Rest periods and can CFS people get really well?

[Hip]

This might be of interest, @Kimsie:
Cytochrome C is a hydrogen peroxide scavenger in mitochondria


By the way, when earlier in this thread you state that catalase was dependent on NADPH for recycling, where did you read this?

Also, does it matter if catalase is dependent on NADPH for recycling? Provided you ensure high levels of catalase through daily supplementation, the fact that catalase is not recycled may not matter. You are just sacrificing the catalase that you take.

 

[Kimsie]

This might be of interest, @Kimsie:
Cytochrome C is a hydrogen peroxide scavenger in mitochondria

By the way, when earlier in this thread you state that catalase was dependent on NADPH for recycling, where did you read this?

Also, does it matter if catalase is dependent on NADPH for recycling? Provided you ensure high levels of catalase through daily supplementation, the fact that catalase is not recycled may not matter. You are just sacrificing the catalase that you take.

I guess it isn't exactly for reclycing, but to keep it from becoming inactavated. It might not work even one time without it.

How are you going to supplement catalase? I checked on that one quite a while ago and I am pretty sure it gets broken down in the gut. I tried giving a heme supplement, but it didn't do anything. If you have found a study that shows that catalase can be delivered to the cells as an oral supplement, I would like to know about it. I couldn't find any.

 

[Tunguska]

Are there major differences in the digestion/metabolism of inosine vs other dietary purines? I relied on sardines and herring to get purines and increase uric acid: http://www.acumedico.com/purine.htm

According to common knowledge it's mostly meat purine sources that increase uric acid. In http://jn.nutrition.org/content/106/3/435.full.pdf there's a table breaks down purine contents. Sardines are dominated by Xanthine followed by guanine. Whereas inosine I know is in chicken breast (here: http://www.researchgate.net/profile/Vinod_Modi/publication/222030597_Degradation_of_inosine-5-monophosphate_(IMP)_in_aqueous_and_in_layering_chicken_muscle_fibre_systems_Effect_of_pH_and_temperature/links/0912f5108f6e29196a000000.pdf - 188.5mg IMP per 100g chicken breast, 135.2 in leg; 103.7mg straight inosine per 100g chicken breast, 31.1 in leg)

Would getting mostly xanthine or other avoid immune-modulating effects of inosine?

For the record I only noticed minor effects from inosine supplement but dietary purines were good to me although obviously more confounded. If inosine increases mast cell it may be something I should avoid for the time being.

 

[Gondwanaland]

According to common knowledge it's mostly meat purine sources that increase uric acid. I

High fructose intake increases uric acid as well
http://www.renalandurologynews.com/...y-decrease-elevated-uric-acid/article/309628/

 

[Hip]

How are you going to supplement catalase? I checked on that one quite a while ago and I am pretty sure it gets broken down in the gut.

I had a look at this catalase supplement website by Invite Health to see if they offered any explanation of how their supplement could prevent catalase breakdown by stomach acids, but found no info. In the case of the Glisodin brand superoxide dismutase supplement, they add gliadin to their SOD to prevent this being broken down by the stomach acids. So I wonder if that catalase supplement also has some system to prevent breakdown. If not, then it would be a bit of a con. Though I guess you could probably take that catalase supplement as a suppository to prevent stomach acid breakdown.

But on the subject of the Glisodin SOD supplement: this is supposed to increase catalase levels by 171%.†

I tried Glisodin myself a few years ago, but did not notice any benefits for my ME/CFS.

 

[Kimsie]

I had a look at this catalase supplement website by Invite Health to see if they offered any explanation of how their supplement could prevent catalase breakdown by stomach acids, but found no info. In the case of the Glisodin brand superoxide dismutase supplement, they add gliadin to their SOD to prevent this being broken down by the stomach acids. So I wonder if that catalase supplement also has some system to prevent breakdown. If not, then it would be a bit of a con. Though I guess you could probably take that catalase supplement as a suppository to prevent stomach acid breakdown.

But on the subject of the Glisodin SOD supplement: this is supposed to increase catalase levels by 171%.†

I tried Glisodin myself a few years ago, but did not notice any benefits for my ME/CFS.

As I am evaluating the things that have helped, I can't really find anything that I can attribute the improvement for sure to increased catalase synthesis, even B6, which I thought helped by increasing heme, etc down to catalase, because B6 might have helped by directing more through the SHMT enzyme instead of the formyltetrahydrofolate dehydrogenase enzyme. In fact, I could attribute the improvement from every single supplement to an increase in NADPH synthesis or a decrease in the drain of NADPH.

This makes me think that perhaps catalase simply doesn't work at all without NADPH. There are other antioxidants that normally use NADPH to be recyled either directly or indirectly, such as GSH and vitamin C which can be used as "suicide" antioxidants, but I don't think catalase can be.

I don't think I trust the assurances of those companies that sell those SOD and catalase supplements.

 

[kangaSue]

Has it been suggested before that the simple answer to muscle fatigue in ME/CFS is due to the inhibition of KATP channels http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3125986/

 

[nandixon]

Slightly off topic, but for a year or so now, I've been extremely confused when it comes to NAD vs. NADH vs. NADPH. SO confusing…

@nandixon, can you explain these as if you were talking to a first grader?

NAD comes from nicotinic acid or niacin, but that's about as far as I understand it, then my brain goes to mush.

Thank you.

Not sure how simple I can make it, but I guess to start with, there really isn't a significant difference between NAD+/NADH and NADP+/NADPH from a general chemistry point of view, in terms of their abilities to perform reduction-oxidation reactions. (You probably know that the "+" versions are the oxidized forms; the "H" versions the reduced forms.)

So while the extra phosphate group in NADPH (or NADP+) doesn't affect its redox abilities relative to NADH (or NAD+), what it does do is give a molecule of NADPH a different shape/binding property from that of NADH, so that NADPH and NADH can be recognized differently and bind as substrates to different sets of enzymes.

This is important so that the cell containing them can regulate NADH and NADPH independently. (Generally speaking, enzymes that use NAD+/NADH don't use NADP+/NADPH, and vice versa.)

So, for example, normally the ratio of NAD+ (the oxidized form) to NADH (the reduced form) inside the cell is kept high (i.e., more oxidizing), while the ratio of NADP+ to NADPH is kept low (i.e., more reducing).

Thus, the role of NADH is mostly in catabolic reactions (breaking down molecules), where NAD+ is needed as an oxidizing agent. During this process, NAD+ receives electrons and hydrogen and is converted to NADH.

Critically, the NADH that is formed can transfer those electrons to the electron transport chain (ETC) to generate ATP. (NADH is converted back to NAD+ with this transfer.)

On the other hand, the role of NADPH is mostly in anabolic reactions (biosynthesis), where NADPH is needed as a reducing agent. So it donates electrons and hydrogen to make new compounds like cholesterol, fatty acids, and others.

Critically, this reducing action of NADPH includes regenerating glutathione that has been oxidized.

NAD+/NADH also has other roles, including reductive synthesis like NADPH. NADP+/NADPH also has other roles too, including oxidative related ones. So things are not black and white by any means.

 

[Hip]

I don't think I trust the assurances of those companies that sell those SOD and catalase supplements.

In the case of GliSODin, there are several published studies on its efficacy (see here). Though I have not seen studies for the catalase supplement, so I am not sure about that one.

 

[dannybex]

Thank you @nandixon . It will take me awhile to absorb that, but I really appreciate your taking the time to explain it.

My question I guess is then, is it best to supplement w/NADH (sublingual) or low-dose niacin/niacinamide -- or…?

 

[nandixon]

Thank you @nandixon . It will take me awhile to absorb that, but I really appreciate your taking the time to explain it.

My question I guess is then, is it best to supplement w/NADH (sublingual) or low-dose niacin/niacinamide -- or…?

Well, even after all these years at least one research group is still looking at NADH, so I guess it might be helping some subgroup of ME/CFS patients, at least in the short term. (http://www.ncbi.nlm.nih.gov/pubmed/25386668/)

But I'd guess that, in general, it's probably not likely to be more helpful than taking the precursors (i.e., niacinamide/niacin), and may actually be worse for some people (for example, by an inhibition of pyruvate dehydrogenase, among other possibilities).

 

[dannybex]

Thank you @nandixon . I still don't get it -- so complex -- but today (and I a couple of days ago) I took a sublingual NADH, and am feeling a lot worse. More hopeless, more anxiety, and COLD…

Edit: Found a study w/niacin that lowered thyroid hormones:

http://www.ncbi.nlm.nih.gov/pubmed/7776715

 

[sueami]

I have been thinking about this physician's recovery from CFS often over the past month of this rest protocol. I haven't had the time/energy to reread his blog (I found it last summer when I was searching for CFS recovery stories) but it reinforces the theory posed in this thread.

http://www.recoveryfromcfs.org/

I will comment more once I've been able to reread his rest schedule segments.

 

[sueami]

Two quick questions:

1) Is anyone else trying this rest protocol of 3 hours a day activity in 15 minute blocks? I'm curious to compare experiences. I'll write more about mine when I have more alert time available. Short version--tiny but noticeable improvements, not yet stable, 3 weeks after I crashed myself completely into the ground.

2) @Kimsie, would taking an antiviral to try to knock down a viral reactivation constitute increasing one's energy output, and therefore be bad to do on this protocol?

 

[Kimsie]

Two quick questions:

1) Is anyone else trying this rest protocol of 3 hours a day activity in 15 minute blocks? I'm curious to compare experiences. I'll write more about mine when I have more alert time available. Short version--tiny but noticeable improvements, not yet stable, 3 weeks after I crashed myself completely into the ground.

2) @Kimsie, would taking an antiviral to try to knock down a viral reactivation constitute increasing one's energy output, and therefore be bad to do on this protocol?

I really don't know anything about antivirals, so I couldn't even guess. No actually I am editing this to add that if you mean inosine or something with inosine in it, I think it would be fine to take it if you tolerate it.

Do you have any idea if you are an overmethylator or undermethylator? I am making a lot of changes to my hypothesis and adding in Walsh's ideas, and so I have come to the conclusion that the niacinamide or at least large amounts of niacinamide are probably not best for undermethylators of histones. I am going to post a new version of my hypothesis soon, but I am still researching to try to find the answers to a couple of questions I have. I will be explaining about the inosine when I do that post.

 

[sueami]

I tried to follow your post on that earlier. I show signs of both, in that anxiety is a common dysfunction for me (rather than depression) and one of the few supps I respond strongly and obviously positively to is my methyl b12 shot , which I gather would lean towards undermethylation. But I also experience seasonal allergies, though not as bad in the last year or two, and that seemed to be an overmethylation symptom. If I had to choose, I'd say I'm under, even with my COMT snps.

 

[Kimsie]

I tried to follow your post on that earlier. I show signs of both, in that anxiety is a common dysfunction for me (rather than depression) and one of the few supps I respond strongly and obviously positively to is my methyl b12 shot , which I gather would lean towards undermethylation. But I also experience seasonal allergies, though not as bad in the last year or two, and that seemed to be an overmethylation symptom. If I had to choose, I'd say I'm under, even with my COMT snps.

Walsh says that seasonal allergies are undermethylation. Anxiety and depression can be either. Have you ever taken antihistamines? A good response to antihistamines is supposed to lean towards undermethylation.

 

[sueami]

I'm likely an undermethylator then. Timed release antihistamines like claritin work well for me. (Benadryl makes me completely spaced out and awful feeling.)

 

[Hanna]

I have been trying (three weeks in) pacing my activity according to the 20 mn activity/15 mn rest pattern. For the time beeing, I can't draw conclusions becquse so many things interracted (reaction to meds). But I am still into this and intend to apply this as much as I can.

How do I know I am under methylating or not ?
I take only little supplement with methyl groups (don't tolerate SamE) like methylB12 (1 mg/day) because otherwise I am wired and feel anxiety. Am allergic to most of the antihystamin stuff, have plenty of other food intolerances (gluten-diary-sulfite etc) and MCS, but no real seasonal allergies.

 

[adreno]

As I have said a few times already, whenever I increase B3 or reduce folate, I run into problems. I do have seasonal allergies. So perhaps I am generally undermethylated.

Almost universally it seems that PWMEs do not tolerate B3 very well, and generally do well with folate, and this is one thing that makes me a bit skeptical about @Kimsie's NAD hypothesis.