Free radicals and Antioxidants

The concept that free radicals were involved with the deterioration of human biochemistry was the biggest advance since the discovery of germs. The discovery that free radicals are at work to impair the human body goes beyond the aging process to include the killer and crippling diseases once thought to be the result of aging. Free radicals are now known to be involved with cancer, heart disease, arthritis and perhaps as many as eighty diseases not caused by "germs".


Antioxidants are intimately involved in the prevention of cellular damage -- the common pathway for cancer, aging, and a variety of diseases. The scientific community has begun to unveil some of the mysteries surrounding this topic, and the media has begun whetting our thirst for knowledge. Athletes have a keen interest because of health concerns and the prospect of enhanced performance and/or recovery from exercise.

It's the radicals, man


Free radicals
Typically, stable molecules contain pairs of electrons. When a chemical reaction breaks the bonds that hold paired electrons together, Free radicals are produced.


Free radicals are atoms or groups of atoms with an odd (unpaired) number of electrons, which makes them unstable, and can be formed when oxygen interacts with certain molecules. Once formed these highly reactive radicals can start a chain reaction, like dominoes. Their chief danger comes from the damage they can do when they react with important cellular components such as DNA, or the cell membrane. Cells may function poorly or die if this occurs. To prevent free radical damage the body has a defense system of antioxidants.
 

Where do they come from?
There are many sources of free radicals both within and external (environmental) to cells. Many are produced by normal ongoing metabolism, especially from the electron transport system in the mitochondria and from a number of normally functioning enzymes, examples are: xanthine oxidase, cytochrome p450, monoamine oxidase, nitric oxide synthase. In the brain, free radicals are produced from the autoxidation of norepinephrine and dopamine. The autoxidation of catechols to quinones generates reduced forms of molecular oxygen, sources of free radicals (e.g., superoxide and hydrogen peroxide). Bruce Ames and his colleagues, leading scientists in the field, claim that oxidants generated by mitochondria are the major source of oxidative lesions that accumulate with age.


What  do they do?
Oxygen free radicals or ROS are implicated in many diseases including neurodegenerative diseases (ALS, Parkinson's, Alzheimer's), cataractogenesis, atherosclerosis, diabetes mellitus, ischemia-reperfusion injury, kwashiorkor, certain toxicities, to mention only a few, as well as in the aging process itself. This has created the impression that all free radicals are highly damaging--in short, all bad. A more informed examination of free radicals reveals a range of unique functions in normal physiology and even in information processing in the brain. Since free radicals can donate an electron to an appropriate acceptor ("reduction reaction") or pair their unpaired electron by taking one from an appropriate donor ("oxidation reaction") they have major influences on the so-called "redox state" in cells--important in normal regulatory reactions. Major targets are molecular complexes that readily give up or acquire a single electron, e.g., those with sulfhydryl/disulfides or with paramagnetic metals (iron, copper). Practically every type of molecule: DNA, protein, lipid, carbohydrate, can be a target and thus be damaged by a "hit" by a highly reactive radical. But it is difficult to measure the highly reactive species in vivo so most of the evidence for their roles is from the identification of products or changes induced by antioxidant chemicals--largely indirect evidence.


Antioxidants
Antioxidants are molecules which can safely interact with free radicals and terminate the chain reaction before vital molecules are damaged. Although there are several enzyme systems within the body that scavenge free radicals, the principle micronutrient (vitamin) antioxidants are vitamin E, beta-carotene, and vitamin C. Additionally, selenium, a trace metal that is required for proper function of one of the body's antioxidant enzyme systems, is sometimes included in this category. The body cannot manufacture these micronutrients so they must be supplied in the diet.


Vitamin E: D-alpha tocopherol. A fat soluble vitamin present in nuts, seeds, vegetable and fish oils, whole grains (esp. wheat germ), fortified cereals, and apricots. Current recommended daily allowance (RDA) is 15 IU per day for men and 12 IU per day for women.

 

Vitamin C : Ascorbic acid is a water soluble vitamin present in citrus fruits and juices, green peppers, cabbage, spinach, broccoli, kale, cantaloupe, kiwi, and strawberries. The RDA is 60 mg per day. Intake above 2000 mg may be associated with adverse side effects in some individuals.


Beta-carotene is a precursor to vitamin A (retinol) and is present in liver, egg yolk, milk, butter, spinach, carrots, squash, broccoli, yams, tomato, cantaloupe, peaches, and grains. Because beta-carotene is converted to vitamin A by the body there is no set requirement. Instead the RDA is expressed as retinol equivalents (RE), to clarify the relationship. (NOTE: Vitamin A has no antioxidant properties and can be quite toxic when taken in excess.)