The 2019 Nutrition Society Spring Conference, which convened in Dundee, focused on the challenges presented by inter-individual differences in the responses to nutrition and in conducting nutritional research. The programme brought together national and international experts to discuss the collective evidence on inter-individual nutritional responses and impacts on health. Speakers and delegates from across the UK, Europe and the USA debated new methods of conducting research in nutrition and discussed the development of appropriate dietary interventions to maintain health and prevent disease in diverse populations. Symposium 1 focused on the effects of ethnicity on nutrient availability and type 2 diabetes and cardio-metabolic disease. Symposium 2 explored sex differences in nutrient availability and health and metabolism. The final symposium examined genetic and phenotypic variation, nutrition and health. The meeting ended with a panel discussion about how we take research to recommendations and concluded with a need to consider inter-individual differences in planning, conducting and analysing nutritional research.

Extensive research demonstrates unequivocally that nutrition plays a fundamental role in maintaining health and preventing disease. In parallel nutrition research provides evidence that the risks and benefits of diet and lifestyle choices do not affect people equally, as people are inherently variable in their responses to nutrition and associated interventions to maintain health and prevent disease. To simplify the inherent complexity of human subjects and their nutrition, with the aim of managing expectations for dietary guidance required to ensure healthy populations and individuals, nutrition researchers often seek to group individuals based on commonly used criteria. This strategy relies on demonstrating meaningful conclusions based on comparison of group mean responses of assigned groups. Such studies are often confounded by the heterogeneous nutrition response. Commonly used criteria applied in grouping study populations and individuals to identify mechanisms and determinants of responses to nutrition often contribute to the problem of interpreting the results of group comparisons. Challenges of interpreting the group mean using diverse populations will be discussed with respect to studies in human subjects, in vivo and in vitro model systems. Future advances in nutrition research to tackle inter-individual variation require a coordinated approach from funders, learned societies, nutrition scientists, publishers and reviewers of the scientific literature. This will be essential to develop and implement improved study design, data recording, analysis and reporting to facilitate more insightful interpretation of the group mean with respect to population diversity and the heterogeneous nutrition response.

Type 2 diabetes (T2D) is a global public health priority, particularly for populations of black African-Caribbean ethnicity, who suffer disproportionately high rates of the disease. While the mechanisms underlying the development of T2D are well documented, there is growing evidence describing distinctions among black African-Caribbean populations. In the present paper, we review the evidence describing the impact of black African-Caribbean ethnicity on T2D pathophysiology. Ethnic differences were first recognised through evidence that metabolic syndrome diagnostic criteria fail to detect T2D risk in black populations due to less central obesity and dyslipidaemia. Subsequently more detailed investigations have recognised other mechanistic differences, particularly lower visceral and hepatic fat accumulation and a distinctly hyperinsulinaemic response to glucose stimulation. While epidemiological studies have reported exaggerated insulin resistance in black populations, more detailed and direct measures of insulin sensitivity have provided evidence that insulin sensitivity is not markedly different to other ethnic groups and does not explain the hyperinsulinaemia that is exhibited. These findings lead us to hypothesise that ectopic fat does not play a pivotal role in driving insulin resistance in black populations. Furthermore, we hypothesise that hyperinsulinaemia is driven by lower rates of hepatic insulin clearance rather than heightened insulin resistance and is a primary defect rather than occurring in compensation for insulin resistance. These hypotheses are being investigated in our ongoing South London Diabetes and Ethnicity Phenotyping study, which will enable a more detailed understanding of ethnic distinctions in the pathophysiology of T2D between men of black African and white European ethnicity.

Several studies on gene–diet interactions (nutrigenetics) have been performed in western populations; however, there are only a few studies to date in lower middle-income countries (LMIC). A large-scale collaborative project called gene–nutrient interactions (GeNuIne) Collaboration, the main objective of which is to investigate the effect of GeNuIne on cardiometabolic traits using population-based studies from various ethnic groups, has been initiated at the University of Reading, UK. While South Asians with higher genetic risk score (GRS) showed a higher risk of obesity in response to a high-carbohydrate diet, South East and Western Asian populations with higher GRS showed an increased risk of central obesity in response to a high-protein diet. The paper also provides a summary of other gene–diet interaction analyses that were performed in LMIC as part of this collaborative project and gives an overview of how these nutrigenetic findings can be translated to personalised and public health approaches for the prevention of cardiometabolic diseases such as obesity, type 2 diabetes and CVD.

The metabolomic profile of a biofluid can be altered by dietary intake, exercise and disease processes and, thus provides an important tool for the study of many physiological processes. However, in addition to perturbation due to disease, the metabolomic profile of urine and plasma has also been shown to vary due to many intrinsic physiological factors such as age, sex, hormonal status and diurnal variation. Characterisation of this normal degree of variation in the metabolomic profiles of human biofluids is a necessary and important step in the development of metabolomics for use in nutrition-related research. The current review focuses on the impact of sex on the metabolomic profile. A number of studies have reported that sex impacts metabolites such as amino acids, lipids, sugars and keto acids. Furthermore, we examine the effect of the menstrual cycle on the metabolomic profile. Responses to dietary interventions can also differ between the sexes and highlighting this is important for the development of the field of precision nutrition.

CVD affect about one-third of the population and are the leading cause of mortality. The prevalence of CVD is closely linked to the prevalence of obesity because obesity is commonly associated with metabolic abnormalities that are important risk factors for CVD, including insulin resistance, pre-diabetes, and type-2 diabetes, atherosclerotic dyslipidaemia, endothelial dysfunction and hypertension. Women have a more beneficial traditional CVD risk profile (lower fasting plasma glucose, less atherogenic lipid profile) and a lower absolute risk for CVD than men. However, the relative risk for CVD associated with hyperglycaemia and dyslipidaemia is several-fold higher in women than in men. The reasons for the sex differences in CVD risk associated with metabolic abnormalities are unclear but could be related to differences in the mechanisms that cause hyperglycaemia and dyslipidaemia in men and women, which could influence the pathogenic processes involved in CVD. In the present paper, we review the influence of a person's sex on key aspects of metabolism involved in the cardiometabolic disease process, including insulin action on endogenous glucose production, tissue glucose disposal, and adipose tissue lipolysis, insulin secretion and insulin plasma clearance, postprandial glucose, fatty acid, and triglyceride kinetics, hepatic lipid metabolism and myocardial substrate use. We conclude that there are marked differences in many aspects of metabolism in men and women that are not all attributable to differences in the sex hormone milieu. The mechanisms responsible for these differences and the clinical implications of these observations are unclear and require further investigation.

α-Linolenic acid (ALA) is an n-3 fatty acid found in plant-derived foods such as linseeds and linseed oil. Mammals can convert this essential fatty acid into longer-chain fatty acids including EPA, docosapentaenoic acid (DPA) and DHA. Women demonstrate greater increases in the EPA status after ALA supplementation than men, and a growing body of animal model research identifies mechanisms by which sex hormones such as oestrogen and progesterone interact with the synthesis of EPA and DHA. Alternatively, EPA, DPA and DHA can be consumed directly, with oily fish being a rich dietary source of these nutrients. However, current National Diet and Nutrition Data reveals a median oily fish intake of 0 g daily across all age ranges and in both sexes. As longer-chain n-3 fatty acids have a crucial role in fetal and neonatal brain development, advice to consume dietary ALA could prove to be a pragmatic and acceptable alternative to advice to consume fish during pregnancy, if benefits upon tissue composition and functional outcomes can be demonstrated. Further research is required to understand the effects of increasing dietary ALA during pregnancy, and will need to simultaneously address conflicts with current dietary advice to only eat ‘small amounts’ of vegetable oils during pregnancy. Improving our understanding of sex-specific differences in fatty acid metabolism and interactions with pregnancy has the potential to inform both personalised nutrition advice and public health policy.

Food phytochemicals are increasingly considered to play a key role in the cardiometabolic health effects of plant foods. However, the heterogeneity in responsiveness to their intake frequently observed in clinical trials can hinder the beneficial effects of these compounds in specific subpopulations. A range of factors, including genetic background, gut microbiota, age, sex and health status, could be involved in these interindividual variations; however, the current knowledge is limited and fragmented. The European network, European Cooperation in Science and Technology (COST)-POSITIVe, has analysed, in a systematic way, existing knowledge with the aim to better understand the factors responsible for the interindividual variation in response to the consumption of the major families of plant food bioactives, regarding their bioavailability and bioefficacy. If differences in bioavailability, likely reflecting differences in human subjects’ genetics or in gut microbiota composition and functionality, are believed to underpin much of the interindividual variability, the key molecular determinants or microbial species remain to be identified. The systematic analysis of published studies conducted to assess the interindividual variation in biomarkers of cardiometabolic risk suggested some factors (such as adiposity and health status) as involved in between-subject variation. However, the contribution of these factors is not demonstrated consistently across the different compounds and biological outcomes and would deserve further investigations. The findings of the network clearly highlight that the human subjects’ intervention studies published so far are not adequate to investigate the relevant determinants of the absorption/metabolism and biological responsiveness. They also emphasise the need for a new generation of intervention studies designed to capture this interindividual variation.

Personalised nutrition allows individual differences in dietary, lifestyle, anthropometry, phenotype and/or genomic profile to be used to direct specific dietary advice. For personalised nutrition advice to be effective both sides need to be considered; firstly, that factors influencing variation in response to dietary intervention are identified and appropriate advice can be derived and secondly; that these are then used effectively in the provision of nutrition advice, resulting in a positive dietary and/or lifestyle behaviour change. There is considerable evidence demonstrating genetic and phenotypic influence on the biological response to the consumption of nutrients and bioactives. However, findings are often mixed, with studies often investigating at the level of a single nutrient/bioactive and/or a single genetic/phenotypic variation, meaning the derivation of specific advice at a dietary level in an individual/group of individuals can be complex. Similarly, the impact of using this information to derive personalised advice is also mixed, with some studies demonstrating no effectiveness and others showing a significant impact. The present paper will outline examples of phenotypic and genetic variation influencing response to nutritional interventions, and will consider how they could be used in the provision of personalised nutrition.