Micronutrient malnutrition, the deficiency of vitamins or minerals, impacts on physical and mental health, in clinical and general populations, across the life course. In older western populations the high prevalence and impact of micronutrient malnutrition is less well recognised. Low- and middle-income countries are experiencing the ‘double burden of disease’ where malnutrition coexists alongside the non-communicable diseases of aging, obesity, type 2 diabetes and cardiovascular disease. Held in December 2020, the Winter Conference of the Nutrition Society was designed to cover new areas of research and concern in micronutrient malnutrition across the life course. Common themes arising from the conference were: 1) The continuing high prevalence of micronutrient malnutrition across the life-course, in diverse populations, in high, middle and low-income countries. 2) That multiple deficiencies of micronutrients frequently exist. 3) The primary cause of deficiency is poor quality diets, of low diversity, low in micronutrient dense foods. 4) Clinical conditions, medications for common non-communicable diseases, and environmental conditions, interact with and exacerbate the effects of poor diet quality. 5) Understanding of the mechanistic effects of micronutrients is still emerging. 6) Micronutrients are necessary for maintaining immune function, which has importance for the COVID-19 epidemic. 7) Better biomarkers are needed detect and understand the effects of deficiency. 7) Dietary recommendations need to be updated regularly. Further research is needed in all these areas. Comprehensive public health and government approaches to ensure access and affordability of good quality foods to populations of all ages, particularly during the ongoing COVID-19 epidemic, are crucial.

The aim of this review paper is to explore the strategies employed to tackle micronutrient deficiencies with illustrations from field-based experience. Hidden hunger is the presence of multiple micronutrient deficiencies (particularly iron, zinc, iodine and vitamin A), which can occur without a deficit in energy intake as a result of consuming an energy-dense, but nutrient-poor diet. It is estimated that it affects more than two billion people worldwide, particularly in low- and middle-income countries where there is a reliance on low-cost food staples and where the diversity of the diet is limited. Finding a way to improve the nutritional quality of diets for the poorest people is central to meeting the UN sustainable development goals particularly sustainable development goal 2: end hunger, achieve food security and improved nutrition and promote sustainable agriculture. As we pass the midpoint of the UN's Decade for Action on Nutrition, it is timely to reflect on progress towards achieving sustainable development goal 2 and the strategies to reduce hidden hunger. Many low- and middle-income countries are falling behind national nutrition targets, and this has been exacerbated by the COVID-19 pandemic as well as other recent shocks to the global food system which have disproportionately impacted the world's most vulnerable communities. Addressing inequalities within the food system must be central to developing a sustainable, cost-effective strategy for improving food quality that delivers benefit to the seldom heard and marginalised communities.

Micronutrient deficiency persists throughout the world, and although the burden is higher in low-resource settings, it is also prevalent in wealthy countries, a phenomenon termed ‘hidden hunger’. Due to their high requirements for vitamins and minerals relative to their energy intake, young women and children are particularly vulnerable to hidden hunger. As they share several risk factors and impact on overlapping outcomes, we consider how deficiency of iron, iodine and vitamin D can have profound impacts on perinatal health and infant development. We review the epidemiology of these micronutrient deficiencies during pregnancy, including social, environmental and dietary risk factors. We identify the main challenges in defining nutritional status of these nutrients using validated diagnostic criteria linked with meaningful clinical outcomes. Public health strategies are urgently required to improve the overall health and nutritional status of women of reproductive age. Obesity prevention and early detection of malnutrition with standardised screening methods would detect pregnant women at increased risk of iron deficiency. Development of sensitive, individual biomarkers of iodine status is required to protect maternal health and fetal/infant brain development. Risk assessments of vitamin D requirements during pregnancy need to be revisited from the perspective of fetal and neonatal requirements. International consensus on standardised approaches to micronutrient assessment, analysis and reporting as well as sensitive, clinically validated infant and child neuro-behavioural outcomes will enable progression of useful observational and intervention studies.

Sometimes referred to as hidden hunger, micronutrient deficiencies persist on a global scale. For some micronutrients this appears to be due to inadequate intake, for others intake may not match increased requirements. However, for most micronutrient deficiencies there is uncertainty as to the dominant driver, and the question about the contribution of malabsorption is open. Environmental enteropathy (EE), formerly referred to as tropical enteropathy and also referred to as environmental enteric dysfunction, is an asymptomatic disorder of small intestinal structure and function which is very highly prevalent in many disadvantaged populations. Recent studies of the pathology and microbiology of this disorder suggest that it is driven by very high pathogen burdens in children and adults living in insanitary environments and is characterised by major derangements of the epithelial cells of the intestinal mucosa. Transcriptomic data suggest that it may lead to impaired digestion and absorption of macronutrients. Given the very high prevalence of EE, marginal malabsorption could have large impacts at population scales. However, the relative contributions of inadequate soil and crop micronutrient contents, inadequate intake, malabsorption and increased requirements are unknown. Malabsorption may compromise attempts to improve micronutrient status, but with the exception of zinc there is currently little evidence to confirm that malabsorption contributes to micronutrient deficiency. Much further research is required to understand the role of malabsorption in hidden hunger, especially in very disadvantaged populations where these deficiencies are most prevalent.

Sarcopenia, a skeletal muscle disorder that is characterised by loss of muscle strength and mass, is common in older populations and associated with poorer health outcomes. Although the individual and economic costs of sarcopenia are widely recognised, current understanding of its pathophysiology is incomplete, limiting efforts to translate research evidence into effective preventive and treatment strategies. While nutrition is a key field of sarcopenia research, the role of differences in habitual diets, and the effectiveness of dietary change as a prevention or treatment strategy, is uncertain. There is a growing evidence base that links low micronutrient intakes to sarcopenia risk and/or its components (low muscle strength and mass, impaired physical performance), although there remain many gaps in understanding. There is some consistency in findings across studies highlighting potential roles for antioxidant nutrients, B vitamins and magnesium; however, the evidence is largely observational and from cross-sectional studies, often describing associations with different muscle outcomes. As low intakes of some micronutrients are common in older populations, there is a need for new research, particularly from well-characterised prospective cohorts, to improve the understanding of their role and importance in the aetiology of sarcopenia and to generate the evidence needed to inform dietary guidelines to promote muscle health.

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.

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.

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.

The objectives are to present an updated synopsis on osteosarcopenic adiposity (OSA) syndrome and evaluate the roles of selected micronutrients in its prevention and management. OSA refers to the concurrent deterioration of bone (osteopenia/osteoporosis), muscle (sarcopenia) and adipose tissue expansion. It portrays the most advanced stage in a continuum of body composition disorders. Although OSA has been widely studied involving the populations of different backgrounds, its prevalence is hard to collate because different methodologies and criteria were used for its diagnosis. Another critical health aspect is the presence of low-grade chronic inflammation (LGCI) which contributes to OSA and vice versa. Nutrition is important in the prevention and management of both OSA and LGCI. Although micronutrients act in numerous metabolic and physiological processes, their roles here are presented in relation to OSA (and its components) and LGCI in general and relevant to the COVID-19 pandemic. These include calcium, magnesium, phosphorus, potassium, sodium and vitamins D and K; their interactions, physiological ratios and synergism/antagonism are discussed as well. In conclusion, calcium, magnesium and vitamin D have a profound impact on OSA and its components, and the latter two also on LGCI. Potassium and vitamin K are vital in bone, muscle functioning and possibly adipose tissue modification. Both, but particularly vitamin D, surfaced as important modulators of immune system with application in COVID-19 infections. While both phosphorus and sodium have important roles in bone, muscle and can impact adiposity, due to their abundance in food, their intake should be curbed to prevent possible damaging effects.

For many people, micronutrient requirement means the amount needed in the diet to ensure adequacy. Dietary reference values (DRV) provide guidance on the daily intake of vitamins and minerals required to ensure the needs of the majority in the population are covered. These are developed on estimates of the quantity of each micronutrient required by the average person, the bioavailability of the micronutrient from a typical diet and the interindividual variability in these amounts. Sex differences are inherent in the requirements for many micronutrients because they are influenced by body size or macronutrient intake. These are reflected in different DRV for males and females for some micronutrients, but not all, either when data from males and females are combined or when there is no evidence of sex differences. Pregnancy and lactation represent times when micronutrient requirements for females may differ from males, and separate DRV are provided. For some micronutrients, no additional requirement is indicated during pregnancy and lactation because of physiological adaptations. To date, little account has been taken of more subtle sex differences in growth and maturation rates, health vulnerabilities and in utero and other programming effects. Over the years, the MRC Nutrition and Bone Health Group has contributed data on micronutrient requirements across the lifecourse, particularly for calcium and vitamin D, and shown that supplementation can have unexpected sex-specific consequences that require further investigation. The present paper outlines the current issues and the need for future research on sex differences in micronutrient requirements.

Dietary reference values (DRV) are estimates of the daily amounts of nutrients or food energy that meet the needs of healthy people. In the UK, three terms are used to express these estimates, assuming a normal distribution of requirements in a population. These are the estimated average requirement, the lower reference nutrient intake and the reference nutrient intake. DRV are for use in a variety of settings, including the assessment of adequacy and safety of nutrient or energy intake in a population group, in the design of meal provision in care settings, in food labelling and in considering food fortification strategies. DRV, and other expressions of nutrient requirements, assume a relationship between the intake of a nutrient and some criterion of adequacy, the outcome. Estimates of requirements are based on a diverse range of measures of adequacy, according to available evidence. The Scientific Advisory Committee on Nutrition (SACN) is the body responsible for reviewing and setting DRV for the UK population. The work of SACN is guided by a framework of evidence that relates food and nutrients to health. There have been calls for the harmonisation of approaches used in the setting of nutrient requirements, globally, and an increased transparency in the decision-making process. Some progress has been made in this regard, but there is a great deal of work to be done.

Policy decisions and the practice of public health nutrition need to be based on solid evidence, developed through rigorous research studies where objective measures are used and results that run counter to dogma are not dismissed but investigated. In recent years, enhancements in study designs, and methodologies for systematic reviews and meta-analysis, have improved the evidence-base for nutrition policy and practice. However, these still rely on a full appreciation of the strengths and limitations of the measures on which conclusions are drawn and on the thorough investigation of outcomes that do not fit expectations or prevailing convictions. The importance of ‘hard facts’ and ‘misfits’ in research designed to advance knowledge and improve public health nutrition is illustrated in this paper through a selection of studies from different stages in my research career, focused on the nutritional requirements of resource-poor populations in Africa and Asia.