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OMF-funded RBC Deformability Paper Published!

Ben H

OMF Volunteer Correspondent
Messages
1,131
Location
U.K.
Hi guys,

As some of you may know the first paper funded by OMF has been published :) a special day indeed.

The study can be found in the link below. Thank you to everyone who supports OMF and the research teams for helping make this possible-this was FULLY funded by OMF and therefore funded by you!

Anyway here is the info straight from OMF:

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Dear Friends,

We are thrilled to share with you that OMF-funded research on Red Blood Cell Deformability by Mohsen Nemat-Gorgani, PhD, of Stanford University, and Anand Ramasubramanian, PhD, of San Jose State University, in collaboration with Ron Davis, PhD, and their teams, has just been published in Blood Journal. This important research could lead to a potential biomarker and diagnostic test.

This critical study has been fully funded by Open Medicine Foundation (OMF) through the support of our generous donors. I extend my personal thank you for your support of our mission to end ME/CFS. The OMF community is standing strong together in support of this urgent research.

Please read the summary from Dr. Ron Davis and the publication below. Every day, together we are breaking ground and moving closer to answers.

With hope for all,

hEOXYT9_-hKDelO8YYEDeTHuLP0C2nz2Ud1juiHoBM1Nr-ezG3oPVnK4K-mxhY8j-g1sD54s7yEOy6z9S-q2ay4YTLbFPrdTPUzxU7-NB_dT22m7FypT5fEO=s0-d-e1-ft

Linda Tannenbaum
Founder & CEO/President

OMF-funded Red Blood Cell Deformability Study Published
Written by Ronald W. Davis, PhD

This paper documents that red blood cells are less deformable in ME/CFS patients compared to healthy controls. It potentially could be a biomarker, and we are proceeding to design new devices that will make a clear distinction between patients and healthy controls. These devices will be hand-held and easy to use by doctors in their offices, or in clinical testing labs. Past work has looked primarily at the shape of red blood cells, which is difficult to quantitate. Our approach will give a clear quantitative number. It measures the ability of red blood cells to deform while squeezing into a capillary, something that blood cells must do for healthy flow. We measure hundreds of cells from each patient, so, because of this, even though the number of patients is low, we get a very statistically significant distinction between patient and healthy cells' deformability. We are putting our energy into developing the new devices as soon as possible.

Erythrocyte Deformability As a Potential Biomarker for Chronic Fatigue Syndrome
Published in Blood Journal

Authors: Amit K. Saha, Brendan R. Schmidt, Julie Wilhelmy, Vy Nguyen, Justin Do, Vineeth C. Suja, Mohsen Nemat-Gorgani, Anand K. Ramasubramanian and Ronald W. Davis

"Our data demonstrates that the significant decrease in deformability of RBCs from ME/CFS patients may have origins in oxidative stress, and suggests that altered microvascular perfusion can be a possible cause for ME/CFS symptoms. Our data also suggests that RBC deformability may serve as a potential biomarker for ME/CFS, albeit further studies are necessary for non-specific classification of the disease." Read the full article here.




Hopefully we can build on this moving forward :)


B

@Janet Dafoe (Rose49) @AshleyHalcyoneH @marilynbsg
 

raghav

Senior Member
Messages
809
Location
India
@Ben H Is it possible to find out from Dr. Ron Davis when these diagnostic tools will be available for purchase so that we can test whether we really have ME/CFS or some other form of chronic fatigue. Thanks in advance.
 

Ben H

OMF Volunteer Correspondent
Messages
1,131
Location
U.K.
@Ben H Is it possible to find out from Dr. Ron Davis when these diagnostic tools will be available for purchase so that we can test whether we really have ME/CFS or some other form of chronic fatigue. Thanks in advance.

Hi @raghav

If you're referring to the eventual handheld Drs equipment I am not sure, not soon I would think as there will be further research on this.

However, it is possible to examine your rbc's under a microscope, in a very primitive way. I have done this, along with one healthy control and one moderate mecfs patients (I am severe) and my serum looked like an absolute warzone, in general but regards to rbc's too. Again on a very primitive level. Controls were not age matched but only gender matched and a sample of 3 :D

The equipment used in this study is far far superior to any home experiment ;)

But it was interesting nonetheless.


B
 

FMMM1

Senior Member
Messages
513
Hi guys,

As some of you may know the first paper funded by OMF has been published :) a special day indeed.

The study can be found in the link below. Thank you to everyone who supports OMF and the research teams for helping make this possible-this was FULLY funded by OMF and therefore funded by you!

Anyway here is the info straight from OMF:

Hopefully we can build on this moving forward :)


B

@Janet Dafoe (Rose49) @AshleyHalcyoneH @marilynbsg

Great to see this.
P values look really good; are these for group values i.e. comparing a group with ME/CFS with a group of healthy controls? @Vassie

If these P values are for group comparisons then can the test currently separate all those with ME/CFS from healthy controls?

I've just looked at this:
"The expression signature of very long non-coding RNA in myalgic encephalomyelitis/chronic fatigue syndrome" [https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-018-1600-x]

I think Ron spoke about the need to ensure there are no false negatives i.e. in a diagnostic test. It might be possible to look at a combination of methods to identify all of those with ME/CFS i.e. to eliminate false negatives.
 

Seven7

Seven
Messages
3,444
Location
USA
So when this happens is automatically accepted as a test, or studies with big participant has to be done to validate???
 
Messages
73
Great news! Beautiful research. I’m hopeful this will lead to a much better understanding of our disease.
 
Messages
60
Location
Seattle
Grateful to the people doing top-notch research in this field! Looking forward to seeing the paper once it's out.

When I looked at the link, I, too, thought that the link went to an abstract. (The abstract also reads more like a conference abstract than an abstract for a paper - which are usually briefer.)
But, papers usually follow abstracts - with some delay.
 

Murph

:)
Messages
1,799
Mostly posting this for fun. :)

Nutr Res. 2017 Mar;39:69-75. doi: 10.1016/j.nutres.2017.03.002. Epub 2017 Mar 7.
Acute dark chocolate ingestion is beneficial for hemodynamics via enhancement of erythrocyte deformability in healthy humans.
Radosinska J1, Horvathova M2, Frimmel K3, Muchova J2, Vidosovicova M4, Vazan R4, Bernatova I5.
Author information
Abstract

Erythrocyte deformability is an important property of erythrocytes that considerably affects blood flow and hemodynamics. The high content of polyphenols present in dark chocolate has been reported to play a protective role in functionality of erythrocytes. We hypothesized that chocolate might influence erythrocytes not only after repeated chronic intake, but also immediately after its ingestion. Thus, we determined the acute effect of dark chocolate and milk (with lower content of biologically active substances) chocolate intake on erythrocyte deformability. We also focused on selected factors that may affect erythrocyte deformability, specifically nitric oxide production in erythrocytes and total antioxidant capacity of plasma.

We determined posttreatment changes in the mentioned parameters 2hours after consumption of chocolate compared with their levels before consumption of chocolate. In contrast to milk chocolate intake, the dark chocolate led to a significantly higher increase in erythrocyte deformability. Nitric oxide production in erythrocytes was not changed after dark chocolate intake, but significantly decreased after milk chocolate. The plasma total antioxidant capacity remained unaffected after ingestion of both chocolates. We conclude that our hypothesis was confirmed. Single ingestion of dark chocolate improved erythrocyte deformability despite unchanged nitric oxide production and antioxidant capacity of plasma. Increased deformability of erythrocytes may considerably improve rheological properties of blood and thus hemodynamics in humans, resulting in better tissue oxygenation.
 

FMMM1

Senior Member
Messages
513
Mostly posting this for fun. :)

Nutr Res. 2017 Mar;39:69-75. doi: 10.1016/j.nutres.2017.03.002. Epub 2017 Mar 7.
Acute dark chocolate ingestion is beneficial for hemodynamics via enhancement of erythrocyte deformability in healthy humans.
Radosinska J1, Horvathova M2, Frimmel K3, Muchova J2, Vidosovicova M4, Vazan R4, Bernatova I5.
Author information
Abstract

Erythrocyte deformability is an important property of erythrocytes that considerably affects blood flow and hemodynamics. The high content of polyphenols present in dark chocolate has been reported to play a protective role in functionality of erythrocytes. We hypothesized that chocolate might influence erythrocytes not only after repeated chronic intake, but also immediately after its ingestion. Thus, we determined the acute effect of dark chocolate and milk (with lower content of biologically active substances) chocolate intake on erythrocyte deformability. We also focused on selected factors that may affect erythrocyte deformability, specifically nitric oxide production in erythrocytes and total antioxidant capacity of plasma.

We determined posttreatment changes in the mentioned parameters 2hours after consumption of chocolate compared with their levels before consumption of chocolate. In contrast to milk chocolate intake, the dark chocolate led to a significantly higher increase in erythrocyte deformability. Nitric oxide production in erythrocytes was not changed after dark chocolate intake, but significantly decreased after milk chocolate. The plasma total antioxidant capacity remained unaffected after ingestion of both chocolates. We conclude that our hypothesis was confirmed. Single ingestion of dark chocolate improved erythrocyte deformability despite unchanged nitric oxide production and antioxidant capacity of plasma. Increased deformability of erythrocytes may considerably improve rheological properties of blood and thus hemodynamics in humans, resulting in better tissue oxygenation.

Good one!
 
Messages
90
Mostly posting this for fun. :)

Nutr Res. 2017 Mar;39:69-75. doi: 10.1016/j.nutres.2017.03.002. Epub 2017 Mar 7.
Acute dark chocolate ingestion is beneficial for hemodynamics via enhancement of erythrocyte deformability in healthy humans.
Radosinska J1, Horvathova M2, Frimmel K3, Muchova J2, Vidosovicova M4, Vazan R4, Bernatova I5.
Author information
Abstract

Erythrocyte deformability is an important property of erythrocytes that considerably affects blood flow and hemodynamics. The high content of polyphenols present in dark chocolate has been reported to play a protective role in functionality of erythrocytes. We hypothesized that chocolate might influence erythrocytes not only after repeated chronic intake, but also immediately after its ingestion. Thus, we determined the acute effect of dark chocolate and milk (with lower content of biologically active substances) chocolate intake on erythrocyte deformability. We also focused on selected factors that may affect erythrocyte deformability, specifically nitric oxide production in erythrocytes and total antioxidant capacity of plasma.

We determined posttreatment changes in the mentioned parameters 2hours after consumption of chocolate compared with their levels before consumption of chocolate. In contrast to milk chocolate intake, the dark chocolate led to a significantly higher increase in erythrocyte deformability. Nitric oxide production in erythrocytes was not changed after dark chocolate intake, but significantly decreased after milk chocolate. The plasma total antioxidant capacity remained unaffected after ingestion of both chocolates. We conclude that our hypothesis was confirmed. Single ingestion of dark chocolate improved erythrocyte deformability despite unchanged nitric oxide production and antioxidant capacity of plasma. Increased deformability of erythrocytes may considerably improve rheological properties of blood and thus hemodynamics in humans, resulting in better tissue oxygenation.

This is serious for me - my breakfast is half a bar of 85%! Hard to function without it. Now I can feel less guilty about it!
 

nandixon

Senior Member
Messages
1,092
I’m hopeful this will lead to a much better understanding of our disease.
I wish that were true, and I haven't read the full paper yet, but this is likely an expected finding more or less.

It's been known for decades that ME/CFS patients have higher than normal levels of oxidative stress through, for example measuring blood levels of lipid peroxidation. In fact, if a person doesn't show higher levels of lipid peroxidation at baseline then I would imagine it's unlikely they even have ME/CFS - or any other significant disease process for that matter. Most comparable diseases like SLE, MS, Sjogren's, Alzheimer's, etc, all are associated with oxidative stress and lipid peroxidation.

Likewise, it's been known for many years that oxidative stress affects RBC deformability. So one would expect to find abnormal RBC deformability in diseases with associated lipid peroxidation, and indeed this has already been found in some of the aforementioned diseases.

(See, for example, Lipid peroxidation affects red blood cells membrane properties in patients with systemic lupus erythematosus)

So it doesn't seem too likely, I don't think, that RBC deformability could become a diagnostic test exclusive for ME/CFS, rather as the title of the study indicates, it would be another biomarker, effectively being a more convenient way for doctors to assess oxidative stress rather than measuring lipid peroxidation by sending a blood sample off for laboratory analysis. It also has a more tangible feel to it that hopefully might give it additional weight with the medical community.

There are some additional possibilities for abnormal RBC deformability but oxidative stress is the most obvious, I believe.
 

Belbyr

Senior Member
Messages
602
Location
Memphis
So perhaps the goal here could be to show that ME/CFS causes the same abnormality as the other diseases you listed, therefore it would prove to the NIH ME/CFS needs funding just like the others... One can hope.

My personal opinion when I saw this article initially was that this will be too broad to use as a diagnostic for just ME/CFS.
 
Messages
73
@nandixon
It doesn’t have to be specific to our disease to be helpful.
The paper states: “Taken together, our data demonstrates that the significant decrease in deformability of RBCs from ME/CFS patients may have origins in oxidative stress, and suggests that altered microvascular perfusion can be a possible cause for ME/CFS symptoms.”

Do you realize how much we would have won when we could have an accepted FDA approved blood test done that shows our doctors that there is a physical problem that can explain our symptoms? This in itself would be major progress. And we can build on from here. That’s how I see it.
 

nandixon

Senior Member
Messages
1,092
@nandixon
It doesn’t have to be specific to our disease to be helpful.
The paper states: “Taken together, our data demonstrates that the significant decrease in deformability of RBCs from ME/CFS patients may have origins in oxidative stress, and suggests that altered microvascular perfusion can be a possible cause for ME/CFS symptoms.”
If it were the cause then all of the other diseases that I noted (and a lot more diseases and conditions as well) which appear to suffer equally from oxidative stress and lipid peroxidation - and therefore potentially reduced RBC deformability - should seemingly exhibit our same ME/CFS symptomatology, unless the impairment of RBC deformability is greater in ME/CFS or is somehow otherwise different.

Do you realize how much we would have won when we could have an accepted FDA approved blood test done that shows our doctors that there is a physical problem that can explain our symptoms?
There's an additional problem that I wasn't going to mention, and that is that oxidative stress is found in psychological conditions as well (which have physical underpinnings of course). In fact, a meta-analysis found lipid peroxidation in major depression (ref), so chances are that (severely) depressed patients may show abnormal RBC deformability as well. An additional study would have to be done to see if that can be excluded and I'm not sure it's worth the money, at least not at this time.

It just seems that this RBC deformability issue is likely to be too common to be of much help for us other than showing oxidative stress is present. And we already knew that, although Dr Davis's methodology looks to be a lot more convenient than measuring malondialdehyde (a lipid peroxidation marker), for instance.
 

Hopeful1976

Senior Member
Messages
345
I'm so disheartened - literally every time something positive and encouraging comes on here, people immediately retort with 'evidence' that it's useless/flawed/false ect. It's seriously getting me down!