Nutrigenomics The answer to the ills of Humankind

2 March 2004 

 

THE MEDICAL RENAISSANCE GROUP

Nutrigenomics: The answer to the ills of Humankind ????

Dear All

This is a fascinating way the Pharmaceutical companies can make money out of Gene Typing

Quote

Beyond the obvious improvements to quality of life and health, we see a new mode for market segmentation. Imagine the possibility to identify small subgroups based on their individual genome, create products to satisfy their needs and then to market diets and products directly to them. The technology to accomplish in an economically feasible way is rapidly becoming a reality.

What they want to do folks is to maintain the 56 billion dollar processed food industry with its ramifications of depleted vitamins and minerals and the resultant onslaught of The metabolic syndrome,cancer, CVD and Obesity

Next they will create niche markets for those genetically compromised individuals who cannot cope with this diet ( Basically all of us )

Then they will Genotype us in the Doctor`s office for a cost ranging to 150 dollars.

We will see we are all genetically compromised and so through this wonderful personalised medicine we will get our tailor made expensive diets with the compliments of a Food Pharmaceutical business consortium

They may even give us vitamins which by then will be only probably available through the pharmaceutical Industry

Our Genes will be the answer to everything, Some lucky people will be able to drink alcohol like fish and smoke like chimneys and eat tons of dairy without toxic effects because so the theory goes --they have friendly Genes

So everything  will be measurable from a drop of blood

This is the future of Medicine ------------:

Doctors the Servants and Reps of large gene and Pharmaceutical companies of course serving the common Good of the Large Trans National Companies

And The Art and Science of Medicine ??

Leave that to Hippocrates

Michael

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Nutrigenomics: The next wave in nutrition research
By Dr.Nancy Fogg-Johnson and Alex Merolli (Life Sciences Alliance,
Pleasanton, CA)

Genes and nutrition will be the target of ongoing rese11arch

Understanding of human nutrition has followed developments in the sciences, primarily chemistry, biochemistry and physiology. During the "Naturalistic Era" (400 B.C.-1750 AD), Hippocrates hypothesized about the body's "innate heat"; during the next 500 years, little happened in either the development of scientific knowledge or nutrition science.

The late 1700's ushered in the "Chemical-Analytical Era" (1750-1900) highlighted by Lavoisier's calorimetry studies (1). He discovered how food is metabolized by oxidation to carbon dioxide, water and heat. He also invented the calorimeter, crucial to further understanding of heat energy. In the 19th century, Liebig recognized that carbohydrates, proteins and fats are oxidized by the body and calculated energy values for each. While chemists were examining the composition of foods and metabolism, physicians were studying the mechanisms and process of digestion, the means by which food is converted to useful, oxidizable components.

The "Biological Era" (1900-present) was founded on advances in chemistry, biochemistry and understanding of the metabolic pathways1. In the early 20th century, considerable research had been done on energy exchange and on the nature of foodstuffs. Nutrition science took a leap forward as evidenced by publication of the "laws of nutrition" by Langworthy. Once understanding of macronutrients was developed and better tools developed, nutrition scientists turned attention to the understanding of micronutrients, mineral and vitamin nutrition2. Most work during the last half of the 20th century (post 1955), the "Cellular Era," focused on understanding functions of essential nutrients and the roles of micronutrients (vitamins and minerals) as cofactors for enzymes and hormones and their subsequent roles in metabolic pathways. The roles of carbohydrates and fats in diseases such as diabetes and atherosclerosis were discovered and actual and potential mechanisms have been uncovered3.

Even in those observations of health and disease, puzzles existed. Why can some individuals consume high fat diets and yet show no evidence of atherosclerotic disease? Genetic differences certainly were suspected, but elucidating and proving cellular, molecular and ultimately genetic-level mechanisms in both healthy and unhealthy individuals proved to be a challenge.

With the continuing developments in tools that enable molecular level exploration of cause-effect phenomena, scientists have begun to develop hypotheses and conduct experiments to lay the foundation for a deeper level of understanding of gene-diet interaction. Today, an emerging field of nutritional research focuses on identifying and understanding molecular-level interaction between nutrients and other dietary bioactives with the human genome during transcription, translation and expression, the processes during which proteins encoded by the genome are produced and expressed.

The Next Step: Nutrigenomics
Continuing and accelerating discoveries in genomics present possibilities for an ever more dynamic era of scientific investigation based on understanding the effects of nutrients in molecular level processes in the body as well as the variable effects nutrients and non-nutritive dietary phytochemicals have on each of us as individuals. We call this the new era in nutritional science the genetic era, or nutrigenomics. On one hand, it represents a logical extension of biotechnology, molecular medicine and pharmacogenomics, while on the other, it is a revolution in how nutrition and diet are viewed.

Enabling science and technology platforms and techniques are essential for development of knowledge and advancements in science. Table 1 shows the key developments that are propelling nutritional science to the genetic level.

Application of the tools and techniques listed in Table 1 forms the basis of a relatively recent approach to drug research and development known as pharmacogenomics, the use of genetic information to predict the safety, toxicity and efficacy of drugs in individual patients or groups of patients. "Personalized medicine" developed through growing knowledge of pharmacogenomics has generated a lot of well-deserved enthusiasm as an important tool for the pharmaceutical industry. Collaborations have been extensively established.

Karl Thiel, staff writer for Biospace.com, creates an interesting scenario4: "You go to the hospital with complaints of chest pain. A doctor diagnoses you with chronic angina and recommends drug therapy. But instead of giving you a prescription, she gives you a quick pinprick blood test. Placed in a small machine, the sample is rapidly, automatically prepared for analysis and through a speedy hybridization or mass spec assay, a relevant portion of your genotype is determined. The results show that you have a genetic polymorphism that makes you unsuitable for the most common type of angina medication-its efficacy will be marginal and you will be likely to have significant side effects."

The application of similar tools and methods to examination of individual responses to macro/micronutrients is at its infancy. But we predict that nutrigenomics will be the next technological and commercial frontier emerging from genomics. How will this happen?

  • Individual genetic differences in response to dietary components have been evident for years: lactose intolerance, alcohol dehydrogenase deficiency, individual and population differences in blood lipid profiles and health outcomes after consumption of high fat diets.
  • Genomic information-including proteomics and SNP's-will be used to understand the basis of individual differences in response to dietary patterns.
  • The resulting nutrigenomic data also will provide a sound basis for development of safe and effective diet therapies for individuals or subgroups of the population.
  • Genomics can aid diet development and health outcomes from dietary patterns by defining specific sub-populations of patients.
  • Refined models of disease mechanism based on understanding the genome may provide new lines of research and possibly new diets. The elaboration of physical and genetic linkage maps combined with techniques to catalog massive databases of genetic information will uncover genes that may interact with diet to influence disease.

"Nutrigenomics will revolutionize wellness and disease management," said Guy Miller M.D., Ph.D., chairman and CEO of Galileo Laboratories, Inc., a biotech company working on cell-based therapeutic nutritionals. "Specifically, by being able to elucidate genetic profiles of individuals, diets will be formulated from crop to fork to confer prevention or retard disease progression. As basic science advances converge with e.commerce, new opportunities will emerge to deliver to consumers, whose genetic susceptibility to specific diets and diseases are known, products tailored to individual dietary needs.

"One driving force for nutrigenomics will be cost savings realized by consumers, employers, government and third party providers, through retarding and preventing disease," he continued. We are embarking on a new era to deliver to consumers exciting technologies to enable wellness."

Mapping Out The Possibilities
Genetic variations occurring in more than 1% of a population would be considered useful polymorphisms for creating a chromosome map showing the relative positions of the known genes on the chromosomes of a given species. A consortium of pharmaceutical companies and academic institutions has undertaken the task of mapping human SNP's. While the initial target of this effort is drug development, diagnostic applications are already developing. Can nutritional applications be far behind? We think not. Dave Evans, president and CEO, Wellgen, Inc., a startup company commercializing Rutgers University technology, agreed, "In less than 10 years, you'll be able to go to a lab and complete a set of genetic tests to identify your personal disease susceptibilities. When you leave you'll be armed with a list of foods to eat and foods to avoid and a recommendation of dietary supplements to help prevent your diseases."

Suppose the person with angina noted above has testing to understand the genetic polymorphisms that interact with diet to influence inception and development of a certain set of conditions or diseases. Specific diets could then be created to retard or block such development. If we have this information early enough, we could benefit future generations with markedly reduced risks of disease.

For instance, if we knew all the genes involved in cardiovascular health-detrimental ones, protective ones and how much each contributes individually and in combination, we might be able to reduce a person's likelihood of cardiovascular disease based on his or her genetic profile, as well as on age, gender and lifestyle habits. A genetic profile would enable individuals to adopt the habits most likely to reduce risk-because different genes or gene combinations respond differently to changes in diet, exercise, smoking, alcohol consumption.

Dr. Ronald Krauss, head of the Molecular Medicine Department at the Lawrence Berkeley National Laboratory, UC Berkeley, observed, "When a large group of people go on the same diet low in saturated fat and cholesterol, their LDL levels can vary widely." The question is "why?" Dr. Krauss further claims that, "recent evidence indicates that genetic factors can contribute to differences in dietary response." Studies with large samples do not satisfactorily predict individual responses due to unique genotypic differences. Dr. Krauss predicts the results of research on the interaction of genes and diet may lead to diet plans and /or drug regimens tailored to an individual's genetic predisposition to heart disease and stroke5.

Richard B. Weinberg, M.D., professor of internal medicine at Wake Forest University Baptist Medical Center reported in the New England Journal of Medicine6 that subjects with the variant gene (apo A-IV-2) showed lower increases in cholesterol and LDL than subjects with the more common gene (apo A-IV-1) when fed high egg diets. He hypothesizes that the variant gene affects dietary responsiveness by altering the efficiency of intestinal absorption of cholesterol. These findings may lead to better understanding of the larger normal population and how to control cholesterol absorption.

Dr. Jose M. Ordovas, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University in Boston, Massachusetts, has identified several of the 40 or so genes so far known to affect cardiovascular health. He estimates that there may be hundreds of genes that will ultimately go into a risk-analysis database. Dr. Ordovas explains that four main components under genetic control contribute to coronary artery disease risk, known as "syndrome x"7:

  • high blood lipids-total and LDL cholesterol, triglycerides
  • impaired glucose tolerance and diabetes
  • high blood pressure
  • obesity (in the abdomen).

Whether the genes for any of these components are manifest depends on an individual's habits as well as age, Dr. Ordovas says. Moreover, manifestation is interrelated. For example, in an obese person, a gene for obesity can trigger a normally beneficial gene for blood lipids to express high LDL cholesterol and triglycerides. However, if the person stays lean, the beneficial gene could prevail-all other things being equal.

Someday, health professionals will have a complete profile of the human genes involved in raising or lowering risk, says Dr. Ordovas. Children could be tested early in life so that diet and other lifestyle changes would be started before damage begins.

Relationships between individual differences in the ability to process milk proteins and highly puzzling neurological diseases such as autism and schizophrenia have been postulated. According to Dr. J. Robert Cade, University of Florida, an intestinal enzyme flaw in some individuals may lead to absorption of beta-casomorphin-7, a portion of the casein molecule. These individuals absorb the 12 amino acid peptide rather than free amino acids. The peptide produces exorphims, morphine-like compounds and are taken up by portions of the brain linked to autism and schizophrenia8.

Dr. Jo Freudenheim, SUNY at Buffalo, studies the role of diet in cancer, particularly breast cancer, risk9. She has examined the role of genetic polymorphism in genes for metabolic enzymes as modifiers of the effect of exposures such as diet and alcohol in cancer risk. According to Dr. Freudenheim, there appears to be an effect of a genetic factor related to alcohol dehydrogenase activity that influences the association between alcohol consumption and breast cancer risk. Among premenopausal women with both the genetic factors related to increased enzymatic activity and who have higher alcohol consumption, there was increased cancer risk. There was no such association for women with lower alcohol consumption or who had the other genotype.

The search for genetic markers for breast cancer susceptibility has led to an increasing number of epidemiological studies of relatively common genetic polymorphisms. These polymorphically expressed genes code for enzymes that may have a role in the metabolism of estrogens or detoxification of drugs and environmental carcinogens. Although the clinical significance and causality of associations with breast cancer is unclear, genetic polymorphisms may account for why some women are more sensitive than others to environmental carcinogens.

Where To From Here?
We certainly can envision concentrated, single bioactive compounds that could be delivered in a variety of forms. These could be enzymes that counter the effects of absent or decreased activities relevant to disease inception or development, autism or schizophrenia, for example. For instance, if a person lacking the intestinal enzyme to hydrolyze the indicated portion of the casein molecule, could take it in pill form prior to consumption of milk products, this may lead to improved quality of life for those suffering from certain neurological disorders. The same may be true for susceptible females who may need to intake alcohol dehydrogenase before consumption of alcohol. The possibilities are manifold.

We can see the development of food/beverage products either as preventive agents or as treatments specific for those with a propensity for disease. The most prevalent current example is the ketogenic diet used for treatment of pediatric epilepsy patients considered intractable, non-responsive to pharmaceutical regimens. The possibilities extend to important segments such as those with propensities for cardiovascular, cancer and others described above.

What does this burgeoning new field of understanding presage? Beyond the obvious improvements to quality of life and health, we see a new mode for market segmentation. Imagine the possibility to identify small subgroups based on their individual genome, create products to satisfy their needs and then to market diets and products directly to them. The technology to accomplish in an economically feasible way is rapidly becoming a reality. According to Dr. B. Michael Silber, Pfizer, "it costs $150 or more to identify each of a person's S.N.P.'s. The goal, he adds, is to get the price down to pennies, which he calls feasible. Some challenge that consumers do not want to know. We think that the drive for prevention and prolongation of life quality will prevail, particularly when costs permit wide diffusion into our culture.

Who will do this? Certainly, the academic community, rich with new tools, is making relevant discoveries daily. Small, entrepreneurial start-up companies who are willing to make the needed investment and take the risk will most likely be first to market. Food processors marketing mainstream products will wait for the products to be created and demand to be established. We will then see them applying their extensive marketing skills to reach ever more segmented groups. Rather than the current demographic or psychographic segmentation tools, the future belongs to those who can adapt to deliver products based upon new applications of genomic tools.

References
1) "A History of Nutrition", E.V. McCollum 1957 QU 145 McCol.

2) Nutrition; An Integrated Approach, Ruth Pike and Myrtle Brown, John Wiley & Sons, 1975, pp 4-8.

3) "Fundamentals of Nutrition", Course Syllabus, University of Vermont.

4) Biospace.com "Pharmacogenomic Medicine: Technology Outpacing the Health Care System."

5) AAAS symposium on "Gene-diet Interactions in Coronary Heart Disease," AHA press release 2/14/98.

6) "Attenuated hypercholesterol response to a high-cholesterol diet in subjects heterozygous for the apolipoprotein A-IV-2 allele," Weiberg et al, N Engl J Med, Vol. 331, No.11, pp 706-710.

7) "Attacking Heart Disease at Its Genetic Base", Agricultural Research, 7/99.

8) Autism and Schizophrenia: Intestinal Disorders, Cade R et al. Nutritional Neuroscience, in press 1999.

9) Symposium: Interactions of diet and Nutrition with Genetic Susceptibility in Cancer, Journal of Nutrition, Vol. 129, 2/99, pp 550S-551S.

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Last updated 19/12/2002

Research Centers

A listing of research source for Nutrigenomics and related studies:

University of California at Davis

www.nutrigenomics.ucdavis.edu

Sciona Ltd.

www.sciona.com

Centre For Human Nutrigenomics

www.nutrigenomics.nl

Nutraceuticals World

www.nutraceuticalsworld.com

Institute of Food Research

www.ifr.bbsrc.ac.uk

University of Guelph

www.uoguelph.ca

 

Molecular Expressions

Uridine