Link: Glutathione Depleted by Chronic Illnesses

[linusbert]

from https://vitamindwiki.com/Glutathione+Depleted+by+Chronic+Illnesses
i just found this kinda interesting:

so if cfs is-50% and diabetes t2 is -73,8% , how much is this combined?

glutathione is also related to emf, mcas allergies?, asthma severity. probably mcs too.

 

[Wishful]

That link focuses on the antioxidant role, but glitathione is also used in biosynthesis of leukotrienes and prostaglandins, so depletion might also be a sign of immune activation (not sure of this).

 

[linusbert]

agree, antioxidants are underrated.. actually almost everything which can oxidize is a antioxidant at some point, and becomes a radical after wards. but they hit different... vitamin c is more like a light ping pong ball... where as iron or copper are like bowling balls crashing through.
but the important metabolic other effects like vitamin c and carnitine synthesis are for the common folk not known, but it makes perfect sense that vitamin c deficiency leads to muscle weakness then or broken fat metabolism.

also for glutathione, though i am not yet read into glutathione 's other functions much.

 

[pamojja]

also for glutathione, though i am not yet read into glutathione 's other functions much.

From perplexity.ai:

Non-Antioxidant Metabolic Functions of Glutathione​

Beyond its well-known role as a cellular antioxidant, glutathione (GSH) is involved in several critical metabolic and regulatory processes:
1. Detoxification of Xenobiotics and Endogenous Compounds

• Glutathione conjugates with a wide variety of toxins, drugs, and metabolic byproducts via glutathione S-transferase enzymes, making them more water-soluble for excretion. This is a key mechanism in liver detoxification and protection against environmental and internal toxins2469.

2. Amino Acid Transport and Cysteine Storage

• GSH participates in the γ-glutamyl cycle, facilitating the transport of amino acids across cell membranes. It also acts as a storage and transport form of cysteine, an essential amino acid for protein synthesis and other metabolic pathways134.

3. Regulation of Cellular Processes

• GSH is involved in:
  • DNA synthesis and repair
  • Protein synthesis
  • Regulation of cell proliferation and apoptosis (programmed cell death)
  • Modulation of gene expression and signal transduction pathways, including redox-sensitive transcription factors569.

4. Immune System Support

• Glutathione supports immune cell function, including the proliferation and activation of lymphocytes and macrophages, and modulates cytokine production, thus influencing immune responses69.

5. Hormone and Mediator Metabolism

• GSH is essential for the metabolism of hormones and inflammatory mediators, including estrogens, prostaglandins, and leukotrienes234.

6. Metal and Iron Homeostasis

• Glutathione binds to and helps regulate the metabolism of metals such as iron, zinc, copper, chromium, cadmium, and lead. It plays a direct role in iron homeostasis, including the synthesis of heme and iron-sulfur clusters necessary for mitochondrial function23.

7. Nitric Oxide and Hydrogen Sulfide Metabolism

• GSH stores and transports nitric oxide and is involved in hydrogen sulfide metabolism, both of which are important signaling molecules in the body34.

8. Mitochondrial Function and Cellular Energy

• It is vital for maintaining mitochondrial function and the integrity of mitochondrial DNA, influencing cellular energy production and apoptosis8.

9. Other Functions

• GSH is involved in the regeneration of other antioxidants (such as vitamins C and E), maintenance of protein thiol status (S-glutathionylation), and modulation of inflammation89.

In summary, glutathione’s metabolic roles extend far beyond antioxidant defense, encompassing detoxification, amino acid transport, immune modulation, hormone metabolism, metal homeostasis, and cellular regulation12345689.

1. https://www.sciencedirect.com/topic...-and-molecular-biology/glutathione-metabolism
2. https://pmc.ncbi.nlm.nih.gov/articles/PMC10376414/
3. https://pmc.ncbi.nlm.nih.gov/articles/PMC3303626/
4. https://en.wikipedia.org/wiki/Glutathione
5. https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2014.00196/full
6. https://www.healthbenefitstimes.com/health-wiki/glutathione/
7. https://todayspractitioner.com/aging/glutathione-physiological-clinical-relevance/
8. https://dialnet.unirioja.es/descarga/articulo/9051454.pdf
9. https://consensus.app/home/blog/wha...tamylcysteinylglycine-glutation-l-glutathion/

 

[linusbert]

thanks

 

[bad1080]

"Glutathione+Depleted+by+Chronic+Illnesses" makes it sound like they found a causal connection but did they or is it just correlation? because on the graph it then says "Glutathione Depleted >in< Chronic Illnesses"

 

[pamojja]

it sound like they found a causal connection but did they or is it just correlation? becauseon the graph it then says "Glutathione Depleted >in< Chronic Illnesses"

Chronic illness causes various damage to the body. Which Glutathione repairs, and thereby becomes depleted. Depending on the illness, between 20 to 80%.

The causal chain: Chronic illness > Glutathione depletion.

Of course, practically - in my case 4 subsequent chronic illnesses, mentioned in the graph - the resulting Glutathione depletion by the first occurring chronic illness makes it much more likely for the following to manifest. With each of my 3 further much more likely.

Me: Chronic liver > -45% > Chronic fatigue > -50% > CVD > -17% - T2D -70%

With each additional chronic disease - if glutathione isn't repleted - the following disease might become more likely to manifest. Because of already depleted glutathione as cofactor.

so if cfs is-50% and diabetes t2 is -73,8% , how much is this combined?

With my combined numbers, it would be 182% Glutathione depletion, and most likely death.

However, first the liver healed, next CVD, T2D, and PEMs last. Am I repleted?

My Glutathione peroxidase lab marker in the optimal range, which does measure the breakdown of Glutathione, does suggest.

 

[Wishful]

Chronic illness causes various damage to the body. Which Glutathione repairs, and thereby becomes depleted.

Is that proven fact, or conjecture? I'm not saying it's untrue, I just don't know whether it's a proven fact rather than a nice, easy-to-understand-but-maybe-wrong theory. I just checked one paper on glutatione depletion and chronic illness, and it claimed a correlation, but didn't state that it was caused by the illness, instead suggesting that depletion made those diseases more likely. The paper also made it sound like glutathione correlation with diseases isn't well-studied.

I'm guessing that another theory might be that glutathione depletion might be a sign of dysfunction in the production mechanism, rather than simply due to reaction with ROS.

 

[Wayne]

Just had a (fairly lengthy) conversation with AI, and asked it the following: "What's the best ways to try to increase bodily glutathione levels? I'm aware of supplementing with NAC. I've also heard of nebulizing it, but don't know how efficient it is. I've heard oral is not absorbed all that well. Could rectal implants work? Thoughts?"

Spoiler: ChatGPT on Raising Glutathione Levels

ChatGPT said:
Great question—glutathione is critical for so many aspects of cellular health! Here’s a concise overview of the best ways to increase your body’s glutathione levels, including some of the routes you mentioned:

---

Key Strategies for Boosting Glutathione
1) NAC (N-acetylcysteine) supplements

• Very well-studied! NAC provides cysteine, a limiting amino acid in glutathione synthesis.
• Oral NAC is well absorbed and reliably increases cysteine and indirectly glutathione.
• Dosage: often 600–1200 mg/day (some go higher for acute issues, but more isn’t always better long-term).

2) Whey protein / cysteine-rich foods

• Undenatured whey protein (like Immunocal) is a natural glutathione precursor.
• Cysteine-rich foods: eggs, garlic, onions.

3) Direct glutathione (GSH) supplementation

• Oral glutathione is somewhat absorbed—more than older claims said, but less than NAC.
• Liposomal glutathione is better absorbed orally because the lipid coating helps it bypass gut breakdown.
• IV or IM glutathione injections are very effective but obviously require a medical setting.
• Nebulized glutathione:
  • Some integrative docs use it, especially for lung issues (like COPD).
  • The data is mixed: It does seem to deliver glutathione to the lungs directly, but it’s not clear how much reaches systemic circulation.
• Rectal glutathione:
  • The rectal route can bypass some digestive enzyme breakdown.
  • Some people anecdotally report benefits from rectal glutathione suppositories, but there’s very little formal data on systemic absorption or safety.
  • Probably more efficient than oral but still less data than IV or liposomal oral.

4) Lifestyle / natural ways

• Exercise (moderate, not overtraining!) can boost glutathione production.
• Cruciferous vegetables (broccoli, Brussels sprouts) contain sulforaphane, which ramps up the NRF2 pathway that drives glutathione production.
• Reduce toxin load and alcohol—both deplete glutathione.

---

Bottom line on methods you mentioned:

Method	Efficiency
Oral NAC	Excellent precursor, well absorbed.
Oral glutathione	Less absorption than NAC, but liposomal forms are decent.
Nebulized glutathione	Good for local lung issues, not well studied for systemic.
Rectal glutathione	Anecdotally promising, but no strong data on systemic levels or optimal dosing.

---

Practical approach
If you’re trying to boost systemic glutathione:

• Start with NAC or whey protein.
• Add liposomal glutathione if you want more direct glutathione support.
• Use rectal suppositories cautiously if you’re familiar with them, but be aware the research is very limited.
• IV glutathione can be very powerful but requires a practitioner.

---

Oral (non-liposomal) glutathione

• Historically, it was thought that most oral glutathione is broken down in the gut and doesn’t meaningfully increase blood levels.
• Newer studies (like Richie et al. 2015) show that oral glutathione can increase plasma glutathione by about 30–40% when taken at higher doses (e.g., 1,000 mg/day) over several weeks.
• However, this increase is still smaller and slower compared to NAC (which fuels glutathione production more robustly).

---

Liposomal glutathione

• Liposomal formulations encapsulate glutathione in fat-based particles that help it avoid gut breakdown and improve absorption into the bloodstream.
• While there’s no definitive “absorption percentage,” small clinical trials and pharmacokinetic data suggest liposomal glutathione raises blood glutathione levels significantly more than regular oral glutathione—some say by 2–3× compared to standard forms.
• Exact bioavailability figures (like “X% absorbed”) aren’t well standardized, but it’s considered the best oral delivery option.

---

NAC vs. direct glutathione

• NAC’s absorption is about 6–10% of the dose (after first-pass liver metabolism), but because it’s a glutathione precursor, it boosts glutathione much more efficiently than oral glutathione.
• NAC increases intracellular glutathione in the liver and other tissues, while oral glutathione mostly boosts plasma (blood) glutathione but has weaker effects inside cells.

---

Summary table

Form	Estimated Effect on Blood Glutathione	Mechanism
Regular oral glutathione	~30–40% increase over 1 month at high doses	Direct absorption, limited by gut breakdown
Liposomal oral glutathione	Up to 2–3× higher blood glutathione than regular	Lipid encapsulation helps bypass gut breakdown
NAC	Strong precursor, indirectly raises intracellular glutathione	Boosts cysteine supply for glutathione production

---

So in short:

• Regular oral glutathione does raise blood glutathione, but modestly.
• Liposomal oral glutathione is significantly better absorbed, ~2–3× improvement.
• NAC doesn’t deliver glutathione directly, but is more potent overall for building your own glutathione reserves.

---

If you want to:
1) Directly raise blood glutathione levels quickly
→ Liposomal glutathione wins.
Delivers glutathione directly, bypasses gut breakdown, faster boost in blood.
Especially useful if you’re dealing with acute oxidative stress, chronic inflammation, or lung issues.
2) Build up your body’s own glutathione stores long-term
→ NAC wins.
Cheaper and more evidence for long-term intracellular glutathione support.
Works by replenishing cysteine, which is the rate-limiting factor for glutathione synthesis.
Better for long-term maintenance or prevention.

---

️ My short verdict:

• Liposomal glutathione: Faster, more direct blood boost—best for immediate antioxidant need.
• NAC: More cost-effective, powerful for long-term support and intracellular stores.

For daily maintenance, NAC is usually enough (plus diet & lifestyle!).
For acute or advanced needs (like during IV detox programs, or in some severe illness cases), liposomal glutathione can be the better choice.
Let me know if you’d like a suggested “stack” or protocol!
You said:
Does it make sense to combine the two?
ChatGPT said:
Yes—it can definitely make sense to combine NAC and liposomal glutathione, especially if you’re dealing with:

• High oxidative stress or inflammation (e.g., illness, toxin exposure, or high-intensity exercise)
• Chronic health conditions (e.g., chronic fatigue, autoimmune issues, neurodegeneration)
• Wanting both immediate glutathione support and longer-term rebuilding

---

Why combining works

• NAC acts as a building block (cysteine donor) to help your cells make more glutathione over time.
• Liposomal glutathione provides an immediate boost of glutathione in your blood, bypassing the synthesis step.

By combining them, you’re:
Directly raising blood glutathione (liposomal)
Supporting your body to rebuild glutathione internally (NAC)

---

How to do it practically

• Typical NAC dose: 600–1200 mg/day
• Typical liposomal glutathione dose: 250–500 mg/day
• You can take them together or stagger them (e.g., NAC morning, liposomal glutathione midday/afternoon).

---

Cautions

• Watch for side effects: Some people get mild nausea or GI upset from NAC, especially if they take too much.
• Don’t overdo it long-term: Both are potent, and with any antioxidant support, cycling or pulsing may be helpful to avoid oversuppression of normal cell signaling (a bit of oxidative stress is actually normal and healthy!).

---

In summary, combining NAC and liposomal glutathione can be a powerful, synergistic strategy to boost glutathione both quickly and sustainably. Let me know if you’d like tips on adding in lifestyle or dietary factors too!

 

[pamojja]

from https://vitamindwiki.com/Glutathione+Depleted+by+Chronic+Illnesses

Which Glutathione repairs, and thereby becomes depleted. Depending on the illness, between 20 to 80%.

Is that proven fact, or conjecture? I'm not saying it's untrue,

The first link was a summary on vitaminDwiki made by perplexity.ai. As always, it comes with many scientific sources. I didn't check all 68 references, but at least some important to verify if this article is based on scientific results.

(I don't read @Wayne's GPT articles, because they aren't reverenced and can't be checked, therefore the burden of proof is wrongly placed on the reader. I requested to ask for added sources, but he seems to ignore my request.)

I just checked one paper on glutatione depletion and chronic illness, and it claimed a correlation, but didn't state that it was caused by the illness, instead suggesting that depletion made those diseases more likely. The paper also made it sound like glutathione correlation with diseases isn't well-studied.

The 68 sources for the article are known, which is the one source of yours? - When checking sources, I do verify how high up in the hierarchy of research different conflicting papers are. But here you too, wrongly ask me to give you the burden of proof for your conjecture. Based on a single paper, unreferenced.

However: GSH depletion can be a co-factor for later chronic disease, as well as its effect (I'm aware of the most determining causes for my NAFLD, COPD, PAD, T2D and PEMs). A single case is higher up in the hierarchy of evidence by being observational. Which thesis speculation isn't.

I'm guessing that another theory might be that glutathione depletion might be a sign of dysfunction in the production mechanism, rather than simply due to reaction with ROS.

As pointed out higher up in the thread, glutathione has many non-antioxidant metabolic functions. 9 are listed. All definitely co-factors additional to the antioxidant function. And thereby impeding its production mechanism in various ways too.

Why you accuse me of merely guessing? While you apparently do (quote above) without reading the whole thread, and check its sources. Instead, leaving your single source unknown?

However, first the liver healed, next CVD, T2D, and PEMs last. Am I repleted?

Glutathione peroxidase (Se dependent), GSH-Px, 4 times tested, roughly correlate: 44, 65, 72, 78 U/gHb with my various remissions.

27.5 - 73.6 normal range

69 - 90 optimal range

Not enough GSH to oxidize first, and increasingly more later. GSH availability correlating with remissions. Also impeded production of GSH first. For example, by not enough Se available for the production of GSH-Px. Most likely a mix of those co-factors. And some unknown.

 

[pamojja]

(I don't read @Wayne's GPT articles, because they aren't reverenced and can't be checked, therefore the burden of proof is wrongly placed on the reader. I requested to ask for added sources, but he seems to ignore my request.)

Just had a (fairly lengthy) conversation with AI, and asked it the following: "What's the best ways to try to increase bodily glutathione levels?

I still value @Wayne 's personal input (other than the bias-confirmation he asks ChatGPT for).

Here what is known, from perplexity.ai. This time I had for the first time to insist twice on sources for everything!

Spoiler: GSH increasing supplements

You are absolutely right: “general knowledge” is not a sufficient or scientific citation, and should not be used as a stand-in for peer-reviewed evidence. For a rigorous and credible comparison, each nutrient’s effect on glutathione (GSH) should be supported by specific, referenced studies, ideally with quantified results.

Below is an improved table with peer-reviewed references and, where available, the percentage increase in GSH for each nutrient. I have included only human studies (unless otherwise noted) and provided links or citations for each.

---

Detailed Table: Nutrients and GSH Increase with Full References​

Nutrient/Supplement	Dose & Duration	Tissue/Cell Type	% GSH Increase	Reference(s)
Vitamin C	1 g/day, 4 weeks	Erythrocytes (RBCs)	28%	Johnston CS, Meyer CG. Vitamin C elevates red blood cell glutathione in healthy adults. Am J Clin Nutr. 1993;58(1):103-5. PubMed
	0.5–2 g/day, 3 weeks	Lymphocytes	18%	Jacob RA, et al. Vitamin C increases red cell glutathione in healthy adults. Am J Clin Nutr. 1995;61(4):805-9. PubMed
N-Acetylcysteine (NAC)	600 mg/day, 8 weeks	Lymphocytes	30%	Kelly GS. Clinical applications of N-acetylcysteine. Altern Med Rev. 1998;3(2):114-27. PubMed
	1200 mg/day, 4 weeks	Whole blood (HIV+)	32%	De Rosa SC, et al. N-acetylcysteine replenishes glutathione in HIV infection. Am J Clin Nutr. 2000;72(4):914-9. PubMed
Alpha-Lipoic Acid (ALA)	600 mg/day, 4 weeks	Erythrocytes (RBCs)	20%	Busse E, et al. Increase of glutathione in erythrocytes of humans and rats following administration of thioctic acid. Int J Vitam Nutr Res. 1992;62(3):241-4. PubMed
	300 mg/day, 4 weeks	Plasma	30%	Packer L, et al. Alpha-lipoic acid as a biological antioxidant. Free Radic Biol Med. 1995;19(2):227-50. PubMed (review)
Whey Protein	20 g/day, 3 months	Lymphocytes	24%	Lands LC, et al. Effect of supplementation with a cysteine donor on muscular performance. J Appl Physiol. 1999;87(4):1381-5. PubMed
Oral Glutathione	500 mg/day, 6 months	Whole blood	30–35%	Richie JP Jr, et al. Randomized controlled trial of oral glutathione supplementation on body stores of glutathione. Eur J Nutr. 2015;54(2):251-63. PubMed

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Additional Review References​

• Vitamin C and GSH:
  • Jacob RA, Sotoudeh G. Vitamin C function and status in chronic disease. Nutr Clin Care. 2002;5(2):66-74. PubMed
• NAC and GSH:
  • Samuni Y, et al. The chemistry and biological activities of N-acetylcysteine. Biochim Biophys Acta. 2013;1830(8):4117-29. PubMed
• ALA and GSH:
  • Shay KP, et al. Alpha-lipoic acid as a dietary supplement: molecular mechanisms and therapeutic potential. Biochim Biophys Acta. 2009;1790(10):1149-60. PubMed
• Whey Protein and GSH:
  • Kent KD, et al. Dietary whey protein increases glutathione content in rat liver and heart. J Nutr. 2003;133(2):402-7. PubMed
• Oral Glutathione and GSH:
  • Allen J, Bradley RD. Effects of oral glutathione supplementation on systemic oxidative stress biomarkers in human volunteers. J Altern Complement Med. 2011;17(9):827-33. PubMed

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Notes on the Evidence

• Vitamin C: Robust, consistent increases in GSH in blood cells at doses up to 2 g/day.
• NAC: Widely used clinically; strong evidence for boosting GSH, especially in deficiency states.
• ALA: Some evidence for modest increases in GSH, both in vitro and in vivo.
• Whey Protein: Provides cysteine, the rate-limiting amino acid for GSH synthesis; increases GSH in immune cells.
• Oral Glutathione: Once thought to be poorly absorbed, but recent studies show significant increases in blood GSH with regular supplementation.

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Summary​

• All values above are based on peer-reviewed human studies, not “general knowledge.”
• Where only animal or in vitro data are available, this is noted.
• For a more nuanced or tissue-specific analysis, further literature review may be needed.

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This table should provide a robust, reference-backed overview of how leading nutrients compare in their ability to raise GSH in humans.

Milk thistle and Selenium dropped from the GSH increasing supplement table, because never directly tested. Though depend mainly on Selenium, on increased availability of GSH, of course too (general knowledge!)

Spoiler: GSH vs. GSH-Px

Your observation is accurate: there is no direct scientific study that specifically examines how selenium-dependent glutathione peroxidase (GSH-Px) activity tracks with or quantifies increases in glutathione (GSH) itself in response to interventions, especially in humans. Most research focuses on how selenium supplementation increases GSH-Px activity, with the assumption that GSH availability is sufficient, but not on how GSH-Px activity reflects or quantifies changes in GSH levels 12367.

What the Research Shows​

• Selenium supplementation reliably increases GSH-Px activity in blood and tissues, provided selenium deficiency is present 1268.
• GSH-Px requires both selenium and GSH to function:
  • Selenium is needed for enzyme synthesis and activity 78.
  • GSH is the substrate; low GSH reduces GSH-Px activity regardless of selenium status 35.
• Some studies note that GSH depletion (e.g., with buthionine sulfoximine) lowers GSH-Px activity, but these are mechanistic and not focused on supplementation or clinical interventions 5.
• No studies have systematically measured how much GSH-Px activity increases as a function of GSH increases due to interventions like high-dose vitamin C, NAC, or other GSH-raising strategies.

Key Points from Literature​

• GSH-Px activity is a marker of selenium status and, to a lesser extent, GSH availability 237.
• Most studies use GSH-Px as a marker of selenium repletion, not as a quantitative marker of GSH increase.
• Your case, where GSH-Px activity closely tracked with clinical remissions and high-dose ascorbic acid intake, is unique and not directly addressed in the literature.

Conclusion​

There is a scientific gap:

• No published studies directly quantify the relationship between increases in GSH (from any intervention) and subsequent changes in selenium-dependent GSH-Px activity in humans.
• GSH-Px activity is influenced by both selenium and GSH, but is not routinely used as a surrogate for GSH status in clinical research.
• Your observation that GSH-Px activity paralleled both selenium and GSH-raising interventions (especially ascorbic acid) is plausible and mechanistically supported, but not directly validated by existing research357.

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References:
1 https://pubmed.ncbi.nlm.nih.gov/7924458/
2 https://www.sciencedirect.com/science/article/pii/S0006497120690036
3 https://pmc.ncbi.nlm.nih.gov/articles/PMC8480288/
5 https://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602007000400005
6 https://www.tandfonline.com/doi/full/10.1080/10715762.2019.1641602
7 https://www.mdpi.com/2076-3921/7/5/66
8 https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2023.1147414/full

On insisting that it couldn't be possibly exactly known for ascorbic acid, since it was never tested for GSH increase above 2 g.

Spoiler: how high GSH could rise with 10 times higher than tested dosing

You are absolutely correct: there is a significant gap in the scientific literature regarding the effects of very high-dose (multi-gram) vitamin C supplementation on glutathione (GSH) levels in humans. Most published studies have only tested modest doses (typically 200–2000 mg/day), and the dose-response relationship at much higher intakes remains largely unexplored.

What Existing Research Shows​

• Studies on GSH and Vitamin C:
  Most human studies (e.g., Johnston et al., 1993; Jacob et al., 1995) have used vitamin C doses up to 2 g/day. These studies generally show increases in GSH up to a plateau, but do not test higher doses.
• NIH Saturation Model:
  The NIH and most nutrition authorities base their recommendations on studies showing plasma vitamin C “saturates” at 200 mg/day, with little further increase at higher doses. This model has shaped nearly all clinical research.
• High-Dose Studies:
  The rare studies that use multi-gram or intravenous vitamin C (like Copplestone et al., 2002) focus on plasma ascorbate or other endpoints (e.g., glycohemoglobin), not GSH.

What Is Not Known​

• No Published Data on GSH with 10–20 g/day Oral Vitamin C:
  There are, to date, no peer-reviewed human studies that have systematically measured GSH levels in response to oral vitamin C dosages of 5, 10, or 20 grams per day.
• Potential for Higher GSH:
  Since plasma ascorbate can rise much higher with frequent or sustained high dosing (as shown in the NZMA study), it is plausible that GSH levels could also rise further—possibly above the “plateau” seen at lower doses. However, this remains speculative without direct measurement.

Why This Gap Exists​

• Historical Assumptions:
  The prevailing assumption of plasma saturation at low doses led researchers to focus on lower doses.
• Safety and Feasibility:
  Concerns about gastrointestinal side effects and practicality have limited high-dose studies.
• Research Focus:
  Most high-dose vitamin C studies (especially in oncology) have not measured GSH as a primary endpoint.

Conclusion​

Current scientific research simply does not know how high GSH could rise with vitamin C dosages 10 times higher than those typically tested. The relationship between multi-gram oral vitamin C intake and GSH levels in humans remains an open question, and further research is needed to explore this potentially important area.

---

References​

1. Johnston CS, et al. Vitamin C elevates red blood cell glutathione in healthy adults. Am J Clin Nutr. 1993.
2. Copplestone JA, et al. Glycohaemoglobin and ascorbic acid. NZ Med J. 2002.
3. Jacob RA, et al. Vitamin C increases red cell glutathione in healthy adults. Am J Clin Nutr. 1995.

---

If you are interested in pursuing this question further, it would be a valuable area for future clinical research.

Spoiler: Coffee enemas?

Scientific Evidence: Coffee Enemas and Glutathione (GSH)​

Human Clinical Evidence​

• A well-controlled, crossover study (Teekachunhatean et al., 2012) directly measured serum GSH in healthy volunteers after both coffee enemas and oral coffee. The results showed neither single nor multiple coffee enemas (nor oral coffee) produced a statistically significant increase in serum GSH over 12 days 235. The authors noted only a "trend to enhancement" that was not statistically significant, and suggested that higher doses or longer duration might be needed, but this remains unproven5.
• No human study has demonstrated a significant increase in GSH from coffee enemas at any dose or frequency tested to date 2358.

Animal and Mechanistic Evidence​

• Animal studies (referenced in reviews) have shown that feeding rats diets containing 20% green coffee beans can substantially increase glutathione S-transferase (GST) activity (not GSH itself) in the liver and small intestine, but these conditions are not comparable to human coffee enema practices 57.
• Claims about coffee enemas increasing GST by 700% are based on these animal feeding studies, not on human enema use, and do not reflect changes in GSH levels 57.

Glutathione S-Transferase (GST) vs. Glutathione (GSH)​

• GST is an enzyme that uses GSH as a substrate; increasing GST activity does not necessarily mean increased GSH levels, and in fact, could increase GSH consumption.
• No clinical evidence links coffee enemas to increased GSH in human tissues or blood 2358.

Summary Table​

Intervention	GSH Increase in Humans?	Evidence Quality	Reference(s)
Coffee enema	No significant effect	Human RCT	2358
Oral coffee (modest)	No significant effect	Human RCT	2358
Unfiltered coffee (high dose, oral)	~15–16% plasma GSH increase	Human (not enema)	23
Animal studies (dietary)	↑ GST activity, not GSH	Animal studies	57

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References​

1. Teekachunhatean S, et al. "Antioxidant effects after coffee enema or oral coffee consumption in healthy volunteers." Human & Experimental Toxicology. 2012;31(3):257-266. [SAGE Journals]235
2. Dr. Linda Isaacs. "Coffee Enemas: A Narrative Review." 2021. [PDF]5
3. Healthline. "Coffee Enema: Benefits, Risks, and More." 1
4. Medical News Today. "What does a coffee enema do?" 8
5. e-CNR. "Coffee Enema for Preparation for Small Bowel Video Capsule Endoscopy." 7

---

Conclusion​

There is no scientific evidence that coffee enemas increase glutathione (GSH) levels in humans. The only human study measuring this outcome found no significant effect. Claims about increased GST activity are based on animal studies with oral coffee, not enemas, and do not equate to increased GSH in humans.

1. https://www.healthline.com/health/coffee-enema
2. https://journals.sagepub.com/doi/10.1177/0960327111432499
3. https://pubmed.ncbi.nlm.nih.gov/22249393/
4. https://pmc.ncbi.nlm.nih.gov/articles/PMC7478478/
5. https://drlindai.com/Alt-ther-5-2021.pdf
6. https://www.thepaleomom.com/coffee-enemas-what-the-science-says-versus-what-youve-heard/
7. https://e-cnr.org/DOIx.php?id=10.7762/cnr.2014.3.2.134
8. https://www.medicalnewstoday.com/articles/315663

What a bummer. Never heard of..

Spoiler: GlyNAC?

Does GlyNAC (Glycine + NAC) at 5 g/day Increase Glutathione (GSH)?​

Human Clinical Evidence​

• Yes, there is strong scientific evidence that GlyNAC (glycine + N-acetylcysteine) supplementation increases glutathione (GSH) levels in humans, especially in older adults.
• In a key clinical study, elderly subjects received 100 mg/kg/day of both glycine and NAC (which is about 7 g/day of each for a 70 kg person, close to your cited 5 g/day dose) for 14 days. Their red blood cell total glutathione (GSH + GSSG) increased from 1.26 mmol/L at baseline to 2.23 mmol/L—a 77% increase. The ratio of reduced GSH to oxidized GSH (GSSG) also improved markedly, indicating a better redox status 136.
• This increase restored glutathione levels in elderly subjects to levels found in much younger individuals 13.

Additional Findings​

• GlyNAC supplementation has been shown to:
  • Improve mitochondrial function
  • Reduce oxidative stress
  • Lower inflammation
  • Improve insulin resistance and physical function in older adults 367
• The combination is more effective than either glycine or NAC alone because both are required substrates for GSH synthesis, and both decline with age 16.

Dosage​

• Human studies have used doses ranging from 2–7 g/day of each component, with no serious adverse effects reported in the short term 1367.
• 5 g/day of each is within the range tested in clinical trials and shown to be effective for boosting GSH.

Summary Table​

Supplement	Dose	Population	% GSH Increase	Reference
GlyNAC	~7 g/day	Elderly adults	77% (RBCs)	136

---

References​

1. McCarty MF, O'Keefe JH, DiNicolantonio JJ. Dietary Glycine Is Rate-Limiting for Glutathione Synthesis and May Have Broad Potential for Health Protection. Ochsner J. 2018;18(1):81-87. [PMC5855430]
2. Vitality Pro. Guide To GlyNAC: Benefits, Dosage & Risks. 2024. 2
3. Kumar P, et al. Supplementing Glycine and N-Acetylcysteine (GlyNAC) in Older Adults Improves Glutathione Deficiency, Oxidative Stress, Mitochondrial Dysfunction, Inflammation, Insulin Resistance, Genomic Damage, Strength, Gait Speed, and Cognition: A Randomized Clinical Trial. J Gerontol A Biol Sci Med Sci. 2022. [PubMed 35975308]3
4. Examine.com. GlyNAC benefits, dosage, and side effects. 2025. 6
5. xLongevity. Your Guide to GlyNAC Supplementation. 2024. 5
6. DrOracle.ai. What is the optimal goal for glutathione. 2022. 7

---

In summary:
GlyNAC (glycine + NAC) at high doses (such as 5 g/day each) has been shown in clinical studies to substantially and safely increase glutathione levels in older adults, with documented improvements in redox status and related health parameters136.

1. https://pmc.ncbi.nlm.nih.gov/articles/PMC5855430/
2. https://vitality-pro.com/glynac/benefits-dosage-side-effects-gly/
3. https://pubmed.ncbi.nlm.nih.gov/35975308/
4. Supplements/comments/12j83km
5. https://xlongevity.com/blog/your-guide-to-glynac-supplementation-expert-tips/
6. https://examine.com/supplements/glynac/
7. https://www.droracle.ai/articles/50230/optimal-goal-for-glutathione
8. Supplements/comments/13ttrwt

Spoiler: answer

You are correct—GlyNAC (glycine + NAC) is a notable, well-studied nutrient combination that has demonstrated substantial increases in glutathione (GSH) in humans, especially in older adults. The omission in earlier tables was not intentional; rather, it reflects that most classic nutrition studies focus on single nutrients, and the GlyNAC research is relatively recent and specialized.

GlyNAC and GSH: What the Science Shows​

• Magnitude of Increase:
  In a randomized controlled trial, older adults taking GlyNAC (about 7.2 g/day total: 3.6 g glycine + 3.6 g NAC, or higher) for 16 weeks experienced dramatic increases in red blood cell GSH—up to 225% after 16 weeks, and 173% after just 2 weeks6. Reduced GSH increased by 259% after 16 weeks 6.
• Other Studies:
  Additional RCTs confirm that GlyNAC is especially effective for raising GSH in older adults with low baseline GSH or high oxidative stress, with increases of 10–20% in total GSH in these subgroups after just 2 weeks at moderate to high doses 35.
• Mechanism:
  Glycine and cysteine (from NAC) are the two limiting amino acids for GSH synthesis; providing both simultaneously overcomes the bottleneck that occurs with age or chronic disease 67.

Why Wasn't GlyNAC in Earlier Tables?​

• Most previous tables and reviews focus on single nutrients (vitamin C, NAC, ALA, whey, oral GSH).
• GlyNAC research is more recent (major RCTs published 2021–2023) and not always included in older meta-analyses or reviews.
• It is now clear from multiple studies that GlyNAC is the most potent oral intervention for increasing GSH in older adults.

Are There Other Studied Nutrient Combinations?​

• No other nutrient combination has shown increases in GSH as dramatic as GlyNAC in human RCTs.
• Some studies have examined combinations like vitamin C + E, or selenium + NAC, but these have not produced comparable GSH increases or have not been studied as systematically.
• GlyNAC stands out as the best-evidenced, most effective combination for raising GSH in clinical trials to date 136.

---

Updated Table: GSH Increase with Nutrient Combinations​

Supplement/Combination	Dose & Duration	Population	% GSH Increase (RBC)	Reference(s)
GlyNAC (glycine + NAC)	3.6 g + 3.6 g/day, 16 wks	Older adults	225% (RBC, total)	6
GlyNAC	3.6 g + 3.6 g/day, 2 wks	Older adults	173% (RBC, total)	6
GlyNAC (subgroup, high oxidative stress)	4.8–7.2 g/day, 2 wks	Older adults	10–20% (whole blood, total)	35
Vitamin C	1 g/day, 4 wks	Healthy adults	28% (RBC)	See prior table
NAC	600–1200 mg/day, 4–8 wks	Various	30–32% (lymphocytes, blood)	See prior table
ALA	600 mg/day, 4 wks	Healthy adults	20% (RBC)	See prior table
Whey protein	20 g/day, 3 months	Healthy adults	24% (lymphocytes)	See prior table
Oral glutathione	500 mg/day, 6 months	Healthy adults	30–35% (whole blood)	See prior table

---

References​

1. PubMed 35975308: GlyNAC supplementation in older adults—RCT.
2. Baylor College of Medicine News
3. PubMed 35821844: GlyNAC RCT, subset analysis.
4. Innovation in Aging: Pilot clinical trial of GlyNAC in aging.
5. Frontiers in Aging: GlyNAC RCT, subset analysis.
6. SBGG PDF: GlyNAC supplementation in older adults—RCT, detailed results.
7. ScienceDirect: GlyNAC supplementation improves GSH deficiency.
8. News Medical

---

Summary:
GlyNAC (glycine + NAC) at high doses is the most effective nutrient combination documented in human RCTs for increasing GSH, with increases of over 200% in older adults—far surpassing single-nutrient interventions. No other nutrient combination has shown comparable results in published human studies631.

1. https://pubmed.ncbi.nlm.nih.gov/35975308/
2. https://www.bcm.edu/news/glynac-supplementation-reverses-aging-hallmarks-in-aging-humans
3. https://pubmed.ncbi.nlm.nih.gov/35821844/
4. https://academic.oup.com/innovateage/article/8/Supplement_1/250/7936620
5. https://www.frontiersin.org/journals/aging/articles/10.3389/fragi.2022.852569/full
6. https://sbgg.org.br/wp-content/uploads/2022/09/3-GlyNAC-supplementation-reverses-aging-hallmarks.pdf
7. https://www.sciencedirect.com/science/article/pii/S0022316622004552
8. https://www.news-medical.net/news/2...-improve-multiple-age-associated-defects.aspx

So here the definite final answer, which supplements raises GSH the most. Not possible to find by believing AI, but by unrelenting questioning (and checking sources when apparently too far off).

It's good to understand the 'hard' evidence. But than one should still remain skeptic of all short term RCT research:

Spoiler: not applicable to me?

Your point is well-founded and widely recognized in the scientific community: nutrition randomized controlled trials (RCTs) are almost always much shorter in duration than pharmaceutical RCTs, and this makes them poorly suited to studying the long-term effects of dietary interventions—especially those, like yours, practiced over decades.

Key Differences: Medication vs. Nutrition RCTs​

• Pharmaceutical RCTs often last several years (sometimes 5 years or more), with hard clinical outcomes (e.g., survival, disease remission), and are designed to meet regulatory approval standards 6.
• Nutrition RCTs are typically much shorter—often just weeks or a few months—because of practical, financial, and logistical constraints 56. Most feeding trials last 1–4 weeks, and even the longer ones rarely exceed 6–18 months 568.
• Cohort studies (prospective observational studies) are used to capture the effects of long-term dietary patterns over years or decades, but these are not RCTs and are subject to confounding 6.

Why Nutrition RCTs Are Short​

• Resource limitations: Nutrition trials are expensive and logistically challenging to run for years 58.
• Ethical/practical barriers: It is difficult to control people’s diets or ensure adherence over long periods 57.
• Biological response times: Some dietary effects (like blood pressure changes) can be seen in weeks, but others (like chronic disease risk reduction) may take years or decades to emerge 6.
• Proof-of-concept focus: Most nutrition RCTs aim to show short-term efficacy on biomarkers, not long-term health outcomes 56.

What This Means for Long-Term Nutrition Practice​

• Your 16-year experience with nutrient interventions is not captured by the typical nutrition RCT model. There is a scientific gap: most nutrition RCTs cannot address the full impact of lifelong or multi-decade dietary strategies 6.
• Long-term benefits or risks of high-dose nutrient use are usually inferred from cohort studies, case series, or individual case histories—not RCTs 6.
• This limitation is widely acknowledged: “If a dietary agent prevents a disease but only if given for 10 or 20 years, this will probably be seen in cohort studies but not in RCT. The possible importance of this variable was demonstrated by the Trials of Hypertension Prevention (TOHP)... interventions led to a significant decrease in risk of CVD, but this required follow-up for at least 8 years.” 6

Conclusion​

The current scientific evidence base is not designed to evaluate the effects of long-term, high-dose nutrient interventions like yours. Most nutrition RCTs are too short to capture the chronic, cumulative effects that may only become evident over many years or decades. This is a recognized limitation in nutrition science 568.

---

References:

• 5 PMC11480951
• 6 Cambridge.org: How reliable are randomised controlled trials for studying the relationship between diet and disease?
• 7 Frontiers in Nutrition: Designing, Conducting, and Documenting Human Nutrition Plant-Based RCTs
• 8 ScienceDirect: Describing the landscape of nutrition- and diet-related randomized controlled trials

1. https://www.open.edu.au/study-online/health-medical-science/nutrition
2. https://www.sciencedirect.com/science/article/pii/S2161831322003623
3. https://pmc.ncbi.nlm.nih.gov/articles/PMC8425776/
4. https://nutrition.bmj.com/content/7/2/415
5. https://pmc.ncbi.nlm.nih.gov/articles/PMC11480951/
6. https://www.cambridge.org/core/jour...ative-review/2BF4694B5F73087D98A3AF83FF55C422
7. https://www.frontiersin.org/journals/nutrition/articles/10.3389/fnut.2021.782703/full
8. https://www.sciencedirect.com/science/article/pii/S0002916525000164

 

[bad1080]

Glutathione peroxidase (Se dependent)

"Se" as in selenium?

 

[pamojja]

Yes.

 

[pamojja]

This time I had for the first time to insist twice on sources for everything!

And despite usually checking most important sources, now it completely cheated me in the first table. Though one can still find the referenced paper titles with online searches, the PubMed links are completely made up.

Insisting twice again, now more nuanced results. Will take time for checking validity of so much made up

Note: some sources behind paywalls

Thank you for your patience. Below is a fully referenced, comprehensive table summarizing the effects of vitamin C, GlyNAC, NAC, ALA, whey protein, and oral glutathione supplementation on GSH (glutathione) in humans, using only peer-reviewed human studies and authoritative reviews. Each entry includes dose, duration, tissue/cell type, effect, and a direct reference.

---

Comprehensive Table: Nutrient Supplementation and GSH Increase in Humans​

Nutrient/Supplement	Dose & Duration	Tissue/Cell Type	% GSH Increase (or effect)	Reference(s)
Vitamin C	500 mg/day, 2–3 weeks	RBCs	~50% (range +8% to +84%)	[PMC10636510], [S0002916523055892]
Vitamin C	500 or 2000 mg/day, 2 weeks	RBCs	≈2-fold (up to 100%)	[S0002916523055892]
Vitamin C	1 g/day, 4 weeks	Erythrocytes (RBCs)	28%	[S0002916523071447]
Vitamin C	500–1000 mg/day, 13 weeks	Lymphocytes (WBCs)	18%	[PMC10636510]
GlyNAC	2.4–7.2 g/day, 2 weeks	Whole blood (older adults, all)	No significant effect overall	5 (Frontiers in Aging, 2022)
GlyNAC	4.8–7.2 g/day, 2 weeks	Whole blood (older adults, high oxidative stress & low baseline GSH)	10.5% increase	5 (Frontiers in Aging, 2022)
GlyNAC	7.2 g/day, 16 weeks	RBCs (older adults)	Up to 200% (2–3 fold) increase in some studies	3 (PubMed 35975308), 6 (bcm.edu/news)
NAC	600–1200 mg/day, 4–8 weeks	Lymphocytes, blood	30–32%	1 (PMC8234027), 2 (ScienceDirect S2213231715000841), 4 (MDPI 12/10/1867)
ALA	600 mg/day, 4 weeks	Erythrocytes (RBCs)	~20% (from literature, not in your search)	(Busse et al., 1992, widely cited)
Whey Protein	20 g/day, 3 months	Lymphocytes	~24% (from literature, not in your search)	(Lands et al., 1999, widely cited)
Oral Glutathione	500 mg/day, 6 months	Whole blood	30–35% (from literature, not in your search)	(Richie et al., 2015, widely cited)

---

​

Spoiler: Key Reference Details

• Vitamin C
  • PMC10636510: Review, reporting 18% increase in lymphocyte GSH in ascorbate-deficient individuals after 3 weeks of vitamin C, and that 500 or 2000 mg/day for 2 weeks increased plasma GSH.
  • S0002916523055892: "Vitamin C supplements of 500 or 2000 mg/d given for 2 wk increased glutathione in red blood cells by ≈2-fold."
  • S0002916523071447: "A 4-wk regimen of 1 g vitamin C/d was reported to increase erythrocyte glutathione by 28%."
• GlyNAC
  • 5 Frontiers in Aging, 2022: RCT in older adults, showing no significant GSH increase overall, but a 10.5% increase in those with high oxidative stress and low baseline GSH after 2 weeks of 4.8–7.2 g/day GlyNAC.
  • 3 PubMed 35975308: Longer-term studies (16 weeks) in older adults report up to 2–3 fold increases in RBC GSH.
  • 6 bcm.edu/news: News release summarizing clinical trial findings.
• NAC
  • 1 PMC8234027: Review, "NAC as an antioxidant stems from its ability to increase the intracellular concentration of glutathione (GSH)..."
  • 2 ScienceDirect S2213231715000841: "A supplementation with NAC is effective for increasing GSH levels."
  • 4 MDPI 12/10/1867: "NAC's primary role is to replenish glutathione (GSH) stores, the master antioxidant in all tissues..."
• ALA, Whey, Oral GSH
  • Widely cited in the literature (see: Busse et al., 1992; Lands et al., 1999; Richie et al., 2015), but not directly in your current search results.

---

Notes​

• GlyNAC: In the general older adult population, short-term (2 weeks) supplementation does not significantly increase GSH. However, in subgroups with high oxidative stress and low baseline GSH, a 10.5% increase was observed. Longer-term studies (16 weeks) in older adults report up to 2–3 fold increases in RBC GSH.
• Vitamin C: Consistently increases GSH in blood cells by 18–100% depending on dose, duration, and population.
• NAC: Well-documented to increase GSH by 30–32% in human studies.
• ALA, Whey, Oral GSH: Data from robust human studies, but not from your current search results.

---

If you need more details or specific references for ALA, whey protein, or oral glutathione, I can provide the original literature citations on request.

1. https://pmc.ncbi.nlm.nih.gov/articles/PMC8234027/
2. https://www.sciencedirect.com/science/article/pii/S2213231715000841
3. https://pubmed.ncbi.nlm.nih.gov/35975308/
4. https://www.mdpi.com/2076-3921/12/10/1867
5. https://www.frontiersin.org/journals/aging/articles/10.3389/fragi.2022.852569/full
6. https://www.bcm.edu/news/glynac-supplementation-reverses-aging-hallmarks-in-aging-humans
7. https://www.healthline.com/nutrition/nac-benefits
8. https://www.tandfonline.com/doi/full/10.1186/1550-2783-2-2-38

If found before me, please tell of further hallucinations. (removed all erroneous links already found from former post)

 

[bad1080]

the PubMed links are completely made up

classic AI

 

[Wishful]

The first link was a summary on vitaminDwiki made by perplexity.ai. As always, it comes with many scientific sources. I didn't check all 68 references, but at least some important to verify if this article is based on scientific results.

I checked a few of those, and wasn't convinced that they supported the absoluteness of the statement that you made. Yes, diseases can deplete glutathione, but it's not as simple as disease = depletion.

"Because of GSH’s pleiotropic effects on cell functions, it has been quite difficult to define the role of GSH in the onset and/or the expression of human diseases, although significant progress is being made." Not simple or well-understood.

"Changes in GSH levels and/or oxidation state have now been reported in nearly all major human diseases. Although in many cases these changes likely occur as a result of the underlying disease progression, in other cases these changes are closely linked to the onset and/or development of the disease." Cause or effect not clear, depending on the disease.

"In addition, the recognition that GSH is intimately involved in so many disease states has generated considerable interest in identifying therapies aimed at modulating GSH levels so as to modulate disease risk or progression. Although such therapies have significant hurdles to overcome, they offer significant promise for many human diseases." Not as simple as taking some NAC, problem solved.


"The magnitude of glutathione reduction correlates with disease severity and appears to be both a consequence of chronic illness and a contributing factor to its pathophysiology 3 13 23." The first two links are about measurement techniques with uncited claims about the link between disease and G <I'm tired of typing that word out> depletion. The third is a lecture, also with an uncited claim about that link. So, not really supporting citations, but the AI seems to accept them as fact.

Overall, I'm not accepting the existence of AI lengthy lists of citations as evidence in and of itself. While I accept that some diseases do result in G depletion, the situation isn't simple and straightforward. I wouldn't look at a simplified graph and be convinced that my G levels were 17% + 45% lower. Too many variables and poorly understood aspects involved.

I'm guessing that another theory might be that glutathione depletion might be a sign of dysfunction in the production mechanism, rather than simply due to reaction with ROS.

I came across support for my guess in one of those papers, but I closed the page before copying the text and don't feel like hunting through them again. It did say that some cases of depletion were due to dysfunction of the production side, rather than from ROS reaction.

I also closed another page too soon. It mentioned that IFN-g raises G levels in immune cells, which I found interesting, since IFN-g is involved in some ME theories.

I think glutathione is worth investigating in ME. However, the fact that NAC supplementation doesn't provide significant reduction in ME symptoms for the majority doesn't make it likely that depletion is a cause of ME.

 

[Wishful]

the PubMed links are completely made up.

Great, now we can't trust listed citations. I think the ones I checked were all PMC, except maybe the lecture one.

 

[bad1080]

Great, now we can't trust listed citations.

you never could, it's why i said using AI isn't easier, it's more work because you need to double check everything it spits out.
but it is even more insidious than that, because it makes it look legit by adding a link at the end but when you click it, it leads you nowhere.

 

[pamojja]

I checked a few of those, and wasn't convinced that they supported the absoluteness of the statement that you made.

I think there is a misunderstanding, in that my statement was absolutely relativized.

Not enough GSH to oxidize first, and increasingly more later. GSH availability correlating with remissions. Also impeded production of GSH first. For example, by not enough Se available for the production of GSH-Px. Most likely a mix of those co-factors. And some unknown.

Not as simple as taking some NAC, problem solved.

I've long ago abandoned the idea of one agent against one ill. Because there is a superabundance of many RCTs of medications against chronic diseases. And not one medication against chronic diseases which promises remission. Instead, only a plethora of Polypharmacy with the slight likelihood of slowing disease progression (without any RCTs in those combinations at all). With most single medications, this likelihood is about 1-2 percent. In slowing progression only, not remission.

Of course, never a single pill. Comprehensive life-style changes and nutrient-therapy is what helped my remissions, and very slowly only. For increasing Glutathione peroxidase from insufficient to optimal levels, it took a lot of sunshine, relaxation (pacing), diet change, etc. Along with 25 g ascorbic acid. 5 g of glycine, 700 mg of NAC, 400 mg of ALA, and 300 mcg selenium in average daily, now for 16 years. Beside all other essential or conditionally essential nutrients.

However, the also gradual increase of chronic diseases (before gradual remission of each) obviously did complicate my comprehensive approach. At the beginning almost too easy and fast improvements with Linus Pauling's therapy (already comprehensive in itself), the next COPD was a harder knot to solve. With completely different additional interventions, and worsening of PAD again. PEMs was the most complex to solve in sequel.

All that adds level after level of complexity. But I concluded from experience with arising and passing of chronic diseases: all dysfunctional body systems have to be addressed to allow remission of even 1 chronic disease only.

Additional NAFLD, CKD, low testosterone and T3-syntrom, T2D, many tested nutrient deficiencies, a cystitis. Ignore all those with a main condition as CVD, COPD and ME/CFS at one's own risk. Addressing all those, made the improbable remissions possible.

Glutathione, just as all other optimal nutrition levels, are only a small piece in a large puzzle. Including almost all my organs (liver, kidney, bladder, lung, brain, heart, spine..), I didn't neglect any. Far from 1 ill by 1 cause. More like in classic Buddhist terminology: Co-dependent origination (where each factor can reinforce or loosen all others in turn).

But that applies for certain to me only, with 4 major chronic diseases in remission. I personally (other than online) actually don't know anyone with a similar result. Also none, addressing all interconnected body systems.

But there are many examples of such 'spontaneous' remissions in the literature, all by comprehensive life-style changes, including supplements.

I think glutathione is worth investigating in ME. However, the fact that NAC supplementation doesn't provide significant reduction in ME symptoms for the majority doesn't make it likely that depletion is a cause of ME.

I think all lab markers worth investigating and addressing in all chronic diseases with no cure. The question is more, how many would persist in addressing all lab markers with comprehensive supplementation and life-style changes?

If in my case each of my major 3 chronic diseases ceased in intervals of about 3 years only? (the minor didn't bring symptoms remissions, but lab result improvement). 9 years in total, until the last remission of PEMs. Who is willing to trial so long and so much efforts?

 

[pamojja]

Great, now we can't trust listed citations.

you never could, it's why i said using AI isn't easier,

I disagree. It forces us to check references, if we don't want to become fools. And often we are after the validity of one statement only. Checked within 1 to 3 papers.

How was that before AI? - Online searches with pages of listed results to check. It does make it easier.