Glutathione Precursor Supplementation with Immunocal® for Inflammaging: An Open-Label Pilot Study Assessing suPAR Modulation in Middle-Aged Adults

Introduction: Chronic low-grade systemic inflammation constitutes a central biological feature of aging and a key factor in the development of multiple chronic diseases [1,2]. The soluble urokinase Plasminogen Activator Receptor (suPAR) has emerged as a robust biomarker of chronic systemic inflammation and biological vulnerability [3-5]. Nutritional strategies aimed at modulating intracellular redox balance may influence upstream inflammatory pathways involved in the regulation of suPAR [6-9]. Objective: To explore whether supplementation with a cysteine-rich whey protein isolate, a glutathione precursor, is associated with changes in circulating suPAR concentrations and health-related quality of life in adults. Methods: An exploratory, open-label, single-arm, longitudinal pre-post intervention proof-of-concept study. Twelve adult participants received oral supplementation with a cysteine-rich whey protein isolate (Immunocal®) for three months. Circulating suPAR concentrations and health-related quality of life, assessed using the SF-36 questionnaire, were measured at baseline and at the end of the intervention. Results: After three months of supplementation, mean suPAR levels decreased from 3.19 to 1.87 ng/mL (mean Δ = 1.31; p < 0.0001). Mean total SF-36 scores increased from 71.77 to 87.39 (mean Δ = 15.61; p < 0.0001). The intervention was well tolerated and no serious adverse events were reported. Conclusion: Supplementation with glutathione precursors using Immunocal® for a three-month period was associated with a significant reduction in circulating suPAR concentrations, a consolidated biomarker of chronic systemic inflammation and immune activation, as well as with concomitant improvements in health-related quality of life in adults.