If glutathione supplements are so bad for B12 deficiency cases, why does Liposomal Glutathione help me so much momentarily?

[godlovesatrier]

I've been taking it for years I get way more benefit from it than I do b12 and zero brainfog.

 

[Nosferatu80]

I've been taking it for years I get way more benefit from it than I do b12 and zero brainfog.

Liposomal or common glutathione? Do you stack with other vitamins?

 

[ironlion37]

I'll just throw in my two cents. I take liposomal glutathione and notice it has a significant effect on B12 delivery. I read somewhere that glutathione is critical for the transport and delivery of B12 in the body.

 

[Nosferatu80]

I'll just throw in my two cents. I take liposomal glutathione and notice it has a significant effect on B12 delivery. I read somewhere that glutathione is critical for the transport and delivery of B12 in the body.

Sad not being able to get my hands on liposomal glutathione here in Brazil, I only have access to common and reduced. What are your daily doses? Take them together?

 

[ironlion37]

Sad not being able to get my hands on liposomal glutathione here in Brazil, I only have access to common and reduced. What are your daily doses? Take them together?

Hi, I take the liposomal glutathione product from this company: https://www.quicksilverscientific.com/
You could ask them if they will ship to Brazil with a cold pack, though maybe it's too far. You could ask them though. I take two squirts from the bottle a day (recommended dose). I don't have to do it every day but I notice things are generally better when I'm including it.

I'm currently stuck regarding B12, trying to find a new, good source. 4mg methylcobalamin powder in 1ml saline intramuscular injection every 48 hours is what gives me 100% health. At least it did, until the place I ordered from switched suppliers.

I've ordered the B12 oils from Australia as I've seem them mentioned on this forum and hope they will work for me. Waiting for them to arrive. I also just had a doctor recommend liposomal B12 which I've never tried, so I'm going to order that shortly.

 

[GreenEdge]

Sad not being able to get my hands on liposomal glutathione here in Brazil, I only have access to common and reduced. What are your daily doses? Take them together?

I get all my hard to get special supplements from iherb.com - I'm pretty sure they deliver to most countries including Brazil. They deliver to Australia.

 

[Nosferatu80]

In recent years many sites are having problems delivering to Brazil because of our post office and customs, many products are lost when they arrive on brazilian soil and this has made many sites stop selling, iherb still sells but I read many reports of lost purchases...from 2017 to 2020 I lost several orders from vitacost, evitamins and luckyvitamins and the few that arrived were taxed up to 60%, lol.

 

[JasonPerth]

I personally have no benifit from Liposomal Glutathione- or any supplements tbh. Some do say it can relieve brain fog symptoms in particular which can be confused with fatigue sometimes. However not me

 

[Algo]

It appears the answer is that Glutathione protects vitamin B12 from depletion by xenobiotics and superoxide.

Superoxide is implicated in the pathophysiology of many inflammatory diseases, whereas vitamin B(12) derivatives are often beneficial in their treatment. We found that cob(II)alamin reacts with superoxide at rates approaching those of superoxide dismutase itself, suggesting a probable mechanism by which vitamin B(12) protects against chronic inflammation and modulates redox homeostasis. https://pubmed.ncbi.nlm.nih.gov/19799418/

the normal plasma and serum concentrations of cobalamins in humans are in the few hundreds picomolar range, which are orders of magnitude lower than concentrations for GSH (low millimolar range). Hence, although cobalamin could act as a scavenger of electrophilic xenobiotics, Cbl(I) could more likely be vulnerable to depletion by alkylation leading to its deficiency in an analogous manner to that caused by the anesthetic nitrous oxide. In addition, we also investigated possible interaction and synergies between vitamin B12 and GSH and made the intriguing discovery that glutathione can prevent the formation and reaction of the Cbl(I) form of vitamin B12 with xenobiotics, such as those formed in the mammalian metabolism of the industrial chemicals styrene (1), chloroprene (2), and 1,3-butadiene https://pubs.acs.org/doi/10.1021/tx0497898

This explains why, prior to finally being rescued by B12 injections 9 months later, my wife almost died after chlorine dioxide. It also explains why glutathione in very high daily doses kept her afloat. In its frailty B12 is amazingly versatile. Given it’s non toxic, is there any real reason for Doctors not to trial everyone with copious amounts by IV?

 

[Algo]

Hi, I take the liposomal glutathione product from this company: https://www.quicksilverscientific.com/
You could ask them if they will ship to Brazil with a cold pack, though maybe it's too far. You could ask them though. I take two squirts from the bottle a day (recommended dose). I don't have to do it every day but I notice things are generally better when I'm including it.

I'm currently stuck regarding B12, trying to find a new, good source. 4mg methylcobalamin powder in 1ml saline intramuscular injection every 48 hours is what gives me 100% health. At least it did, until the place I ordered from switched suppliers.

I've ordered the B12 oils from Australia as I've seem them mentioned on this forum and hope they will work for me. Waiting for them to arrive. I also just had a doctor recommend liposomal B12 which I've never tried, so I'm going to order that shortly.

Will you post in this thread if they work as good as the injections?

My wife is currently taking 1500mcg of hydroxycobalamin 3 subcutaneous injections a day (total: 4500 mcg per day). She also takes a very high dose of NAC and 12 squirts of quicksilver lipossomal glutathione.

I’ve been considering ordering methylcobalamin and adenosylcobalamin injections from Germany once the weather here becomes colder again. Currently too warm to order injectables. Or, if I’ll go the B12 oils route instead.

 

[Algo]

I personally have no benifit from Liposomal Glutathione- or any supplements tbh. Some do say it can relieve brain fog symptoms in particular which can be confused with fatigue sometimes. However not me

Chances are there’s another key aspect of your metabolism that is not being addressed. Like a severe key nutrient deficiency requiring high doses to get the gears moving again. You can get precious information from both the things you don’t react to, and the things you react badly to.

What’s your main symptom?

 

[datadragon]

My wife is currently taking 1500mcg of hydroxycobalamin 3 subcutaneous injections a day (total: 4500 mcg per day). She also takes a very high dose of NAC and 12 squirts of quicksilver lipossomal glutathione.

Hydroxocobalamin is not the same, it has different effects than Methylcobalamin and adenosylcobalamin so keep that in mind. Hydroxocobalamin (OH-Cbl), cobinamide, and dicyanocobinamide (CN(2)-Cbi) potently inhibited all Nitric Oxide isoforms NOS1, NOS2, and NOS3, whereas cyanocobalamin, methylcobalamin, and adenosylcobalamin had much less effect. https://pubmed.ncbi.nlm.nih.gov/19328848/ The extracellular NO scavenger hydroxocobalamin prevented the NMDA-induced release of glutamate providing indirect evidence that the effect of NO may act on the NMDA receptor. These results suggest that low concentration of NO has a role in maintaining the NMDA receptor activation in a cGMP-independent manner. https://link.springer.com/article/10.1007/BF02976435 NAC is also having an effect on glutamate.

This explains why, prior to finally being rescued by B12 injections 9 months later, my wife almost died after chlorine dioxide. It also explains why glutathione in very high daily doses kept her afloat. In its frailty B12 is amazingly versatile. Given it’s non toxic, is there any real reason for Doctors not to trial everyone with copious amounts by IV?

Yes B12 has that useful feature "cob(II)alamin reacts with superoxide at rates approaching those of superoxide dismutase itself, suggesting a probable mechanism by which vitamin B(12) protects against chronic inflammation and modulates redox homeostasis." However there are genetic differences among the population In B12 and its well known some people dont do well with methylcobalamin. Part of the reason seems to be how your body manages inflammation balance (as it lowers homocysteine which activates NLRP3 inflammasome) as well as how it manages methylation balance. When genetics are modified among these areas its for a reason and most with them dont do well bypassing the mutations to make those pathways work more efficiently since your body may have other ways to balance it elsewhere.

 

[Algo]

Hydroxocobalamin is not the same, it has different effects than Methylcobalamin and adenosylcobalamin so keep that in mind. Hydroxocobalamin (OH-Cbl), cobinamide, and dicyanocobinamide (CN(2)-Cbi) potently inhibited all Nitric Oxide isoforms NOS1, NOS2, and NOS3, whereas cyanocobalamin, methylcobalamin, and adenosylcobalamin had much less effect. https://pubmed.ncbi.nlm.nih.gov/19328848/ The extracellular NO scavenger hydroxocobalamin prevented the NMDA-induced release of glutamate providing indirect evidence that the effect of NO may act on the NMDA receptor. These results suggest that low concentration of NO has a role in maintaining the NMDA receptor activation in a cGMP-independent manner. https://link.springer.com/article/10.1007/BF02976435 NAC is also having an effect on glutamate.



Yes B12 has that useful feature "cob(II)alamin reacts with superoxide at rates approaching those of superoxide dismutase itself, suggesting a probable mechanism by which vitamin B(12) protects against chronic inflammation and modulates redox homeostasis." However there are genetic differences among the population In B12 and its well known some people dont do well with methylcobalamin. Part of the reason seems to be how your body manages inflammation balance (as it lowers homocysteine which activates NLRP3 inflammasome) as well as how it manages methylation balance. When genetics are modified among these areas its for a reason and most with them dont do well bypassing the mutations to make those pathways work more efficiently since your body may have other ways to balance it elsewhere.

Does this mean that hydroxycobalamin is specially useful in blocking NMDA receptor activity, or is it the other way around? I’m asking because she has central sensitization on her feet (official diagnosis: complex regional pain syndrome) and one of the purposed root causes is too much NMDA activation. They even use quasi ketamine coma as a therapy.

Personally we have used agmatine, but it had no clear effect on her pain.

 

[datadragon]

Does this mean that hydroxycobalamin is specially useful in blocking NMDA receptor activity, or is it the other way around? I’m asking because she has central sensitization on her feet (official diagnosis: complex regional pain syndrome) and one of the purposed root causes is too much NMDA activation. They even use quasi ketamine coma as a therapy.

It appears from the below that hydroxocobalamin may be useful in preventing NMDA receptor induced release of glutamate through its Nitric Oxide lowering effect. Does it help on its own without taking the other things at the same time? Many things can lead to an increase of Glutamate.

The extracellular NO scavenger hydroxocobalamin prevented the NMDA-induced release of glutamate providing indirect evidence that the effect of NO may act on the NMDA receptor. These results suggest that low concentration of NO has a role in maintaining the NMDA receptor activation in a cGMP-independent manner. In primary cultures of rat cerebellar granule cells, the glutamate receptor agonist N-methyl-D-aspartate (NMDA) stimulates the elevation of intracellular calcium concentration ([Ca2+]i), the release of glutamate, the synthesis of NO and an increase of cGMP.

palmitoylethanolamide which is available over the counter also inhibited the Ca2+-dependent release of glutamate https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4394492/

Palmitoylethanolamide which is one thing that activates PPAR-a was used successfully for chronic and neuropathic pain and inflammation, as demonstrated in clinical trials (and further may have benefits with ME/CFS). These include peripheral neuropathies such as diabetic neuropathy, chemotherapy-induced peripheral neuropathy, carpal tunnel syndrome, sciatic pain, osteoarthritis, low-back pain, failed back surgery syndrome, dental pains, neuropathic pain in stroke and multiple sclerosis, chronic pelvic pain, postherpetic neuralgia, and vaginal pains. https://pubmed.ncbi.nlm.nih.gov/23166447/

Life extension mentioned it also as safer pain alternative https://www.lifeextension.com/magazine/2019/3/turn-off-the-pain-signal https://www.lifeextension.com/magazine/2022/9/turn-off-pain-signals

Functional and biochemical interaction between PPARα receptors and TRPV1 channels: Potential role in PPARα agonists-mediated analgesia. Collectively, these results provide evidence for a PPARα-mediated pathway triggering TRPV1 channel activation and desensitization, and highlight a novel mechanism which might contribute to the analgesic effects shown by PPARα agonists in vivo. https://pubmed.ncbi.nlm.nih.gov/25014183/ administration of PPAR ligands reduces inflammatory pain and neuropathic pain. https://pubmed.ncbi.nlm.nih.gov/19607969/

TRPV1 channels and the progesterone receptor Sig-1R interact to regulate pain. Here we show that TRPV1 physically interacts with the Sigma 1 Receptor (Sig-1R), a chaperone that binds progesterone, an antagonist of Sig-1R and an important neurosteroid associated to the modulation of pain. Antagonism of Sig-1R by progesterone results in the down-regulation of TRPV1 expression in the plasma membrane of sensory neurons and, consequently, a decrease in capsaicin-induced nociceptive responses. This is observed both in males treated with a synthetic antagonist of Sig-1R and in pregnant females where progesterone levels are elevated. https://www.pnas.org/doi/10.1073/pnas.1715972115

CB1-cannabinoid-, TRPV1-vanilloid- and NMDA-glutamatergic-receptor-signalling systems interact in the prelimbic cerebral cortex to control neuropathic pain symptoms https://www.sciencedirect.com/science/article/abs/pii/S0361923020306353

 

[JasonPerth]

Chances are there’s another key aspect of your metabolism that is not being addressed. Like a severe key nutrient deficiency requiring high doses to get the gears moving again. You can get precious information from both the things you don’t react to, and the things you react badly to.

What’s your main symptom?

Fatigue
Weakness
Brainfog
Stomach inflammation
Joints clicking

 

[Violeta]

If you type those symptoms into Google or an AI diagnostic bot, I reckon you'd find dozens of diseases that include those four symptoms. They are all for example typical symptoms that ME/CFS patients struggle with as well.

Yep, I reckon a few persons here reported their symptoms were helped by high-dose thiamine, but they were not cured either, which they should be if it was merely thiamine deficiency.

The reason high-dose thiamine improves fatigue in ME/CFS has unlikely much to do with clinical or any sort of thiamine deficiency, but rather that high dose thiamine provides a co-factor in various metabolic pathways that are speculated to be dysregulated in ME/CFS.

Thiamine is for example a cofactor needed by the enzyme pyruvate dehydrogenase, which is essential in energy metabolism. Pyruvate dehydrogenase is impaired in ME/CFS if we believe the findings of Norwegian ME/CFS researchers Fluge and Mella. The reason is not thiamine deficiency, but rather likely immune mediated.

But let's say an ME/CFS patient takes high-dose thiamine, it may help to allow the pathways involving pyruvate dehydrogenase to function closer to normal at least temporarily, so the result would be improvement in symptoms from thiamine that was unrelated to any clinical thiamine deficiency.

From Fluge and Mella

Pathomechanisms and possible interventions in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)​

https://www.jci.org/articles/view/150377

Several studies have reported metabolic changes in ME/CFS patients, e.g., A. Germain et al. (19) and Ø. Fluge et al. (20). The results suggest altered utilization of substrates for energy metabolism, such as increased use of amino acids and fatty acids for tricarboxylic acid cycle (TCA) fueling, with reduced glucose and pyruvate oxidation. Impaired pyruvate dehydrogenase (PDH) function due to increased expression of PDH kinases (PDKs) (20) may indicate chronic activation of physiological metabolic programs that normally protect cellular energy (ATP) supply under demanding conditions, such as endurance exercise, hypoxia, or starvation. Metabolic adaptations, aiming to maintain and restore energy supply, may be caused by an underlying tissue hypoxia on exertion in ME/CFS. This restriction will compromise homeostasis and promote energy strain and corresponding metabolic responses.

 

[Violeta]

In a study using inducible and reversible SOD2 knockdown in mouse skeletal muscle, researchers found that elevated matrix superoxide reversibly impairs mitochondrial substrate flexibility, specifically impairing pyruvate oxidation. This impairment is characterized by reduced metabolic flexibility, particularly when other substrates are present.

Here's a more detailed explanation:

• SOD2 and its role:
  SOD2, or mitochondrial superoxide dismutase, is an antioxidant protein that protects cells against mitochondrial superoxide.
  
  
• Study Model:
  The researchers used a model where SOD2 expression in skeletal muscle was knocked down and then allowed to recover. This was achieved using RNA interference to silence the SOD2 mRNA.
  
  
• Key Findings:
  • SOD2 knockdown led to impaired pyruvate-driven respiration in permeabilized muscle fibers, especially when other respiratory substrates were present.
    
    
  • The SOD2 knockdown also resulted in elevated reactive oxygen species (ROS) production and impaired mitochondrial aconitase activity.
    
    
  • Interestingly, the bioenergetic changes in mitochondria were reversible with SOD2 protein recovery, suggesting that increased superoxide levels are sufficient to drive changes in mitochondrial energetics.

 

[godlovesatrier]

It's the phosphydyleserine that you're getting the benefit from. Phospholipids used to make me really high and eradicated my brainfog. These days I have long covid that doesn't work but it used to. I also took the same liposomal glutathione product as you did.

So that is highly likely to be what is giving you a boost, it did for me for years. Any product with phospholipids in it had this effect, products without did not. Also there was a dr I forget his name who created a product marketed to ME that had an effect on lipids and had the same ingredient. That stuff makes me really hyper but also gives me a lot of energy. I am afraid I am struggling to remember the name of it though. That happens after nearly ten years of ME i think!

Thank god for AI models:

"Product Overview

• Name: NT Factor® (also included in products like NT Factor Energy, ATP Fuel, and ATP Fuel 360 by Researched Nutritionals)3.
• Key Ingredient: A proprietary blend of phospholipids, including phosphatidylcholine, designed to repair cell membranes and mitochondrial coverings35.
• Mechanism: NT Factor® works through Lipid Replacement Therapy® (LRT®) or Membrane Replacement Therapy (MRT). It restores damaged cell and mitochondrial membranes, improving energy production by enhancing mitochondrial function135."

"

Clinical Use​

• Benefits:
  • Reduces fatigue by up to 40% within 8 weeks of use3.
  • Improves mitochondrial function, which is critical for energy generation13.
  • Repairs oxidative damage caused by immune reactions in conditions like ME/CFS3.
• Research: Supported by clinical trials and studies showing significant improvements in fatigue, mood, and cellular function12.

Key Contributors​

• Dr. Rita Ellithorpe and Prof. Garth Nicolson are notable researchers involved in the development and clinical validation of NT Factor® for fatigue-related conditions2."

So yeah that was what I was trying to remember. In my case it just caused crashes and wasn't supportive enough, "dirty" energy as I call it!

 

[LINE]

In a study using inducible and reversible SOD2 knockdown in mouse skeletal muscle, researchers found that elevated matrix superoxide reversibly impairs mitochondrial substrate flexibility, specifically impairing pyruvate oxidation. This impairment is characterized by reduced metabolic flexibility, particularly when other substrates are present.

Here's a more detailed explanation:

• SOD2 and its role:
  SOD2, or mitochondrial superoxide dismutase, is an antioxidant protein that protects cells against mitochondrial superoxide.
  
  
• Study Model:
  The researchers used a model where SOD2 expression in skeletal muscle was knocked down and then allowed to recover. This was achieved using RNA interference to silence the SOD2 mRNA.
  
  
• Key Findings:
  • SOD2 knockdown led to impaired pyruvate-driven respiration in permeabilized muscle fibers, especially when other respiratory substrates were present.
    
    
  • The SOD2 knockdown also resulted in elevated reactive oxygen species (ROS) production and impaired mitochondrial aconitase activity.
    
    
  • Interestingly, the bioenergetic changes in mitochondria were reversible with SOD2 protein recovery, suggesting that increased superoxide levels are sufficient to drive changes in mitochondrial energetics.

Superoxide dismutase is the chemical the body is supposed to produce to reduce Superoxides. Superoxides are free radicals (specific free radicals) that impair the mitochondria chain as @Violeta suggests. SOD is a close cousin to glutathione and catalase.

I have supplemented with SOD from Solaray and it provides a subtle help. I also use catalase from SuperSmart. Both are enteric coated which enables the molecules to pass through the stomach acids (which destroy both SOD, catalase and glutathione (this is why lipo glutathione works btw).

 

[LINE]

Keep in mind that the antioxidant system is a big loop and by this, I mean that they tend to operate as a coordinated system, e.g. vitamin C will help support glutathione levels (keep them from falling) or you could make a statement that vitamin E will help support vitamin c levels and so on.

And of course, vitamin co-factors, minerals and amino acids also participate in this process as well. Oops, I should not leave out the essential fatty acids.