In patients on hemodialysis, a metabolic block of the pentose phosphate shunt has been described that impairs the reduction of oxidized glutathione. The block results in lack of detoxication of the free hydroxyl radicals produced inside the red blood cell (RBC) and causes oxidative damage to the polyunsaturated fatty acids of the RBC membrane that results in formation of aldehydes. Malonyldialdehyde has been used as an index of the oxidative damage. In a study group of 13 patients on hemodialysis, the authors have tested whether administering reduced glutathione (GSH) at 1200 mg/day for 1 month could minimize oxidative damage to the RBC membranes and improve the hematologic parameters. Treatment with GSH was followed by significant improvement of hematocrit (P = 0.008), hemoglobin (P = 0.03), and RBC count (P = 0.0037); however, oxidative damage to the membranes was increased (P = 0.0004), which suggests that improvement of the hematologic parameters is not related to reduction of the oxidative damage. This is because oxidized glutathione, formed in the oxidative process, cannot be reduced back to GSH because of alteration of the pentose phosphate shunt.