Simultaneous thiol–disulfide homeostasis in both erythrocytes and serum: a critical narrative review

Introduction This review aims to synthesize clinical studies that concurrently evaluate extracellular (serum) and intracellular (erythrocyte) thiol-disulfide homeostasis (TDH) using standardized colorimetric assays to clarify systemic oxidative stress patterns. Content The narrative review integrates findings from 10 human observational studies across different disorders. The included studies simultaneously measured serum disulfide to native thiol (SS/SH) ratios and erythrocyte oxidized to reduced glutathione (GSSG/GSH) ratios in the same individuals. Summary A consistent oxidative shift, featuring decreased thiols and increased disulfides, was observed in both compartments across all examined diseases. However, compartmental dominance is disease-specific. Intracellular glutathione imbalances demonstrated stronger clinical associations in conditions like rheumatoid arthritis, Alzheimer’s disease, subacute stroke and diabetic retinopathy. Conversely, extracellular TDH alterations were more prominent in subclinical hypothyroidism, small-for-gestational-age pregnancies, and substance use disorders. Sepsis states exhibited parallel disturbances without clear predominance. Outlook Simultaneous evaluation of erythrocyte and serum TDH provides complementary, compartment-specific insights into disease pathophysiology. Future prospective validation studies are required to establish these indices as prognostic biomarkers and to guide personalized antioxidant therapies.