Glutathione (GSH) is an important intracellular antioxidant responsible for neutralizing reactive oxygen species (ROS). Our laboratory previously demonstrated that the oral administration of liposomal GSH improves immune function against mycobacterium infections in healthy patients along with patients with HIV and Type 2 diabetes. We aim to determine if the topical application of a glutathione–cyclodextrin nanoparticle complex (GSH-CD) confers a therapeutic effect against mycobacterium infections. In our study, healthy participants received either topical GSH-CD (n = 15) or placebo (n = 15) treatment. Subjects were sprayed four times twice a day for three days topically on the abdomen. Blood draws were collected prior to application, and at 1, 4, and 72 h post-initial topical application. GSH, malondialdehyde (MDA), and cytokine levels were assessed in the processed blood samples of study participants. Additionally, whole blood cultures from study participants were challenged with Mycobacterium avium (M. avium) infection in vitro to assess mycobacterium survival post-treatment. Topical GSH-CD treatment was observed to elevate GSH levels in peripheral blood mononuclear cells (PBMCs) and red blood cells and decrease MDA levels in PBMCs 72 h post-treatment. An increase in plasma IL-2, IFN-γ, IL-12p70, and TNF-α was observed at 72 h post-topical GSH-CD treatment. Enhanced mycobacterium clearance was observed at 4 h and 72 h post-topical GSH-CD treatment. Overall, topical GSH-CD treatment was associated with improved immune function against M. avium infection. The findings of this pilot study suggest GSH–cyclodextrin complex formulation can be used topically as a safe alternative mode of GSH delivery in the peripheral blood.

Oxidative stress (OS) occurs from excessive reactive oxygen species or a deficiency of antioxidants—primarily endogenous glutathione (GSH). There are many illnesses, from acute and post-COVID-19, diabetes, myocardial infarction to Alzheimer’s disease, that are associated with OS. These dissimilar illnesses are, in order, viral infections, metabolic disorders, ischemic events, and neurodegenerative disorders. Evidence is presented that in many illnesses, (1) OS is an early initiator and significant promotor of their progressive pathophysiologic processes, (2) early reduction of OS may prevent later serious and irreversible complications, (3) GSH deficiency is associated with OS, (4) GSH can likely reduce OS and restore adaptive physiology, (5) effective administration of GSH can be accomplished with a novel nano-product, the GSH/cyclodextrin (GC) complex. OS is an overlooked pathological process of many illnesses. Significantly, with the GSH/cyclodextrin (GC) complex, therapeutic administration of GSH is now available to reduce OS. Finally, rigorous prospective studies are needed to confirm the efficacy of this therapeutic approach.

Oxidative stress (OS) occurs from excessive reactive oxygen species or a deficiency of antioxidants – primarily endogenous glutathione (GSH). There are many illnesses, from acute and post-COVID-19, diabetes, myocardial infarction, to Alzheimer’s disease, that are associated with OS. These dissimilar illnesses are in order, a viral infection, a metabolic disorder, an ischemic event, and a neurodegenerative disorder. OS may be an early initiator or a significant promotor of their progressive pathophysiologic processes. Consequently, addressing initial OS-related pathology may avoid subsequent severe and irreversible complications. Early intervention would modulate multiple factors, including cytokine stimulation, complement dysregulation, immuno-thrombosis, fibrosis, and autoimmunity. Past clinical studies that addressed OS have had equivocal results. It may be due to the use of ineffective antioxidants, an untimely delay in their use, or an inefficient delivery system. Experimental studies have used antioxidants that are not available for clinical trials. Although GSH can significantly reduce OS, its exogenous use is hampered by the lack of an effective delivery system. By incorporating GSH into cyclodextrin (CD) through nanotechnology, there is recent evidence that exogenous GSH can be delivered more effectively to prevent or mitigate injury from OS [1]. Future studies using the GSH/cyclodextrin (GC) complex will be needed to confirm its effectiveness and, hopefully, offer a path to treat many sub-optimally managed or currently untreatable illnesses.

Dementia from Alzheimer’s disease (ADz) is an enormous and growing healthcare problem. The economic and societal burden of caring for those who develop Alzheimer’s dementia (ADm) is rising as the population of those over 65 years of age increases. Current treatments are given to manage symptoms or to reverse established pathological insults of ADm. Evidence is presented that oxidative stress (OS) may initiate and promote the development of ADm when ADz is asymptomatic and that the antioxidant, glutathione (GSH), can counter OS. A novel nano-product, the glutathione-cyclodextrin (G-C) complex can effectively deliver GSH. It is proposed that if GSH is administered early in ADz to asymptomatic individuals with ADz it should delay or prevent the development of Adm. The complex is a topically applied non-prescription product that has no significant adverse side effects. As of 2023 GSH has not been studied in any current clinical trials.[1] Rigorous studies will be needed confirm its efficacy. If proven, its use should reduce the burden of ADm.

Early treatments of heart failure (HF) were directed toward management of fluid overload and providing inotropic support. Now, management of HF is multifaceted. Many of these treatments were established from outcomes of clinical trials. Each study has broadened our understanding of HF pathophysiology. The current regimens now include medications directed against the renin-aldosterone, angiotensin system (RAAS), the sympathetic system, and the natriuretic system. Recently, the sodium-glucose transport-2 inhibitors (SGLT2i) that were initially given to treat Type 2 diabetes are now recognized as being effective to treat HF. Since this effect was also beneficial in non-diabetic individuals, it prompted investigations to determine another mechanism of action (MOA) apart from its primary one that inhibits renal glucose reuptake. It led to the discovery of its anti-inflammatory property. This is notable since HF is associated with oxidative stress (OS) that is the result of excessive inflammation. It has highlighted the goal of reducing OS with an antioxidant as another target in HF treatment. Glutathione (GSH) is a well-known anti-inflammatory agent. Studies with its use in HF patients could determine the role of antioxidants in HF by reducing OS. A novel nano-product, the glutathione-cyclodextrin (G-C) complex will be presented that therapeutically delivers GSH. Studies using the G-C complex should determine the efficacy of GSH to suppress OS. If those studies are confirmatory, antioxidants could be another “arrow” in the quiver of HF management.