Ron Davis: Preliminary data shows problems with energy metabolism

[Forbin]

... - though 16SD is still a wild outlier.

Yeah. Knowing nothing of how difficult it would be, my first instinct would be to re-test that particular value several times.

 

[A.B.]

16 SD = 1 / number of atoms in the milky way chance? I'm making stuff up here but it must be something ridiculous like that.

In any case, not being due to chance isn't the same as being true. It could still be an error. XMRV was a lab contamination.

 

[JaimeS]

16 SD = 1 / number of atoms in the milky way chance? I'm kidding but it must be something ridiculous like that.

Well, or the number of atoms in a bowl of fruit, lol.

Remember that 1 g of hydrogen represents 6,022,000,000,000,000,000,000,000 atoms....

 

[Simon]

There are known diseases effecting mitochondrial

Sure, and this isn't a duck, according to researchers who've dicussed mecfs in the context of mito disorders - the exercise test results in particular.

But the mitochondrion is a complex organelle with complex chemistry, and so a ton of different ways to go wrong - not least of which is "something else" triggering the problems, which would be v different to a mito disease, yet still involve the Kreb's cycle.

But the predisposition to the disease can be inherited.

Sure - but @Marco was talking about eg developmental disorders, which would need the mito problem to be manifest from the outset, rather than merely a risk factor.

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.

You can, but the calculations would be different than for comparing means, and the improbabiliy of a single data point much lower. (Not offering to do the calculations, which I have a horrible feeling would involve calculus.)

 

[Simon]

Ron Davis talk - abstract from Invest in ME Journal (PDF)​

(Thanks to Sasha for spotting this)

While we were seeking funding for the Big Data Study we tested some of the technologies on a few severe and not severe CFS and healthy control patients.

We discovered that the metabolome (the small metabolites found in the blood and urine) of the serium gave clear indication of metabolic abnormalities.

Preliminary results indicated that glycolysis may be impaired with glucose being routed to fatty acid synthesis.

Possibly more important, the metabolites in the citric acid cycle in the mitochondria were lower than in healthy controls and some almost undetectable.

This cycle generates most of the energy (ATP) for the body. It makes it clear that this is no psychosomatic disease. From preliminary analysis it would appear that not only ATP is low but also ADP, AMP, GTP and in some cases uracile.

These cofactors are involved in hundreds of molecular reactions in the body including in the brain. Their decrease would cause a large number of body functions to be abnormal.

We don’t know which cells in the body are being affected (possible all cells) and are currently studying the various white and red cells with a variety of commercial and custom technologies.

 

[msf]

Great sleuthing, Sasha!

Anyone care to guess why the body would reroute glucose to fatty acid synthesis? Could it be because of oxidative damage?

 

[Marco]

We don’t know which cells in the body are being affected (possible all cells) and are currently studying the various white and red cells with a variety of commercial and custom technologies.

I'd be more impressed if they were using validated assays.

 

[msf]

Who says they aren´t?

 

[JaimeS]

Anyone care to guess why the body would reroute glucose to fatty acid synthesis? Could it be because of oxidative damage?

YES, omg! On my giant PhD thesis chart, it already says "glycolysis"... "--pushes to--->" "fatty acid synthesis"... and when I follow my arrows back, it relates to infection.

...It's great having brain fog, you get to rediscover everything all over again.

-J

 

[justy]

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.

I'll have a look into that. Due to MCAS I cant take most probiotics, so not sure I would tolerate this one, but thanks for the heads up!

Over and over again I thought I had an inherited mitochondrial disorder of carb metabolism. So symptoms can be quite similar.

Yes me too - I was convinced that I had a mitochondrial disorder - there are also a lot of acquired ones. The Australian mito society has great info and reading their website I couldn't believe how much I sounded like people with those diseases. I do get PEM severely, but I also get very sudden energy drainage when doing a task and get the immediate 'feel like im going to die feeling' this feeling CAN be helped by resting. So early on in the day I may have this after trying to water plants in the garden, I lay down for an hour and then feel OK again (my OK), but I still have to stay within my envelope all the time.

@Bob - I just spotted that mistake too - imagine if I could Hover - amazing super power skill!

 

[justy]

YES, omg! On my giant PhD thesis chart, it already says "glycolysis"... "--pushes to--->" "fatty acid synthesis"... and when I follow my arrows back, it relates to infection.

...It's great having brain fog, you get to rediscover everything all over again.

-J

What does this mean? - Please explain this as if you were explaining it to a 6 year old

 

[JaimeS]

Due to MCAS I cant take most probiotics, so not sure I would tolerate this one, but thanks for the heads up!

I thought I couldn't do them either, but it turns out that at least in my case, it's like food. There are many that make me sicker, but it's not all of them. I'm also using Dr Ohira's now -- no bad reaction at all. There may be one out there that doesn't bother you.

 

[JaimeS]

What does this mean? - Please explain this as if you were explaining it to a 6 year old

Being vague a little deliberately, because so far as I know, no one has published anything that points directly to my hypothesis yet. That could mean it's comically misguided, not brilliant -- trust me, I'm well aware. Or that there is a reason my hypothesis doesn't make sense that I don't yet understand due to lack of background.

But I'm hoping it's something that turns out to be useful, eventually. Def not ready for public consumption.

Jaime

 

[alex3619]

We discovered that the metabolome (the small metabolites found in the blood and urine) of the serium gave clear indication of metabolic abnormalities.

This is where I came into CFS research, in the 90s. Back then it was not well received, but they lacked the technology and scale of research to really prove their point. I think it likely that this time will see some big discoveries being made and validated, and finally give us a big picture on what is happening in CFS and ME.

 

[msf]

YES, omg! On my giant PhD thesis chart, it already says "glycolysis"... "--pushes to--->" "fatty acid synthesis"... and when I follow my arrows back, it relates to infection.

...It's great having brain fog, you get to rediscover everything all over again.

-J

I assume your PhD chart was based on reading the necessary textbooks, articles etc.

P.S. I may publish a theory that seems strangely like yours in the next few days in abstract form...

 

[msf]

P.P.S. That was a joke, I know it´s hard for someone to have a sense of humour about their PhD.

 

[wastwater]

I thought that higher levels of cytokines were toxic and the effect is seen on the mitochondria.
Always thought of this as another side effect.
Toxic (metabolic?)encephalopathy and is the damage permanent

 

[justy]

Being vague a little deliberately, because so far as I know, no one has published anything that points directly to my hypothesis yet. That could mean it's comically misguided, not brilliant -- trust me, I'm well aware. Or that there is a reason my hypothesis doesn't make sense that I don't yet understand due to lack of background.

But I'm hoping it's something that turns out to be useful, eventually. Def not ready for public consumption.

Jaime

when it is ready to be published will you please (pretty please) enter the 'Dance your PHD' contest?

http://www.sciencemag.org/news/2015/11/announcing-2015-dance-your-phd-winner

 

[Sasha]

You can, but the calculations would be different than for comparing means, and the improbabiliy of a single data point much lower. (Not offering to do the calculations, which I have a horrible feeling would involve calculus.)

http://stats.stackexchange.com/ques...sample-size-sample-average-and-popu/1836#1836

 

[Marco]

Who says they aren´t?

They don't say they are - it would be nice if they did. The refer to commercial and custom technologies. These may or may not be externally validated and recognised as such. If not - who knows what they mean if anything. I'm not trying to deliberately critical but it's an important point.