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Pyruvate dehydrogenase function depends on thiamine (B1)

Marky90

Science breeds knowledge, opinion breeds ignorance
Messages
1,253
I'm not sure what you mean by this. I've experienced some tremendous QOL gains from supplementation. Granted, I spend hours and hours on research. My regimen is top notch. I used to be incredibly sick, severe CFS and now I am squarely moderate. Cure? No. That's why I'm pursuing Rituximab.

I simply say that it lacks positive studies behind it. Good to hear, but we still need real medicine, e.g. ritux - which btw needs to prove efficacy in a phase 3 study.
 

eljefe19

Senior Member
Messages
483
I simply say that it lacks positive studies behind it. Good to hear, but we still need real medicine, e.g. ritux - which btw needs to prove efficacy in a phase 3 study.

Thanks for the response. I am all for scientists pursuing real research through high quality clinical trials, however I'm just a sick patient with not much to lose. The reason I'm so interested in this particular mechanism is, it had never been elucidated before, and also because while my supplementation has fixed a lot of my flu like symptoms, something is clearly still wrong with my energy production and PEM is as bad as ever.
 

Chocolove

Tournament of the Phoenix - Rise Again
Messages
548
Researchers involved in the ocrelizumab trials say they think the newer agent will eventually prove to be superior to rituximab -- it is a humanized monoclonal antibody whereas rituximab is chimeric, and infusion reactions and anti-drug antibody responses may be lessened with ocrelizumab (although this remains to be proven.)

Still, taking either drug is no bed of roses and can seriously damage the body.

I am all for trying to discover what nutrients my body needs to recover.
 
Messages
516
I would just add that in my personal experience taking allithiamine per se did nothing unless I also took lipoic acid around the clock

Lipoic acid around the clock - although I completely believe could relieve symptoms - is completely unphysiological and I'd worry to be counterproductive in the long run.

Thiamine on its own will never be enough to enact meaningful change (as you say). PDH is a small part of the picture.

But mTor is a master control switch of anabolism and protein synthesis, so it has more potential for building band-aid solutions.

There is (or is not) a cure, and there is symptom relief. But in between, there's also affecting anabolism/catabolism processes to try to get protein synthesis to offset the degradation from the disease (which may not necessarily coincide with immediate symptom relief). I think is the next best thing to a cure.
 
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eljefe19

Senior Member
Messages
483
There is (or is not) a cure, and there is symptom relief. But in between, there's also affecting anabolism/catabolism processes to try to get protein synthesis to offset the degradation from the disease (which may not necessarily coincide with immediate symptom relief). I think is the next best thing to a cure.

How exactly would this be best done?
 

Sidereal

Senior Member
Messages
4,856
Lipoic acid around the clock - although I completely believe could relieve symptoms - is completely unphysiological and I'd worry to be counterproductive in the long run.

Thiamine on its own will never be enough to enact meaningful change (as you say). PDH is a small part of the picture.

But mTor is a master control switch of anabolism and protein synthesis, so it has more potential for building band-aid solutions.

There is (or is not) a cure, and there is symptom relief. But in between, there's also affecting anabolism/catabolism processes to try to get protein synthesis to offset the degradation from the disease (which may not necessarily coincide with immediate symptom relief). I think is the next best thing to a cure.

Not sure what your beef with ALA is but I'm talking about very low doses of ALA (25 mg every three hours), nowhere near what would be used in studies of diabetic neuropathy for instance (1,200-1,800 mg/day). This supplement got me out of a bedridden situation and had extremely beneficial effects on all kinds of symptoms including very painful problems like peripheral neuropathy and endogenous oxalate production so the risk-benefit ratio was clear. Over time it did start to wear me out and this is something that seems quite common in people who take it chronically.

PDH is obviously far from the primary problem in this disease but I wouldn't go as far as to say it's a small part of the picture. Not being able to extract usable energy (acetyl CoA) from carbohydrates is an enormous problem.
 
Messages
516
How exactly would this be best done?
More or less what nandixon's been doing. Find all the causes of mTor being inhibited, develop a protocol which temporarily reverses those signals during feeding.

Not sure what your beef with ALA is but I'm talking about very low doses of ALA (25 mg every three hours), nowhere near what would be used in studies of diabetic neuropathy for instance (1,200-1,800 mg/day). This supplement got me out of a bedridden situation and had extremely beneficial effects on all kinds of symptoms including very painful problems like peripheral neuropathy and endogenous oxalate production so the risk-benefit ratio was clear. Over time it did start to wear me out and this is something that seems quite common in people who take it chronically.

PDH is obviously far from the primary problem in this disease but I wouldn't go as far as to say it's a small part of the picture. Not being able to extract usable energy (acetyl CoA) from carbohydrates is an enormous problem.

ALA's famous as an AMPK promoter, which is in healthy people works in daily cyclic fashion, opposite to mTor. I'm not sure about 25mg doses though.

The PDH sure is important, but its role is limited, besides that there's a lot more in the mitochondria to make carbs work.
 

Chocolove

Tournament of the Phoenix - Rise Again
Messages
548
Some folks may find this site helpful:
Vitamins: Critical Enzyme Co-Factors
themedicalbiochemistrypage.org/vitamins.php
The Vitamins page provides a detailed description of the structure and function of the water and lipid soluble vitamins and the clinical consequences of deficiencies...
 

Sidereal

Senior Member
Messages
4,856
I'm not sure what you mean by this. I've experienced some tremendous QOL gains from supplementation. Granted, I spend hours and hours on research. My regimen is top notch. I used to be incredibly sick, severe CFS and now I am squarely moderate. Cure? No. That's why I'm pursuing Rituximab.

Glad to hear you're feeling better. I am not knocking supplements, I was just addressing the thiamine deficiency claims in the original post. I had severe ME/CFS which for a while was bordering on very severe / death spiral. Thanks to diet and supplements I am squarely moderate these days, as you put it. Mild during brief stretches of time when I hit on something that really worked. Cure? Not by a long shot but it clearly cannot be said that judicious supplementation with things that actually make sense in terms of the known biochemistry does nothing.

There is no convincing RCT evidence at present that rituximab is a useful treatment for ME/CFS and there are currently no antibody tests that can predict treatment responders. Anecdotal reports over the past few years have not been very encouraging either. I don't think this is an autoimmune disease. Autoantibodies against G-protein coupled receptors are clearly a complicating part of the picture for a certain percentage of us but I don't think B cell depletion therapy is ultimately what is going to fix the core problems.
 

Sidereal

Senior Member
Messages
4,856
ALA's famous as an AMPK promoter, which is in healthy people works in daily cyclic fashion, opposite to mTor. I'm not sure about 25mg doses though.

The PDH sure is important, but its role is limited, besides that there's a lot more in the mitochondria to make carbs work.

Yup, agreed.

Re: ALA, the dose makes all the difference in my experience. This is all anecdotal of course but standard dosing was massive amounts administered infrequently was clearly negative/harmful. Low dosing was shockingly beneficial but the sweet spot dose varied from day to day, week to week, month to month. It required a great deal of intuition and tinkering to get it right. I had to start with just 6 mg and slowly work up to 50 and eventually 100 mg q3h. Then that became too much and I had to go back down to 25 mg. Tricky substance. It seems to raise functional capacity and improve muscle power objectively (for instance, being able to squat and climb stairs for the first time in years) while at the same time increasing that subjective sensation of fatigue. Hard to explain.
 

eljefe19

Senior Member
Messages
483
@Sidereal great response. Thank you! I certainly have a lot to think about in terms of future treatment. It is overwhelming at times. To Rituximab or not to Rituximab?
 

eljefe19

Senior Member
Messages
483
More or less what nandixon's been doing. Find all the causes of mTor being inhibited, develop a protocol which temporarily reverses those signals during feeding.

I have been following nandixon's posts as well. I am trialing a gang of mTorC1 activating supplements and medications. What are the causes of mTor inhibition that we've found so far? What did you mean when you said "during feeding?"
 

nandixon

Senior Member
Messages
1,092
More or less what nandixon's been doing. Find all the causes of mTor being inhibited, develop a protocol which temporarily reverses those signals during feeding.
Just to be clear, I think there are some things that can definitely help mTOR - mTORC1 in particular - but to have a really major solution is probably going to require going farther upstream to at least help with what I think could be impaired sphingosine-1-phosphate (S1P) signaling (whatever is causing that).
 

eljefe19

Senior Member
Messages
483
Just to be clear, I think there are some things that can definitely help mTOR - mTORC1 in particular - but to have a really major solution is probably going to require going farther upstream to at least help with what I think could be impaired sphingosine-1-phosphate (S1P) signaling (whatever is causing that).

Have you found anything so far that may agonize S1P signaling?
 

Chocolove

Tournament of the Phoenix - Rise Again
Messages
548
J Investig Med High Impact Case Rep. 2015 Sep 24;3(3):2324709615607908. doi: 10.1177/2324709615607908.
Mitochondrial Myopathy in Follow-up of a Patient With Chronic Fatigue Syndrome.
Galán F1, de Lavera I2, Cotán D2, Sánchez-Alcázar JA2.
Author information
  • 1University of Seville, Seville, Spain.
  • 2Universidad Pablo de Olavide-Consejo Superior de Investigaciones Científicas-Junta de Andalucía, Seville, Spain.
Abstract
Introduction. Symptoms of mitochondrial diseases and chronic fatigue syndrome (CFS) frequently overlap and can easily be mistaken.

Methods. We report the case of a patient diagnosed with CFS and during follow-up was finally diagnosed with mitochondrial myopathy by histochemical study of muscle biopsy, spectrophotometric analysis of the complexes of the mitochondrial respiratory chain, and genetic studies.

Results. The results revealed 3% fiber-ragged blue and a severe deficiency of complexes I and IV and several mtDNA variants. Mother, sisters, and nephews showed similar symptoms, which strongly suggests a possible maternal inheritance. The patient and his family responded to treatment with high doses of riboflavin and thiamine with a remarkable and sustained fatigue and muscle symptoms improvement.

Conclusions. This case illustrates that initial symptoms of mitochondrial disease in adults can easily be mistaken with CFS, and in these patients a regular reassessment and monitoring of symptoms is recommended to reconfirm or change the diagnosis.

KEYWORDS:
chronic fatigue syndrome; mitochondrial myopathy; myalgic encephalomyelitis; occipital neuralgia; riboflavin therapy

PMID:
26904705
PMCID:
PMC4748504
DOI:
10.1177/2324709615607908

Full article free here:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4748504/
 

Chocolove

Tournament of the Phoenix - Rise Again
Messages
548
@Sidereal According to Dr. Jessica Weiser:

"Both biotin and pantothenic acid–vitamin B5—are absorbed from the intestines via the same receptors..

When taking biotin supplements, the amount of biotin in the gut far outweighs the quantity of vitamin B5,... thereby leading to a relative vitamin B5 deficiency.

Pantothenic acid is thought to regulate the barrier function of the surface layer on skin and can reduce acne lesions. Therefore, a deficiency of pantothenic acid—or excess of biotin—could lead to acne flares.”

In simpler terms, you could be giving yourself a deficiency of B5 by taking an excess of biotin.