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Nutritional Genomics

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Thanks to the development of genetics in 20th century, it has become known that individual reaction of organism to nutrients is conditioned by its genotype. Firstly, scientists researched this regularity on the example of serious hereditary diseases as nutation of the gene, which is responsible for synthesis of leptin hormone, leads to serious obesity rates. Some people have decreased level of lactase ferment, which is responsible for decomposition of lactobiose, since they can hardly digest dairy products. Scientists proved genetic nature of increased arterial tension, tendency to heart attacks, oncological illnesses, diabetes mellitus and other diseases of metabolism.

Therefore, in order to analyze nutrigenomics and its influence on the cardiovascular diseases with subsequent possibility to prevent their appearance, we used different methods of investigations and examinations of the daily nutrition budget and its components with probable impact on the organism on the whole and its systems in particular.

As a result, there were different options discovered. First of all, there are three types of people depending on the nutrigenomics type, which assume certain tendencies to health issues. Secondly, it was found out that the genes we have and the food we consume every day are the core factors that altogether project which diseases we might have. Finally, preservation of food and keeping it in appropriate conditions also has its significant role in the influence on the appearance of certain diseases, associated with food consumption and, therefore, with nutrigenomics.

As a conclusion, it is worth mentioning that still it is almost impossible to invent the diet recommendations to absolutely eliminate the possibility of cardiovascular diseases appearance, since there is little known in the sphere of nutrigenomics and its influence on te human body. Thus, further researches should be done to examine this issue more profoundly.

Contemporary nutrient investigations are oriented at optimization of the process for improvement of individual health state and prevention of diseases growth within the population groups, and focus their attention on issues regarding influence of extra surrounding toxic factors and stress on the human body, and on methods of their control. Correct nutrition presumes achievement of set goals, associated with efficient regulation of metabolism in organism, increase of processes of active and passive protection, and also makes it possible to have the optimal adaptation according to the individual requirements and needs of the human. As Bouchard (2012) mentioned, development of this concept of ongoing improvement of nutrient support for organism or its needs for functional nutrition conditioned better understanding of mechanisms for preventive measures from diseases, effective diagnostics of biomarked molecules, and also their successful implementation within medical centers. Referring to Bidlack (2011), mutations and absence of decrease of activity of certain genes lead to deviation of organic biochemistry with all ensuing consequences. The outcome of development of nutrient science was seen in appearance of new disciplines, such as nutrigenetics and nutrigenomics.

Later on there was found another reverse regularity, since not only genes could determine receptiveness for food, but also food can influence genes by forcing changes in their actions. According to Castle (2009), diet causes deviation of work of DNA apparatus, which leads to activation of “disease genes”, which might lead to development of illnesses. Consequently, if to rationalize the nutrient budget correctly, it might assist in prevention of appearance of different inherited diseases. Thus, the food we eat, the genes we have, and, consequently, the diseases we have afterwards, is investigated by means of nutrigenomics.

Sometimes these two core abovementioned notions are perceived as the same matter. However, nutrigenetics and nutrigenomics are absolutely different concepts. Thus, nutrigenetics investigates genes, responsible for metabolism and food accessibility, when nutrigenomics studies influence of different nutrients, such as proteins, fats and carbohydrates on the expression and action of genes. Challem (2006) admitted that decoding of human genome was finished in 2003 and allowed determining of over three milliards of sequences of nucleotides, which form the human DNA structure. Human cells possess around 24 thousand of genes that content information for each of 100 trillions of cells of the human organism. It is commonly understood that part of genes is rather changeable. Today many of developments are directed at investigation of influence of certain substances, which are consumed with food, on the expression of genes. The basis of nutrigenomics, therefore, increased knowledge about nutrient-dependent single nucleotide polymorphism of genes and phenomenon of epigenetic development under conditions of individual sensibility to complex diet programs.

Investigations also showed that many people hardly bare certain food products – milk, cereals, and proteins of animal origin. On the basis of these data it was established that not only genes determine susceptibility to the food, but also vice versa – food can influence genes, changing their activities. Subsequently, in such a case human health would also be changed. Hence, the core idea of nutrigenomics lies in correct choice of the diet in order to defuse the disease genes or make them passive, if possible.

Therefore, determination of the interconnection between nutrients and most dangerous diseases, such as arterial hypertension and cancer, is to be solved in the future. Besides, in the USA and Europe certain companies appeared, which dealt with personal diets development, based on genetic analysis. Specialists conduct analysis of genes, influencing the condition of bones, heart, ability for detoxication and fixing of antioxidants, sensibility to insulin, and tendency to inflammatory processes. Despres (2008) said that on the basis of received data it is possible to change the dietary budget in order to neutralize genetic aptitude to any diseases.

There is no doubt that for the last 20 years the quantity of publications in nutritional, biological and medical journals about the usefulness of different products is rather significant. A lot of them dealt with the positive effect of vine consumption. Hyman (2006) mentioned that results of those works evidences about the favorable influence of different vine components on the decrease of risk for cardiovascular diseases, thrombosis, arterial hypertension, cardiac accident, ischemic heart disease, plaques aggregation, cerebrovascular accident, DM2, consequences of inflammatory processes, early symptoms of Alzheimer’s disease, and on the increase of the amount of HDL of good cholesterol and preservation of HDL oxidation of bad cholesterol. Still, it is worth mentioning that there is a lot of critical opinions about the use of vine, since the majority of the investigations were carried out in vitro, instead of in vivo course. Moreover, efficiency of certain components is often not scientifically described and proved. Hence, commonly recognized fact of positive effect of direct impact of resveratrol on the cardiovascular diseases was perceived with hesitation, since its amount in grape and vine does not overrate 3-4 mg/l.

Thus, Kaput (2006) outlined that uniqueness of grape in the world history and culture forced EU to create the Franco-Italian syndicate for decoding of Vitis vinifera genome, where around 60 scientists participated. They identified that grape possesses 30434 genes, which is much less then in rice (37554) and poplar (45555). However, gene structure of grape radically differs from the genomes of abovementioned plants, especially regarding quantity of functional genes, responsible for organoleptic peculiarities and influence on the human health. Thus, in the grate genome there were 89 genes identified, which were responsible for synthesis of terpene and tannin – significant components of flavor and taste, and 42 genes, associated with synthesis of stilbene, which are the most effective antioxidants, which might be effective for decreasing the risk of cardiovascular diseases.

Knapp (2011) stated, based on the technologies of nutrigenomics and using the method AIM (Active Ingredient Method), the HIL’s company developed and improved different strategies of formulation of such dietary which could ease clinical implications of different diseases or change their outcomes and correct age deviations in vital activities of organism. Benefits of this method are seen in its simplicity and efficiency. First of all, the level of expression of core genes is determined while development of certain diseases. Then, influence of definite nutrients is investigated in vitro on the expression of core genes. Finally, the result of in vivo implementation of the core nutrients complex is evaluated. The AIM method allows precise choosing of the directed diet therapy for patients much faster than it was done previously.

Outcomes and Measurements of Interest

Harmonious development of the organism from infancy to adulthood requires multiple and rather complicated metabolic and physiological transformations. Many of those processes are regulated by factors of surroundings, including nutritional ones. Core role in such regulation is given to minerals, amino acids, calories and fatty acids, thanks to which in the skeleton structure, activity of the immune system, development of the nervous system and metabolism of cartilaginous tissue there are significant changes occurring all the time.

Mine (2009) outlined that mechanisms development of different nutrients influence with the aim of preventive measures and treatment of different diseases of human-beings at the level of individual health is at the development stage. However, their scientifically analyzed complex usage might these days extend the terms of duration of life. From the other side, it has milder regulatory influence on the level of intracellular signalization than pharmaceuticals. Thus, rationally chosen profile of nutrients within the diet might have more physiologically safe action in case of appearance of early signs of disease. Moreover, food nutrients might become safer in case of permanent usage in comparison to the medications in case of advanced illnesses. Besides, nutrient aspects of healthy way of life are not limited to the sole definition of the somatic health on the molecular level, but it also includes significant role of biomarked molecules of early pathological changes, which search is performed with the aim to conduct nutrient-dependent targeted strategies within medical centers.

Nutrient imbalance is the core predictor for development of many nutrient-deficit conditions, like cardiovascular diseases. Paeschke (2010) signified that, traditionally, specific concentration of nutrients is calculated on the basis of criteria of average nutrient status of the human representative. Unfortunately, required information about the nutrient level today is regulated by diet recommendations on the level of population and is determined by the level of content of certain nutrient in the nutrition products. Today on the basis of contemporary understanding of the nutrient phenotype and role of genetic, epigenetic and nutrient factors in its formation, the molecular mechanism of nutrients’ action and their influence on the biological targets in the cell become more comprehensible.

Important Characteristics and Comparison Factors

Current level of control of quantitative and qualitative contents, and of the safety of the nutritional products, monitoring conduction aimed at stratification of increased risks of appearance of toxic organics in the aliments becomes actual medical and social problematic issue. Effects of genetic purity degree, improper storage, transportation and other factors on the chemical,, biochemical content of food products is also recognized as one of the main problems of the today’s society. Meanwhile, control of BUBD terms and conditions of storage of products is recognized as fundamental problem of the somatic health of consumers. Thus, implementation of bio-analytic methods of investigations of samples of water, fruit, diary and meat products is considered to be actual and modern measure of safety and protection against microbe contamination, biochemical oxidation, changes of amino-acid content, flavor (aromatization profile) in the process of production, processing, transportation and storage.

Therefore, damage of the genome influences all the stages of life. During multiple prospective group investigations, the role of chromosome damage in development of cardiovascular diseases was proved. Those people with expressed degenerative changes in organism on the background of deviation of acid-reactivation processes and/or processes of DNA reactivation had higher probability of damage of the genome on the background of insufficient intake of micronutrients.

Implications for Practice

Rimbach (2005) outlined that the human food should possess around 40 micronutrients. There is no doubt that certain micronutrients (vitamins and minerals) play important role of co-factors or are recognized as structural units of the protein molecules, which participate in synthesis and reparation of DNA, its protection from oxidation damage and stability preservation of the genome. Insufficient intake of these micronutrients might lead to DNA damage and development of the range of serious diseases, like cardiovascular illnesses. Genome damage, conditioned by insufficiency of micronutrients, often reaches the same rate as in the result of impact of aggressive factors of surrounding, such as chemical carcinogens and UV radiation.

Results of epidemiologic investigations allow assuming that genome stability depends on at least nine micronutrients. The investigation of dependency between the regime of consumption and damage of lymphocyte genome was conducted on 190 representatives, with average age of 47 years. Results showed that increased consumption of calcium, folate, nicotinic acid (P-P factor), vitamin E, vitamin A and beta-carotene is associated with preservation of genome stability. From the other side, increased consumption of pantothenic acid (chick antidermatitis factor), anti-egg white injury factor and riboflavin led to increase of genome instability. Moreover, insufficiency of folic acid (Norit eluate factor), niacin (pellagra-preventing factor), vitamin B6 and B12 might increase risk of development of colon cancer, ischemic heart disease (IHD), and neurologic dysfunction as a result of damage in chromosomes and damage of the DNA reparation process. Insufficiency of vitamin C might increase the risk of development of cataract and cancer by means of DNA oxidation processes. Insufficient consumption of vitamin E might also increase the risk of colon cancer, IHD and damage of immune system by means of DNA molecules oxidation. Insufficiency of zink is also associated with memory loss because of deviation of chromosome integration.

Simopoulos (2010) said that content of micronutrients that promote preservation of the genome stability is different in various products. As far as the consumption manner is individual, which depends on the taste preferences that might be already established on the genetic level or under influence of cultural and social factors, in order to refill the needs for micronutrients, it is required to keep to certain conditions and consume nutritional supplementation. Thus, corrections of metabolism by means of changes in the diet, taking into account individual peculiarities of genotype and age, it is possible to decrease damage of chromosome and mitochondrial DNA, improve general health state and quality of life. Supplementation of the optimal micronutrients, sufficient for prevention of the DNA damage, should decrease the risk of development of certain cardiovascular diseases and other degenerative diseases.

Besides, telomere is nucleoid-proteid end structural unit of chromosome, which provides stability for chromosome and promotes breakage of synechia of chromosomes during the process of cell division. According to Wiwanitkit (2010), degradation of telomeres leads to instability of the entire chromosome, which is important risk factor for the development of cancer and cardiovascular diseases. Besides that, telomeres’ shortening is one of the possible fundamental mechanisms of the cells’ ageing. Investigations proved that insufficiency of folate and 3-pyridinecarboxylic acid altogether with increase of oxidation stress might stimulate telomere dysfunction. Such metabolism deviations might explain interconnection between shortening of the telomeres and development of the range of pathologies, including obesity, immune system dysfunction, cancer and cardiovascular diseases.

What is more, folates occupy one of the central places as vitamins that can protect human organism from diverse cardiovascular diseases. Just several nutritional products from the sphere of functional products possess that much of fundamental and different biological peculiarities as folates and vitamins of B group.

Content of folates and typical changes in genes which encrypts folate-dependent fermentsis associated with diverse cancer types, cardiovascular diseases, hereditary defects and epiphonomena after pregnancy. It is conditioned by the fact that certain molecular processes that support genome mechanism, are sensible to the vitamin B and, in particular, react on the interconnection between intake of folates with food and polymorphism of folate-dependent ferment. To those mechanisms it is necessary to address support of methylation of genome CpG for scheduled expression of genes and synthesis of nucleotides for prevention of DNA chain breakage. The same nutrigenomics influences the level of homocysteine in plasma and, consequently, impacts the risk of development of cardiovascular diseases.

On the background of insufficiency of folate in the structure of DNA, the substitution of thymidine by uracil is happening, which leads to damage of chromosome. There are rather persuading data about the fact that deviation of the process of DNA methylation might lead to dysfunction of telomeres. Consequently, it is possible that insufficiency of folates and other donors of methyl groups might lead to instability of telomeres by means of damaging of methylation process. Pellagra-preventive factor is also one of the micronutrients that plays important role in preservation of the integration of the chromosomes and in decrease of cardiovascular diseases development.

DNA damage, formation of lipids and proteins as a result of lipid peroxygenation with the participation of active forms of oxygen might be controlled by antioxidants (for example, vitamins C and E), and also by certain ferments, as superoxide dismutase and catalase. At different states, like during increase of the level of free radicals and/or decrease of the level of antioxidants, there is high possibility of the DNA damage. Several in vitro investigations demonstrated that antioxidants are able to prevent damage of telomeres and increase duration of cell life. However, it is still not distinguished whether this action is preserved in conditions of in vivo state.

Some cases of the insufficiency of micronutrients are conditioned by insufficient nutrition, while others – by genetic variants. In any case, the damage of metabolism of nutrients takes place. Around 50 genetic illnesses of the human-being could be regarded as enzyme-polymorphisms. These genetic options can damage the activity of genes that determine biological accessibility of micronutrients and/or affinity to co-factors of participating ferments, like in DNA metabolism. Enrichment of the food with appropriate vitamins and minerals might in certain cases prevent damage of basic DNA metabolism paths, decreasing the risk of cardiovascular diseases development. Increase of co-factors’ concentration by means of nutrient supplementation is especially efficient in those cases, when gene mutation (polymorphism) decreases affinity to those co-factors, which leads to extension of chemical reactions duration. Hence, nutrigenomics here deals with investigation of the mechanisms of changing the health state in response to nutrient substances, depending on the genetic type.

Referring to Yaktine (2007), investigations of the gene mutation of methylene-tetra-hydro-folate-reductase (MTHFR) demonstrated that these mutations increase the risk of development of congenital pathology and oncological tumors. Moreover, the interdependence was found out, which dealt with interconnection of polymorphism of MTHFR (C677T), its co-factors of riboflavin and Norit eluate factor, and damage of chromosome stability. Thus, in case of increase of riboflavin concentration, there is increase of damage risk to chromosomes on the background of low content of Norit eluate factor.

Moreover, researches also demonstrated that consequences of insufficiency of Norit eluate factor and congenital mutation of MTHFR gene signify that even with insufficiency of Norit eluate factor of average rate there is significant increase of genome instability.

It was also demonstrated that certain genetic variants, except for development of cancer tumors, increase susceptibility to development of diseases, conditioned by insufficiency of micronutrients, among which there are DM2, obesity, cardiovascular diseases, and certain autoimmune diseases. Gene of vitamin D3 (VD3) receptors, for example, encodes nuclear receptors of VD3. It relates to the family of transcriptional regulatory factors. Although the core aim of these receptors lies in regulation of the minerals metabolism, they also take part in development of the immune response and growth of tumorous lesions. VDR gene polymorphism is associated with the change of mineral density of the bone tissue and pathophysiologic mechanisms of different chronic diseases, in particular, cancer tumors, breast cancer, prostate cancer, and malignant melanoma, diabetes mellitus DM2, Parkinson’s disease, pulmonary diseases, gastro-intestinal tract diseases, disseminated sclerosis, and periodontal illnesses.

Moreover, it is pointed by Zoumbaris  (2009) that Mediterranean diet (enriched with mono-undersaturated fatty acids and lean for saturated fatty acids, with high coefficient of omega-3 to omega-6, with polyunsaturated fatty acids, enriched with fruit, vegetables, beans and cereals) possesses more expressive anti-inflammatory peculiarities than Western-European diet. However, it is rather hard to distinguish those components of the diet, which determine these anti-inflammatory features. Besides, it is impossible to eliminate presence of dependence between the genetic type of the human-being and feedback on certain components of the nutrition budget. Thus, nutrigenomics tries to establish these interconnections, relations between certain genotypes, factors of environment, nutrition and risks to health. For example, there has been distinguished the genotype of apolipoprotein E4 (apoE4), which is recognized as the genetic marker of the decrease of risk of cardiovascular pathology and Alzheimer’s disease. It was established that genotype apoE4 has strong influence on the metabolism of vitamin E, which is known for its antioxidant peculiarities. Besides, it is necessary to remember that positive features of the definite food components could appear only in case of presence of other nutrient components or in some other conditions.

Limitations of Findings

In terms of following clinical investigations it is worth analyzing the action of certain microelements, and their combinations in different variants regarding the pathogenesis of inflammatory processes. Moreover, antioxidant micronutrients are irreplaceable for provision of protection against oxidative tissues damage. Investigations demonstrate that certain antioxidants might possess anti-inflammatory features. Except for decrease of concentration of free radicals, they might also decrease intensity of inflammatory processes. Therefore, antioxidant micronutrients are able to positively influence health state of humans during different inflammatory processes.

Another very important gene, AGT gene (angiotensinogen gene), is located at the locus 1q42 at the same region as the rennin gene. While investigation of AGT, over 15 mono-nucleotide polymorphisms were found, where the biggest part of them lead to amino-acid replacements. Those variants were investigated most of all, which were associated with substitution of methionine for threonine in codon 235 (M235T), and threonine for methionine in codon 174 (T1774M). Recently, the new polymorphism was found out in promotor region of gene – change of guanine for adenine in position -6 (-6G/A). This polymorphism was chained with M235T polymorphism, which explains the possible meaning of the last one in the change of the level of expression of AGT and its concentration in blood plasma.

While investigation of M235T polymorphism it was found out that presence of one or two alleles led to significant increase of AGT level in plasma that led to increased content of angiotensin-2, which also explains association of this polymorphism with arterial hypertension.

When analyzing M235T polymorphism regarding AGT, the correlation between T allele and different forms of hypertension was established. Moreover, it was almost in all cases found among the European and Japanese population.

While investigation of the population of the European origin from New Zealand it was found out that variant 235T is independent risk factor of development of heart attack or IHD. At the same time, Japanese population did not demonstrate the association of this polymorphism with IHD. There has not also been found the correlation between M235T.

Thus, these investigations are still rather limited and are not enough to draw clear conclusions. Hence, the abovementioned issues are still needed to be examined more profoundly and in details.

Discussion

All in all, scientists currently made a conclusion that taking into account nutrigenomics, there are three general genotypes of people. And it is worth correcting individual nutritional system according to the specific genotype description in order to eliminate the possibility of appearance of cardiovascular and other chronic diseases.

The first genotype of people is described as the range of people, who are nervous by their nature, have certain rate of memory loss. Those people have the tendency to be calmed down by means of food consumption, especially, sweets. Those people tend to abuse food consumption, and thus, suffer from obesity. Organism does not manage to synthesize hormones of happiness and balance on its own, that it why stress and permanent anxiety influence its ability by decreasing it, which leads to obesity, fatigue and anxiety. Rational nutrition for the genotype #1 means consuming of fish of fatty sorts, like herring, mackerel, salmon, and Pacific saury, since they possess omega-3 fats, which activate hormones that control feeling of hunger. Wheaten pastries are recommended to be substituted with bread of coarse flour.

People of the second genotype are considered as those who always feel hungry. They might also suffer from gastro-intestinal diseases, have long lasting headaches, and increased anxiety. It happens because of the cortisol hormone – stress hormone. This hormone keeps level of sugar in blood on the maximal level, which leads to the feeling of hunger. Such people are recommended to be nervous as less as possible and keep to the rationalized nutritional rates. They might substitute simple carbohydrates with complex ones (to substitute sweets with nuts and porridge, wheat bread with cereals) and consume products, enriched with magnesium.

People of the third genotype even after short physical activity feel pain in muscles; they tend to have insomnia, sharp reaction to noises and strong smell. Such people tend to be in passive condition and depressed. Scientists presume that the problem lies in the absence of gene, responsible for increase of enzymes production in the organism. Enzymes promote excretion of noxious substances from the organism. Thus, the people of the third genotype do not have these substances excreted. Consequently, these substances are accumulated in the connective tissues. Thus, scientists recommend to consume black grape, red grapefruit, and bitter chocolate, since these products are known to stimulate production of enzymes in the organism. Moreover, it is better to substitute sugar with honey, and black tea with green one, if possible.

Evidence Summary

It is vivid that micronutrients play important role in preservation of the genome. Taking into account that genome damage lies in the base of the pathophysiologic mechanisms of diverse diseases, it is worth paying attention to satisfaction of the needs for micronutrients to avoid cardiovascular diseases. Development of nutritional sciences, in particular, of nutrigenomics, altogether with development of methods to enrich food and new food supplementation, directed at preservation of the human genome, might provide the new viable mechanism of saving the health state for individuals, based on diagnostics and personalized nutritional preventative measures, aimed at checking genome for damages (as chromosome aberrance, instability of telomeres) and for degenerative diseases.

Currently, it is not yet possible to develop different diet recommendations with preventive measures for DNA damage checking, based exclusively on genetic type of the human-being. However, it is rational to use all the specter of accessible diagnostic measures for the nutrition structure or content of the nutrient supplementation in order to determine the most optimal way to preservation of the genome and prevention of the cardiovascular diseases.

Definitions

Nutrigenomics is a science investigating how nutrients influence the human organism.

Genome is a unity if genes that possess inherited information of the certain individual.

Telomere is the area of chromosome, located at its end, which are associated with the process of aging.

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