The Treatment of Pulmonary Diseases and Respiratory‐Related Conditions with Inhaled (Nebulized or Aerosolized) Glutathione

Abstract

Reduced glutathione or simply glutathione (γ-glutamylcysteinylglycine; GSH) is found in the cytosol of most cells of the body. GSH in the epithelial lining fluid (ELF) of the lower respiratory tract is thought to be the first line of defense against oxidative stress. Inhalation (nebulized or aerosolized) is the only known method that increases GSH's levels in the ELF. A review of the literature was conducted to examine the clinical effectiveness of inhaled GSH as a treatment for various pulmonary diseases and respiratory-related conditions. This report also discusses clinical and theoretical indications for GSH inhalation, potential concerns with this treatment, its presumed mechanisms of action, optimal doses to be administered and other important details. Reasons for inhaled GSH's effectiveness include its role as a potent antioxidant, and possibly improved oxygenation and host defenses. Theoretical uses of this treatment include Farmer's lung, pre- and postexercise, multiple chemical sensitivity disorder and cigarette smoking. GSH inhalation should not be used as a treatment for primary lung cancer. Testing for sulfites in the urine is recommended prior to GSH inhalation. Minor side effects such as transient coughing and an unpleasant odor are common with this treatment. Major side effects such as bronchoconstriction have only occurred among asthma patients presumed to be sulfite-sensitive. The potential applications of inhaled GSH are numerous when one considers just how many pulmonary diseases and respiratory-related conditions are affected by deficient antioxidant status or an over production of oxidants, poor oxygenation and/or impaired host defenses. More studies are clearly warranted.

Effects of Oral Glutathione Supplementation on Systemic Oxidative Stress Biomarkers in Human Volunteers

“…4 Furthermore, reduced glutathione concentration and/or a disproportionate ratio of GSH:GSSG has been associated with a number of diseases, including cancer, human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS), hepatitis, type 2 diabetes, Parkinson's disease, and cystic fibrosis. 2,[8][9][10][11][12][13][14] Although no experimental research to date has demonstrated disease prevention from GSH supplementation or other strategies to specifically increase GSH, observational research suggests increased dietary glutathione intake has been associated with reduced risk for oral cancer.…”

“…However, to lesser degrees, intravenous, intramuscular, intrabronchial (i.e., nebulized), and intranasal glutathione administrations have all been used to increase circulating or tissue-specific GSH levels. 12,13,21 Minimal experimental evidence has demonstrated significant increases in blood or intracellular levels of GSH through oral supplementation with reduced GSH. Animal in vivo data suggest that oral GSH is absorbed in rats.…”

Biomarkers in Community-Acquired Pneumonia Assessment

“…The protective role of GSH in regard to the lower respiratory tract has been suggested; hence, use of GSH inhalations might be beneficial for cystic fibrosis treatment (Prousky, 2008;Day, 2005). In our study, the relatively small sample size of the patientcohort was a limitation.…”

Regulation of ion transport by oxidants

“…There is ample evidence from the literature indicating that oxidized and reduced GSH can serve as important cell signaling factors (39,69,103). However, the role of S-glutathionylation in ion transport remains unclear, despite widespread clinical treatment of respiratory-related conditions (in oxidatively stressed lung) with inhaled GSH (78).…”