A review on interplay between obesity, lipoprotein profile and nutrigenetics with selected candidate marker genes of type 2 diabetes mellitus.

BACKGROUND: Type 2 diabetes mellitus, a rapidly growing epidemic, and its frequently related complications demand global attention. The two factors commonly attributed to the epidemic are genetic factors and environmental factors. Studies indicate that the genetic makeup at an individual level and the environmental aspects influence the occurrence of the disease. However, there is insufficiency in understanding the mechanisms through which the gene mutations and environmental components individually lead to T2DM. Also, discrepancies have often been noted in the association of gene variants and type 2 diabetes when the gene factor is examined as a sole attribute to the disease. STUDY: In this review initially, we have focused on the proposed ways through which CAPN10, FABP2, GLUT2, TCF7L2, and ENPP1 variants lead to T2DM along with the inconsistencies observed in the gene-disease association. The article also emphasizes on obesity, lipoprotein profile, and nutrition as environmental factors and how they lead to T2DM. Finally, the main objective is explored, the environment-gene-disease association i.e. the influence of each environmental factor on the aforementioned specific gene-T2DM relationship to understand if the disease-causing capability of the gene variants is exacerbated by environmental influences. CONCLUSION: We found that environmental factors may influence the gene-disease relationship. Reciprocally, the genetic factors may alter the environment-disease relationship. To precisely conclude that the two factors act synergistically to lead to T2DM, more attention has to be paid to the combined influence of the genetic variants and environmental factors on T2DM occurrence instead of studying the influence of the factors separately.

Nutrient regulation of the flow of genetic information by O-GlcNAcylation.

O-linked-ß-N-acetylglucosamine (O-GlcNAc) is a post-translational modification (PTM) that is actively added to and removed from thousands of intracellular proteins. As a PTM, O-GlcNAcylation tunes the functions of a protein in various ways, such as enzymatic activity, transcriptional activity, subcellular localization, intermolecular interactions, and degradation. Its regulatory roles often interplay with the phosphorylation of the same protein. Governed by 'the Central Dogma', the flow of genetic information is central to all cellular activities. Many proteins regulating this flow are O-GlcNAc modified, and their functions are tuned by the cycling sugar. Herein, we review the regulatory roles of O-GlcNAcylation on the epigenome, in DNA replication and repair, in transcription and in RNA processing, in protein translation and in protein turnover.

Genetics of Cardiovascular Disease: How Far Are We from Personalized CVD Risk Prediction and Management?

Despite the rapid progress in diagnosis and treatment of cardiovascular disease (CVD), this disease remains a major cause of mortality and morbidity. Recent progress over the last two decades in the field of molecular genetics, especially with new tools such as genome-wide association studies, has helped to identify new genes and their variants, which can be used for calculations of risk, prediction of treatment efficacy, or detection of subjects prone to drug side effects. Although the use of genetic risk scores further improves CVD prediction, the significance is not unambiguous, and some subjects at risk remain undetected. Further research directions should focus on the "second level" of genetic information, namely, regulatory molecules (miRNAs) and epigenetic changes, predominantly DNA methylation and gene-environment interactions.

Role of Physical Exercise and Nutraceuticals in Modulating Molecular Pathways of Osteoarthritis.

Osteoarthritis (OA) is a painful and disabling disease that affects millions of patients. Its etiology is largely unknown, but it is most likely multifactorial. OA pathogenesis involves the catabolism of the cartilage extracellular matrix and is supported by inflammatory and oxidative signaling pathways and marked epigenetic changes. To delay OA progression, a wide range of exercise programs and naturally derived compounds have been suggested. This literature review aims to analyze the main signaling pathways and the evidence about the synergistic effects of these two interventions to counter OA. The converging nutrigenomic and physiogenomic intervention could slow down and reduce the complex pathological features of OA. This review provides a comprehensive picture of a possible signaling approach for targeting OA molecular pathways, initiation, and progression.

Role of Peroxisome Proliferator-Activated Receptors (PPARs) in Energy Homeostasis of Dairy Animals: Exploiting Their Modulation through Nutrigenomic Interventions.

Peroxisome proliferator-activated receptors (PPARs) are the nuclear receptors that could mediate the nutrient-dependent transcriptional activation and regulate metabolic networks through energy homeostasis. However, these receptors cannot work properly under metabolic stress. PPARs and their subtypes can be modulated by nutrigenomic interventions, particularly under stress conditions to restore cellular homeostasis. Many nutrients such as polyunsaturated fatty acids, vitamins, dietary amino acids and phytochemicals have shown their ability for potential activation or inhibition of PPARs. Thus, through different mechanisms, all these nutrients can modulate PPARs and are ultimately helpful to prevent various metabolic disorders, particularly in transition dairy cows. This review aims to provide insights into the crucial role of PPARs in energy metabolism and their potential modulation through nutrigenomic interventions to improve energy homeostasis in dairy animals.

A shifting mutational landscape in 6 nutritional states: Stress-induced mutagenesis as a series of distinct stress input-mutation output relationships.

Environmental stresses increase genetic variation in bacteria, plants, and human cancer cells. The linkage between various environments and mutational outcomes has not been systematically investigated, however. Here, we established the influence of nutritional stresses commonly found in the biosphere (carbon, phosphate, nitrogen, oxygen, or iron limitation) on both the rate and spectrum of mutations in Escherichia coli. We found that each limitation was associated with a remarkably distinct mutational profile. Overall mutation rates were not always elevated, and nitrogen, iron, and oxygen limitation resulted in major spectral changes but no net increase in rate. Our results thus suggest that stress-induced mutagenesis is a diverse series of stress input-mutation output linkages that is distinct in every condition. Environment-specific spectra resulted in the differential emergence of traits needing particular mutations in these settings. Mutations requiring transpositions were highest under iron and oxygen limitation, whereas base-pair substitutions and indels were highest under phosphate limitation. The unexpected diversity of input-output effects explains some important phenomena in the mutational biases of evolving genomes. The prevalence of bacterial insertion sequence transpositions in the mammalian gut or in anaerobically stored cultures is due to environmentally determined mutation availability. Likewise, the much-discussed genomic bias towards transition base substitutions in evolving genomes can now be explained as an environment-specific output. Altogether, our conclusion is that environments influence genetic variation as well as selection.

Alzheimer's Disease and Parkinson's Disease: A Nutritional Toxicology Perspective of the Impact of Oxidative Stress, Mitochondrial Dysfunction, Nutrigenomics and Environmental Chemicals.

Introduction: Alzheimer's disease is primarily a dementia-related disorder from progressive cognitive deterioration and memory impairment, while Parkinson's disease is primarily a movement disorder illness having movement disorder symptoms, bradykinesia (slowness of movements), hypokinesia (reduction of movement amplitude), and akinesia (absence of normal unconscious movements) along with muscle rigidity and tremor at rest. While aging is the main risk factor, epidemiological evidence suggests that the exposure to environmental toxicants, mainly pesticides, metals and solvents could increase the risk of developing neurodegenerative conditions.Oxidative stress in neurodegenerative diseases: Mitochondria function impacts cell respiratory processes, metabolism, energy production, intracellular signaling, free radical production, and apoptosis. In neurodegenerative diseases, mitochondrial dysfunction is associated with a compromised energy production, impaired calcium buffering, activation of proteases and phospholipases, and increased oxidative stress. Oxidative stress induced microglial cells activation, protein aggregation, neuroinflammation and mitochondrial dysfunction lead to neuronal deaths in these disorders.Role of nutrition: Neurodegenerative disease is not curable, but treatment is available to manage the symptoms and slow down the disease progression. The drugs for treating these diseases only reduce the cognitive impairment and behavioral problems, but do not stop the progression of neurodegeneration. Healthy diet, lifestyle improvement and nutraceuticals targeting of oxidative stress, inflammation, abnormal mitochondrial dynamics and the mitochondrial interaction with abnormal disease-related proteins and assessment of impact of environmental contaminants including occupational exposures to pesticides, can be a promising approach in the treatment of neurodegenerative diseases.Conclusion: These innovations can be benchmarked on firm understanding of nutrigenomics and the personalized management of individuals at risk.

Nutrition and Genetics in NAFLD: The Perfect Binomium.

Nonalcoholic fatty liver disease (NAFLD) represents a global healthcare burden since it is epidemiologically related to obesity, type 2 diabetes (T2D) and Metabolic Syndrome (MetS). It embraces a wide spectrum of hepatic injuries, which include simple steatosis, nonalcoholic steatohepatitis (NASH), fibrosis, cirrhosis and hepatocellular carcinoma (HCC). The susceptibility to develop NAFLD is highly variable and it is influenced by several cues including environmental (i.e., dietary habits and physical activity) and inherited (i.e., genetic/epigenetic) risk factors. Nonetheless, even intestinal microbiota and its by-products play a crucial role in NAFLD pathophysiology. The interaction of dietary exposure with the genome is referred to as 'nutritional genomics,' which encompasses both 'nutrigenetics' and 'nutriepigenomics.' It is focused on revealing the biological mechanisms that entail both the acute and persistent genome-nutrient interactions that influence health and it may represent a promising field of study to improve both clinical and health nutrition practices. Thus, the premise of this review is to discuss the relevance of personalized nutritional advices as a novel therapeutic approach in NAFLD tailored management.

Genetic bases of the nutritional approach to migraine.

Migraine is a common multifactorial and polygenic neurological disabling disorder characterized by a genetic background and associated to environmental, hormonal and food stimulations. A large series of evidence suggest a strong correlation between nutrition and migraine and indicates several commonly foods, food additives and beverages that may be involved in the mechanisms triggering the headache attack in migraine-susceptible persons. There are foods and drinks, or ingredients of the same, that can trigger the migraine crisis as well as some foods play a protective function depending on the specific genetic sensitivity of the subject. The recent biotechnological advances have enhanced the identification of some genetic factors involved in onset diseases and the identification of sequence variants of genes responsible for the individual sensitivity to migraine trigger-foods. Therefore many studies are aimed at the analysis of polymorphisms of genes coding for the enzymes involved in the metabolism of food factors in order to clarify the different ways in which people respond to foods based on their genetic constitution. This review discusses the latest knowledge and scientific evidence of the role of gene variants and nutrients, food additives and nutraceuticals interactions in migraine.

Personalized Nutrition: Are We There Yet?

The human genome has been proposed to contribute to interpersonal variability in the way we respond to nutritional intake. However, personalized diets solely based on gene-nutrient interactions have not lived up to their expectations to date. Advances in microbiome research have indicated that a science-based generation of a personalized diet based on a combination of clinical and microbial features may constitute a promising new approach enabling accurate prediction of dietary responses. In addition, scientific advances in our understanding of defined dietary components and their effects on human physiology led to the incorporation and testing of defined diets as preventive and treatment approaches for diseases, such as epilepsy, ulcerative colitis, Crohn disease, and type 1 diabetes mellitus. Additionally, exciting new studies show that tailored diet regiments have the potential to modulate pharmaceutical treatment efficacy in cancer treatment. Overall, the true therapeutic potential of nutritional interventions is coming to light but is also facing substantial challenges in understanding mechanisms of activity, optimization of dietary interventions for specific human subpopulations, and elucidation of adverse effects potentially stemming from some dietary components in a number of individuals.

Comparison of Nutrigenomics Technology Interface Tools for Consumers and Health Professionals: A Sequential Explanatory Mixed Methods Investigation.

BACKGROUND: Nutrigenomics forms the basis of personalized nutrition by customizing an individual's dietary plan based on the integration of life stage, current health status, and genome information. Some common genes that are included in nutrition-based multigene test panels include CYP1A2 (rate of caffeine break down), MTHFR (folate usage), NOS3 (risk of elevated triglyceride levels related to omega-3 fat intake), and ACE (blood pressure response in related to sodium intake). The complexity of gene test-based personalized nutrition presents barriers to its implementation. OBJECTIVE: This study aimed to compare a self-driven approach to gene test-based nutrition education versus an integrated practitioner-facilitated method to help develop improved interface tools for personalized nutrition practice. METHODS: A sequential, explanatory mixed methods investigation of 55 healthy adults (35 to 55 years) was conducted that included (1) a 9-week randomized controlled trial where participants were randomized to receive a standard nutrition-based gene test report (control; n=19) or a practitioner-facilitated personalized nutrition intervention (intervention; n=36) and (2) an interpretative thematic analysis of focus group interview data. Outcome measures included differences in the diet quality score (Healthy Eating Index-Canadian [HEI-C]; proportion [%] of calories from total fat, saturated fat, and sugar; omega 3 fatty acid intake [grams]; sodium intake [milligrams]); as well as health-related quality of life (HRQoL) scale score. RESULTS: Of the 55 (55/58 enrolled, 95%) participants who completed the study, most were aged between 40 and 51 years (n=37, 67%), were female (n=41, 75%), and earned a high household income (n=32, 58%). Compared with baseline measures, group differences were found for the percentage of calories from total fat (mean difference [MD]=-5.1%; Wilks lambda (λ)=0.817, F1,53=11.68; P=.001; eta-squared [η²]=0.183) and saturated fat (MD=-1.7%; λ=0.816; F1,53=11.71; P=.001; η²=0.18) as well as HRQoL scores (MD=8.1 points; λ=0.914; F1,53=4.92; P=.03; η²=0.086) compared with week 9 postintervention measures. Interactions of time-by-group assignment were found for sodium intakes (λ=0.846; F1,53=9.47; P=.003; η²=0.15) and HEI-C scores (λ=0.660; F1,53=27.43; P<.001; η²=0.35). An analysis of phenotypic and genotypic information by group assignment found improved total fat (MD=-5%; λ=0.815; F1,51=11.36; P=.001; η²=0.19) and saturated fat (MD=-1.3%; λ=0.822; F1,51=10.86; P=.002; η²=0.18) intakes. Time-by-group interactions were found for sodium (λ=0.844; F3,51=3.09; P=.04; η²=0.16); a post hoc analysis showed pre/post differences for those in the intervention group that did (preintervention mean 3611 mg, 95% CI 3039-4182; postintervention mean 2135 mg, 95% CI 1564-2705) and did not have the gene risk variant (preintervention mean 3722 mg, 95% CI 2949-4496; postintervention mean 2071 mg, 95% CI 1299-2843). Pre- and postdifferences related to the Dietary Reference Intakes showed increases in the proportion of intervention participants within the acceptable macronutrient distribution ranges for fat (pre/post mean difference=41.2%; P=.02). Analysis of textual data revealed 3 categories of feedback: (1) translation of nutrition-related gene test information to action; (2) facilitation of eating behavior change, particularly for the macronutrients and sodium; and (3) directives for future personalized nutrition practice. CONCLUSIONS: Although improvements were observed in both groups, healthy adults appear to derive more health benefits from practitioner-led personalized nutrition interventions. Further work is needed to better facilitate positive changes in micronutrient intakes. TRIAL REGISTRATION: ClinicalTrials.gov NCT03310814; http://clinicaltrials.gov/ct2/show/NCT03310814. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.2196/resprot.9846.

Prioritization of Variants for Investigation of Genotype-Directed Nutrition in Human Superpopulations.

Dietary guidelines recommended by key health agencies are generally designed for a global population. However, ethnicity affects human disease and environment-gene interactions, including nutrient intake. Historically, isolated human populations with different genetic backgrounds have adapted to distinct environments with varying food sources. Ethnicity is relevant to the interaction of food intake with genes and disease susceptibility; yet major health agencies generally do not recommend food and nutrients codified by population genotypes and their frequencies. In this paper, we have consolidated published nutrigenetic variants and examine their frequencies in human superpopulations to prioritize these variants for future investigation of population-specific genotype-directed nutrition. The nutrients consumed by individuals interact with their genome and may alter disease risk. Herein, we searched the literature, designed a data model, and manually curated hundreds of papers. The resulting database houses 101 variants that reached significance (p < 0.05), from 35 population studies. Nutrigenetic variants associated with modified nutrient intake have the potential to reduce the risk of colorectal cancer, obesity, metabolic syndrome, type 2 diabetes, and several other diseases. Since many nutrigenetic studies have identified a major variant in some populations, we suggest that superpopulation-specific genotype-directed nutrition modifications be prioritized for future study and evaluation. Genotype-directed nutrition approaches to dietary modification have the potential to reduce disease risk in select human populations.

Advances in Research on Diabetes by Human Nutriomics.

The incidence and prevalence of diabetes mellitus (DM) have increased rapidly worldwide over the last two decades. Because the pathogenic factors of DM are heterogeneous, determining clinically effective treatments for DM patients is difficult. Applying various nutrient analyses has yielded new insight and potential treatments for DM patients. In this review, we summarized the omics analysis methods, including nutrigenomics, nutritional-metabolomics, and foodomics. The list of the new targets of SNPs, genes, proteins, and gut microbiota associated with DM has been obtained by the analysis of nutrigenomics and microbiomics within last few years, which provides a reference for the diagnosis of DM. The use of nutrient metabolomics analysis can obtain new targets of amino acids, lipids, and metal elements, which provides a reference for the treatment of DM. Foodomics analysis can provide targeted dietary strategies for DM patients. This review summarizes the DM-associated molecular biomarkers in current applied omics analyses and may provide guidance for diagnosing and treating DM.

Role of Key Micronutrients from Nutrigenetic and Nutrigenomic Perspectives in Cancer Prevention.

Regarding cancer as a genetic multi-factorial disease, a number of aspects need to be investigated and analyzed in terms of cancer's predisposition, development and prognosis. One of these multi-dimensional factors, which has gained increased attention in the oncological field due to its unelucidated role in risk assessment for cancer, is diet. Moreover, as studies advance, a clearer connection between diet and the molecular alteration of patients is becoming identifiable and quantifiable, thereby replacing the old general view associating specific phenotypical changes with the differential intake of nutrients. Respectively, there are two major fields concentrated on the interrelation between genome and diet: nutrigenetics and nutrigenomics. Nutrigenetics studies the effects of nutrition at the gene level, whereas nutrigenomics studies the effect of nutrients on genome and transcriptome patterns. By precisely evaluating the interaction between the genomic profile of patients and their nutrient intake, it is possible to envision a concept of personalized medicine encompassing nutrition and health care. The list of nutrients that could have an inhibitory effect on cancer development is quite extensive, with evidence in the scientific literature. The administration of these nutrients showed significant results in vitro and in vivo regarding cancer inhibition, although more studies regarding administration in effective doses in actual patients need to be done.

Foodomics for human health: current status and perspectives.

INTRODUCTION: In the post-genomic era, the opportunity to combine and integrate cutting-edge analytical platforms and data processing systems allowed the birth of foodomics, 'a discipline that studies the Food and Nutrition domains through the application of advanced omics technologies to improve consumer's well-being, health, and confidence'. Since then, this discipline has rapidly evolved and researchers are now facing the daunting tasks to meet consumers' needs in terms of food traceability, sustainability, quality, safety and integrity. Most importantly, today it is imperative to provide solid evidence of the mechanisms through which food can promote human health and well-being. Areas covered: In this review, the complex relationships connecting food, nutrition and human health will be discussed, with emphasis on the relapses for the development of functional foods and nutraceuticals, personalized nutrition approaches, and the study of the interplay among gut microbiota, diet and health/diseases. Expert commentary: Evidence has been provided supporting the role of various omic platforms in studying the health-promoting effects of food and customized dietary interventions. However, although associated to major analytical challenges, only the proper integration of multi-omics studies and the implementation of bioinformatics tools and databases will help translate findings from clinical practice into effective personalized treatment strategies.

Quantifying the genetic parameters of feed efficiency in juvenile Nile tilapia Oreochromis niloticus.

BACKGROUND: Improving feed efficiency in fish is crucial at the economic, social and environmental levels with respect to developing a more sustainable aquaculture. The important contribution of genetic improvement to achieve this goal has been hampered by the lack of accurate basic information on the genetic parameters of feed efficiency in fish. We used video assessment of feed intake on individual fish reared in groups to estimate the genetic parameters of six growth traits, feed intake, feed conversion ratio (FCR) and residual feed intake in 40 pedigreed families of the GIFT strain of Nile tilapia, Oreochromis niloticus. Feed intake and growth were measured on juvenile fish (22.4 g mean body weight) during 13 consecutive meals, representing 7 days of measurements. We used these data to estimate the FCR response to different selection criteria to assess the potential of genetics as a means of increasing FCR in tilapia. RESULTS: Our results demonstrate genetic control for FCR in tilapia, with a heritability estimate of 0.32 ± 0.11. Response to selection estimates showed FCR could be efficiently improved by selective breeding. Due to low genetic correlations, selection for growth traits would not improve FCR. However, weight loss at fasting has a high genetic correlation with FCR (0.80 ± 0.25) and a moderate heritability (0.23), and could be an easy to measure and efficient criterion to improve FCR by selective breeding in tilapia. CONCLUSION: At this age, FCR is genetically determined in Nile tilapia. A selective breeding program could be possible and could help enabling the development of a more sustainable aquaculture production.

Effect of micronutrient malnutrition on periodontal disease and periodontal therapy.

Periodontitis is a complex chronic inflammatory noncommunicable disease, initiated by the development of a dysbiotic microbial plaque biofilm below the gingival margin. Whilst the pathogenic biofilm is a "necessary cause" of periodontitis, it is insufficient on its own to cause the disease, and a destructive immune-inflammatory response is a key to the translation of risk to destructive events. Other exposures or "component causes" include individual genetic predisposition, lifestyle (including smoking and nutrition), and environmental factors. Dietary nutrients are essential for life as they provide crucial energy sources in the form of macronutrients, as well as important cofactors in the form of micronutrients, which regulate the functionality of enzymes during the regulation of anabolic and catabolic processes in human cells. Moreover, micronutrients can regulate gene transcription factors, such as the proinflammatory nuclear factor kappa B and the anti-inflammatory nuclear factor (erythroid-derived 2)-like 2. This review focuses on the role of vitamins (vitamin A, carotenoids, the vitamin B complex, vitamins C, D, and E, and coenzyme Q10) and minerals (calcium, magnesium, iron, zinc, potassium, copper, manganese, and selenium) in human physiology and the impact of their deficiencies upon periodontal health and disease.

Iodine intake as a risk factor for BRAF mutations in papillary thyroid cancer patients from an iodine-replete area.

PURPOSE: Both deficient and excessive iodine intake leads to thyroid disease, which shows U-shaped curves. Our previous study showed that a relatively low [urinary iodine concentration (UIC) <300 µg/L] and extremely excessive (UIC ≥ 2500 µg/L) iodine intake were associated with thyroid cancer in Korea, an iodine-replete area. Papillary thyroid cancer (PTC) accounts for more than 97 % of thyroid cancer and 80% or more PTC cases harbor the BRAF mutation in Korea. We aimed to investigate the relationship between iodine intake and the prevalence of the BRAF mutation in PTC in Korea. METHODS: UIC was measured by inductively coupled plasma mass spectrometry. The BRAF mutation was detected using both allele-specific polymerase chain reaction and mutant enrichment with 3'-modified oligonucleotide sequencing. Risk factors for the occurrence of BRAF mutations in PTC were evaluated using multivariate logistic regression models. RESULTS: The median UIC in all patients with PTC was 287 µg/L (range from 7 to 7, 426 µg/L). Nearly half of the patients (102/215, 47%) belonged to the excessive iodine intake category (UIC ≥ 300 µg/L) according to the WHO iodine recommendations. The frequency of BRAF mutations was lowest in the 300-499 µg/L UIC group; it was significantly different compared to the relatively low (UIC < 300 µg/L) and more than excessive (UIC ≥ 500 µg/L) iodine intake groups. UIC was an independent predictor for BRAF mutations in PTC. The multivariate-adjusted odds ratios (95% confidence intervals) in the relatively low and more than excessive iodine intake groups for the BRAF mutation were 4.761 (1.764-12.850) and 6.240 (2.080-18.726), respectively, compared to the 300-499 µg/L UIC group. CONCLUSION: Relatively low iodine intake and more than excessive iodine intake seem to be significant risk factors for the occurrence of BRAF mutations in the thyroid and, therefore, may be risk factors for the development of PTC in an iodine-replete area.

Nutrigenomics: Opportunities & challenges for public health nutrition.

The hierarchical information flow through DNA-RNA-protein-metabolite collectively referred to as 'molecular fingerprint' defines both health and disease. Environment and food (quality and quantity) are the key factors known to affect the health of an individual. The fundamental concepts are that the transition from a healthy condition to a disease phenotype must occur by concurrent alterations in the genome expression or by differences in protein synthesis, function and metabolites. In other words, the dietary components directly or indirectly modulate the molecular fingerprint and understanding of which is dealt with nutrigenomics. Although the fundamental principles of nutrigenomics remain similar to that of traditional research, a collection of comprehensive targeted/untargeted data sets in the context of nutrition offers the unique advantage of understanding complex metabolic networks to provide a mechanistic understanding of data from epidemiological and intervention studies. In this review the challenges and opportunities of nutrigenomic tools in addressing the nutritional problems of public health importance are discussed. The application of nutrigenomic tools provided numerous leads on biomarkers of nutrient intake, undernutrition, metabolic syndrome and its complications. Importantly, nutrigenomic studies also led to the discovery of the association of multiple genetic polymorphisms in relation to the variability of micronutrient absorption and metabolism, providing a potential opportunity for further research toward setting personalized dietary recommendations for individuals and population subgroups.

Diet, Nutrition, and Cancer Epigenetics.

The search for a connection between diet and human cancer has a long history in cancer research, as has interest in the mechanisms by which dietary factors might increase or decrease cancer risk. The realization that altering diet can alter the epigenetic state of genes and that these epigenetic alterations might increase or decrease cancer risk is a more modern notion, driven largely by studies in animal models. The connections between diet and epigenetic alterations, on the one hand, and between epigenetic alterations and cancer, on the other, are supported by both observational studies in humans as well as animal models. However, the conclusion that diet is linked directly to epigenetic alterations and that these epigenetic alterations directly increase or decrease the risk of human cancer is much less certain. We suggest that true and measurable effects of diet or dietary supplements on epigenotype and cancer risk are most likely to be observed in longitudinal studies and at the extremes of the intersection of dietary risk factors and human population variability. Careful analysis of such outlier populations is most likely to shed light on the molecular mechanisms by which suspected environmental risk factors drive the process of carcinogenesis.