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Antioxidants

ANTIOXIDANTS

ANTIOXIDANTS. Antioxidants are specific organic compounds that are active in the prevention of very rapid harmful chemical chain reactions with oxygen or nitric oxide, that is, oxidation reactions. In the body, oxidation reactions generally involve highly reactive molecules called free radicals. Free radicals reside primarily in the mitochondria of cells. When free radicals are released from the mitochondria in numbers sufficient to overwhelm the protective biochemical systems of the body, they become a threat to some cellular structures such as lipids, proteins, carbohydrates, and nucleic acids in cell membranes. Compromised cellular structure alters cellular function, and may lead to the initiation of the disease process. In severe oxidative stress, cell death may occur. Antioxidants react with the free radicals before they are able to react with other molecules, thus providing protection from oxidation reactions (Cross et al.).

Chemistry 101: How and Why Cells and Other Molecules Interact

The human body is made up of many different types of cells that are composed of multiple diverse types of molecules. Molecules are put together in such a way that one or more atoms of one or more elements are joined by chemical bonds. Atoms have a nucleus of neutrons and protons which is surrounded by electrons. It is the number of protons (positively charged particles) in the nucleus of the atom that determines the number of orbiting electrons (negatively charged particles). Electrons are involved in chemical reactions and are the substances that bond atoms together to form molecules. Electrons orbit the atom in one or more of the atom's shells. The innermost shell is full when it has two electrons. When the first shell is full, electrons begin to fill the second shell. When the second shell has eight electrons, it is full, and electrons begin to fill the third shell, and so on. The electrons surrounding antioxidants react with the electrons surrounding free radicals, causing them to become much less reactive. Antioxidants may be more effective when one antioxidant is used in combination with another. This synergistic relationship between several antioxidants occurs when, for example, vitamin E donates an electron from its outer shell to a free radical and vitamin C donates an electron to vitamin E, maintaining the ability of vitamin E to continue donating electrons to free radicals. Vitamin C may then receive an electron from glutathione that would enable vitamin C to remain active as an antioxidant. Therefore in this type of situation, an attack on membranes by a free radical results in the participation of three different antioxidants.

In What Forms Are Antioxidants Found and How Are They Metabolized?

Antioxidants are found in many forms. The principal vitamins with antioxidant properties are vitamins E and C, and beta-carotene. Vitamin E (d -alpha tocopherol) is a fat-soluble antioxidant, which means it is stored in body fat and works within the lipid portion of cell membranes to provide an alternative binding site for free radicals, preventing the oxidation of polyunsaturated fatty acids (Chow). Vitamin E is a family of eight compounds synthesized by plants in nature: four tocopherols (alpha, beta, gamma, delta) and four tocotrienols (alpha, beta, gamma, delta). Each has different levels of bioactivity in the body over quite a wide range, but generally speaking, alphatocopherol has greater bioactivity than beta-tocopherol, which has greater bioactivity than gamma-tocopherol, which has greater bioactivity than delta-tocopherol. Only alpha-tocotrienol has bioactivity of any significant amount, which is slightly less than that of beta-tocopherol. Digestion and absorption of vitamin E is greatly improved when consumption is accompanied with dietary lipids or fats. Absorption of vitamin E ranges from 20 to 50 percent, but may be as high as 80 percent, with absorption decreasing as intake increases (Bender, 1992). Dietary vitamin E absorption requires bile and pancreatic enzymes in the small intestine, where it is incorporated into micelles within the lumen of the small intestine. The micelles carry the vitamin E across the brush border of the small intestine and the vitamin E is then taken up by chylomicrons, which are transported by the lymph system to tissues and the liver. Vitamin E may be stored in the liver, adipose tissues, and skeletal muscle. When needed, vitamin E places itself in cell membranes. Excretion of vitamin E is by way of urine, feces, and bile (Wardlaw and Kessel).

Vitamin C (ascorbic acid) is a water-soluble antioxidant and is found in the water compartments of the body where it interacts with free radicals. It has been shown that short-term supplementation of vitamin C lasting two to four weeks can significantly reduce the level of free radicals in the body (Naidoo and Lux). Dietary vitamin C is absorbed primarily by active transport in the small intestine, with absorption decreasing as intake increases. Approximately 70 to 90 percent of vitamin C is absorbed when dietary intake is between 30 and 180 mg/day. The kidneys excrete excess dietary vitamin C in urine, but excrete virtually no vitamin C when intake of the vitamin is very low (Wardlaw and Kessel). After absorption in the small intestine, vitamin C is transported in the blood to cells in its reduced form, ascorbic acid or ascorbate. The concentration of vitamin C varies in different tissues in the body. For instance, vitamin C concentrations are highest in the adrenal and pituitary glands, intermediate in the liver, spleen, heart, kidneys, lungs, pancreas, and white blood cells, and lowest in the muscles and red blood cells (Olson and Hodges). This vitamin may also possess some prooxidant properties, meaning it can participate in oxidizing other molecules such as iron in the blood stream (Alhadeff et al.).

Beta-carotene is a precursor to vitamin A (retinol). Beta-carotene is the most widely known compound in a group known as carotenoids, which are pigment materials in fruits and vegetables that range from yellow to orange to red in color. Carotenoids are also called proformed vitamin A because they can be made into vitamin A by the body when necessary. Carotenoids are pigments that are responsible for the orange color of many fruits and vegetables such as oranges and squash. Other carotenoids present in foods include antheraxanthin, lutein, zeaxanthin, and lycopene. Dietary retinol is usually found bound to fatty acid esters, which are in turn bound to proteins, and must undergo a process called hydrolysis that frees the retinol from the esters, enabling the retinol to then be absorbed in the small intestine. Proteolytic enzymes in the small intestine, such as pepsin, hydrolyze the retinol from the proteins. Approximately 70 to 90 percent of dietary retinol is absorbed provided there is adequate (10 grams or more) fat in the meal consumed (Olson). Carotenoids are absorbed at much lower levels, sometimes at levels as low as 3 percent, with absorption decreasing as intake increases (Brubacher and Weisler). Retinol and the carotenoids are carried through the absorptive cells of the small intestine by micelles for transport through the lymph system to the liver, which then can "repackage" the vitamins to send to other tissues, or act as the storage facility for the vitamins until needed by the body.

There are also enzymes that possess antioxidant properties. Glutathione peroxidase, superoxide dismutase, and catalase are the most well known. Glutathione peroxidase breaks down peroxidized fatty acids, converting them into less harmful substances. Peroxidized fatty acids tend to become free radicals, so the action of glutathione peroxidase serves to protect cells. The activity of glutathione peroxidase is dependent on the mineral selenium, which is the functional part of this enzyme, or the part of the enzyme that makes it have antioxidant activity. Therefore, selenium is considered to have antioxidant properties. Superoxide dismutase and catalase react with free radicals directly, reducing their ability to oxidize molecules and cause cellular damage.

A class of compounds termed isoflavones, which are derived from soy, also have antioxidant activity. Genistein, daidzein, and prunectin are all able to prevent the production of free radicals. Isoflavone activity as an antioxidant plays an important role in the aging process and cancer prevention primarily due to having estrogenrelated biologic activities in humans (Shils et al.).

The polyphenols (epicatechin, epicatechin-3-gallate, epigallocatechin, and epigallocatechin-3-gallate) found in jasmine green tea also possess natural antioxidant properties. Studies have shown that these polyphenols are able to protect red blood cells from destruction upon attack by free radicals (Shils et al.). The polyphenols present in red wine have also been found to be protective against the oxidation of low-density lipoproteins and high-density lipoproteins, which are very important factors in the prevention of the development of atherosclerosis or coronary artery disease (Ivanov et al.).

A final group of compounds, synthetic antioxidants, are often added to foods to prevent discoloration and delay oxidation of the foods after exposure to oxygen. They also help protect fats from rancidity. Rancidity causes fats to develop an unappealing flavor and odor. Most of the antioxidants used in foods are phenolic compounds. There are four antioxidants that are approved for use in foods, particularly fats. They are propyl gallate (PG), tertiary butylhydroquinone (TBHQ), butylated hydroxyanisole (BHA), and butylated hydroxytoluene (BHT) (Charley and Weaver). Sulfites, which are sulfur-based chemicals, are also used as antioxidants in foods. However, because some people may be very sensitive to sulfites and have adverse reactions to them in foods, the Food and Drug Administration has required that labels on foods containing sulfites alert the public to their presence.

Dietary Sources of Antioxidants

Vitamin E is found in egg yolks, milk, plant and vegetable oils (including margarine and to a lesser extent butter), nuts, seeds, fortified whole-grain cereals, flatfish, halibut, shrimp, canned tuna in oil, asparagus, peas, tomatoes, apples, canned apricots in light syrup, blueberries, grapefruit, oranges, peaches, and pears. The milling process of whole grains causes most of the dietary vitamin E to be lost. The Recommended Dietary Allowance (RDA) as established by the U.S. Department of Agriculture currently is 15 International Units (IU) per day for men and 12 IU/day for women. In order for toxic effects to be produced, the amount of vitamin E consumed from foods would have to be 15 to 100 times the amount recommended for humans and this is extremely unlikely to occur (Wardlaw and Kessel). Symptoms and effects of toxicity are discussed in detail in Signs and Symptoms of Antioxidant Deficiency and Toxicity, below.

Vitamin C is present in large amounts in broccoli, asparagus, cabbage, cauliflower, potatoes, tomatoes, apples, applesauce, apricots, bananas, blueberries, cherries, grapefruit, lemons, oranges, peaches, strawberries, kiwi, pineapples, pears, cranberries, and the juices and jams made from these fruits. The Recommended Dietary Allowance for vitamin C currently is 60 mg/day for both males and females. Vitamin C obtained from foods rarely can be consumed in amounts large enough to be toxic to humans (Wardlaw and Kessel).

Beta-carotene is found in liver (primary storage organ in animals for vitamin A), egg yolk, fortified milk, butter, spinach, carrots, squash, sweet potatoes, broccoli, tomatoes, peaches, mangoes, apricots, papaya, cantaloupes, and fortified breakfast cereals. Because beta-carotene is converted to vitamin A by the body, there is no set requirement. However, the RDA for vitamin A is set in Retinol Equivalents (RE) at the level of 625 μg/day RE for men and 500 μg/day RE for women (Wardlaw and Kessel).

Diets High or Low in Antioxidants

Diets that are rich in antioxidants focus on high intakes of a variety of foods, especially large amounts of fruits, vegetables, and foods made from whole grains. Vegetarian diets, especially vegan diets (diets that exclude all foods from animal sources), are made up primarily from fruits, vegetables, whole grains, and legumes, and are an example of the types of diets that incorporate high levels of antioxidants. Another example of a diet that provides optimal levels of antioxidants is the Mediterranean diet. The Mediterranean diet is based on traditional eating habits in Greece, southern Italy, and Crete. This diet is rich in olive oil, foods from whole grains, and tomatoes, and minimizes the daily intake of poultry, eggs, sweets, and red meat. Red wine often accompanies meals in the Mediterranean diet and possesses some antioxidant activity (Murcia and Martinez-Tome). Furthermore, many of the spices used in Mediterranean cooking also have been observed to have some level of antioxidant properties (Martinez-Tome et al.). Asian-American diets also focus primarily on fruits, legumes, nuts, seeds, vegetables, and whole-grain food products, with liberal use of vegetable oils, while a minimum of meat is eaten. The traditional healthy Latin American diet provides beans, whole grains, nuts, fruits, and vegetables at every meal, with fish or shellfish, milk products, plant oils, and poultry being optional for daily intake.

Unfortunately, the typical American diet does not involve adequate intakes of fruits, vegetables, and whole-grain food products. This is not due to the lack of foods that fall into those categories but rather to the fact that too many Americans prefer fast foods and processed foods that are not rich sources of antioxidants. The Food Guide Pyramid developed by the United States Department of Agriculture recommends that six to eleven servings of bread cereal, rice, and pasta be consumed daily; three to five servings of vegetables per day; two to four servings of fruit per day; two to three servings of milk products per day; two to three servings of meat, poultry, fish, dry beans, eggs, and nuts per day; and that the use of fats, oils, and sweets be sparse (Wardlaw and Kessel). Most Americans do not adhere to the guidelines of the Food Guide Pyramid and therefore do not receive adequate amounts of foods that provide large quantities of antioxidants.

Certain disease states make it difficult to obtain adequate amounts of fat-soluble vitamins due to an inability to digest foods with fat properly. The digestion and absorption of fat in foods is required for digesting and absorbing fat-soluble vitamins such as vitamins A and E. Individuals with cystic fibrosis, celiac disease, and Crohn's disease absorb fat very poorly, which also means that the fat-soluble vitamins are poorly absorbed. As the unabsorbed fat passes through the small and large intestine, it carries the fat-soluble vitamins along with it, and is eventually excreted in the feces (Wardlaw and Kessel). Chronic alcoholics are also at risk for not obtaining adequate amounts of antioxidants due to a marked decrease in food intake in favor of the consumption of alcohol. Alcoholism may also result in liver disease, which leads to an inability of the liver to store the fat-soluble antioxidants.

Signs and Symptoms of Antioxidant Deficiency and Toxicity

Obtaining dietary intakes of vitamin E, vitamin C, and vitamin A from foods to meet the recommendations of the Food Guide Pyramid will prevent most healthy individuals from experiencing any deficiencies of these antioxidants. However, in diets that do not provide adequate amounts of fruits, vegetables, and whole grains, deficiencies may occur. It takes longer to develop a deficiency of the fat-soluble antioxidants, vitamins E and A, than it does to develop a deficiency of the water-soluble vitamin C.

Failure to obtain adequate vitamin E in the diet may cause certain medical conditions. Hemolytic anemia is caused by vitamin E deficiency, with an increased breakdown of red blood cells or hemolysis. Premature infants are most susceptible to vitamin E deficiency due to very small stores of the vitamin at birth and the frequently required use of oxygen to accommodate immature lungs. Premature infants are also growing very rapidly and need increased intakes of vitamin E. Special formulas are used to provide vitamin E to help prevent deficiency (Wardlaw and Kessel).

The disease caused by vitamin C deficiency is scurvy. The symptoms of scurvy are fatigue and small, purple spots or hemorrhages (petechiae) that appear around hair follicles on the back of the arms and legs. There are also bleeding gums and joints, impaired wound healing, pain in the bones, fractures, and diarrhea. Consuming a vitamin Cfree diet for as little as 20 days may cause scurvy, but resuming vitamin C intake for one week can cause the reversal of the disease and accompanying symptoms (Wardlaw and Kessel).

Vitamin E toxicity may result from intakes of more than 1,500 IU/day of vitamin E isolated from natural sources and 1,100 IU/day for synthetic vitamin E for adults nineteen years or older. It is only possible to acquire such high doses of either form of vitamin E via supplementation. Use of supplemental vitamin E at such high doses in persons with a compromised health status may lead to complications such as hemorrhaging in individuals who are taking anticoagulants or are vitamin K-deficient (vitamin K is important in blood coagulation) (Wardlaw and Kessel).

Vitamin C toxicity may occur at intakes of 2 g/day or higher. The symptoms of vitamin C toxicity are nausea, abdominal cramps, and osmotic diarrhea. Because vitamin C is a water-soluble vitamin, much of excess vitamin C obtained from supplemental megadoses is excreted in urine (Wardlaw and Kessel).

Small children who do not eat enough vegetables are at an increased risk for vitamin A deficiency. In fact, individuals with very low incomes and the elderly are also at risk for deficiency due to an inability to obtain adequate intakes of foods that are good sources of vitamin A and to the decreased gastrointestinal function that may occur with age. Night blindness is a symptom of vitamin A deficiency, causing the rod cells in the eye to take a longer period of time to recover from flashes of light. Another symptom of vitamin A deficiency is dry eyes caused by deterioration of the mucus-forming cells in the body. In an individual with dry eyes, dirt and other contaminants are not washed away, and this may lead to eye infections. If vitamin A deficiency is not corrected, the condition of the eyes worsens, leading to more serious disorders of the eye; eventually irreversible blindness may result. The skin is also affected by a compromised vitamin A status. Primary symptoms are very dry skin and rough and bumpy texture of the skin surface. When vitamin A supplements are taken long-term at three times the RDA a condition called hypervitaminosis A may develop. This condition can cause spontaneous abortions in pregnant women or birth defects in infants and therefore women of child-bearing age wishing to become pregnant should avoid using high doses of vitamin A supplements (Wardlaw and Kessel).

Maintaining Antioxidant Content in the Foods You Eat

Antioxidants in foods are a valuable addition to a healthy diet and steps can be taken to preserve the antioxidant content of foods until they are ready to be ingested. Keeping fruits and vegetables refrigerated or in a cool, dry place helps to slow down the natural breakdown by enzymes that begins to occur as soon as the foods are picked. Fruits and vegetables should not be trimmed or cut until they are ready to be consumed to prevent unnecessary exposure to oxygen. Cooking by steaming, microwaving, or stir-frying in small amounts of fat for short amounts of time also helps to preserve the vitamin content of foods. If liquids are used to cook fruits or vegetables, do not add fat while cooking if you are planning to discard the liquid before eating the fruits or vegetables, to avoid losing the fat-soluble vitamins that may be in the liquids. Finally, it is important to remember that the skin of some fruits and vegetables contains a higher vitamin content than the inner parts, such as the skin of an apple (Wardlaw and Kessel).

See also: Dietary Assessment ; Dietary Guidelines ; Natural Foods ; Niacin Deficiency (Pellagra) ; Nutrition Transition: Worldwide Diet Change ; Vitamin C ; Vitamins: Overview ; Vitamins: Water-soluble and Fat-soluble Vitamins.

BIBLIOGRAPHY

Alhadeff, L., C. Gualtieri, and M. Lipton. "Toxic Effects of Water-Soluble Vitamins." American Journal of Clinical Nutrition 42 (1984): 3340.

Bender, D. Nutritional Biochemistry of the Vitamins. New York: Cambridge University Press, 1992.

Brubacher, G., and H. Weisler. "The Vitamin A Activity of Beta-carotene." International Journal of Vitamin and Nutrition Research 55 (1985): 515.

Charley, H., and C. Weaver. Foods: A Scientific Approach. Upper Saddle River, N.J.: Prentice-Hall, 1998.

Chow, C. K. "Vitamin E and Oxidative Stress." Free Radical Biology and Medicine 11 (1991): 215232.

Cross, C. E., A. vander Vliet, and C. O'Neil. "Reactive Oxygen Species and the Lung." Lancet 344 (1994): 930933.

Ivanov, V., A. C. Carr, and B. Frei. "Red Wine Antioxidants Bind to Human Lipoproteins and Protect Them from Metal Ion-Dependent and -Independent Oxidation." Journal of Agricultural and Food Chemistry 49(9) (2001): 44424449.

Martinez-Tome, M., A. M. Jimenez, S. Ruggieri, N. Frega, R. Strabbioli, and M. A. Murcia. "Antioxidant Properties of Mediterranean Spices Compared with Common Food Additives." Journal of Food Protection 64(9) (2001): 14121419.

Murcia, M. A., and M. Martinez-Tome. "Antioxidant Activity of Resveratrol Compared with Common Food Additives." Journal of Food Protection 64(3) (2001): 379384.

Naidoo, D., and O. Lux. "The Effect of Vitamin C and E Supplementation on Lipid and Urate Oxidation Products in Plasma." Nutrition Research 18 (1998): 953961.

Olson, J. "Recommended Dietary Intakes (RDI) of Vitamin A in Humans." American Journal of Clinical Nutrition 45 (1987): 704716.

Olson, A., and R. Hodges. "Recommended Dietary Intakes (RDI) of Vitamin A in Humans." American Journal of Clinical Nutrition 45 (1987): 693703.

Shils, M. E., J. A. Olson, M. Shike, and A. C. Ross. Modern Nutrition in Health and Disease. Baltimore: Williams & Wilkins, 1999.

Wardlaw, G. M., and M. Kessel. Perspectives in Nutrition. Boston: McGraw-Hill, 2002.

Rebecca J. (Bryant) McMillian

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Antioxidants

Antioxidants

Description

Antioxidants are a broad group of compounds that destroy single oxygen molecules, also called free radicals, in the body, thereby protecting against oxidative damage to cells. They are essential to good health and are found naturally in a wide variety of foods and plants, including many fruits and vegetables. Many antioxidants, either singly or in combination, are also available as over-the-counter nutritional supplements in tablet or capsule form. The most commonly used antioxidants are vitamin C, vitamin E , and beta carotene . Others include grape seed extract, vitamin A, selenium , and coenzyme Q 10. It is unknown whether or not supplemental antioxidants provide the same benefits as those occurring naturally in foods, however.

General use

In brief, antioxidants destroy free radicals in the body. Free radicals are byproducts of oxygen metabolism that can damage cells and are among the causes of many degenerative diseases, especially diseases associated with aging . They are also associated with the aging process itself. As a person ages, cell damage accumulates, and supplementing the diet with extra antioxidant-rich foods can help slow the oxidative damage done to cells. Scientific studies validate the role of antioxidants in preventing many diseases. Although studies have shown lower rates of cancer and heart disease in people who eat a recommended amount of fruits and vegetables, recent clinical studies have shown that supplementation of diet with antioxidant vitamin therapy does not lower risk of cardiovascular disease or certain other diseases.

Many herbs and medicinal plants are good natural sources of antioxidants. These include carrots, tomatoes, yams, leafy greens, blueberries, billberries, ginkgo biloba, garlic , and green tea , to name a few. A diet rich in vitamin C, vitamin E, and beta carotene may help reduce the risk of some cancers, heart disease, cataracts , and strokes.

Vitamin A

A study by the University of Arizona found that vitamin A has a protective affect against many types of cancer, according to Dr. Michael Colgan in his book, The New Nutrition. Vitamin A is a fat-soluble antioxidant found in animal products but can be made by the body from its precursor, beta carotene. Foods rich in vitamin A are liver, eggs, and fortified dairy products. Vitamin A helps bones and teeth develop, and promotes vision. As an antioxidant, it protects cell membranes and fatty tissue, helps repair damage caused by air pollutants, and boosts the immune system. A deficiency of this vitamin can result in dry skin, brittle hair, vision problems, blindness, and increased susceptibility to respiratory infections .

Vitamin C

Probably the most widely used of all vitamin supplements, vitamin C is a powerful antioxidant that has a myriad of functions and helps strengthen the immune system. It became famous in the 1970s when Nobel Prize-winning scientist Linus Pauling advocated daily mega doses (8-10 grams) of vitamin C to prevent and ease the symptoms of the common cold . Many clinical studies that show vitamin C is superior to over-the-counter medicines in reducing the symptoms, duration, and severity of colds. As an antioxidant, vitamin C may help fight cardiovascular disease by protecting the linings of arteries from oxidative damage. In 2002, debate still continued on the vitamin's effects on heart disease. One study revealed that Vitamins C and E helped reduce arteriosclerosis (hardening of the arteries) following heart transplants. Yet another study demonstrated that vitamin therapy had not effect on preventing heart disease. There is some evidence and research that vitamin C can help prevent cancer. Studies have shown it is also beneficial in protecting the body against the effects of smoking and air pollutants.

Vitamin E

Vitamin E is a potent antioxidant by itself, but its effectiveness is magnified when taken with other antioxidants, especially vitamin C, selenium, and beta carotene. Some scientific evidence indicates that vitamin E helps promote cardiovascular health. Past studies have demonstrated higher vitamin E intake is associated with decreased incidence of heart disease in both men and women. In fact, the combination of Vitamin C and E can slow progression of cardiovascular disease following heart transplant. In 2002, researchers stated that the vitamin combination might also be useful in other organ transplants. In addition, Harvard Medical School reported in the same year that Vitamin E might play a role in helping people live longer, citing its role in strengthening the immune system.

Carotenoids

This class of antioxidants includes beta carotene, lutein , and lycopene . They are found in a variety of fruits and vegetables such as carrots, pumpkins, kale, spinach, tomatoes, and pink grapefruit. Research evidence suggests carotenoids lower the risk of heart disease and some types of cancer, and strengthen the immune system. Lycopene, which is concentrated in the prostate gland, is believed to protect the prostate from cancer. Lutein is thought to prevent macular degeneration , a major cause of blindness, or stop its progression. Beta carotene increases the lungs' defense system in smokers or those exposed to other air-borne pollutants. It also has been used as an immune system stimulator in people with AIDS . In 2002, a report revealed that more than 90% of ophthalmologists and optometrists surveyed believe that lutein helps prevent eye disease.

Bioflavonoids

Bioflavonoids are a group of about 5,000 compounds that act as antioxidants. They occur in fruits, vegetables, green tea, soy products, herbs, and spices. A combination of bioflavonoids has a synergistic effect when taken with vitamin C. They have been shown to be beneficial in treating a variety of conditions, including allergies , arthritis, diabetes, hypertension , and viral infections. One group of bioflavonoids found to be a powerful antioxidant is oligomeric proanthocyanidins (OPCs), also known generically as pycnogenol. Extremely high concentrations of OPCs are found in maritime pine bark (Pinus maritima ) extract, grape seed extract, and grape and peanut skins. Due primarily to its much lower cost, grape seed extract is the most commonly used OPC. Procyanidins, a group of compounds found in the extract, are thought to increase the effectiveness of other antioxidants, especially vitamin C and vitamin E, by helping them regenerate after neutralizing free radicals in the blood and tissue.

Other antioxidants

The other widely used antioxidants are selenium, coenzyme Q10, and certain amino acids . Selenium, especially when teamed with vitamin E, may help protect against lung, colon, prostate, and rectum cancers. The antioxidant benefits of coenzyme Q10 may include slowing the aging process, boosting the immune system, and preventing oxidative damage to the brain. Some still suggest its use to treat a variety of cardiovascular diseases. Amino acids that have strong antioxidant effects include alpha lipoic acid, cysteine, glutathione , and N-acetyl cysteine (NAC).

Preparations

Bottled antioxidant formulae are available in a single pill or as part of a multivitamin. The usual dosages of antioxidants taken individually can vary widely. The United States Department of Agriculture (USDA) has established recommended daily allowance, but these may be conservative amounts for preventing diseases. For instance, the USDA recommendation for vitamin C is 60 mg a day but natural healthcare practitioners commonly recommend 500 mg a day or more. The dosage may also depend on whether it is being taken to treat or prevent a specific condition. With that in mind, the common daily dosages for specific antioxidants are: vitamin A, 5,000-15,000 IU; beta carotene, 15,000-25,000 IU; vitamin C, 250-1,500 mg; vitamin E, 30-400 IU; selenium, 50-400 micrograms; bioflavonoids, 100-500 mg; grape seed extract, 150-200 mg; coenzyme Q10, 90-150 mg; alpha lipoic acid, 20-50 mg or 300-600 mg for elevated blood sugar levels; glutathione, 100 mg; N-acetyl cysteine, 600 mg.

Precautions

Vitamin C: May interfere with some laboratory tests, including urinary sugar spilling for diabetics. Vitamin A: Can be toxic in high doses of more than 15,000 IU per day or chronic doses for months, and may cause birth defects if taken in high doses during pregnancy . In 2002, one study showed that consistent Vitamin A intake could increase the risk of hip fractures in postmenopausal women, but the study was not representative of all women, and more study on the upper limits of safe Vitamin A consumption for women in their 40s and 50s is needed. Vitamin E: Dangerous in very high doses. Carotenoids: No known precautions are indicated for normal doses. Bioflavonoids: No known precautions are indicated for normal doses. Selenium: No precautions indicated at normal doses, but a physician should be consulted before taking daily doses of more than 200 micrograms. Coenzyme Q10: No known precautions are indicated for normal dosage. Amino acids: There are no known precautions indicated for alpha lipoic acid, cysteine, glutathione, or NAC.

Side effects

Vitamin C: Individual tolerances vary. High doses may cause cramps, diarrhea , ulcer flare-ups, kidney stones , and gout in some people. Vitamin A: High doses can lead to headaches, nausea, hair loss , and skin lesions; may cause bone disease in people with chronic kidney failure. Vitamin E: Usually no adverse side effects in doses of up to 400 mg a day, high doses may elevate blood pressure and lead to blood-clotting problems. Carotenoids: No known side effects occur with normal dosage. Bioflavonoids: No known negative side effects in normal doses. Selenium: No reported adverse side effects with normal dosage of 200 micrograms, higher doses may cause dizziness and nausea. Coenzyme Q10: No adverse side effects have been reported. Amino acids: There are no known side effects associated with normal doses of alpha lipoic acid, cysteine, glutathione, or NAC.

Interactions

Vitamin C: No known common adverse interactions with other drugs. Vitamin A: Women taking birth control pills should consult with their doctors before taking extra vitamin A. Vitamin E: Should not be used by persons taking anti-coagulation drugs. Carotenoids: No known negative interactions with other drugs. Bioflavonoids: No known adverse interactions with other drugs. Coenzyme Q10: No negative drug interactions yet reported. Amino acids: There are no adverse reactions yet reported between alpha lipoic acid, cysteine, glutathione, or NAC and other medications.

Resources

BOOKS

Balch, Dr. James F. The Super Antioxidants: Why They Will Change the Face of Health Care in the 21st Century. M. Evans and Co., 1998.

Colgan, Dr. Michael. The New Nutrition. CI Publications, 1996.

Challem, Jack, editor. All About Antioxidants. Avery Publishing Group, 1999.

Hendler, Dr. Sheldon Saul The Doctors'Vitamin and Mineral Encyclopedia. Simon and Shuster, 1990.

Moss, Ralph W. Antioxidants Against Cancer. Equinox Press, 2000.

Murray, Michael T. Natural Alternatives to Over-the-Counter and Prescription Drugs. William Morrow and Co., 1994.

Packer, Lester, et al. The Antioxidant Miracle: Your Complete Plan For Total Health and Healing. John Wiley and Sons, 1999.

Smythies, John R. Every Person's Guide to Antioxidants Rutgers University Press, 1998.

PERIODICALS

Abramowiez, Dr. Mark, editor. "Vitamin Supplements." The Medical Letter (July 31, 1998): 75-77.

"Antioxidant Vitamin E Reported to Strengthen Immune System." Obesity, Fitness & Wellness Week (March 2, 2002): 12.

Fang, James C., et al. "Effect of Vitamins C and E on Progression of Transplant-Associated Arteriosclerosis: A randomized Trial." The Lancet (March 30, 2002): 1108.

Kiningham, Robert."The Value of Antioxidant Vitamin Supplements." American Family Physician (Sept. 1, 1999): 742.

Koch Kubetin, Sally. "Antioxidants Fall Short." OB GYN News (February 1, 2002): 29.

Langer, Stephen."Antioxidants: Our Knights in Shining Armor." Better Nutrition (May 1997): 46-50.

"Lutein Helps Protect Eyes, Doctors Say in Survey." Ophthalmology Times (March 15, 2002): 29.

Raloff, Janet."The Heart-Healthy Side of Lycopene." Science News (Nov. 29, 1997): 348.

Scheer, James F. "Twelve Key Antioxidants: May Their Force Be With You." Better Nutrition (Jan. 1999): 58.

Schindler, Martha."The Magnificent Seven." Vegetarian Times (Feb. 1999): 86.

"Simvastatin Yes, Antioxidant No ñ Two Important New Studies." Clinical Cardiology Alert (January 2002): 1.

Tyler, Varro E."The Miracle of Anti-Aging Herbs." Prevention (Nov. 1999): 105.

"Vitamin A Intake Levels Reaffirmed as Safe and Beneficial." Medical Letter on the CDC & FDA (January 27, 2002): 14.

Ken R. Wells

Teresa G. Odle

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Antioxidants

Antioxidants

Americans spend several billion dollars a year on antioxidants in an effort to improve their health. Science has been looking at antioxidants and their role in everything from preventing cancer and heart disease to boosting the immune system and slowing the aging process. Antioxidants provide a layer of protection for the cells and tissues of the body, just as a thick coat of wax helps protect a car's finish. Specifically, antioxidants protect against free radical damage. What are free radicals ?

People must breathe in oxygen to live. Continuously on the move in the blood stream and transported to every cell, oxygen is necessary for all essential bodily functions. However, a small amount of this oxygen gets loose and produces unstable by-products called free radicals. Body processes, such as metabolism , as well as environmental factors, including pollution and cigarette smoke, can produce free radicals. An overload of free radicals in the body causes damage to the cells, ultimately resulting in disease and accelerated aging.

Antioxidant-rich food may help prevent various cancers, heart disease, and diseases of aging. Vitamins C and E, carotenoids (including beta-carotene), and the mineral selenium are all powerful antioxidants found in food. Vitamin C, a water-soluble vitamin, is also known as ascorbic acid. Most of the vitamin C in the diet (90%) comes from fruits and vegetables. However, since vitamin C is water soluble, cooking can destroy the vitamin C in a food.

Vitamin E, also known as alpha tocopherol, is a fat . Because vitamin E is found in oils, people who follow a low-fat diet may not get enough. Beta-carotene is a member of the carotenoid family. Found mainly in plants, carotenoids provide the vibrant red, yellow, green, and orange colors of fruits and vegetables, with carrots being a major contributor of beta-carotene. Typically, beta-carotene is a conditionally essential nutrient , but when one's intake of vitamin A is low, beta-carotene becomes an essential nutrient, meaning that it must be obtained from food and cannot be manufactured by the body.

Selenium is an essential trace mineral (trace minerals are needed only in small amounts). The amount of selenium found in food is directly related to the amount of selenium in the soil in which the food was grown. It is necessary for healthy immune function and is tied to killer-cell activity and antibody production. The many health benefits of the various antioxidants can be provided by a variety of food sources.

More and more functional foods contain combinations of various supplements. As popular as antioxidants are, an excess amount of them can be toxic. One reason to obtain antioxidants from food is that high doses may

Antioxidant Health benefits Food sources
Selenium Helps maintain healthy hair and nails, enhances immunity, works with vitamin E to protect cells from damage. Reduces the risk of cancer, particularly lung, prostate, and colorectal. Garlic, seeds, Brazil nuts, meat, eggs, poultry, seafood, whole grains. The amount in plant sources varies according to the content of the soil.
Beta-carotene Keeps skin healthy, helps prevent night blindness and infections, promotes growth and bone development. Red, yellow-orange, and leafy green vegetables and fruits, including carrots, apricots, cantaloupe, peppers, tomatoes, spinach, broccoli, sweet potatoes, and pumpkin.
Vitamin E Acts as the protector of essential fats in cell membranes and red blood cells. Reduces risk of cancer, heart disease, and other age-associated diseases. Peanut butter, nuts, seeds, vegetable oils and margarine, wheat germ, avocado, whole grains, salad dressings.
Vitamin C Destroys free radicals inside and outside cells. Helps in the formation of connective tissue, the healing of wounds, and iron absorption, and also helps to prevent bruising and keep gums healthy. May reduce risk of cataracts, heart disease, and cancer. Peppers, tomatoes, citrus fruits and juices, berries, broccoli, spinach, cabbage, potatoes, mango, papaya.
source: The American Dietetic Association And WebMD.

actually promote free radical production, also known as pro-oxidation, increasing the chance for health problems. Those who may benefit most from antioxidants include people dealing with a lot of stress , dieters limiting their calories to 1,200 per day or less, people on a low-fat diet, smokers, older adults, and people with a family history of heart disease or cancer.

see also Functional Foods.

Susan Mitchell

Bibliography

Medical Economics Company (2001). PDR for Nutritional Supplements. Montvale, NJ: Author.

Internet Resources

American Dietetic Association. "Vitamin E: Disease Prevention for Your Good Health." Available from <http://www.eatright.org>

Doheny, Kathleen. "The Supplement Frenzy." Available from <http://www.webmd.com>

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Antioxidants

Antioxidants

Definition

Antioxidants are chemical compounds that can bind to free oxygen radicals preventing these radicals from damaging healthy cells.

Purpose

Preliminary studies have suggested that antioxidants are useful in a number of ways in regards to cancer. For instance, they may improve the effectiveness of chemotherapy , decrease side effects of chemotherapy and radiotherapy, and prevent some types of cancer. Sufficient epidemiological studies have shown that ingesting foods high in antioxidants, such as fruits and vegetables, can decrease the risk of many types of cancer. Studies have also found that cancer patients have lower levels of antioxidants in their blood. The American Cancer Society suggests eating five servings of fruits a day to decrease the risk of cancer.

Precautions

Studies of antioxidant supplements to decrease the risk of cancer have not been conclusive. Most antioxidant research has centered around vitamins A (and its provitamin, beta-carotene), C, E (alpha-tocopherol), and the trace element selenium. While some studies have shown positive effects for antioxidants in preventing cancer, they have been conducted mostly in underfed populations or persons otherwise deficient in these antioxidants. The CARET studies in the early 1990s found that if smokers take beta-carotene and vitamin A supplements they actually increase their risk of developing lung cancer. Rather than isolated antioxidants found in supplements, it may be the combination of antioxidants found in foods that are responsible for decreasing the risk of cancer. The American Institute of Cancer Research warns that antioxidant supplements cannot substitute for whole foods. Individuals who may want to consider supplements include those who are underfed, have certain medical conditions, chronic dieters, some vegetarians, some seniors, and newborns.

Concern has developed about potential negative interactions between high doses of antioxidants and chemotherapy. Anthracycline antitumor antibiotics used as chemotherapy act by creating free oxygen radicals to kill tumor cells through a process known as apoptosis. Although patients taking antioxidants may improve their tolerance to chemotherapy drugs, they may be decreasing the effectiveness of treatment and risking a recurrence of the tumor in the long run. This viewpoint is theoretical, however, and no clinical studies have as yet addressed it. Patients interested in using antioxidants during chemotherapy or radiotherapy should discuss this option with their physicians.

High doses of vitamins and minerals can be toxic. The National Academy of Sciences has suggested safe upper intake levels for adults for some antioxidants. These limits are 2, 000 milligrams of vitamin C per day from both foods and supplements combined, 1, 000 milligrams of vitamin E per day, and 400 micrograms per day of selenium from both supplements and foods. It is not known how higher levels than these will affect healthy persons.

Side effects of vitamin E overdose may include fatigue , intestinal cramping, breast soreness, thrombophlebitis, acne, and diarrhea , and increase in blood pressure in certain people. Blood clotting time has been shown to increase. Also, with 1, 800 IU per day, and vitamin E is antagonistic to iron and patients with anemia who are taking iron supplements should not take the two supplements at the same time. Vitamin E may also interfere with vitamin K. Selenium toxicity is characterized by dermatologic lesions; brittle hair, fragile or black fingernails, metallic taste, dizziness, and nausea.

Description

Free radicals are naturally produced in the body through the normal metabolism of amino acids and fats. These free radicals are unstable molecules that can freely react with and destroy healthy cells. They can bind to and alter the structure of DNA thus leading to mutations and eventually to cancer. Besides cancer, this oxidative stress on the cells can lead to heart, eye, and neurological diseases.

Glutathione, lipoic acid, and CoQ10 are antioxidants formed naturally by the body but their levels decline with age. Vitamins C and E are necessary antioxidants but not produced by the body and must be obtained from the diet. The most common antioxidants are the vitamins A, C, and E. Additional antioxidants are natrol, found in grapes and wine; selenium; and melatonin. Flavonoids consist of a large family of antioxidant compounds found in fruits and vegetables. Among the well-studied flavonoids in terms of cancer prevention are catechins from green tea, genistein from soy, curcumin from turmeric, anthocyanosides from blueberries, and quercetin from yellow vegetables.

Although controversy will surround the topic of supplemental antioxidants for some time, there is little if any controversy that dietary levels of antioxidants are useful in preventing cancer. Because of this evidence, the American Cancer Society suggests five servings of fruits and vegetables each day.

Resources

BOOKS

Moss, Ralph W. Antioxidants Against Cancer. Brooklyn, NY:Equinox Press, Inc., 2000.

PERIODICALS

Kelly, Kara M. "The Labriola/Livingston Article Reviewed."Oncology 13, no. 7 (1999):1008-1011.

Labriola, Dan, and Robert Livingston. "Possible Interactions Between Dietary Antioxidants and Chemotherapy." Oncology 13, no. 7 (1999): 1003-1008.

Lamson, Davis W, and Matthew S. Brignall. "Antioxidants in Cancer Therapy: Their Actions and Interactions with Oncologic Therapies." Alternative Medicine Review 4, no. 5 (1999): 304-329.

ORGANIZATIONS

American Cancer Society. <http://www.cancer.org>

American Institute for Cancer Research. 1759 R Street, NW, PO Box 97167, Washington, DC 20090-7167. (800)843-8114. <http://www.aicr.org>

National Academy of Science. <http://www.nas.edu>

OTHER

<http://clinical.caregroup.org/altmed/interactions/Nutrients/Vitamin_E.htm>

<http://www.medical.com.hk/english_site/pharmacy_site/vitamins_s/selenium/selenium_m.htm>

Cindy Jones, Ph.D.

KEY TERMS

Apoptosis

A type of cell death. A mechanism by which one cell dies if it becomes severely mutated as a means of protecting the entire organism.

Cisplatin

An anticancer drug.

Doxorubicin

An anticancer antibiotic therapy. Its trade name is Adriamycin

Fluorouracil

An anticancer drug. Its trade names include Adrucil, 5-FU, Efudex, and Fluoroplex.

Mutation

A change in the genetic structure of the cell.

Oxidative stress

A condition where the body is producing an excess of oxygen-free radicals.

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antioxidant

antioxidant, substance that prevents or slows the breakdown of another substance by oxygen. Synthetic and natural antioxidants are used to slow the deterioration of gasoline and rubber, and such antioxidants as vitamin C (ascorbic acid), butylated hydroxytoluene (BHT), and butylated hydroxyanisole (BHA) are added to foods (see food additives) to prevent them from becoming rancid or from discoloring.

In the body, nutrients such as beta-carotene (a vitamin A precursor), vitamin C, vitamin E, and selenium have been found to act as antioxidants. They act by scavenging free radicals, molecules with one or more unpaired electrons, which rapidly react with other molecules, starting chain reactions in a process called oxidation. Free radicals are a normal product of metabolism; the body produces its own antioxidants (e.g., the enzyme superoxide dismutase) to keep them in balance. However, stress, aging, and environmental sources such as polluted air and cigarette smoke can add to the number of free radicals in the body, creating an imbalance. The highly reactive free radicals can damage healthy DNA and have been linked to changes that accompany aging (such as age-related macular degeneration, a leading cause of blindness in older people) and with disease processes that lead to cancer, heart disease, and stroke.

Studies have suggested that the antioxidants that occur naturally in fresh fruits and vegetables have a protective effect. For example, vitamin E and beta-carotene appear to protect cell membranes; vitamin C removes free radicals from inside the cell. There is still some question as to whether antioxidants in the form of dietary supplements counteract the effects of increased numbers of free radicals in the body. Some scientists believe that regular consumption of such supplements interferes with the body's own production of antioxidants.

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antioxidants

antioxidants Substances that slow the rate of oxidation reactions. Various antioxidants are used to preserve foodstuffs and to prevent the deterioration of rubber, synthetic plastics, and many other materials. Some antioxidants inhibit the oxidation reaction by removing oxygen free radicals. Naturally occurring antioxidants with this ability include vitamin E, β-carotene, and glutathione; they limit the cell and tissue damage caused by foreign substances, such as toxins and pollutants, in the body.

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antioxidant

antioxidant A substance that retards the oxidative rancidity of fats in stored foods. Many fats, and especially vegetable oils, contain naturally occurring antioxidants, including vitamin E, which protect them against rancidity for some time. Synthetic antioxidants include propyl, octyl, and dodecyl gallates, butylated hydroxyanisole (BHA), and butylated hydroxytoluene (BHT). See also antioxidant nutrients; induction period.

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anti-oxidant

anti-oxidant A compound, usually organic in nature, that prevents or retards the oxidation by molecular oxygen (autoxidation) of materials such as food, rubber, and plastics. It acts by scavenging the free radicals generated in autoxidation chain reactions, and thus provides an alternative oxidation pathway. It does not act indefinitely as it is destroyed in the process.

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anti-oxidant

anti-oxidant A compound, usually organic in nature, that prevents or retards the oxidation by molecular oxygen (autoxidation) of materials such as food, rubber, and plastics. It acts by scavenging the free radicals generated in autoxidation chain reactions, and thus provides an alternative oxidation pathway. It does not act indefinitely as it is destroyed in the process.

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antioxidant

an·ti·ox·i·dant / ˌantēˈäksidənt; ˌantī-/ • n. a substance that inhibits oxidation, esp. one used to counteract the deterioration of stored food products. ∎  a substance such as vitamin C or E that removes potentially damaging oxidizing agents in a living organism.

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antioxidant

antioxidant (anti-oks-i-dănt) n. a substance capable of neutralizing oxygen free radicals, the highly active and damaging atoms and chemical groups produced by various disease processes and by poisons, radiation, smoking, and other agencies. Antioxidants include vitamin C (ascorbic acid), vitamin E (tocopherols), and beta carotene.

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