Who Would Like to Participate in a Simple Study to Measure Blood Lactate Levels?

[pemone]

You might find of interest Myhill, Booth and McLaren-Howard's theory of how PEM arises in ME/CFS, and how it involves lactic acid. See this post (under the section entitled "Sarah Myhill et al's Theory of PEM"):

Mitochondrial and Energy Metabolism Dysfunction in ME/CFS — Myhill, Booth and McLaren-Howard Papers



It is also worth pointing out that in the research of Myhill et al, they found ME/CFS patients divide into two main groups, Group A and Group B.

• Group A patients try to compensate for the mitochondrial ATP shortage by increasing glycolysis to make ATP.
• Group B patients try to compensate for the shortfall in mitochondrial ATP most likely by using the adenylate kinase reaction to make ATP.

See this post for more info.



Note that glycolysis can operate in two modes:

• Anaerobic glycolysis — this is where glycolysis works independently of the mitochondria in order to supply energy in the form of ATP. When glycolysis works independently, it is much less efficient, and also produces lactic acid as part of its operation.
• Aerobic glycolysis — this is where glycolysis works in conjunction with the mitochondria to supply energy in the form of ATP. When glycolysis works in conjunction with the mitochondria, it is much more efficient, and does not produce lactic acid.

According to the research and theories of Myhill, Booth and McLaren-Howard, ME/CFS patients may be forced into generating energy by the inefficient anaerobic glycolysis route because their mitochondria may be dysfunctional.

(The theory is that dysfunctional mitochondria are not able to supply sufficient energy during exercise when there is high energy demand. As a result, in ME/CFS the body has to use alternative routes of ATP energy production during exercise, and one of these alternative routes is glycolysis, which takes place in the cytosol of the cell, rather than in the mitochondria. Dysfunctional mitochondria may also prevent aerobic glycolysis from taking place, since aerobic glycolysis involves the mitochondria; instead, ME/CFS patients may be forced into anaerobic glycolysis, as this works without the involvement of the mitochondria.)

Right, but introducing late-onset mitochondrial disease into the equation makes the diagnosis extremely complex. What I am suggesting is something very trivial as a cause for many of us. Our bodies are not supplying enough oxygen to our cells to drive aerobic respiration. There is no need for any mitochondrial dysfunction to crash aerobic metabolism.

Remember that Complex i of the electron transport chain is rate limited by the amount of oxygen available. No oxygen = no aerobic respiration. No aerobic respiration means NAD+ becomes rapidly depeleted and NADH raises. Rising NADH downregulates Krebs. The cell is now desperate for energy and reverts to glycolysis. Increased glycolysis uses up NAD+ and to maintain NAD+ pyruvate is buffered to lactic acid. The hydrogen proton disassociates and now you have lactate and hydrogen protons.

If my version of this is correct, it suggests the disease is not as complex as many have believed, and it might actually have very straightforward "cures". Too early for me to brag about any success. I'll update as I go. But I'm onto something big.

The really useful thing would be for those of you who obtain lactate meters to start testing different peripheral tissues, and then compare against something closer to a major vein in forearm. Look at values at different times of day. Do you - like me - get evidence of hypoxia that is *localized* to particular tissues? That would be totally missed by your doctor, who is only testing an arm draw, from a major vein.

 

[pemone]

What a post ....sent you a PM

I think you should post your experience with symptom improvement based on temperature change in your environment. What was temperature and your energy pattern and perceived circulation in your limbs before you made the plane trip, and what were those variables after? What independent variables altered, and what dependent variables altered.

I think we can have an interesting discussion around some of what you wrote in your PM here in public. It agrees with some of my experience so far and the jacuzzi experiment....

 

[Hip]

Our bodies are not supplying enough oxygen to our cells to drive aerobic respiration.

How are you proposing that this shortage of oxygen occurs?

If shortage of oxygen were a factor in ME/CFS, then presumably hyperbaric oxygen therapy would make substantial improvements to ME/CFS symptoms, which it does not.

 

[wastwater]

Have a look at FOXO genes as per navieux study they seem to do many things one paper mentioned hypoxia
http://journal.frontiersin.org/article/10.3389/fonc.2013.00096/full

 

[knackers323]

following

 

[gregh286]

Right, but introducing late-onset mitochondrial disease into the equation makes the diagnosis extremely complex. What I am suggesting is something very trivial as a cause for many of us. Our bodies are not supplying enough oxygen to our cells to drive aerobic respiration. There is no need for any mitochondrial dysfunction to crash aerobic metabolism.

Remember that Complex i of the electron transport chain is rate limited by the amount of oxygen available. No oxygen = no aerobic respiration. No aerobic respiration means NAD+ becomes rapidly depeleted and NADH raises. Rising NADH downregulates Krebs. The cell is now desperate for energy and reverts to glycolysis. Increased glycolysis uses up NAD+ and to maintain NAD+ pyruvate is buffered to lactic acid. The hydrogen proton disassociates and now you have lactate and hydrogen protons.

If my version of this is correct, it suggests the disease is not as complex as many have believed, and it might actually have very straightforward "cures". Too early for me to brag about any success. I'll update as I go. But I'm onto something big.

The really useful thing would be for those of you who obtain lactate meters to start testing different peripheral tissues, and then compare against something closer to a major vein in forearm. Look at values at different times of day. Do you - like me - get evidence of hypoxia that is *localized* to particular tissues? That would be totally missed by your doctor, who is only testing an arm draw, from a major vein.

Hi,
A few years ago my lactate levels where much higher that they are now, but energy was still very dampened.
As I put in note to Permone, I have travelled to hot countries with high humidity and seen my lactate disappear in a few hours, giving a feeling of CFS massive relief.

Cue that fact I had a sauna fitted in my home last year such was such the benefit.
I use it daily.
Whilst this 100% helps with lactate sadly it does not fix energy supply so something else at work.
IMO, vasodilation will totally alleviate symptoms, not fix root. I have many posts on this,,,,"better with alcohol" thread,,,,"complete symptom relieve" with NO thread.

At my worst in 2013/14, hot sauna and stuff just made my feel like collapsing,,,,,my energy cycle unable to keep upto demand of higher energy required to maintain sitting in a sauna.
I have used amoldipine, etc,,,,all beneficial, but only to help dissipitate lactate, not cellular energy delivery. Red wine another great job for lactate removal and insulin release.

The ONLY way I can get energy delivery fixed is by ramping up carbs and maintaining high blood sugar through the day,,,or a constant supply of amino acids.
This is what i do now,,,,,drink protein shakes all day.

So, is there a pyruvate dehydrogenase complex (PDH) issue, hell f~~~ng yeah there i bet there is, can be bypassed with aminos.......

"""Fluge and Mella’s unpublished gene expression study suggests a similar pattern is happening in ME/CFS. It also found that men were more likely to grab amino acids from their muscles to fuel glycolysis but women had more trouble breaking down pyruvate to acetyl-CoA."""

Genetic problems with pyruvate dehydrogenase do suggest that something like ME/CFS can occur. They are associated with an abnormal buildup of lactate, low energy and severe lethargy. Pyruvate dehydrogenase has also been pegged as a possible factor in primary biliary cirrhosis – a disease Julia Newton has studied extensively – which shares similar fatigue characteristics with ME/CFS.

 

[TreePerson]

Excuse me butting in - does this mean women can't bypass this process with amino's? Or not as easily?

 

[gregh286]

Excuse me butting in - does this mean women can't bypass this process with amino's? Or not as easily?

seems more difficult.
but easy to try for you.
jeanatte is on facebook, ask her what see thinks

http://www.dailymail.co.uk/health/a...rinking-two-litres-protein-milkshake-DAY.html

 

[TreePerson]

Thanks I will look for her. I have been following this thread because I have always been aware of a lot of vascular type symptoms which were there from day one. Although I suspect now I am too ill to benefit from measuring lactate or hot and cold treatments. One thought I had is that a small burst of adrenalin nearly always improves muscle performance and makes me feel temporarily much better. Presumably at least partly because this increases oxygen to main muscle groups. However always afterwards there is a massive crash, as if in the process I have exhausted something vital and not easily replaced. Which I don't understand and doesn't really fit with the theory that all we need is some more oxygen.

 

[gregh286]

Thanks I will look for her. I have been following this thread because I have always been aware of a lot of vascular type symptoms which were there from day one. Although I suspect now I am too ill to benefit from measuring lactate or hot and cold treatments. One thought I had is that a small burst of adrenalin nearly always improves muscle performance and makes me feel temporarily much better. Presumably at least partly because this increases oxygen to main muscle groups. However always afterwards there is a massive crash, as if in the process I have exhausted something vital and not easily replaced. Which I don't understand and doesn't really fit with the theory that all we need is some more oxygen.

yea adrenaline will always give quick relief followed by crash. adrenaline requires huge energy conversion that our atp cant maintain.

never too ill.....look at jeanette and whitney...jamieson hill....

 

[TreePerson]

Yes I take your point. Though I think maybe I am too ill for cold baths. I think anyway that would stimulate adrenaline.
Re the atp adrenaline thing - I assumed that because oxygen supply is increased temporarily enough atp would be made? But because of the crash that follows I am left with the impression that something else vital gets used up. Like some kind of reserve tank. It seems to mess with the immune system as well.

 

[Seven7]

Which drugs do they have you on?

I am on midodrine, Florinef + beta blocker.

 

[Seven7]

That won't dilate your capillaries. That drug would make it even harder to deliver O2 to deep tissues....

I guess you have low blood pressure issues. That can't be resolved by increasing your fluid volumes?

Somehow the tissue problems I had pain and Latic acid like constant pain is gone. I get better oxygen somehow to tissue. I have very low AT (115bpm) I had the test done to measure it.

My natural BP is 96/64 but since I have POTs when I stand goes even lower so that is to low to compensate.

Yes the midodrine raises my BP. The salt does raise my BP but I am symptomatic. So the salts masks the number issue without addressing the real issue. Vs when I raise BP w the midodrine I take care of the symptoms too.

 

[Hip]

Cue that fact I had a sauna fitted in my home last year such was such the benefit.
I use it daily.
Whilst this 100% helps with lactate sadly it does not fix energy supply so something else at work.

Doing anything to clear the lactic acid build up in the muscles is going to help.

When you get lactic acid build up in the muscles, it is the job of the liver to deal with this: the Cori cycle (aka: lactic acid cycle) in the liver converts this lactic acid to glucose.

However, in order for the Cori cycle to work, you first have to get the lactic acid in the muscles into the bloodstream, and then let it travel to the liver, where the lactic acid is processed by the Cori cycle.

So something like sauna (which dilates blood vessels in the muscles) may be helpful, by encouraging the lactic acid to leave the muscles and travel to the liver.



Anyone dealing with lactic acid build up from physical exertion and the resultant PEM that appears after exertion may want to look at these PEM Buster supplements.

ME/CFS patients on this forum have found that these PEM Buster supplements (such as very high dose Q10, and sodium bicarbonate) are pretty effective in mitigating or even fully eliminating an episode of PEM.

These PEM Buster supplements would appear to work in part by neutralizing lactic acid, or reducing lactic acid production.

 

[bertiedog]

The ONLY way I can get energy delivery fixed is by ramping up carbs and maintaining high blood sugar through the day,,,or a constant supply of amino acids.

I am similar to this, if my blood sugar is down at a normal level of say 4.6 I feel horrendous and can do nothing apart from eat some carbs/fat/protein. Roasted peanuts and cashews between meals really help and I feel much better and can do some physical activity like walk my dog for 25 minutes till my energy is used up and I have to rest. Without those regular top ups I feel lethargic and certainly don't feel up to doing anything physical.

Also for me 30 minutes on my oxygen concentrator (delivering 4 litres per minute) will put back a reasonable amount of energy so the combo of slightly higher blood sugars (around 6) plus 3 sessions of topping up on oxygen allows me to be fairly active with an average over this past year of 8100 steps a day. Pacing is essential with frequents rest periods when I am horizontal.

I also do well on 80 mg slow release Propananol, it really helps my ability to stand. I was on 20 mg standard Propananol but feel better energy wise on the longer acting one except in the mornings when I have to battle feelings of lethargy from the drug. I really have to push myself to do anything but it does wear off and I can feel quite well in the afternoons and evening. In the summer I also need some Fludrocortisone but not in the cooler months. The slow release version of Propananol was given to me as a migraine preventative but it isn't really doing too well in that direction.

Pam

 

[gregh286]

I am similar to this, if my blood sugar is down at a normal level of say 4.6 I feel horrendous and can do nothing apart from eat some carbs/fat/protein. Roasted peanuts and cashews between meals really help and I feel much better and can do some physical activity like walk my dog for 25 minutes till my energy is used up and I have to rest. Without those regular top ups I feel lethargic and certainly don't feel up to doing anything physical.

Also for me 30 minutes on my oxygen concentrator (delivering 4 litres per minute) will put back a reasonable amount of energy so the combo of slightly higher blood sugars (around 6) plus 3 sessions of topping up on oxygen allows me to be fairly active with an average over this past year of 8100 steps a day. Pacing is essential with frequents rest periods when I am horizontal.

Pam

Yea, my diet for many months was tuna and white rice.
Eating it all during day, few mouthfuls at a time.
Kept blood sugar around 6.5/7
I find when you hit a bath or sauna you get a better bang for you buck when you blood sugar is higher.
I believe the glucose is reaching deeper cells under the vasodilation.

Yeah, I found cashews, brazils, peanuts all decent for snacks.

This somehow fuels the Krebs way better, theory of course.

 

[pemone]

How are you proposing that this shortage of oxygen occurs?

I don't believe CFS is a "disease". I believe that CFS is an energy state that is the ultimate result of several very different conditions.

If you are 350 pounds and type 2 diabetic, it's not a mystery why you have CFS due to low oxygen delivery to tissues. You have years of accumulated vascular damage from elevated insulin and insulin resistance. Your deep tissues are chronically hypoxic.

I don't want to elaborate my own case yet because it is quite complex and I have about four moving pieces that are all getting confirmed by testing now. The short version would be that I went on a low carb diet, but I did not understand at the time that I don't digest fats and I also don't metabolize them well. I was suffocating for energy and started to cannibalize my own protein for gluconeogenesis. I became hypometabolic, and at some point in this metabolic collapse my metabolism became highly glycolytic. The details of why can wait.

If shortage of oxygen were a factor in ME/CFS, then presumably hyperbaric oxygen therapy would make substantial improvements to ME/CFS symptoms, which it does not.

Under the Bohr effect, O2 saturation inside the cell and mitochondria require increased CO2, not increased oxygen. A person who hyperventilates passes out for lack of oxygen! It's because of the Bohr effect, and the lower saturation of CO2 in the blood means less O2 gets inside of the cell. You suffocate for oxygen in face of red blood cells that are full of oxygen.

You would be better off bag-breathing, taking sodium bicarb on an empty stomach (only!), or drinking carbonated water. Those strategies will increase CO2 saturation, thereby allowing more oxygen to get inside the cell. Better yet, move to Denver and have increased CO2 saturation 24x7.

All of the above is cosmetic though. Find the reason your tissues are hypoxic, then address the specific cause. You are diabetic and weigh 350 pounds? Do a medically supervised fast for 20 days and you will walk away with at least half the insulin resistance just gone. Follow that up with a diet that keeps insulin low, and then you hope for a reversal of vascular damage that might take a few years.

If you are hypometabolic, find strategies that raise uncoupled metabolism and raise thermogenesis.

Again, I don't want to get into arguments about cures, because so far I am not making any claim about a cure.

Also, none of these studies are measuring (or attempting to measure) localized tissue hypoxia as evidenced by high lactate numbers just in peripheral tissues. It's hard to argue about what strategies do or do not treat or change when they are not even observing the hypothesized potential cause of the problem. If you have the same high lactate numbers I was getting in peripheral tissue, our stories have a common thread and we should share notes. If you have no common symptoms with me, maybe we can't learn as much from each other.

 

[pemone]

Hi,
A few years ago my lactate levels where much higher that they are now, but energy was still very dampened.
As I put in note to Permone, I have travelled to hot countries with high humidity and seen my lactate disappear in a few hours, giving a feeling of CFS massive relief.

Cue that fact I had a sauna fitted in my home last year such was such the benefit.
I use it daily.
Whilst this 100% helps with lactate sadly it does not fix energy supply so something else at work.
IMO, vasodilation will totally alleviate symptoms, not fix root. I have many posts on this,,,,"better with alcohol" thread,,,,"complete symptom relieve" with NO thread.

At my worst in 2013/14, hot sauna and stuff just made my feel like collapsing,,,,,my energy cycle unable to keep upto demand of higher energy required to maintain sitting in a sauna.
I have used amoldipine, etc,,,,all beneficial, but only to help dissipitate lactate, not cellular energy delivery. Red wine another great job for lactate removal and insulin release.

The ONLY way I can get energy delivery fixed is by ramping up carbs and maintaining high blood sugar through the day,,,or a constant supply of amino acids.
This is what i do now,,,,,drink protein shakes all day.

So, is there a pyruvate dehydrogenase complex (PDH) issue, hell f~~~ng yeah there i bet there is, can be bypassed with aminos.......

"""Fluge and Mella’s unpublished gene expression study suggests a similar pattern is happening in ME/CFS. It also found that men were more likely to grab amino acids from their muscles to fuel glycolysis but women had more trouble breaking down pyruvate to acetyl-CoA."""

Genetic problems with pyruvate dehydrogenase do suggest that something like ME/CFS can occur. They are associated with an abnormal buildup of lactate, low energy and severe lethargy. Pyruvate dehydrogenase has also been pegged as a possible factor in primary biliary cirrhosis – a disease Julia Newton has studied extensively – which shares similar fatigue characteristics with ME/CFS.

So parts of this I share with you:

* Hot and cold therapy clears my lactate levels and brings them to normal

* That in turn made me realize part of the problem is my lowered metabolism itself is unable to support adequate blood flow to the peripheral tissues. The simple act of wearing extra layers of clothing, especially long johns to warm the legs, dramatically improved the hypoxia/lactate in those tissues.

* That then started me on research of how to raise metabolism, on the assumption I had become hypometabolic. That led me to good research showing fructose is more thermogenic than glucose, and studies showing cyclists fed glucose+fructose have much higher metabolic rates than cyclists fed glucose. So my dietary strategy completely inverted. I stopped fat (except for the fat on meat). I avoided starch (since that is just glucose). I supplemented calories after a meal of meat and non-starch vegetables with honey (in my case about two tablespoons of honey per meal). The bees have pre-digested that and it is a balanced blend of monosacharrides glucose+fructose. Within two weeks of that dietary change, my metabolism began to rise, and I started to get a distinct feeling of warmth in peripheral tissues that increased more and more over the course of the day. By the next morning, I was back at square one, but I kept at it and after weeks of this I feel metabolism starting to turn around.

Strangely, my overall glucose metabolism appears to have adjusted to high carbs, and my fasting glucose is still about the same as it was on low carb.

Unfortunately, it feels to me like I have done some damage to the brain in this strange three year odyssey through living hell. It feels like the brain is in shock (hypoxic?) from its experience during this period, and as energy starts to come back to muscles, the brain is slower to recover. I have no idea how long that neurological recovery will take, or how much recovery can occur.

In any case, I am on a path that has me seeing light at the end of the tunnel. Given my particular causes for my situation, this therapy is making a difference. I'll update every few weeks.

 

[gregh286]

So parts of this I share with you:

* Hot and cold therapy clears my lactate levels and brings them to normal

* That in turn made me realize part of the problem is my lowered metabolism itself is unable to support adequate blood flow to the peripheral tissues. The simple act of wearing extra layers of clothing, especially long johns to warm the legs, dramatically improved the hypoxia/lactate in those tissues.

* That then started me on research of how to raise metabolism, on the assumption I had become hypometabolic. That led me to good research showing fructose is more thermogenic than glucose, and studies showing cyclists fed glucose+fructose have much higher metabolic rates than cyclists fed glucose. So my dietary strategy completely inverted. I stopped fat (except for the fat on meat). I avoided starch (since that is just glucose). I supplemented calories after a meal of meat and non-starch vegetables with honey (in my case about two tablespoons of honey per meal). The bees have pre-digested that and it is a balanced blend of monosacharrides glucose+fructose. Within two weeks of that dietary change, my metabolism began to rise, and I started to get a distinct feeling of warmth in peripheral tissues that increased more and more over the course of the day. By the next morning, I was back at square one, but I kept at it and after weeks of this I feel metabolism starting to turn around.

Strangely, my overall glucose metabolism appears to have adjusted to high carbs, and my fasting glucose is still about the same as it was on low carb.

Unfortunately, it feels to me like I have done some damage to the brain in this strange three year odyssey through living hell. It feels like the brain is in shock (hypoxic?) from its experience during this period, and as energy starts to come back to muscles, the brain is slower to recover. I have no idea how long that neurological recovery will take, or how much recovery can occur.

In any case, I am on a path that has me seeing light at the end of the tunnel. Given my particular causes for my situation, this therapy is making a difference. I'll update every few weeks.

Hi Permone,
Thats very interesting that you are able to change your metabolic state through diet.
Fructose, I always did well on also.....
So, your diet is now moved away from fat biased to meat and fruit, do you take carbs or not now,,,or just non starch veg only.

Around 3 years ago, I noticed carbs always increased heat in my feet. I assumed it was vasodilation from insulin release.
I think we need the extra carbs to help us overcome the PDH barrier that stopping us putting pyruvate into citric cycle.
On the other hand, if we eliminate carbs completely, then surely body not need the PDH requirement as its burning energy from fat+protein.
All I know without l glutamine, I am horizontal.

Best luck with your new dietary plan.

 

[bertiedog]

If you are 350 pounds and type 2 diabetic, it's not a mystery why you have CFS due to low oxygen delivery to tissues. You have years of accumulated vascular damage from elevated insulin and insulin resistance. Your deep tissues are chronically hypoxic.

This doesn't apply to me as I only weigh 128 lbs and I am slim with a good fasting blood sugar but when I had a test on my autonomic system I had under half the amount of oxygen in my cells, lungs were fine though so there is something else going on in my case.

Pam