Oxidation and Antioxidants: A Key to the Most Baffling Illnesses of Our Time

by Stephen Levine, Ph.D.

In our last issue of Allergy Research Group’s Focus newsletter, we addressed the critical importance of the antioxidant defense system and the crucial role oxidative stress plays in many of the most mystifying diseases of our age. In particular, we covered the landmark work of Dr. Martin Pall, Ph.D., who has gathered substantial evidence that nitric oxide, superoxide, and ultimately peroxynitrite (all are either free radicals or lead to free radicals) play a key role in inflammatory cytokine activity and oxidative cell damage central to many of today’s baffling illnesses. Dr. Pall’s new book is: Explaining “Unexplained Illnesses”: Disease Paradigm for Chronic Fatigue Syndrome, Multiple Chemical Sensitivity, Fibromyalgia, Post Traumatic Stress Disorder, Gulf War Syndrome and Others (1).

Think of metabolism as like a fire. We burn energy to live. Food is our fuel. Oxygen is our elixir, because it’s required for the burning to occur. Optimizing tissue oxygenation is necessary for optimal health. But fires send out dangerous sparks, or in our metabolic fire, free radicals. Unchecked, fires burn to excess, and turn houses and forests into smoldering ash – or damaged tissue. And fires need water to quench and cool the damage, and keep it contained. Antioxidants are our metabolic water, as they cool out the side effects of our burning metabolism.

For good health we need:

• Oxygen. Our tissues need to be well-perfused with oxygen, and our immune system needs to effectively utilize the oxygen in the oxidative ‘burst’ to kill pathogens.  I believe that the oxidative burst is critical in immune function.
• The ability to adapt to chronic oxidative stress, especially from toxins in our environment.
• The ability to quench oxidative stress with a potent store of antioxidants, so that we do not end up with damaged tissue, either from excess free radicals from stress or metabolism, or from free-radical associated hypoxia.

I Sing The Body Electric

At the most fundamental level, the ability to generate energy is electrical. Electron transfer in the mitochondria allows us to produce energy. The oxidative burst of immune cells results in highly unstable oxygen species, such as peroxides and free radicals, to kill pathogens.

But the oxidative burst needs to be just that—a burst, not a continuous fireworks. Free radicals, when chronically elevated, damage cell membranes, enzymes, receptors, and proteins. Rapidly proliferating oxidative reactions initiated by radicals and other activated species of oxygen liberated from damaged blood vessels wreak serious havoc.

Much chemical toxicity is due to the oxidative damage from those chemicals. This includes heavy metals, halogenated  hydrocarbons, photochemical oxidants in smog, and many therapeutic drugs. It is the body’s response to the foreign chemical that leads to the free radical damage and disease.

Chronic oxidative stress so damages tissues that they cannot effectively utilize oxygen, and become hypoxic. The authoritative text, Robbins & Cotran The Pathologic Basis of Disease (2), states, “Hypoxia is probably the most common cause of cell injury and may also be the ultimate mechanism of damage initiated by a variety of physical, biological and chemical agents. Ironically oxidative injury appears to occur from hypoxia.” Halocarbon toxicity studies have consistently shown that if the experimental animal is hypoxic during the halocarbon insult, the resultant liver necrosis is much more extensive. By itself, severe hypoxia produces hepatic cell killing that resembles halocarbon necrosis or alcohol necrosis. Thus a hypoxic tissue state even moderate in degree shifts the halocarbon dose response curve so that halogenated hydrocarbons are far more toxic under hypoxic conditions. This is very relevant to all chronic disease.

A very powerful if tragic example of chronic oxidative stress is mesothelioma—the lung cancer caused by asbestos exposure. Asbestos itself is inert. The lung cancer resulting from exposure is caused by years of free radical damage. Immune cells called phagocytes spew out free radicals to destroy pathogens. These free radicals are a key defense of our immune system. When confronted with asbestos, the phagocytes do their job, and spew out the free radicals, attempting to destroy it. But they can’t. They are actually known in science as “frustrated phagocytes.” It’s the free radical damage over many years that actually leads to the lung cancer—not the fibers themselves. This example demonstrates that even an inert fiber can become toxic via oxidative damage.

Adapt or Die: What Does Darwin’s Insight Really Mean?

Adaptation is associated with an increase in antioxidant function. Stunning research in the 1950’s and early 1960’s found that exposure to one toxic chemical not only led to tolerance to that chemical, but tolerance to other similar chemicals. Rodents made tolerant to ozone also were rendered tolerant to ketene, nitrogen dioxide, nitrosyl chloride, and phosgene. All of these are oxidizing toxins. Upon re-exposure to ozone or a new exposure to any of these other compounds, animals previously made tolerant could now survive levels of exposure that would otherwise be lethal. In short, a prior exposure could be life saving and only one exposure was enough. In contrast, continuous exposure of mice to high, toxic levels of ozone was more injurious than intermittent exposures to the same levels. The intermittent exposures allowed the animals to undergo adaptive processes. So, as stress proceeds to affect us biologically, oxidative damage is a key mechanism. And much of our adaptation to stress occurs via antioxidant adaptation.

A quick review of these powerful key concepts: oxygen is a double edged    sword. Optimum levels are required for health, but chronic oxidative stress leads to permanent tissue damage via free radical damage.  I suggested over 20 years ago, in my first publications about free radical damage, aging, and disease that any serious stress could increase free radical production and that if we could monitor the amount of free radicals we were generating we would have a powerful diagnostic tool in chronic illness (3).

The Conclusion: What Really Counts

Living creatures have evolved a marvelous, ingenious antioxidant defense system since the time, eons ago, when the earth began to shift to an aerobic rather than anaerobic atmosphere. We, air breathing mammals, must have sufficient antioxidants to contain the havoc created by free radical damage. In fact, here we have a distinct advantage. Pathogens, whether viral, bacterial, protozoan, or fungal, are generally more sensitive to free radical damage than we are. For instance, current research into three major classes of antibiotics that kill bacteria by completely different mechanisms found that all three kill bacteria in part via free radical damage. The research, published in the journal Cell in September (4), used a fluorescent dye that lights up in the presence of hydroxyl molecules. The researchers discovered that all three classes of bactericidal drugs ramp up the production of harmful free radicals. Because those different types of antibiotics each initially hit different targets, it had been believed they worked by independent means. The fact is, pathogens don’t have the same sophisticated antioxidant defenses that we do.  Therefore there is a large window for therapy. That’s why oxygen therapies are extremely powerful and effective.

It’s my opinion that the wise use of both oxidative and antioxidative therapies are our best doorways to health and healing.  Using these polarities wisely, we have some of our strongest tools in medicine to prevent stress and aging, and to treat acute illness with pulses of targeted oxidizing therapies.

With an intact antioxidant defense, we can successfully adapt, survive and flourish. If we deplete our antioxidant stores over time, we may suffer mightily over the long run.

It is wonderful to see this work on free radical damage and antioxidants come full circle with new breakthroughs such as Marty Pall’s research, or the latest studies on coenzyme Q10. In sum, we need a fine balance between the oxidative burst and the antioxidant defense. We need to move quickly and effectively between these two polarities and to understand the value of each for a healthy life.

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