Dealing With CFS As Metabolic Acidosis

[pemone]

I came down with something very similar to CFS around December of 2013. In November I had started on a very low carb diet, and that initiated a large water weight loss that I probably could not afford. I started at a lean 170 and went to 159. As I lost the weight extreme fatigue set into my muscles, and no amount of food or water appeared to correct whatever it was I had broken with the diet. I went from working 14 hours a day to three hours, and even during those three hours I had no real muscle energy. I had a strong mental fog as well. I want to describe briefly how I proceeded, and what I have done to treat this.

The first shock for me was that no one in the medical system sees this as a real disease, and once each specialist rules out one of the major diseases that he treats, they simply stop working on your case. I think this is why so many CFS people end up having to become their own general practitioner and do so much research on their own.

At its worst, what would happen is that I would do some high intensity exercise like sprinting, and I would then become desperate for water, and I would spend an entire night exhaling rapidly and drinking large amounts of water. Unfortunately, my body would excrete the water rapidly and I would never get rehydrated. It's really strange to me that I would describe these extreme symptoms to multiple doctors, and none of them registered that this was something worth investigating. It was like I was describing taking out the garbage to them, and what did they have to do with that? To me the patient, these experiences felt like I was in the end stage of a terminal disease. What could be worse than going out for a normal exercise session and ending up fatigued, dehydrated, and your body signaling the abnormality by changing your breathing pattern to rapid deep respirations?

After months of dead ends, my big breakthrough came when I realized that salt water improved my condition. It did not remove the muscle fatigue, but it certainly improved it for about two hours after each salt infusion. That made me believe I had an electrolyte issue, but the electrolyte tests all showed normal ranges. The exception to that was a low sodium result once, but I caused that result by drinking one liter of water every hour during one of these episodes of dehydration. It turns out that low sodium can be caused by drinking too much water.

More researching and then it all came together. What I realized is that my muscles are not releasing lactic acid. Even minor lifting of heavy objects is enough to produce enough lactic acid to fatigue the muscle. And since the body is not clearing that acid, the fatigue it causes extends out to days and weeks, as additional exercise keeps adding onto the lactic overload.

Then I realized that my abnormal breathing was in fact the body compensating for metabolic acidosis. The lactic / metabolic overload of acid in my muscle was causing my body to compensate to lower my pH by forcing my respiration to rapidly exhale CO2. The body is breathing out extra acid in order to keep body pH normalized.

This is when all of the pieces came into place for me. In reading about how to clear lactic acid, I read that many people have luck using sodium bicarbonate. There are reports of vinegar and vitamin c/acetic acid also supporting one of the metabolic cycles that clears lactic acid. A few weeks ago I replaced my salt infusions with sodium bicarbonate. The response was immediate, and rapid. All of the muscle fatigue started to lift. Within two days of taking 1/4 teaspoon of sodium bicarbonate on an empty stomach eight times a day, the muscles felt back to about 60% of normal. And every day since then it gets better.

Unfortunately, this amount of sodium bicarbonate gives you a lot of sodium. So I am looking in the near future to transition to potassium bicarbonate. There is good research showing that potassium in therapeutic doses will spare the body from using calcium as a pH buffer, and bone loss markers improve. The RDA for potassium is around five grams, and most people in US get less than three grams from diet. My goal for now is to start supplementing somewhere around four grams of potassium and maybe 1/2 gram of sodium, to keep the potassium to sodium ratio high, and to minimize any sodium intake.

I am not advocating that anyone do any of the above steps. A person with normal kidney function should be able to easily handle four grams of potassium. Someone with impaired kidney function, or taking certain drugs, might not deal with it well.

At this point it is too early to say I am cured. I feel like I am treating symptoms not causes. But I am starting to gain back the lost weight and starting to recover my muscle energy. The brain fog is still there but is slowly improving. If I can hold the body weight and start exercising, I am hoping I will continue to make progress.

I am curious if any of you have tried to treat CFS as a kind of chronic metabolic acidosis. Have you had luck with any specific therapy that addresses that issue?

 

[Ambrosia_angel]

It's interesting to hear that your issues started after you went low carb. I went low carb and suffered the worst in my life with my muscles. I didn't connect the two until I started back on eating more carbs.

I was drinking sodium bicarbonate at one stage but that wasn't for my muscles even though that was around the time I was having issues with them. I didn't notice a physical improvement but I wasn't deteriorating either.

Thank you for this. I might try drinking bicarb of soda again. Its worth a shot.

 

[alex3619]

Lactic acid does not cause muscle fatigue. It is associated with muscle fatigue, not the same thing. In the short term it relieves muscle fatigue, and fairly directly increases oxygen dumping. In the long term it runs a risk of lactic acidosis, which is indeed an acid state. This is because it indirectly slows oxygen dumping, starving the body of oxygen, which leads to higher lactic acid and a vicious cycle. Bicarbonate stops the vicious cycle, but doesn't treat the trigger, or whatever is causing the high lactic acid production.

The most common cause of lactic acidosis is hypoglycemia. Hypoglycemia is more likely on some diets if the patient has metabolic problems underlying their condition, such as diabetes.

We do not yet know the cause of elevated muscle lactic acid in CFS or ME, but we do know its been found in lab testing and is a result of low mitochondrial function.

Not holding onto water is a common problem though. Electrolyte solutions are often used. Potassium and sodium need to be kept in balance ... its about balance even more than dosage.

We do indeed have abnormal breathing to release excessive carbon dioxide if it occurs. I am not sufficiently familiar with oxygen physiology to say much more than that.

I have a suspicion that carbonate can indeed help, and I have used calcium carbonate for this purpose. However I also think, in ME but maybe not so much in similar conditions, that its not going to be any kind of cure, only an ongoing treatment. As always we have to use the lemon rule, the only way to find it such a thing works at present is to try it to see if it makes a difference.

One mechanism might be by increasing oxygen dumping. As the blood becomes more alkaline, the concentration of a substance called 2,3 bisphosphoglycerate will rise. The oxygen disassociation curve shifts. More oxygen is dumped. This is a very different strategy to hyperbaric oxygen, but results in a similar process, although the body will fight this via homeostatic mechanisms.

However, continued gut alkalinity might induce digestive problems and lead to poor nutrient absorption. Also there is a risk that it can, in the short term, lower oxygen dumping.

Caveat emptor. Let the buyer beware.

 

[pemone]

Lactic acid does not cause muscle fatigue. It is associated with muscle fatigue, not the same thing. In the short term it relieves muscle fatigue, and fairly directly increases oxygen dumping. In the long term it runs a risk of lactic acidosis, which is indeed an acid state. This is because it indirectly slows oxygen dumping, starving the body of oxygen, which leads to higher lactic acid and a vicious cycle. Bicarbonate stops the vicious cycle, but doesn't treat the trigger, or whatever is causing the high lactic acid production.

But this is all okay. Lactic acid becomes lactate, and lactate is actually a very desirable form of energy for some muscles. But the lactate is a *marker* of some other metabolite that is acidic and is being left behind. I'm not sure I need to understand the biochemistry. What is clear is that I exercise and *something* gets left behind in that muscle that results in a sensation of complete fatigue. The muscle becomes almost useless. Rest does not recover the muscle quickly. So there is some underlying metabolic issue here where a byproduct of muscle action is not being cleared correctly.

The most common cause of lactic acidosis is hypoglycemia. Hypoglycemia is more likely on some diets if the patient has metabolic problems underlying their condition, such as diabetes.

I am prediabetic and I monitor my blood sugar constantly. I don't get strong hypo. Exercise of any type rapidly removes excess glucose from my system. That part of my muscle metabolism continues to work under exercise.

We do not yet know the cause of elevated muscle lactic acid in CFS or ME, but we do know its been found in lab testing and is a result of low mitochondrial function.

Not holding onto water is a common problem though. Electrolyte solutions are often used. Potassium and sodium need to be kept in balance ... its about balance even more than dosage.

Would love to read any good research you have found on the above points. It might be very helpful.

We do indeed have abnormal breathing to release excessive carbon dioxide if it occurs. I am not sufficiently familiar with oxygen physiology to say much more than that.

This part is pretty simple. Carbon dioxide collects in blood serum in the form of carbonic acid. When you exhale, this carbonic acid is converted to CO2 and H2O (water). So the act of exhaling removes an acid from the blood. That chemistry trick is a key part of the body's arsenal in fighting metabolic acidosis. The body can use kidneys to make adjustments to pH over a number of days, but when an emergency adjustment to remove acid is required, the lungs can respond rapidly and clear a lot of acid in under 12 hours.

Once I had this key insight, I no longer panicked when I had these abnormal breathing patterns. Suddenly I understood for the first time that my body is responding to some kind of acidity in my metabolism, and the breathing is just evidence that this acidity has overwhelmed the body's other alkaline / acid buffers.

I have a suspicion that carbonate can indeed help, and I have used calcium carbonate for this purpose. However I also think, in ME but maybe not so much in similar conditions, that its not going to be any kind of cure, only an ongoing treatment. As always we have to use the lemon rule, the only way to find it such a thing works at present is to try it to see if it makes a difference.

So a few things here:

1) I don't think you should use calcium. Calcium supplementation is associated with increased risk of death. The fact is it does *NOT* reabsorb to bone well, and it ends up calcifying your arteries. The way to re-establish bone health is to eat an alkaline rich diet and spare your bone calcium from being eaten.

2) I don't understand the chemistry well enough to know if carbonate really works as a substitute for bicarbonate. I only know the research I found used bicarbonates not carbonates, so I would be very careful about making that substitute.

3) I thought hard about which mineral to use with the bicarbonate, and for my money potassium is the clear winner. First, most people have a potassium deficit in their diet. They need more anyway, long term. Potassium salts all tend to be very alkalizing as well. And potassium bicarbonate, unlike sodium bicarbonate, spares the body from using its own bones to generate pH buffers.

As you correctly say, whatever I have "discovered" here probably ends up needing to be used as a long-term therapy, so therefore I think it is very important to choose a substance that will nourish long-term and not just create new, additional dietary imbalances!!

Anyone who experiments around potassium use, it is critical that you get an electrolyte panel often while you are figuring out the right dosing. Excess potassium accumulating in your body can be extremely dangerous. If you find your potassium crawling to high end of the normal range, you need to take action quickly. Don't let that situation get out of hand.

However, continued gut alkalinity might induce digestive problems and lead to poor nutrient absorption. Also there is a risk that it can, in the short term, lower oxygen dumping.

It is VERY important to take any bicarbonate on an EMPTY STOMACH. Take one hour before a meal or two hours after a meal. It will completely screw up your stomach acid, so never never combine it with food. If you are combining with food, it is to treat some stomach or acid excess condition, and that's a very different topic than this one. Don't get the two applications confused.

 

[pemone]

It's interesting to hear that your issues started after you went low carb. I went low carb and suffered the worst in my life with my muscles. I didn't connect the two until I started back on eating more carbs.

So the dirty little secret of diets with under 70 grams of carbs a day is that they are extremely diuretic. It's the loss of water weight and glycogen, early on in the diet, that accounts for the dramatic up-front weight loss on these diets.

In the research literature, they "treat" this problem by giving people five grams of sodium (by dose, not by weight of salt) per day. That's a LOT of sodium. And I'm not convinced that is safe or that it does not create some other imbalances.

I was drinking sodium bicarbonate at one stage but that wasn't for my muscles even though that was around the time I was having issues with them. I didn't notice a physical improvement but I wasn't deteriorating either.

I don't think it would work taken with food. When you eat the stomach closes off the place where it joins to the small intestine and keeps it sealed until it has generated enough stomach acid to digest the food. All that extra acid is going to neutralize with the sodium bicarbonate. I am not sure very much sodium bicarbonate would get past the stomach.

Thank you for this. I might try drinking bicarb of soda again. Its worth a shot.

Report back either way. Remember you would be getting an extra two to four grams of sodium per day doing this. It's a lot of sodium, and people with sodium restricted diets might see their blood pressure explode. Stay on top of that and consult your doctor if you have heart issues. Same advice on doctors applies if you supplement potassium.

 

[alex3619]

The issue with breathing and carbon dioxide is complex. That is why I said I cannot say much more. Sure we can lower carbonic acid concentration by breathing more. But by raising pH this will decrease oxygen dumping. Its acidity that in the short term increases oxygen dumping, as reflected on the oxygen disassociation curve, while at the same time the increased breathing rate will increase oxygen absorption.

There are complex homeostatic mechanisms relating to carbon dioxide, acidity, oxygen and other energy markers. I do not understand the inter-relationships other than in vague generalities. An exercise physiologist might be able to say more.

There are numerous threads involving lactic acid, muscle metabolism etc. on this forum. I suggest a search using a good search engine, not the forum engine.

Sodium bicarbonate is what I think hospitals use to treat lactic acidosis. That and identifying the cause, and treating that. What bicarbonate does is keep you alive long enough so they can sort out the underlying cause. Cardiopulmanary issues and metabolic (glucose) issues are both known causes.

Serum glucose may not be a great indicator of muscle intracellular glucose available for energy production. We just do not know what is causing the metabolic problem. Its something that profoundly affects mitochondrial function, and this is also discussed in a number of places on this forum. It is now simply, repeatedly and reliably measurable using the 2 day CPET, or at least the secondary consequences are. This is directly related to lactic acid issues.

One of the problems we face in ME and CFS is that our muscles are highly alkaline at rest. I think our homeostatic mechanisms overcompensate. This also stuffs up muscle metabolism. However once we exercise this rapidly reverses, we go very acidic, and this acidity is persistent for a long time. A lot of this research is going on in the UK at the moment. Look up Julia Newton's research.

Any alteration of pH can alter our enzymatic activity, producing long term changes in metabolism that go far beyond just energy production. I don't think this has ever been exhaustively investigated, except possibly in elite athletes.

 

[pemone]

The issue with breathing and carbon dioxide is complex. That is why I said I cannot say much more. Sure we can lower carbonic acid concentration by breathing more. But by raising pH this will decrease oxygen dumping. Its acidity that in the short term increases oxygen dumping, as reflected on the oxygen disassociation curve, while at the same time the increased breathing rate will increase oxygen absorption.

There are complex homeostatic mechanisms relating to carbon dioxide, acidity, oxygen and other energy markers. I do not understand the inter-relationships other than in vague generalities. An exercise physiologist might be able to say more.

Right, the body has many, redundant mechanisms for controlling pH. Oxygen dumping is one of those. But why focus on it? Why should we care that we do or do not dump oxygen? Obviously if the body wants to maximize removal of CO2 to become less acidic it will make myriad adjustments to make sure the amount of CO2 in our blood gets maximized. Everything there makes sense.

The interesting questions for me are:

1) Why do we tend toward chronic low-level acidosis in the first place?

2) Assuming you have found a way to correct the acidosis, is the cure therapeutic for the body overall, in the setting of a long-term therapy?

It is easy to get lost in the biochemistry and lose sight of those important issues.

Sodium bicarbonate is what I think hospitals use to treat lactic acidosis. That and identifying the cause, and treating that. What bicarbonate does is keep you alive long enough so they can sort out the underlying cause. Cardiopulmanary issues and metabolic (glucose) issues are both known causes.

Right, although remember they are using sodium bicarbonate in the emergency setting intravenously. That guarantees maximum availability of the bicarbonate to neutralize acids.

Intravenous use bypasses one of the mysteries (for me) of why taking the sodium bicarbonate orally also seems to work. Most people will object that the bicarbonate will neutralize in stomach acid and therefore no bicarbonate makes it to the blood. But how then is it possible that the urine becomes strongly alkaline after you ingest bicarbonates constantly over the course of a day? The kidneys cannot excrete alkaline solution unless something got into the blood serum to extract?

My perspective on this is the opposite of the emergency room's: I want to find a substance that is suitable for long-term use. I want something therapeutic for my overall nutrition, not just a short term fix for acidosis. That's why potassium bicarbonate looks like a really interesting candidate to me.

Serum glucose may not be a great indicator of muscle intracellular glucose available for energy production. We just do not know what is causing the metabolic problem. Its something that profoundly affects mitochondrial function, and this is also discussed in a number of places on this forum. It is now simply, repeatedly and reliably measurable using the 2 day CPET, or at least the secondary consequences are. This is directly related to lactic acid issues.

What type of doctor is using the CPET in reference to a chronic fatigue diagnosis? One of my extreme aggravations in the last six months is understanding which type of specialist I can even see for this.

 

[alex3619]

Lactic acid buildup is associated with failed mitochondrial activity. As mitochondrial power fades, often due to lack of oxygen, then glycolysis releases lactic acid. NADH becomes NAD, and the hydrogen binds to pyruvate, which releases as lactic acid. Its a failure in the Krebs cycle or electron transport chain that drives lactic acid production in most cases. In some instances this is from oxygen deprivation. In exercise its from oxygen debt for example. Prolonged hypoglycemia induces the same thing, as NAD levels plummet.

If you are not following the CPET story, you are missing the biggest story in ME history after the Royal Free epidemic. We have had a test for ME since 1949. Its robust. As of last month it has been independently replicated. The result is so far unique to ME. So it is probably a diagnostic test, and a test of physiological capacity. Its only in 2007 that the Workwell Foundation (then Pacific Fatigue Labs), who are exercise physiologists who do functional capacity testing and research, published that the primary symptom in ME is measurable. ME is not about fatigue. Its about a post exertional crash in energy production.

So far only a small number ME and CFS doctors use the test. However so far the results are dramatic, robust, and unassailable. Its using really old and well understood technology. The US cost is on the order of $2000 but often by experts. The European cost is more like $200 but its up to the doctor to figure things out.

Even on a standard CPET, which is focussed on the wrong signs, over half of mild to moderate patients have signs of severe pathophysiology. Trying to replicate results the second day shows a massive crash in energy production. This is an aerobic crash. Hence its mitochondrial failure, but there are so many plausible causes that its premature to focus on just one.

Most biomedical conferences on ME or CFS since about 2009 have had at least one paper on CPET. Its hard to miss. The 2011 ICC ME criteria refers to it specifically. Now of course we are much more sure that its unique to ME, and unique will probably translate to diagnostic.

 

[pemone]

Lactic acid buildup is associated with failed mitochondrial activity. As mitochondrial power fades, often due to lack of oxygen, then glycolysis releases lactic acid. NADH becomes NAD, and the hydrogen binds to pyruvate, which releases as lactic acid. Its a failure in the Krebs cycle or electron transport chain that drives lactic acid production in most cases. In some instances this is from oxygen deprivation. In exercise its from oxygen debt for example. Prolonged hypoglycemia induces the same thing, as NAD levels plummet.

If you are not following the CPET story, you are missing the biggest story in ME history after the Royal Free epidemic. We have had a test for ME since 1949. Its robust. As of last month it has been independently replicated. The result is so far unique to ME. So it is probably a diagnostic test, and a test of physiological capacity. Its only in 2007 that the Workwell Foundation (then Pacific Fatigue Labs), who are exercise physiologists who do functional capacity testing and research, published that the primary symptom in ME is measurable. ME is not about fatigue. Its about a post exertional crash in energy production.

So far only a small number ME and CFS doctors use the test. However so far the results are dramatic, robust, and unassailable. Its using really old and well understood technology. The US cost is on the order of $2000 but often by experts. The European cost is more like $200 but its up to the doctor to figure things out.

Even on a standard CPET, which is focussed on the wrong signs, over half of mild to moderate patients have signs of severe pathophysiology. Trying to replicate results the second day shows a massive crash in energy production. This is an aerobic crash. Hence its mitochondrial failure, but there are so many plausible causes that its premature to focus on just one.

Most biomedical conferences on ME or CFS since about 2009 have had at least one paper on CPET. Its hard to miss. The 2011 ICC ME criteria refers to it specifically. Now of course we are much more sure that its unique to ME, and unique will probably translate to diagnostic.

This is exciting stuff, and thanks for this.

Does anyone have a recommendation for a practitioner in the Western US who is working with the CPET? $2000 is extreme. Maybe there is an opportunity to tag onto a research project?

Again, who are the specialists who deal with this condition? Is this research all branching from sports physiology, or is there a branch of medicine that directly borrows from sports physiology to make this diagnosis?

What you say about post-exertional energy crash seems spot on correct to me. But my experience so far with the bicarbonate suggests to me that this is not about mitochondria simply failing to work. This is about something in the metabolic soup that is not cleaning up after exercise, and the mitochondria simply cannot perform to specification in that environment. To the extent that the bicarbonate is cleaning up the acidity and resetting the metabolic environment, the mitochondria are able to - at least partly - start working again.

Making this a mitochondrial disease also helps me understand why D-Ribose works so well. This is an alternative way to recharge mitochondria, bypassing normal glucose metabolism.

You may want to get a book named "The Wahls Protocol". This MD cured herself of MS by designing a version of the Paleo diet that specifically targets mitochondrial health. So in theory her diet would be the best therapy for repowering mitochondria, assuming that the disease ends up being some micronutrient deficiency that the mitochondria require to do their work.

Wow, you gave me a month of reading, at least. Thanks for that.

 

[alex3619]

http://www.workwellfoundation.org/

Start here. They are West coast. They are also the most expensive, but then they also have the ability to advise on management and treatment, its not just a test and thank you for the money.

This was originally cardiac testing technology, popularized by the Bruce Protocol from 1963. It is however the case that sports scientists use this kind of testing a lot. Its also used in pulmonary and other diseases to show functional capacity. However only ME has this unique delayed energy crash, at least so far.

Issues with prolonged acidosis alternating with muscle alkalosis may indeed induce long term changes. I am not saying its not important. I am saying we don't yet really understand it.

My awareness day blog touches on these issues:

http://forums.phoenixrising.me/index.php?entries/the-winds-of-change.1597/

 

[pemone]

If you are not following the CPET story, you are missing the biggest story in ME history after the Royal Free epidemic. We have had a test for ME since 1949. Its robust. As of last month it has been independently replicated. The result is so far unique to ME. So it is probably a diagnostic test, and a test of physiological capacity. Its only in 2007 that the Workwell Foundation (then Pacific Fatigue Labs), who are exercise physiologists who do functional capacity testing and research, published that the primary symptom in ME is measurable. ME is not about fatigue. Its about a post exertional crash in energy production.

I'm reading about the Royal Free epidemic now. At the time, this was viewing the disease as related to an inflammation of the brain and spinal cord. Do you know is this still a current view that there is neurological impairment?

It's interesting that at the same time I developed this condition I started to hear a high-pitched constant frequency tone in my ears, 24x7. That certainly makes me wonder if there is in fact some kind of inflammation of the brain or some key structure there.

 

[alex3619]

There is now abundant evidence of brain and spinal inflammation, but much of it is using cutting edge technology, such as specialist PET scans from the Japanese researchers. What is striking about this Japanese research is that the cognitive symptoms match the pattern of abnormality that they think is brain inflammation. Further many of us on autopsy show severe spinal lesions and other things, that do not show up on standard tests.

In the US and other countries there are projects now tracking cytokine and other markers showing probable brain inflammation. There is a hope this might lead to a simple test, but its premature to be sure of this.

The problem with cutting edge technology is that its so new that people are naturally concerned that there might be problems with the research. This is not the case with CPET, its almost ancient technology given that most of our knowledge in science is from after 1949, way way way after.

 

[pemone]

There is now abundant evidence of brain and spinal inflammation, but much of it is using cutting edge technology, such as specialist PET scans from the Japanese researchers. What is striking about this Japanese research is that the cognitive symptoms match the pattern of abnormality that they think is brain inflammation. Further many of us on autopsy show severe spinal lesions and other things, that do not show up on standard tests.

In the US and other countries there are projects now tracking cytokine and other markers showing probable brain inflammation. There is a hope this might lead to a simple test, but its premature to be sure of this.

The problem with cutting edge technology is that its so new that people are naturally concerned that there might be problems with the research. This is not the case with CPET, its almost ancient technology given that most of our knowledge in science is from after 1949, way way way after.

So if I go to a normal neurologist about this and ask for a full workup looking for brain inflammation, is he going to look at me like I am a crazy? Is this something beyond what the technology he uses can find?

Do you have the names of any research groups in the Western US pursuing this inflammation idea as a diagnostic?

What's interesting is that the bicarbonates clear the muscle fatigue, but do NOT clear the brain fog. That kind of reinforces the idea that there might be some separate problem with brain inflammation, and that might require separate therapy.

 

[alex3619]

Most of the tests that show abnormalities in us are not standard tests. They require specialist labs. The very best tests are only done in research labs right now, and they still need proper validation before going commercial.

Most neurologists will not know what tests to run, or not have access to them, or will not even have heard of them. There would be exceptions here and there, but you cannot rely on that.

I am unsure about Western US groups looking at inflammation. Stanford is peripherally involved (via Montoya) as is the Open Medicine Institute. Other than that its hard to say. There is currently no simple option I am aware of. In a few years I expect that will change. Most of the existing studies already have their quota of test subjects too. What you need to do is look for any new studies as they arise.

Patient advocacy will be abuzz with talk once something big happens. Just stay tuned somewhere, and it will happen. I just cannot say when. The current big hope for treatment is the Rituximab study in Norway. They are also trying to get something like this going at the Open Medicine Institute, which is West coast I think.

Finding a good and affordable doctor is one of our big challenges. There are so few doctors who know the research, and some patients even have to travel to other countries for treatment.

 

[pemone]

Most of the tests that show abnormalities in us are not standard tests. They require specialist labs. The very best tests are only done in research labs right now, and they still need proper validation before going commercial.

Most neurologists will not know what tests to run, or not have access to them, or will not even have heard of them. There would be exceptions here and there, but you cannot rely on that.

I am unsure about Western US groups looking at inflammation. Stanford is peripherally involved (via Montoya) as is the Open Medicine Institute. Other than that its hard to say. There is currently no simple option I am aware of. In a few years I expect that will change. Most of the existing studies already have their quota of test subjects too. What you need to do is look for any new studies as they arise.

I have an in to Stanford, so seeing Montoya might be an option for me. It's a start anyway.

 

[pemone]

Lactic acid buildup is associated with failed mitochondrial activity. As mitochondrial power fades, often due to lack of oxygen, then glycolysis releases lactic acid. NADH becomes NAD, and the hydrogen binds to pyruvate, which releases as lactic acid. Its a failure in the Krebs cycle or electron transport chain that drives lactic acid production in most cases. In some instances this is from oxygen deprivation. In exercise its from oxygen debt for example. Prolonged hypoglycemia induces the same thing, as NAD levels plummet.
...
Even on a standard CPET, which is focussed on the wrong signs, over half of mild to moderate patients have signs of severe pathophysiology. Trying to replicate results the second day shows a massive crash in energy production. This is an aerobic crash. Hence its mitochondrial failure, but there are so many plausible causes that its premature to focus on just one.

I wanted to clarify your comments about oxygen above. What I have noticed in my case is that anerobic exercise like sprinting is what makes the post exertional symptoms most acute. Simply walking for 60 minutes doesn't do it in an extreme way like sprinting does. But lifting some heavy objects at home leaves me with significant muscle weakness for days.

This is the exact opposite of what is described in this video describing Workwell's study:

According to that video, anaerobic exercise and lactic acid do NOT cause post exercise muscle pain. According to that video, it is aerobic exercise and carbonic acid (CO2) that are toxic.

So maybe in my case what is happening is that I am combing the anaerobic together with aerobic, and together the result becomes worse. It does throw my understanding of this somewhat upside down.

 

[alex3619]

Its about the anaerobic threshold. At rest, you operate aerobically. We have very short term and short term stored energy. If rested this amounts to on the order of several minutes, and the figure of 2 minutes is often mentioned as an example. When exercising aerobically and healthy people hit the "wall", the body has failed to increase aerobic energy production sufficient to the task. Then the body makes the transition, and suddenly healthy people can keep going. This applies not just to healthy people but also heart failure, MS etc. It does not apply to ME. Instead we start pumping out a lot of lactic acid, indirectly indicating an NAD deficit.

The anaerobic threshold is where the body starts making lots of lactic acid as the aerobic system cannot cope. In us its typically very very low. That is not unknown in highly deconditioned people .What is different in ME is that this capacity crashes even lower the day after. No other disease has this although it was recently reported found one (only) HIV patient. Further there is now some clinical experience in this, showing that the aerobic system cannot be fixed through exercise. What we can do is improve flexibility and strength if we are very very careful and go slowly ... at glacial speed.

Sprinting rapidly creates an oxygen debt. That is the very thing we have to avoid. An oxygen debt, high lactate, and mitochondrial energy deficit, are probably the things that we need to avoid the most, and this is followed by massive changes in our cytokine profile post exercise if we exert too much. Its not a small change, its truly massive. This is the research of the Light's, Allan and Kathleen.

The current thinking is that very light resistance training, with short sets, and very long breaks between sets, is the way to proceed. This is still being investigated. They do not speak of recovery but improved capacity, and they talk of good benefit in months to years, not weeks.

In most people careful aerobic exercise, aimed at not incurring any substantive oxygen debt and proceeding according to graded exercise principles, can result in an improved anaerobic threshold, with increased endurance. That does not appear to be the case with ME.

 

[pemone]

Its about the anaerobic threshold. At rest, you operate aerobically. We have very short term and short term stored energy. If rested this amounts to on the order of several minutes, and the figure of 2 minutes is often mentioned as an example. When exercising aerobically and healthy people hit the "wall", the body has failed to increase aerobic energy production sufficient to the task. Then the body makes the transition, and suddenly healthy people can keep going. This applies not just to healthy people but also heart failure, MS etc. It does not apply to ME. Instead we start pumping out a lot of lactic acid, indirectly indicating an NAD deficit.

The anaerobic threshold is where the body starts making lots of lactic acid as the aerobic system cannot cope. In us its typically very very low. That is not unknown in highly deconditioned people .What is different in ME is that this capacity crashes even lower the day after. No other disease has this although it was recently reported found one (only) HIV patient. Further there is now some clinical experience in this, showing that the aerobic system cannot be fixed through exercise. What we can do is improve flexibility and strength if we are very very careful and go slowly ... at glacial speed.

Sprinting rapidly creates an oxygen debt. That is the very thing we have to avoid. An oxygen debt, high lactate, and mitochondrial energy deficit, are probably the things that we need to avoid the most, and this is followed by massive changes in our cytokine profile post exercise if we exert too much. Its not a small change, its truly massive. This is the research of the Light's, Allan and Kathleen.

The current thinking is that very light resistance training, with short sets, and very long breaks between sets, is the way to proceed. This is still being investigated. They do not speak of recovery but improved capacity, and they talk of good benefit in months to years, not weeks.

In most people careful aerobic exercise, aimed at not incurring any substantive oxygen debt and proceeding according to graded exercise principles, can result in an improved anaerobic threshold, with increased endurance. That does not appear to be the case with ME.

I need to come up to speed on some basics of aerobic and anerobic respiration.

I understand the basics of how sprinting is anaerobic and produces lactate as an end product. At what point does the body convert to aerobic? Are you saying the body is relying on aerobic respiration in normal daily activity, and then the body goes back to aerobic respiration during heavy exercise after anaerobic respiration is exhausted?

I read online that aerobic respiration is made up of three contiguous processes:
1) Glycolysis
2) Krebs Cycle
3) Electron Transport Phosphorylation

At what point in this cycle does the body start burning fat instead of glucose as its primary fuel?

In ordinary low-intensity activity, are we only using glycolysis, or do we utilize the full process 1) to 3)?

Where in the process from 1) to 3) are things breaking down for someone with CFS?

Where in the process from 1) to 3) is carbonic acid / CO2 getting produced?

Since aerobic respiration is producing CO2 as its byproduct, that implies that that burning fatigue that CFS people feel in their muscles is actually carbonic acid / CO2, not lactic acid. And this further makes much clearer why a CFS person might get deep respirations exhaling CO2 after physical activity. The body is directly removing the carbonic acid that is not clearing from the system.

And what would be interesting to understand is what should be clearing the carbonic acid in a normal person?

 

[pemone]

Sprinting rapidly creates an oxygen debt. That is the very thing we have to avoid. An oxygen debt, high lactate, and mitochondrial energy deficit, are probably the things that we need to avoid the most, and this is followed by massive changes in our cytokine profile post exercise if we exert too much. Its not a small change, its truly massive. This is the research of the Light's, Allan and Kathleen.

The current thinking is that very light resistance training, with short sets, and very long breaks between sets, is the way to proceed. This is still being investigated. They do not speak of recovery but improved capacity, and they talk of good benefit in months to years, not weeks.

Just to play devil's advocate here:

Sprinting doesn't use oxygen initially because it is anaerobic. The oxygen debt is created after you stop sprinting IF you continue to exercise aerobically.

This is a key point, and the Workwell video linked above seems to suggest that what a CFS sufferer should really do is anaerobic exercise FOLLOWED BY COMPLETE REST TO RECOVERY. So some possible examples of exercise that might work for CFS:

1) Sprint 30 seconds from one end of a pool to the other and stop. Rest completely and once recovered do another sprint.

2) Run 10 seconds at high intensity, but then sit down and completely relax until the next set. Don't run. Don't even walk briskly. The damage is not done by the sprinting, but by staying in an aerobic exercise state after you finish sprinting.

3) Weight workouts but hold down to about six repetitions each set, to stay inside the anaerobic respiration cycle.

If I'm reading things correctly, lactate is not the source of the acidosis. Lactate is used by the heart for fuel and then converted back to glucose. Maybe something there is breaking down for CFS? But it looks like the muscle burn might be carbonic acid from aerobic respiration not lactate? Not sure where the carbonic acid appears, but common sense tells you that when oxygen gets used up, CO2 has to be showing up as an end product, and combined with water that transports as carbonic acid.

On the final point you make on mitochondrial energy deficit, I'm still not clear on where the ATP stop getting produced or where in the aerobic cycle the mitochondria stop working well. But maybe that is a research topic still in the air?

 

[alex3619]

@pone

Hey, Devil's Advocate is what I do!

Sprinting will indeed create an oxygen debt. All exercise has an aerobic component, but the size of the debt is probably not meaningful and is easily dealt with. The question about the size of the debt, and the individual energy requirements ... its about which systems dominate. Sprinting is indeed dominated by stored energy.

There is also a question on the intensity of exercise, sprinting may be too intense. However the notion that very short sprints with lots of rest might work is unexplored territory. Evidence tends to trump hypothesis.

Sprinting for 30 seconds will very likely move from anaerobic to aerobic energy domination, and in us might then switch to anaerobic again .. the bad kind. Try ten seconds at most, your second option. The intensity is too high, and the two minutes of stored energy at moderate intensity will not last two minutes at high intensity.

In this case I am concerned about what a sudden demand on the mitochondria from sprinting might do. Since we do not know the exact mitochondrial problem, we cannot easily predict the outcome. We do not know what it might trigger. We need good science to give us that answer.

When Workwell talks about anaerobic exercise as useful in CFS and ME, they are talking about four to eight reps (though I think two sets of four) of very light resistance training, not a several hundred meter sprint.

It is indeed claimed that muscle burn is from carbonic acid, which rises when we cannot clear carbon dioxide away fast enough. Muscles do have acid sensors.

Your conclusion that we do not know where the energy block in the mitochondria is explains the current state fairly well. We have clues from various studies though, and growing evidence that ME is at least two different underlying conditions that apply to the mitochondria, but in two different subsets. Multiple studies do point to a problem in both ATP production and NADH/NAD ratio. Clues abound, and so do hypotheses. We await the science to sort it out definitively.

Meanwhile we have patients like you, me and a thousand others, debating what it all means.