What are the indications and guidelines for the use of intravenous (IV) glutathione in patients with conditions characterized by oxidative stress, such as severe liver disease or those undergoing chemotherapy?

Intravenous Glutathione Use

Intravenous glutathione has extremely limited evidence-based indications in clinical medicine, with the strongest data supporting its use only for preventing platinum-based chemotherapy-induced peripheral neuropathy at doses of 1.5-2.5g IV before chemotherapy, though it is ineffective for taxane-induced neuropathy. 1

Evidence-Based Clinical Indications

Chemotherapy-Induced Peripheral Neuropathy (CIPN)

• For platinum-based chemotherapy (cisplatin, oxaliplatin, carboplatin), injectable GSH at 1.5-2.5g IV administered before chemotherapy may reduce peripheral neuropathy through detoxification of platinum-induced reactive intermediates. 1
• Six small randomized trials demonstrated statistically significant reductions in neurotoxicity with GSH administration compared to placebo, including reduced incidence and severity of neuropathy, improvements in nerve conduction, and quality of life. 2
• GSH is completely ineffective for taxane-induced neuropathy prevention, as demonstrated by a placebo-controlled trial in 185 patients receiving paclitaxel/carboplatin therapy, according to the American Society of Clinical Oncology. 2, 1

Contrast-Induced Nephropathy Prevention

• Intravenous GSH at 100 mg/min for 30 minutes before coronary angiography completely abolished the increase in urinary lipid hydroperoxides (5.5 ± 8.8% vs 299.5 ± 94.4% in controls, p<0.01) in patients with reduced renal function. 3
• IV GSH was more effective than oral N-acetylcysteine in preventing contrast medium-induced renal oxidative stress, as NAC failed to prevent the increase in lipid hydroperoxides (196.8 ± 81.3%, p<0.05). 3

Conditions Where IV Glutathione Is NOT Recommended

Oncology Settings

• ESPEN states there are insufficient consistent clinical data to recommend glutamine supplementation during conventional cytotoxic or targeted therapy, and therefore does not recommend its use. 1
• The Cystic Fibrosis Foundation states there are no data supporting the use of glutathione therapy for patients with cystic fibrosis. 1

Critical Care and Renal Disease

• In ICU patients except burn and trauma patients, additional enteral glutamine should not be administered (Grade B recommendation with 92.31% consensus). 1
• The National Kidney Foundation recommends that high-dose parenteral glutamine should not be administered to patients with acute kidney injury or chronic kidney disease with kidney failure. 1

Gastrointestinal and Liver Disease

• ESPEN guidelines state there is insufficient evidence to recommend glutamine supplementation in IBD patients. 1
• The Korean Association for the Study of the Liver guidelines do not recommend glutathione for NAFLD management, despite one small pilot study showing reduced oxidative stress markers. 1, 4

Cosmetic Use

• There are no studies of IV GSH use for skin lightening or of its safety for chronic use for any indication. 5
• The switch from brown to red melanin production may increase the risk of sun-induced skin cancers in previously protected individuals. 5

Critical Safety Considerations and Common Pitfalls

Administration and Dosing

• Only intravenous administration has established evidence in medical literature for therapeutic applications. 1
• Oral and topical formulations lack robust clinical evidence, though one small study showed liposomal oral GSH at 500-1000 mg/day elevated blood GSH levels by 40% in whole blood after 2 weeks. 6

Drug Confusion

• GSH should not be confused with glutamine—they are different compounds with distinct indications and dosing regimens. 1
• Glutamine is an amino acid used for mucosal protection and immune function, while glutathione is a tripeptide antioxidant with different mechanisms of action. 1

Cofactor Requirements

• Glutathione peroxidase requires selenium for optimal enzymatic activity, making adequate selenium status crucial for GSH function. 1
• Red blood cells contain high levels of antioxidants, particularly reduced glutathione, suggesting that anemia management may affect total antioxidative capacity. 2

Oxidative Stress Context in Chronic Kidney Disease

• The K/DOQI guidelines note that red blood cells contain high levels of reduced glutathione, and a rise in red cell mass may increase total antioxidative capacity. 2
• However, the benefit of antioxidant treatment strategies in CKD patients remains undefined, with larger trials needed to assess effects on mortality. 2
• Acetylcysteine (not glutathione) was associated with reduced cardiovascular events in hemodialysis patients in one study. 2

Regulatory and Evidence Gaps

• No published review on IV GSH for any chronic use indication exists, and regulatory assessment by medicines control councils is urgently warranted to protect consumers from potential side-effects and complications of IV infusions. 5
• Studies are needed to determine which oxidative stress pathway is quantitatively most important and which interventions improve clinical outcomes. 2