Many of our strategies in preventive medicine are focused on preventing the number 1 killer of Americans: cardiovascular disease!


If you looked at the ETS then you know that oxygen is essential for adequate energy production. It accepts the electrons generated in glycolysis and Kreb’s. However, oxygen can also be detrimental.

Free radicals are produced from exposure to one of several factors. Inflammation, radiation (i.e. x-rays), aging, high pO2, smog (such as ozone or NO2), re-perfusion injury, and chemicals and drugs can all produce free radicals. Additionally, free radicals are produced as a part of normal metabolism.

For roughly every 26 molecules of oxygen reduced in the ETS, one free radical is produced.


A free radical is an unstable molecule that has an “extra” electron. The molecule is eager to donate its electron to any molecule that will accept it. The accepting molecules can be any number of molecules such as those that compose cell membranes. These extra electrons are damaging to the accepting substances.

In fact, aging has been attributed to oxidative damage. Atherosclerosis may also accurately blame itself on oxidative damage.

To give you an idea about how lethal these reactive oxygen species can be, white blood cells use them as their killing agents. It is what they use to kill and destroy anything that they engulf.

Pretty powerful stuff.

Free radicals are also known as reactive oxygen species. Some of these reactive oxygen species are:

  • O2- (superoxide anion)- it is produced by the ETS and at other sites. It generates other reactive oxygen species but it cannot diffuse far from the site of its origin. It is more reactive than hydrogen peroxide.
  • H2O2 (hydrogen peroxide)– it is not a free radical but it does produce them by reacting with a transition metal (such as ferrous iron). It can diffuse into and through cell membranes.
  • OH· (hydroxyl radical)– This is the most reactive species in attacking biological molecules. It is produced by hydrogen peroxide in the presence of ferrous iron.
  • R· (organic radicals)- An organic free radical produced from RH by OH· attack. RH can be the carbon of a double bond in a fatty acid (resulting in -C·=C-) or RSH (resulting in R-S·).
  • RCOO· (organic peroxide radical)– An organic peroxide radical, such as occurs during lipid degradation.
  • HOCl (hypochlorous acid)– Produced in bacteria during the respiratory burst to destroy invading organisms.
  • O2 (singlet oxygen)– Oxygen with antiparallel spins. Produced at high oxygen tensions from the absorption of energy. Decays with the release of light.

Harbor-Weiss Reaction

O2 + e- -> O2- + e- + 2 H+ -> H2O2 + e- + H+ -> OH·

I put in that reaction to show how some of these molecules can be produced. During infection, WBC’s undergo what is referred to as a respiratory burst. This burst produces more OH· molecules in order to have the firepower to destroy the invading organism.

We’ve already discussed how some of these things can be formed. If we didn’t have any protective mechanisms, we would probably be destroyed as well. Well, we are but the process takes much longer due to protective mechanisms. We talked about how normal metabolism (respiration) produces free radicals.

Anything that increases the need for oxygen increases free radical production. Exercise increases oxygen utilization and, ultimately, free radical production. How, then, can exercise be beneficial? The answer is in the protective mechanisms.

There are three sources of enzymatic defense: superoxide dismutase; catalase; and glutathione peroxidase.

  • Superoxide dismutase converts the superoxide anion to hydrogen peroxide. The superoxide is more reactive (more damaging) than hydrogen peroxide (which ultimately becomes the hydroxyl radical). So, the action of superoxide dismutase is protective.
  • Catalase converts 2 hydrogen peroxides to 2 molecules of water and one molecule of oxygen. Obviously, water is less reactive than hydrogen peroxide so this is also protective.
  • Glutathione peroxidase provides another mechanism for hydrogen peroxide to be converted to water and thus it is also protective.

So we have three enzymes that provide protection against reactive oxygen species (free radicals). That doesn’t answer the exercise question.

Exercise increases the function of these enzymes. Exercise increases the production of free radicals but also increases the protective enzymes. It would seem that these two balance each other out and exercise would be a mute point. However, exercise is short term while the increased activity of the protective enzymes lasts longer. Thus, exercise has a protective role in reducing free radical damage.

Another source of protection is from free radical scavengers (anti-oxidants). There are several chemicals that are known to have anti-oxidant properties.

  • Lipoic acid
  • vitamin E
  • vitamin C
  • beta carotene (vitamin A).

These substances accept the electron and allow themselves to be damaged instead of the cells. These substances can then be safely excreted. However, if you don’t have enough of these substances, your cells take the hit.

Nutritional antioxidant supplementation effectively decreases oxidative stress and can prevent much of this damage.