Currently, the prevention and treatment of CVD have been a global focus since CVD is the number one cause of mortality and morbidity. In the pathogenesis of CVD, it was generally thought that impaired cholesterol homeostasis might be a risk factor. Cholesterol homeostasis is affected by exogenous factors (i.e. diet) and endogenous factors (i.e. certain receptors, enzymes and transcription factors). In this context, the number of studies investigating the potential mechanisms of dietary fatty acids on cholesterol homeostasis have increased in recent years. As well, the cluster of differentiation 36 (CD36) receptor is a multifunctional membrane receptor involved in fatty acid uptake, lipid metabolism, atherothrombosis and inflammation. CD36 is proposed to be a crucial molecule for cholesterol homeostasis in various mechanisms including absorption/reabsorption, synthesis, and transport of cholesterol and bile acids. Moreover, it has been reported that the amount of fatty acids and fatty acid pattern of the diet influence the CD36 level and CD36-mediated cholesterol metabolism principally in the liver, intestine and macrophages. In these processes, CD36-mediated cholesterol and lipoprotein homeostasis might be impaired by dietary SFA and trans-fatty acids, whereas ameliorated by MUFA in the diet. The effects of PUFA on CD36-mediated cholesterol homeostasis are controversial depending on the amount of n-3 PUFA and n-6 PUFA, and the n-3:n-6 PUFA ratio. Thus, since the CD36 receptor is suggested to be a novel nutrient-sensitive biomarker, the role of CD36 and dietary fatty acids in cholesterol metabolism might be considered in medical nutrition therapy in the near future. Therefore, the novel nutritional target of CD36 and interventions that focus on dietary fatty acids and potential mechanisms underlying cholesterol homeostasis are discussed in this review.

Following identification of essential micronutrients, there has been a continuum of research aimed at revealing their absorption, transport, utilization as cofactors, and excretion and secretion. Among those cases that have received our attention are vitamin B6, riboflavin, biotin, lipoate, ascorbate, and certain metal ions. Circulatory transport and cellular uptake of the water-soluble vitamins exhibit relative specificity and facilitated mechanisms at physiological concentrations. Isolation of enzymes and metabolites from micro–organisms and mammals has provided information on pathways involved in cofactor formation and metabolism. Kinases catalysing phosphorylation of B6 and riboflavin have a preference for Zn2+ in stereospecific chelates with adenosine triphosphate. The synthetase for flavin adenine dinucleotide prefers Mg2+. The flavin mononucleotide-dependent oxidase that converts the 5′–phosphates of pyridoxine and of pyridoxamine to pyridoxal phosphate is a connection between B6 and riboflavin and is a primary control point for conversion of B6 to its coenzyme. Sequencing and cloning of a side–chain oxidase for riboflavin was achieved. Details on binding and function have been delineated for some cofactor systems, especially in several flavoproteins. There is both photochemical oxidation and oxidative catabolism of B6 and riboflavin. Both biotin and lipoate undergo oxidation of their acid side chains with redox cleavage of the rings. Applications from our findings include the development of affinity absorbents, enhanced drug delivery, delineation of residues in biopolymer modification, pathogen photoinactivation in blood components, and input into human dietary recommendations. Ongoing and future research in the cofactor arena can be expected to add to this panoply. At the molecular level, the way in which the same cofactor can participate in diverse catalytic reactions resides in interactions with surrounding enzyme structures that must be determined case by case. At the level of human intake, more knowledge is desirable for making micronutrient recommendations based on biochemical indicators, especially for the span between infancy and adulthood.

The micro-organisms which inhabit the human gut (i.e. the intestinal microbiota) influence numerous human biochemical pathways and physiological functions. The present review focuses on two questions, ‘Are intestinal microbiota effects measurable and meaningful?’ and ‘What research methods and variables are influenced by intestinal microbiota effects?’. These questions are considered with respect to doubly labelled water measurements of energy expenditure, heat balance calculations and models, measurements of RMR via indirect calorimetry, and diet-induced energy expenditure. Several lines of evidence suggest that the intestinal microbiota introduces measurement variability and measurement errors which have been overlooked in research studies involving nutrition, bioenergetics, physiology and temperature regulation. Therefore, we recommend that present conceptual models and research techniques be updated via future experiments, to account for the metabolic processes and regulatory influences of the intestinal microbiota.

Following the high-profile studies on hormone replacement therapy which provided little evidence in support of the drug therapy improving future health, there remains a growing demand for dietary solutions for maintaining health and preventing disease as women age. Although interest in the relative importance of phyto-oestrogens to human health has increased dramatically over the last decade, the effective dose for health benefits and hypothetical issues on safety remain to be resolved. Plausible mechanisms and epidemiological data are available to support the concept that phyto-oestrogen-rich diets exert physiological effects, but optimal doses and sources of these compounds have still not been elucidated for specific health benefits. In addition, much of the current mechanistic data are difficult to interpret as the experiments have incorporated levels of phyto-oestrogens that may not be achievable in vivo and have to date only used aglycones and glycosides of the pure compounds rather than examining the biological effects of gut and liver metabolites. The present review will concentrate on the isoflavone subclass of phyto-oestrogens, as, to date, these compounds have received most attention from both a commercial and research perspective.

Despite continued efforts to prevent and control food-borne illness it remains a major cause of morbidity and mortality throughout the world. The problem is made worse by the continuous threat from emerging pathogens that can evolve to adapt to the different environments resulting from ongoing changes in farming or food production. The present review discusses the impact of genomics and post-genomic technologies on research in the area of food-borne bacterial pathogens. Genomics research is moving at a fast pace and these are exciting times for microbial research. The genome sequences of approximately ninety bacterial genomes have recently been completed and genome sequences are already available for several food-borne pathogens and closely related species. Comparative genomics is providing new insights into mechanisms of bacterial evolution and has helped in determining virulence factors of pathogens. Genomics has also provided tools such as DNA microarrays that can be used to examine the genetic composition and whole genome expression profiles of bacterial strains by hybridisation of fluorescently labelled DNA. This is helping to identify genes associated with particular phenotypes such as virulence and host preference, and to identify genes in uncharacterised genomes of closely related organisms. Microarrays are also being developed for the detection of food-borne pathogens and investigation of the evolutionary relationship between different species of bacteria. The review concludes with a discussion of the use of functional genomics tools to investigate bacterial responses to environmental stresses and also host–pathogen interactions. These research areas will be valuable in designing future strategies for controlling food-borne pathogens.

Individuals have varying needs for minerals that are dependent, amongst other things, on their lifestyle, age and genetic makeup. Knowledge of exact individual nutritional requirements should lead to better health, increased quality of life and reduced need for expensive medical care. Bioavailability, nutrient–gene interactions and whole–body metabolism all need to be investigated further if we are to progress towards the goal of defining optimal health and nutritional status. The discussion which follows will critically review the latest developments in the area of metabolism for several of the minerals that are essential for human health: Ca, Zn, Cu and Se. Stable–isotope tracers and mathematical modelling are some of the tools being used to facilitate the greater understanding in uptake, utilisation and excretion of these minerals. Stable isotopes, administered in physiological doses, present little or no risk to volunteers and allow metabolic studies to be carried out in vulnerable population groups such as children and pregnant women. Intrinsic labelling of foodstuffs ensures that the tracer and the native mineral will behave similarly once inside the body. Advances in computing power and software dedicated to solving nutritional problems have made it possible for investigators to use mathematical modelling in their experimental work. Mineral metabolism is ideally suited to a form of modelling known as compartmental analysis, which allows rates of mineral transferand sizes of mineral stores to be calculated accurately without the need for invasive sampling of body tissues

The pyridine nucleotide NAD+ is derived from dietary niacin and serves as the substrate for the synthesis of cyclic ADP-ribose (cADPR), an intracellular Ca signalling molecule that plays an important role in synaptic plasticity in the hippocampus, a region of the brain involved in spatial learning. cADPR is formed in part via the activity of the ADP-ribosyl cyclase enzyme CD38, which is widespread throughout the brain. In the present review, current evidence of the relationship between dietary niacin and behaviour is presented following investigations of the effect of niacin deficiency, pharmacological nicotinamide supplementation and CD38 gene deletion on brain nucleotides and spatial learning ability in mice and rats. In young male rats, both niacin deficiency and nicotinamide supplementation significantly altered brain NAD+ and cADPR, both of which were inversely correlated with spatial learning ability. These results were consistent across three different models of niacin deficiency (pair feeding, partially restricted feeding and niacin recovery). Similar changes in spatial learning ability were observed in Cd38− / −  mice, which also showed decreases in brain cADPR. These findings suggest an inverse relationship between spatial learning ability, dietary niacin intake and cADPR, although a direct link between cADPR and spatial learning ability is still missing. Dietary niacin may therefore play a role in the molecular events regulating learning performance, and further investigations of niacin intake, CD38 and cADPR may help identify potential molecular targets for clinical intervention to enhance learning and prevent or reverse cognitive decline.

Primary schools contribute to promoting healthy eating behaviour and preventing overweight and obesity by providing nutrition education. Research highlights the importance of improving teachers’ programme implementation to enhance intervention effectiveness. An integrative approach has been suggested to reduce time barriers that teachers currently experience in teaching nutrition. This scoping review explores use and effectiveness of integrative teaching in primary-school-based nutrition education programmes. Six databases were searched for primary-school-based interventions on nutrition education. Papers reporting on integration of nutrition topics within core curriculum were included. Abstracts and full texts of potentially relevant articles were screened to determine eligibility. Next, data were extracted and tabulated. Findings were collated and summarised to describe intervention characteristics, subject integration and effectiveness of the included programmes. Data describing integration of nutrition into the primary school curriculum were extracted from 39 eligible papers. Nutrition education programmes often involve lessons about food groups and are frequently embedded within the mathematics, science or literacy syllabus. Although articles report on the integration of nutrition, the use of this approach was not commonly described in detail. Only seven papers discussed student outcomes related to the integration of nutrition education within core subjects. The ability to draw strong conclusions about school-based nutrition intervention effectiveness is limited by the current lack of programme description and methodological issues. Hence, more research is warranted to inform evidence on effectiveness of integrative nutrition education for both teacher and student outcomes. Future studies that include greater detail regarding the integrative approach are needed.

Investigations into the genetic architecture of diet–disease relationships are particularly relevant today with the global epidemic of obesity and chronic disease. Twin studies have demonstrated that genetic makeup plays a significant role in a multitude of dietary phenotypes such as energy and macronutrient intakes, dietary patterns, and specific food group intakes. Besides estimating heritability of dietary assessment, twins provide a naturally unique, case–control experiment. Due to their shared upbringing, matched genes and sex (in the case of monozygotic (MZ) twin pairs), and age, twins provide many advantages over classic epidemiological approaches. Future genetic epidemiological studies could benefit from the twin approach particularly where defining what is ‘normal’ is problematic due to the high inter-individual variability underlying metabolism. Here, we discuss the use of twins to generate heritability estimates of food intake phenotypes. We then highlight the value of discordant MZ pairs to further nutrition research through discovery and validation of biomarkers of intake and health status in collaboration with cutting-edge omics technologies.

Glucagon-like peptide-1 (GLP-1) is an enterohormone with a key role in several processes controlling body homeostasis, including glucose homeostasis and food intake regulation. It is secreted by the intestinal cells in response to nutrients, such as glucose, fat and amino acids. In the present review, we analyse the effect of protein on GLP-1 secretion and clearance. We review the literature on the GLP-1 secretory effects of protein and protein hydrolysates, and the mechanisms through which they exert these effects. We also review the studies on protein from different sources that has inhibitory effects on dipeptidyl peptidase-4 (DPP4), the enzyme responsible for GLP-1 inactivation, with particular emphasis on specific sources and treatments, and the gaps there still are in knowledge. There is evidence that the protein source and the hydrolytic processing applied to them can influence the effects on GLP-1 signalling. The gastrointestinal digestion of proteins, for example, significantly changes their effectiveness at modulating this enterohormone secretion in both in vivo and in vitro studies. Nevertheless, little information is available regarding human studies and more research is required to understand their potential as regulators of glucose homeostasis.

The diversity of the human genome leads to many functional differences between individuals. The present review focuses on genetic variations, both rare and common, that are of relevance to digestion of the sugars and starches that form a major part of human diets, and considers these in relation to the evolution of our species. For example, intolerances of dietary saccharides are not usually life-threatening because symptoms can be avoided by removal of the offending sugar from the diet, and deficiencies of the relevant enzymes are in some cases found at relatively high frequencies in certain populations. This is of evolutionary interest in relation to changes in the human diet, and the lactase-persistence polymorphism, in particular, provides an interesting model. More of the world's adult population are lactase-deficient than have high lactase. The other deficiencies are however much more rare, but the significance of variant alleles at these loci, and also heterozygosity for deficiency alleles, to human nutrition and health is an area that is relatively unexplored.

Dietary restriction of carbohydrate has been demonstrated to be beneficial for nervous system dysfunction in animal models and may be beneficial for human chronic pain. The purpose of this review is to assess the impact of a low-carbohydrate/ketogenic diet on the adult nervous system function and inflammatory biomarkers to inform nutritional research for chronic pain. An electronic database search was carried out in May 2021. Publications were screened for prospective research with dietary carbohydrate intake <130 g per day and duration of ≥2 weeks. Studies were categorised into those reporting adult neurological outcomes to be extracted for analysis and those reporting other adult research outcomes. Both groups were screened again for reported inflammatory biomarkers. From 1548 studies, there were 847 studies included. Sixty-four reported neurological outcomes with 83% showing improvement. Five hundred and twenty-three studies had a different research focus (metabolic n = 394, sport/performance n = 51, cancer n = 33, general n = 30, neurological with non-neuro outcomes n = 12, or gastrointestinal n = 4). The second screen identified sixty-three studies reporting on inflammatory biomarkers, with 71% reporting a reduction in inflammation. The overall results suggest a favourable outcome on the nervous system and inflammatory biomarkers from a reduction in dietary carbohydrates. Both nervous system sensitisation and inflammation occur in chronic pain, and the results from this review indicate it may be improved by low-carbohydrate nutritional therapy. More clinical trials within this population are required to build on the few human trials that have been done.

Research into the cognitive and mood effects of caffeine in human subjects has highlighted some fairly robust and well-accepted effects. However, the majority of these studies have focused on caffeine in isolation; whilst caffeine is normally consumed in the form of plant-derived products and extracts that invariably contain other potentially bioactive phytochemicals. The aim of the present review is to consider the possible mechanisms of action of co-occurring phytochemicals, and any epidemiological evidence suggesting that they contribute to potential health benefits ascribed to caffeine. Intervention studies to date that have been conducted to explore the effects on brain function of the non-caffeine components in caffeine-bearing plants (coffee, tea, cocoa, guaraná), either alone or in combination with caffeine, will also be summarised. Research is beginning to accumulate showing independent effects for several of the phytochemicals that co-occur with caffeine, and/or a modulation of the effects of caffeine when it is co-consumed with these naturally concomitant phytochemicals. The present review highlights that more research aimed at understanding the effects of these compounds is needed and, more importantly, the synergistic relationship that they may have with caffeine.

Intestinal stem cells, which are capable of both self-renewal and differentiation to mature cell types, are responsible for maintaining intestinal epithelial homeostasis. Recent evidence indicates that these processes are mediated, in part, through nutritional status in response to diet. Diverse dietary patterns including caloric restriction, fasting, high-fat diets, ketogenic diets and high-carbohydrate diets as well as other nutrients control intestinal stem cell self-renewal and differentiation through nutrient-sensing pathways such as mammalian target of rapamycin and AMP-activated kinase. Herein, we summarise the current understanding of how intestinal stem cells contribute to intestinal epithelial homeostasis and diseases. We also discuss the effects of diet and nutrient-sensing pathways on intestinal stem cell self-renewal and differentiation, as well as their potential application in the prevention and treatment of intestinal diseases.

The availability of ‘omics’ technologies is transforming scientific approaches to physiological problems from a reductionist viewpoint to that of a holistic viewpoint. This is of profound importance in nutrition, since the integration of multiple systems at the level of gene expression on the synthetic side through to metabolic enzyme activity on the degradative side combine to govern nutrient availability to tissues. Protein activity is central to the process of nutrition from the initial absorption of nutrients via uptake carriers in the gut, through to distribution and transport in the blood, metabolism by degradative enzymes in tissues and excretion through renal tubule exchange proteins. Therefore, the global profiling of the proteome, defined as the entire protein complement of the genome expressed in a particular cell or organ, or in plasma or serum at a particular time, offers the potential for identification of important biomarkers of nutritional state that respond to alterations in diet. The present review considers the published evidence of nutritional modulation of the proteome in vivo which has expanded exponentially over the last 3 years. It highlights some of the challenges faced by researchers using proteomic approaches to understand the interactions of diet with genomic and metabolic–phenotypic variables in normal populations.

Knowing the biological signals associated with appetite control is crucial for understanding the regulation of food intake. Biomarkers of appetite have been defined as physiological measures that relate to subjective appetite ratings, measured food intake, or both. Several metabolites including amino acids, lipids and glucose were proposed as key molecules associated with appetite control over 60 years ago, and along with bile acids are all among possible appetite biomarker candidates. Additional metabolites that have been associated with appetite include endocannabinoids, lactate, cortisol and β-hydroxybutyrate. However, although appetite is a complex integrative process, studies often investigated a limited number of markers in isolation. Metabolomics involves the study of small molecules or metabolites present in biological samples such as urine or blood, and may present a powerful approach to further the understanding of appetite control. Using multiple analytical techniques allows the characterisation of molecules, such as carbohydrates, lipids, amino acids, bile acids and fatty acids. Metabolomics has proven successful in identifying markers of consumption of certain foods and biomarkers implicated in several diseases. However, it has been underexploited in appetite control or obesity. The aim of the present narrative review is to: (1) provide an overview of existing metabolites that have been identified in human biofluids and associated with appetite control; and (2) discuss the potential of metabolomics to deepen understanding of appetite control in humans.