Albumin Supplementation Preserves Systemic Antioxidant Defenses in Critically Ill, Septic Patients: A Prospective Comparative Study

Background/Objectives: Sepsis is a life-threatening syndrome characterized by a dysregulated host response to infection, commonly accompanied by hypoalbuminemia (<30 g/L serum albumin level), associated with excessive production of reactive oxygen and nitrogen species, leading to oxidative stress, endothelial dysfunction, and organ injury. Low serum albumin reflects increased vascular permeability, reduced hepatic synthesis, and enhanced proteolysis. It also indicates the loss of albumin’s antioxidant and anti-inflammatory functions beyond oncotic regulation. Hypoalbuminemia may exacerbate this by reducing plasma antioxidant capacity and free radical scavenging, supporting interest in albumin supplementation as a potential therapeutic strategy. Methods: This prospective, randomized study investigated the effects of 3-day albumin administration in ICU patients (n = 38) with sepsis and hypoalbuminemia by assessing changes in oxidative stress and inflammatory markers. Results: Albumin supplementation increased serum albumin (p < 0.001) and was associated with higher total antioxidant capacity (Day 3 p = 0.045; Day 5 p = 0.004), glutathione levels (Day 3 p = 0.003; Day 5 p = 0.008), and protein sulfhydryl groups (Day 3–5 p = 0.004). Albumin-treated patients showed increased urinary concentration of the oxidative stress–related tyrosine isomers ortho- and meta-tyrosine (p = 0.004 and p = 0.001, respectively). Catalase activity and myeloperoxidase, procalcitonin, and IL-1β levels did not differ between groups, while IL-6 declined over time (p = 0.029). Conclusions: Based on our results, in septic patients with hypoalbuminemia, short-term albumin supplementation seems to restore serum albumin and improve systemic redox status, as evidenced by increased total antioxidant capacity, glutathione, and protein sulfhydryl levels. However, albumin supplementation did not significantly affect systemic inflammatory markers or cytokine dynamics. Albumin appears to act primarily by modulating oxidative stress, supporting its role as an adjunctive therapy to restore redox homeostasis in sepsis.