The Benefits Of Nutrigenomics

Published Date: 02 Nov 2017

20.1 INTRODUCTION

20.1.1 Definitions and terms

Genomics: The study of the genomes of organisms for determining the entire DNA sequence of organisms and fine-scale genetic mapping (Balammal, G., 2012) while the genome is the set of all genes, regulatory sequences, and other information contained within the noncoding regions of DNA of an organism (Frederick, P. Roth et al., 1998).

Nutritional genomics: The science of relationship between human genome, nutrition and health (Ordovas, J.M., 2004) or the genetic manipulation of plants to create vitamins and minerals that will improve human's diet and analysis of an organism's set of genes, so it is an area of science that looks at how environmental factors, such as diet, influence the genetic make-up (Ordovas, J.M., 2004).

Nutrigenetics: It is the interplay between nutrition and genetics of an individual, branch of science concerned with the effect of heredity on diet and nutrition (Simopoulos, A.P., 2010). The term Nutrigenetics refers to the research on the impact of changes in inherited traits of nuclear DNA, on the response to specific metabolic dysfunctions outcomes getting health chronic damages and disorders (Manzelli, Paolo, 2012, Simopoulos, A.P., 2010). According to WHO reports diet factors influence occurrence of more than two third of diseases and most of these factors belong to the categories of nutrigenetics. In other words, nutrigenetics concerns individual differences in the reaction to food based on the genetic factors and analyses direct influences of nutrients on gene expression (Svacina, S., 2007).

Proteomics: the study of structures and functions of protein and makes an analogy with genomics so, it is the study of the genes while proteome is the entire complement of proteins, including the modifications made to a particular set of proteins produced by an organism or system and the word proteome was coined by Marc Wilkins in 1994 by the blend of protein and genome (James, P., 1997, Marc, R. Wilkins et al., 1996).

Metabolomics: The systematic study of the unique chemical fingerprints that specific cellular processes leave behind with study of their small-molecule metabolite profiles and increasingly being used in a variety of health applications including pharmacology, pre-clinical drug trials, toxicology, transplant monitoring, newborn screening and clinical chemistry (Nanda T., 2011) while the metabolome is the collection of all metabolites in a biological cell, tissue, organ or organism, end products of cellular processes (Daviss, Bennett, 2005).

Gene expression: The process by which information from a gene is used in the synthesis of a functional gene product like proteins, but in non-protein coding genes such as ribosomal RNA (rRNA), transfer RNA (tRNA) or small nuclear RNA (snRNA) genes, the product is a functional RNA and this process is used by every living things like eukaryotes, prokaryotes and viruses, to generate the macromoleculs for their body. This process occurs in two major stages, first is transcription in which the gene is copied to produce an RNA molecule with essentially the same sequence as the gene and second, is protein synthesis known as translation (Oliver Brandenberg et al., 2011, Twyman, Richard, 2003).

Genotype: This is the genetic makeup of a cell, an organism, or an individual with reference to a specific character which is the internally coded, inheritable information, carried by all living organisms and this stored information is used as a blueprint or set of instructions for building and maintaining a living creature (Oliver Brandenberg et al., 2011).

Phenotype: The composite of an organism's observable characteristics or traits such as its morphology, development, biochemical or physiological properties, phenology, behavior, and products of behavior like physical parts, the sum of the atoms, molecules, macromolecules, cells, structures, metabolism, energy utilization, tissues, organs, reflexes and behaviors of a living organism (Oliver Brandenberg et al., 2011).

Polymorphism: Polymorphism in biology occurs when two or more clearly different phenotypes exist in the same population of a species, the occurrence of more than one form or morph. (Oliver Brandenberg et al., 2011).

Allele: An allele is one of two or more forms of a gene or a genetic locus used for an abbreviation of allelomorph and different alleles can result in different observable phenotypic traits, such as different pigmentation. (Oliver Brandenberg et al., 2011).

Epigenetic: A modification of gene expression that is independent of the DNA sequence of the gene (Egger, G., Liang G., et al., 2004). The current definition of epigenetics is the study of heritable changes in gene expression that occur independent of changes in the primary DNA sequence and these heritable changes are established during differentiation and are stably maintained through multiple cycles of cell division, enabling cells to have distinct identities while containing the same genetic information. This heritability of gene expression patterns is mediated by epigenetic modifications, which include methylation of cytosine bases in DNA, posttranslational modifications of histone proteins as well as the positioning of nucleosomes along the DNA (Sharma, Shikhar, 2010).

20.1.2 Nutrigenomics: Let food be thy medicine and medicine thy food (Hippocrates 400 B.C.)

Nutrigenomics is the study of how naturally occurring chemicals in foods alter molecular expression of genetic information in each individual. The term nutrigenomics refers the effect of diet on gene expression or to the impact of inherited on the response to a specific dietary pattern, functional food or supplement on a specific health outcome (Fenech, M., 2005) so called as the "next frontier in the post genomic era" (Castle, D. 2007). It can be described as the study of the relationship between genes, diet lifestyle and health that is nutrition regulate gene function like transcription, translation and metabolism i.e. diet gene interaction (Ordovas, J.M., 2004).

Nutrigenomics focuses on understanding that nutrition influences metabolism and maintenance of the internal equilibrium in the body and this regulation affects the diet related diseases (Ordovas J.M., 2004) and offers a powerful and exiting approach to unravel the effect of diet on health. In the past the nutrition research concentrated on nutrient deficiency and impairment of health but nutrigenomics creates a junction between health diet and genomics and it will promotes an increased understanding of how nutrition influences metabolic pathway and homeostasis control.

Biomedical researcher, private sector firm, public (Caulfield, T., 2008) and food industry recognizes the need for nutrigenomics research as a basis for developing the concept of "personalized diet" for identifying molecular biomarkers. Over the past few years, there has been rapid increase in the interest in nutrigenomics as a research topic because it is an area that has been viewed as worthy public funding, both as a topic of basic scientific inquiry and as a field with health care and commercialization possibilities (Ordovas, J. M., 2004). The new scientific understanding of nutrigenomics has led to the increase of commercial development of nutraceutical and functional foods that can be modify negative health effect of individual genetic profiles (Francesco, Marotta et al., 2012).

The main aim of the nutrigenomics is that to improve dilatory advice, development of health promoting supplements, preventive strategies and the reduction of healthcare cost (Ordovas, J.M., 2004). The coming years will likely require patience, realistic expectations and strong advocacy for the needed research funding and a major focus of nutrition research is on prevention of chronic disease such as cardiovascular disease, metabolic disorder and cancer (Afman, L. et al., 2006).

More than simply managing or treating disease or the symptoms associated with disease, the nutrigenomics will be used to identify susceptibilities to disease and implement proactive measures to help individuals avoid contracting said disease in the first place and we can say that nutrigenomics research will lead to development of evidence based healthful food and lifestyle advice and dietary intervention for contemporary humans (Ordovas, J.M., 2004). The advent of modern science led to the realization that not only are certain nutrition essential but also that specific quantity of each were necessary for optimal health thereby leading to such notions as dilatory recommendations, nutritional epidemiology, and the realization that food can directly contribute to disease onset. In this regard human development to disease onset is clearly defined by both environmental influences like diet, smoking education, physical activity etc. and heredity indicating that both aspects must be considered to optimize health (Ordovas, J.M., 2004).

The excitement about nutrigenomics comes from a growing awareness of the potential for modifications of food or diet to support health and reduce the risk of diet related diseases thus by identifying individual genetic predispositions for chronic diseases and the potential for individuals response to dietary intervention, these diseases may be effectively prevented by properly dietary intake. For this nutrigenomics brings together the science of bioinformatics nutrition, molecular biology genomics, epidemiology and molecular medicine (Neeha, V.S., 2012).

Nutrigenomics is the application of high-throughput genomics tools to the study of diet-gene interactions in order to identify dietetic components having beneficial or detrimental health effects (Miggiano, G.A., 2006). Traditionally biomarkers related to onset of disease or organ damage were used to quantify the effects but now it becomes necessary to quantify phenotype changes which are very close or within the range of health state (Ben Van Omen, 2008) and has primarily focused on nutrient deficiencies and the relation between nutrition and health. The advent of genomics has created unprecedented opportunities for increasing understanding of nutrients modulating gene and protein expression and ultimately influence cellular and organizational metabolism (Maria, C. Busstra et al., 2007).

Normally nutrigenomics embodies three normative concepts; first, food is exclusively interpreted in terms of disease prevention. Second, striving for health is interpreted as the quantification of risks and prevention of diseases through positive food-gene interactions and third, normative idea is that disease prevention by the minimization of risks is an individual's task (Korthals, M., 2011).

Nutritional factors are thought to be the cause of 30-60% of cancer; diabetes, cardiovascular diseases, and obesity are expensing rapidly (Zeisel, S.H., 2010). The conceptual basis for this new branch of genomic research can best be summarized by the following five tenets of nutrigenomics (Debusk, R., 2005):

Under certain circumstances and in some individuals, diet can be a serious risk factor for a number of diseases.

Common dietary chemicals can act on the human genome, either directly or indirectly to alter gene expression or structure.

The degree to which diet influences the balance between healthy and disease states may depend on individual’s genetic makeup.

Some diet regulated genes are likely to play a role in the onset, incidence, progression and severity of chronic disease

Dietary intervention based on knowledge of nutritional requirement, nutritional status and genotype can be used to prevent, mitigate or cure chronic diseases.

Nutrigenomics is therefore significant not only as a matter of improving public health but becomes it can have wide spread. Implicates on the way to understand and practice nutrition.

20.1.3 Benefits of nutrigenomics

Scientific studies show that nutrients in food can cause changes in the behavior of genes and the finding suggest that nutrients play peoples risk for cancer and other disease and through it, researchers hope to find ways to use food to prevent, cure and reduce the risk of diet related disease and benefits include a growth in concern on one's health and the chance to have a personalized nutrition optimized for good health, discovering genetic vulnerabilities which can be a strong motivating factor to encourage people to make the necessary dietary and lifestyle changes, and the high chances of heeding the advice that they have paid for. Profiling and analyzing one's DNA may cost between $300 and $3,000 and large-scale food corporations are spending fortunes on nutrigenomics, and on development of enhanced or fortified products to deliver personalized diets and multi-national corporations specializing in skin care, aging and beauty products are using nutrigenomics (Castle, D. 2007).

The main aims of nutrigenomics are:

Obtaining a personalized dietary regimen may encourage people to become more health conscious.

People are more likely to heed advice that they pay for.

Discovering genetic susceptibilities can be a strong motivator for making dietary and lifestyle changes.

The safe upper and lower limits for essential macro-nutrients like proteins, carbohydrates, fats and micronutrients such as vitamins and minerals will be better defined and understood.

Diseases may be avoided or ameliorated.

Unnecessary vitamins and other dietary supplements can be avoided.

People whose health is relatively unaffected by diet can continue to eat foods that they enjoy.

Lifespan may be extended.

Following commercial interests are responding to established market segments of early adopters seeking new tools to enhance health.

Nutrigenomics: The genes can tells that to eat

The ability of cells to adapt to environmental change by regulation of gene expression is essential for organism survival and organisms vary their gene expression in the absence or presence of nutrients by increasing and decreasing production of cellular proteins necessary for life sustaining function. A perfect example of this evolutionary process is the development of a gene mutation that alters the ability to tolerate lactose and adult mammals typically are unable to digest lactose. Ultimately, the science of nutrigenomics promises to offer the health practitioner greater knowledge, enabling them to predict potential genetic responses to nutritional intake and to target and modify associated behavior (Zeisel, S.H. et al., 2005).

Nutrigenomics explains omega-3's immune health benefits

Omega-3 fatty acids not only lower LDL cholesterol, but also help raise good HDL cholesterol and protection against certain cancers to prevention of heart disease, arthritis, degenerative eye disease, and high blood pressure, are found in walnuts, canola oil, and flax seeds but the best source is cold water fish. A specific omega-3 fatty acid called eicosapentaenoic acid was shown to reduce expression of inflammatory genes in arthritic canine cells (Bouwens, M., 2009, Bahadori, B., et al., 2010, Balk, E.M., et al., 2006).

Omega-3 fatty acids are highly concentrated in the brain and appear to be important for brain memory and performance, behavioral function. In fact, infants who do not get enough omega-3 fatty acids from their mothers during pregnancy are at risk for developing vision and nerve problems and symptoms of omega-3 fatty acid deficiency include fatigue, poor memory, dry skin, heart problems, mood swings or depression, and poor circulation. It is important to have the proper ratio of omega-3 and omega-6 in the diet because omega-3 fatty acids help reduce inflammation, and most omega-6 fatty acids tend to promote inflammation (Aben, A., 2010, Angerer, P., 2000, Aronson, W.J. et al., 2001).

Nutrigenomics shows blood pressure benefits of cocoa

A new nutrigenomics study shows that potential of polyphenol compounds in cocoa to reduce blood pressure is related to genotype. Activity of the antiotensin-converting enzyme (ACE), a target for blood pressure medication which was significantly inhibited by dark chocolate containing 72 % cocoa, with the degree of inhibition dependent upon the genotype of the human subjects. ACE inhibitors work by inhibiting the conversion of angiotensin-I to the potent vasoconstrictor, angiotensin-II, thereby improving blood flow and blood pressure (Daniells, S., 2011).

Nutrigenomics shows benefit of magnesium's metabolic actions

Magnesium may up and down-regulate a number of genes linked to metabolism and shows favorable effects on certain metabolic pathways are associated with changes in gene expression (Chacko, S.A., 2011) and magnesium supplementation was associated with a decrease in levels of C-peptide, a marker of improved insulin sensitivity. The mineral was also linked to down-regulation of certain genes related to metabolic and inflammatory pathways, the report also says that in terms of gene expression, 24 genes were up-regulated, and 36 genes were down-regulated in response to magnesium supplementation and some findings are also indicated a systemic effect of magnesium supplementation give measurable physiologic changes in the urinary proteome after treatment with magnesium for four weeks, which warrants further investigation into these changes and identification of the proteins involved (Chacko, S.A., 2011).

Nutrigenomics supports evidence for health benefits of anthocyanins

Anthocyanins, a large sub-group of flavonoids present in many vegetables and fruits, are safe and potent antioxidants. They exhibit diverse potential health benefits including cardioprotection, anti-atherosclerotic activity, anti-cancer, anti-diabetic, and anti-inflammation properties (Izabela, Konczak, 2004). Anthocyanins can cross the blood brain barrier and distribute in the central nervous system. The studies indicate that anthocyanins represent novel neuroprotective agents and may be beneficial in ameliorating ethanol neurotoxicity (Gang, Chen and Jia, Luo, 2010). Recently, it is demonstrated that anthocyanins, which are pigments widespread in the plant kingdom, have the potency of anti-obesity in mice and the enhancement adipocytokine secretion and adipocyte gene expression in adipocytes (Tsuda, T. et al., 2005).

Nutrigenomics could provide nutrition-relevant biomarkers

Changes to messenger RNA and the corresponding proteins control the transport of certain nutrients and metabolites in the biochemical pathway. Nutrigenomics could also provide a new set of biomarkers with relevance to nutrition (Van Der Werf, M.J., 2006).

Benefits of nutrigenomics diet for skin

Many skin problems such as acne, eczema, psoriasis, dry skin and premature aging of the skin is associated with diet and inadequate nutrition substantially contribute to the deterioration of such skin conditions and vice versa, with a proper diet the appearance and health of the skin can be significantly improved. The most advisable is beneficial for the blood type and genotype are minimally processed fruits, vegetables, legumes, nuts and seeds, and fermented products from unpasteurized and not homogenized milk. These foods contain nutrients necessary for healthy skin like vitamins B and E and minerals such as calcium, magnesium, potassium, iron, copper and manganese and to all blood groups are friendly flax seed, almonds and walnuts. In the fruits a great choice for all blood types are pineapple, blueberries, raspberries and cranberries. Turkey is the only generally available meat that is suitable for all blood types and genotypes. The leading way to beauty and health, healthy diet, lifestyle and products that are tailored to your nutrigenomics diet profile (Ravi Subbiah, M.T., 2010).

Health economics of nutrigenomics in weight management

There is a theoretical modeling study where they sought to evaluate the health economics implications of a nutrigenomic product for weight loss for which constructed a nutrigenomic economic model by linking the published study data related to the efficacy of a product and/or ingredients and validated clinical assessments that have already been tied to health economics data with data involving condition prevalence and overall cost of illness. In this theoretical model, the demonstration is that LG839 variant positively reduces the cost of illness at the macroeconomic and microeconomic level based upon a cost-effectiveness and cost-benefit analysis, have forecasted the prognostic health economic implications of a nutrigenomic intervention to demonstrate a theoretical model of nutrigenomic economics. This study is hypothesis-generating and should be used in the definition of protocols to prospectively test the health economic benefits of nutrigenomics (Brian, Meshkin, 2008).

Nutrigenetic association of the 5-lipoxygenase gene with myocardial infarction

5-Lipoxygenase (5-LO) catalyzes the rate-limiting step of the biosynthesis of proinflammatory leukotrienes from arachidonic acid and has been associated with atherosclerosis in animal models and humans and previously reports says that variants of a 5-LO promoter repeat polymorphism were associated with carotid atherosclerosis in humans, an effect that was exacerbated by high dietary amino acids but mitigated by high dietary N-3 fatty acids. The 5-LO polymorphism was genotyped by Costa Rican case-control pairs and tested for association with myocardial infarction and today, scientists are working with powerful databases to identify variations among genes in individuals and are working to establish correlations for susceptibility to various health conditions, as well as to understand the influence of such genetic variations on responses to dietary components (Allayee, H., 2006).

20.1.2 Persons involved in nutrigenomics

Clinical pharmacologists, biostatisticians, and clinicians need to give thoughtful consideration to the type and quantity of evidence to support dosing changes in clinical practice or approved labels intended to improve either the efficacy or safety of a nutrigenomic treatment (Lesko, L.J., 2007, Afman, L., 2006, De Busk, R., 2012, Debusk, R.M., 2005, German, J.B., 2005, Trujillo, E., 2006).

Dietitians

The nutrigenomics practitioner will develop gene-directed nutrition approaches and coach people in how to use food, dietary supplements and lifestyle choices in general in ways that are most appropriate for their genetic makeup. Disease management is expected to become increasingly effective as nutritional genomics is integrated into practice and even more eagerly anticipated is the opening up of new horizons for health care professionals in terms of expertise in health promotion while the ability to identify disease susceptibilities for an individual provides a solid foundation for effective health promotion efforts in ways never before possible (Ruth, M., 2012). Two men of the same age eat a diet low in fruits and vegetables and high in sodium and saturated fat, one develops hypertension, hypercholesterolemia, and eventually atherosclerosis, while the other lives a long life without such chronic disease. In another case, two postmenopausal women consume similar diets low in choline, one develops liver dysfunction due to the choline deficiency, but the other does not. However, because there are several genes involved in the development of these and other polygenic illnesses, dietitians and other healthcare professionals don’t fully understand the relationship between diet and disease risk, which stifles our ability to make personalized dietary recommendations as a preventive measure (Megan, D. Baumler, 2012).

Epidemiologists

Epidemiological studies have been helpful in identifying environmental factors associated with incidence or severity of certain diseases. However, these are statistical associations and as such, do not indicated the exact cause of the disease. Indeed, as the number of environmental variables increase, there is a corresponding need for larger population sizes in order to discriminate between statistically significant and insignificant factors (Malats, N., 2003), so the meta-analysis may be helpful in this regard if studies record similar data elements and use similar environmental survey instruments for their populations. Alternatively, well-designed laboratory animal studies and comparative genomics will be helpful in confirming and extending associations between diet and disease (Megan, D. Baumler, 2012).

Molecular biologists

The diverse tissue and organ-specific effects of bioactive dietary components include gene expression patterns organization of the chromatin, protein expression patterns including post-translational modifications as well as metabolite profiles (Corthesy-Theulaz, I., 2005).

Physicians

The physician with help of nutrigenomics can see the blueprints and better understand the raw materials required by body because incomplete or bad food causes toxic by-products which accelerate the aging and disease process and free radicals produced by non-specific foods and supplements wreak havoc on our body and in the past two decades, physicians, geneticists, and nutritionists have begun to study the effects of genetic variation and gene-nutrient interactions in the management of chronic diseases, such as coronary heart disease, hypertension, cancer, diabetes and obesity; and the role of nutrients in gene expression (Artemis, P.S., 2002).

Geneticists

Advances in molecular and recombinant DNA technology have led to exquisite studies in the field of genetics and the recognition in a much more specific way, through DNA sequencing and the extent to which genetic variation occurs. The importance of the effects of genetic variation has been extensively studied and applied by pharmacologists in drug development and evaluation of drug metabolism and adverse reactions to drugs (Artemis, P.S., 2002).

Bioinformatic specialists

The role of bioinformatics in nutrigenomics is multifold i.e. to create nutrigenomic databases, to setup special ontologies in using available resources, setup and track laboratory samples being tested and their results, pattern recognition, classification, and data mining, simulation of complex interactions between genomes, nutrition and health disparities (David Schaffer, J. et al., 2006).

Food scientists

Because of current rise in diet-related diseases is compromising health and devaluing many aspects of modern agriculture. The food scientists may use nutrigenomics to provide balanced and healthy diet for a person, and also apply the concept of personalized diet and steps to increase the nutritional quality of individual foods will assist in personalizing health and in guiding individuals to achieve superior health (German, J.B., 2011).

20.1.5 Limitations of nutrigenomics

Nutrigenomics risks includes the knowledge of disease susceptibility may cause high levels of anxiety and stress, genetic testing raises privacy concerns and some companies already sell the results of their genetic profiling to other companies while those with known genetic susceptibilities may be discriminated against in employment or health insurance. Physicians may not be qualified to interpret nutrigenomic reports and make appropriate decisions based on them so the demand for nutrigenomic evaluations may eventually overtax the healthcare system. The high cost of the screening and genotype diagnosis of developing novel and functional foods and the poor availability of functional health systems make even the possibility of tailored diets an impossible dream for most populations relying on poorly functioning and poorly resourced health systems (Zeisel, S.H., 2005). Dietetic practitioners arguably stand to gain the most by developing competency in nutritional genomics.They already have competency in nutrition and professional skills in patient counseling regarding diet and health. As with physicians, financial and other barriers limit comprehensive genetics training in dietetic education and dietetic practitioners face similar pressures in daily practice that will slow uptake of genetics into their practice (Burton, H., 2003).

20.2. Technologies involved in nutrigenomics

20.2.1 Nutrigenetics

The study of genetic variations on the interaction between diet and health with implications to susceptible subgroups such as people with an enzyme deficiency caused by mutations in the enzyme phenylalanine hydroxylase cannot metabolize foods containing the amino acid phenylalanine and must modify their diets to minimize consumption (Ordovas, J.M., 2004). This process has several phases that have grown into corresponding new fields within nutrigenomics are transcriptomics, proteinomics and metabolomics. Considers all metabolites in a human cell or organ, is capable of generating large amounts of data at low cost that detects subtle differences in metabolism that contribute to obesity as well as fluctuations in weight (David, M. Mutch, 2005).

20.2.2 Transcriptomics

The study of complete set of RNA transcripts produced by the genome at a time while transcriptome is the set of all RNA molecules, including mRNA, rRNA, tRNA, and other non-coding RNA produced in one or a population of cells (Hocquette, J.F., 2009). It is the total set of transcripts in a given organism, or to the specific subset of transcripts present in a particular cell type, unlike the genome, which is roughly fixed for a given cell line, can vary with external environmental conditions because it includes all mRNA transcripts in the cell, the transcriptome reflects the genes that are being actively expressed at any given time, with the exception of mRNA degradation phenomena such as transcriptional attenuation (Wang, Z., 2009). This technique is used for expression profiling, examines the expression level of mRNAs in a given cell population, often using high-throughput techniques based on DNA microarray technology and the use of next-generation sequencing technology to study the transcriptome at the nucleotide level is known as RNA-Seq (Gupta, Krishna Sen, 2011).

The transcriptomes can be created by two methods, first, maps sequence reads onto a reference genome of organism or related species and second, de novo transcriptome assembly which utilizes algorithms to built assembly software for generation of transcripts from short sequence reads. DNA microarrays can provide a method for comparing on a genome-wide basis the abundance of DNAs in the same samples and DNA in spots can only be PCR products that are specific for individual genes. A DNA copy of RNA is made using the enzyme reverse transcriptase and sequencing is now being used instead of gene arrays to quantify DNA levels, at least semi quantitatively (Katayama, S., 2005).

For understanding of the molecular mechanisms and signaling pathways controlling early embryonic development the analysis of the transcriptomes of human oocytes and embryos is used for proper embryo selection in vitro fertilization (Subramanium, A., 2005). The analysis of relative mRNA expression levels can be complicated by the fact that relatively small changes in mRNA expression can produce large changes in the total amount of the corresponding protein present in the cell, can be done by Gene Set Enrichment Analysis which identifies coregulated gene networks rather than individual genes that are up- or down-regulated in different cell populations (Katayama, S., 2005). The number of protein molecules synthesized using a given mRNA molecule as a template is highly dependent on translation-initiation features of the mRNA sequence and the ability of the translation initiation sequence is a key determinant in the recruiting of ribosomes for protein translation (Velculescu, V.E., 1997).

20.2.3 Metabolomics

The quantitative measurement of the dynamic multiparametric metabolic response of living systems to pathophysiological stimuli or genetic modification is known as metabolomics. The word origin is from the Greek meta meaning change and nomos meaning a rule set or set of laws (Nicholson, J.K., 2006) for the scientific study of chemical processes involving metabolites or systematic study of the unique chemical fingerprints that specific cellular processes leave behind and the study of their small-molecule metabolite profiles (Daviss, 2005) while metabolome represents the collection of all metabolites, end products of cellular processes, in a biological cell, tissue, organ or organism (Jordan, 2009).

Metabolites are the intermediates or end products of metabolism and in the context of metabolomics, a metabolite is usually defined as any molecule less than 1 kDa in size (Samuelsson, 2008). However, there are exceptions to this depending on the sample and detection method like macromolecules such as lipoproteins and albumin are reliably detected in NMR-based metabolomics studies of blood plasma (Nicooholson, J.K., 1995). Human-based metabolomics is more common to describe metabolites as being either endogenous or exogenous (Nordstrom, A., 2006). Metabolites of foreign substances such as drugs are termed xenometabolites (Crockford, D.J., 2008) and metabolome forms a large network of metabolic reactions, where outputs from one enzymatic chemical reaction are inputs to other chemical reactions, such systems have been described as hypercycles used for the toxicity assessment/toxicology (Robertson, 2005), metabolic profiling can be used to detect the physiological changes caused by toxic insult of a chemical and in many cases, the observed changes can be related to specific syndromes like a specific lesion in liver or kidney. This is of particular relevance to pharmaceutical companies wanting to test the toxicity of potential drug candidates and if a compound can be eliminated before it reaches clinical trials on the grounds of adverse toxicity, it saves the enormous expense of the trials (Saghatelian, A., 2004, Chiang, K.P., 2006), so it can be an excellent tool for determining the phenotype caused by a genetic manipulation like gene deletion or insertion (Gibney, M.J., 2005).

20.2.4 Proteomics

Proteomics is the large scale study of proteins, particularly their structures and functions (Anderson, N.L., 1998, Blackstock, W.P., 1999), can give better understanding of an organism, first, the level of transcription of a gene gives only a rough estimate of its level of expression into a protein (Steven, P. Gygi, 1999) and an mRNA produced in abundance may be degraded rapidly or translated inefficiently, resulting in a small amount of protein and second, many proteins experience post-translational modifications that profoundly affect their activities for example some proteins are not active until they become phosphorylated and for study of post-translational modifications phosphoproteomics, glycoproteomics methods are used. Third, many transcripts give rise to more than one protein through alternative splicing or alternative post-translational modifications and fourth, many proteins form complexes with other proteins or RNA molecules and finally, protein degradation rate plays an important role in protein content (Belle, Archana, 2006).

The practical applications of proteomics are the identification of potential new drugs for the treatment of disease and this relies on genome and proteome information to identify proteins associated with a disease, which computer software can then use as targets for new drugs, for example, if a certain protein is implicated in a disease and its 3D structure provides the information to design drugs to interfere with the action of the protein (Sreedhar, A., 2011). Another use of proteomics is using specific protein biomarkers to diagnose disease and a number of techniques allow testing for proteins produced during a particular disease, which helps to diagnose the disease quickly by many techniques include western blot, immunohistochemical staining, enzyme linked immunosorbent assay (ELISA) or mass spectrometry (Klopfleisc, R., 2010).

Secretomics, a branch of proteomics deals with studies of secretion pathways and secreted proteins using approaches of proteomics emerges as an important tool for the discovery of biomarkers of disease (Hathout, Yetrib, 2007). Proteomic technologies such as mass spectrometry are used for improving gene annotations and play an important role in drug discovery, diagnostics and molecular medicine because is the link between genes, proteins and disease. Advances in proteomics may help scientists eventually create medications that are "personalized" for different individuals to be more effective and have fewer side effects (Lesko, L.J. 2007).

20.3. Nutrients modulating genome expression

Numerous dietary components can alter genetic events in addition to the essential nutrients, such as carbohydrates, amino acids, fatty acids, calcium, zinc, selenium, folate, and vitamin A, C and E, there is a variety of nonessential bioactive components that seem to significantly influence health (Corthesy-Theulaz et al., 2005, Trujillo et al., 2006).

20.3.1. Effect of carbohydrate on gene expression

Glucose, the most abundant monosaccharide in nature, provides a very good example of how organisms have developed regulatory mechanisms to cope with a fluctuating level of nutrient supply (Sophie, Vaulont, 2000). In mammals the response to dietary glucose is complex because it combines effects related to glucose metabolism itself and effects secondary to glucose-dependent hormonal modifications, mainly pancreatic stimulation of insulin secretion and inhibition of glucagon secretion (Sophie, Vaulont, 2000). In the pancreatic cells, glucose is the primary physiological stimulus for the regulation of insulin In the liver, glucose, in the presence of insulin, induces expression of genes encoding glucose transporters and glycolytic and lipogenic enzymes, e.g. L-type pyruvate kinase, acetyl-CoA carboxylase, and fatty acid synthase, and represses genes of the gluconeogenic pathway, such as the phosphoenolpyruvate carboxykinase gene (Michael, W. King, 2012). Although insulin and glucagon were long known as critical in regulating gene expression, it is only recently that glucose also has been shown to play a key role in transcriptional regulation synthesis and secretion (Sophie, Vaulont, 2000).

Feeding high-energy diet to rats leads to early development of obesity and metabolic syndrome, apparently through an inability to cope with energy density of the diet. Obesity is associated with decrease in mRNA levels for the oxygenic neuropeptides, neuropeptides Y, Agouti related peptide etc and the effect of hyperglycemia on liver angiotensinogen gene expression and found that hyperglycemia activated AGT gene expression in liver increased approximately 3 fold (Gabriely, I., 2001).

20.3.2. Regulation of gene expression by dietary fat

In addition to its role as an energy source and its effects on membrane lipid composition, dietary fat has profound effects on gene expression, leading to changes in metabolism, growth, and cell differentiation. The effects of dietary fat on gene expression reflect an adaptive response to changes in the quantity and type of fat ingested (Jump, D.B., 1999). In mammals, fatty acid regulated transcription factors include peroxisome proliferator activated receptors (PPARα, -β, and -γ), HNF4α, NFκB, and SREBP1c (Koji, Nagao, 2008). These factors are regulated by direct binding of fatty acids, fatty acyl coenzyme A, or oxidized fatty acids oxidized fatty acid regulation of G-protein-linked cell surface receptors and activation of signaling cascades targeting the nucleus oxidized fatty acid regulation of intracellular calcium levels, which affect cell signaling cascades targeting the nucleus (Jump, D.B., 1999).

20.3.3. Role of PUFA on gene expression

Lipogenic enzymes in liver decreased as result of feeding a diet containing 60 % linoleic acid. Fatty acids stimulated the expression of adipocyte fatty acid binding protein (ap2) mRNA. In the 3T3-L1 adipocyte cell line, arachidonic acid (n-6) decreased SCD1 mRNA stability in a dose dependent manner (80% maximum repression), as did linoleic and eicosapentanoic acids (Tandon, Mayank, 2012).

20.3.4. Effect of protein on gene expression

Protein is very essential for growth, to develop immunity, normal maintenance of body function and structure apart from reproduction and production and in many developing countries protein insufficiency is still remains a major and serious problem (Tandon, Mayank, 2012). The function of protein in body is not only at macro level but it also functions at gene level and a variety or number of genes responds to dietary protein both protein quantity as well as quality influences gene expression. Insulin secretion was reduced in rats, which are fed with low protein diet due to reduction in pancreatic b-cell mass lower response of remaining b-cells to nutrients and lowered protein kinase activity (PKA) (Fabiano, Ferreira, 2004) which is involved in potentiating of glucose induced insulin secretion by gastrointestinal hormones such as glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide (Sarah Melissa, P., 2009). Low protein diet feeding to rats altered the many gene expression, which are responsible for proteins related to insulin biosynthesis, secretion and cellular remodeling. Normal insulin secretion is influenced by level of Protein Kinase C, K+ channel protein, calcium ion (Ca2+) and PKAa and increased ATP to ADP ratio achieved through glucose metabolism, close the K+ ATP channel, which leads to depolarization of b-cells results in opening of voltage dependent Ca2+ channels which results in influx of calcium leads to exocytosis of insulin granules while feeding low protein diet also increased expression of PFK in islets results in defective glucose metabolism and it further leads to deceased glucose induced insulin secretion and also decreases insulin level, it also acts through decreased movement of intracellular calcium (Tandon, Mayank, 2012).

20.3.5. Influence of amino acids on gene expression

The first step of protein translation is the formation of the 43s pre-initiation complex containing methionyl tRNA, eukaroyotic elongation factor 2 (eIF2), GTP, followed by the assocoiation of methionyl tRNA and eIF2–GTP that bind to the 40s ribosomal sub unit then GTP is hydrolyzed late in the initiation process, and eIF2 is released from the ribosome as an inactive eIF2–GTP complexresults in formation of eIF2–GTP is mediated by the guanine nucleotide exchange factor eIF2B. The mechanism to regulate eIF2B activity may be at the level of the ribosomal protein S6 and eEF-2 which is phosphorylated in response to many agents, including growth factors and hormones initiation process and amino acids regulate protein translation through modulation of eIF2B activity, 4 E–BP phosphorylation and protein S6 phosphorylation (Tandon, Mayank, 2012).

20.3.6. Effect of minerals on gene expression

Zinc (Zn) is an essential trace element with cofactor functions in a large number of proteins of intermediary metabolism, hormone secretion pathways and immune defense mechanism, involved in regulation of small intestinal, thymus and hepatocytes gene expression (Kindermann, B., 2004). MTF-I (Metal Responsive element Factor- I) is a Zn dependent transcriptional activator regulates mettalothionin I and II through MRE. Zn depedent KLF4 transcription factor is involved in protein preparation of HT-29 cells. The other protein have Zn in it as constituents are ATP synathase, cytochrome c, a, NADP dehydrogenase I and II. Deficiency of one or more mineral in diet lead to impaired body functions Geographical differences in mineral level of Soil/Plants (diet) have effects up to gene level such as Iron, Iodine, Selenium deficiency or excess of heavy metal ions like Anaemia (Vallee, B.L., 1990, Wu, F.Y., 1987).

20.3.7. Effect of vitamins on gene expression

Vitamins are micronutrients needed in very small quantity and are involved in gene expression. Vitamin A is involved in gene expression of Phospho Enol Pyruvate Kinase (PEPCK) is vitamin, insulin like growth factor (IGF 9) (Tandon, Mayank, 2012). Vitamin C is involved in hepatic gene expression. PEPCK is involved in conversion of oxaloacetate to phospho enol pyruvate, one of the important steps in gluconeogenesis. Vitamin A deficiency condition leads to changes in chromosomal structure of Retinoic Acid Responsive Element (RARE), which further leads to change in co regulator binding and activity. PEPCK-RARE and pre initiation complex interaction leads to RNA polymerase II association with PEPCK promoter is reduced, finally all results in insufficient PEPCK or no PEPCK leads to improvement of gluconeogenesis. In vitamin A sufficient mice PEPCK gene expression is highly induced in the food deprived state, when blood glucose levels are reduced (Tandon, Mayank, 2012).

Biotin is involved in various essential proteins or enzymes synthesis at gene level (Dakshinamurti, K., 2005). Vitamins B12, B6, and folic acid converge at the homocysteine metabolic junction where they support the activities of two key enzymes involved in intracellular homocysteine management, methionine synthase (MS) and cystathionine beta-synthase. B12 supplementation does not alter mRNA or protein turnover rates but induces translational up-regulation of MS by shifting the mRNA from the ribonucleoprotein to the polysome pool. The B12-responsive element has been localized by deletion analysis using a reporter gene assay to a 70-bp region located at the 3' end of the 5'-untranslated region of the MS mRNA. The cellular consequence of the B12 response is a 2- and 3.5-fold increase in the flux of homocysteine through the MS-dependent transmethylation pathway in HepG2 and 293 cells, respectively (Oltean, S., 2003).

20.4. Nutrition gene and diseases

20.4.1 Metabolic hereditary diseases

Some hereditary disorders of metabolism can be diagnosed in the fetus by using amniocentesis or chorionic villus sampling and blood test or examination of a tissue sample to determine whether a specific enzyme is deficient or missing (Lee, M. Sanders, 2009).

In most inherited metabolic disorders, a single enzyme is either not produced by the body at all, or is produced in a non-working form. Depending on the function of that enzyme, toxic chemicals may build up, or an essential product may not be produced. The code or blueprint to produce an enzyme is usually contained on a pair of genes and most people with inherited metabolic disorders inherit two defective copies of the gene one from each parent. Both parents are carriers of the bad gene, meaning they carry one defective copy and one normal copy. Inherited metabolic disorders may affect about 1 in 1,000 to 2,500 newborns. The symptoms of genetic metabolic disorders vary widely depending on the metabolism problem present, includes lethargy, poor appetite, abdominal pain, vomiting, weight loss, jaundice, failure to gain weight or grow, developmental delay, seizures, coma, abnormal odor of urine, breath, sweat, or saliva. Symptoms may be brought on by foods, medications, dehydration, minor illnesses, or other factors. Hundreds of inherited metabolic disorders have been identified, and new ones continue to be discovered. Some of the more common and important genetic metabolic disorders (Scriver, C., 2001) includes lysosomal storage disorders like Hurler syndrome, Niemann-Pick disease, Tay-Sachs disease, Gaucher disease , Fabry disease, Krabbe disease, Galactosemia, Maple syrup urine disease in which deficiency of an enzyme called branched-chain alpha-keto acid dehydrogenase causes buildup of amino acids in the body and the urine smells like syrup (Muranjan, M., 2010), Phenylketonuria, deficiency of the enzyme PAH results in high levels of phenylalanine in the blood (Mitchell, J.J., 2010), glycogen storage diseases, Friedreich ataxia i.e. problems related to a protein called frataxin cause nerve damage and often heart problems (Hasan, Ozen, 2007).

Peroxisomal disorders include Zellweger syndrome (abnormal facial features, enlarged liver, and nerve damage in infants) and Adrenoleukodystrophy , metal metabolism disorders like Wilson disease (toxic copper levels accumulate in the liver, brain, and other organs) and hemochromatosis (the intestines absorb excessive iron, which builds up in the liver, pancreas, joints, and heart, causing damage), organic acidemias, urea cycle disorders including ornithine transcarbamylase deficiency and citrullinemia are the few examples of metabolic hereditary disorders (Hasan, Ozen, 2007) and inborn errors of metabolism referred as "silent killers" because they can strike healthy-appearing full-term infants without warning and display hypoglycemia or poor feeding (Enns, G.M., 2005).

Failures of energy production or utilization result from defects in the liver, myocardium, muscle, or brain and disrupt cytoplasmic or mitochondrial energy production, including the fatty acid oxidation disorders and the congenital lactic acidemias, present with a variety of findings, but a consistent symptom is hypoglycemia with clinical features are lactic acidosis, hypotonia, and cardiac involvement (Saudubray, J.M., 2002) while hypoglycemia related to fasting can signal a fatty acid oxidation disorder, while hypoglycemia following eating is characteristic of hereditary fructose intolerance (Garganta, C.L., 2005).

20.4.2 Multifactorial diseases

A multifactorial disease has a combination of distinctive characteristics that can be differentiated from clear-cut Mendelian or sex-limited conditions including the disease can occur in isolation and affected children born to unaffected parents. Although familial aggregation is also common, there is no clear Mendelian pattern of inheritance, Environmental influences can increase or decrease the risk of the disease, the disease occurs more frequently in one gender than in the other, but it is not a sex-limited trait. In addition, first-degree relatives of individuals belonging to the more rarely affected gender have a higher risk of bearing the disease. The concordance rates, is a measure of the rate at which both twins bear a specific disease. The disease occurs more frequently in a specific ethnic group (i.e., Caucasians, Africans, Asians, Hispanics, etc.) (Lobo, Ingrid, 2008) in monozygotic and dizygotic twins contradict Mendelian proportions. On a pedigree, polygenic diseases do tend to run in families, but the inheritance does not fit simple patterns as with Mendelian diseases (Burmeister, Margit, 1999).

20.4.3 Monogenic and multigenic diseases

Monogenic diseases result from modifications in a single gene occurring in all cells of the body and they affect millions of people worldwide as scientists currently estimate that over 10,000 of human diseases (Ikonen, E. 2006) and according to WHO, single-gene or monogenic diseases can be classified into three main categories like dominant, recessive and x-linked with the global prevalence of all single gene diseases at birth is approximately 10/1000 (WHO, 2012). Thalassaemia is a blood related genetic disorder which involves the absence of or errors in genes responsible for production of haemoglobin, a protein present in the red blood cells while sickle-cell anemia is a blood related disorder that affects the haemoglobin molecule, and causes the entire blood cell to change shape under stressed conditions (Weatherall, D. J., 2000) while haemophilia is a hereditary bleeding disorder, in which there is a partial or total lack of an essential blood clotting factor, lifelong disorder, that results in excessive bleeding, and many times spontaneous bleeding and Haemophilia A is the most common form, referred to as classical haemophilia results from the deficiency in clotting factor 8, while haemophilia B is a deficiency in clotting factor 9, a sex-linked recessive disorder (WHO, 2012).

Cystic fibrosis is a genetic disorder that affects the respiratory, digestive and reproductive systems involving the production of abnormally thick mucus linings in the lungs and can lead to fatal lung infections results in various obstructions of the pancreas, hindering digestion (WHO, 2012). The other example is Tay-Sachs disease; a fatal genetic disorder in which harmful quantities of a fatty substance called ganglioside GM2 accumulate in the nerve cells in the brain (WHO, 2012) caused by a decrease in the functioning of the hexosaminidase A enzyme while Fragile X syndrome is caused by a "fragile" site at the end of the long arm of the X-chromosome, genetic disorder that manifests itself through a complex range of behavioral and cognitive phenotypes (McMillan, J., 2006).

20.5. Nutrigenomics and communication

Nutrient-gene interactions are responsible for maintaining health and preventing or delaying disease. Unbalanced diets for a given genotype lead to chronic diseases such as obesity, diabetes, cardiovascular, and are likely to contribute to increased severity and/or early-onset of many age-related diseases. Many nutrition and many genetic studies still fail to properly include both variables in the design, execution, and analyses of human, laboratory animal, or cell culture experiments (Kaput, J., 2006). The complexity of nutrient-gene interaction has led to the realization that strategic international alliances are needed to improve the completeness of nutrigenomic studies, a task beyond the capabilities of a single laboratory team. Eighty-eight researchers from twenty two countries recently outlined the issues and challenges for harnessing the nutritional genomics for public and personal health. The next step in the process of forming productive international alliances is the development of a virtual center for organizing collaborations and communications that foster resources sharing, best practices improvements, and creation of databases. There is a requirement of nutrigenomics information portal, a web-based resource for the international nutrigenomics society and this portal aims at becoming the prime source of information and interaction for nutrigenomics scientists through a collaborative effort (Kaput, J., 2006).

20.6. Nutrigenomics and bioactive nutrients

20.6.1 Elk antler velvet

Elk antler velvet (EAV) is the fast -growing, soft cartilaginous tissue that develops out of the frontal bone of the Cervus species that rises from skin covered pedicles before it calicifies and hardens. Antlers are unique in nature and different from horns because they are naturally re-grown and cut off each year. Elk antler velvet, pumped tight with blood and pulsing with hormones, is the most regenerative mammal tissue known, capable of growing over half an inch in one day. The active ingredients have been found to include a variety of minerals, proteins, collagens, fatty acids, and glycosaminoglycans in varying concentrations with the effects like increased growth (Ko, K.M., 1986), improved immunity (Suh, J.S., 1999), anti fungal (Park, H.S., 1998), cardiovascular effects (Clifford, D.H., 1979), promotion of rapid healing in tissues and bones, relief of symptoms in arthritis and gout, and pain reduction associated with disease or injury to muscles and joints. It is an excellent source of chondronitin sulfate, glucosamine sulfate, type II collagen and prostaglandins having benefits for free radical scavenger (Wang, B.X., 1988), arthritis, antiulcer activity (Wang, B.X., 1985), anti-infective (Dai, Ting-Yeu, 2011), reduce inflammation (Shin, K.H., 1989) anti-narcotic addiction activity (Kim, H.S, 1999) and anti aging properties (Chen, X., 1992).

20.6.2 Vegan chyawanprash

India’s most famous anti-aging recipes is chyawanprash and according to ayurveda, chyawanprash comes under the category of rasayana (Jose, J.K., 2000) used for maintaining youthfulness (Manjunatha, S., 2001), vigor, vitality of the body and keeping away aging process, senility and debility and maintains the proper functioning of the cells and rejuvenates the cells and also keeps away diseases (Jose, J.K., 2000). This ayurvedic tonic consisting of about 35 natural herbs including amla (Embellica Officinalis), the richest natural source of vitamin C, works on the immune system of the body protecting body against everyday infections like cough, cold, fever and hepatoprotective (Jose, J.K., 2000) and thus it is very useful in children, old persons, tubercular patients, bidi smokers (Yadav, J.S., 2003) and debilitated persons.

20.6.3 Mangosteen

Mangosteen is cultivated in Thailand under the most stringent conditions for this amazing superfood, contains a class of naturally occurring polyphenolic compounds known as xanthones which provide beneficial effects on cardiovascular diseases, including ischemic heart disease, atherosclerosis, hypertension, (Lourith, N., 2011) anti-invasive activities (Wang, J.J., 2012) and thrombosis (Chin, Y.W., 2011). Xanthones, have unique antioxidants properties (Martinez, A., 2011) which help to heal cells damaged by free radicals (Robb-Nicholson, C., 2012), slow aging (Ngawhirunpat T, 2010), and physical (Ryu, H.W., 2012) and mental deterioration (Robb-Nicholson, C., 2012) and rind of partially ripe Mangosteen fruit yields a polyhydroxy-xanthone derivative termed mangostin and beta-mangostin while fully ripe fruits contains the xanthones gartanin, beta-disoxygartanin, and normangostin, beneficial in various serious ailments like anti-fatigue, anti-obesity, antidiabetic (Ryu, H.W., 2011), anti-anxiety (Shiozaki, T., 2012), antitumor (Kosem, N., 2012), anti-seborrheic (Wang, J.J., 2012), anti-glaucoma, anti-pyretic, anthelminthic (Keiser, J., 2012), anti-neuralgia (Reyes-Fermín, L.M., 2012), anti-arthritis, anti-inflammatory (Jang, H.Y., 2012, Liu, S.H., 2012), anti-ulcer and anticancer (Robb-Nicholson, C., 2012, Chang, H.F. 2012). Mangosteen also shows inhibitory action against these harmful bacteria organisms (Koh, J.J., 2012) in addition to its antibacterial (Temrangsee, P., 2011), strong antifungal properties and effective in boosting weak immune systems.

20.6.4 Kaunch

Mucuna prurita Baker (Fabaceae), Kaunch (seed) is well known spermopiotic plant of ayurveda contains alkaloidal content like mucuadine, mucuadinine, mucucuadinine, pruriendine, mucunine, mucunadine, nicotine (Saksena, S. 1987) used as ayurvedic medicine which increases testosterone, libido, reduces spasms, lowers blood sugar, lowers blood pressure, increases urination, relieves pain, reduces inflammation, kills parasites, (Meena, Ajay Kumar, 2009) calms nerves, reduces fever, lowers cholesterol, also used as an aphrodisiac, spermatogenetic (Saksena, S. 1987), androgenic, retentive, L-Dopa alternative, menstrual promoter, uterine stimulant, nerve tonic, anti-Parkinson's, (Meena, Ajay Kumar, 2009) hypoglycemic, anabolic etc (Agrawal, Archana, 2010) and also produces an antidepressant effect in patients suffering from depressive neurosis. Due to the high concentration of L-dopa in the seeds, considered as an alternative to the pharmaceutical medication levodopa in Parkinson's disease also has reported with anabolic and growth hormone stimulant properties (Agrawal, Archana, 2010).

20.6.5 Blue lotus flowers

Egyptian medicinal practitioners used this flower to stimulate blood flow, and as an anti aging treatment while traditionally used to relieve pain, increase memory, increase circulation, promote sexual desire, and creates feelings of well-being, euphoria and ecstasy, without the use of narcotics (Emboden, W.A., 1981), including two 2S, 3S, 4S-trihydroxypentanoic acid, and myricetin 3-O-(3''-O-acetyl)-alpha-L-rhamnoside, along with the known myricetin 3-O-alpha-L-rhamnoside, myricetin 3-O-beta-D-glucoside, quercetin 3-O-(3''-O-acetyl)-alpha-L-rhamnoside, quercetin 3-O-alpha-L-rhamnoside, quercetin 3-O-beta-D-glucoside, kaempferol 3-O-(3''-O-acetyl)-alpha-L-rhamnoside, kaempferol 3-O-beta-D-glucoside, naringenin, (S)-naringenin 5-O-beta-D-glucoside, isosalipurposide, beta-sitosterol, beta-sitosterol palmitate, 24-methylenecholesterol palmitate, 4 alpha-methyl-5alpha-ergosta-7,24-diene-3 beta, 4 beta-diol, ethyl gallate, gallic acid, p-coumaric acid, and 4-methoxybenzoic acid, used as a hypnotic, sedative, euphoric and anti-spasmodic and also produces an opiate-like intoxication with antioxidant activity (Agnihotri, V.K., 2008).

20.6.6 Shilajit

Shilajit is a thick rich paste oozing out from the rocks (Agarwal, S.P., 2007) in the towering cliffs in the Himalayan mountains (Ghosal, Shibnath, 1990), used historically for general physical strengthening, anti-aging (Gaikwad, N.S., 2012), libido, injury healing, urinary tract rejuvenation, enhanced brain functioning potency, bone healing, kidney rejuvenation, immune system strengthening (Ghosal, Shibnath, 1990), arthritis, hypertension (Gaikwad, N.S., 2012), obesity and has unmatched powers of arresting and reversing the aging process. Shilajit is spermatogenic and ovogenic (Park, J.S., 2006), also counteracts Diabetes and regulates the blood sugar level with purifies blood (Sharma, P., 2003) and improve functioning of pancreas and strengthen digestion and promotes the movement of minerals, especially calcium, phosphorous, and magnesium into muscle tissue and bone also stimulates the immune system (Ghosal, Shibnath, 1990) and improves restoration after exercise so counteracts debility and general fatigue (Wilson, E., 2011).

20.6.7 Folate

A gene variant is responsible for increasing homocysteine levels in some people, subsequently leading to a higher risk of cardiovascular diseases and certain cancers. Folate, however, helps to negate this risk. Therefore, people with this identified gene variant are encouraged to consume plenty of folate-rich foods (Yang, Q.H., 2008, Pfeiffer, C.M., 2008).

20.6.8 Green tea

It is used in Crohn's disease (Alic, M., 1999), on thermogenesis and energy intake (Belza, A., 2009), human prostate cancer (Bettuzzi, S., 2006), gastrointestinal cancer (Borrelli, F., 2004), skin problems (Katiyar, S.K., 2000), on weight maintenance after body-weight loss (Kovacs, E.M., 2004) reduces body fat and cardiovascular risks (Nagao, T., 2007) help prevent breast cancer (Inoue, M., 2001).

20.6.9 Tumeric

The turmeric is used for anti-inflammatory (Arora, R.B., 1971), management of neurodegenerative disease (Auddy, B., 2003), on lipid profile (Desphande, U.R., 1997), cancer chemoprevention (Gescher, A.J., 2001), specific inhibition of cyclooxygenase-2 (COX-2) expression by dietary curcumin in HT-29 human colon cancer cells (Goel, A., 2001) and inhibition of HIV-1 and HIV-2 proteases (Sui, Z., 1993) with antidepressant activity (Yu, Z.F., 2002). Turmeric suppresses a gene that makes inflammatory properties, which is possibly useful in preventing colon cancer and Alzheimer’s disease.

20.6.10 Vitamin D

Vitamin D is the sunshine vitamin, synthesized in our skin during sun exposure and most relevant dietary sources of vitamin D are fatty fish and full-fat milk. Most of the vitamin D in blood (80-90%) is bound to this protein and transported all over the body to the target organs. Variations in two more genes (DHCR7 and CYP2R1) have been confirmed for Caucasians and both genes are coding key enzymes in vitamin D metabolism pathway (Teresa, Kulie, 2009). Vitamin D mediates expression of human cathelicidin antimicrobial peptide in bronchial epithelial cells (Schrumpf, J.A.et al., 2012) and modifies the susceptibility to schizophrenia bipolar mood disorder by regulation of dopamine D1 receptor gene expression (Ahmadi, S.et al., 2012). It also helpful in the management of Alzheimer’s disease (Annweiler, C., 2012), multiple sclerosis (Holmoy, T., 2012, Bartosik-Psujek, H., 2010), blood pressure (Caro, Y., 2012), common cold (Linder, J.A., 2012) and also prevents the fracture in bones (Paterson, C.R., 2012) and osteoporosis (Curtis, J.R., 2012, Lakatos, P., 2011). Pharmacological studies shows that vitamin D prevents progression of peritoneal fibrosis (Hirose, M., 2012), vitiligo (Colucci R., 2012), asthma (Iqbal, S.F., 2011), polyarthraritis (Moghaddami, M., 2012) and enhance the action of parathyroid gland (Bienaime, F., 2011). It also useful in treatment of cancer, inflammation (Krishnan, A.V. 2012), kidney diseases (Ele