The Benefits and Hazards of Antioxidants: Controlling Apoptosis and Other Protective Mechanisms in Cancer Patients and the Human Population

AbstractCellular oxidants, called reactive oxygen species (ROS), are constantly produced in animal and human cells. Excessive ROS can induce oxidative damage in cell constituents and promote a number of degenerative diseases and aging. Cellular antioxidants protect against the damaging effects of ROS. However, in moderate concentrations, ROS are necessary for a number of protective reactions. Thus, ROS are essential mediators of antimicrobial phagocytosis, detoxification reactions carried out by the cytochrome P-450 complex, and apoptosis which eliminates cancerous and other life-threatening cells. Excessive antioxidants could dangerously interfere with these protective functions, while temporary depletion of antioxidants can enhance anti-cancer effects of apoptosis. Experimental data are presented supporting these notions. The human population is heterogeneous regarding ROS levels. Intake of exogenous antioxidants (vitamins E, C, beta-carotene and others) could protect against cancer and other degenerative diseases in people with innate or acquired high levels of ROS. However, abundant antioxidants might suppress these protective functions, particularly in people with a low innate baseline level of ROS. Screening human populations for ROS levels could help identify groups with a high level of ROS that are at a risk of developing cancer and other degenerative diseases. It also could identify groups with a low level of ROS that are at a risk of down-regulating ROS-dependent anti-cancer and other protective reactions. Screening populations could provide a scientifically grounded application of antioxidant supplements, which could significantly contribute to the nation's health.Keywordsoxidantsantioxidantsapoptosiscancer Key teaching points: • The human population is heterogeneous in relation to levels of ROS, as well as to almost all other features.• People who over-generate ROS are at high risk for developing cancer, cardiovascular diseases, cataracts and other degenerative diseases because of the oxidative damage to cell constituents (DNA, proteins, lipids, etc) and cell structures.• People with a low level of ROS might be in danger of harboring low activity of highly important protective reactions. These include apoptosis, which deletes precancerous, cancer, virus-infected and other cells threatening human health; phagocytosis, which fights infectious microorganisms; and detoxification reactions provided by cytochrome P-450 complexes. The ROS are essential triggers and mediators of all these protective reactions. Consequently, a low ROS level limits the activity of these protective reactions.• Antioxidants protect people with a high level of ROS, whereas antioxidants might be detrimental in people with a low level of ROS by further decreasing the activity of ROS-dependent protective mechanisms.• Screening the human population for ROS levels could provide a scientifically well-grounded, controlled application of antioxidants and might significantly contribute to improvement of human health. Key teaching points: • The human population is heterogeneous in relation to levels of ROS, as well as to almost all other features.• People who over-generate ROS are at high risk for developing cancer, cardiovascular diseases, cataracts and other degenerative diseases because of the oxidative damage to cell constituents (DNA, proteins, lipids, etc) and cell structures.• People with a low level of ROS might be in danger of harboring low activity of highly important protective reactions. These include apoptosis, which deletes precancerous, cancer, virus-infected and other cells threatening human health; phagocytosis, which fights infectious microorganisms; and detoxification reactions provided by cytochrome P-450 complexes. The ROS are essential triggers and mediators of all these protective reactions. Consequently, a low ROS level limits the activity of these protective reactions.• Antioxidants protect people with a high level of ROS, whereas antioxidants might be detrimental in people with a low level of ROS by further decreasing the activity of ROS-dependent protective mechanisms.• Screening the human population for ROS levels could provide a scientifically well-grounded, controlled application of antioxidants and might significantly contribute to improvement of human health.This work was supported by a grant from the Institute of Nutrition of the University of North Carolina.NotesPresented in part at the Ross Products Research Conference on Medical Issues, "Synergy in Medical and Nutritional Therapy," November 6–8, 2000, Key Largo, Florida.