Is there evidence of clinical benefit for glutathione (Glutathione) supplementation?

From the Guidelines

Glutathione supplementation may be beneficial for patients with chronic oxidative stress or malabsorption, with a recommended dose of 200-500 mg/day, as suggested by the espen micronutrient guideline 1. When considering the use of glutathione supplements, it's essential to note that oral glutathione has poor bioavailability due to breakdown during digestion, making it challenging to significantly raise blood levels through oral supplementation. Some studies suggest potential benefits of glutathione supplementation for specific conditions, such as fatty liver disease, insulin resistance, and certain skin conditions, but these findings are preliminary and require further research. Injectable or intravenous glutathione may have better bioavailability, but it lacks robust clinical evidence for most claimed benefits. In contrast, N-acetylcysteine (NAC), a precursor that helps the body produce glutathione, has better evidence for clinical use, particularly for acetaminophen overdose and respiratory conditions. For those interested in supporting natural glutathione production, consuming sulfur-rich foods, getting adequate protein, and ensuring sufficient vitamin C and E intake may be more effective approaches than direct supplementation. The body naturally produces glutathione, which functions as an important antioxidant that helps neutralize free radicals and supports detoxification processes, but supplementation may not significantly enhance these natural processes in most healthy individuals. Key points to consider when evaluating the benefits of glutathione supplementation include:

• The patient's underlying medical condition and potential for oxidative stress or malabsorption
• The recommended dose and duration of supplementation
• The potential benefits and limitations of different forms of glutathione supplementation, including oral, injectable, and intravenous routes
• The availability of alternative approaches to support natural glutathione production, such as dietary modifications and NAC supplementation. It is also important to consider the findings of recent studies, such as the one published in the Journal of Clinical Oncology 1, which evaluated the protective effects of glutathione against platinum-based neurotoxicity and found mixed results, with some trials reporting a statistically significant reduction in neurotoxicity and others finding no benefit.

From the Research

Clinical Benefit of Glutathione Supplementation

• There is evidence to suggest that glutathione supplementation can have clinical benefits, including elevating body stores of glutathione and markers of immune function 2.
• A study published in the European Journal of Clinical Nutrition found that oral supplementation with liposomal glutathione increased glutathione levels in whole blood, erythrocytes, plasma, and peripheral blood mononuclear cells, and enhanced immune function markers such as natural killer cell cytotoxicity and lymphocyte proliferation 2.
• Another study published in the European Journal of Nutrition found that oral glutathione supplementation increased body stores of glutathione in healthy adults, with significant increases in glutathione levels in blood, erythrocytes, plasma, lymphocytes, and exfoliated buccal mucosal cells 3.
• The potential health benefits of glutathione supplementation are thought to be related to its ability to reduce oxidative stress and improve immune function, which may have implications for the prevention and treatment of various diseases 4, 3.

Mechanisms of Action

• Glutathione is a critical regulator of oxidative stress and immune function, and its supplementation may help to maintain optimal tissue levels of glutathione 2, 3.
• The mechanisms of action of glutathione supplementation are thought to involve the reduction of oxidative stress biomarkers, such as 8-isoprostane and oxidized:reduced glutathione ratios, and the enhancement of immune function markers, such as natural killer cell cytotoxicity and lymphocyte proliferation 2, 3.
• Dietary glycine, a biosynthetic precursor of glutathione, may also play a role in promoting glutathione synthesis and reducing oxidative stress 4.

Potential Health Outcomes

• The potential health benefits of glutathione supplementation include improving endothelial function, preventing cardiac hypertrophy, aiding control of metabolic syndrome, preventing the complications of diabetes, dampening inflammation, protecting the liver, and promoting effective sleep 4.
• Additionally, glutathione supplementation may have implications for the prevention and treatment of various diseases, including those related to oxidative stress and immune dysfunction 2, 3.