Glutathione in redox homeostasis: Bridging molecular mechanisms, bioavailability constraints, and translational challenges in systemic therapeutics

Glutathione (GSH) is a key intracellular thiol and a master regulator of redox homeostasis, playing a vital role in detoxification, mitochondrial function, and cellular signaling. Despite its well-established mechanistic importance, the clinical translation of GSH-based therapies remains hindered by significant pharmacokinetic barriers and inconsistent therapeutic outcomes. This study integrates a systematic review (PRISMA) with scientometric mapping to identify the landscape of glutathione research and address the gaps between fundamental biochemistry and systemic therapeutics. Studies published between 2004 and 2025 were analyzed according to PRISMA guidelines, focusing on redox signaling, delivery strategies, and translational outcomes Scientometric mapping revealed glutathione as a highly connected hub across diverse research areas, specifically bridging oxidative stress, neurodevelopmental disorders (e.g., ASD), and inflammatory conditions. However, the analysis highlights a persistent disconnect while fundamental research focuses on molecular pathways, clinical studies frequently struggle with low oral bioavailability and rapid enzymatic degradation. Advanced delivery systems, such as liposomal, intranasal, and sublingual formulations, may improve glutathione stability and systemic availability; however, evidence that these pharmacokinetic advantages result in clinically meaningful benefits remains limited. Current findings primarily support the mechanistic and pharmacokinetic relevance of glutathione rather than its established therapeutic efficacy. Future studies should determine whether biomarker-guided and optimized delivery strategies improve patient-centered outcomes while considering the potential risk of reductive stress.