Optimising micronutrient status globally is a major health priority. Nutritional biomarkers are critical for the identification of nutrient inadequacies in light of the limitations of dietary assessment methods. Early diagnosis and prevention of nutrient inadequacies require sensitive, validated and harmonised methods to determine and monitor micronutrient status in individual healthcare and population-based surveys. Important criteria in the identification, validation and implementation of nutritional biomarkers include the testing of biomarker specificity and sensitivity, and their response to dietary as well as physiologic changes, e.g. age or pregnancy. Nutritional status can be categorised into deficient, suboptimal, adequate and excess status, where appropriate, and provided cut-offs are available. Cut-offs are quantitative measures to reflect health outcomes and are important in validating nutritional surveys, interventions and monitoring of populations. For many biomarkers, available cut-offs have limited interpretability and are most commonly derived in adult populations only. For the comparison of studies from across the globe, the harmonisation of analytical methods is essential and can be realised with the use of internationally available reference material and interlaboratory comparison studies. This narrative review describes current efforts on identifying and validating existing and new biomarkers, the derivation of biomarker cut-offs, and international efforts on harmonisation of laboratory methods for biomarker quantitation and their interpretation, in the example of B-vitamins. Establishing sensitive, reliable and cost-efficient biomarkers and related cut-offs for use in populations across the globe are critical to facilitating the early diagnosis of micronutrient inadequacies on the clinical and community-based level for timely intervention and disease prevention.

Africa is experiencing a sharp rise in non-communicable diseases (NCD) related to rapid globalisation and urbanisation leading to shifts in dietary and lifestyle patterns characterised by increased energy intake and physical inactivity. However, unlike more resource-endowed regions, Africa has a double burden of disease: NCD co-exist with infectious diseases including lower respiratory tract infections, HIV/AIDS and diarrhoeal diseases. The African economy is also relatively weaker, making it difficult to cope with this burden. It is postulated that NCD will soon overtake infectious diseases as the number one cause of death in the African region. The recognition of NCD as diseases and obesity as a related risk factor is weak in Africa, compounded by stigma associated with wasting in HIV/AIDS and obesity being perceived as a sign of wealth, achievement and care. There is also a dearth of data on overweight and obesity in the region and little knowledge that infant feeding practices, such as breast-feeding, are linked to reduced risk of NCD in both children and mothers. While complex multi-sectoral approaches to address this NCD menace are needed, Africa may benefit from taking simple initial steps to address NCD risk factors including: (1) behaviour change communication to challenge perceptions on NCD; (2) promoting and protecting breast-feeding; (3) formulating policies and regulations limiting wide availability of unhealthy foods; (4) mainstream nutrition education in school curricula and (5) collection of accurate data based on indicators that can reflect the double burden of disease and malnutrition; and fostering multi-sectoral actions against NCD.

This review examines the metabolic adaptations that occur in response to negative energy balance and their potential putative or functional impact on appetite and food intake. Sustained negative energy balance will result in weight loss, with body composition changes similar for different dietary interventions if total energy and protein intake are equated. During periods of underfeeding, compensatory metabolic and behavioural responses occur that attenuate the prescribed energy deficit. While losses of metabolically active tissue during energy deficit result in reduced energy expenditure, an additional down-regulation in expenditure has been noted that cannot be explained by changes in body tissue (e.g. adaptive thermogenesis). Sustained negative energy balance is also associated with an increase in orexigenic drive and changes in appetite-related peptides during weight loss that may act as cues for increased hunger and food intake. It has also been suggested that losses of fat-free mass (FFM) could also act as an orexigenic signal during weight loss, but more data are needed to support these findings and the signalling pathways linking FFM and energy intake remain unclear. Taken together, these metabolic and behavioural responses to weight loss point to a highly complex and dynamic energy balance system in which perturbations to individual components can cause co-ordinated and inter-related compensatory responses elsewhere. The strength of these compensatory responses is individually subtle, and early identification of this variability may help identify individuals that respond well or poorly to an intervention.

Overweight-related metabolic diseases are an important threat to health in the Western world. Dietary habits are one of the main causative factors for metabolic syndrome, CVD and type 2 diabetes. The human gut microbiota is emerging as an important player in the interaction between diet and metabolic health. Gut microbial communities contribute to human metabolism through fermentation of dietary fibre and the result of intestinal saccharolytic fermentation is production of SCFA. Acetate, propionate and butyrate positively influence satiety, endocrine system, glucose homeostasis, adipogenesis, lipid oxidation, thermoregulation, hepatic gluconeogenesis, endothelial function and gut barrier integrity, and these mechanisms have all been linked to protection from type 2 diabetes, hypertension and cardiovascular health. The gut microbiota is also involved in bile acid metabolism and regulating their cell signalling potential, which has also been shown to modify pathways involved in metabolic health. Similarly, the gut microbiota renders recalcitrant plant polyphenols into biologically active small phenolic compounds which then act systemically to reduce metabolic disease risk. This review summarises how dietary patterns, specific foods and a healthy lifestyle may modulate metabolic health through the gut microbiota and their molecular cross-talk with the host.

Hashimoto's thyroiditis (HT) and Graves’ disease (GD) are examples of autoimmune thyroid disease (AITD), the commonest autoimmune condition. Antibodies to thyroid peroxidase (TPO), the enzyme that catalyses thyroid-hormone production and antibodies to the receptor for the thyroid-stimulating hormone, are characteristic of HT and GD, respectively. It is presently accepted that genetic susceptibility, environmental factors, including nutritional factors and immune disorders contribute to the development of AITD. Aiming to investigate the effect of iodine, iron and selenium in the risk, pathogenesis and treatment of thyroid disease, PubMed and the Cochrane Library were searched for relevant publications to provide a narrative review. Iodine: chronic exposure to excess iodine intake induces autoimmune thyroiditis, partly because highly-iodinated thyroglobulin (Tg) is more immunogenic. The recent introduction of universal salt iodisation can have a similar, although transient, effect. Iron: iron deficiency impairs thyroid metabolism. TPO is a haem enzyme that becomes active only after binding haem. AITD patients are frequently iron-deficient since autoimmune gastritis, which reduces iron absorption and coeliac disease which causes iron loss, are frequent co-morbidities. In two-thirds of women with persistent symptoms of hypothyroidism despite appropriate levothyroxine therapy, restoration of serum ferritin above 100 µg/l ameliorated symptoms. Selenium: selenoproteins are essential to thyroid action. In particular, the glutathione peroxidases remove excessive hydrogen peroxide produced there for the iodination of Tg to form thyroid hormones. There is evidence from observational studies and randomised controlled trials that selenium, probably as selenoproteins, can reduce TPO-antibody concentration, hypothyroidism and postpartum thyroiditis. Appropriate status of iodine, iron and selenium is crucial to thyroid health.

Africa is currently experiencing rapid urbanisation impacting on people's food environments and dietary habits. Such changes are associated with higher prevalence of obesity coexisting with undernutrition. The present paper provides an overview of the healthiness of African urban food environments. We discuss the ways that food environments can be characterised and summarise the methods that can be used to investigate and intervene in the food environment. Data for Africa over a 50-year period (1961–2013) suggest an increasing availability of energy, animal products, fruit and vegetables, vegetable oils, sugar and sweeteners but a decrease in animal fats. There is a lack of evidence about how social, physical and macro-environments drive dietary habits in urban Africa, as most research has focused on the individual level. Examining how food consumption is embedded in everyday life, by investigating social environments is crucial to developing effective interventions. The informal food sector plays an important role in the retail food environment. Macro-level food price changes are an important factor influencing nutritional quality of African diets. The rapid expansion of food/beverages advertising in Africa threatens traditional food habits. Liberalisation of food trade is already impacting on the nutritional quality of food available. Improving African food environments represents a pressing public health concern and has the potential to prevent all forms of malnutrition. Hence, by conducting research into the role of urban social, physical and macro-environments, emerging interventions and policies are likely to positively impact on nutritional status, thereby enhancing social and economic development.

Non-alcoholic fatty liver disease (NAFLD) is now a major public health concern with an estimated prevalence of 25–30% of adults in many countries. Strongly associated with obesity and the metabolic syndrome, the pathogenesis of NAFLD is dependent on complex interactions between genetic and environmental factors that are not completely understood. Weight loss through diet and lifestyle modification underpins clinical management; however, the roles of individual dietary nutrients (e.g. saturated and n-3 fatty acids; fructose, vitamin D, vitamin E) in the pathogenesis or treatment of NAFLD are only partially understood. Systems biology offers valuable interdisciplinary methods that are arguably ideal for application to the studying of chronic diseases such as NAFLD, and the roles of nutrition and diet in their molecular pathogenesis. Although present in silico models are incomplete, computational tools are rapidly evolving and human metabolism can now be simulated at the genome scale. This paper will review NAFLD and its pathogenesis, including the roles of genetics and nutrition in the development and progression of disease. In addition, the paper introduces the concept of systems biology and reviews recent work utilising genome-scale metabolic networks and developing multi-scale models of liver metabolism relevant to NAFLD. A future is envisioned where individual genetic, proteomic and metabolomic information can be integrated computationally with clinical data, yielding mechanistic insight into the pathogenesis of chronic diseases such as NAFLD, and informing personalised nutrition and stratified medicine approaches for improving prognosis.

Non-communicable diseases (NCD) such as type-2 diabetes and CVD are now highly prevalent in both developed and developing countries. Evidence from both human and animal studies shows that early-life nutrition is an important determinant of NCD risk in later life. The mechanism by which the early-life environment influences future disease risk has been suggested to include the altered epigenetic regulation of gene expression. Epigenetic processes regulate the accessibility of genes to the cellular proteins that control gene transcription, determining where and when a gene is switched on and its level of activity. Epigenetic processes not only play a central role in regulating gene expression but also allow an organism to adapt to the environment. In this review, we will focus on how both maternal and paternal nutrition can alter the epigenome and the evidence that these changes are causally involved in determining future disease risk.

The purpose of this review is to consider the effects of the long-chain n-3 fatty acids found in marine foods, EPA and DHA, on risk for CVD, particularly fatal outcomes. It will examine both epidemiological and randomised controlled trial findings. The former studies usually examine associations between the dietary intake or the blood levels of EPA + DHA and CVD outcomes or, on occasion, total mortality. For example, our studies in the Framingham Heart Study and in the Women's Health Initiative Memory Study have demonstrated significant inverse relations between erythrocyte EPA + DHA levels (i.e. the Omega-3 Index) and total mortality. Recent data from the Cardiovascular Health Study reported the same relations between plasma phospholipid n-3 levels and overall healthy ageing. As regards randomised trials, studies in the 1990s and early 2000s were generally supportive of a cardiovascular benefit for fish oils (which contain EPA + DHA), but later trials were generally not able to duplicate these findings, at least for total CVD events. However, when restricted to effects on risk for fatal events, meta-analyses have shown consistent benefits for n-3 treatment. Taken together, the evidence is strong for a cardioprotective effect of EPA + DHA, especially when consumed in sufficient amounts to raise blood levels into healthy ranges. Establishing target EPA + DHA intakes to reduce risk for cardiovascular death is a high priority.

Bone health is determined by the rate of accrual in early life, followed by the rate of age-associated bone loss. Dietary protein intake might have a role in bone health across both of these phases via pleiotropic mechanistic pathways. Herein we summarise the pathways through which protein may exert either a positive or negative influence on bone. In the introduction, we describe the acid-ash hypothesis, which states that a high-protein intake may lead to an acidic residue that must be neutralised through the leaching of calcium and other minerals from the bone, subsequently leading to demineralisation and bone weakening. Conversely, and as described in the ‘Against: mechanisms through which protein may negatively impact bone’ section, protein intake may act to strengthen the bone by stimulating the activity of various anabolic hormones and growth factors, or by optimising muscle mass and functionality, which itself has an osteogenic influence. The net effect of these contrasting pathways is described in the ‘For: mechanisms through which protein may positively impact bone’ section, where a number of meta-analyses have demonstrated that higher protein intakes have a small positive impact on bone mass and fracture risk. Sometimes higher than recommended protein intakes are advised, e.g. during the earlier and later phases of the lifespan or during reduced energy availability. We conclude that protein is an essential nutrient for bone health, although further research is required to clarify the mechanistic pathways through which it exerts its influence, along with the clarification of the quantities, food sources and timing to allow for the optimisation of this protective influence and ultimately a reduction in fracture risk.

Dietary assessment methods including FFQ and food diaries are associated with many measurement errors including energy under-reporting and incorrect estimation of portion sizes. Such errors can lead to inconsistent results especially when investigating the relationship between food intake and disease causation. To improve the classification of a person's dietary intake and therefore clarify proposed links between diet and disease, reliable and accurate dietary assessment methods are essential. Dietary biomarkers have emerged as a complementary approach to the traditional methods, and in recent years, metabolomics has developed as a key technology for the identification of new dietary biomarkers. The objective of this review is to give an overview of the approaches used for the identification of biomarkers and potential use of the biomarkers. Over the years, a number of strategies have emerged for the discovery of dietary biomarkers including acute and medium term interventions and cross-sectional/cohort study approaches. Examples of the different approaches will be presented. Concomitant with the focus on single biomarkers of specific foods, there is an interest in the development of biomarker signatures for the identification of dietary patterns. In the present review, we present an overview of the techniques used in food intake biomarker discover, including the experimental approaches used and challenges faced in the field. While significant progress has been achieved in the field of dietary biomarkers in recent years, a number of challenges remain. Addressing these challenges will be key to ensure success in implementing use of dietary biomarkers.

Micronutrients such as trace elements and vitamins are important as enzyme cofactors in the metabolism of all cells in the body and therefore key to determining nutritional status. The present systematic review examined the evidence of the impact of the systemic inflammatory response on plasma micronutrient status in acute (surgical) and chronic tissue injury. A literature review using targeted subject headings was carried out. Plasma C-reactive protein was used to classify minor (<10 mg/l), moderate (11–80 mg/l) and major (>80 mg/l) inflammation. The literature search produced 2344 publications and plasma vitamin D, zinc and carotenoids were most commonly studied and plasma vitamins K, B2 and B6 were least studied. In acute injury thirteen studies (all prospective) and in chronic injury twenty-four studies (largely retrospective) were included in the review. There was consistent evidence that most common measured micronutrients in the plasma (zinc, selenium, vitamins A, D, E, K, B2, B6, B12, C, lutein, lycopene, α- and β-carotene) were significantly lowered from minor to moderate to major inflammation. The results of the present systematic review indicate that most plasma micronutrients fall as part of the systemic inflammatory response irrespective of acute or chronic injury. Therefore, in the presence of a systemic inflammation, plasma micronutrient concentrations should be interpreted with caution. There are a number of methods applied to adjust plasma micronutrient concentrations to avoid misdiagnosis of deficiency. Alternatively, intracellular measurements appear to obviate the need for such plasma adjustment to assess micronutrient status.

Dietary intake and nutritional status is an important environmental factor which can modulate metabolic-inflammation. In recent years, research has made significant advances in terms of understanding the impact of dietary components on metabolic-inflammation, within the context of obesity, type-2 diabetes (T2D) and CVD risk. Our work demonstrated that different fatty acids differentially modulate metabolic-inflammation, initially focusing on Nod-like receptor family, pyrin domain-containing three protein (NLRP3) inflammasome mediated IL-1β biology and insulin signalling. However, the paradigm is more complex, wherein data from the immunology field clearly show that nature of cellular energy metabolism is a key determinant of inflammation. Whilst metabolic-inflammation is a critical biological interaction, there is a paucity of data in relation to the nature and the extent to which nutritional status affects metabolic-inflammation. The complex paradigm will be discussed within the context of if/how dietary components, in particular fatty acids, may modulate obesity, T2D and CVD risk, via inflammatory and metabolic processes.

Health effects of fatty acids have been very controversial. Total mortality is inversely associated with the amount of total fat consumed. In contrast, trans fatty acids or SFA intake is positively related to mortality while the inverse is observed with consumption of MUFA or PUFA. Among PUFA, long-chain (LC) n-3 PUFA have many beneficial effects. Dietary intake of some types of fatty acids is specific to Africa. Energy from saturated fat does not exceed 14% and energy from n-6 PUFA does not exceed 8% of total energy intake. Dietary intake of LC n-3 PUFA is less than 100 mg/d whereas international recommendations promote 250–500 mg/d. Consumption of plant n-3 PUFA mainly α-linolenic acid (ALA) is highly variable depending on the country. Both fish and ALA availability are low in several African countries. The prevalence of diabetes and cardiovascular events remain very low in Africa, partly explained by the fact that the whole dietary pattern is globally the best of all continents. One objective of ‘fat for Africa’ could be to increase, as much as possible, the dietary intake of LC n-3 PUFA by promoting sustainable aquaculture and to maintain as much as possible traditional dietary pattern by preventing a tendency to westernisation, provided that the amount of energy and protein is sufficient to fight against wasting and stunting where it still exists.