Vol. 2, # 38
October 1, 2005

Q: What are antioxidants and what are they good for? - Layperson

A: To understand the way that free radicals and antioxidants interact, you must first understand a bit about cells and molecules. So here's a (very) brief refresher course in Physiology/Chemistry 101: The human [Oxygen atom]body is composed of many different types of cells. Cells are composed of many different types of molecules. Molecules consist of one or more atoms of one or more elements joined by chemical bonds.

As you probably remember from your old high school days, atoms consist of a nucleus, neutrons, protons and electrons. The number of protons (positively charged particles) in the atom's nucleus determines the number of electrons (negatively charged particles) surrounding the atom. Electrons are involved in chemical reactions and are the substance that bonds atoms together to form molecules. Electrons surround, or "orbit" an atom in one or more 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 so on. 

[O2 molecule]The most important structural feature of an atom for determining its chemical behavior is the number of electrons in its outer shell. A substance that has a full outer shell tends not to enter in chemical reactions (an inert substance). Because atoms seek to reach a state of maximum stability, an atom will try to fill it’s outer shell by:

  • Gaining or losing electrons to either fill or empty its outer shell
  • Sharing its electrons by bonding together with other atoms in order to complete its outer shell

Atoms often complete their outer shells by sharing electrons with other atoms. By sharing electrons, the atoms are bound together and satisfy the conditions of maximum stability for the molecule.

Normally, bonds don't split in a way that leaves a molecule with an odd, unpaired electron. But when weak bonds split, free radicals are formed. Free radicals are very unstable and react quickly with other compounds, trying to capture the needed electron to gain stability. Generally, free radicals attack the nearest stable molecule, "stealing" its electron. When the "attacked" molecule loses its electron, it becomes a free radical itself, beginning a chain reaction. Once the process is started, it can cascade, finally resulting in the disruption of a living cell.

Some free radicals arise normally during metabolism. Sometimes the body's immune system's cells purposefully create them to neutralize viruses and bacteria. However, environmental factors such as pollution, radiation, cigarette smoke and herbicides can also spawn free radicals.

Normally, the body can handle free radicals, but if antioxidants are unavailable, or if the free-radical production becomes excessive, damage can occur. Of particular importance is that free radical damage accumulates with age.

The vitamins C and E, are thought to protect the body against the destructive effects of free radicals. Antioxidants neutralize free radicals by donating one of their own electrons, ending the electron-"stealing" reaction. The antioxidant nutrients themselves don't become free radicals by donating an electron because they are stable in either form They act as scavengers, helping to prevent cell and tissue damage that could lead to cellular damage and disease.

         Vitamin A (Retinol or beta-carotene) has been discovered to protect dark green, yellow and orange vegetables and fruits from solar radiation damage, and is thought to play a similar role in human body. Carrots, squash, broccoli, sweet potatoes, tomatoes, kale, ollards,        cantaloupe, peaches, and apricots are particularly rich sources of beta-carotene. 

          Vitamin C:  The most abundant water-soluble antioxidant in the body. Acts primarily in cellular fluid. Of particular note in combating free-radical formation caused by pollution and cigarette smoke. Also helps return vitamin E to its active form. Sources include citrus fruits (such as oranges, sweet lime, etc.), green peppers, broccoli, green leafy vegetables, strawberries, raw cabbage, and tomatoes.

          Vitamin E:  The most abundant fat-soluble antioxidant in the body. One of the most efficient chain-breaking antioxidants available. Primary defender against oxidation. Primary defender against lipid peroxidation (creation of unstable molecules containing more oxygen than is usual). Sources include wheat germ, nuts, seeds, whole grains, green leafy vegetables, vegetable oil, and fish-liver oil. CAUTION:  Ecessive vitamin E can interfere with the action of warfarin, a blood-thinning medicine often prescribed for patients with heart disease.             

             Selenium  is best obtained through foods, as large doses of the supplement form can be toxic. Good food sources include fish, shellfish, red meat, grains, eggs, chicken, garlic, and brazil nuts. Vegetables can also be a good source if grown in selenium-rich soils

  • Heart Disease:  Vitamin E may protect against cardiovascular disease by defending against LDL oxidation and artery-clogging plaque formation.
  • Cancer:  Many studies have correlated high vitamin C intakes with low rates of cancer, particularly cancers of the mouth, larynx and esophagus.
Free radicals are atoms or groups of atoms with an odd (unpaired) number of electrons 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.

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.)

Epidemiologic observations show lower cancer rates in people whose diets are rich in fruits and vegetables. This has lead to the theory that these diets contain substances, possibly antioxidants, which protect against the development of cancer. There is currently intense scientific investigation into this topic. Thus far, none of the large, well designed studies have shown that dietary supplementation with extra antioxidants reduces the risk of developing cancer. In fact one study demonstrated an increased risk of lung cancer in male smokers who took antioxidants vs. male smoker who did not supplement. Whether this effect was from the antioxidants is unknown but it does raise the issue that antioxidants may be harmful under certain conditions.

Antioxidants are also thought to have a role in slowing the aging process and preventing heart disease and strokes, but the data is still inconclusive. Therefore from a public health perspective it is premature to make recommendations regarding antioxidant supplements and disease prevention. New data from ongoing studies will be available in the next few years and will shed more light on this constantly evolving area. Perhaps the best advice, which comes from several authorities in cancer prevention, is to eat 5 servings of fruit or vegetables per day.

Endurance exercise can increase oxygen utilization from 10 to 20 times over the resting state. This greatly increases the generation of free radicals, prompting concern about enhanced damage to muscles and other tissues. The question that arises is, how effectively can athletes defend against the increased free radicals resulting from exercise? Do athletes need to take extra antioxidants?

Because it is not possible to directly measure free radicals in the body, scientists have approached this question by measuring the by-products that result from free radical reactions. If the generation of free radicals exceeds the antioxidant defenses then one would expect to see more of these by-products. These measurements have been performed in athletes under a variety of conditions.

Several interesting concepts have emerged from these types of experimental studies. Regular physical exercise enhances the antioxidant defense system and protects against exercise induced free radical damage. This is an important finding because it shows how smart the body is about adapting to the demands of exercise. These changes occur slowly over time and appear to parallel other adaptations to exercise.

On the other hand, intense exercise in untrained individuals overwhelms defenses resulting in increased free radical damage. Thus, the "weekend warrior" who is predominantly sedentary during the week but engages in vigorous bouts of exercise during the weekend may be doing more harm than good. To this end there are many factors which may determine whether exercise induced free radical damage occurs, including degree of conditioning of the athlete, intensity of exercise, and diet.

Although it is well known that vitamin deficiencies can create difficulties in training and recovery, the role of antioxidant supplementation in a well nourished athlete is controversial. The experimental studies are often conflicting and conclusions are difficult to reach. Nevertheless, most of the data suggest that increased intake of vitamin E is protective against exercise induced oxidative damage. It is hypothesized that vitamin E is also involved in the recovery process following exercise. Currently, the amount of vitamin E needed to produce these effects is unknown. The diet may supply enough vitamin E in most athletes, but some may require supplementation. There is no firm data to support the use of increased amounts of the other antioxidants.

In general, antioxidant supplements have not been shown to be useful as performance enhancers. The one exception to this is vitamin E which has been shown to be useful in athletes exercising at high altitudes. A placebo controlled study done on mountaineers demonstrated less free radical damage and decline in anaerobic threshold in those athletes supplemented with vitamin E. Although difficult to generalize, this finding suggests that supplementation with vitamin E might be beneficial in those triathletes who are adapting to higher elevations.

Although there is little doubt that antioxidants are a necessary component for good health, no one knows if supplements should be taken and, if so, how much. Antioxidants supplements were once thought to be harmless but increasingly we are becoming aware of interactions and potential toxicity. It is interesting to note that, in the normal concentrations found in the body, vitamin C and beta-carotene are antioxidants; but at higher concentrations they are pro-oxidants and, thus, harmful. Also, very little is known about the long term consequences of megadoses of antioxidants. The body's finely tuned mechanisms are carefully balanced to withstand a variety of insults. Taking chemicals without a complete understanding of all of their effects may disrupt this balance.

It should also be noted that many berries, especially blueberries and blackberries, have particularly high concentrations of antioxidants, as do some types of tea, especially green tea.

Several food additives (including ascorbic acid and tocopherol-derived compounds) are used as antioxidants to help guard against deterioration of food.

Other antioxidants are enzymes. These include glutathione peroxidase, superoxide dismutase and catalase.

Much damage is done by free radicals in mitochondria as a byproduct of oxidative phosphorylation. Superoxide radicals are generated which can damage mitochodrial DNA and mitochondrial membranes. Unlike DNA in the cell nucleus, mitochondrial DNA has only a few DNA-repair enzymes and the DNA is not protected by histones.

Many antioxidants, however (including vitamin C and vitamin E) can't get into mitochondria for various reasons (e.g. because too hydrophilic to cross mitochondrial membranes or too hydrophobic to cross the cytoplasm). A group of scientists in Russia (led by V. Skulachev) has created a custom antioxidant (a Skulachev ion forms the point of the molecule and penetrates the mitochondrial membrane; the antioxidising part is attached behind it) that can enter the mitochondria and stays there preventing damage to DNA.

Although there is little doubt that antioxidants are a necessary component for good health, there is considerable doubt as to the most beneficial antioxidant and as to the optimal amount for results. Due to the complex nature of the interactions of antioxidants with the body, it is difficult to interpret the results of many experiments designed to test such things.

For example, recent studies are suggesting that at high levels, antioxidant vitamins may prove to have pro-oxidant effects: increasing the formation of free radicals.

In short, get as many and as much of the antioxidants as possible from a diet  high in fruits and vegetables and use supplements in moderation.


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DISCLAIMER:  The information in this column, is NOT intended to diagnose and/or treat any health related issues and is provided solely for informational purposes only. Consult the appropriate healthcare professional before making any changes to your healthcare regime. Even what may seem like simple changes in the diet for example, can interact with, and alter, the efficiency of medications and/or the body's response to the medications. Many herbs and supplements exert powerful medicinal effects. Neither the author, nor the website designers, assume any responsibility for the reader's use or misuse of this information.

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