APPENDIX B—OXIDATIVE STRESS

Oxidation is a chemical reaction that removes electrons from an atom or molecule. The term originally was used to describe reactions involving oxygen, but it has become a general term for chemical processes in which electrons are lost. In chemical reactions involving electron transfer, a reactant that donates an electron is oxidized and the reactant accepting the electron is reduced. An oxidizing agent may be thought of as a thief that attempts to steal electrons from other chemicals. There are hundreds of oxidation-reduction (redox) reactions in the human body that are essential to good health. However, many disease conditions involve oxidative stress, a condition in which natural antioxidant protectors are insufficient to prevent excessive release of free radicals and undesirable chemical reactions. Free radicals are highly reactive, unstable atoms or molecules capable of damaging proteins, membranes, DNA, and other essential biochemicals.

Modest levels of oxidative stress are needed for several essential chemical processes, including immune function. For example, oxidative stress combats bacterial infections by surrounding bacteria with H2O2 (a powerful oxidizing agent) that kills the unwanted organisms. In another example, superoxide and nitric oxide are oxidizing agents that regulate important processes, such as controlling vascular tone. Regulation of free radicals is accomplished by numerous antioxidant chemicals, such as glutathione, cysteine, zinc, selenium, catalase, metallothionein, and vitamins C and E. These natural biochemicals are essential to cope with environmental toxins, disease processes, and other sources of free radicals. This may be thought of as a war between the oxidative free radicals and the body’s antioxidant protectors. Disease conditions can result from either overwhelming assaults by oxidative agents or insufficient levels of natural antioxidants. Conditions associated with oxidative stress include aging, heart disease, cancer, autism, Alzheimer’s, and most mental illnesses. Environmental sources of oxidative stress include toxic metals, smog, pesticides, cigarettes, nuclear radiation, and industrial waste products.

Most free radicals encountered in the body can be neutralized by glutathione, zinc, catalase, melatonin, vitamin C, etc. However, the highly aggressive superoxide free radical (O2-) requires a special deactivation mechanism. Superoxide radicals leak from the mitochondria of all cells during natural processes and must be destroyed to avoid damage to DNA, proteins, membranes, etc. This is accomplished by a one-two punch in which a chemical known as a dismutase converts superoxide to H2O2 and O2 that can be neutralized by glutathione and other antioxidants. The primary dismutases are metalloenzymes containing copper, zinc, or manganese. Ceruloplasmin, the major copper-carrying protein in the blood, also functions as a dismutase.

There has been a recent surge in research studying the role of oxidative stress in mental disorders. An increasing number of experts have proposed that oxidative stress is the primary cause of schizophrenia, bipolar disorder, autism, Alzheimer’s disease, and Parkinson’s disease. Advanced antioxidant therapies hold great promise for patients challenged by these disorders.