Chemical Sensitivities: Free Radical Pathology



Stephen Levine, Ph.D., N.B. Holley
Biocurrents Research Development, 944 Lake St., San Francisco, CA 94118

According to the Second Law of Thermodynamics, all physical or chemical changes tend to proceed irreversibly toward a decrease in utilizable energy and an increase in entropy (disorder). These changes equilibrate when the entropy is the maximum possible under existing conditions.* This law must be consistent with the degeneration that occurs in disease, as viewed from the atomic, molecular or supramolecular level. The dynamic progression from health (low entropy) towards death and decay (increasing entropy) underlies all disease processes, whether induced by environmental chemicals, infection or emotional stress. These degenerative processes are initiated through lipid peroxidation, free radical damage, the consequent release of inflammatory mediators, and immune suppression. The immune system is a delicate redox system, which when functioning optimally retards entropic decay.

Most research on chemical hypersensitivity has been directed only at the symptoms produced by these chemicals. If we can understand the biochemical mechanisms that underlie this disease, then protective and therapeutic modalities should become evident.

Many symptoms in ecological illness are consistent with deterioration in the antioxidant defense system. This system is composed of enzymes and the very antioxidant nutrients that are most required for immune defense (vitamins A, C and E, Ze, and Se). Effectiveness of antioxidants resides in their electron-rich chemistry. Toxic chemicals either themselves cause oxidant damage, or are metabolized to free radical toxins in vivo, their toxicity resulting from their reactivity as oxidants or reductants. When a nonradical molecule loses an electron it becomes unstable, since electrons like to group in pairs. Chemicals are constantly losing and gaining electrons in normal cellular energetics, which is naturally regulated by cellular redox balance and the antioxidant system. In abnormal (stressed) metabolism, the balance is shifted towards an increase in single electron transfer (electron leakage) leading to increased production of radical species. If each radical species is not stabilized with the addition of an electron (supplied by antioxidant molecules) then an electron will be taken from a cellular molecule, often an unsaturated lipid from a cellular membrane, resulting in membrane damage, release of inflammatory prostaglandin-leukotriene agents via membrane peroxidation, formation of (-)foreign(-) antigenic (haptenic) complexes due to covalent modification of tissue macromolecules, and ultimately cell death and necrosis.

Imagine a fire burning in a fireplace. The fire represents normal metabolism, the burning fuel producing energy for bodily functions. Sparks flying from the fire represent the free radicals, which are unstable products of incomplete burning of the fuel. Unrestrained, the sparks can react with other material and damage one’s home, even to the point of destroying it. With a screen in front of the fire, the sparks are prevented from doing harm. This is a purposefully simplistic image of antioxidant function. Antioxidants can neutralize the dangerous free radical byproducts from the metabolism of foods, environmental chemicals or drugs. Oxidant stress can locally exhaust or overwhelm the antioxidant defense capability to neutralize free radicals. Reserve antioxidant defenses can be mobilized, as occurs in the lung. However prolonged (chronic) oxidant stress will eventually lead to systemic exhaustion and inflammatory or autoimmune degeneration.

A particularly important antioxidant enzyme, glutathione peroxidase, detoxifies peroxides, using reduced glutathione and selenium as cofactors. A recent clinical study demonstrated that petrochemically sensitive patients improve with the use of Se. Dr. A. Zamm found three basic responses to treatment with Se as selenite. One group improved slowly, over a two month period. Another group benefitted immediately, within days. The third group initially reacted unfavorably to the Se preparation, but eventually did improve. Those most sensitive patients were started with minute doses, and the doses gradually increased. The improvements in chemical tolerance with Se is a full-spectrum one, supporting my hypothesis that environmental chemicals are consistently toxic to biological systems via redox mechanisms. Selenium is known to modulate the adaptive responses of the antioxidant enzymes, which then provide increased protection against transient increases in oxidant stress.

Selenium has also been proven effective in the treatment of Candida albicans (yeast) infections. Selenium-deficient neutrophils can phagocytize yeast cells, but are unable to kill them. Clinically, supplying Se along with the nystatin antibiotic often assists patients in recovering from yeast infections. Our antioxidant defenses also determine our cellular immune capability. Ascorbate and vitamin E improve immune function, by protecting phagocyte cell membranes against damage from the very oxidants that these cells produce to kill pathogens.

The themes underlying degenerative disease are consistently those of oxidant stress, free radical attack, lipid peroxidation with consequent inflammation, and hapten formation leading to immune dysregulation. Individual cases will vary, but degenerative disease processes must inevitably follow upon universal laws established by the electrochemical nature of physical reality. The present extensive use of (-)anti-inflammatory(-) drugs and (-)antidepressants(-) may be largely replaced by the use of nutritional factors which approach the problem at a more primary level. Clearly this approach to healing or slowing oxidative degeneration will position nutritional medicine as a primary treatment modality.

*Lehninger AL, Principles of Biochemistry, 1982, P. 362.