Acetyl L- Glutathione, ATP, Baking Soda, Sam-e & Catalase = No PEM after exercise

[Sidereal]

Can you post links to Cheney's thoughts?

It is important that the oxidation and redox be BALANCED. Too much of either is bad. The problem with the CFS literature is that everyone talks theories all day long, and none of it gets reduced to clinical guidance. Saying that everyone is overly reduced, or everyone is overly oxidized, is advice that is worth what you paid for it.

What I am saying is TEST your redox balance. If you are overly reduced, experiment with oxidants. If you are overly oxidized, I struggle to understand how you have CFS in the first place, because apparently your electron transport chain (which drives aerobic metabolism) is chugging along very well.

If a person is overly reduced, they have low NAD+ Low NAD+ will downregulate all kinds of metabolic processes, including by the way glycolysis. How can it be healthy for anyone to live with an NAD+/NADH ratio of 200 when the average person has a ratio 500 to 2000?



Yes, but just as sad is that people do things that benefit them and abandon them because they had no way to measure a result and relied on subjective feeling alone.



How can we take action on a hypothesis we cannot test?

Like I said, there are no handy links since he doesn't publish papers. He is a clinician who has been treating CFS patients since the Incline Village outbreak in 1984. There's a recent lecture on youtube, might be a good place to start for an overview of his ideas.

There is no accepted/validated test for this condition or any of the myriad hypotheses we have about aetiology. Part of surviving with this illness in the long term is coming to grips with this uncertainty.

 

[pemone]

There is no accepted/validated test for this condition or any of the myriad hypotheses we have about aetiology. Part of surviving with this illness in the long term is coming to grips with this uncertainty.

The fact that 100 talking heads cannot agree on the reasons a car sits on the side of the road does not mean we cannot ask a specific question. A specific question in that case might be "Is the engine dead?"

I can ask the question to any person who claims to have CFS: Is your electron transport chain / aerobic metabolism working? I don't need to understand the cause for it not working. I don't need to understand the reason it does not work (yet). I only want to know does it work or not.

You build success on facts. After you have a fact, you can build a new hypothesis, raise a new experiment - which can be tested - and that leads to more facts. That is the scientific process. I think a good starting point for that process, with this disease, is to establish whether your electron transport chain works or not, without trying to understand any specific reason it does not work. That's all I am trying to test by NAD+/NADH ratios and by looking at the level of ATP output. I'm testing the two endpoints of the electron transport chain, trying to establish that the problem lies somewhere in between.

It doesn't matter if there is hypoxia, or if there are mitochondrial transporter problems, or if there is mercury binding to iron-sulfur complexes in the ETC. That's all detail for later. Just start with something simple, like does the ETC itself not work, and you can work backwards to the ultimate cause later.

 

[MeSci]

I didn't run a test but have SOD SNPs and many symptoms of low SOD. I am taking Extramel French melon extract and I find it energizing, PEM reducing, increased sun tolerance

I have one SOD SNP identified, but it seems that the free genetic test I got only looks at a few. The one I know I have is very common - in fact it is the norm.

 

[MeSci]

Someone just take a gun and shoot the allopathic medical industry. I mean Omega-3 to fix your nitric oxide? Wow.

As you say, they don't want to cure anything.

Research the foods that contain nitrates. Get the test strips. Start out slow and observe subjective feeling as well as measure nitrite levels on the strips. Scale up.

Do that for two months and I expect to see you back here with a smile on your face. It can make a dramatic difference in how you feel. It is not a cure for CFS, probably.

Sorry if I wasn't clear - it was the genetic testing company that recommended increasing omega-3 intake. The doctor prescribed an ACE inhibitor for the high blood pressure, which turns out to have been a very bad idea as I suffered severe side effects soon after, which the doc failed to link to the drug, so that I continued with it for 7 years with worsened health. I am now on a beta blocker which I now recall I chose partly because it raises nitric oxide! Not enough though, I suspect.

I think I eat plenty of high-nitrate foods, but I don't think I have yet been convinced of your arguments re nitric oxide, nitrates and test strips. I'm acting on other lines of evidence and watching and recording the results of those. I have tried some things that didn't work, and continue to experiment with one change at a time.

Be careful not to give direct advice - it is against PR rules.

 

[MeSci]

One thing I don't think is very helpful is ATP. Ribose should be much more effective as a supplement. An entire bottle of ATP pills would give you enough energy for only a few minutes, though it would boost the substrate pool. Ribose also boosts AMP and ADP synthesis, but much more cheaply.

Just a quick cautionary note - some people cannot tolerate (d-)ribose. I am one of them, and had a particularly bad response.

 

[alex3619]

Again, I am trying to establish the fundamental fact of the disease that the electron transport chain is in fact broken. You keep getting lost in detail.

Actually the opposite - I keep looking at the larger picture. The ETC might not be broken. That is a possible miscategorization, and can lead to poor conclusions.

I am just saying measure the effect, establish the fact that ETC does not work, and then work back to details from that.

This is something that has yet to be shown. The system is not working, where the problem is, and whether or not its even inside the system, is not established. Its only hypothesized. It might be right, or not.

In terms of establishing a failure in aerobic metabolism, that was done in the 80s but remains unpublished (its part of the Ampligen studies). Workwell first published in 2007. We need mechanisms, not a vague problem.

NADH should hurt not help. If ETC does not work NADH piles up from outputs of the krebs cycle. It is NAD+ we need. A person in a highly reduced state with low NAD+/NADH needs oxidants, in absence of a functioning ETC.

There are two considerations here. The first is as you suggest, that NADH will inhibit the Krebs cycle and boost lactate production. Its not good, but its not very bad either. Taking NADH prior to exercise is probably not the best idea though.

What this view ignores is the NAD-NADH pool. This is not a static thing, its a dynamic pool. The ratio is high, variously 3 to 700 for NAD/NADH in mammals. Over time the ratio of the two will probably stabilize, unless there are confounding factors. However confounding factors will put the NAD out of commission very fast ... you wont be able to supplement enough but have to address whatever the confounding factors are.

The fastest way to boost the NAD/NADH pool is to take NADH. Doing other things to improve the ratio is probably desirable however. Its very hard to boost NAD directly (I say more on this below). Its nearly always indirect, and aimed at increasing synthesis, unless taking NADH. I suspect the reason for this is that NADH is a more stable molecule so easier to market. Taking B3 relies on it being converted adequately, as its only a precursor. Yet boosting that path is probably also a good idea.

If you can find a stable NAD supplement that is cheaper than an NADH supplement, then its a better idea. Otherwise everything is trying to work around the issue that its hard to directly supplement NAD. I know there are some sublingual tabs on the market. Most other "NAD" supplements sold are NADH or precursors. You will find though that if you are taking NAD by swallowing it then very likely you will be absorbing NADH as it will be converted in stomach acid. So why bother?

Now there are other potentially useful substances, though most of the work on things like resveratrol have not been adequately researched on human subjects. It works fine in a test tube though to boost NAD.

Let me emphasize again though the importance of CoQ10 and therefore of other antioxidants including even C and E. Glutathione is critical here, so any methylation issues may need to be addressed.

 

[MeSci]

I am not sure if any research has been done to determine whether in sickness behavior we feel fatigued and low in energy because the brain goes into a mode designed to make us feel that way, or whether there is a real physical shortage of energy in the body, perhaps because the body enters into an energy-conserving mode during infection, in order to save as much energy as possible for fighting the infection.

In other words, in sickness behavior, is there a real energy shortage making us feel fatigue, or is the the brain just "faking" the fatigue feeling, as part of the normal behavioral response to infection?

Could uncoupling (of ATP production from the ETC) be involved, I wonder? We often get a fever with an infection. Lower energy + increased heat can be due to uncoupling.

 

[alex3619]

Just a quick cautionary note - some people cannot tolerate (d-)ribose. I am one of them, and had a particularly bad response.

Its about intended effect. To increase the AMP-ADP pool we need ribose. As with all things though our tolerance varies patient by patient. A serious reaction to ribose might be something worth investigating, as I suspect it might give you clues to your personal biochemistry. What are the secondary consequences of consuming ribose? I have not investigated this.

 

[pemone]

I think I eat plenty of high-nitrate foods, but I don't think I have yet been convinced of your arguments re nitric oxide, nitrates and test strips. I'm acting on other lines of evidence and watching and recording the results of those. I have tried some things that didn't work, and continue to experiment with one change at a time.

I thought I ate plenty of high nitrate foods too. The test strips allowed me to discover that I only get a positive benefit when I eat a huge amount of those foods. Your mileage will vary.

If I were in your shoes, I would think that conducting a few experiments is almost free. You lose nothing if you eat three cups of butter lettuce and it does not affect your nitrites. You would be no worse than you are now. If you have a positive reaction, that gives you a clue for further experimentation.

 

[alex3619]

To discuss this we might have to also look at the NADP/NADPH ratio and how that is maintained. I have not spent much time looking at that.

I think that the whole NAD-CoQ10-antioxidant-revsveratrol-ribose thing may fail if someone has big methylation problems. This kind of therapy is linked to methylation therapy.

 

[MeSci]

I can ask the question to any person who claims to have CFS: Is your electron transport chain / aerobic metabolism working? I don't need to understand the cause for it not working. I don't need to understand the reason it does not work (yet). I only want to know does it work or not.

You build success on facts. After you have a fact, you can build a new hypothesis, raise a new experiment - which can be tested - and that leads to more facts. That is the scientific process. I think a good starting point for that process, with this disease, is to establish whether your electron transport chain works or not, without trying to understand any specific reason it does not work. That's all I am trying to test by NAD+/NADH ratios and by looking at the level of ATP output. I'm testing the two endpoints of the electron transport chain, trying to establish that the problem lies somewhere in between.

It doesn't matter if there is hypoxia, or if there are mitochondrial transporter problems, or if there is mercury binding to iron-sulfur complexes in the ETC. That's all detail for later. Just start with something simple, like does the ETC itself not work, and you can work backwards to the ultimate cause later.

As a scientist myself, I would say that before you can construct a useful hypothesis you need to look at all the existing research data in the areas relating to your hunch.

I would start here with the research into mitochondrial dysfunction. Much (all?) has been discussed on here at some time. I've just found one here which I haven't read yet. Julia Newton has looked at ME/CFS myocytes in vitro - can't remember if she has looked at mitochondria/ETC/oxygen.

No point in reinventing the wheel until you have fully studied the existing wheel. By all means throw out ideas though. Brainstorming is good (especially as our individual brains tend to leave much to be desired with brain fog!).

 

[MeSci]

Its about intended effect. To increase the AMP-ADP pool we need ribose. As with all things though our tolerance varies patient by patient. A serious reaction to ribose might be something worth investigating, as I suspect it might give you clues to your personal biochemistry. What are the secondary consequences of consuming ribose? I have not investigated this.

One effect is hypoglycaemia due to an insulin spike.

 

[MeSci]

If I were in your shoes, I would think that conducting a few experiments is almost free.

I have been experimenting for years.

 

[pemone]

Actually the opposite - I keep looking at the larger picture. The ETC might not be broken. That is a possible miscategorization, and can lead to poor conclusions.

That's right, which is why you ask the question is the ETC broken, and one of the possible responses to that question is no it is not.

This is something that has yet to be shown. The system is not working, where the problem is, and whether or not its even inside the system, is not established. Its only hypothesized. It might be right, or not.

In terms of establishing a failure in aerobic metabolism, that was done in the 80s but remains unpublished (its part of the Ampligen studies). Workwell first published in 2007. We need mechanisms, not a vague problem.

You can bury yourself in 100 possible causes for an effect. I'm going to start by establishing that the effect does or does not apply to my case, and only once the answer is yes will I then work back to causes.

I won't invalidate your right of free will, but I don't think any problem could ever be solved by requiring as your first step a holistic solution to to the entire problem.

There are two considerations here. The first is as you suggest, that NADH will inhibit the Krebs cycle and boost lactate production. Its not good, but its not very bad eiter. Taking NADH prior to exercise is probably not the best idea though.

What this view ignores is the NAD-NADH pool. This is not a static thing, its a dynamic pool. The ratio is high, variously 3 to 700 for NAD/NADH in mammals. Over time the ratio of the two will probably stabilize, unless there are confounding factors. However confounding factors will put the NAD out of commission very fast ... you wont be able to supplement enough but have to address whatever the confounding factors are.

That's a great point, but over time as you repeat tests you will establish patterns. There is a lot of research literature that establishes the average values for people and those published values never go 3 to 700. A normal person has an NAD+/NADH between 500 and 2000 (that's the actual range). Moreover, the experimental way to measure this is to use lactate and pyruvate in a formula, and those metabolites do not swing wildly but seek values based on averages. If you test once every month and discover that:
* at rest you vary from 400 to 600 NAD+/NADH
* after light exercise you vary from 300 to 500 NAD+/NADH
* after heavy exercise a day later you are at 200 to 300 NAD+/NADH

You can objectify your condition from such data. Then you test therapies and see the result. You measure progress against increases in those numbers.

The fastest way to boost the NAD/NADH pool is to take NADH. Doing other things to improve the ratio is probably desirable however. Its very hard to boost NAD directly. Its always indirect, and aimed at increasing synthesis, unless taking NADH. I suspect the reason for this is that NADH is a more stable molecule so easier to market. Taking B3 relies on it being converted adequately, as its only a precursor. Yet boosting that path is probably also a good idea.

You can boost the pool, but what converts the NADH to NAD+. NAD+ drives a lot of processes. It's ETC complex I that does that conversion, so take all the NADH you want and if ETC does not work you are not going anywhere.

If you can find a stable NAD supplement that is cheaper than an NADH supplement, then its a better idea. Otherwise everything is trying to work around the issue that its hard to directly supplement NAD. I know there are some sublingual tabs on the market. Most other "NAD" supplements sold are NADH or precursors. You will find though that if you are taking NAD by swallowing it then very likely you will be absorbing NADH as it will be converted in stomach acid. So why bother?

I don't think there are any NAD+ supplements, probably it is too unstable? Instead there are precursors, like Nicotinamide Riboside. And there are oxidative therapies like ozone that supposedly convert NADH to NAD+ in a pretty spectacular way.

Now there are other potentially useful substances, though most of the work on things like resveratrol have not been adequately researched on human subjects. It works fine in a test tube though to boost NAD.

Resveratrol is certainly a curious thing. It has never made me feel better is all I can say for sure.[/QUOTE][/QUOTE]

 

[alex3619]

There are a few sublingual NAD supplements. You have to bypass the stomach or you just absorb NADH.

 

[Sidereal]

I can ask the question to any person who claims to have CFS: Is your electron transport chain / aerobic metabolism working? I don't need to understand the cause for it not working. I don't need to understand the reason it does not work (yet). I only want to know does it work or not.

I don't think anyone knows that. And actually, the reason why something isn't working is very important because the solution may depend on understanding the underlying cause. It may also help weed out dangerous or ineffective treatments.

And lets not confuse the concept of aerobic metabolism with electron transport chain. ETC could be working fine in principle and yet could be producing insufficient energy because you have problems before the ETC, say in the Krebs cycle or the pyruvate dehydrogenase complex.

 

[pemone]

Could uncoupling (of ATP production from the ETC) be involved, I wonder? We often get a fever with an infection. Lower energy + increased heat can be due to uncoupling.

These are crude numbers:
1) Glycolysis forms a net 2 ATP and 2 NADH
2) Pyruvate when oxidized forms Acetyl-CoA and produces 1 NADH per cycle, so 2 NADH per glucose molecule.
3) The Krebs Cycle forms 6 NADH and 2 FADH2 per glucose molecule (2 cycles).
4. 2 GTP converted to ATP

Once these get fed to the electron transport chain you end up with net 36 ATP (roughly).

So, seriously, how do you propose to uncouple ATP production from the electron transport chain, when almost all of the ATP is being produced by the ETC?! If your ETC is broken, you really are stuck in glycolysis, with its miserable 2 net ATP per glucose molecule.

Of course in reality you cannot lose the ETC entirely, or you would be dead in about 10 seconds. So this is mainly about ETC getting degraded, not breaking completely.

 

[pemone]

There are a few sublingual NAD supplements. You have to bypass the stomach or you just absorb NADH.

Can you post a few links to those?

Now you have me wondering: could you design a liposomal delivery system for that? That would be an exciting therapy to try.

 

[pemone]

As a scientist myself, I would say that before you can construct a useful hypothesis you need to look at all the existing research data in the areas relating to your hunch.

I would start here with the research into mitochondrial dysfunction. Much (all?) has been discussed on here at some time. I've just found one here which I haven't read yet. Julia Newton has looked at ME/CFS myocytes in vitro - can't remember if she has looked at mitochondria/ETC/oxygen.

No point in reinventing the wheel until you have fully studied the existing wheel. By all means throw out ideas though. Brainstorming is good (especially as our individual brains tend to leave much to be desired with brain fog!).

And how did I find a way to use pyruvate and lactate to approximate NAD+/NADH if I didn't read literature?

I'm asking a specific question about the ETC: how well does it work. I don't have to read every study ever published to ask that question. I'm not testing a hypothesis. I am establishing a fact.

 

[alex3619]

Can you post a few links to those?

Here is one: http://www.iherb.com/Source-Naturals-Coenzymated-B-3-Sublingual-25-mg-60-Tablets/1039

Its a B3 and NAD combo.