Pyruvate dehydrogenase function depends on thiamine (B1)

[eljefe19]

Lipoic acid and thiamine are cofactors in the pyruvate dehydrogenase complex. If you want to understand why ALA helps a bit in ME/CFS sometimes, it would be best to read the recent scientific studies about metabolomics in ME/CFS instead of regurgitating Cutler's writings from 15+ years ago when nothing was known about this condition.

Dammmn dude
Vicious...
So you're saying if I'm taking Allithiamine that I would want to take ALA with it? Form and dosing?

 

[Sidereal]

So you're saying if I'm taking Allithiamine that I would want to take ALA with it? Form and dosing?

I'm not saying you should or shouldn't be taking anything. We can't give medical advice on this forum.

 

[eljefe19]

I'm not saying you should or shouldn't be taking anything. We can't give medical advice on this forum.

Alright. Let me rephrase. On a molecular level, does the PDH enzyme, in vitro, benefit from the combination of thiamine and ALA, over just thiamine?

I ask because I believe I read this has been demonstrated in the lab correct?

 

[Sidereal]

Alright. Let me rephrase. On a molecular level, does the PDH enzyme, in vitro, benefit from the combination of thiamine and ALA, over just thiamine?

It's impossible to say what will happen to anyone who takes these, either together or individually. Some people respond, some people don't.

 

[nandixon]

Alright. Let me rephrase. On a molecular level, does the PDH enzyme, in vitro, benefit from the combination of thiamine and ALA, over just thiamine?

Whenever alpha-lipoic acid is taken, it's always being taken in a pharmaceutical (drug-like) way. Humans are not able to incorporate ALA directly into the critical enzymes, and ALA is naturally only found in the body in extremely small (trace) amounts... because it interferes with energy metabolism in multiple different ways (including sequestration of acetyl-CoA, down-regulation of mTORC1, etc). It is not supplementable as a cofactor like thiamine is to be directly incorporated into the relevant enzymes.

However, as with all drugs and supplements, there is potentially a therapeutic window for some people where ALA's benefits, including antioxidant ability (among dozens of other effects), can outweigh its detriments.

Generally people with ME/CFS will only be able to tolerate small amounts of ALA (although some people may be able to build up to larger amounts over time). If a person with ME/CFS is able to tolerate a large amount of ALA from the outset (i.e., hundreds of milligrams) that would be unusual, I'd guess, and they may actually be diabetic or trending that way.

See also this post:

The situation is even worse with respect to the high SIRT4 which Fluge & Mella also found. That enzyme removes the lipoic acid "cofactor" from the second subunit of the PDH complex, essentially destroying it because humans do not have an enzyme that can reattach this. Thus supplemental lipoic acid is of no help in that regard (despite what you may read on hundreds of websites suggesting that you can supplement lipoic acid as a cofactor). (When the PDH complex is initially assembled, the lipoic acid group is built up in pieces directly onto the 2nd subunit, starting from, e.g., octanoic/caprylic acid. Lipoic acid itself is not used.)

 

[eljefe19]

Thanks @nandixon!

 

[alicec]

Humans are not able to incorporate ALA directly into the critical enzymes, and ALA is naturally only found in the body in extremely small (trace) amounts... because it interferes with energy metabolism in multiple different ways (including sequestration of acetyl-CoA, down-regulation of mTORC1, etc).

Long term use of ALA would therefore have the likely effect of downregulating PDH through down-regulation of mTOR.

The experience of @Sidereal suggests that high dose allithiamine was able to rescue the enzyme activity.

On a molecular level, does the PDH enzyme, in vitro, benefit from the combination of thiamine and ALA, over just thiamine?

Thiamine would thus seem a necessary accompaniment to ALA supplements but not the other way round.

 

[Asklipia]

Sulbutiamine + Fursultiamine Day 1
Yesterday I took 200 mg Sulbutiamine for the first time in my life, on top of the fursultiamine. In the morning as usual at breakfast I took one Alimamin Plus (33 mg fursultiamine) + some magnesium, at lunch I took 200 mg Sulbutiamine and at dinner one Alinamin again.
Very interesting changes! Sulbutiamine obviously reaches the parts other beers cannot reach!
Half an hour after taking the Sulbutiamine I went to lie down in a quiet place to feel the effects. I could feel it going by waves down to the pubis, with a slight tingling in the clitoris (that part did not last, in fact it only happened once).
I could hear the internal sound at the lower octave, a sign of activation of the muladhara chakra (prostate area). The upper side of the middle toes were getting warmer and warmer.
After that, nothing, so I got up and went on with my life.
At about 5 pm someone called me and I realized that I was full of energy and fun, but the mind was faster than my ability to pronounce the words. Not worried yet, we'll see if I don't manage to master the gift of the gab.
After that I realized that some pimples had appeared, those horrible ones under the skin that hurt and have no heads. On the chin and over eyebrows.
Nothing special until bedtime, I was not tired going to bed. I could feel something happening behind the heart, in the lymphatic pump, a kind of choking. Unpleasant, but I fell asleep immediately and I had a good night. No dream recall.
Upon waking this morning my brain has shrinked!!!!! (or is it shrunk?) Something is happening behind my left eye as a result! Most probably my eye problems stem from a lack of drainage in that area, due to my swollen brain?
The good news is that the pimples have disappeared without trace. But I feel pain behind both ears.
After a good shower all is normal again.
Best wishes to all!

 

[Asklipia]

Do you happen to have a source on the allithiamine not being affected by thiaminase?

I found it in this report of the WHO Thiamin Deficiency and its Prevention and Control in Major Emergencies p. 26

It has been reported that allicin in garlic reacts with thiamine to form alithiamine which is more readily absorbed in the intestine, is more stable than thiamine and is not decomposed by thiaminase (Williams, 1961).

Williams, 1961 =
Williams RR. Toward the conquest of beriberi. Cambridge, Massachusets, Harvard University Press, 1961.

 

[Sidereal]

A couple of thiamine threads that may be of interest:

http://forums.phoenixrising.me/inde...ent-story-focus-on-thiamine-deficiency.24059/

http://www.dinet.org/forums/topic/9262-vitamin-b1-and-dysautonomia/

 

[ukxmrv]

Generally people with ME/CFS will only be able to tolerate small amounts of ALA (although some people may be able to build up to larger amounts over time). If a person with ME/CFS is able to tolerate a large amount of ALA from the outset (i.e., hundreds of milligrams) that would be unusual, I'd guess, and they may actually be diabetic or trending that way.
:

Hi @nandixon,

I really appreciate your insightful contributions to these complicated topics.

I'm ME (by Ramsay) and for the last 2 years have been taking L-Carnitine & ALA as 2 tablets in the morning (each tablet contains 200mg of L-Carnitine and 50mg of Alpha Lipoic Acid).

There was a noticeable lift in my physical functioning when I started them. Can't afford many supplements but due to the unusually good response I buy them every month. There was no noticeable bad response and I started on 1 tablet and quickly changed to 2.

There's always going to be someone who is odd. I'm not diabetic and don't seem to be heading that way.

As an aside I'd like to mention that there seem to be 2 different areas in my ME. There is the prominent immunological one of sore throats, glands, frequent cold and flus and the physical strength one (that things like the Carnitine/ALA, CoQ10 and NADH help me with).

If I am in an immunological stage (which can last for months or a year or more) then no amount of the "physical supplements" help. It's flogging a dead horse.

I need to wait until this passes and I have less viral symptoms to start adding them again and I can build up my strength and ability to do things like walk.

 

[nandixon]

There was no noticeable bad response and I started on 1 tablet and quickly changed to 2.

There's always going to be someone who is odd. I'm not diabetic and don't seem to be heading that way.

I was thinking in terms of a typical diabetic dose for alpha-lipoic acid, i.e., minimum of 500 mg per day, as being problematic, especially if immediately tolerated.

 

[caledonia]

I didn't. I read his books years ago and followed his ALA dosing protocol because I was intrigued to read on chelation forums that some people were improving on the ALA which they attributed to an obviously completely incorrect explanation (mercury chelation). ALA was very helpful but after a number of months of doing this, ALA worsened my peripheral neuropathy and started to really wear me out. These problems were eliminated with allithiamine.

Lipoic acid and thiamine are cofactors in the pyruvate dehydrogenase complex. If you want to understand why ALA helps a bit in ME/CFS sometimes, it would be best to read the recent scientific studies about metabolomics in ME/CFS instead of regurgitating Cutler's writings from 15+ years ago when nothing was known about this condition.

I'm sorry the chelation didn't work out for you.

 

[Chocolove]

I found it in this report of the WHO Thiamin Deficiency and its Prevention and Control in Major Emergencies p. 26

That report has an incredible amount of information that many folks here could find useful.
@rebar Check out the WHO report!

 

[Asklipia]

Very interesting historical :
Alinamin® and Dr. Motonori Fujiwara
As I thought colour and light!!!!!
One day, Dr. Fujiwara experimented with a variety of reagents available in his laboratory and left the test tubes by the window. Exposed to sun’s UV rays, one of the tubes glowed in the waning late-afternoon daylight and caught his eyes...

@Chocolove It explains about the allitiamine not being affected by the thiochrome reaction.
And
Each member took and swallowed the bitter-tasting vitamin B1 cocktail of their preference, containing garlic, chive, or scallion, thinking that this “toasting” ceremony would mark the end of the project. To their amazement, however, the results completely betrayed their expectations...

A really fascinating read!

 

[Asklipia]

Sulbutiamine + Fursultiamine Day 2
Yesterday in the morning at breakfast I took one Alinamin Ex Plus (33 mg fursultiamine) + some magnesium, at lunch I took 200 mg Sulbutiamine and at dinner one Alinamin again + some B2 + one long magnesium sulphate bath.
During the afternoon rest I felt a couple of waves of warmth in my left toes, together with two warm crescents in the lower back, exactly following the upper crests of the ilium bones.
I heard the internal sound again, at a slighly higher pitch that the day before.
This was quite pleasurable but when I got up I noticed a dull heavy vague pain behind the womb. I tried to shake it off by going for a long walk (4 kms) to look for some stuff I can't find near home.
No way, when I came back it was just the same (hence the magnesium bath).
I also noticed twice that my perception of smell was more acute than normal, but not in a bothersome way like when the liver is overworked, just more precise.
I think my eyesight is a tad better too.
I slept like a lamb and woke up completely refreshed, with just a very faint feeling behind the womb.

This morning I have plenty of energy, a good mood.
I notice that I don't need to eat so much. I have appetite, but I take smaller servings.
Best wishes to all!

 

[Chocolove]

Alinamin® and Dr. Motonori Fujiwara

"Moreover, they found that substances that convert vitamin B1 into compounds unresponsive to the thiochrome reaction are present in plant parts such as sweet potato vine, burdock root, butterbur stalk, and garlic bulb"

Well that might explain the good reputation that butterbur has in preventing migraines - Thiamine.

 

[Chocolove]

Eur J Paediatr Neurol. 2015 Sep;19(5):497-503. doi: 10.1016/j.ejpn.2015.04.008. Epub 2015 May 14.
Pyruvate dehydrogenase deficiency presenting as isolated paroxysmal exercise induced dystonia successfully reversed with thiamine supplementation. Case report and mini-review.
Castiglioni C1, Verrigni D2, Okuma C3, Diaz A4, Alvarez K5, Rizza T2, Carrozzo R2, Bertini E2, Miranda M6.
Author information

• 1Unit of Neurology, Dept. of Pediatrics and Dept. of Neurology, Clínica las Condes, Santiago, Chile. Electronic address: ccastiglioni@clc.cl.
• 2Unit of Neuromuscular and Neurodegenerative Disorders, Laboratory of Molecular Medicine, Bambino Gesu' Children's Hospital IRCCS, Rome, Italy.
• 3Dept. of Radiology, Clínica las Condes, Santiago, Chile.
• 4National Institute of Rehabilitation, INRPAC, Santiago, Chile.
• 5Laboratory of Molecular Genetics and Oncology, Clínica las Condes, Santiago, Chile.
• 6Unit of Neurology, Dept. of Pediatrics and Dept. of Neurology, Clínica las Condes, Santiago, Chile.

Abstract
BACKGROUND:
Pyruvate dehydrogenase (PDH) deficiency is a disorder of energy metabolism with variable clinical presentations, ranging from severe infantile lactic acidosis to milder chronic neurological disorders. The spectrum of clinical manifestations is continuously expanding.

METHODS AND RESULTS:
We report on a 19-year-old intelligent female with PDH deficiency caused by a Leu216Ser mutation in PDHA1. She presented with recurrent hemidystonic attacks, triggered by prolonged walking or running, as the unique clinical manifestation that manifested since childhood. Laboratory workup and neuroimages were initially normal but bilateral globus pallidum involvement appeared later on brain MRI.

Dystonia completely remitted after high doses of thiamine, remaining free of symptoms after 3 years of follow up. We reviewed the literature for similar observations.

CONCLUSIONS:
Dystonia precipitated by exercise may be the only symptom of a PDH deficiency, and the hallmark of the disease as high serum lactate or bilateral striatal necrosis at neuroimaging may be absent. A high index of suspicion and follow up is necessary for diagnosis. The clinical presentation of this patient meets the criteria for a Paroxysmal Exercise induced Dystonia, leading us to add this entity as another potential etiology for this type of paroxysmal dyskinesia, which is besides a treatable condition that responds to thiamine supplementation.

Copyright © 2015 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

KEYWORDS:
Brain MRS; Paroxysmal exercise-induced dystonia; Pyruvate dehydrogenase deficiency; Thiamine-responsive dystonia

PMID: 26008863
DOI: 10.1016/j.ejpn.2015.04.008
[PubMed - indexed for MEDLINE]

 

[Chocolove]

Sulbutiamine

@Asklipia
CAUTION:
Taking Sulbutiamine for longer than two weeks can cause a person to gain tolerance to the supplement, causing it not to work as it used to. Long term use can also cause someone to be addicted to the medication...Sulbutiamine withdrawal can be problematic.

Reddit and Loungecity reviewers have reported had a lot of success with the use of Sulbutiamine when taken correctly and in cycles.

If you do decide to take sulbutiamine it is important to note that tolerance can set in as quickly with its positive effects beginning to diminish sometimes in less than a week. That is why it is recommended to either cycle sulbutiamine or to save it specifically for days that can use that extra boost.

Perhaps the most common side effect is an increase in anxiety and irritability.
http://www.braintropic.com/nootropics/sulbutiamine/

 

[aquariusgirl]

I have red that ALA causes a person to retain copper?