The link between genome instability and adverse health outcomes during the various stages of life, such as infertility, fetal development and cancer, is briefly reviewed against a background of evidence indicating that genome instability, in the absence of overt exposure to genotoxins, is itself a sensitive marker of nutritional deficiency. The latter is illustrated with cross-sectional and dietary intervention data obtained using the micronucleus assay, an efficient biomarker for diagnosing genome instability and nutritional deficiency. The concept of recommended dietary allowances for genome stability and how this could be achieved is discussed together with the emerging field of nutritional genomics for genome stability. The review concludes with a vision for a disease-prevention strategy based on the diagnosis and nutritional treatment of genome instability, i.e. ‘Genome Health Clinics’.

Mechanistic models of microbial metabolism in the rumen aim at an improved understanding and integration for research purposes or at an improved prediction for practical purposes. The standard way of representing such models is the rate : state formalism. The system is defined by a number of state variables and a set of differential equations describe the change of the state variables with time. Three different types of solution to these dynamic models are distinguished, and examples of these solutions are described to illustrate the applications and contributions of dynamic modelling in the study of the rumen microbial ecosystem. Type I solutions are obtained when the system is in steady state and the differential equations are solved by setting the differentials to zero. An application of the type I solution is the indirect approach to quantifying the fibrolytic anaerobic fungi in the rumen. The solutions of the model describing the alternate life cycle of rumen fungi, with its free-swimming dispersal and particle-attached stages, appear to be consistent with ruminal and faecal observations. Type II solutions are obtained when the system is not in steady state but the differential equations can be integrated analytically. An application of this type of solution is the quantification of the growth and growth yield in batch cultures. Such models help to quantify the degradation of substrates in the rumen and to elucidate the interactions between groups of rumen micro-organisms. Type III solutions are obtained when the system is not in steady state and when the differential equations have to be solved numerically. Applications of the type III solutions are the rumen simulation models that describe substrate degradation, endproduct formation and microbial metabolism in an integrated manner. To illustrate this type III solution, a model of lactic acid metabolism in the rumen is defined, and its contribution to understanding of the paths and rates of lactic acid disappearance described. It is essential that the models are based on sound mathematical and biological principles. However, the various applications described in the paper show that models need not necessarily be complex and very detailed to contribute to better understanding.

The relevance of dairy produce for the diminishment of osteoporotic risk is still a matter of scientific debate due to the outcome of a few single observational studies. This review will address the most robust point estimate on the role of dairy products, as reported in systematic reviews and meta-analyses on randomised controlled trials in the case of bone mineralisation or prospective studies in the case of fracture risk. Plain dairy products or those fortified with Ca and/or vitamin D improve total body bone mineral content (BMC) by 45–50 g over 1 year when the daily baseline Ca intake is lower than 750 mg in Caucasians and Chinese girls. In Caucasian and Chinese women, Ca from (fortified) dairy products increases bone mineral density (BMD) by 0·7–1·8 % over 2 years dependent on the site of measurement. Despite the results on BMC, there are currently no studies that have investigated the potential of dairy products to reduce fracture risk in children. In adult Caucasian women, daily intake of 200–250 ml of milk is associated with a reduction in fracture risk of 5 % or higher. In conclusion, the role of dairy products for BMC or BMD has been sufficiently established in Chinese and Caucasian girls and women. In Caucasian women, drinking milk also reduces fracture risk. More research on the role of dairy products within the context of bone health-promoting diets is needed in specific ethnicities, other than Chinese and Caucasians, and in men.

It has been nearly 70 years since the discovery that strict adherence to a diet low in phenylalanine prevents severe neurological sequelae in patients with phenylalanine hydroxylase deficiency (phenylketonuria; PKU). Today, dietary treatment with restricted phenylalanine intake supplemented with non-phenylalanine amino acids to support growth and maintain a healthy body composition remains the mainstay of therapy. However, a better understanding is needed of the factors that influence N balance in the context of amino acid supplementation. The aim of the present paper is to summarise considerations for improving N balance in patients with PKU, with a focus on gaining greater understanding of amino acid absorption, disposition and utilisation. In addition, the impact of phenylalanine-free amino acids on 24 h blood phenylalanine/tyrosine circadian rhythm is evaluated. We compare the effects of administering intact protein v. free amino acid on protein metabolism and discuss the possibility of improving outcomes by administering amino acid mixtures so that their absorption profile mimics that of intact protein. Protein substitutes with the ability to delay absorption of phenylalanine and tyrosine, mimicking physiological absorption kinetics, are expected to improve the rate of assimilation into protein and minimise fluctuations in quantitative plasma amino acid levels. They may also help maintain normal glycaemia and satiety sensation. This is likely to play an important role in improving the management of patients with PKU.

Asthma is one of the most common and prevalent problems worldwide affecting over 300 million individuals. There is some evidence from observational and intervention studies to suggest a beneficial effect of n-3 PUFA in inflammatory diseases, specifically asthma. Marine-based n-3 PUFA have therefore been proposed as a possible complementary/alternative therapy for asthma. The proposed anti-inflammatory effects of n-3 fatty acids may be linked to a change in cell membrane composition. This altered membrane composition following n-3 fatty acid supplementation (primarily EPA and DHA) can modify lipid mediator generation via the production of eicosanoids with a reduced inflammatory potential/impact. A recently identified group of lipid mediators derived from EPA including E-series resolvins are proposed to be important in the resolution of inflammation. Reduced inflammation attenuates the severity of asthma including symptoms (dyspnoea) and exerts a bronchodilatory effect. There have been no major health side effects reported with the dietary supplementation of n-3 fatty acids or their mediators; consequently supplementing with n-3 fatty acids is an attractive non-pharmacological intervention which may benefit asthma.

For more than 200 years the fibre in plant foods has been known by animal nutritionists to have significant effects on digestion. Its role in human nutrition began to be investigated towards the end of the 19th century. However, between 1966 and 1972, Denis Burkitt, a surgeon who had recently returned from Africa, brought together ideas from a range of disciplines together with observations from his own experience to propose a radical view of the role of fibre in human health. Burkitt came late to the fibre story but built on the work of three physicians (Peter Cleave, G. D. Campbell and Hugh Trowell), a surgeon (Neil Painter) and a biochemist (Alec Walker) to propose that diets low in fibre increase the risk of CHD, obesity, diabetes, dental caries, various vascular disorders and large bowel conditions such as cancer, appendicitis and diverticulosis. Simply grouping these diseases together as having a common cause was groundbreaking. Proposing fibre as the key stimulated much research but also controversy. Credit for the dietary fibre hypothesis is given largely to Burkitt who became known as the ‘Fibre Man’. This paper sets out the story of the development of the fibre hypothesis, and the contribution to it of these individuals.

Food-derived bioactive peptides are regarded as important modulators of several physiological processes occurring both systemically and locally within the gastrointestinal tract (GIT). However, the concentrations of food-derived bioactive peptides in the GIT, and therefore attendant physiological effects, are likely to be highly variable given the wide variation in the type and amount of dietary protein consumed either during the day or on a day-to-day basis. In contrast, gut endogenous proteins (e.g. cell proteins, mucin, serum albumin and digestive enzymes) are a consistent and significant potential source of peptides for the GIT. With up to 80 % of gut endogenous proteins being digested in the GIT, it is possible that a wide range of peptides is generated, but until now the significance of the gut endogenous proteins as a source of bioactive peptides has not been considered. A hypothesis is promulgated that the gut endogenous proteins may have a hidden role as a consistent and quantitatively important source of bioactive peptides in the GIT.

Guidelines for sugars intake range from a population mean of less than 10 % energy from free sugars, to a maximum for individuals of 25 % energy from added sugars. The aim of the present review was to examine the evidence for micronutrient dilution by sugars and evaluate its nutritional significance. From a web-based search of MEDLINE and hand search of linked papers, forty-eight relevant publications were identified on sugars (total sugars, non-milk extrinsic sugars, or added sugars) or sugar-containing drinks. These included five reports from expert committees, six reviews, thirty-three observational studies and four small-scale interventions. There was inconsistency between studies as to the relationship between sugars intake (however expressed) and micronutrients. The statistical patterns varied between nutrients and population groups. Curvilinear associations were found in some analyses, with lower nutrient intakes at both extremes of sugar intake; however, factors such as dieting and under-reporting may confound the associations observed. Some studies found statistically significant inverse associations but these were weak, with sugars explaining less than 5 % of the variance. Mean intakes of most micronutrients were above the RDA or reference nutrient intake except among very high consumers of sugars. The available evidence does not allow for firm conclusions on an optimal level of added sugars intake for micronutrient adequacy and the trends that exist may have little biological significance except for a few nutrients (for example, Fe). It is established that energy intake is the prime predictor of micronutrient adequacy. A better understanding of valid approaches to energy adjustment, misreporting and the assessment of micronutrient adequacy is crucial to further progress in this area.

We critically review potential involvement of trimethylamine N-oxide (TMAO) as a link between diet, the gut microbiota and CVD. Generated primarily from dietary choline and carnitine by gut bacteria and hepatic flavin-containing mono-oxygenase (FMO) activity, TMAO could promote cardiometabolic disease when chronically elevated. However, control of circulating TMAO is poorly understood, and diet, age, body mass, sex hormones, renal clearance, FMO3 expression and genetic background may explain as little as 25 % of TMAO variance. The basis of elevations with obesity, diabetes, atherosclerosis or CHD is similarly ill-defined, although gut microbiota profiles/remodelling appear critical. Elevated TMAO could promote CVD via inflammation, oxidative stress, scavenger receptor up-regulation, reverse cholesterol transport (RCT) inhibition, and cardiovascular dysfunction. However, concentrations influencing inflammation, scavenger receptors and RCT (≥100 µm) are only achieved in advanced heart failure or chronic kidney disease (CKD), and greatly exceed pathogenicity of <1–5 µm levels implied in some TMAO–CVD associations. There is also evidence that CVD risk is insensitive to TMAO variance beyond these levels in omnivores and vegetarians, and that major TMAO sources are cardioprotective. Assessing available evidence suggests that modest elevations in TMAO (≤10 µm) are a non-pathogenic consequence of diverse risk factors (ageing, obesity, dyslipidaemia, insulin resistance/diabetes, renal dysfunction), indirectly reflecting CVD risk without participating mechanistically. Nonetheless, TMAO may surpass a pathogenic threshold as a consequence of CVD/CKD, secondarily promoting disease progression. TMAO might thus reflect early CVD risk while providing a prognostic biomarker or secondary target in established disease, although mechanistic contributions to CVD await confirmation.

The demand for organic foods is constantly increasing mainly due to consumers' perception that they are healthier and safer than conventional foods. There is a need for information related to food safety to inform consumers of the health benefits and/or hazards of food products of both origins, in order to optimise the impact on health and minimise the risks. Several gaps and limitations in scientific knowledge with regard to food risk evaluation make it difficult to draw generalised conclusions. Still, some organic foods can be expected to contain fewer agrochemical residues and lower levels of nitrate than conventionally grown alternatives. On the other hand, environmental contaminants are equally present in foods of both origins. With regard to other food hazards, such as natural chemicals, microbial pathogens and mycotoxins, no clear conclusions can be drawn, although several interesting points can be highlighted. It is difficult, therefore, to weigh the risks, but what should be made clear to consumers is that ‘organic’ does not equal ‘safe’. If producers adopt proper agricultural practices and consumers maintain hygienic conditions, risks associated with food contaminants can be minimised, regardless of the food's organic or conventional origin.

The aim of the present review is to synthesise and summarise our recent knowledge on the involvement of cholecystokinin (CCK) and gastrin peptides and their receptors in the control of digestive functions and more generally their role in the field of nutrition in mammals. First, we examined the release of these peptides from the gut, focusing on their molecular forms, the factors regulating their release and the signalling pathways mediating their effects. Second, general physiological effects of CCK and gastrin peptides are described with regard to their specific receptors and the role of CCK on vagal mucosal afferent nerve activities. Local effects of CCK and gastrin in the gut are also reported, including gut development, gastrointestinal motility and control of pancreatic functions through vagal afferent pathways, including NO. Third, some examples of the intervention of the CCK and gastrin peptides are exposed in diseases, taking into account intervention of the classical receptor subtypes (CCK1 and CCK2 receptors) and their heterodimerisation as well as CCK-C receptor subtype. Finally, applications and future challenges are suggested in the nutritional field (performances) and in therapy with regards to the molecular forms or in relation with the type of receptor as well as new techniques to be utilised in detection or in therapy of disease. In conclusion, the present review underlines recent developments in this field: CCK and gastrin peptides and their receptors are the key factor of nutritional aspects; a better understanding of the mechanisms involved may increase the efficiency of the nutritional functions and the treatment of abnormalities under pathological conditions.

Early-life nutrition plays a critical role in fetal growth and development. Food intake absence and excess are the two main types of energy malnutrition that predispose to the appearance of diseases in adulthood, according to the hypothesis of ‘developmental origins of health and disease’. Epidemiological data have shown an association between early-life malnutrition and the metabolic syndrome in later life. Evidence has also demonstrated that nutrition during this period of life can affect the development of the immune system through epigenetic mechanisms. Thus, epigenetics has an essential role in the complex interplay between environmental factors and genetics. Altogether, this leads to the inflammatory response that is commonly seen in non-alcoholic fatty liver disease (NAFLD), the hepatic manifestation of the metabolic syndrome. In conjunction, DNA methylation, covalent modification of histones and the expression of non-coding RNA are the epigenetic phenomena that affect inflammatory processes in the context of NAFLD. Here, we highlight current understanding of the mechanisms underlying developmental programming of NAFLD linked to epigenetic modulation of the immune system and environmental factors, such as malnutrition.

Osteoporosis and related fractures are a major global health issue, but there are few preventative strategies. Previously reported associations between higher intakes of fruits and vegetables and skeletal health have been suggested to be partly attributable to vitamin C. To date, there is some evidence for a potential role of vitamin C in osteoporosis and fracture prevention but an overall consensus of published studies has not yet been drawn. The present review aims to provide a summary of the proposed underlying mechanisms of vitamin C on bone and reviews the current evidence in the literature, examining a potential link between vitamin C intake and status with osteoporosis and fractures. The Bradford Hill criteria were used to assess reported associations. Recent animal studies have provided insights into the involvement of vitamin C in osteoclastogenesis and osteoblastogenesis, and its role as a mediator of bone matrix deposition, affecting both the quantity and quality of bone collagen. Observational studies have provided some evidence for this in the general population, showing positive associations between dietary vitamin C intake and supplements and higher bone mineral density or reduced fracture risk. However, previous intervention studies were not sufficiently well designed to evaluate these associations. Epidemiological data are particularly limited for vitamin C status and for fracture risk and good-quality randomised controlled trials are needed to confirm previous epidemiological findings. The present review also highlights that associations between vitamin C and bone health may be non-linear and further research is needed to ascertain optimal intakes for osteoporosis and fracture prevention.

Abdominal obesity is a risk factor for cardiometabolic disease, and has become a major public health problem in the world. Waist circumference is generally used as a simple surrogate marker to define abdominal obesity for population screening. An increasing number of publications solely rely on the method that maximises sensitivity and specificity to define ‘optimal’ cut-off values. It is well documented that the optimal cut-off values of waist circumference vary across different ethnicities. However, it is not clear if the variation in cut-off values is a true biological phenomenon or an artifact of the method for identifying optimal cut-off points. The objective of the present review was to assess the relationship between optimal cut-offs and population waist circumference levels. Among sixty-one research papers, optimal cut-off values ranged from 65·5 to 101·2 cm for women and 72·5 to 103·0 cm for men. Reported optimal cut-off values were highly correlated with population means (correlation coefficient: 0·91 for men and 0·93 for women). Such a strong association was independent of waist circumference measurement techniques or the health outcomes (dyslipidaemia, hypertension or hyperglycaemia), and existed in some homogeneous populations such as the Chinese and Japanese. Our findings raised some concerns about applying the sensitivity and specificity approach to determine cut-off values. Further research is needed to understand whether the differences among populations in waist circumference were genetically or environmentally determined, and to understand whether using region-specific cut-off points can identify individuals with the same absolute risk levels of metabolic and cardiovascular outcomes among different populations.

Advances in knowledge of ruminant nutrition and metabolism during the second half of the twentieth century have been reviewed. Part I is concerned with metabolism in the rumen: Part II discusses utilization of nutrients absorbed from the rumen and lower tract to support growth and reproduction. The time frame was prompted by the crucial advances in ruminant physiology which arose from the work of Sir Jospeh Barcroft and his colleagues at Cambridge in the 1940s and 50s, and by the brilliant studies of Robert Hungate on rumen microbiology at much the same time.

In reviewing the growth of knowledge of the role of bacteria, protozoa, fungi and bacteriophages in the rumen, outstanding developments have included the identification and characterization of fungi and the recognition that the utilization of polysaccharides in the rumen is accomplished by the sequential activities of consortia of rumen microorganisms. The role of protozoa is discussed in relation to the long standing debate on whether or not the removal of protozoa (defaunation) improves the efficiency of ruminant production. In relation to nitrogen (N) metabolism, the predation of bacteria by protozoa increases protein turnover in the rumen and reduces the efficiency of microbial protein production. This may account for the beneficial effects of defaunation where dietary N intakes are low and possibly rate limiting for growth and production.

Current approaches to the measurement of rates of production of short chain fatty acids (SCFA) in the rumen based on the mathematical modelling of isotope dilution data are outlined. The absorption of SCFA from the rumen and hindgut is primarily a passive permeation process.

The role of microorganisms in N metabolism in the rumen has been discussed in relation to ammonia and urea interrelationships and to current inadequacies in the measurement of both protein degradation in the rumen and microbial protein synthesis. The growth of knowledge of digestion and absorption of dietary lipids has been reviewed with emphasis on the antimicrobial activity of lipids and the biohydrogenation of unsaturated fatty acids. The protection of unsaturated dietary fats from ruminal biohydrogenation is an approach to the manipulation of the fatty acid composition of meat and dairy products.

Discussion of the production of toxins in the rumen and the role of microorganisms in detoxification has focused on the metabolism of oxalate, nitrate, mycotoxins, saponins and the amino acid mimosine. Mimosine occurs in the tropical shrub leucaena, which is toxic to cattle in Australia but not in Hawaii. Tolerance to leucaena stems from the presence of a bacterium found in the rumen of Hawaiian cattle, which when transferred to Australian cattle survives and confers protection from mimosine. The genetic modification of rumen microorganisms to improve their capacity to ultilize nutrients or to detoxify antinutritive factors is an attractive strategy which has been pursued with outstanding success in the case of fluoroacetate. A common rumen bacterium has been genetically modified to express the enzyme fluoroacetate dehalogenase. The modified organism has been shown to survive in the rumen at metabolically significant levels and to confer substantial protection from fluoroacetate poisoning.

Food and nutrition studies in animals and human beings often meet with technical difficulties and sometimes with ethical questions. An alternative to research in living animals is the dynamic multicompartmental in vitro model for the gastrointestinal tract described by Minekus et al. (1995) and Havenaar & Minekus (1996). The dynamic conditions that are simulated in this model are peristaltic movements, transit times, pH responses, secretion of enzymes and electrolytes and absorption of nutrients and water. To obtain data for an in vitro model of the dog gastrointestinal tract, the literature was surveyed for physiological responses to different types of dog food. These included: values of enzyme activities, electrolyte concentrations, gastric emptying and intestinal transit times, pH values, secretion and composition of bile and absorption rates in different parts of the dog gastrointestinal tract. The review focuses on research carried out on healthy, adult dogs of 10–20 kg and on parameters related to the oral cavity, stomach and small intestine. This literature research gives sufficient data on the physiology of the canine digestive tract for the development of an in vitro dynamic model that adequately simulates the functions of the stomach and small intestine of the dog.

The spectrum of gluten-related disorders includes coeliac disease (CD), wheat allergy (WA) and the suggested entity of non-coeliac gluten sensitivity (NCGS). An increasing number of the world’s population are avoiding gluten due to the assumption of health benefits and self-diagnosed gastrointestinal and/or extra-intestinal symptoms. Unlike CD and WA, NCGS is a relatively new entity with an unknown prevalence and mechanisms, complicated by recent literature suggesting that gluten is not the only food component that may trigger symptoms experienced by this group of patients. The term ‘non-coeliac wheat sensitivity’ has been proposed as a more accurate term, allowing inclusion of other non-gluten wheat components such as fructans and amylase–trypsin inhibitors. There is inconsistent evidence when evaluating the effects of a gluten challenge in patients with suspected NCGS and there is a need for a standardised procedure to confirm the diagnosis, ultimately enabling the optimisation of clinical care. The present review will give an overview of the different gluten-related disorders and discuss the most recent scientific evidence investigating NCGS.