Ron Davis: Preliminary data shows problems with energy metabolism

[JaimeS]

I don't believe every single patient will be totally different as we could not get a biomarker that way, based off of TCA if that happens to be the case.

We could end up with hundreds of biomarkers that all lead to dysfunction in glycolysis, fatty acid oxidation, the citric acid cycle, or all three. We might be able to address the particular cog we've slipped, even before we discover a root cause, however.

Even if some turn out to be untouchable, imagine what it would be like to get support, respect and empathy from friends, family and the medical community, and to be recognized as actually being sick.

Hard for a lot of us to even imagine -- to have people not immediately dismiss your illness and devalue your experience would be invaluable to all of us.

-J

 

[JaimeS]

I think you can pay for your own testing at metabolon.com ? Some study was offering free testing for 1500 donation.

Any idea where you saw this? I'd love to do it!

 

[aimossy]

@aimossy. Gordon Medical was offering the tests for a $1500.00 donation but I can't find that on his site anymore. He was offering it originally in an effort to raise the $400,000.00 needed for his follow up study that OMF is now funding.

@JaimeS RL_sparky found it but looks like might no longer be available but I guess here might be a good place to maybe get access through?

 

[aimossy]

Janet Dafoe may know if access to testing is possible somewhere @JaimeS

 

[JaimeS]

Wow, $1500 still a chunk of change, but probably worth it. I sent something to the company Davis is going through, but I made it clear I wasn't sick enough to be part of his study. I asked how much it would cost just to look at glycolysis and citric acid cycle metabolites.

One of those situations where you just KNOW you sound totally ignorant, but you give it a go anyhow.

@Rose49 , do you have any info on this? Know you are busy and hate to bother you.

-J

 

[aimossy]

I think that $1,500 was a donation amount they asked for which included free testing, but RL_sparky explained they could no longer see that available on the site.

 

[Justin30]

So we know that its a mitochondrial problem but whats seems to be missing to me is why the bacteria, virus, parasite or autoimmune response cause it?

Why then is rituximab working for some?

Why are antivirals working for others?

Etc.

The one thing that rings true to me is that the main symptom of a Mito Disease is Encepholomylietis.

In Naviauxs CDR theory I want to know if the brainstem portion is damaged in his eyes which messes with GUT and all other Autonomic functions?

 

[Justin30]

I am very greatful to OMF for everything they have done and are doing.

 

[justy]

Going back to @alex3619 's first post in the thread re Glutathione and Richvank, jut anecdotally 6 weeks of IV glutathione lasyt year gave me 8 of the best weeks ive had in 7 years - was out of bed all day, gardening, hovering, cooking (for fun) started planning to drive again, walking without my wheelchair. Then it ended and now back to square one again. Cant affrord iv Glut in the UK. (I was also having myers type cocktails so may have helped a deficiency, which I seem to have plenty of despite good diet)

Like @Sasha I also had a long remission, which ended 7 years ago. I know I can get better and feel better - why cant we sustain it? but if we can have it in the past, we can have it again!

 

[Simon]

Are ME/CFS symptoms and epidemiology consistent with inherited or acquired defects of the Krebs cycle? Even partial defects often result in pretty unmissable signs such as developmental delay and often early death.

Not inherited, these findings are from severely-affected patients who weren't born that way. We don't know if it's a defect in the cylce, or a downstream result from problems elsewhere. But early death? Not sure there's good epidemiological evidence for that (as opposed to individual cases), though I'm not sure that's a reason to rule out Kreb's cycle problems. We need to know more about the defects, what might be causing them and how widespread they are in the patients population.

Isn't it part of the NIH intramural study? I can't remember, but they're doing loads.

It is indeed, see the power of #MEpedia
1.1.3 Aim 3 - To determine if there are abnormal immune or microbiome profiles
". We will also fully explore the gut and oral microbiome and apply proteomics and metabolomics approaches to the cerebral spinal fluid."[2]"

Don't know if they are doing blood too, but spinal fluid gives a reading on the brain, which would be pretty interesting.

How extreme is 16SD for a single data point?

Great graph showing the significance of 16 standard deviations, @JaimeS!

It's great

"Extreme" is almost an understatement. In a normal distribution, 3 standard deviations below the mean equates to 1 finding in a population of 741 samples (with another sample three SD above the mean). The percentage of a population 4 SD below average would be 1 in 31,457.

Most look-up tables don't go any lower or higher than 4 SD, but I did find one online calculator that went as far as 8 standard deviations.

Good work, I couldn't find one past 4SD

But a critical point is that those tables etc are for looking at means of groups, not inidividual data points. I think the mean may have been the 5SD figure quoted in a tweet (if so, it would have been heavily affected by Whitney's 16SD data point; the other two would have been much closer to the mean), not for individual data points. It's much more common to have extreme single data point than it is to have an extreme group mean - though 16SD is still a wild outlier.

 

[alex3619]

Not inherited, these findings are from severely-affected patients who weren't born that way. We don't know if it's a defect in the cylce, or a downstream result from problems elsewhere.

I think this is likely to be correct but its not certain. For example if this starts with one or more defects in secondary maintenance processes, which might be inherited, such as clearance of defective enzymes, then when this process is overwhelmed the mitochondria shut down.

People like to talk of vicious cycles, even psychs, but metabolic cycles are possible too where the hole is so deep the body cannot climb out until we identify and deal with the issues preventing recovery.

I do think this is unlikely for most of us. Spontaneous temporary remissions do occur. They are hard to explain if an inherited disorder is a primary issue.

 

[lansbergen]

I do think this is unlikely for most of us. Spontaneous temporary remissions do occur. They are hard to explain if an inherited disorder is a primary issue.

yes

 

[Marco]

Not inherited, these findings are from severely-affected patients who weren't born that way. We don't know if it's a defect in the cylce, or a downstream result from problems elsewhere. But early death? Not sure there's good epidemiological evidence for that (as opposed to individual cases), though I'm not sure that's a reason to rule out Kreb's cycle problems. We need to know more about the defects, what might be causing them and how widespread they are in the patients population.

I agree that we need to know more which also applies to the extreme findings (whether they be 5 or 16 SDs below means). While these measures may be extreme are they physiologically meaningful (as a less extreme example many PWME have very low to zero SED rates but only high SED rates are considered a problem. We don't know which metabolites they measured but I'd be a little surprised if there were robust 'norms' in place for many of them from which to derive means and SDs.

Re inherited or acquited Kreb's cycle defects - what I was getting at basically was if it doesn't look or walk like a duck then it probably isn't a duck. There are known diseases effecting mitochondrial or carbohydrate metabolism function - some rare, some not so. Do any of these resemble ME/CFS?

 

[Justin30]

I just wanted to through this out their that in 2009 KDM in a video said down the chain after the viral insult, immune disruption, detox mechamism not working and finally Kreb cycyle dysfunction leading to high levels of heavy metals and toxification.

 

[Bob]

...a critical point is that those tables etc are for looking at means of groups, not inidividual data points. I think the mean may have been the 5SD figure quoted in a tweet (if so, it would have been heavily affected by Whitney's 16SD data point; the other two would have been much closer to the mean), not for individual data points. It's much more common to have extreme single data point than it is to have an extreme group mean - though 16SD is still a wild outlier.

Thanks for that info.

 

[Bob]

Not inherited, these findings are from severely-affected patients who weren't born that way.

But the predisposition to the disease can be inherited.

 

[Bob]

6 weeks of IV glutathione last year gave me 8 of the best weeks ive had in 7 years - was out of bed all day ... hovering...

Crikey, so it's effects were much greater than expected?!? (Sorry, Justy! Couldn't help myself!) Sorry that you've gone back to square one again.

 

[Sasha]

But a critical point is that those tables etc are for looking at means of groups, not inidividual data points. I think the mean may have been the 5SD figure quoted in a tweet (if so, it would have been heavily affected by Whitney's 16SD data point; the other two would have been much closer to the mean), not for individual data points. It's much more common to have extreme single data point than it is to have an extreme group mean - though 16SD is still a wild outlier.

I don't know what data you're talking about but I think one could look at the probability of a single observation in relation to the mean of a group.

 

[lansbergen]

But the predisposition to the disease can be inherited.

As with almost everything.

 

[JaimeS]

Going back to @alex3619 's first post in the thread re Glutathione and Richvank, jut anecdotally 6 weeks of IV glutathione lasyt year gave me 8 of the best weeks ive had in 7 years - was out of bed all day, gardening, hovering, cooking (for fun) started planning to drive again, walking without my wheelchair. Then it ended and now back to square one again. Cant affrord iv Glut in the UK. (I was also having myers type cocktails so may have helped a deficiency, which I seem to have plenty of despite good diet)

Like @Sasha I also had a long remission, which ended 7 years ago. I know I can get better and feel better - why cant we sustain it? but if we can have it in the past, we can have it again!

@justy , my symptom-twin... I've started using Regactiv's Detox & Liver Health probiotic. I'm talking it up everywhere, but I have no stake in the company. They've engineered a strain of Lactobacillus that releases glutathione into the gut. It doesn't last long, so you have to keep on taking it, but the results are awesome. Probably nothing close to getting an injection, but may still be helpful for you if it was for me.

So we know that its a mitochondrial problem but whats seems to be missing to me is why the bacteria, virus, parasite or autoimmune response cause it?

Just spitballing here, but it may be that immune cells require more energy-molecules to function than other cells; and so might neurons. The immune system, nervous system, and muscles may 'feel' the lack most, because they require a lot of energy to do their jobs.

When the immune system tanks, that leaves the road open for a wide variety of opportunistic pathogens. Some of these pathogens actually suck up the molecules we require for energy molecule production, compounding the problem. For example, there are pathogens that really like B12 and will use it before your own cells if they can.

There are known diseases effecting mitochondrial or carbohydrate metabolism function - some rare, some not so. Do any of these resemble ME/CFS?

They do enough that I kept thinking I had one of them. I was not one of the 'obviously infectious onset' patients -- I had a series of adverse health events from which I never fully recovered, over and over again -- which, to me, pointed to an endocrine issue. Over and over again I thought I had an inherited mitochondrial disorder of carb metabolism. So symptoms can be quite similar.

There are even some -- more than you'd think -- that strike a person in their late 20s, early 30s. There's something mystical about that time period in the human body.

-J