• Welcome to Phoenix Rising!

    Created in 2008, Phoenix Rising is the largest and oldest forum dedicated to furthering the understanding of and finding treatments for complex chronic illnesses such as chronic fatigue syndrome (ME/CFS), fibromyalgia (FM), long COVID, postural orthostatic tachycardia syndrome (POTS), mast cell activation syndrome (MCAS), and allied diseases.

    To become a member, simply click the Register button at the top right.

List of ME/CFS abnormalities explainable by the GD-MCB hypothesis

richvank

Senior Member
Messages
2,732
Here is my current list of the abnormalities found in ME/CFS that I believe can be explained by the Glutathione Depletion--Methylation Cycle Block hypothesis:

1. Glutathione depletion
2. Oxidative stress
3. Alcohol intolerance
4. Buildup of toxins
5. Multiple chemical sensitivities
6. Shift to Th2 immune response
7. Failure of T lymphocytes to proliferate when stimulated by mitogens
8. Persistence of RNase-L activation and cleavage to form LMW RNase-L
9. Reactivation of viral and intracellular bacterial infections
10. Accumulation of infections over time
11. Lymphadenopathy
12. Low or dysregulated secretion of some peptide hormones.
13. Misfolding of proteins
14. Disruption of the sleep-wake cycle
15. Deficiency of perforin secretion
16. Depletion of intracellular magnesium
17. Muscle twitching
18. Mitral valve prolapse
19. Blunting of the HPA axis
20. Sensitivity to stress
21. Panic attacks
22. Hypoglycemia
23. Low blood pressure
24. Low secretory IgA
25. Mitochondrial dysfunction
26. Low VO2 max
27. Hypocapnia
28. Low peripheral body temperature
29. Fatigue and post-exertional exhaustion
30. Weight gain and weight loss
31. Low serum amino acids levels
32. Shortness of breath
33. Weakness
34. Elevated methylmalonate
35. Elevated homocysteine
36. Parasthesia, neuropathy
37. Elevated formiminoglutamate
38. Low WBC
39. Low RBC
40. Elevated MCV and MCH
41. Deficits in synthesis of creatine, choline, carnitine, coenzyme Q10 and melatonin
42. Rise in histamine
43. Neurotransmitter abnormalities
44. Emotional lability
45. Excitotoxicity (anxiety, nervousness, insomnia, sensory sensitization)
46. Myelin disrepair
47. Slow mental processing speed
48. Electromagnetic hypersensitivity
49. Diastolic dysfunction and low cardiac output
50. Diabetes insipidus (polyuria, constant thirst)
51. Low total blood volume
52. Orthostatic hypotension and POTS
53. Loss of temperature regulation
54. Low stomach acid production
55. Slow gastric emptying and GERD
56. Bacterial dysbiosis, yeast infections
57. Irritable bowel syndrome (bloating, abdominal pain, diarrhea, constipation)
58. Leaky gut syndrome
59. Food sensitivities
60. Hashimotos thyroiditis


Best regards,

Rich
 

Enid

Senior Member
Messages
3,309
Location
UK
Thanks Rich for this and all your work in understanding and aiding us here.
 

Sasha

Fine, thank you
Messages
17,863
Location
UK
That's some list, rich! More than one for every week of the year. What a menu of horrible symptoms our bodies are choosing from. Very interesting that your hypothesis covers them.
 

richvank

Senior Member
Messages
2,732
That's quite a list. Are there any symptoms which are not yet explained by the GD-MCB hypothesis?

Hi, fla.

Pain is one I haven't figured out a good mechanism for, but the people in the clinical study of the methylation treatment reported a significant decrease in pain, so it must be connected as well. Perhaps the threshold of pain is lowered when the mitochondria of the pain sensing cells or others in their neuronal pathways become dysfunctional due to glutathione depletion.

One can always come up with hypotheses, but I try to make sure there is a basis in biochemistry when I cook up a hypothesis to explain one of the abnormalities in ME/CFS, so that I can have some confidence that it is likely to be valid. Of course, until proven, it is still a hypothesis.

As you probably know, there is a huge number of symptoms in ME/CFS if you add up all the symptoms that various people report. I haven't studied all of them, but in view of the fact that so many appear to stem from the vicious circle mechanism described by the GC-MCB hypothesis, I would guess that very few of them are not produced by this mechanism.

I should note that there can be comorbidities. For example, some people have Lyme disease that has caused the onset of ME/CFS, so they have both. Some of their symptoms will be caused specifically by the Borrelia bacteria in that case.

Best regards,

Rich
 

fla

Senior Member
Messages
234
Location
Montreal, Canada
Are PENE muscle pain and headaches two different mechanisms? Are both forms of pain unexplained by the GC-MCB hypothesis so far? Sorry for all the questions but your knowledge is invaluable and finding the missing pieces will someday give us the full picture.
 

richvank

Senior Member
Messages
2,732
Are PENE muscle pain and headaches two different mechanisms? Are both forms of pain unexplained by the GC-MCB hypothesis so far? Sorry for all the questions but your knowledge is invaluable and finding the missing pieces will someday give us the full picture.

Hi, fla.

I don't know. Pain is a topic I would like to understand better. I've signed up for the fibromyalgia workshops at the upcoming Ottawa conference, hoping to learn a little more about this.
As I mentioned earlier, the women who were treated to lift the partial methylation cycle block reported a lessening of their pain, so it does seem that pain is linked to the vicious cycle mechanism described by the GD-MCB hypothesis. I just don't understand the detailed mechanism so far, and I think I have identified biochemical mechanisms for the other abnormalities that I've listed. From my point of view, I would say that the mechanisms I have identified for a large number of the abnormalities in ME/CFS do suggest that this vicious circle is the core mechanism in the pathophysiology of this disorder, and the observation that the major symptoms improve across the board for most of those who treat to lift the partial methylation cycle block is consistent with this. I think that all of this provides a good basis for saying that this type of treatment is likely to be beneficial for most people with ME/CFS, and that it should be more widely used.

Best regards,

Rich
 

richvank

Senior Member
Messages
2,732
Pain could be caused be multiple of the abnormalities already in your list.

Hi, hixxy.

I think you're right about this. For example, the depletion of glutathione could be producing mito dysfunction in neurons in the pain-sensing pathways, lowering their pain thresholds, and causing them to produce the sensation of pain when there is no tissue damage going on, and no reason for the pain signal to be sent. Maybe I should just offer that as a hypothesis for the pain in ME/CFS, but I would like to do a little more study before I am ready to add pain to my list.

Thanks for your comment.

Rich
 

drex13

Senior Member
Messages
186
Location
Columbus, Ohio
Hi Rich,

Thanks for the comprehensive list. I would would like to throw in my two cents in regards to the pain issue. Prior to starting Hydroxo b12 and Methymate B, I was one who experienced muscle, joint pain, and /or what I would term non specific or generalised pain. One of the things I have noticed since adding those two supplements (along with some lauricidin), and basically having no cofactors in place other than magnesium and potassium (which I did find to be important), is a significant reduction in pain. I have recently added the folinic acid, will be ordering phosphatydil serine tomorrow, but am still up in the air about the Yasko multi (since it has folic acid). I like the idea of a multi, rather than having to figure out and take a bunch of individual pills.

In my limited experience with the SMP, I have found what I consider to be a significant improvement in pain. My pain was not constant, but would flare up once or twice a week, and my entire body would hurt. I have not experienced this in several weeks.
 

Sallysblooms

P.O.T.S. now SO MUCH BETTER!
Messages
1,768
Location
Southern USA
Douglas Labs Ultra Preventive X is really good, my doctor likes it for a multi. I don't take all of the pills it calls for each day though since it has b6 and I cannot take much, sensitive to it. I don't think you can put all you need into a multi. Lipo GSH and C, powders etc cannot be added. I have many supplements to address all of my needs.
 

drex13

Senior Member
Messages
186
Location
Columbus, Ohio
Douglas Labs Ultra Preventive X is really good, my doctor likes it for a multi. I don't take all of the pills it calls for each day though since it has b6 and I cannot take much, sensitive to it. I don't think you can put all you need into a multi. Lipo GSH and C, powders etc cannot be added. I have many supplements to address all of my needs.
.
Thanks, I'll check it out
 

fla

Senior Member
Messages
234
Location
Montreal, Canada
I asked my GP to follow me through this protocol and he (says he) read it and did not want to do it because he's not sure about it. I'm seeing an immunologist next month who knows a little about M.E. (which is rare around these parts) and I'll bounce it off of him.

Why aren't more people trying this protocol? Trouble getting a Dr to follow you through it or other reasons?
 
Messages
66
Fla - I gave up with my GP in England a long time ago. If I'd listened to their advice I'd still be on painkillers, antidepressants and learning to live with it. I hope there are some other folk who have more positive experiences but my view on the NHS treating people with FMS / CFS is that they do a terrible job.

I wish there were more options for people like us in the UK.... It's a sad state of affairs IMHO.

Fla- nutritional support has turned my life around and I urge you to try it if at all possible.
 
Messages
15,786
I asked my GP to follow me through this protocol and he (says he) read it and did not want to do it because he's not sure about it. I'm seeing an immunologist next month who knows a little about M.E. (which is rare around these parts) and I'll bounce it off of him.

Odd that he's nervous about it ... it's just supplements, which most GPs don't think have any affect anyhow :) It's all available without a doctor being involved, for the truly desperate, but it's very nice to work with a doctor that understands the general theories as well, and can help test and guide things.
 

Sasha

Fine, thank you
Messages
17,863
Location
UK
Why aren't more people trying this protocol? Trouble getting a Dr to follow you through it or other reasons?

Hi fla - I think that's a really important question. I'm also in the UK and trying Freddd's protocol but now at rich's doses, and without the help of a doctor.

I didn't consider trying the protocol for a long time because, with no background at all in biology, I didn't understand it and it looked incredibly complicated, with (to my anxious perception!) people having horrible reactions and asking complicated questions with complicated answers about what they should do about it.

However, so many people seemed to be benefitting that I started on Freddd's protocol. Being brain foggy, even with the summary that he provides, I found it difficult to understand (I still don't think I understand it - I need something very "1. Do A. 2. Do B. If C happens, do D. If E happens, do F." and so on).

So, I started it without understanding the biochemistry. I had problems, but I posted about them and got informative replies both from Freddd and rich, plus others. I still don't understand the biochemistry and I'd have been forced to have given up weeks ago if it hadn't been for Freddd and rich's support.

I wonder if a lot of other PWME have the same problem with trying the protocols: brainfog and lack of specialist knowledge in the face of a complex intervention plus a protocol that requires a great deal of knowledge to fix things if it presents problems.

I would so love to have a doctor to help me with this - to give me the genetic and blood tests that would rule out the blind alleys and keep my electrolyte levels safe. I don't think this protocol is easy. But I hope that if enough of us do it with good enough results, it will lead to pressure for research and eventually doctor-assisted application of the protocol.
 

richvank

Senior Member
Messages
2,732
Rich, this looks like an excellent multi. If you get a chance to look at it, I'd love to know what you think.

Madie

Hi. Madie.

Yes, the Douglas Labs Ultra Preventive X does look like a very good formula. I note that its folate is in the form of Metafolin, and its B12 is in the form of methylcobalamin.
There is always the possibility that an individual person might have a sensitivity to one or more of the ingredients, as is true in other comprehensive multis, including the Yasko multi, but generally speaking, I would say that this one looks very good.

For people who need a more "bare bones" multi because of sensitivities, another one to try might be the Thorne Basic Nutrients IV, which doesn't have as many ingredients, but is designed to be hypoallergenic.

Best regards,

Rich

Rich
 

heapsreal

iherb 10% discount code OPA989,
Messages
10,089
Location
australia (brisbane)
Hi Rich,

one more for your list is nk dysfunction which i thought was a biggy.
Also failure of T-lymphocytes to be stimulated, does this mean low T cells? As my t cells and some others i know have had hi numbers, from other stuff i have read is that cfsers have abnormal t-cells ie high or low t-cells numbers. I recently read where it may not be a numbers thing just like nk cells but a matter of function. Maybe for myself im producing more t-cells to compensate for their poor function or even producing more to compensate for poor nk function.
Also from this dysfunctional immune system comes herpes virus reactivation for many like ebv, cmv hhv6 etc. and bacterial infections, or just co-infections in general.

cheers!!!