Genes have become the Rosetta stone of modern biomedical research, the much sought after keys to understanding why people inevitably grow old and develop diseases. The increasing pace of genetic research has tantalized us with one discovery after anotherÑthe so-called cancer gene, the Alzheimer's gene, the obesity gene, and dozens of others.
But in the quest to apply this newfound knowledge in gene therapy, many researchers have overlooked simpler and more practical ways of keeping genes healthy and lowering the risk of disease. Vitamins and other nutrients play integral roles in how your body's cells synthesize and repair genes. Research has clearly shown that vitamins supplements can enhance the performance of genes and to protect them from damage.
The DNA-Nutrition Link
Genes, built from microscopic double-strands of deoxyribonucleic acid (DNA), direct the behavior of your body's 60 trillion cells. They define your body's outward physical features, such as the color of your eyes and hair, and how efficiently it works on the inside. When your genes work well, they enable you live to a ripe old age with a low risk of disease. When genes don't, they can accelerate your body's aging process and increase your risk for cancer and other diseases.
How does all this happen? The information in your genes is written in the chemical language of DNA. The letters in this alphabet are sequences of molecules called nucleotides. Each letter is constructed around one of four substances called DNA bases: adenine (A), cytosine (C), guanine (G), and thymine (T).
Different arrangements of these four nucleotides spell different words, and long strings of DNA (e.g., TACGACCTGA) form the genes that instruct cells to make specific enzymes and proteins. These enzymes, in turn, catalyze a host of other biochemical reactions, and the proteins form the structure of hormones and tissue.
All of this remarkable activity depends on nutrients. The DNA in the protein you eat is broken down and reconstructed into your own distinctive DNA. Vitamins B3 and B6 are needed for thymine synthesis, folic acid for guanine and adenine, and B3 for cytosine. When these nutrients are lacking, DNA cannot be synthesizedÑand its instructions cannot be carried out.
"Diet and genetics interact in numerous ways to influence chronic disease risk," Gregory D. Miller, Ph.D., and Susan M. Groziak, Ph.D., recently observed in the Journal of the American College of Nutrition. "Genetics influences the absorption, excretion, and metabolism of nutrients. Genetics also influences the human body's physiological response to diet. Diet, in turn, may influence the expression [activation] of genes related to specific chronic diseases."
The Causes of DNA Damage
DNA, however, is easily mutated, or damaged. Much of this damage is caused by molecules called free radicals, according to Denham Harman, M.D., Ph.D., of the University of Nebraska, Omaha. Most free radicals are formed as a byproduct of burning food for energy and fighting infections, but others are generated by ultraviolet sunlight, cigarette smoke, and pollutants. Free radicals delete sections of DNA, rearrange it, or cut it into pieces, and the end result is analogous to typographical errors that distort DNA's instructions.
Other DNA damage takes place during normal cell division. When a cell divides into two, it replicates its DNA, but not perfectly. A small number of errors creep in during each cell division, much the way misspellings are inadvertently inserted when a person retypes a written page. As the number of DNA errors increases, instructions for normal cell functions become more garbled.
The consequences of these DNA mutations eventually become catastrophicÑand are the reason why all living creatures age, says Harman. For example, the cells of a 70-year-old man contain far more damaged DNA, work less efficiently, and outwardly look very different from the cells of a 13-year-old girl.
Sometimes, the errors in DNA create wildly growing, unstoppable cancer cells. According to Aziz Sancar, Ph.D., of the University of North Carolina Medical School, Chapel Hill, 80-90 percent of all cancers result from DNA damage - in effect, from genetic instructions loaded with errors. Other times, cells in one organ, such as the heart, acquire DNA damage faster than do cells in other organs. When this happens, heart function decreases and eventually dies - usually taking the rest of the body with it.
Antioxidants Protect DNA From Damage
The likelihood of developing cancer and other diseases increases with age, principally because DNA has accumulated more damage and is more likely to malfunction. The aging of DNA is inevitable, but the process doesn't always occur at the same pace. Furthermore, a variety of experiments, some with people, have shown that nutritional supplements can reduce the rate of DNA damage and, in doing so, slow age-related changes to cells. Chief among these nutrients are antioxidants, including vitamins C and E, which neutralize free radicals.
In one such experiment, V. J. McKelvey-Martin, Ph.D., of the University of Ulster, Northern Ireland, exposed human lymph cells to various doses of x-rays or hydrogen peroxide, both potent generators of free radicals. Using sophisticated analytical techniques, McKelvey-Martin noted that DNA damage increased after the cells were exposed to x-rays and hydrogen peroxide.
However, McKelvey-Martin found, adding vitamins C and E to the cell culture reduced the rate of DNA damage. Vitamin C, a water-soluble antioxidant, protected against x-ray damage, whereas vitamin E, a fat-soluble antioxidant, shielded DNA from hydrogen-peroxide.
In a study at the Rowett Research Institute, Aberdeen, Scotland, Susan J. Duthie, Ph.D., studied how antioxidant supplements reduced DNA damage in 100 smokers and nonsmokers. Half of the subjects received a daily supplement containing 100 mg of vitamin C, 280 mg of vitamin E, and 25 mg of beta-carotene for 20 weeks.
Duthie counted the number of DNA breaks in white blood cells obtained from all of the subjects. She reported in the journal Cancer Research that the DNA of smokers and nonsmokers taking supplements was more resistant to free radical damage and had one-third fewer DNA breaks, compared with DNA from people who did not take supplements.
Just recently, German researchers analyzed DNA oxidation and breaks in lymph cells from 23 healthy men while eating their regular diet and an experimental diet low in beta-carotene and related carotenoids. They reported in the journal Carcinogenesis that specific high-carotenoid foods significantly lowered the amount of DNA damage. Carrots, high in beta- and alpha-carotene, had the most dramatic impact, reducing both DNA free radical damage and breaks. Tomatoes (high in lycopene) and spinach (rich in lutein) reduced the number of DNA breaks.
Garlic, another food rich in antioxidants and sulfur (a component of some amino acids) also can prevent breaks in DNA strands. In a study with laboratory rats, French researchers noted how aflatoxin (a fungus sometimes found in peanuts) and two other chemicals caused DNA breaks. However, when mice were pretreated with garlic extracts, most DNA breaks were prevented.
Nutrients that Repair DNA
DNA has the remarkable ability to proofread itself and to correct many errors before they become permanent. However, nutrient deficiencies can interfere with both the synthesis and repair of DNA.
For example, low intake of folic acid interferes with the production of thymine, one of DNA's four bases. When cells cannot make thymine, they replace it in DNA with uracil (one of the bases of ribonucleic acid, or RNA, which helps carry out DNA's instructions). But when DNA repair enzymes scan the DNA, it removes the uracil and leaves breaks in the DNA, according to recent research by Bruce N. Ames, Ph.D., of the University of California, Berkeley.
Last year, in the Proceedings of the National Academy of Sciences, Ames noted out that breaks in a single stand of DNA can usually be repaired. However, folic acid deficiency leads to large numbers of uracil deposits in DNA - so many deposits that they dramatically increase the risk of double-strand DNA breaks. Double-strand breaks are not as easily repaired and are more likely to result in permanent damage to DNA.
Such DNA breaks may be occurring in large numbers of people, increasing their risk of cancer, heart disease, and Alzheimer's, according to Ames. He says that folic acid deficiency affects about 10 percent of the U.S. population overall and about one-half of adolescents, elderly, and low-income African-Americans. When Ames gave folic acid supplements to people deficient in the vitamin, the amount of uracil being incorporated into DNA decreased significantly. This suggests, wrote Ames, that "in folate-deficient people, increased folate intake may decrease the risk of many types of cancer."
In fact, large numbers of people may have subtle genetic defects that interfere with utilization of folic acid and, presumably, other nutrients as well. In a recent study, John Scott, D.Sc., of Trinity College, Dublin, found that one in seven Irish women inherited mutations in the gene that creates 5,10-methylenetetrahydrofolate, an enzyme essential for folic acid activity in the body. The occurrence of this genetic defects varies in the populationÑone study found it present in 38 percent of French Canadians. Such people have an increased need for folic acid that often can be satisfied only with supplements.
The Interplay of DNA Stresses and Nutrition
The rate of DNA damage in your cells is the result of an constant interplay of factors. In a recent study of patients with head and neck cancers, Stimson P. Schantz, M.D., of the Memorial Sloan-Kettering Cancer Center, New York, investigated the complex interrelationships between exposure to hazardous substances, free radical damage to DNA, protective antioxidants, and DNA's repair mechanisms.
Schantz found that smoking cigarettes, or being exposed to second-hand tobacco smoke, generated large numbers of free radicals, which increased the number of DNA mutations. People who ate relatively few antioxidant-rich foods (fruits and vegetables), drank large amounts of alcohol, and those with poor DNA repair mechanisms were far more likely to develop head and neck cancers. In contrast, people who consumed large amounts of antioxidants - particularly vitamins C and E and lycopene - were more resistant to DNA damage and less likely to develop head and neck cancers.
Based on this research, how can you enhance the quality of your DNA? One way is to minimize your exposure to substances that damage DNA. You can't, however, live in a bubble, which means it's important to eat the nutrients that fortify your DNA against damage. Fruits and vegetables are particularly important because they are rich in many different antioxidants. For maximal benefit, it might be wise to also to supplement with B-complex vitamins and antioxidants.
REFERENCES
Miller GD and Groziak SM, "Diet and gene interactions," Journal of the American College of Nutrition, 1997, 16:293-295.
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Duthie SJ, Ma A, Ross MA, et al., "Antioxidant supplementation decreases oxidative DNA damage in human lymphocytes," Cancer Research, 1996;56:1291-1295.
Pool-Zobel BL, Bub A, Muller H, et al., "Consumption of vegetables reduces genetic damage in humans: first results of a human intervention trial with carotenoid-rich foods," Carcinogenesis, 1997;18:1847-1850.
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Blount BC, Mack MM, Wehr CM, et al., "Folate deficiency causes uracil misincorporation into human DNA and chromosome breakage: implications for cancer and neuronal damage," Proceedings of the National Academy of Sciences of the USA, 1997;94:3290-3295.
Molloy AM, Daly S, Mills JL, et al., "Thermolabile variant of 5,10-methylenetetrahydrofolate reductase associated with low red-cell folates: implications for folate intake recommendations," Lancet, 1997;349:1591-1593.
Schantz SP, Zhang Z-F, Spitz MS, et al., "Genetic susceptibility to head andneck cancer: interaction between nutrition and mutagen sensitivity," Laryngoscope, 1997;107:765-781.