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

[pemone]

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.

Anyone can know that. Get a pyruvate and a lactate together. Plug into formula. You know what your NAD+/NADH status is, and if the ratio is low you know your ETC doesn't work well because ETC is what converts NADH to NAD+.

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.

That's right, which is why I suggest testing ETC at its endpoints. You test NAD+/NADH to establish that Krebs is working and ETC is not. Krebs creates high NADH. ETC converts NADH to NAD+.

Test ATP at the ETC output. If that is low, metabolism is not running correctly, and if NAD+/NADH is low Krebs is pushing on the ETC and ETC is not responding well. The problem must exist between the place where NAD+ is created and where ATP is output. And the only thing that lives between those tested endpoints is the ETC itself.

 

[Sidereal]

Anyone can know that. Get a pyruvate and a lactate together. Plug into formula. You know what your NAD+/NADH status is, and if the ratio is low you know your ETC doesn't work well because ETC is what converts NADH to NAD+.

Do we know that the formula works for every condition and doesn't break down in specific situations? If we assume it does work, would the ratio of pyruvate to lactate in the blood reflect the intracellular NAD+/NADH ratio, say in the muscle?

 

[pemone]

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

Its a B3 and NAD combo.

As you know, there are three niacin precursors to NAD+:
* niacin
* niacinamide
* nicotinamide riboside

I think that ad is simply selling niacin and hiding the fact that it is a precursor to NAD. I don't think you are eating NAD+ directly.

Something I don't understand well at all is quantitatively how much NAD+ can be derived from niacin or its other precursors that you eat versus the quantities that are recovered through the electron transport chain. Common sense tells you that a few niacin pills cannot compete with the NADH to NAD+ conversion going on in the entire body in the electron transport chain?

 

[pemone]

Do we know that the formula works for every condition and doesn't break down in specific situations? If we assume it does work, would the ratio of pyruvate to lactate in the blood reflect the intracellular NAD+/NADH ratio, say in the muscle?

It needs to be plugged into a research formula, based on Krebs' original research. And I'm still validating the values of constants in that formula with a researcher.

To my understanding these two metabolites have a direct relationship based on NAD+/NADH ratios that would be very very hard to nullify.

 

[alex3619]

Niacin (as inositol hexanicotinate 27 mg and nicotinamide adenine dinucleotide 25 mg)

(my bolding and underlining.)

 

[pemone]

(my bolding and underlining.)

You are right the ingredient list has NAD. So it's a matter of would it survive digestion, and I guess the answer is no.

 

[alex3619]

Do we know that the formula works for every condition and doesn't break down in specific situations? If we assume it does work, would the ratio of pyruvate to lactate in the blood reflect the intracellular NAD+/NADH ratio, say in the muscle?

Blood and tissue (especially muscle) NAD/NADH ratios need to be measured separately. In us the brain tissue ratio would also be important. Its unclear that there is an easy way to do this in brain, though I think we can use scans to detect some metabolites ... I do not recall if lactate is one. Lactate might be a good surrogate marker though, and would probably serve in most cases. You can also measure it in spinal fluid.

In any case if the NAD/NADH ratio was normalized then lactate should fall to normal production, so while maybe not equivalent it might still be easier to figure out and use. You cannot easily use pH as a surrogate though due to the acidification from carbon dioxide.

 

[alex3619]

You are right the ingredient list has NAD. So it's a matter of would it survive digestion, and I guess the answer is no.

It does not survive digestion, hence its sublingual. When digested you would most likely get NADH instead.

 

[pemone]

Blood and tissue (especially muscle) NAD/NADH ratios need to be measured separately. In us the brain tissue ratio would also be important. Its unclear that there is an easy way to do this in brain, though I think we can use scans to detect some metabolites ... I do not recall if lactate is one. Lactate might be a good surrogate marker though, and would probably serve in most cases. You can also measure it in spinal fluid.

In any case if the NAD/NADH ratio was normalized then lactate should fall to normal production, so while maybe not equivalent it might still be easier to figure out and use. You cannot easily use pH as a surrogate though due to the acidification from carbon dioxide.

In a perfect world we would test every tissue in the body and look for differences against established averages for those tissues. In the real world, we are not going to biopsy your brain, your heart, etc. So we need a proxy for the entire system.

Can you imagine any case where someone has poor NAD/NADH in their plasma but everything runs splendidly well in their tissue cells? If you feel like you have no energy, and the plasma test says your NAD/NADH is compromised, it isn't a stretch to say your tissue biopsy would give a similar result. Plasma is just a proxy here.

The point of this test is not to establish any absolute truth about your tissue NAD+/NADH. Rather, it is to establish a numeric benchmark against which you can test therapies as you progress. As tissue metabolism improves, so should plasma numbers. That's the assumption, and it would be weird if that assumption were wrong.

 

[pemone]

It does not survive digestion, hence its sublingual. When digested you would most likely get NADH instead.

It's interesting. Will have to ask my coaches about that one. You think it is getting converted to NADH even if you leave under tongue?

I just wonder about the quantity you are getting. I mean how much NAD+ can they really affect compared to the amount the body actually needs to run when the ETC is not working well?

 

[Sidereal]

In a perfect world we would test every tissue in the body and look for differences against established averages for those tissues. In the real world, we are not going to biopsy your brain, your heart, etc. So we need a proxy for the entire system.

Can you imagine any case where someone has poor NAD/NADH in their plasma but everything runs splendidly well in their tissue cells? If you feel like you have no energy, and the plasma test says your NAD/NADH is compromised, it isn't a stretch to say your tissue biopsy would give a similar result. Plasma is just a proxy here.

The point of this test is not to establish any absolute truth about your tissue NAD+/NADH. Rather, it is to establish a numeric benchmark against which you can test therapies as you progress. As tissue metabolism improves, so should plasma numbers. That's the assumption, and it would be weird if that assumption were wrong.

Well, it's not an unreasonable assumption that there may be tissue differences in NAD+/NADH ratio. pH differs from tissue to tissue. You don't need a tissue biopsy to measure some things. A previous study for instance measured lactate in CFS patients' cerebral ventricles using magnetic resonance spectroscopy. This is non-invasive.

 

[alex3619]

It's interesting. Will have to ask my coaches about that one. You think it is getting converted to NADH even if you leave under tongue?

I just wonder about the quantity you are getting. I mean how much NAD+ can they really affect compared to the amount the body actually needs to run when the ETC is not working well?

Saliva is alkaline, so I think the NAD would survive. However it becomes unstable when dissolved (its stable dry and at cool temperatures away from sunlight). The time it takes to absorb however should not leave it vulnerable to regular chemical instability.

 

[alex3619]

So we need a proxy for the entire system.

I suspect this is a fundamental reason why the research has failed to advance in decades. I realized in 1999 that this is a bad idea, its a big part of why I went back to university to finish my biochem degree. Using this view we did NOT have any aerobic or ETC problem. It tests fine at rest (in the vast majority of mild patients). Why test it under a challenge? Yet when special conditions are used, the body under metabolic stress (such as exercise) that we see major issues arising.

Its the special conditions, when and where things happen, that give you vital clues as to what is actually happening.

 

[Sherpa]

I'm taking SOD in the PM and have not noticed any effect. Do you feel like it immediately has some stimulative effect? Maybe I should follow you and take in morning?

The first time I took it, in the afternoon, it had an immediate stimulative effect that was pronounced and slightly uncomfortable. A buzz like too much CoQ10. I take this reaction to mean I was very low. On subsequent days it smoothed out and the buzz is not (as) noticeable. But my problems with sun exposure and fatigue are less noticeable, too.

 

[MeSci]

As you know, there are three niacin precursors to NAD+:
* niacin
* niacinamide
* nicotinamide riboside

I think that ad is simply selling niacin and hiding the fact that it is a precursor to NAD. I don't think you are eating NAD+ directly.

Something I don't understand well at all is quantitatively how much NAD+ can be derived from niacin or its other precursors that you eat versus the quantities that are recovered through the electron transport chain. Common sense tells you that a few niacin pills cannot compete with the NADH to NAD+ conversion going on in the entire body in the electron transport chain?

There is a summary of info about niacin supplementation here.

 

[MeSci]

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.

I'm not sure what you are saying here. Uncoupling does occur in living creatures, for example hibernating animals. There are references in several threads.

Here is one paper that links uncoupling to ME/CFS.

 

[Hip]

No I am not equating the feeling of fatigue with reduced energy production. The whole point of my post is that I am MEASURING decreased ETC function, and I am basing my actions on those measurements.

What I am saying is that the fatigue symptoms that an ME/CFS patient has may be nothing to do with the mitochondria, but more to do with sickness behavior and its associated pro-inflammatory cytokines in the brain.

The cytokines associated with sickness behavior are primarily IL-1β, IL-6 and TNF-α. Now interestingly enough, it has been shown that even when healthy people were injected with IL-6, this caused them to get fatigued and reduced their ability to concentrate (ie, brain fog-like effects). IL-6 is released by the muscles in massive quantities during exercise — so this could well help explain PEM.

The increase in lactate levels after exercise will also increase inflammation in the brain, as lactate has been shown to ramp up the production of IL-1β, IL-6 and TNF-α in rat brain cell cultures, which would worsen sickness behavior. So both IL-6 and lactate when released during exercise may be the driving force behind PEM; this duo may dramatically worsen sickness behavior, thus giving rise to fatigue and PEM.



Though it's quite possible that there are different subtypes of ME/CFS, and in one subtype the mitochondria may be fine and the ME/CFS may arise from the sickness behavior cytokines IL-1β, IL-6 and TNF-α; whereas in another subtype, it may be mitochondrial problems that underpin many of the ME/CFS symptoms.

What you might consider is trying a cocktail of supplements that support mitochondria. A while ago I experimented with this mitochondria cocktail:

Mitochondrial cocktail:
Deprenyl 5 mg
Rhodiola rosea 350 mg
Lecithin 1200 mg
IGF-1 Nutronics Labs (139ng/drop) 4 drops sublingual
Lithium orotate 125 mg
7-keto DHEA 50 mg
Leucine 5 grams
Glutamine 5 grams
Niacinamide 1000 mg
Ginkgo biloba (24%) 60 mg
Piracetam 2 grams
Q10 200 mg
Magnesium (as malate) 280 mg
Lauricidin (monolaurin) ½ scoop
Taurine 1000 mg
Acetyl-L-carnitine 800 mg
Alpha lipoic acid 250 mg
Pyrroloquinoline quinone (PQQ) 20 mg
Benfotiamine 80 mg
Carnosine 1000 mg
Sodium bicarbonate ¼ tsp
Creatine monohydrate 2 grams

All the above have one or more supportive effects in the mitochondria, whether it's supporting the mitochondrial membranes, or boosting the various mitochondrial complexes. These supplements did not help me much, but they might help patients who have mitochondrial problems.

Some other mitochondrial boosting or mitochondrial supportive supplements and drugs are given in the first post of this thread, along with some references.

 

[alex3619]

Fatigue and lack of energy are NOT the same thing. In that I agree with you @Hip. Fatigue is likely hormone and central nervous system related to a large extent, though the Light's research does show peripheral sensitivity to acid if I recall correctly. The issue in question though is whether or not the low energy is contributing to central nervous system dysfunction. It would be nice if restoring brain energy reduced microglial activation or something. Normalizing lactic acid production should help a lot, even if it turns out its not on the causal pathway/s.

 

[MeSci]

Fatigue and lack of energy are NOT the same thing. In that I agree with you @Hip. Fatigue is likely hormone and central nervous system related to a large extent, though the Light's research does show peripheral sensitivity to acid if I recall correctly. The issue in question though is whether or not the low energy is contributing to central nervous system dysfunction. It would be nice if restoring brain energy reduced microglial activation or something. Normalizing lactic acid production should help a lot, even if it turns out its not on the causal pathway/s.

Do we know whether it's excessive lactic acid production that is the problem, or a failure to dispose of it quickly enough? Hypoxia would cause the latter, wouldn't it? This paper examines different causes of hyperlactaemia. Here is another interesting one about lactic acidosis, which includes reference to uncoupling and sodium bicarbonate.

 

[Mya Symons]

One interesting thing about taking sodium bicarbonate to treat systemic acidosis is that while this alkalizes the body, bicarbonate can have an acidifying effect in the brain tissues, according to this study.

However the study authors found that when they used Carbicarb, which is just a mixture of sodium bicarbonate (baking soda) and sodium carbonate (washing soda), this achieved alkalization of both the body and the brain tissues.

I actually bough some food grade sodium carbonate a while ago, in order to make my own Carbicarb, as I thought that ensuring both the brain and body get alkalized might have greater benefit. But I did not do that much experimentation with Carbicarb. In the light of this thread, I may start using Carbicarb again, and comparing it to bicarbonate.



The main problem I get with alkalization is that it makes me feel unpleasantly lightheaded. I understand that becoming lightheaded from alkalizing diets or alkalizing supplements is not uncommon. A while ago I speculated why alkalizing may cause lightheadedness, and my conclusions I quote below:

Hip, where do you get the Carbicarb? Can you buy it online? If not, how much of each did you mix together? I would also like to try this to see if it works even better.