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  • Boost Your Immune System to Fight The Flu

    Posted on October 12th, 2009 editor No comments
    Below is an interesting article on how to protect yourself from the flu and boosting your immune system.  The information presented is sound and for many health conscious individuals, already known.  What you may not know is there are genetically guided nutritional products that allow you to achieve the desired results, without guessing what specific products you personally may need.  If you are interested in learning more about DNA guided nutrition, please click here.

    Written by Kristi Runyon

    Monday, 12 October 2009 17:33
    altUntil H1N1 vaccines are available the general public has little or no protection against swine flu.   So what can you do to arm yourself against the flu?  You can start by taking steps to strengthen your immune system.

    Several factors can contribute to a healthy immune system.  Your body’s ability to fight off illness can be affected by diet, exercise, sleep, and stress.
    The Cleveland Clinic offers some good advice on how your daily habits can either strengthen or weaken your immune system:

    Source: my.clevelandclinic.org/

    How can I strengthen my immune system?
    While it is difficult to enhance a normal functioning immune system, there are things that you can do to protect and strengthen your immune system during periods of illness or in the face of chronic disease. The three areas that are most important in protecting and bolstering the immune system are diet and nutrition, exercise, and stress reduction.

    Diet, nutrition, and immunity
    There have been many excellent books written about the relationship between diet, nutrition, and immunity. (Please refer to the reading list below.) There are two major changes you can make in your diet to help your immune system. First, you can enrich your diet with antioxidants and, second, you can make sure you are getting enough nutrients and micronutrients.

    Antioxidants
    Antioxidants are vitamins and minerals, found in foods and available as supplements, that remove harmful oxidants from the bloodstream. Oxidants, also known as free radicals, are the toxic byproducts our bodies make when we turn food into energy. They are also byproducts of cigarette smoke, pollution, sunlight exposure, and other environmental factors. Free radicals are capable of damaging DNA and suppressing the body’s immune system.

    Free radicals also play an important role in the development of many human diseases. In fact, there are several journals now dedicated to their study and investigation. Nearly all types of cancers have been related to diets that are poor in antioxidants. Data from some research also suggest that a diet high in antioxidants might also protect against cancer.

    Heart disease and atherosclerosis (hardening of the arteries) are also brought about, in part, by free radicals. Certain diseases of the central nervous system — such as dementia and some forms of kidney, gastrointestinal, and skin disease — also involve free radicals. You cannot prevent these diseases simply by taking antioxidants. You can, however, ensure that you are doing everything possible to lessen their effects. Most importantly, you should eliminate environmental factors that promote the production of free radicals.

    Nutrients and micronutrients
    Marginal nutrient deficiencies in the diet can also weaken the immune system. Marginal deficiency is a state of gradual vitamin loss that can lead to a general lack of well being and impairment of certain biochemical reactions. Marginal deficiencies of micronutrients (nutrients required only in a small amount) do not cause obvious symptoms of disease, but they can affect your mental abilities, your coping abilities, and your body’s ability to resist disease and infection. They might also slow your recovery from surgery.

    Marginal nutrient deficiencies are very common in both younger and older individuals. The typical American diet is often deficient in a variety of nutrients including calcium, iron, vitamin A, and vitamin C. Furthermore, the recommended daily allowance (RDA) for many nutrients might be well below what is needed to optimally protect the immune system. For this reason, vitamin and mineral supplements are used to protect us against micronutrient deficiencies.

    Foods
    You can further modify your diet by eating less saturated fat and animal protein (particularly red meat), by limiting dairy products (particularly those with fat), by modifying your use of oils and fats, and by eating more fresh fruits, vegetables, and whole grains.

    Take a minute to examine your diet. How many times a week do you eat fried foods or red meat? What types of oils do you use in your cooking? Do these oils include cooking oil as well as butter and margarine? What types of garnishes and sauces do you use? Do they contain egg yokes or oils? What types of dairy are you consuming? If you drink milk, which is good for you, is it anything less than skim or 1%? Do the yogurts and cheeses you eat contain a lot of fat?

    Recommendations
    Try eliminating red meat from your diet or, if necessary, eat it no more than once every 10 days. Also eliminate or reduce your intake of fried meats. Try to replace the meats in your diet with servings of fish, particularly oily fish such as salmon. Salmon contains a rich form of an oil known as omega-3 fatty acids, which has natural anti-inflammatory properties.
    Use only olive oil in your cooking. Olive oil is rich in mono-saturated fats. All other oils, with the possible exception of canola oil, have unfavorable types of fats for the immune system. Avoid excessive use of margarine. Though most margarines are unsaturated in their fat content they are artificially prepared and the long-term effects of their use are not known. Try to minimize the use of all fats, but wherever possible use olive oil in cooking and for dressing salads.
    Eat more fruits and vegetables. Green leafy vegetables such as broccoli are very rich in antioxidants. Add several servings a week to your diet. Do not overcook them and think of creative ways to prepare them. Add more servings of other fruits and vegetables to your diet, as they are rich sources of antioxidants as well.
    Add fiber to your diet. Fiber can be found in many types of whole grains. If you are going to add rice, which is healthy, try to add brown rice. Brans and cereals are also helpful, but avoid those with any form of artificial sugar.
    Drink plenty of water.
    If you follow these guidelines, you will move your diet in the proper direction toward protecting your immune system. As an added benefit, you will be following a diet that is also good for your cardiovascular system. (These recommendations are similar those of the STEP II diet promoted by the American Heart Association.)

    Ideally, fat should account for less than 30 percent of your total calories. Less than 7 percent of your total calories should come from saturated fats. In addition, you should try to eat less than 200 milligrams (mg) of cholesterol per day.

    Nutritional supplements
    Much has been said about nutritional supplements and their ability to enhance or protect health. While there is a lot of debate in the medical literature, and many doctors do not discuss their use with their patients, some CFS specialists believe that nutrients can provide a measure of protection for the immune system. No matter how well you design your diet for nutrition, you can still augment it with supplemental antioxidants. Some of the best studied and most readily available as supplements are beta carotene, selenium, vitamin C, vitamin E, and vitamin A.

    Supplementing your diet with a balanced multivitamin is essential. To do this, you should add beta carotene in a dose of 25,000 international units (IU) twice per day. In addition, vitamin C in doses of at least 500 to 1000 mg a day is recommended. Why these vitamins? Beta carotene is one of the most potent nutrients and can protect the body from oxidative stress. Populations that have diets high in beta carotene have a lower incidence of certain forms of cancer.

    Several studies have shown that beta carotene supplements can do little to reduce cancers in people who smoke cigarettes. This fact should not be surprising. Dietary modifications are made to bring back a failing immune system or to protect a healthy immune system, not to overcome overwhelming toxic effects of activities such as smoking.

    Vitamin C is also an extraordinarily important antioxidant. While many studies have shown that daily ingestion of vitamin C does little to protect you from the common cold, it can reduce the severity of colds. Furthermore, there are several controlled studies performed in populations of people working under heavy stress that have shown a profound protective effect of vitamin C in terms of common colds and pneumonia.

    Other nutrients that might be helpful include selenium in doses of 200 micrograms (mcg) per day and vitamin E in doses of 400 IU per day. Many over-the-counter vitamins with similar doses are available. There is no difference between natural vitamins and synthetic vitamins.

    Exercise and immunity
    Even more so than nutrition, exercise has the capacity to protect and even enhance the immune response. Experimental studies have shown that a regular exercise program of brisk walking can bolster many defenses of the immune system, including the antibody response and the natural killer (T cell) response.

    Fortunately, the intensity and duration of exercise needed to support the immune system is less than that needed to provide the best cardiovascular training. Thus, even relatively low levels of aerobic exercise can protect your immune system. Twenty to 30 minutes of brisk walking five days per week is an ideal training program for maintaining a healthy immune response.

    Exercise can also improve your mental wellness. Regular aerobic exercise can help relieve mild to moderate degrees of depression and anxiety. People who exercise also have less loneliness and anger, and are better able to control their own destiny. It is not clear whether exercise boosts the immune system directly or works through a link with the brain and nervous system.

    Stress and immunity
    The final component for fine-tuning your immune system is reducing the stress in your life by achieving a higher level of spiritual harmony. Altered mood states such as depression, anxiety, and panic are harmful to the body in many ways. Secondary symptoms such as fatigue, difficulties with memory and concentration, aches and pains, and problems with sleep are common in people with mood disorders. Mood disorders also harm the immune system.

    There are many techniques you can use to reduce stress and anxiety in your life. Guided imagery involves focusing on mental images, such as a serene setting. You can also try yoga or tai chi, which combine both mental and physical exercise, and can help heal the mind and the body. You might consider using biofeedback, a process in which you monitor certain functions of the body, such as blood pressure, and learn to alter these functions through relaxation. Other simple techniques include breathing exercises or taking a walk and appreciating the beauty in the world around you.

    For people who have severe mood disorders, antidepressants and other psychotropic medicines, as well as counseling, are essential.

    Putting it all together
    Diseases such as chronic fatigue syndrome, fibromyalgia, and many other poorly understood illnesses should no longer be viewed as disorders of either the mind or the body. The mind and body act as one unit and thus we must approach them together.

    To maintain the strongest immune system possible, you must have a nutritious diet, get regular exercise, and reduce stress in your life. You must attend to all three of these areas to achieve your optimum health.

    Some people eat a nutritious diet and exercise regularly, but are so keyed up in their lives that their stress levels overcome all of the success they achieve in the first two areas. Other people might have successfully modified their mental and spiritual state but are eating unhealthy diets or are sedentary. Others might make significant advances in all three areas, but are doing foolish and harmful things to their bodies, such as smoking or using excessive alcohol, which take away from their achievements.

    Dr. Andrew Weil, noted author and director of the program in integrative medicine at the University of Arizona, has written extensively about the body’s ability to heal itself. Many health care providers have witnessed people overcome complex medical illnesses without the assistance of medicine. Though medicines are vital for overcoming many acute illnesses, they might be less important in overcoming chronic diseases.

    You can take advantage of the body’s inner ability to heal by eating well, exercising regularly, and striving for spiritual well-being. Eliminate other negative factors such as drugs, alcohol, tobacco, and other insults to the your body. Only you can put it all together and it cannot be achieved overnight. There is no better time to start than now.

    DNAWellnessinfo.com Resource:  http://www.wtvq.com/health/537-boost-your-immune-system-to-fight-the-flu

    DNA Guided Nutrition:  To learn more click here.

  • New era of gene-based personalized medicine’ dawning

    Posted on June 14th, 2009 editor No comments
    Posted on Sunday, 06.14.09 on miamiherald.com

    By ROBERT S. BOYD

    McClatchy Newspapers

    WASHINGTON — Six years ago, scientists announced the completion of the Human Genome Project, a historic effort to decipher each of the 3 billion letters in the genetic instruction book for our species. A single anonymous male from Buffalo, N.Y. – code name RP11 – provided the bulk of the DNA used for the project.

    Now, many thousands more people are contributing DNA samples for a wide array of follow-on studies designed to turn the project’s findings to practical use in health care, genetics and biological research.

    Researchers and doctors have opened a new era of “personalized medicine” that seeks to tailor therapies to patients based on their unique genetic makeups and medical histories.

    According to the National Cancer Institute, the days are passing when most cancer tumors were thought to be essentially the same and patients got the same drugs.

    “We’re not very good at selecting therapies for individual patients,” Dr. Rick Hockett, the chief medical officer of Affymetrix, a genetics firm in Santa Clara, Calif., told a conference on personalized medicine this month in Washington. “Targeted therapy,” he said, can “improve the benefit-risk ratio for patients.”

    For example, Hockett said that heart patients who took the popular anti-clotting drug Plavix had a greatly increased risk of serious problems, including death, if they had two tiny mutations in their genes.

    Massachusetts General Hospital in Boston and the Memorial Sloan-Kettering Cancer Center in New York have begun to screen lung tumors for genetic abnormalities that could reveal whether a particular treatment is likely to work or should be avoided.

    Last year, Dr. Richard Wilson, the director of the Genome Sequencing Center at Washington University in St. Louis, compared 20,000 genes in cancer cells from a woman who died of leukemia with healthy cells also taken from her body. Wilson identified 10 mutations – or genetic mistakes – related to her cancer, including one that blocks chemotherapy drugs from getting inside the cancerous cell.

    Other developments in the approaching world of personalized medicine include:

    -A “Personal Genome Project” led by George Church, a geneticist at Harvard Medical School in Boston, aims to recruit 100,000 people of diverse backgrounds to analyze their genomes and medical histories.

    The first 10 participants already have published their personal data – including their pictures, weights and smoking and drinking habits, as well as their DNA – on the Internet for anyone to see at www.personalgenomes.org/pgp10.html.

    To take part, volunteers donate hair and saliva samples for DNA analysis. So far, 13,000 people have asked to be enrolled. For privacy, their data will be encoded by number, not by individual names.

    The goal is to discover which genetic variations are related to which diseases, so that targeted therapies can be designed. According to Church, at least 1,449 genes have been linked to potential illnesses. For instance, a gene called ApoE is associated with a higher risk of Alzheimer’s.

    -The National Human Genome Research Institute in Bethesda, Md., has launched a “1000 Genomes Project,” which has started to collect DNA from 1,000 individuals from Africa, Asia and Europe. The goal is to provide much broader and deeper information than the original, limited Human Genome Project could.

    Researchers are seeking clues to individual differences in susceptibility to disease, response to drugs and sensitivity to the environment.

    Just as astronomers see farther and more clearly into the universe with bigger telescopes, the results of the 1000 Genomes Project will give us greater resolution as we view our own genetic blueprint,” Francis Collins, the former director of the National Human Genome Research Institute, said in a statement explaining the plan. “We’ll be able to see more things more clearly than before, and that will be important for understanding the genetic contributions to health and illness.”

    -The National Geographic Society is collecting DNA from about 300,000 people for a “Genographic Project” that traces their distant ancestries from continent to continent all the way back to their African roots.

    Researchers at 10 centers around the world collect DNA samples from local populations. A team led by Spencer Wells, a genetic anthropologist and the magazine’s “explorer in residence” in Washington, will analyze the samples.

    In addition, anyone who wishes to can buy a $100 self-testing kit and provide a saliva sample to the Genographic project. Participants will get back reports that describe in general terms the migration of their ancestors from their original roots in Africa some 60,000 years ago.

    -A booming, but controversial, genetic testing industry also has sprouted, offering to analyze a person’s DNA – at a price – for possible susceptibility to cancer, Alzheimer’s and dozens of other diseases.

    More than 1,000 such tests are on the market, Kathy Hudson, the director of the Genetics and Public Policy Center at Johns Hopkins University in Washington, told a congressional committee.

    According to the Human Genome Project’s Web site, some genetic tests have “greatly improved or even saved lives,” but there are concerns that they might be used by insurance companies to deny coverage or by employers deciding whom to hire or promote.

    To meet these concerns, Congress passed a “Genetic Information Non-Discrimination Act” last year, which is just starting to have an impact.

    “The portions of it relating to health insurance just went into effect on May 21, and so will apply to next year’s (health) plan for most people,” said Susannah Baruch, of the Genetics and Public Policy Center. The parts of the new law that relate to the use of genetic information on the job won’t take effect until Nov. 21, but the Equal Employment Opportunity Commission already has drafted regulations.

    ON THE WEB

    More on personalized medicine: www.personalizedmedicinecoalition.org

    Personal Genome Project: http://www.personalgenomes.org

    1000 Genomes Project: http://www.1000genomes.org/page.php

    National Geographic’s Genographic Project: https://genographic.nationalgeographic.com

    DNAWellnessinfo.com Resource:  http://www.miamiherald.com/news/politics/AP/story/1096679.html

    DNA Guided Nutrition Breakthrough:  http://www.dnaguidedwellnessproducts.com

    127x16 1 New era of gene based personalized medicine dawning

  • Can taking a multivitamin extend life?

    Posted on May 29th, 2009 editor No comments

    Los Angeles Times – Health

    3:22 PM, May 29, 2009

    Multivitamins Among the keys to longevity are telomeres, DNA sequences at the end of chromosomes that shorten as we age. When cells replicate, telomeres shorten. Thus, preserving the length of telomeres is thought to be a possible key to living longer.

    A study in the new issue of the American Journal of Clinical Nutrition found that people who take multivitamins daily had telomeres that were 5.1% longer, on average, than non-vitamin users. The researchers, from the National Institutes of Health, looked at multivitamin use and nutrient intake, as well as telomere length, in 586 women ages 35 to 74. They also found a link between telomere length and intake of vitamins C and E.

    How multivitamins may affect telomeres is unknown. But studies have shown that telomeres are vulnerable to oxidative stress, and some vitamins are antioxidants. But since the study is epidemiology, not a cause-and-effect study, it will take more research to know whether multivitamins really impact telomere length.

    “To our knowledge, this was the first epidemiological study of multivitamin use and telomere length,” Dr. Honglei Chen, of the National Institute of Environmental Health Sciences, wrote in the report. “Regular multivitamin users tend to follow a healthy lifestyle and have a higher intake of micronutrients, which sometimes makes it difficult to interpret epidemiological observations in multivitamin use.” But, they added, “the results are consistent with experimental findings that vitamins C and E protect telomeres in vitro.”

    – Shari Roan

    Photo credit: Los Angeles Times

    DNAWellnessInfo.com Resource:  http://latimesblogs.latimes.com/booster_shots/2009/05/can-taking-a-multivitamin-extend-life.html

    DNA Guided Nutrition Breakthrough:  http://www.dnaguidedwellnessproducts.com

    127x16 1 Can taking a multivitamin extend life?

  • Customized vitamins a fix for genetic flaws?

    Posted on June 6th, 2008 dna4wellness No comments

    (06-05) 20:01 PDT — UC Berkeley scientists are exploring whether high-speed gene-reading machines – like those used to decode the human genome – will be able to find subtle genetic flaws that can harm health and can be cured by treatments as simple as vitamins.

    Eventually, they hope, these scans will help nutritionists customize a course of vitamins to match the strengths and weaknesses of every individual. “Think of it as a metabolic tuneup,” said Berkeley researcher Nicholas Marini.

    Marini and a team of researchers reported this week that they had found, in DNA samples from over 500 people, four types of genetic mutations that were treatable with folate, a well-known member of the vitamin B family. One of the four had already been identified as a relatively common genetic defect that responded to the vitamin. The three others were new.

    Although the research is years away from practical tests on humans, the study published Monday in the journal Proceedings of the National Academy of Sciences is a first step showing that such tuneups might be possible.

    Marini cautioned that there is much about the interaction of genes and nutrition that is still unknown. “The reality is, we don’t know how to interpret a lot of this information,” he said.

    Raising ethical questions

    The study was partially funded by the Department of Defense, which saw the potential to improve human performance on the battlefield. Medical ethicists are now pondering what it will mean for those seeking to enhance performance in sports, in schools or on the job.

    “There is no doubt that athletes will try to take advantage of DNA markers,” said Steven Ungerleider, a research psychologist in Eugene, Ore., and author of “Faust’s Gold,” the story of the East German Olympic doping scandal. “The flip side of this wonderful medical technology is that it will be abused.”

    Arthur Caplan, director of the University of Pennsylvania Center for Bioethics, said the issues surrounding the use of genetic information to enhance performance are complex. “The idea that we are going to modify diet, modify sleep, modify exercise is well established in sports,” he said. “On the one hand, we don’t like steroids, we don’t want blood doping. On the other hand, most top-flight athletes have a dietician and nutritionist watching every calorie.”

    Caplan believes that if the technology is shown to be effective, such testing might be required in the workplace, particularly among those competing for elite positions. For example, he asked, would such testing be required for astronauts or even by ordinary businesses looking for a competitive edge?

    People commonly take vitamins in the hope of filling gaps in their diet or improving their daily health, but UC’s Marini pointed out that most of the recommended daily allowances established for supplements are derived from nutrition studies conducted in the 1940s. “They are based on the assumption that, biochemically, we are all the same,” he said.

    In fact, studies like this one are affirming that a wide variety of genetic mutations occur among humans. Every person is likely to have a mix of defective genes, and many of the less apparent, minor variants might have a cumulative negative effect on health.

    The Berkeley team noted that humans produce about 600 different enzymes that need vitamins and minerals to carry out their work. They estimate that each person can carry five different defective enzyme genes that are repairable with a higher dose of the related vitamin.

    Researcher Jasper Rine, a co-author of the study, said gene scans such as those used in the experiment are expensive and not even available to consumers, but there is a push to develop a test that can be run for less than $1,000.

    Genetically engineered yeast

    The scientists carried out their experiment using sophisticated computers, cutting-edge DNA sequencers and genetically engineered yeast. They screened DNA samples from 564 people who donated specimens to an international gene bank. They studied just one gene, which serves as a blueprint for the production of an enzyme that requires folate to work properly.

    A total of 14 mutations of the same gene were collected from the group – some appeared rarely, less than 1 percent of the time – while others were more common, with as many as 1 in 3 samples carrying the defect.

    The studies were not carried out in people. Instead, the defective genes were transplanted into yeast cells, which were then tested to see whether folate could restore the function of the flawed enzymes. In four out of five cases, increased levels of folate compensated for the most heavily damaged genes. People carrying those genes would be likely to benefit from higher dosages of folate in their diet, or by taking vitamin supplements.

    Rine said studies are now under way to explore other vitamin-gene relationships. In collaboration with Children’s Hospital Oakland Research Institute, the scientists are scanning genes for every enzyme known to interact with folate. Eventually, he believes researchers will have a catalog of mutations affecting all 600 enzymes that require a vitamin or mineral to function properly.

    If the suppositions of the researchers are correct, every person is likely to carry a handful of genetic defects that can be remedied by higher consumption of specific vitamins. One strategy, long used by consumers, is simply to down high doses of all vitamins. Rine believes that it simply makes more sense to match vitamin consumption to each individual’s genetically determined vitamin requirements. It avoids waste of vitamins and potential health problems caused by toxic levels of some supplements.

    People are also more likely to take a higher dose of a specific vitamin regularly if they know for certain that they need it and also know what pills they don’t have to take. “Try to swallow 10 Centrums,” said Rine. “That is a lot of swallowing.”

    Path to improved health?

    What: UC Berkeley researchers are searching for genetic flaws that can be fixed by simply taking vitamin and mineral supplements.

    How: By knowing which genes are defective, people will know which vitamins they need.

    Goal: Eventually, a person’s entire genome may be scanned for flaws, and a set of vitamins could be prescribed for optimum health.

    E-mail Sabin Russell at srussell@sfchronicle.com.

    This article appeared on page A – 1 of the San Francisco Chronicle

    DNA News Resource:  http://www.sfgate.com/cgi-bin/article.cgi?f=/c/a/2008/06/06/MNV1112S4P.DTL

    DNA Nutritional Breakthrough:  http://www.dnaguidedwellnessproducts.com

    127x16 1 Customized vitamins a fix for genetic flaws?

  • Personal genomes may lead to personalized vitamin supplements

    Posted on June 2nd, 2008 dna4wellness No comments

    By Robert Sanders, Media Relations | 02 June 2008

    – As the cost of sequencing a single human genome drops rapidly, with one company predicting a price of $100 per person in five years, soon the only reason not to look at your “personal genome” will be fear of what bad news lies in your genes.

    University of California, Berkeley, scientists, however, have found a welcome reason to delve into your genetic heritage: to find the slight genetic flaws that can be fixed with remedies as simple as vitamin or mineral supplements.

    “I’m looking for the good news in the human genome,” said Jasper Rine, UC Berkeley professor of molecular and cell biology.

    “Headlines for the last 20 years have really been about the triumph of biomedical research in finding disease genes, which is biologically interesting, genetically important and frightening to people who get this information,” Rine said. “I became obsessed with trying to decide if there is some other class of information that will make people want to look at their genome sequence.”

    What Rine and colleagues found and report this week in the online early edition of the journal Proceedings of the National Academy of Sciences (PNAS) is that there are many genetic differences that make people’s enzymes less efficient than normal, and that simple supplementation with vitamins can often restore some of these deficient enzymes to full working order.

    First author Nicholas Marini, a UC Berkeley research scientist, noted that physicians prescribe vitamins to “cure” many rare and potentially fatal metabolic defects caused by mutations in critical enzymes. But those affected by these metabolic diseases are people with two bad copies, or alleles, of an essential enzyme. Many others may be walking around with only one bad gene, or two copies of slightly defective genes, throwing their enzyme levels off slightly and causing subtle effects that also could be eliminated with vitamin supplements.

    “Our studies have convinced us that there is a lot of variation in the population in these enzymes, and a lot of it affects function, and a lot of it is responsive to vitamins,” Marini said. “I wouldn’t be surprised if everybody is going to require a different optimal dose of vitamins based on their genetic makeup, based upon the kind of variance they are harboring in vitamin-dependent enzymes.”

    Though this initial study tested the function of human gene variants by transplanting them into yeast cells, where the function of the variants can be accurately assessed, Rine and Marini are confident the results will hold up in humans. Their research, partially supported by the Defense Advanced Research Projects Agency (DARPA) and the U.S. Army, may enable them to employ U.S. soldiers to test the theory that vitamin supplementation can tune up defective enzymes.

    “Our soldiers, like top athletes, operate under extreme conditions that may well be limited by their physiology,” Rine said. “We’re now working with the defense department to identify variants of enzymes that are remediable, and ultimately hope to identify troops that have these variants and test whether performance can be enhanced by appropriate supplementation.”

    In the PNAS paper, Rine, Marini and their colleagues report on their initial analysis of variants of a human enzyme called methylenetetrahydrofolate reductase, or MTHFR. The enzyme, which requires the B vitamin folate to work properly, plays a key role in synthesizing molecules that go into the nucleotide building blocks of DNA. Some cancer drugs, such as methotrexate, target MTHFR to shut down DNA synthesis and prevent tumor growth.

    Using DNA samples from 564 individuals of many races and ethnicities, colleagues at Applied Biosystems of Foster City, Calif., sequenced for each person the two alleles that code for the MTHFR enzyme. Consistent with earlier studies, they found three common variants of the enzyme, but also 11 uncommon variants, each of the latter accounting for less than one percent of the sample.

    They then synthesized the gene for each variant of the enzyme, and Marini, Rine and their UC Berkeley colleagues inserted these genes into separate yeast cells in order to judge the activity of each variant. Yeast use many of the same enzymes and cofactor vitamins and minerals as humans and are an excellent model for human metabolism, Rine said.

    The researchers found that four different mutations affected the functioning of the human enzyme in yeast. One of these mutations is well known: Nearly 30 percent of the population has one copy, and nine percent has two copies.

    The researchers were able to supplement the diet of the cultured yeast with folate, however, and restore full functionality to the most common variant, and to all but one of the less common variants.

    Since this experiment, the researchers have found 30 other variants of the MTHFR enzyme and tested about 15 of them, “and more than half interfere with the function of the enzyme, producing a hundred-fold range of enzyme activity. The majority of these can be either partially or completely restored to normal activity by adding more folate. And that is a surprise,” Rine said.

    Most scientists think that harmful mutations are disfavored by evolution, but Rine pointed out that this applies only to mutations that affect reproductive fitness. Mutations that affect our health in later years are not efficiently removed by evolution and may remain in our genome forever.

    The health effects of tuning up this enzyme in humans are unclear, he said, but folate is already known to protect against birth defects and seems to protect against heart disease and cancer. At least one defect in the MTHFR enzyme produces elevated levels in the blood of the metabolite homocysteine, which is linked to an increased risk of heart disease and stroke, conditions that typically affect people in their post-reproductive years.

    “In those people, supplementation of folate in the diet can reduce levels of that metabolite and reduce disease risk,” Marini said.

    Marini and Rine estimate that the average person has five rare mutant enzymes, and perhaps other not-so-rare variants, that could be improved with vitamin or mineral supplements.

    “There are over 600 human enzymes that use vitamins or minerals as cofactors, and this study reports just what we found by studying one of them,” Rine said. “What this means is that, even if the odds of an individual having a defect in one gene is low, with 600 genes, we are all likely to have some mutations that limit one or more of our enzymes.”

    The subtle effects of variation in enzyme activity may well account for conflicting results of some clinical trials, including the confusing data on the effect of vitamin supplements, he noted. In the future, the enzyme profile of research subjects will have to be taken into account in analyzing the outcome of clinical trials.

    If one considers not just vitamin-dependent enzymes but all the 30,000 human proteins in the genome, “every individual would harbor approximately 250 deleterious substitutions considering only the low-frequency variants. These numbers suggest that the aggregate incidence of low-frequency variants could have a significant physiological impact,” the researchers wrote in their paper.

    All the more reason to poke around in one’s genome, Rine said.

    “If you don’t give people a reason to become interested in their genome and to become comfortable with their personal genomic information, then the benefits of much of the biomedical research, which is indexed to particular genetic states, won’t be embraced in a time frame that most people can benefit from,” Rine said. “So, my motivation is partly scientific, partly an education project and, in some ways, a partly political project.”

    Marini and Rine credit Bruce Ames, a UC Berkeley professor emeritus of molecular and cell biology now on the research staff at Children’s Hospital Oakland Research Institute, with the research that motivated them to look at enzyme variation. Ames found in the 1970s that many bacteria that could not produce a specific amino acid could do so if given more vitamin B6, and in recent years he has continued exploring the link between micronutrients and health.

    “Looked at in one way, Bruce found that you can cure a genetic disease in bacteria by treating it with vitamins,” Rine said. Because the human genome contains about 6 billion DNA base pairs, each one subject to mutation, there could be between 3 and 6 million DNA sequence differences between any two people. Given those numbers, he reasoned that, as in bacteria, “there should be people who are genetically different in terms of the amount of vitamin needed for optimal performance of their enzymes.”

    This touches on what Rine considers one of the key biomedical questions today. “Now that we have the complete genome sequences of all the common model organisms, including humans, it’s obvious that the defining challenge of biology in the 21st century is not what the genes are, but what the variation in the genes does,” he said.

    Rine, Marini and their colleagues are continuing to study variation in the human MTHFR gene as well as other folate utilizing enzymes, particularly with respect to how defects in these enzymes may lead to birth defects. Rine also is taking advantage of the 1,500 students in his Biology 1A lab course to investigate variants of a second vitamin B6-dependent enzyme, cystathionine beta-synthase.

    He also is investigating how enzyme cofactors like vitamins and minerals fix defective enzymes. He suspects that supplements work by acting as chaperones to stabilize the proper folding of the enzyme, which is critical to its catalytic activity. “That is a new principle that may be applicable to drug design,” Rine said.

    Coauthors with Rine and Marini are UC Berkeley research assistant Jennifer Gin and Janet Ziegle, Kathryn Hunkapiller Keho, David Ginzinger and Dennis A. Gilbert of Applied Biosystems, which also funded part of the study. The work was supported by a University of California Discovery Grant, DARPA and the National Institutes of Health.

    For further information, link to:

    PNAS paper by Marini, et al

    Rine lab Web site

    DNA News Resource:  http://berkeley.edu/news/media/releases/2008/06/02_genomes.shtml

    DNA Nutritional Resource:  http://www.dnaguidedwellnessproducts.com

    127x16 1 Personal genomes may lead to personalized vitamin supplements

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