Reducing elevated LDL-cholesterol is a key public health challenge. There is substantial evidence from randomised controlled trials (RCT) that a number of foods and food components can significantly reduce LDL-cholesterol. Data from RCT have been reviewed to determine whether effects are additive when two or more of these components are consumed together. Typically components, such as plant stanols and sterols, soya protein, β-glucans and tree nuts, when consumed individually at their target rate, reduce LDL-cholesterol by 3–9 %. Improved dietary fat quality, achieved by replacing SFA with unsaturated fat, reduces LDL-cholesterol and can increase HDL-cholesterol, further improving blood lipid profile. It appears that the effect of combining these interventions is largely additive; however, compliance with multiple changes may reduce over time. Food combinations used in ten ‘portfolio diet’ studies have been reviewed. In clinical efficacy studies of about 1 month where all foods were provided, LDL-cholesterol is reduced by 22–30 %, whereas in community-based studies of >6 months' duration, where dietary advice is the basis of the intervention, reduction in LDL-cholesterol is about 15 %. Inclusion of MUFA into ‘portfolio diets’ increases HDL-cholesterol, in addition to LDL-cholesterol effects. Compliance with some of these dietary changes can be achieved more easily compared with others. By careful food component selection, appropriate to the individual, the effect of including only two components in the diet with good compliance could be a sustainable 10 % reduction in LDL-cholesterol; this is sufficient to make a substantial impact on cholesterol management and reduce the need for pharmaceutical intervention.

Insulin resistance underlies type 2 diabetes, CVD and the metabolic syndrome, driven by changes in diet, lifestyle, energy over–consumption and obesity. Nutritional recommendations for insulin resistance remain an area of controversy, particularly the quantity and types of dietary carbohydrate. The present review gives an overview of insulin resistance, its relationship to impaired insulin secretion and the metabolic syndrome, research methodologies used to measure insulin action and the epidemiological and intervention studies on the relationship between dietary carbohydrate and insulin resistance. Epidemiological studies provide little evidence to suggest that total dietary carbohydrate predicts risk of type 2 diabetes, and high–carbohydrate, high–fibre diets with low–glycaemic index (GI) may even contribute to diabetes prevention. Despite inherent limitations associated with techniques used to measure insulin resistance and dietary assessment, most intervention studies reveal an increase in glucose tolerance or insulin sensitivity with high–carbohydrate, low–fat diets in non–diabetic and diabetic individuals. When energy is restricted the source or reduced content of carbohydrate does not appear to be as important as fat for body weight. Thus, low energy intake is key to weight loss and augmentation of insulin sensitivity. Given this, widespread adoption of popular low–carbohydrate high–fat diets highlights the necessity to evaluate dietary interventions regarding safety and metabolic effects. While current evidence supports FAO/WHO recommendations to maintain a high–carbohydrate diet with low–GI foods, the relationships between carbohydrate and insulin sensitivity remains an important research area. Emerging technologies should further enhance understanding of gene–diet interactions in insulin resistance, providing useful information for future nutrition policy decisions.

Considerable debate exists regarding the potential antineoplastic effect of dietary long-chain n-3 PUFA contained in fatty fishes. Since the majority of published data has proven that their intake does not induce toxic or carcinogenic effects in humans, their possible preventive use against cancer has been suggested. On the other hand, it is unlikely that they could be effective in cancer patients as a single therapy. Nevertheless, a considerable effort has been put forth in recent years to evaluate the hypothesis that n-3 PUFA might improve the antineoplastic efficiency of currently used anticancer agents. The rationale for this therapeutic combinatory strategy is trying to increase cancer sensitivity to conventional therapies. This could allow the use of lower drug/radiation doses and, thereby, a reduction in the detrimental health effects associated with these treatments. We will here critically examine the studies that have investigated this possibility, by focusing particularly on the biological and molecular mechanisms underlying the antineoplastic effect of these combined treatments. A possible use of n-3 PUFA in combination with the innovative single-targeted anti-cancer therapies, that often are not completely devoid of dangerous side-effects, is also suggested.

Events such as BSE, foot and mouth disease and avian influenza illustrate the importance of animal health on a global basis. The only practical solution to deal with such problems has usually been mass culling of millions of animals at great effort and expense. Serious consideration needs to be given to nutrition as a practical solution for health maintenance and disease avoidance of animals raised for food. Health or disease derives from a triad of interacting factors; diet–disease agent, diet–host and disease agent–host. Various nutrients and other bioactive feed ingredients, nutricines, directly influence health by inhibiting growth of pathogens or by modulating pathogen virulence. It is possible to transform plant-based feed ingredients to produce vaccines against important diseases and these could be fed directly to animals. Nutrients and nutricines contribute to three major factors important in the diet–host interaction; maintenance of gastrointestinal integrity, support of the immune system and the modulation of oxidative stress. Nutrition-based health is the next challenge in modern animal production and will be important to maintain economic viability and also to satisfy consumer demands in terms of food quality, safety and price. This must be accomplished largely through nutritional strategies making optimum use of both nutrients and nutricines.

Accelerator mass spectrometry (AMS) is an ultrasensitive analytical technique for measuring rare nuclides such as 14C, 26Al and 41Ca. The low detection limit and wide dynamic range of AMS allow long-term and highly sensitive tracer studies in nutrition that cannot be performed with other methods. The present paper is intended to provide a description of AMS to the interested nutritionist and present proven applications. AMS is compared to liquid scintillation counting and stable isotope MS. A description of common AMS methodology is presented that consists of determining the dose, preparing the sample, diluting the sample (if necessary), and measuring the sample. Applications include Ca metabolism, Al uptake from the environment, dietary intake of carcinogens, fat meta-bolism and folate metabolism. Throughout this discussion the experimental advantages (small doses that pose no health risk, extremely long experimental lifetime, small sample sizes and high sensitivity) made possible by the unique analytical capabilities of AMS are emphasized. The future of AMS is discussed. As the number of AMS centres, instruments, and studies increases, the number of nutritional applications that employ AMS will continue to grow. The coupling of AMS with other analytical techniques (e.g. high performance liquid chromatography) will be developed as access to AMS improves.

CVD is the leading cause of death worldwide, a consequence of mostly poor lifestyle and dietary behaviours. Although whole fruit and vegetable consumption has been consistently shown to reduce CVD risk, the exact protective constituents of these foods are yet to be clearly identified. A recent and biologically plausible hypothesis supporting the cardioprotective effects of vegetables has been linked to their inorganic nitrate content. Approximately 60–80 % inorganic nitrate exposure in the human diet is contributed by vegetable consumption. Although inorganic nitrate is a relatively stable molecule, under specific conditions it can be metabolised in the body to produce NO via the newly discovered nitrate–nitrite–NO pathway. NO is a major signalling molecule in the human body, and has a key role in maintaining vascular tone, smooth muscle cell proliferation, platelet activity and inflammation. Currently, there is accumulating evidence demonstrating that inorganic nitrate can lead to lower blood pressure and improved vascular compliance in humans. The aim of this review is to present an informative, balanced and critical review of the current evidence investigating the role of inorganic nitrate and nitrite in the development, prevention and/or treatment of CVD. Although there is evidence supporting short-term inorganic nitrate intakes for reduced blood pressure, there is a severe lack of research examining the role of long-term nitrate intakes in the treatment and/or prevention of hard CVD outcomes, such as myocardial infarction and cardiovascular mortality. Epidemiological evidence is needed in this field to justify continued research efforts.

The prevalence of calcium oxalate (CaOx) uroliths detected in cats with lower urinary tract disease has shown a sharp increase over the last decades with a concomitant reciprocal decrease in the occurrence of struvite (magnesium ammonium phosphate) uroliths. CaOx stone-preventative diets are available nowadays, but seem to be marginally effective, as CaOx urolith recurrence occurs in patients fed these diets. In order to improve the preventative measures against CaOx urolithiasis, it is important to understand its aetiopathogenesis. The main research focus in CaOx formation in cats has been on the role of Ca, whereas little research effort has been directed towards the role and origin of urinary oxalates. As in man, the exogenous origin of urinary oxalates in cats is thought to be of minor importance, although the precise contribution of dietary oxalates remains unclear. The generally accepted dietary risk factors for CaOx urolithiasis in cats are discussed and a model for the biosynthetic pathways of oxalate in feline liver is provided. Alanine:glyoxylate aminotransferase 1 (AGT1) in endogenous oxalate metabolism is a liver-specific enzyme targeted in the mitochondria in cats, and allows for efficient conversion of glyoxylate to glycine when fed a carnivorous diet. The low peroxisomal activity of AGT1 in cat liver is compatible with the view that felids utilised a low-carbohydrate diet throughout evolution. Future research should focus on understanding de novo biosynthesis of oxalate in cats and their adaptation(s) in oxalate metabolism, and on dietary oxalate intake and absorption by cats.

Most dairy cows exhibit different degrees of hypocalcaemia around calving because the gestational Ca requirements shift to the disproportionately high Ca requirements of lactation. Ca homeostasis is a robust system that effectively adapts to changes in Ca demand or supply. However, these adaptations often are not rapid enough to avoid hypocalcaemia. A delay in the reconfiguration of intestinal Ca absorption and bone resorption is probably the underlying cause of this transient hypocalcaemia. Several dietary factors that affect different aspects of Ca metabolism are known to reduce the incidence of milk fever. The present review describes the interactions between nutrition and Ca homeostasis using observations from cattle and extrapolations from other species and aims to quantitatively model the effects of the nutritional approaches that are used to induce dry cows into an early adaptation of Ca metabolism. The present model suggests that reducing dietary cation–anion difference (DCAD) increases Ca clearance from the blood by dietary induction of systemic acidosis, which results in hypercalciuria due to the loss of function of the renal Ca transient receptor potential vanilloid channel TRPV5. Alternatively, reducing the gastrointestinal availability of Ca by reducing dietary Ca or its nutritional availability will also induce the activation of Ca metabolism to compensate for basal blood Ca clearance. Our model of gastrointestinal Ca availability as well as blood Ca clearance in the transition dairy cow allowed us to conclude that the most common dietary strategies for milk fever prevention may have analogous modes of action that are based on the principle of metabolic adaptation before calving.

A major challenge in taste research is to overcome the flavour imperfections in food products and to build nutritious strategies to combat against obesity as well as other related metabolic syndromes. The field of molecular taste research and chemical senses has contributed to an enormous development in understanding the taste receptors and mechanisms of taste perception. Accordingly, the development of taste-modifying compounds or taste modulators that alter the perception of basic taste modalities has gained significant prominence in the recent past. The beneficial aspects of these substances are overwhelming while considering their potential taste-modifying properties. The objective of the present review is to provide an impression about the taste-modulating compounds and their distinctive taste-modifying properties with reference to their targets and proposed mechanisms of action. The present review also makes an effort to discuss the basic mechanism involved in oro-gustatory taste perception as well as on the effector molecules involved in signal transduction downstream to the activation of taste receptors.

Obesity in the UK was assumed to have developed against a population decline in physical activity, with health messages focused on diet and exercise prevention strategies. Doubly-labelled water (DLW) studies of energy expenditure have indicated the alternative scenario that the increased obesity prevalence reflects excessive food energy intake with physical activity levels unchanged. This analysis is questionable, deriving in part from a weakness of the DLW methodology in identifying changing physical activity levels within populations of increasing body weight. This has resulted in an underestimation of the reduction in physical activity in the overweight and obese, as revealed by direct studies of such behaviour. Furthermore, a close examination of food energy supply, household food purchases and individual food energy consumption since 1955, in relation to likely estimates of current intakes indicated by simple modelling of predicted energy expenditure, identifies: (a) food energy supply as markedly overestimating energy intakes; (b) individual food energy consumption as markedly underestimating energy intakes; and (c) household food purchase data as the closest match to predicted current food energy intakes. Energy intakes indicated by this latter method have fallen by between 20 to 30 %, suggesting comparable falls in physical activity. Although unequivocal evidence for a matching UK trend in falling physical activity is limited, as is evidence that obesity follows reductions in physical activity, such a link has been recently suggested in a large prospective study in adolescents. Thus, for the UK, obesity has developed within a ‘move less–eat somewhat less but still too much’ scenario. A focus on both diet and exercise should remain the appropriate public health policy.

Psychosocial stress, uncontrolled eating and obesity are three interrelated epidemiological phenomena already present during youth. This broad narrative conceptual review summarises main biological underpinnings of the stress–diet–obesity pathway and how new techniques can further knowledge. Cortisol seems the main biological factor from stress towards central adiposity; and diet, physical activity and sleep are the main behavioural pathways. Within stress–diet, the concepts of comfort food and emotional eating are highlighted, as cortisol affects reward pathways and appetite brain centres with a role for insulin, leptin, neuropeptide Y (NPY), endocannabinoids, orexin and gastrointestinal hormones. More recently researched biological underpinnings are microbiota, epigenetic modifications and metabolites. First, the gut microbiota reaches the stress-regulating and appetite-regulating brain centres via the gut–brain axis. Second, epigenetic analyses are recommended as diet, obesity, stress and gut microbiota can change gene expression which then affects appetite, energy homeostasis and stress reactivity. Finally, metabolomics would be a good technique to disentangle stress–diet–obesity interactions as multiple biological pathways are involved. Saliva might be an ideal biological matrix as it allows metagenomic (oral microbiota), epigenomic and metabolomic analyses. In conclusion, stress and diet/obesity research should be combined in interdisciplinary collaborations with implementation of several -omics analyses.

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 increasing prevalence of non-alcoholic fatty liver disease (NAFLD) poses a growing challenge in terms of its prevention and treatment. The ‘multiple hits’ hypothesis of multiple insults, such as dietary fat intake, de novo lipogenesis, insulin resistance, oxidative stress, mitochondrial dysfunction, gut dysbiosis and hepatic inflammation, can provide a more accurate explanation of the pathogenesis of NAFLD. Betaine plays important roles in regulating the genes associated with NAFLD through anti-inflammatory effects, increased free fatty oxidation, anti-lipogenic effects and improved insulin resistance and mitochondrial function; however, the mechanism of betaine remains elusive.

Currently, there is considerable emphasis on the relationship between dietary sugar consumption and various health outcomes, with some countries and regions implementing national sugar reduction campaigns. This has resulted in significant efforts to quantify dietary sugar intakes, to agree on terms to describe dietary sugars and to establish associated recommendations. However, this information is infrequently collated on a global basis and in a regularised manner. The present review provides context regarding sugar definitions and recommendations. It provides a global review of the available data regarding dietary sugar intake, considering forms such as total, free and added sugars. A comprehensive breakdown of intakes is provided by age group, country and sugar form. This analysis shows that free sugar intakes as a percentage of total energy (%E) are the highest for children and adolescents (12–14%E) and the lowest for older adults (8%E). This trend across lifecycle stages has also been observed for added sugars. The available data also suggest that, while some reductions in sugar intake are observed in a few individual studies, overall intakes of free/added sugars remain above recommendations. However, any wider conclusions are hampered by a lack of detailed high-quality data on sugar intake, especially in developing countries. Furthermore, there is a need for harmonisation of terms describing sugars (ideally driven by public health objectives) and for collaborative efforts to ensure that the most up-to-date food composition data are used to underpin recommendations and any estimates of intake or modelling scenarios.

As obesity and metabolic diseases rise, there is need to investigate physiological and behavioural aspects associated with their development. Circadian rhythms have a profound influence on metabolic processes, as they prepare the body to optimise energy use and storage. Moreover, food-related signals confer temporal order to organs involved in metabolic regulation. Therefore food intake should be synchronised with the suprachiasmatic nucleus (SCN) to elaborate efficient responses to environmental challenges. Human studies suggest that a loss of synchrony between mealtime and the SCN promotes obesity and metabolic disturbances. Animal research using different paradigms has been performed to characterise the effects of timing of food intake on metabolic profiles. Therefore the purpose of the present review is to critically examine the evidence of animal studies, to provide a state of the art on metabolic findings and to assess whether the paradigms used in rodent models give the evidence to support a ‘best time’ for food intake. First we analyse and compare the current findings of studies where mealtime has been shifted out of phase from the light–dark cycle. Then, we analyse studies restricting meal times to different moments within the active period. So far animal studies correlate well with human studies, demonstrating that restricting food intake to the active phase limits metabolic disturbances produced by high-energy diets and that eating during the inactive/sleep phase leads to a worse metabolic outcome. Based on the latter we discuss the missing elements and possible mechanisms leading to the metabolic consequences, as these are still lacking.

Tremendous progress has been made in the field of ferroptosis since this regulated cell death process was first named in 2012. Ferroptosis is initiated upon redox imbalance and driven by excessive phospholipid peroxidation. Levels of multiple intracellular nutrients (iron, selenium, vitamin E and coenzyme Q10) are intimately related to the cellular antioxidant system and participate in the regulation of ferroptosis. Dietary intake of monounsaturated fatty acids (MUFA) and polyunsaturated fatty acids (PUFA) regulates ferroptosis by directly modifying the fatty acid composition in cell membranes. In addition, amino acids and glucose (energy stress) manipulate the ferroptosis pathway through the nutrient-sensitive kinases mechanistic target of rapamycin complex 1 (mTORC1) and AMP-activated protein kinase (AMPK). Understanding the molecular interaction between nutrient signals and ferroptosis sensors might help in the identification of the roles of ferroptosis in normal physiology and in the development of novel pharmacological targets for the treatment of ferroptosis-related diseases.

Ruminants are recognised to suffer from Cu-responsive disorders. Present understanding of Cu transport and metabolism is limited and inconsistent across vets and veterinary professionals. There has been much progress from the studies of the 1980s and early 1990s in cellular Cu transport and liver metabolism which has not been translated into agricultural practice. Cu metabolism operates in regulated pathways of Cu trafficking rather than in pools of Cu lability. Cu in the cell is chaperoned to enzyme production, retention within metallothionein or excretion via the Golgi into the blood. The hepatocyte differs in that Cu-containing caeruloplasmin can be synthesised to provide systemic Cu supply and excess Cu is excreted via bile. The aim of the present review is to improve understanding and highlight the relevant progress in relation to ruminants through the translation of newer findings from medicine and non-ruminant animal models into ruminants.

Three areas in the brain continuously generate new neurons throughout life: the subventricular zone lining the lateral ventricles, the dentate gyrus in the hippocampus and the median eminence in the hypothalamus. These areas harbour neural stem cells, which contribute to neural repair by generating daughter cells that then become functional neurons or glia. Impaired neurogenesis leads to detrimental consequences, such as depression, decline of cognitive abilities and obesity. Adult neurogenesis is a versatile process that can be modulated either positively or negatively by many effectors, external or endogenous. Diet can modify neurogenesis both ways, either directly by ways of food-borne molecules, or possibly by the modifications induced on gut microbiota composition. It is therefore critical to define dietary strategies optimal for the maintenance of the stem cell pools.