Glutathione Intolerance: Getting to the Bottom of It | Masterjohn Q&A Files #308
Feb 6, 2023
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Explore the causes of glutathione intolerance and learn about various hypotheses and tests to determine the factors contributing to it. Delve into the breakdown and synthesis of glutathione, as well as the metabolism of cysteine. Discover the potential toxic by-products associated with different options for metabolizing cysteine and find out about recommended interventions for glutathione intolerance.
Intolerance to glutathione may be due to imbalanced or exhausted pathways in glutathione metabolism, leading to low levels and causing symptoms like brain fog.
The breakdown of glutathione can produce toxic byproducts such as ammonia, propionyl CoA, and hydrogen sulfide, which can impact metabolism and contribute to intolerance.
Deep dives
Understanding why some chronically ill individuals don't tolerate glutathione
Many individuals with chronic illness experience intolerance to glutathione, vitamin C, and other glutathione precursors like NAC and vitamin B6. The intolerance often manifests as extreme brain fog, which seems to worsen with larger glutathione doses. This intolerance may be due to an imbalanced or exhausted pathway in the glutathione metabolism system, leading to low or minimal glutathione levels. Different proportions of glutathione precursors and supporting nutrients may be necessary to improve tolerance. To isolate the source of the problem and explore potential solutions, several home experiments can be conducted. Tests involving L-glutamate, glycine, ammonia reduction, and molybdenum supplementation can help identify specific issues and guide appropriate supplementation strategies.
Exploring the breakdown and metabolism of glutathione
Glutathione, when broken down, yields glutamate, cysteine, and glycine. Glutamate enters the citric acid cycle, glycine contributes to folate methylation, and cysteine follows a complex pathway that generates ammonia. The breakdown of cysteine can result in the accumulation of propinyl-CoA, leading to potential toxicity and impairment of the urea cycle. Additionally, cysteine metabolism can produce hydrogen sulfide gas, which can act as a vasodilator or a mitochondrial poison. Sulfide accumulation may also occur, further affecting metabolism. Understanding these breakdown processes can help identify potential toxic byproducts and guide targeted interventions.
Testing hypotheses and potential solutions for glutathione intolerance
To investigate the underlying causes of glutathione intolerance, several hypotheses can be tested through home experiments. These include evaluating the role of glutamate toxicity, glycine as an inhibitory neurotransmitter, and ammonia production. Testing for ammonia can be done by modifying urine pH and supplementing glutamate. Experiments involving cysteine-specific hypotheses can be conducted by replicating the glutathione intolerance symptoms with L-cysteine or N-acetylcysteine. Additional tests targeting propinyl-CoA accumulation, hydrogen sulfide gas, sulfide toxicity, and taurine sensitivity can help narrow down the potential sources of glutathione intolerance. Depending on the results, specific interventions such as dosage adjustments, supplementation with specific nutrients, or metabolic pathway modulation can be considered.
Short Answer: It could be byproducts of any of the three amino acids that make up the glutathione molecule, which include the individual amino acids, ammonia, hydrogen sulfide, sulfite, and propionyl CoA, or it could be microbial metabolites of glutathione produced in the gut. The full answer contains seven hypothesis-driven tests that can be done at home to determine the cause.
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In that batch of free episodes you will also find the answers to these questions:
Statins Vs. Sulfur for Heart Disease
Why Plasma Zinc is the Best Marker of Zinc Status
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This snippet is from the October 12, 2022 AMA. The full recording and transcript is reserved for Masterpass members. Here is a preview of what’s included:
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