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Oxidative damage to cells is thought to be a causative factor in disease and aging. The culprits are free radicals or reactive species of oxygen, nitrogen or chlorine. Superoxide, hydroxyl ions, hydrogen peroxide, and nitric oxide are examples of free radicals. These are atoms or molecules with an unpaired electron. Free radicals are naturally occurring and an important part of biological functions such as immunity, inflammation, growth and repair. Free radicals can have negative effects when they damage proteins, lipids and nucleic acids. They are normally held in balance in biological systems by antioxidant defense mechanisms. Environmental insults, infections, smoking, radiation and sunlight can also cause the formation of free radicals.
Antioxidant defenses act in concert in cell differentiation and growth, immune responses, cell membrane integrity, and normal DNA repair. Oxidative stress occurs when there are more free radicals than can be dealt with due to environmental insult, disease or malnutrition. Even exercise, because of an increase in oxygen demand and utilization, increases the formation of free radicals. However, regular exercise builds up body defense systems and protects against damage. An improper balance between formation and destruction of free radicals may play a role in degenerative disease and aging. Antioxidants in the diet may prevent disease and deficiencies may be deleterious to fetal and childhood development.
Antioxidant micronutrients must be supplied in the diet. Fruits, vegetables and whole grains are better sources of antioxidants than pill forms, but, in general, supplementation is beneficial. A balanced diet including several servings per day of fruits and vegetables is recommended.
Vitamin C (176.12 MW, C6H8O6) is a water soluble antioxidant found in fruits and vegetables that directly scavenges some free radicals and recycles vitamin E. It is also known as ascorbic acid and is used in various foodstuffs to prevent rancidity, in meat curing, and to prevent fruit discoloration. It is unstable to heat and oxidation but survives freezing.
Most animals can make this vitamin, with the exception of primates, guinea pigs and some bats. The deficiency disease is called scurvy and manifests by numerous defects in connective and epithelial tissue maintenance and repair. Scurvy takes 3-4 months to develop because it takes that long for bodily vitamin C stores to be depleted. The RDA is 60 mg/day but higher doses are well tolerated up to about 1800 mg/day; even if there is no evidence that megadoses are beneficial. Vitamin C has been suggested to be protective against coronary heart disease, presumably because it prevents LDL oxidation.
Beta carotene (536.85 MW, C40H56) is a water soluble precursor to Vitamin A, but is an antioxidant in itself. Vitamin A has no antioxidant activity. Beta carotene gives vegetables such as corn, squash and carrots their rich yellow color. It is found in many other pigmented fruits and veggies, egg yolk, butter, and milk as well.
Vitamin E (430.69 MW, C29H50O2) comes in six naturally occurring forms (found in whole grains, fish oils, nuts and seeds) but alpha tocopherol is the most potent as a vitamin and is widely distributed in food. Vitamin E is the most potent and least toxic fat soluble antioxidant and is important in protecting cell membranes from oxidative damage. It is absorbed in the small intestine, delivered to the liver, and packaged into lipoproteins for delivery to the tissues. Tissues or structures exposed to the highest amounts of oxygen, such as erythrocytes, mitochondria, and cells of the respiratory tree, seem to accumulate more vitamin E than other structures or tissues. The RDA is 10 IU for men and 8 IU for women and normal blood levels are in the range of 0.5-0.7 mg/dL. Deficiency has not been seen in otherwise healthy children or adults, but experimentally the symptoms include muscular weakness and fragile erythrocytes.
Flavanoids are antioxidant molecules found in plant sources such as fruit, flowers, roots, stems, tea, wine, grains and vegetables. They are often responsible for the beautiful coloring of plant structures. Indeed, a general rule of nutrition is the relationship of the vibrancy or depth of color to the nutritional content of the fruit or vegetable. More pigment is usually associated with greater nutritional value.
Flavanoids have been shown to have antiviral, antiallergic , anti-inflammatory, antithrombogenic and anticarcinogenic effects in vitro. Flavanoids act as antioxidants by directly scavenging free radicals, chelating reactive elements such as iron, or by inhibiting oxidative enzymes. Many of the other actions are mediated by their inhibitory action on prostaglandin synthesis and mediators of inflammation. Flavanoids also inhibit tyrosine kinases, many of which are involved in cell growth and proliferation.
Some 4000 flavanoids have been found. There are four main groups of flavanoids; 1) flavones, 2) flavanones, 3) catechins, and 4) anthocyanins. It is the flavones and catechins that appear to be important flavanoids in oxidation defenses.
Perhaps the most important flavone is quercetin found in apples, onions, broccoli and berries. The flavanones are found primarily in citrus fruits and peels. Catechins are found in teas and red wine. Anthocyanins are present in cherries, berries, wine, grapes and tea. No daily requirement for flavanoids has been established, but a balanced diet containing fresh fruits and vegetables, tea, and moderate amounts of red wine is recommended.
Selenium (at.wt. 78.96) is an essential trace element in the diet that is distributed in the earth’s crust at 0.09 ppm. The RDA for selenium is 70 ug/day for adults. Selenium toxicity has been seen at higher levels. Glutathion peroxidase is a free radical scavenging enzyme that contains selenium. It acts to destroy peroxides and thus protects lipid membranes as does Vitamin E. Indeed, these two antioxidant defense mechanisms work in concert and spare one another.
Superoxide dismutase is an enzyme that, in concert with the enzyme catalase, can disarm and destroy free radicals, particularly superoxide. Claims that taking supplements is beneficial to forestall or reduce the effects of aging have not been proven. In fact, superoxide dismutase taken orally (even sublingually) is destroyed in the digestive system. Copper and zinc are required in the functioning of cytosolic superoxide dismutase and manganese is required for the mitochondrial version.
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