N and S metabolisms are closely interwoven throughout both the plant and animal kingdoms. The essentiality of S relates to its participation in the structure of S-containing amino acids (SAA), to its inclusion in many sulfonated molecules, and to a myriad of metabolic and catalytic reactions of vital importance. Methionine (Met) is the indispensable SAA supplied by food proteins and its plasma homeostasis is achieved via a number of highly efficient regulatory mechanisms. In all conditions characterised by a negative body protein balance such as in dietary restriction or cytokine-induced hypercatabolic losses, N and S endogenous pools manifest parallel tissue depletion rates. Adaptive conservation of N and S body stores is reached by a functional restraint of the trans-sulfuration cascade, through the depression of cystathionine β-synthase activity. As a result, upstream accumulation of homocysteine favours its re-methylation conversion to Met which helps maintain metabolic pathways of survival value. In addition to the measurement of vitamin indices, that of plasma transthyretin, a sensitive marker of protein nutritional status, is proposed to identify the fluctuations of the total body N component accountable for the alterations of homocysteine concentrations in body fluids.

A review of the literature concerning the design, utilisation and validation of food-frequency questionnaires (FFQ) has been carried out using a semi-systematic approach to obtaining, reviewing and extracting data from articles. Databases were searched from 1980 to 1999. The present review identified 227 validation (from 1980 to September 1999) and 164 utilisation (for 1998 only) studies. A number of design issues have been evaluated through the present review. These include: the need to consider how portion sizes have been described, self-defined giving higher mean correlations; how an FFQ was administered, interviewer-administered giving higher mean correlations for some nutrients; how many items to include on an FFQ, those with the largest number of items having higher correlations. Validation techniques were described. Most validation studies involved comparing an FFQ against another dietary assessment method; only 19 % compared an FFQ to a biomarker. Measurement differences were most commonly assessed by correlation coefficients as opposed to other more appropriate methods. Mean correlation coefficients were highest for Ca and fat, and lowest for vitamin A and vegetables. The utilisation studies showed that FFQ were most commonly used in cross-sectional surveys, with ninety-three of the FFQ being designed to be disease-specific. The present review results were presented to a group of experts and a consensus arrived at concerning the development, validation and use of FFQ. Recommendations derived from the consensus arising from the literature review are presented as an appendix to the present paper.

Obesity is associated with insulin resistance, the metabolic syndrome (a clustering of three or more of increased waist circumference, blood pressure, fasting glucose and fasting plasma triacylglycerol levels and reduced HDL levels), and a marked increase in the risk of type 2 diabetes and CHD. The impact of obesity differs between individuals, particularly between men and women and between ethnic groups. For example, in South Asians, although overall obesity is less prevalent, central obesity and the metabolic syndrome are more prevalent than in Europeans and this pattern is associated with the development of type 2 diabetes and CHD at an earlier age. It is important to examine individual risk factors contributing to obesity because they may have a different impact in population subgroups. Many factors contribute to the aetiology of obesity and there is increasing evidence to suggest that altered early development is one such factor and is associated with abnormal fat accumulation, the metabolic syndrome and type 2 diabetes in later life. The present review presents this evidence and discusses some of the mechanisms that may be involved in the pathogenesis of the programming of obesity.

Food insecurity is one of the most important social issues faced today, with 840 million individuals enduring chronic hunger and three billion individuals suffering from nutrient deficiencies. Most of these individuals are poverty stricken and live in developing countries. Strategies to address food insecurity must aim to increase agricultural productivity in the developing world in order to tackle poverty, and must provide long-term improvements in crop yields to keep up with demand as the world's population grows. Genetically enhanced plants provide one route to sustainable higher yields, either by increasing the intrinsic yield capability of crop plants or by protecting them from biotic and abiotic constraints. The present paper discusses a range of transgenic approaches that could increase agricultural productivity if applied on a large scale, including the introduction of genes that confer resistance to pests and diseases, or tolerance of harsh environments, and genes that help to lift the intrinsic yield capacity by increasing metabolic flux towards storage carbohydrates, proteins and oils. The paper also explores how the nutritional value of plants can be improved by genetic engineering. Transgenic plants, as a component of integrated strategies to relieve poverty and deliver sustainable agriculture to subsistence farmers in developing countries, could have a significant impact on food security now and in the future.

The early hominids and their successors, the nomadic hunter–gatherers, were evolutionarily adapted to an omnivorous diet. Their food was well balanced nutritionally and they acquired adequate supplies with relatively little expenditure of energy. The complete change to a fixed agricultural lifestyle (the Neolithic revolution) took place only some 12 000 years ago and was the most momentous event in human history. Being tied to the land that they worked led eventually to the city states and the great civilisations of history, which brought with them wars and epidemics of infectious diseases. Much more serious were the insidious effects of the new cereal-based diet which persisted until the twentieth century. Not only was it labour intensive, but also for the bulk of the population it was often deficient in vitamins, minerals and energy, particularly at certain times of the year. Time-series analysis reveals a regular short wavelength oscillation in the grain supply that persisted for at least 350 years and dominated the population dynamics of pre-industrial England. In addition to reducing fertility, it acted primarily via its effects on the nutrition of the pregnant woman. Malnutrition during one of the critical trimesters of pregnancy could have far-reaching effects not only on the health of the fetus and neonate but also on the illnesses of later, adult life. These consequences were insidiously and inevitably carried forward to the subsequent generations. Girls who were born with a low birth weight produced daughters and granddaughters of low birth weight, irrespective of their nutrition during childhood. These intergenerational, knock-on effects established a vicious circle from which there was little chance of escape.

The present review covers current knowledge about the ageing of oral physiology related to mastication and its effects on eating behaviour. Mastication is the first process undergone by a food during feeding. It has a key role in the maintenance of nutritional status in two respects. First, the perceptions of food's sensory properties elicited during chewing and swallowing are one of the major determinants of the pleasure which drives us to eat; second, the properties of the swallowed bolus are affected by oral conditions and this may modulate the subsequent phases of digestion. Ageing in healthy dentate subjects induces moderate changes in oral physiology. Changes in neuromuscular activity are partly compensated by changes in chewing behaviour. No clear age effect is seen in texture perception, although this does impact on food bolus properties. In contrast, great alterations in both chewing behaviour and food bolus properties are observed when ageing is associated with a compromised dentition, general health alterations and drug intake. Eating behaviour is far more complex than just chewing behaviour and the concerns of the elderly about food cannot be explained solely by oral physiology. Discrepancies are often noticed with older subjects between various objective measurements of oral performance and corresponding measures of self-perception. In addition, although more foods are recognised as hard to chew with increasing age, there is no clear shift in preference towards food that is easy to chew. Food choices and food consumption are also driven by memory, psychology and economic factors. Advances in the understanding of food choice in the elderly need a sustained collaborative research effort between sensory physiologists, nutritionists, and food scientists.

Evidence from epidemiological studies suggests that diets rich in n-3 PUFA may be associated with reduced cancer risk. These observations have formed the rationale for exploring the mechanisms by which n-3 PUFA may be chemoprotective and have resulted in significant advances in our mechanistic understanding of n-3 PUFA action on tumour growth. Various interrelated and integrated mechanisms may be at work by which n-3 PUFA influence cancer at all stages of initiation, promotion, progression, and neoplastic transformation. More recently, experimental studies have reported enhanced tumour cell death with chemotherapy when fish oil is provided while toxic side effects to the host are reduced. Furthermore, cancer-associated wasting has been shown to be attenuated by fish oil supplementation. Clinical evidence suggests that the n-3 PUFA status of newly diagnosed cancer patients and individuals undergoing chemotherapy is low. Therefore, both the disease itself and therapeutic treatments may be contributing factors in the decline of n-3 PUFA status. Dietary supplementation to maintain and replenish n-3 PUFA status at key points in the cancer disease trajectory may provide additional health benefits and an enhanced quality of life. The present review will focus on and critically examine current research efforts related to the putative anti-cancer effects of n-3 PUFA and their suggested ability to palliate cancer-associated and treatment-associated symptoms.

The number of elderly individuals is growing rapidly worldwide and degenerative diseases constitute an increasing problem in terms of both public health and cost. Nutrition plays a role in the ageing process and there has been intensive research during the last decade on B vitamin-related risk factors in vascular and neurological diseases and cancers. Data from epidemiological studies indicate that subclinical deficiency in most water-soluble B vitamins may occur gradually during ageing, possibly due to environmental, metabolic, genetic, nutritional and pathological determinants, as well as to lifestyle, gender and drug consumption. Older adults have distinct absorption, cell transport and metabolism characteristics that may alter B vitamin bioavailability. Case–control and longitudinal studies have shown that, concurrent with an insufficient status of certain B vitamins, hyperhomocysteinaemia and impaired methylation reactions may be some of the mechanisms involved before a degenerative pathology becomes evident. The question that arises is whether B vitamin inadequacies contribute to the development of degenerative diseases or result from ageing and disease. The present paper aims to give an overview of these issues at the epidemiological, clinical and molecular levels and to discuss possible strategies to prevent B vitamin deficiency during ageing.

Sarcopenia, the loss of muscle mass and function with ageing, is a multifactorial condition that slowly develops over decades and becomes a significant contributor to disability in the older population. Malnutrition and alterations in the muscle anabolic response to nutritional stimuli have been identified as potentially preventable factors that may significantly contribute to sarcopenia. In the present article we review the most recent findings regarding the role of nutritional factors in the development, prevention and treatment of sarcopenia. Specifically, we focus on the nutritional needs of the elderly; the age-related changes in the response of muscle protein metabolism to feeding and to the endogenous hormones released during feeding; and the role played by the splanchnic tissues in the response of muscle proteins to feeding. Finally, we review the issues relative to the potential use of nutritional therapies, including supplementation, for the prevention and treatment of sarcopenia.

The amino acid arginine and one of its metabolites NO have gathered broad attention in the last decade. Although arginine is regarded as a conditionally essential amino acid in disease, L-arginine supplementation in severe illness has not found its way into clinical practice. This might be due to the invalid interpretation of results from studies with immune-enhancing diets containing L-arginine amongst other pharmaconutrients. However, not much attention is given to research using L-arginine as a monotherapy and the possibility of the alternative hypothesis: that L-arginine supplementation is beneficial in disease. The present review will discuss data from studies in healthy and diseased animals and patients with monotherapy of L-arginine to come to an objective overview of positive and negative aspects of L-arginine supplementation in disease with special emphasis on sepsis, cancer, liver failure and wound healing.

Sepsis initiates a unique series of modifications in the homeostasis of N metabolism and profoundly alters the integration of inter-organ cooperatively in the overall N and energy economy of the host. The net effect of these alterations is an overall N catabolic state, which seriously compromises recovery and is semi-refractory to treatment with current therapies. These alterations lead to a functional redistribution of N (amino acids and proteins) and substrate metabolism among injured tissues and major body organs. The redistribution of amino acids and proteins results in a quantitative reordering of the usual pathways of C and N flow within and among regions of the body with a resultant depletion of the required substrates and cofactors in important organs. The metabolic response to sepsis is a highly integrated, complex series of reactions. To understand the regulation of the response to sepsis, a comprehensive, integrated analysis of the fundamental physiological relationships of key metabolic pathways and mechanisms in sepsis is essential. The catabolism of skeletal muscles, which is manifested by an increase in protein degradation and a decrease in synthesis, persists despite state-of-the-art nutritional care. Much effort has focused on the modulation of the overall amount of nutrients given to septic patients in a hope to improve efficiencies in utilisation and N economies, rather than the support of specific end-organ targets. The present review examines current understanding of the processes affected by sepsis and testable means to circumvent the sepsis-induced defects in protein synthesis in skeletal muscle through increasing provision of amino acids (leucine, glutamine, or arginine) that in turn act as nutrient signals to regulate a number of cellular processes.

The objective of the present review is to examine critically the consequences of interactions that micronutrients undergo with nutrients and non-nutrients (mainly prescribed medicines) in diets and lifestyle factors (smoking, tea and alcohol consumption). In addition, the review describes recent work on interactions between nutrients and genes, the influence of gene polymorphisms on micronutrients, the impact of immune responses on micronutrients and specific interactions of antioxidant micronutrients in disease processes to minimise potential pro-oxidant damage.

Although the biological requirement for vitamin D can be met by epidermal exposure to UV light, there are a number of conditions where this production does not occur or is not sufficient to meet biological needs. When this happens, vitamin D must be consumed and is a nutrient. However, two distinct observations have caused researchers to rethink certain dogma in vitamin D biology. First, it appears that in addition to the hormonally active form of 1,25 dihydroxyvitamin D (1,25(OH)2D), circulating levels of 25 hydroxyvitamin D have a critical importance for optimal human health. This and other data suggest that extra-renal production of 1,25(OH)2D contributes to Ca homeostasis and cancer prevention. Second, in addition to its role in the transcriptional activation of genes through the vitamin D receptor there is now compelling evidence that 1,25(OH)2D has a second molecular mode of action; the rapid activation of second-messenger and kinase pathways. The purpose of this second mode of action is only now being explored. The present review will discuss how these two areas are reshaping our understanding of vitamin D metabolism and action.

The concept of prebiotic food ingredients is an important recent development in nutrition. The concept has attracted a great deal of attention, and many food ingredients (mainly dietary carbohydrates) have been claimed to be ‘prebiotic’. It is emphasised that in order to be called prebiotic, a compound should be: (1) non-digestible; (2) fermentable; (3) fermentable in a selective way. These properties should be demonstrated in human volunteers in at least two independent dietary intervention trials. On the basis of published and unpublished results, it is shown in the present paper that the way in which a prebiotic influences intestinal fermentation is the key to its physiological properties. This statement is illustrated mainly by considering an established group of prebiotics, the β(2–1) fructans. These linear molecules show a strong discontinuity in physicochemical properties as the chains become longer. The β(2–1) fructans with a chain length of up to ten monomer units are very soluble and are particularly ‘bifidogenic’. Longer chains (ten to sixty-five monomer units) are poorly soluble in water, they have less pronounced bifidogenic properties, and they are fermented more slowly. It was observed that a combination of short-chain and long-chain fructans (Synergy1) is physiologically (for example, increasing mineral absorption, suppressing carcinogenesis, modulating lipid metabolism, etc) more active than the individual fractions. A possible mechanism is described in the present review. From an in-depth overview of the literature it is confirmed that for prebiotic action, the ‘selectivity principle’ for intestinal fermentation is determinative for the type and for the efficiency of physiological activity. It is confirmed that prebiotics act through their influence on intestinal fermentation.

The present review examines the importance of dietary organic anions in preventive nutrition. Organic anions are chiefly supplied by plant foods, as partially neutralised K salts such as potassium citrate, potassium malate and, to a lesser extent, oxalate or tartrate salts. Animal products may also supply K anions, essentially as phosphate, but also as lactate as a result of fermentative or maturation processes, but these K salts have little alkalinising significance. Citrate and malate anions are absorbed in the upper digestive tract, while a substantial proportion is probably metabolised in the splanchnic area. Whatever their site of metabolism, these anions finally yield KHCO3 which is used by the kidneys to neutralise fixed acidity. This acidity essentially reflects the oxidation of excess S amino acids to sulfate ions, which is mainly related to the dietary protein level. Failure to neutralise acidity leads to low-grade metabolic acidosis, with possible long-term deleterious effects on bone Ca status and on protein status. Furthermore, low-grade acidosis is liable to affect other metabolic processes, such as peroxidation of biological structures. These metabolic disturbances could be connected with the relatively high incidence of osteoporosis and muscle-protein wasting problems observed in ageing individuals in Europe and Northern America. Providing a sufficient supply of K organic anions through fruit and vegetable intake should be recommended, fostering the actual motivational campaigns ('five (or ten) per d') already launched to promote the intake of plant foods rich in complex carbohydrates and various micronutrients.

Epidemiological studies find that whole-grain intake is protective against cancer, CVD, diabetes, and obesity. Despite recommendations to consume three servings of whole grains daily, usual intake in Western countries is only about one serving/d. Whole grains are rich in nutrients and phytochemicals with known health benefits. Whole grains have high concentrations of dietary fibre, resistant starch, and oligosaccharides. Whole grains are rich in antioxidants including trace minerals and phenolic compounds and these compounds have been linked to disease prevention. Other protective compounds in whole grains include phytate, phyto-oestrogens such as lignan, plant stanols and sterols, and vitamins and minerals. Published whole-grain feeding studies report improvements in biomarkers with whole-grain consumption, such as weight loss, blood-lipid improvement, and antioxidant protection. Although it is difficult to separate the protective properties of whole grains from dietary fibre and other components, the disease protection seen from whole grains in prospective epidemiological studies far exceeds the protection from isolated nutrients and phytochemicals in whole grains.

Wine polyphenols are considered to have beneficial effects on CHD and atherosclerosis. The consumption of red wine is high in Italy and France, approximately four times greater than that in the UK. This disparity in red wine consumption is thought to be the reason for the ‘French paradox’, where France was shown to have a coronary mortality rate close to that of China or Japan despite saturated fat intakes and cholesterol levels similar to the UK and USA. In the present review, we discuss the effects of wine and some of its polyphenol constituents on early pathological indicators of CHD such as plasma lipids, the endothelium and vasculature, platelets and serum antioxidant activity. The review also examines whether the polyphenols or the alcohol in wine is responsible for the effects on markers of heart disease. The present review concludes that red wine polyphenols have little effect on plasma lipid concentrations but wine consumption appears to reduce the susceptibility of LDL to oxidation and increase serum antioxidant capacity. However, these effects do depend on the amount of wine and period of supplementation. Authors who have examined specific polyphenols suggest that some phenolics appear to have endothelium-dependent vaso-relaxing abilities and some a positive effect on NO concentrations. Red wine phenolics also have an inhibitory effect on platelet aggregation, and individual phenolics also have a similar effect in vitro, although it should be noted that there are often discrepancies as large as ten-fold between the concentrations of polyphenolics tested in vitro and their measured levels in vivo. Evidence suggests that alcohol has a positive synergistic effect with wine polyphenols on some atherosclerotic risk factors. Thus evidence that wine drinking is beneficial for cardiac health continues to accumulate but more research is required to understand fully and exactly the functions of red wine polyphenols.

Prebiotics are non-digestible (by the host) food ingredients that have a beneficial effect through their selective metabolism in the intestinal tract. Key to this is the specificity of microbial changes. The present paper reviews the concept in terms of three criteria: (a) resistance to gastric acidity, hydrolysis by mammalian enzymes and gastrointestinal absorption; (b) fermentation by intestinal microflora; (c) selective stimulation of the growth and/or activity of intestinal bacteria associated with health and wellbeing. The conclusion is that prebiotics that currently fulfil these three criteria are fructo-oligosaccharides, galacto-oligosaccharides and lactulose, although promise does exist with several other dietary carbohydrates. Given the range of food vehicles that may be fortified by prebiotics, their ability to confer positive microflora changes and the health aspects that may accrue, it is important that robust technologies to assay functionality are used. This would include a molecular-based approach to determine flora changes. The future use of prebiotics may allow species-level changes in the microbiota, an extrapolation into genera other than the bifidobacteria and lactobacilli, and allow preferential use in disease-prone areas of the body.