A growing number of studies in recent years have highlighted the importance of molecular nutrition as a potential determinant of health and disease. In particular, the ability of micronutrients to regulate the final expression of gene products via modulation of transcription and translation is now being recognised. Modulation of microRNA (miRNA) by nutrients is one pathway by which nutrition may mediate gene expression. miRNA, a class of non-coding RNA, can directly regulate gene expression post-transcriptionally. In addition, miRNA are able to indirectly influence gene expression potential at the transcriptional level via modulation of the function of components of the epigenetic machinery (DNA methylation and histone modifications). These mechanisms interact to form a complex, bi-directional regulatory circuit modulating gene expression. Disease-specific miRNA profiles have been identified in multiple disease states, including those with known dietary risk factors. Therefore, the role that nutritional components, in particular, vitamins and minerals, play in the modulation of miRNA profiles, and consequently health and disease, is increasingly being investigated, and as such is a timely subject for review. The recently posited potential for viable exogenous miRNA to enter human blood circulation from food sources adds another interesting dimension to the potential for dietary miRNA to contribute to gene modulation.

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.

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.

Magnesium (Mg2+) is an essential mineral without known specific regulatory mechanisms. In ruminants, plasma Mg2+ concentration depends primarily on the balance between Mg2+ absorption and Mg2+ excretion. The primary site of Mg2+ absorption is the rumen, where Mg2+ is apically absorbed by both potential-dependent and potential-independent uptake mechanisms, reflecting involvement of ion channels and electroneutral transporters, respectively. Transport is energised in a secondary active manner by a basolateral Na+/Mg2+ exchanger. Ruminal transport of Mg2+ is significantly influenced by a variety of factors such as high K+ concentration, sudden increases of ammonia, pH, and the concentration of SCFA. Impaired Mg2+ absorption in the rumen is not compensated for by increased transport in the small or large intestine. While renal excretion can be adjusted to compensate precisely for any surplus in Mg2+ uptake, a shortage in dietary Mg2+ cannot be compensated for either via skeletal mobilisation of Mg2+ or via up-regulation of ruminal absorption. In such situations, hypomagnesaemia will lead to decrease of a Mg2+ in the cerebrospinal fluid and clinical manifestations of tetany. Improved knowledge concerning the factors governing Mg2+ homeostasis will allow reliable recommendations for an adequate Mg2+ intake and for the avoidance of possible disturbances. Future research should clarify the molecular identity of the suggested Mg2+ transport proteins and the regulatory mechanisms controlling renal Mg excretion as parameters influencing Mg2+ homeostasis.

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 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’.

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.

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.

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.

Worldwide obesity is increasing at an alarming rate in children and adolescents, with the consequent emergence of co-morbidities. Moreover, the maternal environment during pregnancy plays an important role in obesity, contributing to transgenerational transmission of the same and metabolic dysfunction. White adipose tissue represents a prime target of metabolic programming induced by maternal milieu. In this article, we review adipose tissue physiology and development, as well as maternal influences during the perinatal period that may lead to obesity in early postnatal life and adulthood. First, we describe the adipose tissue cell composition, distribution and hormonal action, together with the evidence of hormonal factors participating in fetal/postnatal programming. Subsequently, we describe the critical periods of adipose tissue development and the relationship of gestational and early postnatal life with healthy fetal adipose tissue expansion. Furthermore, we discuss the evidence showing that adipose tissue is an important target for nutritional, hormonal and epigenetic signals to modulate fetal growth. Finally, we describe nutritional, hormonal, epigenetic and microbiome changes observed in maternal obesity, and whether their disruption alters fetal growth and adiposity. The presented evidence supports the developmental origins of health and disease concept, which proposes that the homeostatic system is affected during gestational and postnatal development, impeding the ability to regulate body weight after birth, thereby resulting in adult obesity. Consequently, we anticipate that promoting a healthy early-life programming of adipose tissue and increasing the knowledge of the mechanisms by which maternal factors affect the health of future generations may offer novel strategies for explaining and addressing worldwide health problems such as obesity.

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.

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.

Nutritional intake during infancy is a critical aspect of child development and health that is of significant public health concern. Although there is extensive research on breast-feeding and timing of solid food introduction, there is less evidence on types of solid foods fed to infants, specifically commercially prepared infant foods. The consumption of commercially prepared infant foods is very prevalent in many developed countries, exceeding the consumption of homemade foods in some situations. Although these food products may have practical advantages, there are concerns about their nutritional composition, sweet taste, bioavailability of micronutrients, diversity of ingredients and long-term health effects. The extent that the manufacturing, fortification and promotion of these products are regulated by legislation varies between countries and regions. The aim of the present narrative review is to investigate, appraise and summarise these aspects. Overall there are very few studies directly comparing homemade and commercial infant foods and a lack of longitudinal studies to draw firm conclusions on whether commercial infant foods are mostly beneficial or unfavourable to infant health.

Advanced glycation endproducts (AGE) are a group of complex and heterogeneous molecules, sharing some common characteristics such as covalent cross-link formation among proteins, the effect of transforming the colour of food products into yellow-brown colours and fluorescence formation. AGE are linked to many diseases including diabetes, renal diseases, CVD, liver diseases, neuro-degenerative and eye disorders, female reproductive dysfunction, and even cancer. AGE are formed endogenously but are also provided from exogenous sources including diet and tobacco. Western diet, rich in processed and/or heat-treated foods, fat and sugar, increases the exposure to AGE. The foods that contain high levels of fat and protein are generally rich in terms of AGE, and are also prone to AGE formation during cooking compared with carbohydrate-rich foods such as vegetables, fruits, legumes and whole grains. The present article aimed to review the literature about the effects of different cooking methods and conditions on the AGE content of food and AGE formation mechanisms using a comprehensive approach.

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.