Revised Glutathione Depletion--Methylation Cycle Block Hypothesis for ME/CFS

Creon do work great and I can get them for $5.50 / month for 500 capsules in Australia. Unfortunately this is one of the things MCS stole from me..

Thank you Rich!

So, what would be the best sequence in which to treat this illness? From what your write Rich, you are suggesting working on the gut and the methylation at the SAME time. Correct?

1) Take B12 and Folic/Folinic Acid (challenge here is that good doses of B12 interferes with sleep)
2) If there are deficiences in amino acids or vitamins, supplement with these.
3)Should the glutathione (liposomal) be taken every day?
4)Eradicate gut infections and restore flora (this is a huge challenge for some reason)

How are the challenges to be overcome? So many of us just go in circles because of these.

Thank you for all your hard, hard work.

Hi, Sushi.

Normally, calcium is maintained at a low concentration inside the cells, relative to the blood level of calcium, so it is normally pumped out. If the calcium channels are stuck open, I think the calcium concentration would be too high inside the cells, rather than too low. I've heard your doc express this view before, and I think it's based on work his group did involving RNase-L.
I don't know the details of this, but if it's based on the RNase-L problem, my view is that this will be corrected by lifting the methylation cycle partial block so that glutathione can come up to normal.

Best regards,

Rich

Hi Rich,
Thanks for the update! I like this improved model, particularly given the recent Mella & Fluge study where they lowered the immune stress on CFS patients and had some patients with dramatic improvement. Seems we do need to focus more on finding and reducing our oxidative stress load in order to improve our natural methylation, going to whatever is the source of that load. That seems like a major 'aha' about the SMP. More of a focus on freeing our natural methylation, which of course includes supporting the process with the bypass supplements.

So right now I am thinking of the SMP as a supportive and perhaps adjunctive therapy, with the main emphasis for treating CFS in the future being to find the original causes of the glutathione depletion and treating those causes. So if there is autoimmune, treat that. If there are chronic enteroviruses, treat them. If lyme, treat that. Treat mold problems, digestive, leaky gut, candida, etc. Pretty much Dr. Nathan's approach, or the approach of a competent integrated or functional medicine doc. And during all this support the methylation with SMP type therapies.

But we also need to support all the damaged and low-functioning biological processes for any of this to work. And stop any adrenal-looping or other internal stress. I think that is where many patients get stuck, not knowing how to treat the broken adrenals, low blood volume and dehydration, dysfunctional immune system, developing stress management and coping skills, etc. We do well self-treating with nutrients, not hard today to find vitamins and supplements to get better nutrients. But treating these specific functional problems, while at the same time sorting out the original cause of the glutathione depletion and also supporting methylation seems like a real chicken-or-egg problem. Pretty hard for brain-fogged patients.

***Hi, Helene.

Thank you Rich!

***You're welcome!

So, what would be the best sequence in which to treat this illness? From what your write Rich, you are suggesting working on the gut and the methylation at the SAME time. Correct?

***I think so, yes.

1) Take B12 and Folic/Folinic Acid (challenge here is that good doses of B12 interferes with sleep)

***I'm not fond of folic. Folinic works for some people. Methylfolate gives direct support to the methionine synthase enzyme.

2) If there are deficiences in amino acids or vitamins, supplement with these.

***Right. And amino acids may need to be supplemented, too.

3)Should the glutathione (liposomal) be taken every day?

***I think you will have to experiment with that. I don't have a good answer for you.

4)Eradicate gut infections and restore flora (this is a huge challenge for some reason)

***Yes. They can be quite stubborn, maybe because they hide in biofilms.

How are the challenges to be overcome? So many of us just go in circles because of these.

***I think they have to be worked out on a case-by-case basis, with testing to see what the issues are.

Thank you for all your hard, hard work.

***Again, you are very welcome.

***Best regards,

***Rich

Hi, Kurt.

Thanks for your input. I agree that other treatments are usually needed in addition to the methylation treatment. I'm not clear yet on how many of the processes you discussed need to be treated directly. Some may resolve automatically if the etiologies, the deficiencies and the methylation cycle are taken care of. We still have a lot to learn.

Best regards,

Rich

"I know that it is unpopular with some to suggest that psychological or emotional stress is a factor in causing some cases of ME/CFS, because they interpret this to mean that there must be a psychiatric problem or a character flaw involved. I don't see it this way at all. The fact is that the body's stress response system (whether responding to physical, chemical, biological or psychological/emotional stress) does place demands on glutathione. If these demands become too high, compared to the body's capacity to make and recycle glutathione, ME/CFS is the result. We are all human, and if subjected to a large enough load of stress for a long enough time, our health will crack. It's just a question of how it will crack. For people who have inherited certain polymorphisms, this "crack" will involve the development of ME/CFS. This is my opinion, and I realize not everyone agrees with it."

Rich, I totally agree with your statement here. That is exactly what happened to me. My body simply "cracked" under extreme amounts of stress I endured for two years. I was never aware until I became sick, that I was deficient in B12 and I think that was also a factor. I have made progress though (at a snails pace). I've come from spending 16 to 18 hrs a day in bed, to one nap a day. I might not ever be completely 100 % but I am very grateful for every day I am given. Thanks for your time.
Lee Ann

Hi, Lee Ann.

Thanks for your comments. I'm glad to hear about the progress you've made, and here's hoping it keeps up!

Best regards,

Rich

Rich I think the answer to some of this is just some people cannot covert certain b vitamins and folate to their active forms due to genetics? My entire family has struggled with addiction and fatigue. I also think insulin sensitivity is greatly influenced by the active forms of these vitAmins or lack of. We eat a lot more sugary nutrition less crap than we did forty years ago so there is another reason. And we have higher shbg levels from higher exposure to xenoestrogens which lower free circulating sex hormones. Can't forget the power of hormones in influencing every body system. We also probably don't eat enough fiber today.

Hi Rich,

This is a question regarding possible betaine HCL supplementation. I have read about the burp test and so on and I have always been unable to burp (since childhood and always had trouble with overly fizzy/carbonated sodas) except for rare occasions. However I assumed that low stomach acid would go along with very few bowel movements and generally low gut motility and likely also the tendency to gain weight and none of that has been true for me (except for gaining weight easier as we age when the metabolism slows down but nothing dramatic). I have always usually had at least 2 BM per day and sometimes rather what's called a "nervous" stomach as opposed to a "lazy" stomach. So I never tried it, are my assumptions wrong? Can someone with low stomach acid still have high gut motility? I took acid reducers a long time ago against my gut-feeling bc one doc "just wanted me to try it" on it and it was a disaster (although h2 blockers were not that bad but the PPIs were horrible), then I read about the burping thing and that clicked with me. Thanks in advance for your help!

Hi, mellster.

Based on what you have reported, my guess is that you must have a very tight gastroesophageal sphincter, based on inability to burp after drinking carbonated sodas. How about vomiting when you have been ill? Have you been able to do that, and if so, is it very difficult or painful? Also, do you have any difficulty in swallowing?

Your bad experience with acid reducing drugs suggests that you did have stomach acid when you tried them. Otherwise, I don't think these drugs would have had such negative effects on you.

Best regards,

Rich

Hi Rich,

I don't have trouble swallowing but it is a process that feels slow and "feelable" to me, esp. when I don't use fluid to aid (I also have big tonsils). I rarely ever vomited in my life, but when they did they gastroscopy and I opted out of sedation last year I had a good gag reflex going and vomited the very little that was left (as you are not supposed to eat much) and I remember being sore for much much longer than the doc said, like 1-2 weeks at least. Also the few episodes I remeber vomiting seem to have been at least somewhat painful, so you assessment might be accurate. I just wonder why the doc that did the endoscopy did not comment on this, or is this somewhat of a common phenomenon within the genetically variable reference range that people can differ in the widths of the gastroesophageal sphincter? Thanks and cheers!

Rich Thank you very much for your efforts. Is there a place to donate toward your work?

Just my two cents:
I think if people don't do well on a methyl protocol is because the side effects are to strong for them or they have not been able to absorb the vast amount of knowledge to tailor the treatment for there spacific case. Not saying this in a negative way but we have to be experts at it or it won't get solved. Some people with sever brain fog can't get through it. My hope is that they are able to get an advocate to help them through.

I also believe that ME is linked to Autism. I used to teach children with special needs and we are very similar. Also, my family has a long history of enginerds, back more than 120 years. With my generation and my children's generation we have seen ADD and Autism develop. I was diagnosed with ADD at age 8. Nephew was dx with mild Autism/Aspergers. Autism HAS a genetic component. I have serviced many families with multiple children with the disorder. Moreover, each of the effected child varies on severity on the autism scale. So clearly there is something that is expressing these genes a various rates.