Nutrigenomics

The increase in the average lifespan and the consequent proportional growth of the elderly segment of society has furthered the interest in studying ageing processes. Ageing may be considered a multifactorial process derived from the interaction between genetic and environmental factors including lifestyle. There is ample evidence in many species that the maximum age attainable (maximum lifespan potential, MLSP) is genetically determined and several mitochondrial DNA polymorphisms are associated with longevity. Many studies have shown that most of the phenotypic characteristics observed in the aging process are the result of the occurrence, with age, of a low grade chronic pro-inflammatory status called "inflammaging", partially under genetic control. The term indicate that aging is accompanied by a low degree of chronic inflammatory, an up-regulation of inflammatory response and that inflammatory changes are common to many age-related diseases. Therefore, the theory of ox...

The PREDIMED (Prevención con Dieta Mediterránea) study was designed to assess the long-term effects of the Mediterranean diet (MeDiet) without any energy restriction on incident cardiovascular disease (CVD) as a multicenter, randomized, primary prevention trial in individuals at high risk. Participants were randomly assigned to 3 diet groups: 1) MeDiet supplemented with extra-virgin olive oil (EVOO); 2) MeDiet supplemented with nuts; and 3) control diet (advice on a low-fat diet). After 4.8 y, 288 major CVD events occurred in 7447 participants; crude hazard ratios were 0.70 (95% CI: 0.53, 0.91) for the MeDiet + EVOO and 0.70 (95% CI: 0.53, 0.94) for the MeDiet + nuts compared with the control group. Respective hazard ratios for incident diabetes (273 cases) among 3541 participants without diabetes were 0.60 (95% CI: 0.43, 0.85) and 0.82 (95% CI: 0.61, 1.10) compared with the control group. After 1-y follow-up, participants in the MeDiet + nuts group showed a significant 13.7% reduct...

The maintenance of health and the prevention and treatment of chronic diseases are influenced by naturally occurring chemicals in foods. In addition to supplying the substrates for producing energy, a large number of dietary chemicals are bioactive – that is, they alter the regulation of biological processes and, either directly or indirectly, the expression of genetic information. Nutrients and bioactives may produce different physiological phenotypes among individuals because of genetic variability and not only alter health, but also disease initiation, progression and severity. The study and application of gene–nutrient interactions is called nutritional genomics or nutrigenomics. Nutrigenomic concepts, research strategies and clinical implementation are similar to and overlap those of pharmacogenomics, and both are fundamental to the treatment of disease and maintenance of optimal health.

Alzheimer's disease (AD) is the major cause of dementia and no preventive or effective treatment has been established to date. The etiology of AD is poorly understood, but genetic and environmental factors seem to play a role in its onset and progression. In particular, factors affecting the one-carbon metabolism (OCM) are thought to be important and elevated homocysteine (Hcy) levels, indicating impaired OCM, have been associated with AD. We aimed at evaluating the role of polymorphisms of key OCM enzymes in the etiology of AD, particularly when intakes of relevant B-vitamins are inadequate. Our review indicates that a range of compensatory mechanisms exist to maintain a metabolic balance. However, these become overwhelmed if the activity of more than one enzyme is reduced due to genetic factors or insufficient folate, riboflavin, vitamin B6 and/or vitamin B12 levels. Consequences include increased Hcy levels and reduced capacity to synthetize, methylate and repair DNA, and/or ...

A B S T R A C T Ruminants have a very special niche in the animal kingdom, and are the most important livestock species providing milk, meat, and wool for humans from consumption of highly-fibrous feedstuffs. Cattle, goat and sheep have been widely-used for years as models to study ruminal fermentation and the mechanisms whereby tissues utilize nutrients for milk synthesis, growth, wool accretion, and reproduction. The advent of high-throughput technologies to study an animal's genome, proteome, and metabolome (i.e., " omics " tools) offered ruminant scientists the opportunity to study multiple levels of biological information to better understand the whole animal response to nutrition, environment, physiological state, and their interactions. The omics revolution gave rise to the field of nutrigenomics, i.e. the study of the genome-wide influences of nutrition through alteration in mRNA, protein, and metabolite expression or abundance. This field of research is relatively new in ruminants, and particularly sheep and goats. Dietary compounds affect gene expression directly or indirectly via interactions with transcription factors including ligand-dependent nuclear receptors. New knowledge generated through the application of functional analyses of transcriptomic, proteomic, and metabolomic data sets in goat and sheep is discussed.

The modern food system feeds six billion people with remarkable diversity, safety, and nutrition. Yet, the current rise in diet-related diseases is compromising health and devaluing many aspects of modern agriculture. Steps to increase the nutritional quality of individual foods will assist in personalizing health and in guiding individuals to achieve superior health. Nutrigenomics is the scientific field of the genetic basis for varying susceptibilities to disease and the diverse responses to foods. Although some of these genetic determinants will be simple and amenable to personal genotyping as the means to predict health, in practice most will not. As a result, genotyping will not be the secret to personalizing diet and health. Human assessment technologies from imaging to proteomics and metabolomics are providing tools to both understand and accurately assess the nutritional phenotype of individuals. The business models are also emerging to bring these assessment capabilities to...

Evolutionary medicine has gained increasing attention in recent years by implying that a food selection similar to that of the Paleolithic may prevent diseases. This article is an attempt to characterize the food selection during hominid evolution based on current paleontologic research. Hominid evolution can be divided into multiple phases; and the nutrition ecology of the plio-pleistocene hominids can be tentatively characterized. According to new results of isotope analysis, the Australopithecines did ingest small amounts of animal food already 4.5–2.5 million years ago, while consuming a mainly plant based abrasive diet, which was similar to that of recent chimpanzees. Compared to the Australopithecines, the first representatives of Homo such as H. erectus and H. habilis (2.5–1.5 million years before today) were likely to consume a diet providing more energy and nutrients, which might also have been related to the more gracile dentition. Like H. sapiens the members of this species also consumed an omnivore diet. Assumptions about the nutrition ecology of the archaic and the modern H. sapiens are often concluded by analogies based on the living of historic and recent foragers (hunter-gatherers). As the few detailed ethnographic data show, the diet composition of the individual hunter-gatherer groups varied considerably and ranged from a nearly pure animal-based diet to a diet dominated by plants. All in all the eating behaviour of prehistoric humans was, like that of their pleistocene ancestors, very flexible. Except for focussing on an energy and nutrient-rich diet there was neither specialization in certain foods, nor a typical plant-animal ratio nor a defined macronutrient distribution. Correspondingly, it is impossible to justify details given by representatives of evolutionary medicine on "the Paleolithic diet" empirically. Die These, wonach eine an der Nahrungsauswahl des Paläolithikums orientierte Ernährungsweise von präventivmedizinischer Relevanz sein soll, ist in den letzten Jahren auf wachsendes Interesse gestoßen. Vor diesem Hintergrund stellt dieser Beitrag den Versuch dar, die Nahrungsauswahl im Verlauf der Hominisation auf Basis der aktuellen paläontologischen Forschungsergebnisse zu rekonstruieren. Bei der Hominisation lassen sich mehrere Stadien differenzieren und die Ernährungsökologie der plio-pleistozänen Homininen versuchsweise charakterisieren. Neueren Isotopen-Auswertungen zufolge sollen die Australopithecinen im Zeitraum von vor 4,5–2,5 Mio. Jahren bereits geringe Mengen tierischer Nahrung aufgenommen, jedoch eine vorwiegend harte, abrasive pflanzliche Kost konsumiert haben, die der rezenter Schimpansen ähnelte. Im Vergleich zu den Australopithecinen dürften die ersten Vertreter von Homo wie H. erectus und H. habilis (2,5–1,5 Mio Jahre vor heute) eine energetisch gehaltvollere, nährstoffkonzentriertere Kost verzehrt haben, was auch mit der Grazilisierung des Gebisses in Verbindung steht. Wie H. sapiens sollen die Mitglieder dieser Spezies eine omnivore Ernährungsstrategie verfolgt haben. Aussagen zur Ernährungsökologie des archaischen und des modernen H. sapiens gründen vielfach auf Analogieschlüssen zur Lebensweise historischer und rezenter Wildbeuter (Jäger und Sammler). Wie die wenigen detaillierten ethnographischen Daten zeigen, variiert die Zusammensetzung der Kost bei den einzelnen Jägern und Sammlern erheblich und reicht von einer fast rein animalischen bis hin zu einer vorwiegend auf pflanzlichen Ressourcen basierenden Nahrung. Insgesamt stellt sich das Ernährungsverhalten des prähistorischen Menschen wie das seiner pleistozänen Vorfahren als sehr flexibel dar. Mit Ausnahme der Fokussierung auf eine energetisch hochwertige, nährstoffreiche Kost lässt sich keine Spezialisierung auf bestimmte Lebensmittel, ein charakteristisches Pflanzen-Tier-Verhältnis oder eine definierte Makronährstoffverteilung erkennen. Entsprechend ist keine empirisch begründete Aussage dazu möglich, wie die vielfach als "artgerecht" propagierte "Steinzeiternährung" im Detail beschaffen war.

Inflammatory bowel disease (IBD) encompassed several chronic inflammatory disorders leading to damage of the gastrointestinal tract (GI). The 2 principal forms of these disorders are ulcerative colitis (UC) and Crohn disease (CD). Bacteria are involved in the etiology of IBD, and the genetic susceptibility, environmental factors, and lifestyle factors can affect the individual's predisposition to IBD. The review discusses the potential role of environmental factors such as diet and microbiota as well as genetics in the etiology of IBD. It is suggested that microbial ecosystem in the human bowel colonizing the gut in many different microhabitats can be influence by diet, leading to formation of metabolic processes that are essential form the bowel metabolism.

Nutrigenomics is an area of epigenomics that explores and defines the rapidly evolving field of diet-genome interactions.
Lifestyle and diet can significantly influence epigeneticmechanisms,which cause heritable changes in
gene expression without changes in DNA sequence. Nutrient-dependent epigenetic variations can significantly
affect genome stability, mRNA and protein expression, and metabolic changes, which in turn influence food absorption
and the activity of its constituents. Dietary bioactive compounds can affect epigenetic alterations,which
are accumulated over time and are shown to be involved in the pathogenesis of age-related diseases such as diabetes,
cancer, and cardiovascular disease. Histone acetylation is an epigeneticmodification mediated by histone
acetyl transferases (HATs) and histone deacetylases (HDACs) critically involved in regulating affinity binding between
the histones and DNA backbone. The HDAC-mediated increase in histone affinity to DNA causes DNA condensation,
preventing transcription, whereas HAT-acetylated chromatin is transcriptionally active. HDAC and
HAT activities are reported to be associated with signal transduction, cell growth and death, as well as with the
pathogenesis of various diseases. The aim of this review was to evaluate the role of diet and dietary bioactive
compounds on the regulation of HATs and HDACs in epigenetic diseases. Dietary bioactive compounds such as
genistein, phenylisothiocyanate, curcumin, resveratrol, indole-3-carbinol, and epigallocatechin-3-gallate can
regulate HDAC and HAT activities and acetylation of histones and non-histone chromatin proteins, and their
health benefits are thought to be attributed to these epigenetic mechanisms. The intake of dietary compounds
that regulate epigenetic modifications can provide significant health effects and may prevent various pathological
processes involved in the development of cancer and other life-threatening diseases.

Orange juice (OJ) is among the most consumed fruit juices worldwide, and its chemopreventive action is fairly addressed in the literature. This review critically presents the available evidence linking OJ with cancer chemoprevention and on discussing the putative mechanisms and negative health effects. The chemopreventive action of OJ is related to its effect on metabolic enzymes and its antiinflammatory, cytoprotective/apoptotic, hormonal, cell signaling-modulating, antioxidant, and antigenotoxic effects. Most studies on OJ are in vitro, and few are conducted in vivo. Results from in vitro studies must be interpreted carefully because these findings do not consider in vivo bioavailability. However, such results are useful for studying the impact of different processing and storage methods on OJ's chemopreventive effect. Evidence of OJ's chemoprevention in humans is limited. OJ is antimutagenic in bacteria and antigenotoxic in humans and rodents. Studies using rodent cancer models showed that OJ is cancer chemopreventive, influencing either the induction stage or the promotion stage. The composition and, therefore, the chemopreventive action of OJ might be influenced by different cultivars, climates, extraction methods, packaging, storage temperatures, and shelf lives, among other factors. Epidemiological studies and randomized controlled intervention studies in humans evaluating the chemopreventive effect of OJ, taking into consideration variability in OJ composition, are needed.

Lycopene is the predominant and bioactive carotenoid present in the tomato (Solanum lycopersicum), a widely appreciated healthful vegetable. In vivo, in vitro and clinical studies conducted in recent years have revealed an inverse association between the dietary intakes of lycopene with the risk of prostate cancer (PCa). Lycopene has been proposed to protect against PCa by the reduction of lipid oxidation, inhibition of cancer cell proliferation , and its antioxidative properties. Attention has been paid towards the interactive impact of lycopene and its genetic predisposition with the prostate carcinogenesis. In particular, lycopene is believed to play a key role in regulating the gene expressions and modulating the development of PCa. This paper presents a state of art review of the lycopene × gene interaction for the protective treatment of PCa. The key pathway for deoxyribonucleic acid (DNA) repair, insulin-like growth factor (IGF), cell cycle, androgen receptor, steroid signaling, inflammation and inflammatory cytokines, gap junction communications, carotenoid cleavage enzymes , and endogenous antioxidant enzymes are concisely elucidated. Furthermore, the evidence underlying its potent impacts on the integrin, nitric oxide synthase (NOS), prostate specific antigen (PSA) and urokinase plasminogen activator receptor (uPAR) expressions is outlined.

There is definitive evidence that iron overload induces oxidative stress and DNA damage, which can enhance carcinogenic risk. However, other evidence suggests that iron deficiency and anemia also increase oxidative stress and DNA damage, which might increase carcinogenesis risk, especially in the gastrointestinal (GI) tract. The aim of this review is to provide essential background information for the accurate interpretation of future research on iron deficiency and increased GI cancer risk. Based on clinical, epidemiological, and experimental evidence, we discuss how iron deficiency might contribute to increased cancer risk through the impairment of several iron-dependent metabolic functions that are related to genome protection and maintenance (e.g., immune responses against cancer-initiated cells, metabolism of toxic compounds, and redox regulation of DNA biosynthesis and repair). Some epidemiological studies have indicated increased risk of GI tumors among individuals with low iron intake or low somatic iron stores, and in vivo data from rodent cancer models indicates the early progression of GI tumors during iron deficiency. Given the preliminary but consistent evidence relating iron deficiency to cancer risk

The predictive ability of metabolic profiling to detect obesity-induced perturbations in metabolism has not been clearly established. Complex aetiologies interacting with environmental factors highlight the need to understand how specific manipulations alter metabolite profiles in this state. The aim of this study was to determine if targeted metabolomic profiling could be employed as a reliable tool to detect dietary-induced insulin resistance in a small subset of experimental animals (n = 10/treatment). Following weaning, male C57BL/6J littermates were randomly divided into two dietary groups: chow and high fat. Following 12 weeks of dietary manipulation, mice were fasted for 5 h prior to serum collection. The resultant high fat–fed animals were obese and insulin resistant as shown by a euglycaemic-hyperinsulinaemic clamp. Sera were analysed by proton nuclear magnetic resonance spectroscopy, and 46 known compounds were identified and quantified. Multivariate analysis by orthogonal partial least squares discriminant analysis, a projection method for class separation, was then used to establish models of each treatment. Models were able to predict class separation between diets with 90% accuracy. Variable importance plots revealed the most important metabolites in this discrimination to include lysine, glycine, citrate, leucine, suberate and acetate. These metabolites are involved in energy metabolism and may be representative of the perturbations taking place with insulin resistance. Results show metabolomics to reliably describe the metabolic effects of insulin resistance in a small subset of samples and are an initial step in establishing metabolomics as a tool to understand the biochemical signature of insulin resistance.

Mediterranean Diet (MedDiet) adherence has been proven to produce numerous health benefits. In addition, nutrigenetic studies have explained some individual variations in the response to specific dietary patterns. The present research aimed to explore associations and potential interactions between MedDiet adherence and genetic background throughout the Food4Me web-based nutritional intervention. Dietary, anthropometrical and biochemical data from volunteers of the Food4Me study were collected at baseline and after 6 months. Several genetic variants related to metabolic risk features were also analysed. A Genetic Risk Score (GRS) was derived from risk alleles and a Mediterranean Diet Score (MDS), based on validated food intake data, was estimated. At baseline, there were no interactions between GRS and MDS categories for metabolic traits. Linear mixed model repeated measures analyses showed a significantly greater decrease in total cholesterol in participants with a low GRS after a ...