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    Created in 2008, Phoenix Rising is the largest and oldest forum dedicated to furthering the understanding of and finding treatments for complex chronic illnesses such as chronic fatigue syndrome (ME/CFS), fibromyalgia (FM), long COVID, postural orthostatic tachycardia syndrome (POTS), mast cell activation syndrome (MCAS), and allied diseases.

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We Got Lactate on our Brains!

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George

Guest
Frank just posted this over in the library. It's a really great study. I have a picture from the power point presentation given by Dr. Vernon last Thursday. This is your CFIDS research dollars at work!

Ventricular cerebrospinal fluid lactate is increased in chronic fatigue syndrome compared with generalized anxiety disorder: an in vivo 3.0 T (1)H MRS imaging study.

Mathew SJ, Mao X, Keegan KA, Levine SM, Smith EL, Heier LA, Otcheretko V, Coplan JD, Shungu DC.

Department of Psychiatry, Mount Sinai School of Medicine, New York, NY, USA.

Chronic fatigue syndrome (CFS) is a controversial diagnosis because of the lack of biomarkers for the illness and its symptom overlap with neuropsychiatric, infectious, and rheumatological disorders. We compared lateral ventricular volumes derived from tissue-segmented T(1)-weighted volumetric MRI data and cerebrospinal fluid (CSF) lactate concentrations measured by proton MRS imaging ((1)H MRSI) in 16 subjects with CFS (modified US Centers for Disease Control and Prevention criteria) with those in 14 patients with generalized anxiety disorder (GAD) and in 15 healthy volunteers, matched group-wise for age, sex, body mass index, handedness, and IQ. Mean lateral ventricular lactate concentrations measured by (1)H MRSI in CFS were increased by 297% compared with those in GAD (P < 0.001) and by 348% compared with those in healthy volunteers (P < 0.001), even after controlling for ventricular volume, which did not differ significantly between the groups. Regression analysis revealed that diagnosis accounted for 43% of the variance in ventricular lactate. CFS is associated with significantly raised concentrations of ventricular lactate, potentially consistent with recent evidence of decreased cortical blood flow, secondary mitochondrial dysfunction, and/or oxidative stress abnormalities in the disorder.

There is a great picture on the CFIDS website where the webinar stuff is. I'm to tired to get it tonight!



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Sunday

Senior Member
Messages
733
I hope this leads to bigger studies - it'd be a big step to have some clear markers for this disease (other than PEM, which people can argue over). Then, when people say it's in our heads, we can say, "We know. It's the lactate!"
 

leelaplay

member
Messages
1,576
I hope this leads to bigger studies - it'd be a big step to have some clear markers for this disease (other than PEM, which people can argue over). Then, when people say it's in our heads, we can say, "We know. It's the lactate!"

Oh my gosh Sunday - out loud belly laugh. Thanks.
 
G

Gerwyn

Guest
Frank just posted this over in the library. It's a really great study. I have a picture from the power point presentation given by Dr. Vernon last Thursday. This is your CFIDS research dollars at work!

Ventricular cerebrospinal fluid lactate is increased in chronic fatigue syndrome compared with generalized anxiety disorder: an in vivo 3.0 T (1)H MRS imaging study.

Mathew SJ, Mao X, Keegan KA, Levine SM, Smith EL, Heier LA, Otcheretko V, Coplan JD, Shungu DC.

Department of Psychiatry, Mount Sinai School of Medicine, New York, NY, USA.

Chronic fatigue syndrome (CFS) is a controversial diagnosis because of the lack of biomarkers for the illness and its symptom overlap with neuropsychiatric, infectious, and rheumatological disorders. We compared lateral ventricular volumes derived from tissue-segmented T(1)-weighted volumetric MRI data and cerebrospinal fluid (CSF) lactate concentrations measured by proton MRS imaging ((1)H MRSI) in 16 subjects with CFS (modified US Centers for Disease Control and Prevention criteria) with those in 14 patients with generalized anxiety disorder (GAD) and in 15 healthy volunteers, matched group-wise for age, sex, body mass index, handedness, and IQ. Mean lateral ventricular lactate concentrations measured by (1)H MRSI in CFS were increased by 297% compared with those in GAD (P < 0.001) and by 348% compared with those in healthy volunteers (P < 0.001), even after controlling for ventricular volume, which did not differ significantly between the groups. Regression analysis revealed that diagnosis accounted for 43% of the variance in ventricular lactate. CFS is associated with significantly raised concentrations of ventricular lactate, potentially consistent with recent evidence of decreased cortical blood flow, secondary mitochondrial dysfunction, and/or oxidative stress abnormalities in the disorder.

There is a great picture on the CFIDS website where the webinar stuff is. I'm to tired to get it tonight!



moz-screenshot-4.png


good science matched groups healthy controls gad is rare more commonly symptoms of generalised anxiety have their roots in the other side of the coin depression more evidence that feduka CAN diagnose but oxford cant it would have excluded symptoms associated with cerebellar insufficiency.We need you guys to help us here
 
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Gerwyn

Guest
george i,ve just realised that lactate is a marker for mito problems
 
G

George

Guest
george i,ve just realised that lactate is a marker for mito problems

Doesn't lactic 'acid' build up in muscles when PWC exercise because of inability to use oxygen correctly due to mitochondria damage in PWC's?????

The evidence is really building up.
 

richvank

Senior Member
Messages
2,732
Hi, all.

There is a lot of evidence now for mito dysfunction in CFS, and elevated lactate is part of it. Note that in the abstract of the paper by Shungu's group, there were three features that may be associated with elevated lactate:

"decreased cortical blood flow, secondary mitochondrial dysfunction, and/or oxidative stress abnormalities in the disorder."

In the GD--MCB hypothesis, depletion of glutathione causes oxidative stress, and that in turn causes the mito dysfunction. The problems with blood flow are caused by low total blood volume, due to low secretion of antidiuretic hormone, in turn caused by glutathione depletion in the hypothalamus/pituitary, and also by diastolic dysfunction in the heart, caused by mito dysfunction in the heart muscle cells, also due to oxidative stress caused by glutathione depletion there.

Glutathione depletion in CFS is maintained in a vicious circle mechanism involving a partial block in the methylation cycle, and this is what causes CFS to be a chronic condition. To raise glutathione on a permanent basis, it is necessary to lift this block. That should be the key to correcting these other problems. I've posted the Simplified Treatment Approach elsewhere in this forum, as well as information on the Vitamin Diagnostics methyation pathways panel, which tests for these issues.

Best regards,

Rich
 
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George

Guest
Hi Rich

Rich what do you think about a retrovirus causing the cycle to start? and what are your thoughts on the cycle being held by a retrovirus infection?

I ask this in good faith cause I get the impression and it's just my interpretation via a foggy brain that you believe that if people would follow your protocol and take the right supplements they would be cured, eventually, and I don't get that.

Could you comment please.
 

CBS

Senior Member
Messages
1,522
Ventricular lactic acid vs. peripheral LA?

I find this interesting from a personal perspective. Last year when I was going through some serious CNS issues (5-6 TIA's a day and erratic spikes in BP and HR - 120/70 to 200/160 in minutes and 70 BPM to 180 bpm in the same short period) one blood test that had the docs taking my condition very seriously but still at a complete loss was arterial lactic acid levels three times the upper end of the ref. range. Does anyone know if peripheral artieral LA is related to ventricular LA?
 

JT1024

Senior Member
Messages
582
Location
Massachusetts
:thumbsup:

Great posts from you all.

My CSF lactate must be exceedingly high right now. I try to follow all the news you post because it is exciting yet scary.

I think George mentioned a "library". I'm not familiar with this. Can someone explain further?

I am fortunate enough to still work full time...barely...in a clinical laboratory (not what I want but what I can manage right now). Strangely, several people at work (or their children) have similar symptoms and are not diagnosed with ME/CFS but with everything from FM and MS to Celiac Disease.

Keep posting and sharing! I try to share as much as I can with people down the intellectual food chain because not everyone is at the top as you guys are! I struggle at times understanding when the posts are extremely technical but I love the challenge.

I have been on this site and one other. By far, this site has the best group of researchers, scientists, and camaradie.

I used to work for a major healthcare information technology company and most often I helped the clinical folks, the business folks, and the engineersn understand each other. My ability to translate essentially helped "grease the engine" so we could effectively provide valuable solutions to healthcare clients. I feel like I'm doing a similar function now by translating info learned here and posting when I can to the other site. I'm not posting much though because there is so much happening so fast, many posts here, and I don't have time.

Keep up the great work!

JT
 

Stuart

Senior Member
Messages
154
I recall a study that detailed the lactic acid in the brain and CSF, I will post a link if I find it. There is a very good discussion of this on Dr. Sarah Myhill's web site. A surprise I had returning there is that the site has been redesigned in a wiki format, nice! Check it out - http://drmyhill.co.uk/wiki/CFS_-_The_Central_Cause:_Mitochondrial_Failure worth the read.

One key bit I recalled was when the demand exceed supply of ATP, there is a metabolic path that produces lactic acid. “If the body is very short of ATP, it can make a very small amount of ATP directly from glucose by converting it into lactic acid.”

She seems to have some of this wired, certainly few doctors have such a thought out theory and put it out online without charge. Kudos to Dr. Myhill.

I found this site to have a nice section on it as well - http://potsweb.50webs.com/atp.html its a nice bit for those who deal with POTS, OI, NMH, Dysautonomia, as well as CFS.

ETA: Well at least one major paper had Dr. Myhill as principal author -
Chronic Fatigue Syndrome and Mitochondrial Dysfunction http://www.ijcem.com/files/IJCEM812001.pdf
 

richvank

Senior Member
Messages
2,732
Rich what do you think about a retrovirus causing the cycle to start? and what are your thoughts on the cycle being held by a retrovirus infection?

I ask this in good faith cause I get the impression and it's just my interpretation via a foggy brain that you believe that if people would follow your protocol and take the right supplements they would be cured, eventually, and I don't get that.

Could you comment please.

Hi, George.

I don't think anyone knows for sure yet how XMRV is involved with CFS. It could be a first cause (maybe even THE first cause), but until the differences between the studies reported so far are ironed out, I don't think we can know for sure. As far as my GD--MCB hypothesis is concerned, I think it would mesh with the XMRV in either of two ways: either the XMRV acts as a first cause and contributes to the depletion of glutathione, or XMRV gets involved later in the pathogenesis as a result of the dysfunction of the immune system that results from glutathione depletion, methylation cycle block, and draining of the folate metabolites from the cells. It appears that lots of other latent viruses reactivate when the immune system becomes dysfunctional.

With regard to whether I think that if people would follow the simplified protocol they would be cured, I don't think I'm ready to go that far, at least in most cases. The evidence so far is that in most cases lifting the methylation cycle block does make a major contribution, but it also seems to be necessary to deal with some other things that either occurred first, and brought down the methylation cycle, such as Lyme disease or mold illness, or things that occurred as a result of the detox system or the immune system being dysfunctional, which was caused by glutathione depletion and the partial block in the methylation cycle. Some of these latter things are major buildup of mercury or other toxic metals, or a viral infection becoming particularly entrenched. I do believe that the partial methylation cycle block is the core issue in the biochemistry of CFS, but I don't think it's the only thing that most people with CFS have to specifically deal with, especially if they have been ill for a long time, so that other things have accumulated while the defenses were down.

When I first proposed this hypothesis, I was more optimistic that fixing this central issue would do the whole job for people, but I do pay attention to evidence, and more of that is coming in all the time, and is suggesting that fixing this partial block won't be all that many people will have to do. I still believe that this is a big deal, though, and I would especially like to see the response of more people who haven't been ill very long, because that would test what I have just written above.

Best regards,

Rich