What are the recommendations for glutathione (Glutathione) supplementation?

Glutathione Supplementation Recommendations

There is insufficient evidence to recommend routine glutathione supplementation for the general population, as clinical guidelines specifically state there are no data supporting its use in conditions like cystic fibrosis. 1

Current Clinical Evidence and Guidelines

• Clinical guidelines from the Cystic Fibrosis Foundation explicitly state there are no data supporting the use of glutathione therapy in patients with cystic fibrosis 1
• The ESPEN micronutrient guidelines do not include glutathione among recommended supplements, focusing instead on other antioxidants like selenium which is an essential constituent in the antioxidant glutathione peroxidase 1
• Selenium is important as it forms part of glutathione peroxidase, but selenium itself has a narrow therapeutic range and fatalities have been reported with inorganic selenium supplementation in people with cystic fibrosis 1

Specific Clinical Applications

• In methemoglobinemia, particularly in patients with G6PD deficiency, ascorbic acid is recommended over methylene blue as it can help reduce oxidative stress, which indirectly supports glutathione function 1
• For patients undergoing hematopoietic stem cell transplantation (HSCT), parenteral glutamine (not glutathione) supplementation may be considered at doses of 0.35-0.6 g/kg/day 2, 1
• For surgical patients who cannot be fed enterally and require parenteral nutrition, glutamine supplementation may be considered, but not glutathione specifically 2

Research on Glutathione Supplementation

• A randomized controlled trial showed that oral glutathione supplementation (250 or 1,000 mg/day) increased glutathione levels in blood, erythrocytes, plasma, and lymphocytes after 6 months of supplementation 3
• Liposomal glutathione administration (500 and 1000 mg daily) demonstrated increased glutathione levels in whole blood, erythrocytes, plasma, and peripheral blood mononuclear cells after 2 weeks 4
• Research suggests that glutathione deficiency in elderly humans occurs due to reduced synthesis, and dietary supplementation with glutathione precursors (cysteine and glycine) can restore glutathione synthesis and concentrations 5

Important Cautions and Contraindications

• High-dose glutamine (not glutathione) supplementation has been associated with increased mortality in critically ill patients with multi-organ failure 2
• Patients with renal failure should avoid high-dose parenteral glutamine supplementation 2
• Selenium, which is part of glutathione peroxidase, should not be routinely supplemented outside of very limited geographical areas where low serum selenium can result from low selenium content in soil 1

Monitoring Recommendations

• For patients receiving selenium supplementation (which supports glutathione function), plasma selenium levels should be monitored regularly in long-term parenteral nutrition and in patients with renal failure 1
• In patients with suspected glutathione deficiency, glutathione reductase activity in red blood cells can be assessed 1

Practical Approach to Glutathione Support

1. Focus on addressing underlying causes of oxidative stress rather than direct supplementation
2. Consider precursor supplementation (cysteine and glycine) rather than direct glutathione supplementation in elderly patients with evidence of oxidative stress 5
3. If considering direct supplementation, liposomal forms may have better bioavailability than standard oral forms 4
4. Ensure adequate selenium intake (but not excessive) as it is an essential component of glutathione peroxidase 1

While some research suggests potential benefits of glutathione supplementation for oxidative stress-related conditions 6, current clinical guidelines do not support routine supplementation with glutathione for most conditions.