All tissues are in a constant state of turnover, with a tightly controlled regulation of protein synthesis and breakdown rates. Due to the relative ease of sampling skeletal muscle tissue, basal muscle protein synthesis rates and the protein synthetic responses to various anabolic stimuli have been well defined in human subjects. In contrast, only limited data are available on tissue protein synthesis rates in other organs. Several organs such as the brain, liver and pancreas, show substantially higher (basal) protein synthesis rates when compared to skeletal muscle tissue. Such data suggest that these tissues may also possess a high level of plasticity. It remains to be determined whether protein synthesis rates in these tissues can be modulated by external stimuli. Whole-body protein synthesis rates are highly responsive to protein intake. As the contribution of muscle protein synthesis rates to whole-body protein synthesis rates is relatively small considering the large amount of muscle mass, this suggests that other organ tissues may also be responsive to (protein) feeding. Whole-body protein synthesis rates in the fasted or fed state can be quantified by measuring plasma amino acid kinetics, although this requires the production of intrinsically labelled protein. Protein intake requirements to maximise whole-body protein synthesis may also be determined by the indicator amino acid oxidation technique, but the technique does not allow the assessment of actual protein synthesis and breakdown rates. Both approaches have several other methodological and inferential limitations that will be discussed in detail in this paper.

The enteroendocrine system is located in the gastrointestinal (GI) tract, and makes up the largest endocrine system in the human body. Despite that, its roles and functions remain incompletely understood. Gut regulatory peptides are the main products of enteroendocrine cells, and play an integral role in the digestion and absorption of nutrients through their effect on intestinal secretions and gut motility. Several peptides, such as cholecystokinin, polypeptide YY and glucagon-like peptide-1, have traditionally been reported to suppress appetite following food intake, so-called satiety hormones. In this review, we propose that, in the healthy individual, this system to regulate appetite does not play a dominant role in normal food intake regulation, and that there is insufficient evidence to wholly link postprandial endogenous gut peptides with appetite-related behaviours. Instead, or additionally, top-down, hedonic drive and neurocognitive factors may have more of an impact on food intake. In GI disease however, supraphysiological levels of these hormones may have more of an impact on appetite regulation as well as contributing to other unpleasant abdominal symptoms, potentially as part of an innate response to injury. Further work is required to better understand the mechanisms involved in appetite control and unlock the therapeutic potential offered by the enteroendocrine system in GI disease and obesity.

Vitamin E, discovered in 1922, is essential for pregnant rats to carry their babies to term. However, 100 years later, the molecular mechanisms for the vitamin E requirement during embryogenesis remain unknown. Vitamin E's role during pregnancy has been difficult to study and thus, a vitamin E-deficient (E–) zebrafish embryo model was developed. Vitamin E deficiency in zebrafish embryos initiates lipid peroxidation, depletes a specific phospholipid (DHA-phosphatidyl choline), causes secondary deficiencies of choline, betaine and critical thiols (such as glutathione), and dysregulates energy metabolism. Vitamin E deficiency not only distorts the carefully programmed development of the nervous system, but it leads to defects in several developing organs. Both the α-tocopherol transfer protein and vitamin E are necessary for embryonic development, neurogenesis and cognition in this model and likely in human embryos. Elucidation of the control mechanisms for the cellular and metabolic pathways involved in the molecular dysregulation caused by vitamin E deficiency will lead to important insights into abnormal neurogenesis and embryonic malformations.

This review outlines the current use of magnetic resonance (MR) techniques to study digestion and highlights their potential for providing markers of digestive processes such as texture changes and nutrient breakdown. In vivo digestion research can be challenging due to practical constraints and biological complexity. Therefore, digestion is primarily studied using in vitro models. These would benefit from further in vivo validation. NMR is widely used to characterise food systems. MRI is a related technique that can be used to study both in vitro model systems and in vivo gastro-intestinal processes. MRI allows visualisation and quantification of gastric processes such as gastric emptying and coagulation. Both MRI and NMR scan sequences can be configured to be sensitive to different aspects of gastric or intestinal contents. For example, magnetisation transfer and chemical exchange saturation transfer can detect proton (1H) exchange between water and proteins. MRI techniques have the potential to provide molecular-level and quantitative information on in vivo gastric (protein) digestion. This requires careful validation in order to understand what these MR markers of digestion mean in a specific digestion context. Combined with other measures they can be used to validate and inform in vitro digestion models. This may bridge the gap between in vitro and in vivo digestion research and can aid the optimisation of food properties for different applications in health and disease.

Gene–nutrient interactions (GeNuIne) collaboration, a large-scale collaborative project, has been initiated to investigate the impact of gene–nutrient interactions on cardiometabolic diseases using population-based studies from ethnically diverse populations. In this project, the relationship between deficiencies of vitamins B12 and D, and metabolic diseases was explored using a nutrigenetic approach. A genetic risk score (GRS) analysis was used to examine the combined effect of several genetic variations that have been shown to be associated with metabolic diseases and vitamin B12 and D deficiencies, respectively. In Sri Lankan, Indonesian and Brazilian populations, those carrying a high B12-GRS had an increased risk of metabolic diseases under the influence of dietary protein, fibre and carbohydrate intakes, respectively; however, in Asian Indians, genetically instrumented metabolic disease risk showed a significant association with low vitamin B12 status. With regards to nutrigenetic studies on vitamin D status, although high metabolic-GRS showed an interaction with dietary carbohydrate intake on vitamin D status, the study in Indonesian women demonstrated a vitamin D GRS–carbohydrate interaction on body fat percentage. In summary, these nutrigenetic studies from multiple ethnic groups have provided evidence for the influence of the dietary factors on the relationship between vitamin B12/D deficiency and metabolic outcomes. Furthermore, these studies highlight the existence of genetic heterogeneity in gene–diet interactions across ethnically diverse populations, which further implicates the significance of personalised dietary approaches for the prevention of these micronutrient deficiencies and metabolic diseases.

Magnesium (Mg2+) plays an essential role in many biological processes. Mg2+ deficiency is therefore associated with a wide range of clinical effects including muscle cramps, fatigue, seizures and arrhythmias. To maintain sufficient Mg2+ levels, (re)absorption of Mg2+ in the intestine and kidney is tightly regulated. Genetic defects that disturb Mg2+ uptake pathways, as well as drugs interfering with Mg2+ (re)absorption cause hypomagnesemia. The aim of this review is to provide an overview of the molecular mechanisms underlying genetic and drug-induced Mg2+ deficiencies. This leads to the identification of four main mechanisms that are affected by hypomagnesemia-causing mutations or drugs: luminal transient receptor potential melastatin type 6/7-mediated Mg2+ uptake, paracellular Mg2+ reabsorption in the thick ascending limb of Henle's loop, structural integrity of the distal convoluted tubule and Na+-dependent Mg2+ extrusion driven by the Na+/K+-ATPase. Our analysis demonstrates that genetic and drug-induced causes of hypomagnesemia share common molecular mechanisms. Targeting these shared pathways can lead to novel treatment options for patients with hypomagnesemia.

The preventability estimate for colorectal cancer (CRC) is approximately 50%, highlighting the huge potential for altering modifiable lifestyle factors (including diet and body fatness) in order to reduce risk of this common malignancy. There is strong evidence that dietary factors (including intake of wholegrains, fibre, red and processed meat and alcohol) affect CRC risk. The lack of positive intervention trials and limited mechanistic understanding likely explain limited public health impact of epidemiological observations, to date. An alternative strategy for nutritional prevention of CRC is use of supplements that provide higher individual nutrient exposure than obtained through the diet (chemoprevention). There are positive data for calcium and/or vitamin D and the n-3 fatty acid EPA from polyp prevention trials using colorectal adenoma as a CRC risk biomarker. Although CRC is an obesity-related malignancy, there remains a paucity of observational data supporting intentional weight loss for CRC risk reduction. Some types of obesity surgeries (Roux-en-Y gastric bypass) might actually increase subsequent CRC risk due to alteration of local intestinal factors. There is intense interest in nutritional therapy of patients after diagnosis of CRC, in order to impact on recurrence and overall survival (now often termed cancer interception). In conclusion, nutritional prevention of CRC continues to hold much promise. Increased mechanistic understanding of the role of individual nutrients (linked to intestinal microbiota), as well as a precision medicine approach to CRC chemoprevention and interception based on both tumour and host factors, should enable translation of nutritional interventions into effective CRC risk reduction measures.

In parallel with increased public awareness of the health and environmental benefits of consuming a plant-based diet, the numbers of people who identify as vegan has increased sharply. The question of whether vegetarian and vegan diets are appropriate for children is a longstanding and unresolved controversy. The more restrictive the diet and the younger the child, the greater the risk of nutritional deficiency. Nutrients of potential concern are protein quantity and quality, iron, zinc, selenium, calcium, riboflavin, vitamins A, D, B12 and essential fatty acids. Although intakes and status of some nutrients (e.g. vitamin D and iron) are low in many children, vegan children are particularly susceptible due to inadequate supply and/or excess dietary fibre as well as other components that limit bioavailability. Although position papers from North America state that well-planned vegetarian and vegan diets, supplemented appropriately, are suitable for all life stages, European statements include strong recommendations to parents that vegan diets should not be adopted by children without medical and dietetic supervision. Case histories of malnutrition and serious harm persist, including irreversible neurological damage due to vitamin B12 deficiency among un-supplemented children. The evidence available to evaluate the nutritional appropriateness of vegetarian diets for children is inadequate and dated. Although nutritionally adequate vegetarian diets are more easily achieved, successful provision of a complete vegan diet for a young child requires substantial commitment, expert guidance, planning, resources and supplementation.

Nutrition and gastrointestinal cancer are inextricably linked. The metabolic effects of cancer along with changes in dietary intake, the development of cancer cachexia and the presence of sarcopenia can influence changes in body composition. These have a negative impact on quality of life and tolerance to cancer treatment. Treatment for cancer presents some significant nutritional challenges as nutrition impact symptoms may develop, be exacerbated by treatment and may contribute to a worsening in nutritional status. Nutrition screening and assessment should be an integral part of holistic patient care. The provision of appropriate, evidence-based dietary advice should occur before, during and after cancer treatment. Appropriate and timely methods of nutritional support across the spectrum of gastrointestinal cancer are needed to ensure that people are adequately supported during courses of treatment that can span weeks and months. These can range from standard approaches of supplementing oral intake to complex interventions such as managing high output intestinal stomas. The gastrointestinal tract is particularly susceptible to impact from systemic anti-cancer treatments and radiotherapy. Gastrointestinal late effects of cancer treatment are now recognised to present particular challenges in terms of both medical and nutritional management. These late effects have a significant impact on the individual and their quality of life in addition to implications for the health service. Dietary intake following cancer treatment has an impact on quality of life and future research may demonstrate its influence on the risk of recurrence of gastrointestinal cancer.

In an ageing society, the preservation of health and function is becoming increasingly important. The present paper acknowledges that ageing is malleable and focuses on diets and key nutritional concerns later in life. It presents evidence for the importance of healthful dietary patterns and points towards specific nutritional concerns later in life and conveys three main messages: (1) considering health maintenance and malnutrition risk, both dietary quality in terms of healthful dietary patterns and dietary quantity are important later in life, (2) ageing-related changes in nutrient physiology and metabolism contribute to the risk of inadequacies or deficiencies for specific nutrients, e.g. vitamin D, vitamin B12 and protein and (3) that current food-based dietary guidelines propagate a shift into the direction of Mediterranean type of diets including more plant-based foods. Limited scientific evidence on nutritional requirements of older adults, along with envisaged shifts towards diets rich in plant foods, are challenges that need to be addressed in order to develop tailored nutritional recommendations and dietary guidance for older adults.