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

[pemone]

I find that I must limit my intake of high nitrate foods. I don't understand the implications of it yet.

Which specific foods, and why?

 

[Sidereal]

How did you fix this problem for yourself?

I wouldn't assume that the problem is fixable.

If mankind was so fragile that a change in diet composition was enough to kill us, I don't think we would have made it as a species. I think it was common for our ancestors to eat vastly different diets from one month to the next. You eat what is available on a given day or week. You are ketogenic one week, eating 80% fruit the next week, eating mostly protein and fats when you catch some fish, etc. That kind of metabolic flexibility must be hard wired into our species, and it explains why we have so many metabolic pathways for creating energy. The body has to be able to adjust to such things, and it cannot be so fragile that it requires a specific balance of carb/protein/fats to survive.

This is a commonly used argument by people who say that changing your macronutrient ratios couldn't possibly have made you sick. It's a fallacy. It doesn't matter what hypothetical healthy humans roaming the savannah could or could not eat. What matters to your situation is only is how fragile your body is, and if you find yourself needing to post on PR, it's unlikely that you are very robust. Sickly people with fatigue who couldn't keep up with the rest would have likely died very quickly anyway. It's only due to the luxuries of modernity that we get to sit here and speculate about what they ate.

It's important to also keep in mind that ancestors weren't eating heavy cream and steak when they were ketogenic. The modern ketogenic diet doesn't make you sick because of what you eat but rather because of what you DON'T eat. Think algae, insects, roots covered with soil, tree bark etc. Most people when they go low carb remove what paltry amount of fibre they were eating before so now you are providing virtually no prebiotic substrate to feed your beneficial bacteria, thus setting yourself up for really big problems. Yes, this can cause a complete metabolic breakdown.

I don't want to drag the thread off-topic so I'll just add a couple of brief comments. With ME/CFS it's really easy to make yourself worse with incorrect assumptions and supplements that stem from those. Based on your comments about having tried to raise NO and believing we are suffering from excess NADH, i.e. reductive stress, I think there is a danger of making yourself sicker because shifting the redox state in an even less favourable direction is the worst thing you could do in this illness since it is the core pathology we're all trying to address. I would recommend familiarising yourself with Paul Cheney's thoughts on the redox issue and the methodology he has used to study this in his patients and what happens when he gives them supplemental oxygen or supplements commonly recommended around here like fish oil, methylcobalamin, 5-MTHF etc. I don't have any handy links since he doesn't publish anything; it's all lectures or transcripts of conversations he's had with his patients. Martin Pall's work on NO/ONOO is also very important.

Sadly, as you've already discovered with low carb and random ALA dosing, people with CFS and those predisposed to develop it are far from robust and sometimes never recover from some seemingly banal experiments/supplements/meds so all I can say is be careful.

Seeing as you have not been sick very long, I would suggest not getting wedded to any particular theory but rather trying to get as much information as possible from clinicians who have dealt with us for decades and have developed an intuitive feel for what works and what doesn't. If you have mercury toxicity, by all means chelate the mercury. No doubt the amalgams and mercury in vaccines are a public health catastrophe which has contributed to the epidemic of chronic illness. But Dr Cutler's protocol has been around for 15 years and if mercury were THE answer, as opposed to an answer for some people some of the time, we would have seen a lot more cures.

Regarding the microbiome, there is an emerging and pretty compelling literature that it is involved in all kinds of chronic disease and I can't possibly summarise it here. Genova and other currently available commercial tests are worthless since the likely problem isn't some huge pathogen in the gut but rather an absence of key anaerobic species that produce butyrate among many other functions. There is a whole subforum here on PR about the gut where you can get a lot of useful information.

 

[alex3619]

Do you have a link to her claim that CFS patients are alkaline at rest?

Hi @pone, no I don't have a link handy. I think it was discussed in a video conference last year, but I am not sure the paper is published yet.

I started to reply earlier but needed to do some research to be sure what I was saying was accurate.

With regard to 2,3 bisphosphoglycerate, there was an interest in this in the late 90s but repeated testing (probably unpublished) could not confirm a deficiency. If this is normal then lactic acidosis is not present. In fact, privately, I was informed that repeat lab testing shows high 2,3bpg, which indicates alkalinity not acidity. However as a marker this is a time average .. it indicates (indirectly) average blood pH . Spot pH will depend on activity, and the activity we use to get a test done may make us acidic. So only in a fully rested state will we get to see alkalinity, and even then not until a while after activity stops.

We will indeed produce lactic acid, but its not that we are stuck in glycolysis but the Krebs cycle cannot ramp up to meet need. Why this is happening is still being debated and investigated. There are lots of theories, and most have some evidence for them. It may also be that several theories are right but its combinations of things or right for different subgroups.

At rest though, in milder patients, we should not see much lactic acid in blood. Now, we might in spinal fluid if our brains are being pushed. In exercise we can expect huge rises in lactic acid.

I first got interested in this line of research in the 90s. Its been looked at for that long. However a decade and a half of testing has failed to find the cause.

All bets are off for the severely disabled with ME. Just surviving might push them in to lactic acid overload. They are the people most at risk.

This table lists many triggers for lactic acidosis:

Hypoxia and carbon monoxide poisoning have both been considered in ME.

http://wp.nyu.edu/biochemistryshowc...14/01/Biochemj-MulQuiney-Kuchel-MCA-23BPG.pdf

Another aspect of 2,3-BPG metabolism that had not been fully explored was whether the rate of metabolite flow through the 2,3- BPG shunt is biologically important. In by-passing phospho- glycerate kinase the shunt allows the metabolism of glucose without net production of ATP. In other words, the extent of flux through the shunt relative to the flux through the main glycolytic pathway will affect the glucose ATP stoichiometry which could vary from 0:1 to 2:1. Thus it has been suggested that the 2,3- BPG shunt `uncouples' the supply of NADH from the pro- duction of ATP [23] NADH production is particularly important in erythrocytes because it serves to maintain Hb in its functional Fe(II) state by acting as a cofactor in the reduction of met- haemoglobin (Met-Hb) [Fe(III)] by NADH:Met-Hb reductase.

(This paper is not very readable, but this comment comes from the intro.)

The shunt is a name for the pathway in which 2,3 BPG is synthesized. It is also known as the Rapoport Leubering Cycle. It is primarily active in red blood cells. I am unsure it makes much of a difference in other tissues. If it disturbs NADH metabolism then it might mean our blood NAD/NADH ratio might not reflect our tissue NAD/NADH ratio. What is more clear is that the NADH/ATP or NAD/ATP ratio in the blood might be disturbed.

What is of interest here is that any form of hypoxia/anoxia might result in these issues, and that includes a bad NAD/NADH ratio as a possible cause out of maybe hundreds of possible causes.

Since there are a great many factors that can cause this, it may be that we are a population with a range of different issues but similar final result. Or it may be that a combination of factors might drive this, and that combination might vary slightly patient by patient.

This last view is the one I favour ... we know of many risk factors, and some like B12 deficiency, EDS and small fiber polyneuropathy may indicate problems with the regulation of peripheral vasculature, resulting in local tissue hypoxia. I am currently of the view that many factors combine to induce final pathophysiology.

 

[MeSci]

The biggest and most rapid acidifier of urine is inflammation/allergy. I knew a woman with migraines who used her allergy to corn to successfully treat her migraine attacks. The early (prodromal) state for migraines is alkaline-anaerobic-anabolic stress, which shows in non-inflammed individuals as an alkaline trend in the urine which reaches an alkaline threshold (a different pH reading in each individual), at which time prostaglandins are produced to quickly acidify the body/blood stream and produce the full-blown migraine symptoms.

Do you have a reference for prostaglandins acidifying the blood/body? I can't find anything that says this; in fact this page says

Prostaglandins are involved in several other organs such as the gastrointestinal tract (inhibit acid synthesis and increase secretion of protective mucus)...

 

[MeSci]

With regard to 2,3 bisphosphoglycerate, there was an interest in this in the late 90s but repeated testing (probably unpublished) could not confirm a deficiency. If this is normal then lactic acidosis is not present. In fact, privately, I was informed that repeat lab testing shows high 2,3bpg, which indicates alkalinity not acidity. However as a marker this is a time average .. it indicates (indirectly) average blood pH . Spot pH will depend on activity, and the activity we use to get a test done may make us acidic. So only in a fully rested state will we get to see alkalinity, and even then not until a while after activity stops.

We will indeed produce lactic acid, but its not that we are stuck in glycolysis but the Krebs cycle cannot ramp up to meet need. Why this is happening is still being debated and investigated. There are lots of theories, and most have some evidence for them. It may also be that several theories are right but its combinations of things or right for different subgroups.

At rest though, in milder patients, we should not see much lactic acid in blood. Now, we might in spinal fluid if our brains are being pushed. In exercise we can expect huge rises in lactic acid.

I first got interested in this line of research in the 90s. Its been looked at for that long. However a decade and a half of testing has failed to find the cause.

All bets are off for the severely disabled with ME. Just surviving might push them in to lactic acid overload. They are the people most at risk.

This table lists many triggers for lactic acidosis:

Hypoxia and carbon monoxide poisoning have both been considered in ME.

http://wp.nyu.edu/biochemistryshowc...14/01/Biochemj-MulQuiney-Kuchel-MCA-23BPG.pdf


(This paper is not very readable, but this comment comes from the intro.)

The shunt is a name for the pathway in which 2,3 BPG is synthesized. It is also known as the Rapoport Leubering Cycle. It is primarily active in red blood cells. I am unsure it makes much of a difference in other tissues. If it disturbs NADH metabolism then it might mean our blood NAD/NADH ratio might not reflect our tissue NAD/NADH ratio. What is more clear is that the NADH/ATP or NAD/ATP ratio in the blood might be disturbed.

What is of interest here is that any form of hypoxia/anoxia might result in these issues, and that includes a bad NAD/NADH ratio as a possible cause out of maybe hundreds of possible causes.

Since there are a great many factors that can cause this, it may be that we are a population with a range of different issues but similar final result. Or it may be that a combination of factors might drive this, and that combination might vary slightly patient by patient.

This last view is the one I favour ... we know of many risk factors, and some like B12 deficiency, EDS and small fiber polyneuropathy may indicate problems with the regulation of peripheral vasculature, resulting in local tissue hypoxia. I am currently of the view that many factors combine to induce final pathophysiology.

Very interesting, thank you, @alex3619. As I looked at your table, I had the same thought as you - a number of the listed factors appear likely, both hypoxic and non-hypoxic, so a combination - which may vary between patients - seems likely.

I have for some years suspected uncoupling, but was unclear as to the mechanism that might cause it. The reason I suspected it is that when I exert myself, the exhaustion is accompanied by feeling extremely hot, which could indicate uncoupling - instead of producing ATP, the body produces heat, as in the non-shivering thermogenesis used by hibernating animals.

I wonder whether I could deduce anything from taking my temperature before and after exertion. I'd need to have the thermometer ready, as when I get exhausted and hot I have to sit down! Would an oral temperature reading pick up any temperature change?

 

[MeSci]

Sorry everyone for the cross-talk and for going a little off-topic (it's all related after all...)

I never got sustained benefit from probx. I feel that both prebx and probx are immunostimulants and harmful to me right now (trigger inflammation).

My own prebiotics are food. I don't take prebiotic supplements. My vegan diet should provide plenty.

 

[alex3619]

Prostaglandins are the full range of vasodilator, inflammatory, antiinflammatory and more. WHICH prostaglandins are produced and in what amounts are the key. They are critical for healing. They are also critical for inflammation. Its a broad family of hormones, and I do not fully understand them - not even close. The research on this is broad, deep, and confused, or was the last time I looked. I suspect prostaglandins are not even fully understood by "experts".

Think of them this way. They are one of several classes of hormones that a cell uses to communicate with itself and with nearby cells. Whatever its triggering can then become a chain reaction throughout a tissue. Half-lives are typically only seconds. Some breakdown products tend to be more stable though, and often these are what we measure and then infer the presence of the prostaglandin.

Prostaglandins fit within a larger family of hormones called eicosanoids.

If someone finds a really good text on them, online, free, please post a link.

PS If COX is the key, then all the eicosanoids may be affected, not just prostaglandins.

 

[alex3619]

I wonder whether I could deduce anything from taking my temperature before and after exertion. I'd need to have the thermometer ready, as when I get exhausted and hot I have to sit down! Would an oral temperature reading pick up any temperature change?

Maybe, in a large controlled study. As an individual, how do you tell what is due simply to activity? Exercise produces heat anyway. To use temperature as a measure would, I think, require many samples and statistical analysis.

 

[Sidereal]

My own prebiotics are food. I don't take prebiotic supplements. My vegan diet should provide plenty.

A vegan diet probably provides a lot of resistant starch but there are many different types of prebiotics which feed different bacteria and thus produce vastly different effects. Diet is generally not enough to steer things in the gut in a better direction. A lot of people with ME/CFS eat really great clean diets and are still sick.

 

[Gondwanaland]

Which specific foods, and why?

Celery, beets, lettuce, herbal teas. I feel like I am suffocating if I overdo with them (especially around the thymus and the glottis). I eat them regularly, but small amounts at a time.

Sickly people with fatigue who couldn't keep up with the rest would have likely died very quickly anyway.

And I doubt the healthiest ones would live more than 30 years. With my SNPs and lifestyle, my real problems only started at 42.

 

[Gondwanaland]

How about if I throw in the phrase "[something] Benefits PEM"? (get it?)

In my defense, several months ago I bought a rebounder and could only use it for about 3-4 times for no longer than 30-40 seconds.

 

[Sherlock]

How does [rouleaux] get diagnosed and what is the consequence?

-by microscope
-a fast SED

Yeah, I am probably taking on some risk by thinning my fibrin without knowing what to test later to track effects.

you can look for gums bleeding, or easy bruising

[edit: the chances of a problem are probably very small, unless you have some special risk]

Can you explain the other comment about non-CAD non-CVA danger?

hypercoaguable blood would be a risk in Coronary Artery Disease (plaques, e.g) or Cerebral Vascular Accident (stroke) -- then also DVT, claudication (leg pain from blocked arteries), etc

The thing is, I don't actually have proof that I am hypercoagulable do I? There was no bleeding study done for me. What was done was a sedimentation rate test, and this is normally used to assess inflammation. If the blood is not viscous and particles fall through quickly, this is a marker of high inflammation. My blood was at the far end of the other range, which one osteopath commented meant that my blood is "thick". That's not the way the test is normally used probably.

I'd guess you'd want PT PTT INR or whatever, That's beyond me.

Thick blood might be from dehydration, then you'd see that in creatinine, BUN ratio (I think)

 

[Sherlock]

For NO to be harmful

There are the POTS people and others who would get more syncope from more NO mediated vasodilation --> lowered BP.

 

[MeSci]

Dave Whitlock says ME/CFS has low NO, whereas Prof Martin Pall says the opposite, that ME/CFS has high NO (and high peroxynitrite).

I have an idea that they both might be right:

To fight an infection, the immune system may generate a hell of a lot of NO via the iNOS enzyme, which is secreted by the immune system. For antimicrobial purposes, iNOS pumps out NO at levels 1000 times higher than the NO generated by the other two NO enzymes, eNOS and nNOS.

So my idea is that when iNOS is at a high level on a long term basis (as a result of fighting the chronic infections found in ME/CFS), after some time the body might up-regulate the processes that break down iNOS, to ensure blood levels if iNOS-generated NO don't get too high. These processes that break down iNOS may then start breaking down eNOS (which makes NO for vasodilation) and nNOS (which makes NO for neurotransmission) as well. So what may happen is that high levels of iNOS may inadvertently cause a reduced levels of eNOS and nNOS.

Either that, or the chronic high levels of NO generated by iNOS may cause epigenetic changes that down-regulate the gene expression of eNOS and nNOS, so that you don't get sufficient NO made for vasodilation or neurotransmission.

So in summary, my idea is that the chronically high levels of iNOS might conceivably have a paradoxical effect of lowering eNOS and nNOS.


Anyway, this is how I speculate ME/CFS may involve both high NO in the areas of infection, and low NO everywhere else. Just an idea.


Note that asymmetric dimethylarginine (ADMA) and N(G)-monomethyl-l-arginine (l-NMMA) are the body's inhibitors of the NOS enzymes. ADMA levels are increased in patients with fibromyalgia. 1

I have just realised that I have a genetic polymorphism (SNP) in the eNOS gene. The SNP is
G894T, which according to some sources leads to less nitric oxide, so less smooth muscle relaxation, and reduced platelet activity. Other names and details re the SNP:

• eNOS aka NOS3
  
• Ex8-63G>T
• rs1799983
  
• amino acid change Glu298Asp

I wonder how many of us have this?

The recommendation I have been given for this SNP is to take more omega-3, and I am now, but am also on a beta blocker for seriously-high blood pressure. I have long wondered why I suddenly developed high BP after it being normal for decades, and about ten years after getting ME. Something must have affected/amplified the way the SNP affects me, or maybe removed/inhibited something that was countering it. I did become briefly borderline obese about five years before the hypertension was spotted, and was overweight for maybe a decade.

But I always suspected that the immediate cause of my high bp was excessive vasoconstriction. Shame some/most doctors appear to have no interest in the cause of things and just throw drugs at them in a random way.

Looks like I could do with something that boosts nitric oxide.

 

[Sherlock]

Looks like I could do with something that boosts nitric oxide.

How about a book from a Nobel Prize winning co-discoverer of NO, Louis Ignarro?
http://www.amazon.com/More-Heart-Disease-Prevent--Even-Reverse--Heart/dp/0312335822

Arginine, Citrulline, maybe also Mg. Probably won't work, though. I see he also has a newer book now.

 

[Hip]

@MeSci
Though my NOS3 gene when looked up here on 23andme has a set of 35 different SNP rs codes under it, the rs1799983 code you mentioned above does not seem to be there in that set.

 

[MeSci]

How about a book from a Nobel Prize winning co-discoverer of NO, Louis Ignarro?
http://www.amazon.com/More-Heart-Disease-Prevent--Even-Reverse--Heart/dp/0312335822

Arginine, Citrulline, maybe also Mg. Probably won't work, though. I see he also has a newer book now.

I don't have the time or energy to read books, I'm afraid. I have lots I haven't got round to reading! But I may try Mg sometime.

 

[MeSci]

@MeSci
Though my NOS3 gene when looked up here on 23andme has a set of 35 different SNP rs codes under it, the rs1799983 code you mentioned above does not seem to be there in that set.

What are the other details about your NOS3 SNP? The letters, amino acids, etc. (I can't get into that site as I'm not registered.)

 

[Hip]

What are the other details about your NOS3 SNP? The letters, amino acids, etc.

Here is what my own 23andme results look like for the NOS3 gene:

GENE ---------------------- POSITION -------- SNP ------- VERSIONS ---- MY GENOTYPE

 

[drob31]

This is probably way off topic but I was researching sodium bicarbonate in a round about kind of way. I was trying to find a natural ACE inhibitor and stumbled upon SB. It's very interesting that it could be used for PEM as well. I don't have PEM anymore, but I have NO issues which I think may be related to ammonia, or histamines. It seems to all fit together somehow.