A Metabolic Trap for ME/CFS?

[Mary]

I dont ever recall wishing summer to end, until now.

Not to take this thread off topic, but didn't Mark Twain say the coldest winter he ever spent was summer in San Francisco? (I couldn't resist - I love summer and heat - I live in the high desert of So Cal so it gets quite warm but my swamp cooler does a fabulous job. I used to live near the coast, and the summers were very often cold and depressing!)

But I too would willingly give up my summer even here in the high desert to get an answer!

 

[raghav]

Latest update from Dr. Ron Davis on current research as of May 2018

 

[chris160]

[Moderator note: according to this post, Dr. Phair now now has enough 23andMe data but could still use whole exome or whole genome data.]

Help Dr. Phair with his research and send in your genome!

rphair@integrativebioinformatics.com

Your data would be most comprehensive and powerful in the form of .VCF (Variant Call Format) file but we will work to find a way to analyze your data in any format you are able to provide.

Please also tell us your age and gender and write a paragraph or a page with a description of how you came down with ME/CFS. A list of current symptoms is optional, but desirable.

E-mail from Dr. Phair regarding 23andme data:

Yes, the .txt format will work. 23andMe only covers three of the five genetic variants that are important for the metabolic trap theory, but I can say that even this limited information is useful.

The 23and Me file that I need has a filename like this: genome_firstName_lastName_Full_date_time_in_digits.txt
so if it was mine it would be something like
genome_Robert_Phair_Full_20180315085441.txt
.zip instead of .txt is also fine
If you can open the file in a text editor it should begin with a header that looks like this:
# This data file generated by 23andMe at: Wed Jun 14 12:04:30 2017
#
# This file contains raw genotype data, including data that is not used in 23andMe reports.
Regards,

Robert D Phair PhD | Chief Science Officer | Integrative Bioinformatics Inc
Mountain View, CA
www.integrativebioinformatics.com


Edit: Dr. Phair now now has enough 23andMe data but could still use whole exome or whole genome data

My dd had WES testing. It was done at Baylor. They only provided her the results. Is there a way to get the data. I was told by her geneticist that Baylor will not supply the data. Does anyone know if that is correct?

 

[Janet Dafoe]

Hi @Janet Dafoe (Rose49) ,

Thank you for sharing this. I am so intrigued by the metabolic trap theory. And although I know the treatment cannot be released yet, could you at least confirm that the proposed treatment is not a ketogenic diet?

Thanks!

-Brian

I think that is highly unlikely. The reason I can't tell you is because I don't know what the treatment will be and I don't know what to avoid. They are working on it. they have some hypotheses about this but really, they can't release those or everyone will start trying things and that really could be harmful. things are moving right along though! They got a little slowed down because there was a sign up for the mass spectrometer and it was full for a week. So they planned more tests and did more modeling so they would be ready to do even more when the machine is available. Never a dull moment!

 

[valentinelynx]

Not to take this thread off topic, but didn't Mark Twain say the coldest winter he ever spent was summer in San Francisco?

OK, off thread... yes, I used to teach swimming lessons in the summer in the SF Bay Area. My hands would turn blue in the cold foggy days... I want to go back!!

 

[Kenshin]

A biomarker soon followed by a cure.
That is heaven.

 

[valentinelynx]

I would need air con 24/7,

That’s a given here in summertime! And I hate A/C (indoor allergies worse than outdoor...) Like you heat makes me ill. First 100 degree day early April (I was in Phoenix that day, which is even hotter than Tucson).

Ok, I’ll stop detailing thread now!

 

[raghav]

New $1 million donation for ME/CFS research!


OMF received a $1 million anonymous pledge to escalate Dr. Ron Davis’s systems biology approach with Robert Phair, PhD, at the ME/CFS Collaborative Research Center at Stanford University. This will expand the search for and testing of their “metabolic trap” hypothesis, and will enable Dr. Davis to hire an additional scientist with experience in complex metabolic analysis to accelerate this research. Watch for research updates to keep informed about their progress on this exciting project.

For more information on this project click here.

Thank you.

With hope for all,

Linda Tannenbaum
CEO/President

 

[Sundancer]

deep gratitude for the anonymous donor,

 

[Hopeful1976]

Could the fact that for so many of us, medicines that initially help quickly stop working, be evidence of a skewed metabolism?? I've been thinking this today.. So often I've taken alternative remedies that seem to offer help, but they soon stop after a month or so and I can never understand how I become so tolerant so quickly?

 

[ljimbo423]

Could the fact that for so many of us, medicines that initially help quickly stop working, be evidence of a skewed metabolism??

That certainly rings true for me. I don't know exactly how that would work but it makes sense.

I'm fairly confident that there is significant mitochondrial dysfunction in CFS and that is playing a big role in symptoms.

Jim

 

[maybe some day]

A biomarker soon followed by a cure.
That is heaven.

Makes life worth sticking around for.

 

[alex3619]

Could the fact that for so many of us, medicines that initially help quickly stop working, be evidence of a skewed metabolism?? I've been thinking this today.. So often I've taken alternative remedies that seem to offer help, but they soon stop after a month or so and I can never understand how I become so tolerant so quickly?

A lot of patients have been thinking exactly this for a long time now. Trying to fix the problem often just means it deepens or a particularly promising treatment fails. Its like trying to fix a problem without fixing the underlying cause. Its sticky tape. Eventually the sticky tape peels off or rips or degrades.

 

[bthompsonjr1993]

I think that is highly unlikely. The reason I can't tell you is because I don't know what the treatment will be and I don't know what to avoid. They are working on it. they have some hypotheses about this but really, they can't release those or everyone will start trying things and that really could be harmful. things are moving right along though! They got a little slowed down because there was a sign up for the mass spectrometer and it was full for a week. So they planned more tests and did more modeling so they would be ready to do even more when the machine is available. Never a dull moment!

Awesome! Thank you for the informative reply, and for everything you do! Also, I hope you are doing well after your procedure.

 

[J.G]

Could the fact that for so many of us, medicines that initially help quickly stop working, be evidence of a skewed metabolism?? I've been thinking this today.. So often I've taken alternative remedies that seem to offer help, but they soon stop after a month or so and I can never understand how I become so tolerant so quickly?

Yeah, this makes sense to me. I remember @alex3619 and myself discussing something similar ~2 years ago when the Naviaux study and its altered state 'dauer' hypothesis first came out.

EDIT: Found the thread / posts: https://forums.phoenixrising.me/ind...udy-pnas-august-2016.46524/page-2#post-758940

I wrote:

"The 'altered state' potentially explains why for so many PWME certain combinations of supplements seem to bring brief improvement before losing their effectiveness. The supplements are quickly subsumed under pre-existing altered state metabolism, and insufficient by themselves to drag the body out of it."

Still looks like that might be accurate.

 

[HowToEscape?]

Yeah, this makes sense to me. I remember @alex3619 and myself discussing something similar ~2 years ago when the Naviaux study and its altered state 'dauer' hypothesis first came out.

EDIT: Found the thread / posts: https://forums.phoenixrising.me/ind...udy-pnas-august-2016.46524/page-2#post-758940

I wrote:

"The 'altered state' potentially explains why for so many PWME certain combinations of supplements seem to bring brief improvement before losing their effectiveness. The supplements are quickly subsumed under pre-existing altered state metabolism, and insufficient by themselves to drag the body out of it."

Still looks like that might be accurate.

Throwing a dart here, as I know zero about the metabolic process: Perhaps the reason a wide variety of supplements seem to work is that some simply have a stimulant function in our oddly dysfunctioning systems. Those that are beneficial to us continue to work for some time, but others that were of no benefit created a temporary stimulant effect.
Does this make biological sense?

 

[jpcv]

@Learner1

Just to clarify regarding Niacin : I am not suggesting that one should take or not. What is known however is that to people having Liver Disease, Niacin can cause problems. One might say that since Liver Enzymes are normal, this means that the Liver is fine. This is not true unfortunately. The only way to assess Liver function is through Liver Biopsy. I have a few examples of ME/CFS Patients with F2 - F3 Fibrosis being completely asymptomatic and without having elevated Liver Enzymes.

Myself, for exemple. I have Hep B, normal liver enzymes, no viral replication ( Antigen E negative , Anti Epositive) but F3 fibrosis.

 

[ukxmrv]

When Dr Ramsay descried his ME patients he spoke about how their symptoms fluctuated during the day and night.

I know this has been said before but I'm wondering how it fits into the theory of a switch, there is the night / day phenomenon whereby some patients like myself go to bed feeling the best that they do all day only to sleep have revert back to crap the next morning,

What is the "switch" that occurs overnight in this group of patients ? Can this be related to a metabolic switch or is it just another symptom?

I've learned that the best way for me to set this in motion for the best functioning during the day is to sleep as late as I can in the mornings (as for me the "switch" occurs between 4am and 7am so need to avoid these times) and to save my activities for the afternoon and evening. I know that this corresponded with my cortisol production but may be there are other things happening as well.

For me this bad "switch" is to do with sleep. It transforms me each night. If i could live eternally in the evening and not sleep I'd be happier.

 

[J.G]

@Ben H
Unfortunately to this day we do not know :

1) What is the prevalence of ME/CFS patients with previous Liver insults (Hepatitis, Gilbert's, Hemochromatosis, EBV, Lyme, Certain Medications) and/or Gallbladder (Stones, Gallbladder removal, Cholestasis) issues vs Controls

You can add two more to that list:
- Epstein-Barr Virus (EBV), which is known to disrupt liver function (e.g. here).
- Accutane / isotretinoin. This is an oral acne drug that is nothing more than ultra-high dose Vitamin A, which gets stored by the liver and may mess up its functioning. Accutane is known to cause elevated liver enzymes years after use, and may in some cases lead to fibrosis. Point of note: in high quantities, Vitamin A is hugely toxic to mitochondria. Make of that what you will in relation to ME/CFS as a potential chronic cell-danger response (e.g. Naviaux's research). (I know a few ME/CFS patients who took Accutane some months / years before falling ill.) De Oliviera's article on Accutane, liver damage and oxidative stress is interesting regarding both of the above. This one, also by De Oliviera titled "Vitamin A and Retinoids as Mitochondrial Toxicants", possibly even more so.

EDIT: Woops, EBV was on your list already. Oh well.

@Learner1
The only way to assess Liver function is through Liver Biopsy.

FibroScan is a quick and painless alternative that gives good information on the structural integrity of the liver. Patients may still suffer from functional liver disorders even if the tissues look good, though, much like functional bowel / pancreatic disorders may be present even if those organs look fine optically.

 

[caledonia]

Since then, he’s been creating model simulations to test his hypothesis. Thus far, he’s created kinetic models of the central metabolic systems in the body (mitochondrial electron transport chain, TCA cycle, fatty acid beta oxidation, amino acid oxidation, glycolysis and pentose phosphate pathway, purine synthesis and degradation, and NAD synthesis).

Can somebody explain what a kinetic model is? Is it a computer simulation, or something literally built out of cells, or something else?