetic data continuously and with sufficient time resolution during muscle exercise. The present paper provides an introductory overview of the current status of in vivo31P MRS of skeletal muscle, focusing on human applications, but with some illustrative examples from studies on transgenic mice. Topics which are described in the present paper are the information content of the 31P magnetic resonance spectrum of skeletal muscle, some practical issues in the performance of this MRS methodology, related muscle biochemistry and the validity of interpreting results in terms of biochemical processes, the possibility of investigating reaction kinetics in vivo and some indications for fibre-type heterogeneity as seen in spectra obtained during exercise.

Lung cancer is the most common cancer in the world, and smoking is the major risk factor, accounting for about 90% of the cases. Diet has also been implicated in the development of lung cancer, although the specific nutrients remain to be elucidated. Vitamins with antioxidant activity have received much attention. β-Carotene, the most efficient provitamin A, was found to be inversely related to the risk of lung cancer in many prospective epidemiological studies, especially in studies measuring serum concentrations of β-carotene. The findings from controlled trials, however, contradict the hypothesis that β-carotene could prevent lung cancer, but rather suggest increased risk of lung cancer with supplementary β-carotene. Data from both prospective studies and a controlled trial suggest no role for vitamin E in lung carcinogenesis. Some prospective epidemiological studies suggest an inverse relationship between dietary vitamin C and the risk of lung cancer, but due to the high correlation between dietary vitamin C and vegetable and fruit intake the independent role of dietary vitamin C is difficult to estimate. Studies using prediagnostic plasma concentrations of ascorbic acid do not support the involvement of vitamin C in lung carcinogenesis, and no controlled trials of vitamin C on lung cancer have been published. Thus, supplementation with antioxidant vitamins cannot be recommended for the prevention of lung cancer. Non-smoking is the most important target in the prevention of lung cancer. High i ntakes of vegetables and fruits may provide additional protection and are unlikely to be harmful.

The goal of this review is to develop the hypothesis, and review the evidence, that protein restriction, through synergistic effects on multiple organ systems predisposes to loss of normal regulation of fuel homeostasis that plays the central role in the development of type 2 (non-insulin-dependent) diabetes mellitus. The ability of insulin to regulate glucose production and disposal varies between individuals. These differences, together with the various compensatory mechanisms that are invoked to attempt to normalize fuel homeostasis, are of fundamental importance in the development and clinical course of type 2 diabetes mellitus. Protein deprivation impacts on both insulin secretion and insulin action. These effects may persist even when a diet containing adequate protein is presented subsequently. Data are presented that suggest that protein restriction results in an impaired ability of pancreatic β-cells to compensate adequately for the defect in insulin action in insulin-resistant individuals. This persistent impairment of insulin secretion resulting from protein restriction predisposes to loss of glucoregulatory control and impaired insulin action after the subsequent imposition of a diabetogenic challenge. This inability to maintain the degree of compensatory hyperinsulinaemia necessary to prevent loss of glucose tolerance may have relevance to the increased incidence of diabetes on changing from a nutritionally-poor diet to a Western diet, and to the hypothesis that some cases of type 2 diabetes in adulthood may be related to poor early nutrition.

The bioavailability in human subjects of non-nutrient plant factors, including dietary flavonoids and phyto-oestrogens, is of great importance relative to their reported health protective effects. These effects include protection against heart disease, and also in the case of the phyto-oestrogens, hormone-dependent cancers. Epidemiological studies have shown flavonoid intake (mostly quercetin) to be inversely associated with mortality from CHD. Quercetin is a potent antioxidant in vitro, and protection against the oxidative damage to LDL implicated in atherogenesis has been suggested as a possible mechanism. Human subjects can absorb significant amounts of quercetin (particularly in the glucoside form) and it would appear to be sufficiently bioavailable to act as an antioxidant in vivo; however, following our recent study (J O'Reilly, TAB Sanders and H Wiseman, unpublished results), it is currently less clear whether quercetin really can act as an antioxidant in vivo. The isoflavone phyto-oestrogens genistein and daidzein are much less effective antioxidants than quercetin in vitro, however, they are well-absorbed by human subjects and appear to be sufficiently bioavailable to act as antioxidants in vivo. In our recent study (O'Reilly et al. 1998) lower plasma isoprostane concentrations and increased resistance of LDL to oxidation were observed following the high-isoflavone dietary phase compared with the low-isoflavone dietary phase. Considerable inter-individual variation in isoflavone metabolite excretion has been observed, in particular the production of equol (the gut bacterial metabolite of daidzein; a more potent antioxidant and more oestrogenic than daidzein), and this appears to be influenced by habitual diet. Further studies on the bioavailability of these non-nutrient plant factors and related influencing factors are clearly still required.

The arterio-venous difference technique is now well established in the study of organ and tissue metabolism. This technique requires samples to be obtained of the arterial blood supplying and the venous drainage from a tissue, together with a measurement of the blood flow through the tissue. The technique is most appropriate when the arterial concentration and tissue metabolism of a substance are constant, and when the blood flow is stable. If these criteria are not satisfied, care is needed in the interpretation of the results obtained. It should be recognized that the arterio-venous difference technique only measures the net exchange of a substance with the tissue, and that tracers are needed if unidirectional flux needs to be estimated. The other factors which must be borne in mind when intending to use this technique are the transit times of blood and the substance of interest through a tissue, the volume of distribution of the substance in the tissue, and the possibility that the venous samples obtained are derived from a mixture of different tissues.

Public health concern has tended to focus on the dangers of obesity, but there is evidence that undernutrition may also pose a risk to physical and mental well-being, particularly in those who are already ill. Using the General Practice Research Database (see office for Population Censuses and Surveys, 1995), we followed up 10 128 men and women aged 18 years and over who had been diagnosed with cancer or cardiovascular disease to examine whether nutritional status, as indicated by BMI, affected rates of use of health care resources and mortality. In both diagnostic groups, patients with a BMI below 20 kg/m 2 had higher rates of consultation with GP, higher rates of prescription and higher death rates during the follow-up period compared with those with a BMI of 20 – < 25 kg/m 2. In men and women with cardiovascular disease, poor nutritional status was associated with a sharply increased risk of hospital admission. Patients whose BMI was 30 – <40 kg/m 2 also tended to have increased rates of GP consultation and prescription, and if they were under the age of 65 years, they had an increased risk of death. The results of the present study suggest that in men and women with cancer or cardiovascular disease, even minor degrees of undernutrition are associated with a marked increase in morbidity and mortality.

The present paper explores possible implications of the globalization of the food system for diet and health. The paper poses five key questions to clarify the relationship between food and globalization. The first question is what is globalization. The paper suggests that it is helpful to distinguish between economic, political, ideological and cultural processes. Globalization is also marked by internal oppositional dynamics: there are re-localization and regional tendencies which counter the global. The second question is whether there is anything new about globalization. Food has been a much traded commodity for millennia. The paper concludes that what is new about the current phases of globalization is the pace and scale of the change, and the fact that power is being concentrated into so few hands. New marketing techniques and supply-chain management consolidate these features. The third question is who is in control of the globalization era and who benefits and loses from the processes of globalization. It is argued that modern food economies are hypermarket rather than market economies, with power accruing to the distributor more than has been recognized. The fourth question concerns governance of the food system. Historically, systems of local and national government have regulated the food supply where appropriate. Now, new international systems are emerging, partly using existing bodies and partly creating new ones. The final question is of the future. Globalization is a value-laden area of study, yet its implications for dietary change and for health are considerable. The paper argues that dimensions of change can be discerned, although it would be rash to bet on which end of each dimension will emerge as dominant in the 21st century.

In 1996 the population of China reached 1.23 billion, 22 % of the world population, and is expected to increase to 1.5 billion by 2020. As China has only 7 % of the world's arable land such population increases are likely to have an important impact on food supply in China and the world. Projections of the potential impact are discussed. The restructuring of Chinese agriculture at the end of the 1970s has led to dramatic increases in agricultural production and food consumption, in particular of animal products, fruit and vegetables. Along with these rapid changes there is evidence of a nutrition transition in which diseases associated with affluence are becoming more prevalent than deficiency diseases. This transition has led to concern about the evolving dietary pattern. The replacement of legumes, including soyabean, by meat and other animal products as rich sources of protein and other nutrients has been controversially argued on grounds of nutritional health, ecological impact, economic effects and world food supply. These arguments are reviewed and the pressures internal and external to China concerning the production and consumption of animal v. legume products are presented. It is concluded that nutritional policies to promote the consumption of soyabean are unlikely to be effective in the context of an increasingly free and global market.

Lipoprotein metabolism plays a significant role in the pathogenesis of atherosclerosis and risk of vascular disease. Elevated levels of LDL and low levels of HDL are linked to the risk of cardiovascular disease. It is now widely accepted that oxidative modification of LDL affects the metabolism of lipoproteins, leading to their increased accumulation in arterial intima. The present paper will examine some of the accumulating evidence from studies showing relationships between dietary intake of antioxidant nutrients, i.e. vitamins E and C, the carotenoids and the flavonoids, and their influence on lipoprotein metabolism. In particular, the present paper will review the available literature on the affect of antioxidant supplementation on lipoprotein oxidation, and hence metabolism of LDL in human subjects.

The absorption of metal ions in the mammalian single-stomached gut is fortunately highly selective, and both luminal and tissue regulation occur. Initially, assimilation of metal ions in an available form is facilitated by the intestinal secretions, chiefly soluble mucus (mucin) that retards hydrolysis of ions such as Cu, Fe and Zn. Metal ions then bind and traverse the mucosally-adherent mucus layer with an efficiency M+ > M2+ > M3+. At the mucosa Fe3+ is probably uniquely reduced to Fe2+, and all divalent cations (including Fe2+) are transported by a membrane protein (such as divalent cation transporter 1) into the cell. This minimizes absorption of toxic trivalent metals (e.g. A13+). Intracellular metal-binding molecules (such as mobilferrin) may be present at the intracellular side of the apical membrane, anchored to a transmembrane protein such as an integrin complex. This mobilferrin would receive the metal ion from divalent cation transporter 1 and, with part of the integrin molecule, transport the metal to the cytosol for safe sequestration in a larger complex such as ferritin or‘paraferritin’. β2-Microglobulin and HFE (previously termed human leucocyte antigen H) may be involved in stabilizing metal mobilferrin-integrin to form this latter complex. Finally, a systemic metal-binding protein such as transferrin may enter the antiluminal (basolateral) side of the cell for binding of the sequestered metal ion and delivery to the circulation. Regulatory proteins, such as HFE, may determine the degree of ion transport from intestinal cells to the circulation. Gradients in pH and perhaps pCa or even pNa could allow the switching of ions between the different transporters throughout this mechanism.

The metabolism of white adipose tissue is regulated by many factors, including hormones and substrates delivered in the blood, the activity of the autonomic nervous system and the rate of flow of blood through the tissue. An integrated view of adipose tissue metabolism can only be gained, therefore, from studies in vivo. Of the various techniques available for studying adipose tissue metabolism in vivo, the measurement of arterio-venous differences offers some unique possibilities. In human subjects this technique has been performed mostly by catheterization of the venous drainage of the subcutaneous abdominal depot. Studies using this technique indicate that adipose tissue has an active pattern of metabolism, responding rapidly to meal ingestion by suppressing the release of non-esterified fatty acids, or to exercise with an increase in fat mobilization. Adipose tissue blood flow may also change rapidly in these situations; for instance, it increases markedly after a meal, potentially increasing the delivery of triacylglycerol to the enzyme lipoprotein lipase (EC 3.1.1.34) for hydrolysis. During exercise, there is evidence that adipose tissue blood flow does not increase sufficiently to allow delivery of all the fatty acids released into the systemic circulation. The various adipose tissue depots have their own characteristic metabolic properties, although in human subjects these are difficult to study with the arterio-venous difference technique. A combination of tracer infusion with selective catheterization allows measurements of leg, splanchnic and non-splanchnic upper-body fat mobilization and triacylglycerol clearance. Development of such techniques may open up new possibilities in the future for obtaining an integrated picture of adipose tissue function and its depot-specific variations.

As disasters and conflict increase, a higher proportion of total food aid is given as humanitarian aid. Most food aid is in the form of cereals, primarily wheat. The main donors are the USA and the EU, but there is an increase in the numbers of donors, including non-governmental organizations, buying food rather than using surpluses. Alongside the greater diversity and complexity of food aid, there is more controversy about policy and practice. If disasters are development failures, emergency food aid must be a step in the continuum from relief to rehabilitation. Comparisons of the seventeen countries that were major recipients of food aid (> 10 000 t) in 1997, show diversity in social development, dietary pattern, number of refugees, relative food inadequacy and wasting (i.e. % standard weight-for-height > 2 SD). In the absence of information of consistent quality, what influences the scale of emergency aid is unclear and susceptible to politicization, so that need and supply may not be matched. Local considerations seem to be as important as external food aid for the nutrition of the recipients. Challenges for the future include assuring the nutritional quality of rations to solve deficiency problems. The implications for the professional public health nutritionist working on emergency food provision include continuing professional development to enhance the technical expertise necessary to design appropriate feeds or rations. These public health nutritionists, more than others, require a grounding in social science theories that underpin management, ethics of professionalism and the politics of food aid.

There is growing need for accurate information regarding the bioavailability of carotenoids, both with respect to carotenoids per se and to the vitamin A value of provitamin A carotenoids in foods or supplement preparations. Little quantitative information is currently available, owing primarily to the lack of adequate methods to assess carotenoid bioavailability. Methods applied to xenobiotic drugs are in most cases not useful for carotenoids, many of which circulate in appreciable quantities in human plasma. Reported ranges of carotenoid bioavailability (% dose absorbed) range from 1–99, and variability is generally high both within and between treatments. With the current methods, relative bioavailability is more readily assessed than absolute bioavailability. The most commonly applied methods include measuring the increase in plasma carotenoid concentration following chronic intervention, and use of postprandial chylomicron (PPC) carotenoid or retinyl ester response following a single dose of carotenoid. The advantages and limitations of these approaches, together with examples of each, are discussed. A new PPC approach utilizing extrinsic-stable-isotope-labelled vitamin A (2H4-labelled retinyl acetate) is under development in our laboratory, and examples of its application are presented. The currently available data suggest that oil solutions of carotenoids are more bioavailable than those from food matrices, and heating can improve the bioavailability of carotenoids from some food products. Increased availability of labelled carotenoids and retinoids should aid the development of reliable methods of carotenoid bioavailability assessment. Such data are needed for dietary recommendations, supplement formulation, and design of intervention strategies involving carotenoids.

Much of the current literature regarding the biological effects of antioxidant nutrients has concentrated on their potential role in inhibiting or preventing tissue damage induced by free radical species produced during metabolism. Recent findings indicate that antioxidants may also have more subtle roles, regulating changes in gene expression induced by oxidizing free radical species. There is increasing evidence that free radicals act as signals for cell adaptation in a variety of cell types and the nature of the mechanisms by which free radical species influence gene expression is the subject of much current research. Processes such as these may be particularly important in tissues regularly exposed to varying amounts of oxidative stress as part of their normal physiological functions. Examples of such tissues include skin exposed to u.v. light and skeletal muscle subjected to repeated bouts of exercise.

The aim of the present review is to present techniques used for measuring blood flow in human subjects and advice as to when they may be applicable. Since blood flow is required to estimate substrate fluxes, energy turnover and metabolic rate of skeletal muscle, accurate measurements of blood flow are of extreme importance. Several techniques have therefore been developed to enable estimates to be made of the arterial inflow to, venous outflow from, or local blood flow within the muscle. Regional measurements have been performed using electromagnetic flow meters, plethysmography, indicator methods (e.g. thermodilution and indo-cyanine green dye infusion), ultrasound Doppler, and magnetic resonance velocity imaging. Local estimates have been made using 133Xe clearance, microdialysis, near i.r. spectroscopy, positron emission tomography and laser Doppler. In principle, the aim of the study, the type of interventions and the limitations of each technique determine which method may be most appropriate. Ultrasound Doppler and continuous indo-cyanine green dye infusion gives the most accurate limb blood flow measurements at rest. Moreover, the ultrasound Doppler is unique, as it does not demand a steady-state, and because its high temporal resolution allows detection of normal physiological variations as well as continuous measurements during transitional states such as at onset of and in recovery from exercise. During steady-state exercise thermodilution can be used in addition to indo-cyanine green dye infusion and ultrasound Doppler, where the latter is restricted to exercise modes with a fixed vessel position. Magnetic resonance velocity imaging may in addition be used to determine blood flow within deep single vessels. Positron emission tomography seems to be the most promising tool for local skeletal muscle blood-flow measurements in relation to metabolic activity, although the mode and intensity of exercise will be restricted by the apparatus design.