Vitamin D is both a nutrient and a neurologic hormone that plays a critical role in modulating immune responses. While low levels of vitamin D are associated with increased susceptibility to infections and immune-related disorders, vitamin D supplementation has demonstrated immunomodulatory effects that can be protective against various diseases and infections. Vitamin D receptor is expressed in immune cells that have the ability to synthesise the active vitamin D metabolite. Thus, vitamin D acts in an autocrine manner in a local immunologic milieu in fighting against infections. Nutrigenetics and nutrigenomics are the new disciplines of nutritional science that explore the interaction between nutrients and genes using distinct approaches to decipher the mechanisms by which nutrients can influence disease development. Though molecular and observational studies have proved the immunomodulatory effects of vitamin D, only very few studies have documented the molecular insights of vitamin D supplementation. Until recently, researchers have investigated only a few selected genes involved in the vitamin D metabolic pathway that may influence the response to vitamin D supplementation and possibly disease risk. This review summarises the impact of vitamin D supplementation on immune markers from nutrigenetics and nutrigenomics perspective based on evidence collected through a structured search using PubMed, EMBASE, Science Direct and Web of Science. The research gaps and shortcomings from the existing data and future research direction of vitamin D supplementation on various immune-related disorders are discussed.

Evidence shows that genetic polymorphisms in perilipin 1 gene (PLIN1) are associated with excessive accumulation of body fat and disturbances in cardiometabolic markers. Therefore, the aim of this study was to verify whether the SNP PLIN1 11482 G>A (rs894160) interacts with nutrient intake, anthropometric, body composition and cardiometabolic markers in adults with normal-weight obesity (NWO) syndrome. A cross-sectional study was carried out with 116 individuals aged 20–59 years, with normal BMI and high percentage of body fat. Anthropometric and body composition measures, glycaemic control and serum lipid markers, SNP PLIN1 11482 G>A and nutrient intake were evaluated. Interactions between nutrient intake and the SNP were determined by regression models and adjusted for potential confounders. The SNP frequency was 56·0 % GG, 38·8 % GA and 5·2 % AA. Anthropometric measures and biochemical markers were not different according to genotype, except for total cholesterol (TC), LDL-cholesterol and non-HDL-cholesterol concentrations. However, important interactions between the SNP and dietary intake were observed. Carbohydrate intake interacted with the SNP PLIN1 11482 G>A to modulate waist circumference (WC) and the homeostatic model assessment of insulin resistance index. Interaction of lipid intake and the SNP modulated TC and LDL-cholesterol concentrations, and the interaction between protein intake and the SNP tended to modulate weight, WC and BMI. The SNP PLIN1 11482 G>A seems to modulate responses in anthropometric and lipid profile biomarkers of subjects with NWO depending on the dietary macronutrient composition, which may have long-term impact on cardiometabolic markers.

Diets varying in SFA and MUFA content can impact glycaemic control; however, whether underlying differences in genetic make-up can influence blood glucose responses to these dietary fatty acids is unknown. We examined the impact of dietary oils varying in SFA/MUFA content on changes in blood glucose levels (primary outcome) and whether these changes were modified by variants in the stearoyl-CoA desaturase (SCD) gene (secondary outcome). Obese men and women participating in the randomised, crossover, isoenergetic, controlled-feeding Canola Oil Multicenter Intervention Trial II consumed three dietary oils for 6 weeks, with washout periods of ˜6 weeks between each treatment. Diets studied included a high SFA/low MUFA Control oil (36·6 % SFA/28·2 % MUFA), a conventional canola oil (6·2 % SFA/63·1 % MUFA) and a high-oleic acid canola oil (5·8 % SFA/74·7 % MUFA). No differences in fasting blood glucose were observed following the consumption of the dietary oils. However, when stratified by SCD genotypes, significant SNP-by-treatment interactions on blood glucose response were found with additive models for rs1502593 (P = 0·01), rs3071 (P = 0·02) and rs522951 (P = 0·03). The interaction for rs3071 remained significant (P = 0·005) when analysed with a recessive model, where individuals carrying the CC genotype showed an increase (0·14 (sem 0·09) mmol/l) in blood glucose levels with the Control oil diet, but reductions in blood glucose with both MUFA oil diets. Individuals carrying the AA and AC genotypes experienced reductions in blood glucose in response to all three oils. These findings identify a potential new target for personalised nutrition approaches aimed at improving glycaemic control.

Sustaining adequate nutritional needs of a population is a challenging task in normal times and a priority in times of crisis. There is no ‘one-size-fits-all’ solution that addresses nutrition. In relevance to the COVID-19 (coronavirus disease 2019) pandemic crisis, viral infections in general and RNA viruses in particular are known to induce and promote oxidative stress, consequently increasing the body’s demand for micronutrients, especially those related to antioxidant enzymic systems, thus draining the body of micronutrients, and so hindering the human body’s ability to cope optimally with oxidative stress. Common polymorphisms in major antioxidant enzymes, with world population minor allele frequencies ranging from 0·5 to 50 %, are related to altered enzymic function, with substantial potential effects on the body’s ability to cope with viral infection-induced oxidative stress. In this review we highlight common SNP of the major antioxidant enzymes relevant to nutritional components in the context of viral infections, namely: superoxide dismutases, glutathione peroxidases and catalase. We delineate functional polymorphisms in several human antioxidant enzymes that require, especially during a viral crisis, adequate and potentially additional nutritional support to cope with the pathological consequences of disease. Thus, in face of the COVID-19 pandemic, nutrition should be tightly monitored and possibly supplemented, with special attention to those carrying common polymorphisms in antioxidant enzymes.

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.

There is increasing evidence documenting gene-by-environment (G × E) interactions for CVD related traits. However, the underlying mechanisms are still unclear. DNA methylation may represent one of such potential mechanisms. The objective of this review paper is to summarise the current evidence supporting the interplay among DNA methylation, genetic variants, and environmental factors, specifically (1) the association between SNP and DNA methylation; (2) the role that DNA methylation plays in G × E interactions. The current evidence supports the notion that genotype-dependent methylation may account, in part, for the mechanisms underlying observed G × E interactions in loci such as APOE, IL6 and ATP-binding cassette A1. However, these findings should be validated using intervention studies with high level of scientific evidence. The ultimate goal is to apply the knowledge and the technology generated by this research towards genetically based strategies for the development of personalised nutrition and medicine.

The concept that interactions between nutrition and genetics determine phenotype was established by Garrod at the beginning of the 20th century through his ground-breaking work on inborn errors of metabolism. A century later, the science and technologies involved in sequencing of the human genome stimulated development of the scientific discipline which we now recognise as nutritional genomics (nutrigenomics). Much of the early hype around possible applications of this new science was unhelpful and raised expectations, which have not been realised as quickly as some would have hoped. However, major advances have been made in quantifying the contribution of genetic variation to a wide range of phenotypes and it is now clear that for nutrition-related phenotypes, such as obesity and common complex diseases, the genetic contribution made by SNP alone is often modest. There is much scope for innovative research to understand the roles of less well explored types of genomic structural variation, e.g. copy number variants, and of interactions between genotype and dietary factors, in phenotype determination. New tools and models, including stem cell-based approaches and genome editing, have huge potential to transform mechanistic nutrition research. Finally, the application of nutrigenomics research offers substantial potential to improve public health e.g. through the use of metabolomics approaches to identify novel biomarkers of food intake, which will lead to more objective and robust measures of dietary exposure. In addition, nutrigenomics may have applications in the development of personalised nutrition interventions, which may facilitate larger, more appropriate and sustained changes in eating (and other lifestyle) behaviours and help to reduce health inequalities.

This study examines if lactase non-persistent (LNP) children and adolescents differ from those who are lactase persistent (LP) as regards milk avoidance and Ca intake. We also studied potential differences in anthropometric features related to obesity, and examined if milk avoidance is associated with lactase-persistence status. Additionally, we aimed to determine if heterozygous subjects showed an intermediary phenotype as regards Ca intake. Furthermore, we tested if LP and LNP influence vitamin D intake. The European Youth Heart Study is an ongoing international, multi-centre cohort study primarily designed to address CVD risk factors. Children (n 298, mean age 9·6 years) and adolescents (n 386, mean age 15·6 years) belonging to the Swedish part of the European Youth Heart Study were genotyped for the LCT-13910 C > T polymorphism. Mendelian randomisation was used. Milk avoidance was significantly more common in LNP adolescents (OR 3·2; 95% CI 1·5, 7·3). LP subjects had higher milk consumption (P < 0·001). Accordingly, energy consumption derived from milk and Ca intake was lower in LNP (P < 0·05 and P < 0·001, respectively). Heterozygous subjects did not show an intermediary phenotype concerning milk consumption. LP or LNP status did not affect vitamin D intake or anthropometric variables. LNP in children and adolescents is associated with reduced intake of milk and some milk-product-related nutritional components, in particular Ca. This reduced intake did not affect the studied anthropometric variables, indicators of body fat or estimated vitamin D intake. However, independently of genotype, age and sex, daily vitamin D intake was below the recommended intakes. Milk avoidance among adolescents but not children was associated with LNP.

Direct-to-consumer (DTC) genetic tests have aroused controversy. Critics have argued many of the tests are not backed by scientific evidence, misguide their customers and should be regulated more stringently. Proponents suggest that finding out genetic susceptibilities for diseases could encourage healthier behaviours and makes the results of genetics research available to the public. This paper reviews the state of play in DTC genetic testing, focusing on tests identifying susceptibilities for lifestyle-related diseases. It will start with mapping the market for the tests. The paper will review (1) research on the content of the online marketing of DTC tests, (2) studies on the effects of DTC genetic tests on customers and (3) academic and policy proposals on how to regulate the tests. Current studies suggest that the marketing of DTC genetic tests often exaggerates their predictive powers, which could misguide consumers. However, research indicates that the tests do not seem to have major negative effects (worry and confusion) but neither do they engender positive effects (lifestyle change) on current users. Research on regulation of the tests has most commonly suggested regulating the marketing claims of the companies. In conclusion, the risks and benefits of DTC genetic tests are less significant than what has been predicted by critics and proponents, which will be argued reflects broader historical trends transforming health and medicine.

Ten years ago, it was assumed that disease risk prediction and personalised nutrition based on genetic information would now be in widespread use. However, this has not (yet) transpired. The interaction of genetic make-up, diet and health is far more complex and subtle than originally thought. With a few notable exceptions, the impact of identified common genetic variants on phenotype is relatively small and variable in their penetrance. Furthermore, the known variants account for only a fraction of what we believe to be the total genetic contribution to disease risk and heterogeneity in response to environmental change. Here, the question ‘how far have we progressed and are we likely to get there’ (Rimbach and Minihane, 2009) is revisited with regard to the translation of genetic knowledge into public health benefit. It is concluded that progress to date has been modest. It is hoped that recent technological developments allowing the detection of rarer variants and future use of more hypothesis-driven targeted data analysis will reveal most of the currently ‘hidden’ significant genetic variability.

The efficacy by which dietary interventions influence risk markers of multi-factorial diseases is mainly determined by taking population-based approaches. However, there exists considerable inter-individual variation in response to dietary interventions, and some interventions may benefit certain individuals or population subgroups more than others. This review evaluates the application of nutrigenomic technologies to further the concept of personalised nutrition, as well as the process to take personalised nutrition to the marketplace. The modulation of an individual's response is influenced by both genetic and environmental factors. Many nutrigenetics studies have attempted to explain variability in responses based on a single or a few genotypes so that a genotype may be used to define personalised dietary advice. It has, however, proven very challenging to define an individual's responsiveness to complex diets based on common genetic variations. In addition, there is a limited understanding of what constitutes an optimal response because we lack key health biomarkers and signatures. In conclusion, advances in nutrigenomics will undoubtedly further the understanding of the complex interplay between genotype, phenotype and environment, which are required to enhance the development of personalised nutrition in the future. At the same time, however, issues relating to consumer acceptance, privacy protection as well as marketing and distribution of personalised products need to be addressed before personalised nutrition can become commercially viable.

Nutritional genomics has undergone rapid development and the concept is now very popular with the general public. Therefore, there is increasing demand for knowledge on adapting dietary composition to the genome. Our aim has been to undertake a systematic review so as to find out the level of evidence existing on whether the effects of n-3 fatty acids on health can be modulated by genetic variation. A systematic literature search was conducted on studies that jointly analyse the effect of one or more genetic variants in candidate genes and n-3 fatty acids. Both observational and experimental studies were included. Results are classified in accordance with whether the study was undertaken on intermediate phenotypes (plasma lipid concentrations, glucose, inflammation markers, anthropometric measurements) or disease phenotypes (cancer, cardiovascular diseases, metabolic syndrome, etc) and whether it was experimental or observational. A wide diversity of genetic variants and little consistency in the publication of replication studies was found. Greater consistency was observed in studies that involved the FADS1 and FADS2 locus in the determination of n-3 fatty acid concentrations in biological samples. Most of the studies were designed to measure gene-diet interactions and not diet-gene interactions. Despite the fact that multiple studies have shown statistically significant interactions between n-3 fatty acids and certain genetic variants on intermediate and disease phenotypes, the individual level of evidence is very low and recommendations cannot be made on increasing or reducing the intake of n-3 fatty acids based on each individual's genotype.

The SNP rs1260326 (P446L) and rs1799884 ( − 30G>A) for the glucokinase regulatory protein (GCKR) and glucokinase (GCK) genes, respectively, have been associated with opposing effects on TAG and glucose concentrations. However, their genetic modulation by diet (dietary patterns or foods) remains to be investigated. We studied 945 high-cardiovascular risk subjects aged 67 (sd 6) years who participated in the PREvención con DIeta MEDiterránea-Valencia Study. Demographic, clinical, biochemical and genetic data were obtained. Adherence to the Mediterranean diet (MD) and food intake were measured by validated questionnaires. Carriers of the L allele of GKCR had significantly higher TAG concentrations (PP: 1·34 (sd 0·05) mmol/l v. PL+LL: 1·54 (sd 0·03) mmol/l; P= 0·014) and LL carriers had lower glucose concentrations (PL+PP: 6·85 (sd 0·08) mmol/l v. LL: 6·40 (sd 0·16) mmol/l; P= 0·032) after multivariate adjustment. Conversely, homozygous subjects for the variant allele (A) in the GCK gene had significantly lower TAG (GG+GA: 1·48 (sd 0·03) mmol/l v. AA: 1·17 (sd 0·18) mmol/l; P= 0·033) and a higher risk of diabetes (OR 3·3, 95 % CI 1·2, 9·2). Combined effects for both SNP increased TAG concentrations by 37 % (P= 0·033). Adherence to the MD modulated the effects of GCKR polymorphism on TAG: subjects with genetic risk had lower TAG (L-allele carriers; PP: 1·48 (sd 0·14) mmol/l v. PL+LL: 1·51 (sd 0·08) mmol/l; P= 0·917) compared with those with a higher adherence. Analysis of the joint effects of the GCKR and individual food items identified significant associations (olive oil (P= 0·035), vegetables (P= 0·012), red meat (P= 0·017), butter (P= 0·039), sweetened carbonated beverages (P= 0·036) and nuts (P= 0·038)). In conclusion, we found that rs1260326 (GCKR) is significantly associated with higher TAG concentrations, but is modulated by adherence to the MD.

Nutritional genomics has reached the public through applications of the Human Genome Project offered direct to consumers (DTC). The ability to pursue nutrigenetic testing without the involvement of a health care professional has received considerable attention from academic and policy commentators. To better understand the knowledge and attitudes of Canadian health care professionals regarding nutritional genomics and nutrigenetic testing, qualitative research in the form of focus group discussions was undertaken. Four key themes emerged: (1) concerns over DTC testing; (2) lack of health care professional competency; (3) genetic scepticism and inevitability; (4) expectation of regulation. Together, they indicate that health care professionals have little knowledge about nutritional genomics and hold contradictory attitudes towards genomics in general, and to nutritional genomics in particular. Respondents argue in favour of a delivery model where health care professionals act as intermediaries. They are also aware of their lack of competency to provide such services. To ensure greater public protection, respondents cite the importance of more stringent regulatory oversight of DTC genetic testing. Whether such an approach is necessary to address the various ethical and social issues raised by nutrigenetic testing remains an open debate.

Nutrigenetics and personalised nutrition are components of the concept that in the future genotyping will be used as a means of defining dietary recommendations to suit the individual. Over the last two decades there has been an explosion of research in this area, with often conflicting findings reported in the literature. Reviews of the literature in the area of apoE genotype and cardiovascular health, apoA5 genotype and postprandial lipaemia and perilipin and adiposity are used to demonstrate the complexities of genotype–phenotype associations and the aetiology of apparent between-study inconsistencies in the significance and size of effects. Furthermore, genetic research currently often takes a very reductionist approach, examining the interactions between individual genotypes and individual disease biomarkers and how they are modified by isolated dietary components or foods. Each individual possesses potentially hundreds of ‘at-risk’ gene variants and consumes a highly-complex diet. In order for nutrigenetics to become a useful public health tool, there is a great need to use mathematical and bioinformatic tools to develop strategies to examine the combined impact of multiple gene variants on a range of health outcomes and establish how these associations can be modified using combined dietary strategies.

CVD is a common killer in both the Western world and the developing world. It is a multifactorial disease that is influenced by many environmental and genetic factors. Although public health advice to date has been principally in the form of prescribed population-based recommendations, this approach has been surprisingly unsuccessful in reducing CVD risk. This outcome may be explained, in part, by the extreme variability in response to dietary manipulations between individuals and interactions between diet and an individual's genetic background, which are defined by the term ‘nutrigenetics’. The shift towards personalised nutritional advice is a very attractive proposition. In principle an individual could be genotyped and given dietary advice specifically tailored to their genetic make-up. Evidence-based research into interactions between fixed genetic variants, nutrient intake and biomarkers of CVD risk is increasing, but still limited. The present paper will review the evidence for interactions between dietary fat and three common polymorphisms in the apoE, apoAI and PPARγ genes. Increased knowledge of how these and other genes influence dietary response should increase the understanding of personalised nutrition. While targeted dietary advice may have considerable potential for reducing CVD risk, the ethical issues associated with its routine use need careful consideration.

Complex chemical processes termed non-enzymic glycation that operate in vivo and similar chemical interactions between sugars and proteins that occur during thermal processing of food (known as the Maillard reaction) are one of the interesting examples of a potentially-harmful interaction between nutrition and disease. Non-enzymic glycation comprises a series of reactions between sugars, α-oxoaldehydes and other sugar derivatives and amino groups of amino acids, peptides and proteins leading to the formation of heterogeneous moieties collectively termed advanced glycation end products (AGE). AGE possess a wide range of chemical and biological properties and play a role in diabetes-related pathology as well as in several other diseases. Diabetes is, nevertheless, of particular interest for several reasons: (1) chronic hyperglycaemia provides the substrates for extracellular glycation as well as intracellular glycation; (2) hyperglycaemia-induced oxidative stress accelerates AGE formation in the process of glycoxidation; (3) AGE-modified proteins are subject to rapid intracellular proteolytic degradation releasing free AGE adducts into the circulation where they can bind to several pro-inflammatory receptors, especially receptor of AGE; (4) kidneys, which are principally involved in the excretion of free AGE adducts, might be damaged by diabetic nephropathy, which further enhances AGE toxicity because of diminished AGE clearance. Increased dietary intake of AGE in highly-processed foods may represent an additional exogenous metabolic burden in addition to AGE already present endogenously in subjects with diabetes. Finally, inter-individual genetic and functional variability in genes encoding enzymes and receptors involved in either the formation or the degradation of AGE could have important pathogenic, nutrigenomic and nutrigenetic consequences.

The objective of the study was to determine whether Plasminogen Activator Inhibitor Type 1 (PAI-1) -675 4G/5G polymorphism is associated with the response of functional plasma PAI-1 concentrations to changes in the amount and quality of dietary fat in healthy subjects. PAI-1 is the major inhibitor of fibrinolysis, and a lower level of fibrinolytic activity could be implicated in an increased risk of IHD. Fifty-nine healthy Spanish volunteers (ten 4G/4G homozygotes, twenty-eight heterozygotes 4G/5G and twenty-one 5G/5G homozygotes) consumed three diets for periods of 4 weeks each: a SFA-rich diet (38 % fat, 20 % SFA), followed by a carbohydrate-rich diet (30 % fat, 55 % carbohydrate) and a MUFA-rich diet (38 % fat, 22 % MUFA) according to a randomized crossover design. At the end of each dietary period plasma lipid and functional plasma PAI-1 concentrations were determined. Subjects carrying the 4G allele (4G/4G and 4G/5G) showed a significant decrease in PAI-1 concentrations after the MUFA diet, compared with the SFA-rich and carbohydrate-rich diets (genotype ×  diet interaction: P = 0·028). 5G/5G homozygotes had the lowest plasma PAI-1 concentrations compared with 4G/4G and 4G/5G subjects (genotype: P = 0·002), without any changes as a result of the amount and the quality of the dietary fat. In summary, no differences in plasma PAI-1 concentration response were found after changes in dietary fat intake in 5G/5G homozygotes, although these subjects displayed the lowest concentrations of PAI-1. On the other hand, carriers of the 4G allele are more likely to hyper-respond to the presence of MUFA in the diet because of a greater decrease in PAI-1 concentrations.

Diet–gene interactions have become the focus of much research in recent years. However, little is known about UK dietitians' involvement, confidence and knowledge in genetics and diet–gene interactions. A validated postal questionnaire sent to a randomly selected sample of 600 dietitians in the UK resulted in 390 responses (65 %). Most dietitians had no involvement in eleven activities relating to genetics and diet–gene interactions and lacked confidence in undertaking such activities. However, a significant positive association was found between involvement and confidence for all activities tested (P < 0·0001). A mean knowledge score of 41 % (sd 19) indicated generally low levels of knowledge in genetics and diet–gene interactions. Knowledge scores were higher for those who reported discussing the genetic basis of disease or discussing how diet–gene interactions affected risk (P < 0·05). For the majority of activities, dietitians who reported higher confidence had higher knowledge scores. Given the importance of interactions between genetics and nutrition in preventing and managing disease, this study identifies a need to increase the involvement, confidence and knowledge in genetics and diet–gene interactions of dietitians in the UK.

Personalised, genotype-based nutrition is a concept that links genotyping with specific nutritional advice in order to improve the prevention of nutrition-associated, chronic diseases. This review describes the current scientific basis of the concept and discusses its problems. There is convincing evidence that variant genes may indeed determine the biological response to nutrients. The effects of single-gene variants on risk or risk factor levels of a complex disease are, however, usually small and sometimes inconsistent. Thus, information on the effects of combinations of relevant gene variants appears to be required in order to improve the predictive precision of the genetic information. Furthermore, very few associations between genotype and response have been tested for causality in human intervention studies, and little is known about potential adverse effects of a genotype-derived intervention. These issues need to be addressed before genotyping can become an acceptable method to guide nutritional recommendations.