Ron Davis Update

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I don't think he's a confident communicator. His mind doesn't work like that it seems. Hence Janet being there to draw out stuff
This is true. I spoke to him on the phone once. I had connections to people with a large pool of money from which they were able to make a donation. I explained over email to him that when I called him and put him on the phone with these people, he would need to talk up his work and let them know how confident he is that he can figure this out. Because the people with this money really didn't know anything about him or his work. I heard the conversation over speaker phone. I have to say I was pretty disappointed in his ability to talk encouragingly and excitedly about his work. It was like pulling teeth. I ended up having to talk it up for him to these people after the call ended.
All that to say, he is a genius and a CFS hero, but the way he talks about his work can definitely land flat to non sciency people or people who aren't familiar with him.
 
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No, it was just that the interview questions didn’t elicit much that was new and interesting. I imediately noticed this and proposed that I interview him because I know what’s happening and exciting in the lab. So I am going to make a bunch of videos with everything that’s going on in the lab. So far we have nine planned. And I just solicited Robert Phair, and I’m going to interview him so he can explain the itaconate shunt better and show his beautiful diagrams. I am considering interviewing other people too. I seem to be able to summarize things in a way that patients can understand and get researchers to explain things and tell us what is exciting to them. I’m kind of excited about this project and I am learning about how to record on zoom . Feedback is definitely welcome!
My feedback is that you're incredible and thank you! I hope you understand the value of these videos for me as a patient. They pump my spirits up 10x what they would otherwise be. I am constantly looking forward to Ron Davis updates. You guys are heroes to me.
 
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Manganese Grant: Ron Davis

The second thing that Ron is excited about.

The department of defence 1.6 million dollars over 3 years and they have gotten the first payment.

Made an observation a few years ago when taking hair samples from patients and analyzing the metals they had in their hair.

Driven by Laurel Crosby worrying about environmental contamination

Can take long hair and use it as a clock to see when people were exposed to contaminants.

Very cheap and easy to test because patients can send in their own hair.

Noticed that in patients hair manganese was the lowest and second lowest was copper.

These are essential metals for use in enzymes for the enzyme to function.

A lot is known about normal people's hair and what levels likely effect enzymatic activity.

In these cases the patients with manganese and copper as well as iron were very low in the sense that they were likely having a problem.

They then looked at patients blood levels which weren't always consistent. Sometimes normal levels in the blood even when their hair was low.

The hair levels come from cells.

It's important that it reaches the cells to be healthy.

It being in the blood does not mean it is reaching the cells.

Where they are looking at it is in ezymes in the mitochondria where it is used.

One of the enzymes is at the beginning of the glycolysis pathway. When glucose is burnt.

Could be why glucose is not used very well in MECFS patients.

Vinod Khosla helps support at low levels of all the preliminary data for the manganese work, for them to continue to explore it.

They want to explore whether there is manganese in the cell, or in the mitochondria because it will need to be digested. Transported from the gut into the blood. From the blood into the cell, and from the cell into the mitochondria.

It can get blocked at any of those levels.

It has to be in the mitochondria to be functioning properly.

The plan is to run enzymatic activities of cells and look at the cells in the mitochondria to see if they're functioning at a normal level.

They will then add manganese and see if it increases activity.

They have also noticed that there are a number of very important enzymes in what's called the urea cycle.

When you burn amino acids, which patients probably are. That's where some/ a lot of their energy is coming from. Then you have to get rid of the nitrogen through the urea cycle. So it is a very important cycle for the patients.

Very important ammonia is not produced from the nitrogen, because it is very toxic.

They are trying to measure ammonia levels but are struggling to find it.

The nitrogen needs to become urea instead of ammonia or you will suffer from toxicity.

They are going to track all of these different enzymes.

Also looking at selenium although it is also important in oxidation.

Three year grant which opens a lot of possibilities over time.

Do not take these metals because it is dangerous to supplement them unless you are shown to be low with a blood test and under medical care.

All of these metals are toxic.

Low manganese will effect your ability to burn glucose, which is a major source of fuel that the body uses.

It will also effect the urea cycle possibly leading to toxicity.

There are indications that there are problems in both of these cycles in patients.

It is a matter of them doing hardcore biochemistry which is Ron's speciality. He believes in data rather than guesswork.

He said to Janet previously that manganese may be at the very core of what is going on in MECFS.

He says this because it is at the core of so many of the enzymes that we know are a problem.

Could be related to the itaconate pathway and BH4. It intersect with BH4 in this pathway.

It is most exciting because this would be so easily corrected if it is true.

It's aboyt transport.

Also the urea cycle is involved with making spermine and spermidine.

This is interesting because a recent publication found that levels of these were important indicators of who would come down with MECFS when getting mononucleosis.

Spermine was one of the top candidates for why you might get MECFS if you've got a viral infection.

Spermidine was too low and spermine was too high.

They act as ion channel blockers and could also Block how things like manganese gets into the cell.

The grant will allow them to explore all of these things.

Will allow them to do biochemistry and metabolite and genetic work.

Will allow them to look at more patients than they have been able to in the past. As many as 100 patients.

There are several other metabolites which have never been seen in mass spectrometry experiments but have never been looked at.

Mike Jensen who works in the lab has worked out assays for electrophoresis HPLC instrument which was purchased with the funds from the OMF. With the special fundraiser for Whitney's birthday.

Nobody has looked at these compounds before and they're really central in terms of regulation. In relation to mangense and they regulate spermine and spermadine.

Ron is excited about this.

Spermine and spermadine are related to sperm and have a strong positive charge and is used in sperm as well in a lot of other places in the body.
 

BrightCandle

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Another update Video -
The manganese grant

- 3 year grant $1.6 million from the department of defence (NIH wouldn't fund these research.)
- Looking at hair some patients its useful as a clock and as a cellular source
- Hair can be used to find metals and its easy and cheap
- But its bad for Zinc since it comes from shampoo
- Manganese was very low and next lowest was copper in ME patients and these are essential metals for enzymes to function. Iron was also found to be low.
- Its low enough to be a problem.

- They took blood and compared but it wasn't consistent, sometimes saw a normal level in the blood.
- Hair comes from cells, just because its in the blood doesn't mean its in the cell
- Ron is interested in it because its involved with a number of enzymes in the mitochondria
- One of those enzymes is the begining of glucolysis.
- If managanese is low you may not be able to burn glucose well.

- Want to track the manganese and ensure it gets from the gut into the blood into the cell and into the mitochondria for it to work.
- Will be looking at if these enzymes are running normally and then adding manganese to them and see if that increases activity.
- It also impacts the Urea cycle - Me patients burn amino acids which produces nitrogen that you have to get rid of and you don't want ammonia to be made. Trying to measure this.
- Ammonia is toxic.
- Might be looking at Selenium not extensively focussed on manganese

- All these things are easy to supplement, but high levels are toxic so don't take them if you aren't low.
- Need to monitor the levels, blood monitoring, needs to be done under medical care.

- The impact is that low manganese reduces ability to burn glucose, also affects how to get rid of Nitrogen. Indications in both of these as a problem.
- Manganese could be the core problem, maybe BH4 since it intersects with this pathway.
- Speremine and Spermidine recent publication levels were involved with mononucleosis and coming down with ME/CFS.
- They can block ion channels and could block manganese
- Will now be able to look at Metabolities that have never been looked at before. HDLC instrument bought on Whitneys fund raiser will allow an assay looking at them related to maganese which regulate spermadine and spermaline, might be important.
- Speremine and Spermidine come from nitrogen impact DNA for sperm but also used throughout the body

- Has the ability to sample 100 patients now which is much better than 10 before. May be a request for volunteers soon.
- Streamlining blood collection with a device on the shoulder
 
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BrightCandle

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On a personal level I did a hair analysis and found both my Copper, Manganese and selenium were low, but so was my Iron and other things too. On top of that treating my body as if it has excess Nitrogen is part of Joshua Liesks protocol and when managing crashes I still take drugs that he suggested for excreting ammonia from the body. These particular areas really speak to what I know is happening in my body, this is a really promising area of research as its definitely something ME patients find to be wrong and targets another area and way energy might be getting restricted.
 

lenora

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Congratulations on obtaining the Manganese Grant. It sounds very interesting. Thank-you also, to Dr. Janet Dafoe and Laurel for her work on studying this matter.

How is Whitney doing? I haven't read an update in a while. Thanks again to both of you....I know you're both very busy people (as well as VIP's!). Yours Lenora.
 
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Here are my thoughts:
I do think ME/CFS has many clusters and I am likely only in one of them.
I dont think Manganese is the root cause of ME/CFS, although my sample size is 1, here is what I found upon experimenting on myself. I took a few times RDA worth of manganese and it had no effect. To Ron's point it has to get through to the mitochondria.
On iron, iron is involved in Fe-S clusters in the mitochondria/energy production and thus iron seems to play a big role at least for me. I supplement with iron bisglycinate and I have a candida infection which I believe is taking my iron away, thus supplementation for me in necessary.
For urea cycle, I found arginine-alpha keto-glutarate helped get out excess urea and I didnt need to pee at night anymore. Note that the urea and citric acid cycles are intimately linked.
For selenium, I found that my selenium and zinc level was slightly high in blood after taking gumweed for covid when I had it.
I had mentioned BH4 before in previous posts.

I still think iron levels in the various forms in the body such as HGb, ferritin, iron, etc are good areas to explore.
 

Woof!

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Hi @Janet Dafoe. Seeing the People article on you, Ron and Whitney is what got me to PR last year. Thank you for that.

I've got a long-standing observation and question, if you've got a moment free to answer...

As a FM/ME-CFS/Sjogrens patient of many decades, and as a medical professional (Cornell doctorate - retired) taught to "look at the entire forest, and not just the trees of interest," I often find myself explaining to others how important it is for me to avoid a long list of environmental and dietary triggers. Common triggers (such as dust, dustmites, cornstarch, smoke & fragrances) didn't start my FM, ME-CFS or Sjogrens, but many of my symptoms are significantly reduced when I avoid them,* and my life (especially when housebound) is soooo much better for the effort. I went from bedridden/severe (for 2 years) to moderate solely with rest and a focus on identifying the triggers I needed to avoid. No drug, nutraceutical or procedure ever made that much difference.

* The opposite is also true: introduce any of these triggers into my environment or diet, and I'm very sick, very fast.

Like having a clean lab in which to do research, it's my feeling that conducting research on patients like us requires avoiding at least the most common environmental triggers, beginning with the ones listed above. In other words: clean lab + clean subjects... After all, it can't hurt any of us to live in a more allergen-free environ. It can only help (and that help can be significant).

Your thoughts?
 

Oliver3

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Hi @Janet Dafoe. Seeing the People article on you, Ron and Whitney is what got me to PR last year. Thank you for that.

I've got a long-standing observation and question, if you've got a moment free to answer...

As a FM/ME-CFS/Sjogrens patient of many decades, and as a medical professional (Cornell doctorate - retired) taught to "look at the entire forest, and not just the trees of interest," I often find myself explaining to others how important it is for me to avoid a long list of environmental and dietary triggers. Common triggers (such as dust, dustmites, cornstarch, smoke & fragrances) didn't start my FM, ME-CFS or Sjogrens, but many of my symptoms are significantly reduced when I avoid them,* and my life (especially when housebound) is soooo much better for the effort. I went from bedridden/severe (for 2 years) to moderate solely with rest and a focus on identifying the triggers I needed to avoid. No drug, nutraceutical or procedure ever made that much difference.

* The opposite is also true: introduce any of these triggers into my environment or diet, and I'm very sick, very fast.

Like having a clean lab in which to do research, it's my feeling that conducting research on patients like us requires avoiding at least the most common environmental triggers, beginning with the ones listed above. In other words: clean lab + clean subjects... After all, it can't hurt any of us to live in a more allergen-free environ. It can only help (and that help can be significant).

Your thoughts?
There is something wrong in the connective tissue...why do these mineral deficits occur in us. I found the idea that supplementing to restore health....haven't CFS people been trying that for decades.
I mean, I'm a layman so who knows just my gut feeling.
I agree with your clean living approach. Just why do we have to peddle so hard to stand still or be able to get out of bed, when there's people smoking, drinking, then running 10 Kms.
Aren't there deficits in people with Asperger's...I dunno just feels like ground zero is connective tissue type
 

Oliver3

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This is true. I spoke to him on the phone once. I had connections to people with a large pool of money from which they were able to make a donation. I explained over email to him that when I called him and put him on the phone with these people, he would need to talk up his work and let them know how confident he is that he can figure this out. Because the people with this money really didn't know anything about him or his work. I heard the conversation over speaker phone. I have to say I was pretty disappointed in his ability to talk encouragingly and excitedly about his work. It was like pulling teeth. I ended up having to talk it up for him to these people after the call ended.
All that to say, he is a genius and a CFS hero, but the way he talks about his work can definitely land flat to non sciency people or people who aren't familiar with him.
Nice work getting the donation
 
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There is something wrong in the connective tissue...why do these mineral deficits occur in us. I found the idea that supplementing to restore health....haven't CFS people been trying that for decades.
I mean, I'm a layman so who knows just my gut feeling.
I'm with you on connective tissue: mine is shot. I see it all over my body. And it correlates with my more severe right side illness. (my left side is far less sick). Its been a lifetime of break down.

Personally I'm a bad supplement taker. But I see others have plenty of enthusiasm for it.

this research should be pursued as it may lead to yet more revelations beyond: just take a bit more manganese.

A question I have:

DOD funded this project. I therefore assume its Gulf War related funding? Is there any background on the grant that the public can look at?
 

Oliver3

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I'm with you on connective tissue: mine is shot. I see it all over my body. And it correlates with my more severe right side illness. (my left side is far less sick). Its been a lifetime of break down.

Personally I'm a bad supplement taker. But I see others have plenty of enthusiasm for it.

this research should be pursued as it may lead to yet more revelations beyond: just take a bit more manganese.

A question I have:

DOD funded this project. I therefore assume its Gulf War related funding? Is there any background on the grant that the public can look at?
Yes. I know Jen Brea is keen on looking into connective tissue types. It doesn't make sense that only certain people seem to get this regularly and that's the sensitive s.
But why re they sensitive??? Why re these people more prone to stress, viral infection and autoimmunity etc. Were deffo not all clean sltes.
I know Ron et Al must've looked at this but it just seems such an across the board unifying thing.
I have a friend with eds. His symptoms are exactly the sane as mine except he has a small anuerysm behind the eye. But we both have pots, intolerant to mold, sensorial issues, energy problems etc etc.
We've both been exhausted since high school. Not a great look. None of my " normie friends" were like this. So what gives.
I think the entry point is the tissue and everything else is downstream.
Autistic people ae renowned for being bad detoxifiers and hold onto metals.
What I'm driving at is, can crispr or stem cells help here.
Cos it seems to me that this will keep happening even if we adjust the deficiency.
Of course I hope I'm wildly wrong and all this has been covered.
Just , I've become obsessed by connective tissue.
I can spot an m.em person a mile off. I'm sure we all can
 
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Another update Video -
The manganese grant

- 3 year grant $1.6 million from the department of defence (NIH wouldn't fund these research.)
- Looking at hair some patients its useful as a clock and as a cellular source
- Hair can be used to find metals and its easy and cheap
- But its bad for Zinc since it comes from shampoo
- Manganese was very low and next lowest was copper in ME patients and these are essential metals for enzymes to function. Iron was also found to be low.
- Its low enough to be a problem.

- They took blood and compared but it wasn't consistent, sometimes saw a normal level in the blood.
- Hair comes from cells, just because its in the blood doesn't mean its in the cell
- Ron is interested in it because its involved with a number of enzymes in the mitochondria
- One of those enzymes is the begining of glucolysis.
- If managanese is low you may not be able to burn glucose well.

- Want to track the manganese and ensure it gets from the gut into the blood into the cell and into the mitochondria for it to work.
- Will be looking at if these enzymes are running normally and then adding manganese to them and see if that increases activity.
- It also impacts the Urea cycle - Me patients burn amino acids which produces nitrogen that you have to get rid of and you don't want ammonia to be made. Trying to measure this.
- Ammonia is toxic.
- Might be looking at Selenium not extensively focussed on manganese

- All these things are easy to supplement, but high levels are toxic so don't take them if you aren't low.
- Need to monitor the levels, blood monitoring, needs to be done under medical care.

- The impact is that low manganese reduces ability to burn glucose, also affects how to get rid of Nitrogen. Indications in both of these as a problem.
- Manganese could be the core problem, maybe BH4 since it intersects with this pathway.
- Speremine and Spermidine recent publication levels were involved with mononucleosis and coming down with ME/CFS.
- They can block ion channels and could block manganese
- Will now be able to look at Metabolities that have never been looked at before. HDLC instrument bought on Whitneys fund raiser will allow an assay looking at them related to maganese which regulate spermadine and spermaline, might be important.
- Speremine and Spermidine come from nitrogen impact DNA for sperm but also used throughout the body

- Has the ability to sample 100 patients now which is much better than 10 before. May be a request for volunteers soon.
- Streamlining blood collection with a device on the shoulder
Just got my HTMA back and I am undetectable for manganese lolll. And yes copper also low.. And a few others. Will post when I'm better, doing very badly atm.

2 months of high dose (3 - 8 mg) copper took it from like 8.7 to 9.8 or something, population average 33..?
 

lenora

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Hello everyone.....I've been a part of communities just getting ME/FM/CFS (whatever!) off the ground since the beginning of the AIDS epidemic. I'm now 75 yrs. old and have seen a lot of research and cures come and go BUT progress has been made in some medicines. I'm also a believer in using vitamins, supplements and herbs to help ourselves.

Our illness as composed of many things (I believe), and who knows when a cure will come? There will be many, I believe, but in the meantime we try to treat as many symptoms as possible. Research is slow because it has to be thorough and proven by other researchers before it enters the medical community.

I can remember when EDS was placed in with our illness(es) and it seemed so odd at the time. Like it wasn't known where to place these people...b/c of past groups, I've kept in touch with some of these original victims and they're just like us, except that many things don't work for them and some are fine and working all these years later (have problems like most people, but they're managing) while others do have serious problems to worry about.
We help ourselves as much as possible without causing more damage. We support research and that means contributing as much as we can....small or large, the amount doesn't matter. It all accrues. We can only do what is necessary to feel better ourselves and often it seems it's the right thing. So yes, connective tissue problems seem to be a part of many of our lives. Be patient and be hopeful....the answers will come in stages. One thorough investigation at a time. Again, we thank the Dafoe/Davis family for what they're doing to help us. Perhaps it wont' be the total answer....but a part of it,, and I'm all for that as I know most of us are. Yours, Lenora
 
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Oliver3

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Hello everyone.....I've been a part of communities just getting ME/FM/CFS (whatever!) off the ground since the beginning of the AIDS epidemic. I'm now 75 yrs. old and have seen a lot of research and cures come and go BUT progress has been made in some medicines. I'm also a believer in using vitamins, supplements and herbs to help ourselves.

Our illness as composed of many things (I believe), and who knows when a cure will come? There will be many, I believe, but in the meantime we try to treat as many symptoms as possible. Research is slow because it has to be thorough and proven by other researchers before it enters the medical community.

I can remember when EDS was placed in with our illness(es) and it seemed so odd at the time. Like it wasn't known where to place these people...b/c of past groups, I've kept in touch with some of these original victims and they're just like us, except that many things don't work for them and some are fine and working all these years later (have problems like most people, but they're managing) while others do have serious problems to worry about.
We help ourselves as much as possible without causing more damage. We support research and that means contributing as much as we can....small or large, the amount doesn't matter. It all accrues. We can only do what is necessary to feel better ourselves and often it seems it's the right thing. So yes, connective tissue problems seem to be a part of many of our lives. Be patient and be hopeful....the answers will come in stages. One thorough investigation at a time. Again, we thank the Dafoe/Davis family for what they're doing to help us. Perhaps it wont' be the total answer....but a part of it,, and I'm all for that as I know most of us are. Yours, Lenora
Ron has eds.
I'm not saying that I'm not glad this research is happening. Of course I am!!! And I'm grateful they're looking into this. Every thing that is looked at is a step forward
I know people who have had CFS( so they were diagnosed as) who are now functional.
It's ok to post your feelings and thoughts.
I'm not being disrespectful in the slightest to Ron and Janet.
I honestly think of them everyday and wonder how they're getting on and feel grateful such decent and grounded but expert people are working on this.
It's ok as a sufferer to express your feelings and to posit any feedback, however inavluable it may seem, as you just never know.
Eds is not fully understood yet. All its permutations and expressions are not either.
This study is great. If that's not clear, I'm REALLY grateful it's happening.
I'm just asking,WHY us as sufferers become sick.
There's no such thing as blind chance. Everything occurs because of smthg. Connective tissue seems to be the unifying factor in our illnesses. To me.
It's ok to say it. Otherwise, why are we on this site?
I respect your desire to wait and see. Great too.
But I just want it clear, because connective tissue really bothers me. It's always there in family, or in the sufferer themselves.
And I guess my fear is that if manganese is the key, then why did we lose it and will it happen again.
Which is why this study is good. Any road will get us closer won't it?
 

Alvin2

The good news is patients don't die the bad news..
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@Janet Dafoe

It seems hair analysis is the wild west, apparently many labs are not repeatable by third party testing.
So i am curious does OMF do the hair analysis in their own lab or have you found a lab that you use that is solid?
If third party can you tell us who it is if we want to get our own analyses done privately?

Also the video mentioned looking for patient volunteers in the future, where will that be advertised?
 
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So i am curious does OMF do the hair analysis in their own lab or have you found a lab
sort of tried to figure that out...Dr. Laura Crosby is the phd in Engineering working on the hair analysis and they did some previously but I cannot find methods described.

(I think they are doing the analysis there at Stanford)

And thats a good question: does accurate hair analysis exist for others to check their own levels?