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The recent advance in genetics helped to understand the mechanisms of gene-diet interactions at molecular level and launch the study of nutrigenomics. In addition to this the worldwide epidemic of obesity and increase in other diet-related diseases, significance of nutrition research changed accordingly. Many studies conducted recently have discovered the role that certain nutrients have in gene expression. One of the well established examples includes cardioprotective effects of fish-oils fatty acids consumption and differences in such response between sexes and individual genotypes. Increased risk for ischemic heart disease and stroke also has been proven to be associated with single nucleotide polymorphism (SNP) that has an effect of metabolism of homocystein (Hcy). Furthermore, the results have also found that diet can be effectively used for disease treatment in many conditions without need for taking medications. However, due to the fact that nutrigenomics is an emerging science, there are many ethical, social and legal issues that constantly arise and have to be addressed. This paper reviews the literature and examines various clinical and epidemiological studies that have been published in the last ten years and which illustrate the coherence of the available data and therefore the importance of nutrigenomic science. The dissertation looks also into more details at the controversy and concerns standing behind this science.
Key words: * nutrigenomics * contemporary tool * disease prevention *
* genetics * lifestyle * single nucleotide polymorphism *
In recent years, there has been increasing progress in understanding the science of nutrigenomics. Its advance was possible due to the continuing developments of post-genomic technologies that has been termed the 'trilogy of omics' and are named respectively: transcriptomics, proteomics and metabolomics (Bland, 2005). Those tools provided the means to explore deeper the molecular level and mechanisms of cause-effect and gene-diet interactions. Applying this knowledge, nutrigenomics is proposing new approach in dietary assessment and intervention with regard to individual genetic profile and differences in subject's genotypes. This will revolutionize course of health promotion and disease prevention programs and provide new opportunities such as personalized diet tailored to individual dietary needs, lifestyle and genetic background.
The emerging field of nutrigenomics has a great importance in the Public Health arena. In modern world, which is facing a drastic increase in nutrition related health problems such as type 2 diabetes, overnutrition and obesity, focus on nutrition research changed accordingly. This dynamically expanding science gives a perspective of saving tremendous amount of money which is currently spend in a greater degree on treatment than disease prevention. Nutrigenomics can provide better insight into food interactions in our homeostatic systems and estimate possible adverse or beneficial effects of food compounds before a disease state occur. Thus, more attention will be drawn to disease prevention and promoting healthy lifestyle than to treatment of diet-related diseases which complications are very costly. In addition, as nutrition related health problems are considered as a one of the biggest concerns for Public Health and burden for National Health Service, the perspective of avoiding undesirable costs should be a driving force for government to invest in the nutrigenomics. Such actions will allow this area, which is currently at very early stage in deciphering gene-nutrient interactions, to conduct clinical trials and research studies in order to elaborate clear mechanisms involved and become meaningful in the world of science.
Origins of the concept that diet affect health dates back to the ancient times. Around 400 B.C., Hippocrates, an ancient Greek who is considered as 'the father of medicine' advised physicians using words: 'Leave your drug in the chemist's pot if you can healsyour patient with food'. Likewise, it has also been known for a very long period of time that human beings can vary in the requirements for a particular nutrient or response to dietary component.
The science of nutrigenomics includes various genetic diseases, which involve mutation in a single gene and therefore cause disorders of metabolism. These often called 'inherited metabolic diseases' or 'inborn errors of metabolism' has been known for several decades and are effectively treated and managed by dietary regimen or manipulation. One of the examples of this disorder is phenylketonuria (PKU). The individuals suffering from PKU are deficient in enzyme phenylalanine hydroxylase (PAH) and therefore cannot metabolize amino acid phenylalanine (Phe). The disease is cured by exclusion of food containing Phe from the diet (Koch, 1987). Other examples include alcohol dehydrogenase deficiency, lactose intolerance and galactosemia.
Further rapid change in technology and evolution of ideas were initiated by 'the age of molecular medicine' pioneered by work of investigators such as Linus Pauling, Watson and Crick that described the structure of DNA in 1953 (Bland, 2005). However, before the human genome was sequenced scientists did not have knowledge about precise mechanisms of how DNA operated. Therefore, in the late twentieth century, after the innovation in molecular genetics started with the Human Genome Project (HGP) (1990-2003) this knowledge became widely available. The project aimed to determine the sequence of 3 billion chemical base pairs and identify numerous genes on the 23 pairs of human chromosomes that make up DNA and was successfully completed in 2003. The nature and content of human genetic information helped to identify genetic diseases as well as their interaction of genes with dietary factors and various components of diet (Lander et al., 2001). Successful completion of the Human Genome Project is therefore considered as the beginning of the new era in nutritional science - nutrigenomics.
2. Review of Literature
2.1 Nutrigenomics as contemporary tool for disease prevention
According to Simopoulos (2003), nutrition is one of the most important environmental factors that influence health and disease relationship. Additionally, recent progress in fields of genetics and nutrition shed a light on the genetic differences in dietary response and the role that substances in a diet have on gene expression. It has been concluded that 50% of difference in cholesterol concentration in plasma, 75% in bone density and 30-60 % of the variance in blood pressure is genetically determined. Therefore, since the diet is a cofactor in each of these genetically influenced conditions it is clearly important to determine the mechanisms of diet-genotype interactions in individuals at risk of the disease.
It's essential to emphasis that genes are not responsible for occurrence of particular disease per se. However, there are a code for a various strengths and weaknesses that in turn contribute towards resistance or susceptibility for particular disease when triggered by certain dietary factors. What's more nutrient may support optimal genetic expression that promotes good function what is considered as 'genetic potential through nutrition' (Bland, 2005).
Many studies have been conducted in a field of nutrigenomics that provided the evidence of beneficial influence on health of certain substances in a diet. One of the investigation demonstrated that omega-3 fatty acids have a role in balancing gene expression and reduction of synthesis and secretion of messenger molecules that are related to type 2 diabetes, CVD and dyslipidemia risk (North et al., 2003; Babcock et al., 2004). This clinical nutrigenomic intervention trial have proven that administration with 3-6 grams of an omega-3, eicosapentaenoic acid (EPA) supplement can reduce insulin resistance and risk of vascular complications. The results stating of cardioprotective actions of the fish-oil fatty acids are consistent with other studies conducted by Wang et al., (2006) and Whelton et al., (2004).
The objective of FINGEN Study that enrolled 312 mixed gender aged 20-70 participants was to determine the effect of moderate EPA and DHA supplementation (<2g EPA & DHA/d) on the plasma fatty acid profile in regard to sex and apolipoprotein E (APOE) genotype of the subjects (Caslake et al., 2008). According to the results obtained by Caslake et al., (2008) intakes of fish-oil fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) has a higher triacylglycerol-lowering response in man than in women. It was also concluded that APOE4 genotype can influence responsiveness to lowering effect achieved by fish oils. The analysis has shown a high positive trend towards greater reaction in carriers of Îµ4 allele. The FINGEN study is considered as the most comprehensive study that investigated the effects of fish oil supplementation on plasma lipid and first to look into this relationship in regard to sex and APOE genotype.
Other study that involved 755 male and 822 female subjects, was designed o analyze the association between HDL-cholesterol concentration, essential fatty acids intake (n-3 and n-6 polyunsaturated fatty acids - PUFAs) and genotype APOA1 (Ordovas, 2002). The participants were divided into low, medium and high PUFA intake groups. It has been concluded that in women with A allele, high intake of PUFA caused an increase in HDL-cholesterol. However in women homozygous for the G allele the reaction was opposite. There was no significant difference in regard to males. All the interactions are shown in Figure 1. Further investigation of these correlations, may in the future serve as a basis for individualized nutritional advice based on individual genetic makeup where women with A allele should consume high dose of PUFAs in order to increase HDL-cholesterol and lower the risk of cardiovascular disease. On the other hand G/G females should follow opposite recommendations (Ordovas, 2006).
The figure shows mean (+SE) HDL-cholesterol concentration (mmol/L) by APOA1 genotype categorised into polyunsaturated fatty acid (PUFA) groups (where â-¡ <4%; â- 4%-8%; â- >8% of energy) in women (G/G, A/A) and men (G/A).
(Modified from Ordovas, 2006)
Another well-studied example that proves the significance of nutrigenomics examined the effects of homocysteine (Hcy) in reducing ischemic heart disease and stroke. Current investigations have recognized several genetic polymorphisms that have an effect on metabolic pathway of Hcy. One of most widely studied is methylentetrahydrofolate reductase (MTHFR) C677T polymorphism. People with homozygous type in this single nucleotide polymorphism (SNP), estimated 10-15% of general population, have diminished ability of conversion of folic acid into active 5-methylene tetrahydrofolate (5-MTHF) form (Gerdes et al., 2004). This in result cause impaired conversion of Hcy to methionine. Individuals will require higher dose of folate or administration with 5-MTHF to maintain low levels of Hcy and reduce risk of homocysteine related cardiovascular diseases (CVD) and neural-tube defect (Molloy et al., 1997). As reported by Molloy (1997) dietary referenced values regarding folate intake as well as other nutrients, may have to be adjusted. This is due to the fact that they apply only to general population and do not take into account individuals genetic variations and metabolic abnormalities that may compromise status of some nutrients and substantially increase ones needs.
The nutrigenomic and lifestyle intervention may also serve as a substitute for medications, which are often associated with many concerns. This is due to the fact that drugs are artificially manufactured and therefore, they can cause serious adverse effects and at the same time they are usually expensive. The application of drugs is also associated with a later stage of disease that very often manifests irreversible changes. There is a various range of conditions that can be cured without medications such as high cholesterol, acne, depression and digestive complaints (Bland, 2005). A study conducted in 2001 by the National Institutes of Diabetes and Digestive and Kidney Diseases investigated the influence of diet and exercise on risk of developing type 2 diabetes mellitus (DM). The findings were really consistent and in result the study was terminated a year early, concluding that diet and physical activity can significantly reduce the risk of developing type 2 DM (Hawthorne, 2003).
2.2 Controversy in a field of nutrigenomics
Nutrigenomics as a relatively new science raises many concerns in regard to ethical, social and legal issues (Castle & Ries, 2007). Its practical application is associated with genetic testing in order to reveal predisposition to conditions that can be prevented with dietary intervention. However, as the science has not existed long enough and involves many interrelated fields such as genetics and nutritional science there is no regulations specific to this field. For that reason, the European Nutrigenomic Organisation (NuGO, 2007) has formulated bioethics guidelines to help address issues for concerns in nutrigenomic studies such as data protection and privacy.
Due to the increase in marketing genotyping services, food and supplements designed for individual needs, it is also essential to consider concerns associated with direct to consumer (DTC) marketing (Castle et al., 2006). These include protection of consumers from unproven tests, and supplement regimens with no scientific proof, insurance companies which may use the genetic information for risk rating of their clients.
The experiment conducted by United States Government Accountability Office has drawn the attention to that problem. The GAO examined results from genetic samples of 14 'fictitious consumers' sent to 4 nutrigenomic companies advertised on the internet (US GAO, 2006). It has been concluded that the results made medically unproven health-related predictions so enigmatic that did not provide valuable information for consumers. In addition, expensive supplements sold by them were not as falsely claimed designed in accordance to individual DNA and were potentially harmful. Therefore it is important to address the ethical and legal issues arising from the current situation. First of all, support nutrigenomic education and progress in research and at the same time develop means to protect consumers from disreputable companies.
In conclusion, the review of literature and various epidemiological and clinical studies has explained the great importance of nutrigenomics. This science has an enormous potential, since not that long ago we have learned that food is more than implement to provide calories and prevent diseases associated with nutrients deficiencies. But also, carry important information that affect gene expression, proteins as products of gene expression and metabolism comprised of all the processes occurring in the body. In addition, science of nutrigenomics can be considered as a tool that might be used oppose to general dietary guidelines that are not taking in consideration genetic variations occurring between individuals. It is therefore important to expand the knowledge of nutrigenomics, as its application will be much more cost-effective in chronic diseases management than the present system of public health, based on a concept that 'one size fits all'. Clinical nutrigenomics will allow greater precision in achieving favourable outcomes, due to application of personalised intervention. In result, it can serve to increase outcomes of intervention as well as reduce unnecessary healthcare expenditure. Nutrigenomics will also change the nature of health care, and enable people to learn how to nourish themselves to prolong and optimize their life span in good health. Individuals that will accustom genetic testing will also have greater degree of compliance to the recommended diet and therefore improved outcomes.
However, there is still much to do in regard to investigations into clear mechanisms of nutrient-gene interactions and a variety of ethical concerns to address. Undoubtedly, the field of nutrigenomics is a science of the future that will have a remarkable meaning and influence on the area of human genomics and molecular nutrition.