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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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Antioxidants

Antioxidants

Definition

Purpose

Description

Precautions

Interactions

Complications

Parental concerns

Resources

Definition

Antioxidants are molecules that prevent oxygen molecules from interacting with other molecules in a process called oxidation. In the body, antioxidants combine with potentially damaging molecules called free radicals to prevent the free radicals from causing damage to cell membranes, DNA, and proteins in the cell. Common antioxidants important to human health are vitamins A, C, E, beta-carotene, and selenium. In the mid-2000s, about 20% of North Americans and Europeans were taking at least one antioxidant dietary supplement.

Purpose

The role of antioxidants in the body is complex and not completely understood. Antioxidants combine with free radicals so that the free radicals cannot react with, or oxidize, other molecules. In this way, antioxidants help slow or prevent damage to cells. Damage caused by free radicals is thought to cause or contribute to cardiovascular disease, cancer, Alzheimer’s disease, age-related changes in vision, and other signs of aging. However, no direct cause and effect relationship between antioxidant intake and disease prevention has been proven. Antioxidants unrelated to those of importance in the body have commercial uses in the preservation of processed food and in many industrial processes.

Description

Oxygen is essential to many reactions that occur within cells. Free radicals form mainly as a result of normal cellular metabolism involving oxygen. They can also form in abnormally large amounts when the body is exposed to radiation, ultraviolet light, and toxins such as cigarette smoke or certain chemicals.

Health benefits of antioxidants and their food sources

AntioxidantHealth benefitsFood sources
SeleniumHelps 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-caroteneKeeps 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 EActs 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 CDestroys 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

(Illustration by GGS Information Services/Thomson Gale.)

The common feature of free radicals is that their molecular structure contains and unpaired electron. Free radical molecules with an unpaired electron are unstable and have a strong tendency to react with other molecules by ‘stealing’ an electron from them to form a more stable electron pair. This reaction is called oxidation (even when it happens with molecules other than oxygen). In the body, free radicals cause damage when they react with deoxyribonucleic acid (DNA—genetic material), proteins, and lipids (fats ). Antioxidants are molecules that react with free radicals in ways that neutralize them so they no longer are able to ‘steal’ electrons and cause damage.

Some important human antioxidants must be acquired through diet, while others can be made by the body. Vitamin C (ascorbic acid), vitamin E (alphatocopherol), vitamin A (retinol), and beta-carotene are the most important antioxidants the body must obtain from food sources. Flavonoids found in tea, chocolate, grapes, berries, onions, and wine also appear to have antioxidant activity, although their role in health is unclear. Selenium is sometimes classified as an antioxidant, although strictly, it is not. Selenium is a mineral that must be acquired through diet. Plants grown in geographic locations with selenium rich soil provide a rich source of this mineral. Brazil nuts and tuna also have high levels of selenium. It is a necessary part of enzymes involved in antioxidant reactions. Glutathione and coenzyme Q (ubiquinone) are the most important antioxidants the body can make for itself.

Antioxidants and health

When free radicals build up faster than antioxidants can neutralize them, the body develops a conditioncalled oxidative stress. Oxidative stress reduces the body’s ability to deal with damage to cells and is thought to play a role in the development of chronic diseases such as cardiovascular disease, cancer, and Alzheimer’s disease. Researchers know that a diet high in fruits and vegetables containing antioxidants promotes health and decreases the risk of developing some chronic diseases such as atherosclerosis (hardening of the arteries). In the early 2000s, dietary supplements containing antioxidants were popularized as a way to reduce oxidative stress, prevent health problems such as cancer, stroke, heart attack, and dementia, and live longer. Research has since shown that although there are relationships between antioxidant levels and health, antioxidant dietary supplements are not magic bullets to prevent age-related diseases.

One problem in determining whether there is a cause and effect relationship between oxidative stress and disease is that often it is not possible to tell if oxidative stress causes a disease or if the disease brings about oxidative stress as a result of biochemical changes in diseased cells. Also, everyone develops oxidative stress as they age, but not everyone develops the same diseases. The interactions between an individual’s diet, environment, genetic make-up, and health are complex and still not well understood. Antioxidants remain of great interest to researchers seeking ways to prevent and cure chronic disease. Many clinical trials are underway to determine safety and effectiveness of different antioxidants, both alone and in combination with other drugs and supplements.

CARDIOVASCULAR DISEASE. The strongest link between antioxidant levels and health is related to the development of cardiovascular disease. Low-density lipoprotein cholesterol (LDL or ‘bad cholesterol’) appears to react with free radicals. This changes the LDL cholesterol in a way that allows it to accumulate in cells lining the blood vessels. These cholesterol-loaded cells are precursors to the development of plaque, hard deposits that line blood vessels and cause cardiovascular disease, heart attack, and stroke.

Researchers thought increasing the amount of antioxidants in the blood by taking supplements would decrease the number of free radicals available to interact with LDL cholesterol and thus lower the risk of developing cardiovascular disease. This theory has not been proved. In fact, a paper published in the Journal of the American Medical Association on February 28, 2007, analyzed 68 trials of antioxidant supplements involving about 232,600 patients. The authors concluded that antioxidant supplements did not prolong life. In fact, when only rigorous, well-controlled studies were analyzed, the risk of dying increased 5%. This analysis is quite controversial, with some experts questioning the analytical methods used. However, the American Heart Association and similar organizations in other countries advocate cardiovascular disease prevention through consumption of fruits, vegetables, whole grains and nuts high in antioxidants and other heart-protecting nutrients instead of antioxidant supplements.

CANCER. Free radicals damage DNA, and sometimes this damage leads to development of cancer. In laboratory cell cultures and animal studies, antioxidants appear to slow the development of cancer. The results have been mixed in studies where humans took antioxidant dietary supplements. A large study of 29,000 men showed that when a beta-carotene dietary supplement was taken by men who smoked, they developed lung cancer at a rate 18% higher and died at a rate 8% higher than men who did not receive the supplement. Another study that gave men dietary supplements of beta-carotene and vitamin A was stopped when researchers found the men receiving the beta-carotene had a 46% greater chance of dying from lung cancer than those who did not receive the supplement. Other large studies have shown either no or only slight protective effects against cancer. The position of the American Cancer Society, the National Cancer Institute, and several international health organizations is that antioxidants should come from a healthy diet high in fruits and vegetables and low in fat and not from dietary supplements.

AGE-RELATED VISION IMPAIRMENT. Cataracts and age-related macular degeneration are two types of vision impairment common in older individuals. Cataracts

KEY TERMS

Coenzyme— Also called a cofactor; a small non-protein molecule that binds to an enzyme and catalyzes (stimulates) enzyme-mediated reactions.

Dietary supplement— A product, such as a vitamin, mineral, herb, amino acid, or enzyme, intended to be consumed in addition to an individual’s diet with the expectation that it will improve health.

Enzyme— A protein that changes the rate of a chemical reaction within the body without themselves being used up in the reaction.

Free radical— A molecule with an unpaired electron that has a strong tendency to react with other molecules in deoxyribonucleic acid (DNA), proteins, and lipids (fats), resulting in damage to cells. Free radicals are neutralized by antioxidants.

Mineral— An inorganic substance found in the earth that is necessary in small quantities for the body to maintain a health. Examples: zinc, copper, iron.

Oxidation— Interaction in which one molecule removes an electron from another molecule to stabilize itself.

Retina— The layer of light-sensitive cells on the back of the eyeball that function in converting light into nerve impulses.

Vitamin— An essential nutrient the body needs in small amounts to remain healthy but that the body cannot manufacture for itself and must acquire through diet.

develop because of changes in the protein in the lens of the eye. These changes cause the lens to become cloudy and limit vision. The changes may be due to damage by free radicals. Age-related macular degeneration is an irreversible disease of the retina that causes blindness. Two carotenoid antioxidants, zeaxanthin and lutein, are found in the retina and are essential to vision. However, study participants who took antioxidant supplements over several years did not have a reduced risk of developing these diseases.

Precautions

The mixed results obtained in human studies of antioxidant supplements suggests that all antioxidants should come from foods and not from dietary supplements. There is also little information on the safety of antioxidant supplements in children and women who are pregnant or breastfeeding .

Interactions

The interaction among various antioxidants, enzymes, coenzymes, drugs, herbal and dietary supplements is complex and incompletely understood. Specific antioxidants may have known interactions and should be discussed with a physician.

Complications

Antioxidants acquired by eating fruits and vegetables promote health. No complications are expected from antioxidants in food. Antioxidant dietary supplements may interact with other supplements, prescription drugs, over-the-counter drugs, and herbal supplements in ways that cause undesirable side effects. Consult a physician prior to taking an antioxidant supplement.

Parental concerns

Parents should encourage their children to eat a healthy and varied diet high in fruits, vegetables, and whole grains. There is no need to give children antioxidant dietary supplements. The safety of these supplements in children has not been studied.

Resources

BOOKS

DeCava, Judith A. The Real Truth about Vitamins and Antioxidants, 2nd ed. Fort Collins, CO: Selene River Press, 2006.

Challem, Jack and Marie Moneysmith. Basic Health Publications User’s Guide to Carotenoids & Flavonoids: Learn How to Harness the Health Benefits of Natural Plant Antioxidants North Bergen, NJ: Basic Health Publications, 2005.

Frei, Balz, ed. Natural Antioxidants in Human Health and Disease San Diego: Academic Press, 2006.

Panglossi, Harold V., ed. Antioxidants: New Research New York: Nova Science Publishers, 2006.

Wildman, Robert E. C., ed. Handbook of Nutraceuticals and Functional Foods, 2nd ed Boca Raton, FL: CRC/ Taylor&Francis, 2007.

PERIODICALS

Bjelakovic, G., D. Nikolova, L.L. Gluud, R.G. Simonetti, and C. Gluud. ‘Mortality in Randomized Trials of Antioxidant Supplements for Primary and Secondary Prevention: Systematic Review and Meta-analysis’. Journal of the American Medical Association 297 (February 28, 2007): 842-57.

Kushi, Lawrence H., Tim Byers, Colleen Doyle, et al. ‘American Cancer Society Guidelines on Nutrition and Physical Activity for Cancer Prevention.’ CA: Cancer Journal for Clinicians 56 (2006): 254-281. <http://caonline.amcancersoc.org/cgi/content/full/56/5/254>

ORGANIZATIONS

American Cancer Society. 1599 Clifton Road NE, Atlanta GA 30329-4251. Telephone: 800 ACS-2345. Website: <http://www.cancer.org>.

American Dietetic Association. 120 South Riverside Plaza, Suite 2000, Chicago, IL 60606-6995. Telephone: (800) 877-1600. Website: <http://www.eatright.org>.

American Heart Association. 7272 Greenville Avenue, Dallas, TX 75231. Telephone: (800) 242-8721. Website: <http://www.americanheart.org>.

Linus Pauling Institute. Oregon State University. 571 Weniger Hall, Corvallis, OR 97331-6512. Telephone: (541) 717-5075. Fax: (541) 737-5077. Website: <http://lpi.oregonstate.edu>.

Office of Dietary Supplements, National Institutes of Health. 6100 Executive Blvd., Room 3B01, MSC 7517, Bethesda, MD 20892-7517 Telephone: (301)435-2920. Fax: (301)480-1845. Website: <http://dietarysupplements.info.nih.gov>.

OTHER

American Cancer Society. ‘Antioxidants and Cancer: The Jury’s Still Out’. American Cancer Society. September 8, 2005. [cited April 28, 2007] <http://www.cancer.org/docroot/NWS/content/NWS_2_1x_Antioxidants_and_Cancer_The_Jurys_Still_Out.asp>.

International Food Information Council. ‘Functional Foods Fact Sheet: Antioxidants.’ International Food Information Council. March 2006. [cited April 28, 2007]. <http://www.ific.org/publications/factsheets/antioxidantfs.cfm>.

Mayo Clinic Staff. ‘Anti-aging Therapies: Too Good to Be True?’ MayoClinic.com. May 11, 2005. [cited April 28, 2007]. <http://www.mayoclinic.com/health/anti-aging/HQ00233>.

Medline Plus. ‘Antioxidants May Slightly Raise Risk of Death.’ National Institutes of Health. February 28, 2007. [cited April 28, 2007]. <http://www.nlm.nih/gov/medlineplus/news/fullstory_45846.html>.

National Cancer Institute. ‘Antioxidants and Cancer Prevention: Fact Sheet.’ National Institutes of Health. July 28, 2004. [cited April 28, 2007] <http://www.cancer.gov/cancertopics/factsheet/antioxidantsprevention>.

Tish Davidson, A.M.

Antiscorbutic vitamin seeVitamin C

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Antioxidants

Antioxidants

Vitamins as antioxidants

The vitamins

Current research on antioxidants

Resources

Antioxidants are molecules that prevent or slow down the breakdown of other substances by oxygen.

In biology, antioxidants are scavengers of small, reactive molecules known as free radicals; they include intra-cellular enzymes such as superoxide dismutase (SOD), catalase, and glutathione peroxidase. Free radicals are molecules with one or more unpaired electrons, which can react rapidly with other molecules in processes of oxidation. Free radicals possess a great deal of energy and so can cause a great deal of damage to cells.

To generate energy, cells must produce millions of chemical reactions. During this process, some oxygen molecules finish up with an odd instead of even number of electrons. Because each electron needs a mate, an unpaired electron makes the oxygen molecule unstable. These unstable molecules, called free radicals, then take an electron from a neighboring cell. The neighboring cell then becomes unstable, and affects its neighboring cell, starting a chain reaction. This domino effect becomes dangerous when the cell membrane or DNA is attacked, causing the cell to function poorly or die.

Antioxidants act by neutralizing free radicals, which are atoms or groups of atoms that become destructive to cells when produced in large quantities. By scavenging free radicals, antioxidants help protect cells from damage and can lengthen the effective life of cells. Antioxidants can be extracellular, originating as exogenous cofactors such as vitamins. Nutrients functioning as antioxidants include vitamins, for example ascorbic acid (vitamin C), tocopherol (vitamin E), and vitamin A. Trace elements such as the divalent metal ions selenium and zinc also have antioxidant activity, as does uric acid, an endogenous product of purine metabolism. While the human body naturally manufactures some antioxidant enzymes, it cannot manufacture selenium, the trace mineral necessary to produce these enzymes, nor can it manufacture the essential micro-nutrient antioxidants vitamins C, E, and beta-carotene and other carotinoids. These must be obtained by eating foods rich in these essential nutrients and, in some cases, supporting the diet with vitamin supplements.

When the body is unable to produce enough antioxidants to counteract free radicals, the resultant cell damage can cause certain types of cancer, heart disease, premature aging, cataracts, and other serious illnesses. For example, when free radicals damage artery walls, fatty deposits accumulate around the scar tissue, causing atherosclerosis and heart disease.

The brain is particularly vulnerable to oxidative stress. Free radicals play an important role in a number of neurological conditions including stroke, Parkinson disease, Alzheimers disease, epilepsy, and schizophrenia. Some other diseases in which oxidative stress and depletion of antioxidant defense mechanisms are prominent features include hepatic cirrhosis, preeclampsia, pancreatitis, rheumatoid arthritis, mitochondrial diseases, systemic sclerosis, malaria, neonatal oxidative stress, and renal dialysis.

Free radicals are the normal products of metabolism and are usually controlled by the antioxidants produced by the body or taken in as nutrients. 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 nucleic acids and have been linked to changes that accompany aging (such as age-related macular degeneration, an important cause of blindness in older people) and with disease processes that lead to cancer, heart disease, and stroke.

Most of the bodys cells are continually exposed to free radicals, the creation of which is also stimulated by external sources such as tobacco smoke, smog, radiation, herbicides, and other environmental pollutants. Antioxidants are the bodys mechanism for stabilizing free radicals. They work by donating one of their electrons to the unstable molecule, preventing the unpaired electron from stealing from another cell. Unlike oxygen molecules, antioxidants remain stable, even after donating an electron.

Vitamins as antioxidants

Vitamins play a vital role in the bodys healthy functioning. Researchers now know that vitamins E, C, B1, B2, and B3, the carotenoids (beta-carotene, lycopene, and lutein), selenium, and magnesium, are important antioxidants in the bodys continuous fight against free radicals. These essential nutrients are readily available in fresh fruit and vegetables and many studies have linked fruit and vegetable consumption to a lowered risk of certain diseases.

The vitamins

Carotenoids, excellent antioxidants, are available in abundance in red, orange, and deep yellow vegetables and fruits such as tomatoes, sweet potatoes, winter squash, carrots, peaches, and cantaloupe; dark green leafy vegetables such as spinach and broccoli; as well as liver, egg yolks, milk, and butter. Studies show that men with the lowest levels of beta-carotene are at the highest risk for prostate cancer. Vitamin A, a fat-soluble vitamin, is notas is sometimes suggested an antioxidant. However, beta-carotenea vitamin A analog, or precursor, is converted into vitamin A by the body. Because it is stored in the liver, vitamin A can be toxic when taken in large quantities. Lycopene, another carotenoid and one of the most powerful antioxidants, is believed to be effective against many diseases including cancers of the mouth, pharynx, esophagus, stomach, colon, rectum, and cervix. Early in 1999, studies showed that tomatoes and their byproducts drastically increase blood levels of lycopene and reduce cellular damage from free radicals. Lutein, also a carotenoid, is believed to decrease the risk of macular degeneration.

Vitamin E, a fat-soluble vitamin, is not only essential for promoting general good health in the areas of aging, infertility, and athletic performance, research has also shown this antioxidant counteracts cell damage that leads to cancer, heart disease, and cataracts. It is also known to work together with other antioxidants, such as vitamin C, to help prevent some chronic illnesses. Available in vegetable oils, margarine, wheat germ, nuts, seeds, and peanut butter, supplementation of this important vitamin may be necessary to maintain adequate amounts within the body.

Vitamin C (also called ascorbic acid) is a water-soluble vitamin and is not easily stored in the body. Therefore, daily intake is required. This antioxidant workhorse is perhaps the most famous, and research has shown its effectiveness in lowering the risk of cataracts and other eye problems, lowering blood pressure and cholesterol levels, and reducing the risk of heart attacks and strokes. Researchers have also found that people suffering from asthma, arthritis, cancer, and diabetes have low levels of vitamin C. Excellent dietary sources of vitamin C include citrus

KEY TERMS

Fat-soluble vitamin Vitamins that can be dissolved in oil or fat and are stored in the bodys fatty tissue.

Free radicals Unstable molecules containing an odd number of electrons and, therefore, seeking an electron from another molecule.

Water-soluble vitamin Vitamins that can be dissolved in water and are excreted from the body through the kidneys.

fruits (especially oranges and grapefruit), kiwi fruit, strawberries, red peppers, broccoli, and potatoes.

Current research on antioxidants

A higher consumption of vitamin E and, to a lesser extent, beta-carotene is associated with a large decrease in the rate of coronary arterial disease. Furthermore, a diet rich in fruits and vegetables leads to a marked decline in the cancer rate in most organs with the exception of blood, breast, and prostate. Antioxidants play a major role in this. It is now abundantly clear that toxic free radicals play an important role in carcinogenesis. High cancer rates have been linked to low blood levels of antioxidants, particularly vitamin E. Similarly, vitamin C is thought to protect against stomach cancer by scavenging carcinogenic nitrosamines in the stomach.

Resources

BOOKS

Abbas, Abul K., and Andrew Lichtman. Cellular and Molecular Immunology. Updated ed. New York: Saunders, 2005.

Alberts, Bruce, et al. Essential Cell Biology. 2nd ed. New York: Garland Science/Taylor & Francis Group, 2004.

Janeway, C. Immunobiology. New York: Garland Science, 2004.

Judyth Sassoon
Larry Blaser

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Antioxidants

Antioxidants

Definition

An antioxidant is a substance that prevents oxidation reactions. In the body, these oxidation reactions can cause tissue damage. Common antioxidants include vitamin C, vitamin E , beta carotene and selenium. Antioxidants are also called free radical scavengers.

Description

To understand what an antioxidant is it is necessary to understand what an oxidant is. Oxidants are called free radicals or reactive oxygen species. Oxidant molecules attack other molecules in the body changing their chemical structure and causing damage in the body. Oxidants come about from various environmental sources including cigarette smoke, pollution, and ultraviolet light, but they are also formed by the body or can be found in certain foods, including high fat and fried foods.

Oxidation can harm a number of molecules in the body including fats, proteins and carbohydrates , but are probably most dangerous when they attack DNA. Oxidative damage is thought to be responsible for a number of diseases including heart disease, cancer , macular degeneration and cataracts, rheumatoid arthritis , neurological diseases such as Alzheimer's and Parkinson's diseases, multiple sclerosis and muscular dystrophy. Oxidation reactions are thought to contribute to aging in general. Antioxidants are added to food to help prevent deterioration of food that occurs with exposure to air and sunlight. Oxidation of oils or fats such as butter causes rancidity.

The only thing that will stop damaging oxidative reactions is an antioxidant. The body produces some of its own antioxidants such as glutathione and superoxide dismutase, but antioxidants can also be taken into the body through foods and supplements. Vitamins A, C and E and selenium are common antioxidants that are both found in foods or taken as supplements. Fruits and vegetables are the best source of antioxidants. Antioxidants known as flavonoids are also found in fruits and vegetables. Antioxidant flavonoids quercetin, genistein, anthocyanins or lycopene.

Uses for specific antioxidants

  • Vitamin CVitamin C is called ascorbic acid and plays an important role in production of connective tissue in bone, cartilage and skin. It helps stimulate wound healing and stimulates the immune system. Vitamin C may play a role in protection from cancer, cardiovascular disease and aging. Deficiency of vitamin C can lead to bleeding gums, joint pain, bruising and dry skin. Foods high in vitamin C include oranges, sweet peppers, strawberries and broccoli.
  • Vitamin A or carotenoids—Vitamin A and carotenoids are very similar and some carotenoids are converted into vitamin A in the body. Carotenoids include carotene, lycopene, lutein and zeaxanthin. Carotenoids help prevent the development of cancer, cardiovascular disease and several eye and vision problems. Foods high in carotenoids include carrots, tomatoes, sweet potatoes, pumpkin, spinach, and apricots.
  • Vitamin EVitamin E is also called tocopherol and is found in oils such as soybean oil or wheat germ oil. Vitamin E is important for maintaining the immune system and it works with vitamin C to enhance immune function. Vitamin E can also help prevent some eye problems such as cataracts and macular degeneration. Deficiencies of vitamin E are rare, but can result in nerve damage, inability to concentrate, low thyroid levels and decreased immune response. Some research suggests that slight deficiencies in vitamin E can increase the risk of cardiovascular disease and cancer. Foods high in vitamin E include vegetable oils, whole grains and eggs.
  • Selenium—Selenium is a mineral rather than a vitamin and is important for the immune system and the cardiovascular system. Because selenium is found in soil, it is in most foods unless there is a deficiency in that soil. Selenium is also found in organ meats and seafood.

Recommended dosage

Medical studies have repeatedly shown health benefits from eating a diet high in fruits and vegetables. Specific dietary recommendations, however, are not well established. Several organizations including the Department of Health and Human Services as well as the U.S. Department of Agriculture (USDA) recommends five servings of fruits and vegetables daily. These recommendations may increase to nine servings per day based on research showing that nine is more beneficial than five. The benefits of a diet high in fruits and vegetables have been attributed primarily to high antioxidant levels found in these foods.

Diets high in fruits and vegetables are associated with a lower risk of cancer, heart disease, and neurological diseases. Research studies that have focused on supplements rather than food as a source for antioxidants have not been as promising. Determining dietary recommendations for specific antioxidants is difficult. The following are some recommendations made by Institute of Medicine.

Recommended dosages for specific antioxidants

  • Vitamin C—The recommended daily allowance (RDA) for vitamin C is 75 mg/day for women and 90 mg/day for men not to exceed 2,000 mg/day. Many people take higher amounts without side effects. Those who need more vitamin C include smokers, and those who take aspirin, estrogen, antibiotics, corticosteroids or drink alcohol.
  • Vitamin A and carotenoids—The RDA for vitamin A and the carotenoids are the most difficult to establish and are the least reliable. The current RDA is 700 mcg/day for women and 900 mcg/day for men. The upper limit is 3,000 mcg/day.
  • Vitamin E—The RDA for vitamin E is 15 mg/day for both men and women. The upper limit is 1,000 mg/day. Since vitamin E is a fat, it must be taken with other fats to be adequately absorbed.
  • Selenium—The RDA for selenium is 55 mcg/day with the upper limit being 400 mcg/day.

Precautions

Many studies have found that antioxidants taken as food can prevent disease. However, when taken as dietary supplements in pill form antioxidants have not been found to have beneficial effects and in some cases have been found to have negative effects on health.

Side effects

There are no known side effects for ingesting antioxidants in food. Some side effects have been identified for specific antioxidants taken as supplements.

Side effects for specific antioxidants

  • Vitamin C—Since vitamin C is a water soluble vitamin it does not build up in the body. High amounts of vitamin C can cause diarrhea, cramping, nausea, excess urination and skin rashes. The occurrence of kidney stones has been identified with excessive consumption of vitamin C. People with renal problems are more likely to experience side effects.
  • Vitamin A—High doses of vitamin A can lead to a yellowing of the skin. Vitamin A given as supplements has been associated with an increased risk of lung cancer, especially among smokers.
  • Vitamin E—Short term doses of vitamin E are not associated with risks, but long term administration of high doses can lead to bleeding, diarrhea, abdominal pain, fatigue and reduced immunity.
  • Selenium—High doses of selenium can result in fatigue, irritability and dry hair.

Interactions

No significant interactions have been identified for antioxidant consumption.

Caregiver concerns

No caregiver concerns are noted for antioxidant consumption.

Resources

PERIODICALS

Bjelakovic, G., et al. “Mortality in Randomized Trials of Antioxidant Supplements for Primary and Secondary Prevention: Systematic Review and Meta-analysis.” Journal of the American Medical Association (JAMA) 297 (2007): 842–857.

OTHER

Dietary Reference Intakes.” Institute of Medicine of the National Academies. March 21, 2008 [cited April 10, 2008]. http://www.iom.edu/CMS/3788/4574.aspx.

Fruit & Vegetable Benefits. CDC—Centers for Disease Control. [cited April 10, 2008]. http://www.fruitsandveggiesmatter.gov/benefits/index.html

Hughes, Sue. “Antioxidant Vitamins May Increase Mortality.” Medscape Medical News. March 1, 2007 [cited April 10, 2008]. http://www.medscape.com/viewarticle/552910.

McDermott, June. “Antioxidant Nutrients: Current Dietary Recommendations and Research Update.” Journal of the American Pharmaceutical Association 40, no. 6 (2000): 785–799 [cited April 10, 2008]. http://www.medscape.com/viewarticle/406705.

ORGANIZATIONS

Institute of Medicine, 500 Fifth Street NW, Washington, DC, 20001, (202) 334-2352, [email protected], http://www.iom.edu.

Cindy L.A. Jones Ph.D.

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Antioxidants

Antioxidants

Antioxidants are molecules that prevent or slow down the breakdown of other substances by oxygen .

In biology , antioxidants are scavengers of small, reactive molecules known as free radicals and include intracellular enzymes such as superoxide dismutase (SOD), catalase and glutathione peroxidase. Antioxidants can also be extracellular originating as exogenous cofactors such as vitamins. Nutrients functioning as antioxidants include vitamins, for example ascorbic acid (vitamin C), tocopherol (vitamin E) and vitamin A. Trace elements such as the divalent metal ions selenium and zinc also have antioxidant activity as does uric acid, an endogenous product of purine metabolism . Free radicals are molecules with one or more unpaired electrons, which can react rapidly with other molecules in processes of oxidation. They are the normal products of metabolism and are usually controlled by the antioxidants produced by the body or taken in as nutrients. 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 nucleic acids and have been linked to changes that accompany aging (such as age-related macular degeneration, an important cause of blindness in older people) and with disease processes that lead to cancer , heart disease, and stroke .

The brain is particularly vulnerable to oxidative stress. Free radicals play an important role in a number of neurological conditions including stroke, Parkinson disease , Alzheimer disease , epilepsy and schizophrenia . Some other diseases in which oxidative stress and depletion of antioxidant defence mechanisms are prominent features include hepatic cirrhosis , pre-eclampsia, pancreatitis, rheumatoid arthritis , mitochondrial diseases, systemic sclerosis, malaria , neonatal oxidative stress and renal dialysis .

Antioxidant simply refers to a molecule that protects cells from a process called oxidation, the negative effect of oxygen. Antioxidants act by neutralizing free radicals, which are atoms or groups of atoms that become destructive to cells when produced in large quantities. While our bodies naturally manufacture some antioxidant enzymes, it cannot manufacture selenium, the trace mineral necessary to produce these enzymes, nor can it manufacture the essential micronutrient antioxidants vitamins C, E, and beta-carotene and other carotinoids. They must be obtained by eating foods rich in these essential nutrients and, in some cases, supporting the diet with vitamin supplements.

To generate energy , cells must produce millions of chemical reactions . During this process, some oxygen molecules finish up with an odd instead of even number of electrons. Because each electron needs a mate, an unpaired electron makes the oxygen molecule unstable. These unstable molecules, called free radicals, then take an electron from a neighboring cell . The neighboring cell then becomes unstable, and affects its neighboring cell, starting a chain reaction. This domino effect becomes dangerous when the cell membrane or DNA is attacked, causing the cell to function poorly or die. When the body is unable to produce enough antioxidants to counteract free radicals, the resultant cell damage can cause certain types of cancer, heart disease, premature aging, cataracts, and other serious illnesses. For example, when free radicals damage artery walls, fatty deposits accumulate around the scar tissue , causing atherosclerosis and heart disease.

Most of the body's cells are continually exposed to free radicals, the creation of which is also stimulated by external sources such as tobacco smoke, smog , radiation , herbicides , and other environmental pollutants. Antioxidants are the body's mechanism for stabilizing free radicals. They work by donating one of their electrons to the unstable molecule, preventing the unpaired electron from "stealing" from another cell. Unlike oxygen molecules, antioxidants remain stable, even after donating an electron.


Vitamins as antioxidants

Vitamins play a vital role in the body's healthy functioning. Researchers now know that vitamins E, C, B1, B2, and B3, the carotenoids (beta-carotene, lycopene, and lutein), selenium, and magnesium , are important antioxidants in the body's continuous fight against free radicals. These essential nutrients are readily available in fresh fruit and vegetables and many studies have linked fruit and vegetable consumption to a lowered risk of certain diseases. While vitamin supplements may be helpful in fighting free radicals, there is no comparable evidence to show their effectiveness. Most traditional health authorities recommend three to five servings of fruit and vegetables daily, along with vitamin supplements, if necessary, for a total daily intake of 6–15 mg beta-carotene, 250–500 mg vitamin C, and 200–800 IU vitamin E.


The vitamins

Carotenoids, excellent antioxidants, are available in abundance in red, orange, and deep yellow vegetables and fruit such as tomatoes, sweet potatoes, winter squash, carrots, peaches, and cantaloupe; dark green leafy vegetables such as spinach and broccoli; as well as liver, egg yolks, milk, and butter. Studies show that men with the lowest levels of beta-carotene are at the highest risk for prostate cancer. (Vitamin A, a fat-soluble vitamin, is not—as is sometimes suggested—an antioxidant. However, beta-carotene—a vitamin A analog, or precursor, is converted into vitamin A by the body. Because it is stored in the liver, vitamin A can be toxic when taken in large quantities.) Lycopene, another carotenoid and one of the most powerful antioxidants, is believed to be effective against many diseases including cancers of the mouth, pharynx, esophagus, stomach, colon, rectum, and cervix. Early in 1999, studies showed that tomatoes and their byproducts drastically increase blood levels of lycopene and reduce cellular damage from free radicals. Lutein, also a carotenoid, is believed to decrease the risk of macular degeneration.

Vitamin E, a fat-soluble vitamin, is not only essential for promoting general good health in the areas of aging, infertility , and athletic performance, research has also shown this antioxidant counteracts cell damage that leads to cancer, heart disease, and cataracts. It is also known to work together with other antioxidants, such as vitamin C, to help prevent some chronic illnesses. Available in vegetable oils, margarine, wheat germ, nuts, seeds , and peanut butter, supplementation of this important vitamin may be necessary to maintain adequate amounts within the body.

Vitamin C (also called ascorbic acid) is a water-soluble vitamin and is not easily stored in the body. Therefore, daily intake is required. This "antioxidant workhorse" is perhaps the most famous, and research has shown its effectiveness in lowering the risk of cataracts and other eye problems, lowering blood pressure and cholesterol levels, and reducing the risk of heart attacks and strokes. Researchers have also found low levels of vitamin C in people suffering from asthma , arthritis, cancer, and diabetes. Excellent dietary sources of vitamin C include citrus fruits (especially oranges and grapefruit), kiwi fruit, strawberries, red peppers, broccoli, and potatoes.


Current research on antioxidants

The last few years have witnessed an explosion of information on the role of oxidative stress in causing a number of serious diseases, and there appears to be a potential therapeutic role for antioxidants in preventing such diseases. For example, recent epidemiological studies have shown that a higher consumption of vitamin E and to a lesser extent β-carotene is associated with a large decrease in the rate of coronary arterial disease. The most effective dose of vitamin E is apparently 400–800 mg/day. Other studies have shown that a diet rich in fruits and vegetables leads to a marked decline in the cancer rate in most organs with the exception of blood, breast and prostate. Antioxidants play a major role in this. It is now abundantly clear that toxic free radicals play an important role in carcinogenesis. In several studies high cancer rates were associated with low blood levels of antioxidants particularly vitamin E. Similarly, vitamin C is thought to protect against stomach cancer by scavenging carcinogenic nitrosamines in the stomach.

Studies have suggested that the antioxidants occurring naturally in fresh fruits and vegetables are very beneficial and protect against excessive oxidative stress. There is still some question as to whether antioxidants in the form of dietary supplements are equally beneficial. Some scientists believe that regular consumption of such supplements interferes with the body's own production of antioxidants.

See also Alternative medicine; Biochemistry; Nutrition.

Judyth Sassoon Larry Blaser

Resources

books

Mahan, L. Kathleen and Sylvia Escott-Stump. Krause's Food,Nutrition, and Diet Therapy. Philadelphia: W.B. Saunders, 2000.

Packer, Lester, et. al Antioxidant Food Supplements in HumanHealth. Academic Press, 1999.


other

National Cancer Institute. NCI Fact Sheet: "Tea and Cancer Prevention" December 6, 2002 [cited February 5, 2003]. <http://www.cancer.gov/newscenter/content_nav.aspx?viewid=afc8f2c0-f3df-4f6c-9c30-28fc15c0054e>.

National Eye Institute. United States National Library of Medicine. Clinical Advisory: "Antioxidant Vitamins and Zinc Reduce Vision Loss from Age-Related Macular Degeneration" October 25, 2001 [cited February 5, 2003]. <http://www.nlm.nih.gov/databases/alerts/amd.html>.

KEY TERMS

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Antioxidant

—A molecule that protects cells from the process of oxidation, the negative effect of oxygen.

Fat-soluble vitamin

—Vitamins that can be dissolved in oil or fat and are stored in the body's fatty tissue.

Free radicals

—Unstable molecules containing an odd number of electrons and, therefore, seeking an electron from another molecule.

Water-soluble vitamin

—Vitamins that can be dissolved in water and are excreted from the body through the kidneys.

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Antioxidants

Antioxidants

Antioxidant is the descriptive term given to a group of organic substances that generally function within the body to promote health through their counteraction against the potentially destructive effect of oxygen in human tissues, as carried out by agents known as free radicals. The best known anti-oxidants are vitamin C (ascorbic acid), vitamin E, selenium (a mineral), and the carotenoids, the class of the pigmentation substances that color many fruits and vegetables. An example of a carotenoid is betacarotene, the substance that produces the color in carrots.

Human diet is subdivided into two general classifications for the purpose of basic nutritional assessment. The first classification is macronutrients, the term that refers to all of the food products that contain carbohydrate, protein, and/or fat. The second classification is micronutrients, the term that defines all of the vitamins and most of the minerals that are absorbed into the body through food digestion. Phytochemicals are the trace substances found in plants and plant food products that are absorbed into the body as a part of either macronutrients or micronutrients; many phytochemicals also possess antioxidant properties.

An understanding of the function of antioxidants begins with the process of oxidation within the body. Oxidation occurs in a number of biological processes that are beneficial to the body. The essential role of oxygen within the aerobic energy system, and the oxidation of various harmful bacteria that invade the body are two examples of oxygen and its positive relation to human cell function.

Oxidation has a negative impact on the health of cells in certain conditions. While the oxygen molecule, described by the chemical equation O2, is often present in the body, it is not always as a stable, electrically neutral substance, but as the chemical structure known as free radicals, in which either atoms or molecules have one or more unpaired electron. When the cells have used oxygen, free radicals are often created as a byproduct of that process.

Atoms or molecules in which all electrons within the structure are paired tend to be stable; free radicals are unstable and are therefore highly reactive with other molecules. The free radicals seek out atoms or molecules from which they may "steal" an electron to create electrochemical balance within the radical; this results in instability in the unbalanced molecule, which will in turn seek to address its newly unstable state. This process will lead to a chain reaction of electron theft, which produces damage to both the membrane of cells and the contents of cells. Heart disease, increased incidence of stroke, diabetes, cancer, macular degeneration (a disease affecting the function of the macula, a small but vital area of the retina within the eye), and the acceleration of the general aging process have all been scientifically linked to the actions of free radicals within the body.

The micro-effects of oxidation within the body are similar to commonly observed oxidation in the world at large, such as the formation of rust (iron oxide) when bare steel is exposed to the elements.

Antioxidants do not attack these free radicals so much as they are scavengers of them. Antioxidants possess the ability to "donate" electrons, typically from a present hydrogen atom with the antioxidant structure, to electrically neutralize the free radical. Different types of antioxidants perform specialized types of scavenging and free radical-neutralizing work within the body.

Vitamin A is a fat-soluble vitamin, meaning that it may be stored within the body, either in the adipose (fat storage) tissue or in the liver. Common sources of vitamin A and other betacarotenoids are carrots, squash, and broccoli, as well as all other brightly colored fruits. Vitamin E is also fat soluble; it operates to specifically protect the free fatty acids in the bloodstream and the cell structures from oxidation; the presence of these fatty acids places an important role in the overall healthy function of cells. Vitamin E is present in many types of nuts, seeds, vegetable oils, and many types of whole grains.

The antioxidant role performed by vitamin C within the body is one of the many important functions of this chemical; vitamin C is essential to the manufacture of collagen, the protein that is the primary building material in bones and connective tissue. Vitamin C is water soluble, and it acts as a scavenger against waterborne free radicals before these agents can act against fat-soluble compounds, an event that creates the damaging chain reactions associated with cellular damage.

The chemical reaction between vitamin C and the encountered free radical results in the donation of a hydrogen atom to the oxidizing radical. The presence of enzymes creates a recycling effect on the vitamin C, permitting it to scavenge other radicals. The rate at which vitamin C can scavenge free radicals is increased by a factor of approximately ten times if the scavenging process occurs in the presence of phosphates. Vitamin E has been to shown to work as an excellent co-antioxidant with vitamin C. Vitamin C is present in all varieties of citrus fruits, as well as broccoli, strawberries, and tomatoes.

Selenium is plentiful in fish, red meats, and grains. It most commonly acts as an antioxidant in conjunction with glutathione peroxidase, a nonessential amino acid (an amino acid produced by the body), to protect white blood cells from the adverse effects of free radicals.

The antioxidants that are contained within various phytochemicals have also been the subject of specialized research in recent years. The best known of these substances are the flavanoids, a group of polyphenols (compounds with a hydrocarbon-based structure), found in soy, red wine, raw grapes, and cranberries. Lycopene, the chemical that is responsible for the red pigmentation of tomatoes and watermelon, is a powerful carotenoid. Lignan, a chemical found in flax, barley, and oatmeal, has also been identified as a water-soluble antioxidant.

Lutein is the antioxidant linked to the onset of macular degeneration; research suggests that a lutein deficiency is an underlying cause of the degenerative condition.

The body is capable of producing its own anti-oxidant defenses through its manufacture of two different enzymes, glutathione peroxidase, and superoxide dismutase (SOD). Enzymes are proteins manufactured by the body, primarily in the liver. Enzymes function as catalysts for a specific chemical reaction or series of reactions. When it comes into contact with a free radical oxygen molecule, SOD is the fastest reacting antioxidant available, in that it can neutralize more free radicals more quickly than any other substance within the body.

Significant publicity has been generated worldwide as to whether the consumption of antioxidants through dietary supplements, in larger quantities than are otherwise available through regular diet, will have a proportionately greater and beneficial effect on health. Numerous antioxidant products are marketed on the basis of claims that the products will either eliminate or reduce the risks associated with various types of cardiovascular disease, cancer, and a multitude of conditions that occur as a result of aging.

Scientific research has proved inconclusive as to whether this type of supplementation in fact achieves an antioxidant result. Studies that were specifically directed about the relationship between supplement consumption and the effect on the low density lipoproteins (LDLs) present in the blood vessels were conducted between 2003 and 2005 in the United States. LDL molecules were known to be particularly vulnerable to oxidation by free radicals, tending to cause the LDL molecules to proliferate on arterial walls, leading to the formation of plaque and creating stenosis, an unhealthy narrowing of the blood vessel that renders the individual more vulnerable to arteriosclerosis and stroke. The research in this area has proved to be inconclusive. Further studies where the test subjects were provided with large doses of vitamin A, vitamin C, and vitamin E as supplements failed to establish any evidence of increased disease prevention.

It is well established in the diet and nutritional sciences that the best manner in which to ingest nutrients of any kind and to have the nutrients effectively absorbed into the body is through food, and not supplements. The reduction of LDL and other unhealthy cholesterols in the bloodstream is most effectively addressed by examining the components of the foods consumed, as opposed to eating poor foods and then addressing a perceived cholesterol or LDL concern. Most nations of the world have published food guidelines that are similar in their scope to those advanced by the United States Department of Agriculture (the "Food Pyramid") and the American Heart Association. In general terms, the guidelines state that, as an alternative to antioxidant supplements, a healthy adult, eating six or more servings of grain products (bread, pastas, etc.), five servings of fruit or vegetables, between two to four servings of low fat dairy products, and a maximum of 6 oz (200 g) of lean meat or fish, will ingest 100% of the recommended daily allowances of the vitamins and minerals with antioxidant properties.

see also Cardiovascular system; Minerals; Phytochemicals; Vitamin C; Vitamin E.

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