Low glutathione causes mitochondrial dysfunction...

Discussion in 'Fibromyalgia Main Forum' started by ljimbo42, Jul 15, 2014.

  1. ljimbo42

    ljimbo42 Active Member

    Here are 3 studies showing that low glutathione levels cause mitochondrial dysfunction, AND MUCH MORE! Also I have a link here to a forth study, that is posted here at Prohealth, that shows the amount of fatigue in CFS, is directly related to the amount of mitochondrial dysfunction and vise versa. The first study says, "Our data suggest that depletion of mitochondrial glutathione leads to mitochondrial dysfunction and apoptosis (cell death)."

    The second study says, "Among the arsenal of antioxidants and detoxifying enzymes existing in mitochondria, mitochondrial glutathione emerges as the main line of defense for the maintenance of the appropriate mitochondrial redox environment to avoid or repair oxidative modifications leading to mitochondrial dysfunction and cell death."

    The third study says, "Glutathione depletion and concomitant increase in oxidative and nitrosative stress and mitochondrial dysfunctions play a role in the pathophysiology of diverse neuroimmune disorders, including depression, myalgic encephalomyelitis/chronic fatigue syndrome and Parkinson's disease, suggesting that depleted glutathione is an integral part of these diseases."

    The third study also says "Adequate levels of glutathione are essential for the optimal functioning of the immune system in general and T cell activation and differentiation in particular" and "Depletion of glutathione levels leads to exacerbation of damage by oxidative and nitrosative stress, hypernitrosylation, increased levels of proinflammatory mediators and inflammatory potential, dysfunctions of intracellular signaling networks, nuclear factor-kb, and Janus kinases, decreased cell proliferation and DNA synthesis."

    So to sum this up, these studies say that low glutathione causes immune system dysfunction, increased inflammation, mitochondrial dysfunction, early cell death, and decreased cell proliferation and DNA synthesis. Decreased cell proliferation and DNA synthesis means the body can't heal as fast as it should, because it can't make DNA and new cells very well without enough glutathione.

    Rich von Konynenburg said this for years, this is what his partial methylation block theory was about- low glutathione. I now believe Rich was right based on dramatic symptom relief I have following methylation treatment. My ability to function has gone from about 10-15% to 35-40%. I am walking 20 minutes every other day and doing 2-3 hours of chores around home every day. Just over 2 months ago I struggled to walk 10 minutes once or twice a week.

    Now walking 20 minutes every other day is no big deal and I have been seriously disabled with CFS/FM since 1989 and collecting social security disabilty since 1993. I just want say that I fully believe that optimizing methylation is the path to healing. I also found out that low doses of methylfolate, will not work for most people. I needed 6,400 mcg of methylfolate with sublingual methylcobalamin and other co-factors to break through the methylation cycle block that Rich talked about.

    When I did break through it though, I had a huge increase in energy, literally overnight! A clear sign to me that some thing profound had happened. I believe over the next several months as my body continues to heal, my energy levels will continue to go up and my health will continue to improve. Best of luck to all!... Jim

    This is the first study- http://www.ncbi.nlm.nih.gov/pubmed/23494481

    This is the second study-http://www.ncbi.nlm.nih.gov/pubmed/19558212

    This is the third study-http://www.ncbi.nlm.nih.gov/pubmed/24752591#

    Here is the study from Prohealth saying the level of mitochondrial dysfunction is in direct relationship to the fatigue level of CFS patients and vise versa-the level of fatigue correlated with the amount of mitochondrial dysfunction. http://www.prohealth.com/library/showarticle.cfm?libid=17086
    Last edited: Jul 30, 2014
  2. IanH

    IanH Active Member

    This is all good. However it is always difficult, if not impossible to identify a single item of a regime which induces symptom changes. Rich's protocol and my amended version are extensive regimes. Rich did not specifically recommend glutathione but his protocol was designed to increase glutathione reduction (via methylation).

    The idea of a "partial methylation block" remains theoretical and your idea of "breaking through the methylation block is therefore an idea not a factual process.

    Solely taking glutathione sublingual (which does raise blood glutathione) or NAC+MTHF often does not resolve people's energy problems. However the total regime more often does, which includes B12, B6, CoQ10, magnesium, and creatine.

    While taking massive doses of MTHF may be helpful it is unlikely to help many people. It is more likely that the total regime is correcting a number of interacting deficiencies. Because of the involvement of the immune system in ME/CFS and FM I recommended vitamin D3 and vitamin K2 be added.

    If, as you have found, that massive doses of MTHF have made a significant change for you then maybe you should have your genetic profile taken to see if you have one of the many SNPs of the MTHFR gene.
  3. ljimbo42

    ljimbo42 Active Member

    Hi Ian- You wrote "However it is always difficult, if not impossible to identify a single item of a regime which induces symptom changes."

    I don't believe there is one supplement that will turn around CFS/FM. I wrote "I needed 6,400 mcg of methylfolate with sublingual methylcobalamin and other co-factors to break through the methylation cycle block that Rich talked about." I said I am taking methylfolate, methylcobalamin, and other co-factors to address methylation. I am also treating dysbiosis, leaky gut, and mitochondrial dysfunction, all consequences of poor methylation and a poor lifestyle I lived for many years. I grew up living on quisp, cocoa puffs, cap't crunch etc. for the first ten years of my life and that was just the start. :)

    Ian wrote-"Rich did not specifically recommend glutathione but his protocol was designed to increase glutathione reduction (via methylation)."

    I agree, glutathione in and of itself cannot get into the cells and specifically the mitochondria where it is needed most. It needs to be raised by optimizing methylation.

    Ian wrote-"The idea of a "partial methylation block" remains theoretical and your idea of "breaking through the methylation block is therefore an idea not a factual process."

    I used the words "partial methylation block" because those are the words Rich used and because as I said above. When I reached 6,400mcg a day of methyfolate, the very next day my energy tripled. It was like a dam broke in my methylation cycle. Yes, a partial methylation block is still a theory, but low methylation or poor methylation and it's consequences are not. Poor methylation leading to low glutathione, and the many problems that causes has a lot of science behind it, as the studies above point out.

    Ian wrote- "While taking massive doses of MTHF may be helpful it is unlikely to help many people."

    6,400mcg methylfolate is not considered a "massive" dose if you have a MTHFR mutation, which I believe most of us do. The study I posted a couple of paragraphs below states the "MTHFR incidence in the CFS/FMS patients was significantly higher than general population averages. The "medicinal food" Deplin (which is methylfolate) is designed for treating MTHFR and it comes in 2 strengths 7.5mg (7,500mcg) and 15mg (15,000mcg).

    Ian wrote-"If, as you have found, that massive doses of MTHF have made a significant change for you then maybe you should have your genetic profile taken to see if you have one of the many SNPs of the MTHFR gene."

    There is a very good chance I do have at least one MTHFR SNP. At LEAST 40% of us do have a MTHFR polymorphism or mutation, because that is the statistic for the general population. Here is a study that points out the higher MTHFR polymorphisms in CFS/FM. Specifically 2 polymorphisms have a much higher prevalence in CFS/FM, compound heterozygous (53% higher in cfs/fm) and homozygous 677T (44% higher in cfs/fm).
    mthfr_fms_cfs_anderson_study.PDF


    There are also many people now with cfs/fm doing genetic testing and posting their results in their signatures at Phoenix Rising and other places. I have read 50-60 or more and found only 1-2 people that didn't have at least one MTHFR mutation, that's almost 100%. That's a huge number considering only about 40% of the general population has a mutation!

    I don't want to make it sound like I stumbled across this in the middle of the night somehow. :) I have tried most of the leading protocols over the last 7 years, without success. I treated candida, small intestinal bacterial overgrowth, leaky gut, adrenal fatigue, and mitochondrial dysfunction and still was functioning at about 10-15%.

    This why I know adding the methylation protocol is what made the huge change, it's the only change I made. Treating cfs/fm is not easy and I believe that the best benefits will be gained by treating dysbiosis, mitochondrial dysfunction, leaky gut, and methylation.

    Dr Ben Lynch (an expert on methylation) says the best place to start is by supporting the mitochondria with coQ10 or ubiquinol (the reduced form of coQ10), acetyl-carnitine or carnitine, magnesium, creatine, phospholipids ( phosphatidylcholine, DHA and EPA) molybdenum and Ribose if you can afford it, Ribose is expensive. A word of caution here, treating methylation can cause profound detox symptoms or over-methylation, so go very slowly if you try it.

    Treating dysbiosis and leaky gut to lower the amount of toxins being absorbed into the bloodstream, will minimize detox symptoms from supplementing methylfolate, and should be the next step after mitochondrial support. My experience says that treating the gut makes taking methylfolate dramatically easier, because the detox symptoms are greatly minimized. All the best - Jim

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    Last edited: Aug 9, 2014