Ron Davis: Preliminary data shows problems with energy metabolism

[Groggy Doggy]

I am watching the temperature factor right now as I am in an area that is experiencing a severe heat wave (100 F +). I try to stay inside in an air-conditioned space but yesterday I went out for only 5 minutes to get the mail etc. I felt much more ill for the rest of the day--it was immediate, headache and all.

I also have a cooling vest that I freeze and use when I have to go out. I wear an HR monitor and tried to walk (without the vest) about 50 yards right before dusk when the temperature had dropped a lot but was still uncomfortable. I noted a raised HR. I backtracked, put on the vest and tried again. My HR was 10 points lower.

@Sushi
Ditto to everything you just said. My resting HR, when feeling good is 70...when feeling crummy is about 85. Where can I buy a cooling vest?

GD

 

[Comet]

In Ron (et al)'s trauma study some of the patients were bed bound (some for over a year) burn victims. Preliminary anaslyis looks like their metabolite levels are quite different from both bed bound and non-bedbound ME/CFS patients. Needs to be looked at further.

Since I'm not a scientist, can someone explain this a bit? Wouldn't the bodies of burn victims have different needs in order to heal than pwme?
Wouldn't it be expected that the results would be different?

Not trying to be argumentative, just want to understand better.

Thank you @Rose49 for taking your precious time to post here for us!

 

[Sushi]

@Sushi
Ditto to everything you just said. My resting HR, when feeling good is 70...when feeling crummy is about 85. Where can I buy a cooling vest?
GD

I started a new thread to reply.

 

[alex3619]

I backtracked, put on the vest and tried again. My HR was 10 points lower.

Colder skin will result in vasoconstriction of the blood vessels in the skin, leading to more internal blood supply, including the brain. Hot skin will cause flushing, resulting in less blood available to the internal organs. If you have OI then heat can be an even bigger issue. If this pattern occurs reliably then I suspect its an indicator of decreased blood volume.

 

[Sushi]

Just a thought. A lot of us have done Genova's NutrEval which analyzes the Krebs cycle and a good number of metabolites. Would our results be of use/interest to Ron and team as a way of increasing the patient data? It might be an apples to oranges situation as Ron's team is using more sophisticated testing methods, but it might also show patterns in a larger patient data base.

What do you think @Rose49? I'd guess that most of us who have done this test would be happy to send the reports to the team.

 

[Seven7]

To be honest all this researcher should take all the tests we can give.

 

[Athene*]

A lot of people (me included) have done OAT (Organic Acid Test) too, revealing the metabolic byproducts of cellular metabolism. @Sushi @Rose49.

I was told I have low B12, low B2, problems with metabolising folate, and deficits at Citric Acid Cycle. I am taking B12, B2 and 5MTHF. (My Biotin was normal).

Mightn't the OATs be of use too?

 

[valentinelynx]

Here's Ron and Janet on a rare occasion when they have alone time:

Ron, my eyes are up here! Ok, getting out of control...

 

[valentinelynx]

I am watching the temperature factor right now as I am in an area that is experiencing a severe heat wave (100 F +). I try to stay inside in an air-conditioned space but yesterday I went out for only 5 minutes to get the mail etc. I felt much more ill for the rest of the day--it was immediate, headache and all.

I also have a cooling vest that I freeze and use when I have to go out. I wear an HR monitor and tried to walk (without the vest) about 50 yards right before dusk when the temperature had dropped a lot but was still uncomfortable. I noted a raised HR. I backtracked, put on the vest and tried again. My HR was 10 points lower.

Interesting. Idea for surviving summer here in Tucson. I have to go to Phoenix tomorrow, in this heat wave, where it is supposed to be 120. "Only" 118 in Tucson. The heat kills me. I love it when it's really cold.

 

[Simon]

Burn victims as a possible way to measure the effect of deconditioning on energy metabolic profile

In Ron (et al)'s trauma study some of the patients were bed bound (some for over a year) burn victims. Preliminary anaslyis looks like their metabolite levels are quite different from both bed bound and non-bedbound ME/CFS patients. Needs to be looked at further.

Thanks, @Rose49, this looks very interesting.

Since I'm not a scientist, can someone explain this a bit? Wouldn't the bodies of burn victims have different needs in order to heal than pwme? Wouldn't it be expected that the results would be different?

Yes the metabolites of the burn victims are also different from healthy people.

So my take on this is that first yes, naturally burns patients would be expected to have a different metabolomic profile than both healthy controls and mecfs patients. However, comparing the bedbound vs not-bedbound burns patients could provide an answer.

You might expect to see a stronger 'burns profile' in the presumably-more-severely-affected bedbound burns cases. However, the bedbound burns patients would also be severely deconditioned, like bedbound mecfs patients, as a result of being so immobile. So if deconditioning alone causes major changes in the energy metabolome, that would show up in the bedbound vs not-bedbound burns cases*. If being bedbound in burns cases doesn't cause major changes along the lines of those seen in severe mecfs cases, it's evidence that the energy changes are a consequence (or even cause) of mecfs, not a simple confound resulting from severe deconditioning.

Maybe there is other metabolic data for other patient groups, bedbound vs not, that would throw further light on this.


[*unless burns themselves cause major changes to energy metabolism, in which case it would be hard to intepret...].

 

[Vassie]

Rose49, Janet,
I signed up specially to thank you and your husband for your amazing efforts. This sort of research is exactly what is needed in medicine.

I was in a similar state as your son. For me ME was a misdiagnosis though, because it turned out to be Neuroborreliosis. Thankfully I have made a partial recovery with treatment. I know this is not the answer for most ME patients though. I have read your son's story and I fervently hope your husband's research will lead to a cure for him and so many others around the world.

I understand your husband is also a member of Stanford's Lyme Disease Working Group. He is a great example of how much an open-minded and dedicated scientist can accomplish. It is wonderful to see how many brilliant scientists have become involved. This focused approach is incredibly valuable and it really gives me hope that there will be better treatments for all in the future. And also that progression to this extreme level of disability can be avoided altogether.

I remember a researcher once said that in medicine the lower hanging fruit has already been harvested and that the fruit that is still left, is high up in the tree and a lot more difficult to reach. You and your husband are clearly aiming for the highest and I am sure this will help us all forward.
Thank you for that!

My best wishes to you both and especially to your son. If you can, tell him to keep fighting, because it is more than worth it.

 

[Comet]

Burn victims as a possible way to measure the effect of deconditioning on energy metabolic profile


Thanks, @Rose49, this looks very interesting.



So my take on this is that first yes, naturally burns patients would be expected to have a different metabolomic profile than both healthy controls and mecfs patients. However, comparing the bedbound vs not-bedbound burns patients could provide an answer.

You might expect to see a stronger 'burns profile' in the presumably-more-severely-affected bedbound burns cases. However, the bedbound burns patients would also be severely deconditioned, like bedbound mecfs patients, as a result of being so immobile. So if deconditioning alone causes major changes in the energy metabolome, that would show up in the bedbound vs not-bedbound burns cases*. If being bedbound in burns cases doesn't cause major changes along the lines of those seen in severe mecfs cases, it's evidence that the energy changes are a consequence (or even cause) of mecfs, not a simple confound resulting from severe deconditioning.

Maybe there is other metabolic data for other patient groups, bedbound vs not, that would throw further light on this.


[*unless burns themselves cause major changes to energy metabolism, in which case it would be hard to intepret...].

Thank you @Simon. This explains it perfectly!

 

[eastcoast12]

Rose49, Janet,
I signed up specially to thank you and your husband for your amazing efforts. This sort of research is exactly what is needed in medicine.

I was in a similar state as your son. For me ME was a misdiagnosis though, because it turned out to be Neuroborreliosis. Thankfully I have made a partial recovery with treatment. I know this is not the answer for most ME patients though. I have read your son's story and I fervently hope your husband's research will lead to a cure for him and so many others around the world.

I understand your husband is also a member of Stanford's Lyme Disease Working Group. He is a great example of how much an open-minded and dedicated scientist can accomplish. It is wonderful to see how many brilliant scientists have become involved. This focused approach is incredibly valuable and it really gives me hope that there will be better treatments for all in the future. And also that progression to this extreme level of disability can be avoided altogether.

I remember a researcher once said that in medicine the lower hanging fruit has already been harvested and that the fruit that is still left, is high up in the tree and a lot more difficult to reach. You and your husband are clearly aiming for the highest and I am sure this will help us all forward.
Thank you for that!

My best wishes to you both and especially to your son. If you can, tell him to keep fighting, because it is more than worth it.

 

[Sasha]

Rose49, Janet,
I signed up specially to thank you and your husband for your amazing efforts. This sort of research is exactly what is needed in medicine.

I was in a similar state as your son. For me ME was a misdiagnosis though, because it turned out to be Neuroborreliosis. Thankfully I have made a partial recovery with treatment. I know this is not the answer for most ME patients though. I have read your son's story and I fervently hope your husband's research will lead to a cure for him and so many others around the world.

I understand your husband is also a member of Stanford's Lyme Disease Working Group. He is a great example of how much an open-minded and dedicated scientist can accomplish. It is wonderful to see how many brilliant scientists have become involved. This focused approach is incredibly valuable and it really gives me hope that there will be better treatments for all in the future. And also that progression to this extreme level of disability can be avoided altogether.

I remember a researcher once said that in medicine the lower hanging fruit has already been harvested and that the fruit that is still left, is high up in the tree and a lot more difficult to reach. You and your husband are clearly aiming for the highest and I am sure this will help us all forward.
Thank you for that!

My best wishes to you both and especially to your son. If you can, tell him to keep fighting, because it is more than worth it.

@Rose49 - tagging you to make sure you've seen this.

 

[out2lunch]

Well, I feel ancient a lot of the time.

My possible trigger was measles encephalitis. I wonder if they are thinking along the lines that some cells may be damaged in the brain stem and that this causes improper signaling.

Hmm. Food for thought. I'm now wondering if mine was caused by viral meningitis. Worst illness of my life. Left me with nerve root clumping in my lumbar spine. And brain stem damage? Very likely. I ran a fever of 105° for two days. Probably cooked it good.

I wonder how many others in our community had brain illnesses like these. Should be studied.

 

[Riley]

Hmm. Food for thought. I'm now wondering if mine was caused by viral meningitis. Worst illness of my life. Left me with nerve root clumping in my lumbar spine. And brain stem damage? Very likely. I ran a fever of 105° for two days. Probably cooked it good.

I wonder how many others in our community had brain illnesses like these. Should be studied.

I had viral meningitis as a baby and nearly died. I didn't become ill with CFS until 21.

 

[Janet Dafoe]

Rose49, Janet,
I signed up specially to thank you and your husband for your amazing efforts. This sort of research is exactly what is needed in medicine.

I was in a similar state as your son. For me ME was a misdiagnosis though, because it turned out to be Neuroborreliosis. Thankfully I have made a partial recovery with treatment. I know this is not the answer for most ME patients though. I have read your son's story and I fervently hope your husband's research will lead to a cure for him and so many others around the world.

I understand your husband is also a member of Stanford's Lyme Disease Working Group. He is a great example of how much an open-minded and dedicated scientist can accomplish. It is wonderful to see how many brilliant scientists have become involved. This focused approach is incredibly valuable and it really gives me hope that there will be better treatments for all in the future. And also that progression to this extreme level of disability can be avoided altogether.

I remember a researcher once said that in medicine the lower hanging fruit has already been harvested and that the fruit that is still left, is high up in the tree and a lot more difficult to reach. You and your husband are clearly aiming for the highest and I am sure this will help us all forward.
Thank you for that!

My best wishes to you both and especially to your son. If you can, tell him to keep fighting, because it is more than worth it.

Thank you so much! Life is hard for us right now. We just keep going each day doing the best we can. I'm glad you found some recovery!

 

[Research 1st]

Regarding Dr Davis and his recent research.....

At my worst with ME, I waste away to the extent I have been accused of having anorexia, or paranoid about food due to phobias (56lb weight loss despite eating MORE). Because I followed research even then, I had a test on urinary metabolites for the Kreb Cyle (correct me if I'm wrong) but whatever it was, it showed very high urinary citrate (at rest).

Sound familiar to anyone?

The doctor said a Mitochondrial disorder might explain why I was so underweight and muscles wasting away,(they asked if I had HIV in ER) as apparently I had catabolic state of muscle damage. (e.g. your muscles are used by the body as a source of energy - at rest!). The muscle biopsy was normal though. I had uncontrolled starvation feeling (like a permanent low blood sugar feeling) but worse.

Each time I relapse massively and end up bedridden this exact phenomena happens (over a decade), and it always starts with an infection. I tfeel like I'll starve to death and will collapse from a vital lack of something - hormones?. When I eat sugar, it only goes off a bit, then gets massively worse (excess insulin?) after. If I don't each sugar at all, I literally don't have the energy to breathe. It got to the point every few hours I had to eat sugar, and if not, I'd start getting respiratory problems and by autonomic nervous system would go crazy. My breathing also goes deranged, like I don't know how to breathe and I have to consiocusly breathe or there is no 'impulse'. (Reverse of hyperventilation).

It nearly killed me one day (circulatory collapse and respiratory emergency in resus which showed hypokalemia and high white blood cell count). It gave me daily cardiac arrythmia's, panic attacks, a pain in my back (kidneys?), unbearable stomach pain, chest pain and a sensation of feeling profoundly faint (much worse tha normal ME/POTS faintness), as in on the floor amazed you're still conscious. The pain was of ofcourse much worse than usual, like you're full of acid. I went from being housebound, to unable to even sit upright. Each time this feeling 'sticks' I eventually end up Hospitalised, usually for 6 months+ at a time as I am so weak and 'no one knows why'.

I wonder if it's to do with an autoimmune attack on mitochondria? It feels a bit like being in shock, like an emergency feeling you must get help or perish, like something essential to life-force is absent.

Twice I managed to get some tests done during an attack. One time, high 24hr calcium, another, low 24hr calcium. Inorganic phosphate and something else (phosphatase) always low. Also low blood sugar episodes and ketones in urine (without Diabetes, seen in starvation/anorexia interestingly and also severe pain).

Wanted to share as it might be interesting to see if this weid on/off attacks I get are something to do with ME and maybe Dr Davis's/Dr Navieux's research will explain it all. Someone once thought I had 'periodic paralysis', but I don't think there's a test for it, or you have to have it during the attack?

This is why ME is so dangerous. No one knows what 'it' is, and what 'it' can do, and each patient reports with different set of disabling symptoms, incorrectly presumed to be based on feeling fatigued when we have a massively complex multi systemic disease process.

 

[Ben H]

Regarding Dr Davis and his recent research.....

At my worst with ME, I waste away to the extent I have been accused of having anorexia, or paranoid about food due to phobias (56lb weight loss despite eating MORE). Because I followed research even then, I had a test on urinary metabolites for the Kreb Cyle (correct me if I'm wrong) but whatever it was, it showed very high urinary citrate (at rest).

Sound familiar to anyone?

The doctor said a Mitochondrial disorder might explain why I was so underweight and muscles wasting away,(they asked if I had HIV in ER) as apparently I had catabolic state of muscle damage. (e.g. your muscles are used by the body as a source of energy - at rest!). The muscle biopsy was normal though. I had uncontrolled starvation feeling (like a permanent low blood sugar feeling) but worse.

Each time I relapse massively and end up bedridden this exact phenomena happens (over a decade), and it always starts with an infection. I tfeel like I'll starve to death and will collapse from a vital lack of something - hormones?. When I eat sugar, it only goes off a bit, then gets massively worse (excess insulin?) after. If I don't each sugar at all, I literally don't have the energy to breathe. It got to the point every few hours I had to eat sugar, and if not, I'd start getting respiratory problems and by autonomic nervous system would go crazy. My breathing also goes deranged, like I don't know how to breathe and I have to consiocusly breathe or there is no 'impulse'. (Reverse of hyperventilation).

It nearly killed me one day (circulatory collapse and respiratory emergency in resus which showed hypokalemia and high white blood cell count). It gave me daily cardiac arrythmia's, panic attacks, a pain in my back (kidneys?), unbearable stomach pain, chest pain and a sensation of feeling profoundly faint (much worse tha normal ME/POTS faintness), as in on the floor amazed you're still conscious. The pain was of ofcourse much worse than usual, like you're full of acid. I went from being housebound, to unable to even sit upright. Each time this feeling 'sticks' I eventually end up Hospitalised, usually for 6 months+ at a time as I am so weak and 'no one knows why'.

I wonder if it's to do with an autoimmune attack on mitochondria? It feels a bit like being in shock, like an emergency feeling you must get help or perish, like something essential to life-force is absent.

Twice I managed to get some tests done during an attack. One time, high 24hr calcium, another, low 24hr calcium. Inorganic phosphate and something else (phosphatase) always low. Also low blood sugar episodes and ketones in urine (without Diabetes, seen in starvation/anorexia interestingly and also severe pain).

Wanted to share as it might be interesting to see if this weid on/off attacks I get are something to do with ME and maybe Dr Davis's/Dr Navieux's research will explain it all. Someone once thought I had 'periodic paralysis', but I don't think there's a test for it, or you have to have it during the attack?

This is why ME is so dangerous. No one knows what 'it' is, and what 'it' can do, and each patient reports with different set of disabling symptoms, incorrectly presumed to be based on feeling fatigued when we have a massively complex multi systemic disease process.

Makes a huge amount of sense from a metabolic point of view as im sure you realise. Your krebs cycle is not humming like it should, lack of co factors, inhibitors, or an underlying mechanism. Possibly all 3. Im sure Davis's next paper will explain much. This is such a FUNDAMENTAL process to life, its not suprising the extent the illness can get to. Im sorry its been so bad for you.

That is why M.E is so dangerous-no one knows exactly what it is yet, no one is equipped to deal with it.

The hospital visits themselves are horrendous, cause crashes, and can only support basic levels of few things. The inevitable serving of skepticism that ive encountered is not welcome or helpful either, they just cannot believe you can be that ill when basic bloods usually come back normal. Nothing in the krebs cycle is measured, bar (serum) magnesium usually, and many doctors dont have a clue about the cycle anyway, bar the name, and ofcourse no treatment.

Desperate, desperate situation.


B

 

[Groggy Doggy]

@Research 1st

Yes, it all sounds familiar, a metabolic disorder that impacts the krebs cycle. I am sorry you land up in the hospital. Has anything helped? I almost think we have a disorder where we suffer to the equivalant of someone with untreated severe diabetes. It seems the longer we have untreated ME, the more it takes a toll on the rest of the body.

I think some ME metabolic answers will be coming soon, along with diagnostics and treatments.

The NIH and CDC will look like fools for ignoring us for over 30 years.

Take Care

GD