Usage
L-Glutathione (GSH) is used as an adjunct therapy in chemotherapy to mitigate toxicity. It is also used for male infertility, atherosclerosis, various cancers, diabetes, liver diseases, lung diseases (inhaled use), memory loss, and Parkinson’s disease. It acts as an antioxidant, antitoxin, and immunostimulant. Its pharmacological classifications include antioxidant, detoxifying agent, and immunomodulator. GSH replenishes intracellular GSH levels, thereby neutralizing free radicals and reactive oxygen species.
Alternate Names
GSH, Gamma-L-Glutamyl-L-cysteinylglycine, N-(N-L-gamma-glutamyl-L-cysteinyl) glycine. Brand names vary depending on the manufacturer and formulation (e.g., liposomal glutathione).
How It Works
Pharmacodynamics: GSH is a potent antioxidant, protecting cells from oxidative damage by scavenging free radicals. It plays a crucial role in detoxification processes in the liver, conjugating with toxins to facilitate their excretion. It also modulates immune function, enhancing the activity of lymphocytes.
Pharmacokinetics: Oral absorption of standard GSH is limited. Liposomal formulations enhance bioavailability. Intravenous and intramuscular routes provide direct systemic delivery. GSH is metabolized within cells. Elimination pathways are not fully elucidated.
Mode of Action: GSH acts by directly reacting with free radicals and electrophiles, reducing them to less harmful substances. It also serves as a cofactor for glutathione peroxidase, an enzyme that catalyzes the detoxification of hydrogen peroxide. No specific receptor binding or neurotransmitter modulation has been identified. Elimination is believed to occur through both renal and hepatic routes.
Dosage
Dosage guidelines are not standardized and vary depending on the route of administration and clinical indication.
Standard Dosage
Adults:
Oral: 250-1000 mg daily, often divided into multiple doses.
Intravenous: 1.5 g/m² before chemotherapy; 600 mg/day on days 2-5 of chemotherapy cycle.
Intramuscular: 600 mg every other day for male infertility (for two months).
Inhaled: 600 mg twice daily via nebulizer.
Children:
Liposomal Glutathione: 1/4 teaspoon per 30 lb body weight daily.
Special Cases:
Dosage adjustments are not well-defined for elderly patients or those with renal or hepatic impairment. Clinical judgment is necessary based on individual patient characteristics.
Clinical Use Cases
Dosage recommendations for specific clinical settings (intubation, surgical procedures, mechanical ventilation, ICU use, emergency situations) are not established.
Dosage Adjustments:
Due to limited clinical data, specific dosage modifications for renal/hepatic dysfunction, metabolic disorders, or genetic polymorphisms are not established.
Side Effects
Common Side Effects:
Abdominal cramping, bloating, nausea, vomiting, diarrhea, and allergic reactions (rash, hives). Inhaled GSH can cause bronchospasm, particularly in asthmatic individuals.
Rare but Serious Side Effects:
Severe hepatic injury (with intravenous administration).
Long-Term Effects:
Potential long-term effects are not well-studied. Chronic use might be associated with decreased zinc levels.
Adverse Drug Reactions (ADR):
Clinically significant ADRs requiring immediate intervention are rare but could include severe allergic reactions or hepatic injury.
Contraindications
Hypersensitivity to glutathione. Inhaled glutathione is contraindicated in patients with asthma. Use with caution during pregnancy and breastfeeding due to insufficient safety data.
Drug Interactions
High doses of acetaminophen can deplete glutathione stores. Interactions with chemotherapy agents (cisplatin, carboplatin) and antihypertensive medications (losartan, amlodipine) have been reported. Information on CYP450 interactions is limited. Consult a healthcare professional for potential interactions with specific medications, OTC drugs, and supplements. Alcohol, smoking, and certain foods might interfere with glutathione’s efficacy.
Pregnancy and Breastfeeding
Safety during pregnancy and breastfeeding is not established. Avoid use unless the potential benefits outweigh the risks.
Drug Profile Summary
- Mechanism of Action: Antioxidant, detoxifying agent, immunomodulator.
- Side Effects: Abdominal discomfort, allergic reactions, bronchospasm (inhaled).
- Contraindications: Asthma (inhaled), hypersensitivity.
- Drug Interactions: Acetaminophen, some chemotherapy and antihypertensive agents.
- Pregnancy & Breastfeeding: Avoid unless benefits outweigh risks.
- Dosage: Varies widely depending on the route and indication.
- Monitoring Parameters: Monitor for allergic reactions, hepatic function (with IV use), and respiratory function (with inhaled use).
Popular Combinations
Often combined with vitamin C, other antioxidants, or amino acid precursors (cysteine, glycine) to enhance efficacy.
Precautions
Assess for allergies, asthma, pregnancy, and breastfeeding. Inform patients about potential drug and lifestyle interactions.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for L-Glutathione?
A: Dosage is not standardized and varies significantly depending on the administration route and clinical indication.
Q2: Is L-Glutathione safe during pregnancy?
A: Insufficient safety data is available. Use with caution during pregnancy and breastfeeding.
Q3: What are the potential side effects of inhaled glutathione?
A: Bronchospasm, particularly in individuals with asthma.
Q4: How does L-Glutathione interact with acetaminophen?
A: High doses of acetaminophen can deplete glutathione stores.
Q5: What is the role of L-Glutathione in chemotherapy?
A: Used as adjunctive therapy to reduce chemotherapy-induced toxicity.
Q6: Can L-Glutathione be used to whiten skin?
A: While some promote this use, scientific evidence is limited and further research is needed.
Q7: How does liposomal glutathione differ from standard glutathione supplements?
A: Liposomal formulations improve the bioavailability of glutathione.
Q8: Does L-Glutathione interact with any medications?
A: Potential interactions have been reported with some chemotherapy drugs and antihypertensives.
Q9: What lifestyle factors can affect glutathione levels?
A: Smoking, alcohol consumption, and poor diet can negatively impact glutathione levels.
