The Health Dividend of Glutathione
Abstract
Glutathione (GSH) is a naturally occurring chemical used by the human body to protect against chemical and environmental threats. As a consequence of aging, lifestyle, diet, and disease, a gap can develop between the needs and availability of GSH. GSH decreases in association with risk factors for disease and undergoes a diurnal variation with lowest values beginning in the morning and extending through midday. Decreased GSH has been associated with specific diseases, including cardiovascular disease and diabetes, and has been implicated in many others. Abundant biochemical data support a direct causal link between low GSH, impaired defenses, and cellular susceptibility in model systems. Emerging personalized health strategies utilize GSH as a quantitative indicator of health with the expectation that diet selection, GSH supplementation, and lifestyle approaches can be used to manage GSH status, thereby providing a health dividend by protecting against disease development.
Introduction
More than 100 years of research and 81,000 scientific papers have established glutathione (GSH) as one of the most important protective molecules in the human body. The present article provides a brief overview of GSH and its functions in health and disease. Low GSH has been implicated in neuronal, hepatic, renal, pulmonary, cardiac, musculoskeletal, pancreatic, gastrointestinal, visual, auditory, and infectious diseases. Accumulating data have established that poor diet and age-related disease can create a functional disparity between the body’s natural GSH defenses and the levels needed for optimal health. The purpose of this article is to provide practical considerations for health professionals concerning the evolving use of GSH as a strategy for maintenance of health.
What is Glutathione?
GSH is a component of defenses for both acute and chronic health challenges. Acute deficiency can be caused by exposure to toxic chemicals and endogenous oxidative reactions. Under acute GSH deficiency, cells cannot maintain normal cell functions, lose ability to divide normally, and can undergo either necrotic or apoptotic cell death. Under chronic conditions, variations in GSH levels occur due to nutrition, environmental exposures, and activation of the immune system. These variations affect risk of chronic and age-related diseases by limiting protective functions. The protective functions include elimination of cancer-causing chemicals, enhancement of antioxidant defenses, and maintenance of homeostatic conditions of the epithelial barriers. GSH protects against hundreds of cancer-causing chemicals. GSH is at the apex of a group of protective chemicals, including vitamins C and E, which guard against oxidative damage to tissues. Interorgan transport of GSH is part of a homeostatic control system3 that maintains a “redox” environment essential for life. The term “redox” refers to chemical reactions involving electron transfer. Adenosine triphosphate (ATP) is obtained from redox reactions in the mitochondria. In this process, most electron transfer occurs with reduction of O2 to water, but a small fraction is reduced to hydrogen peroxide and toxic oxygen radical species. GSH is critical for elimination of these oxidants.