Pyruvate dehydrogenase function depends on thiamine (B1)

[Asklipia]

@Asklipia
What's your current B1 regiment? How long have you been doing this? How long did it take to "heal" and/or replenish B1? Thanks

@JasonUT I started with one Alinamex Plus a day from January 2016 I think, maybe earlier, not sure. Then
Since March 2017 :
I have been taking thiamine in various forms throughout the day not everything everyday, just two or three helpings at random)
- 150 mg benfotiamine + leucine
- 50 mg Allitiamine
- 33 mg fursultiamine Alinamex Plus (contains other things like B6)
- 200 mg sulbutiamine
+ B2 25 mg a day
Since 1st May 2017 I do all this everyday. Sometimes I take a Neurobion (thiamine HCl 100 mg + some B12 and B6 as well, because this is all I found whilst traveling and I have some left I want to finish.
I feel not only well, better, but I feel myself. It has been slow but is is getting spectacular .
I don't think I am totally healed yet, because it is healing some things I had all my life and did not know they could be healed, and some others are not healed yet. Too old? I just turned 65. I suspect all this takes time. I am perfectly functional, but I feel like saving my energy for this fantastic inside regrowth, so I just laze around as much as possible. In a very good mood. Reading a lot of scientific literature on Thiamine!
I never had any tests because they are not available where I am and because I trust my instinct 100%. I'll stop when I understand there is no improvement possible.
Of course if I could just pop out and get the Transketolase tests done I would do them.
I should say the improvements sharply increased when I started carcinine.
I DO NOT RECOMMEND ANYTHING!!!!
Good luck and be well!

 

[junkcrap50]

@Asklipia

What's your current B1 regiment? How long have you been doing this? How long did it take to "heal" and/or replenish B1? Thanks

Also, did you have any lactic acid feeling or buildup easily in muscles prior to your healing/improvement? If so, did it go away with taking your B1 regiment?

 

[Asklipia]

Also, did you have any lactic acid feeling or buildup easily in muscles prior to your healing/improvement? If so, did it go away with taking your B1 regiment?

yes, and yes 99,9 %. I still happens a bit, like every 20 days or so.

 

[Chocolove]

@Eastman Looks like they are starting a new nicotinimide clincial trial for Alzheimer's patients although at this time not yet recruiting:
Nicotinamide as an Early Alzheimer's Disease Treatment (NEAT)

https://clinicaltrials.gov/ct2/show/NCT03061474

Experimental: Nicotinamide
1500mg twice daily: 2, 750mg tablets taken orally twice daily
Drug: Nicotinamide
Niacinamide (nicotinamide; 99%) is produced in a 750 mg sustained release tablet.

Nicotinamide, the amide of nicotinic acid (vitamin B3/niacin), is an oral therapy with a wealth of clinical data in a variety of therapeutic areas, including preliminary data supporting its safety in Alzheimer's disease (AD). Preclinical work in a mouse model that develops both plaques and tangles supports the hypothesis that nicotinamide can act as a histone deacetylase (HDAC) inhibitor to reduce phosphorylation of tau.

The study will implement a group sequential design, incorporating a futility analysis with a go/no-go decision conditional on cerebral spinal fluid CSF biomarker outcomes at 12-months. The primary outcome for the trial is change in p-tau231.

Joshua Grill, Associate Professor, Psychiatry & Human Behavior, University of California, Irvine

Green KN, Steffan JS, Martinez-Coria H, Sun X, Schreiber SS, Thompson LM, LaFerla FM. Nicotinamide restores cognition in Alzheimer's disease transgenic mice via a mechanism involving sirtuin inhibition and selective reduction of Thr231-phosphotau. J Neurosci. 2008 Nov 5;28(45):11500-10. doi: 10.1523/JNEUROSCI.3203-08.2008.

Liu D, Pitta M, Jiang H, Lee JH, Zhang G, Chen X, Kawamoto EM, Mattson MP. Nicotinamide forestalls pathology and cognitive decline in Alzheimer mice: evidence for improved neuronal bioenergetics and autophagy procession. Neurobiol Aging. 2013 Jun;34(6):1564-80. doi: 10.1016/j.neurobiolaging.2012.11.020. Epub 2012 Dec 25. Erratum in: Neurobiol Aging. 2013 Sep;34(9):e3.
**************************************************
NOTE:

Protein: NMNA2_HUMAN
Nicotinamide mononucleotide adenylyltransferase 2

FUNCTION: Catalyzes the formation of NAD(+) from nicotinamide mononucleotide (NMN) and ATP. Can also use the deamidated form; nicotinic acid mononucleotide (NaMN) as substrate but with a lower efficiency. Cannnot use triazofurin monophosphate (TrMP) as substrate. Also catalyzes the reverse reaction, i.e. the pyrophosphorolytic cleavage of NAD(+). For the pyrophosphorolytic activity prefers NAD(+), NADH and NAAD as substrates and degrades nicotinic acid adenine dinucleotide phosphate (NHD) less effectively. Fails to cleave phosphorylated dinucleotides NADP(+), NADPH and NAADP(+). CATALYTIC ACTIVITY: ATP + nicotinamide ribonucleotide = diphosphate + NAD(+). CATALYTIC ACTIVITY: ATP + nicotinate ribonucleotide = diphosphate + deamido-NAD(+). COFACTOR: Divalent metal cations. Magnesium confers the highest activity.

PATHWAY: Cofactor biosynthesis; NAD(+) biosynthesis; NAD(+) from nicotinamide D-ribonucleotide: step 1/1.

TISSUE SPECIFICITY: Highly expressed in brain, in particular in cerebrum, cerebellum, occipital lobe, frontal lobe, temporal lobe and putamen. Also found in the heart, skeletal muscle, pancreas and islets of Langerhans.

From: http://www.pathwaycommons.org/pc/record2.do?id=118034

 

[Chocolove]

@Asklipia Perhaps you are having such wonderful effects from carnosine +thiamine because they are both antiglycation agents? Alzheimer's is now sometimes being referred to as Diabetes III...

http://www.tritolonen.fi/files/pdf/Sourris_2008.pdf
p102
Annals of the New York Academy of Sciences
TABLE 1. A summary of advanced glycation end
product (AGE)-lowering therapies with diverse
mechanisms of action

I feel not only well, better, but I feel myself. It has been slow but is is getting spectacular

 

[Asklipia]

@Asklipia
What's your current B1 regimen?

I forgot to add, but it is related, that I also take magnesium daily, in several takes away from the thiamine intake, as
- ionic magnesium
- magnesium sulfate baths (not every day)
- as per Lonsdale recommendation as magnesium/potassium aspartate
- bathe in the cold sea as often as possible, stay at least 30 mns in the water.

And unrelated (?)
- 4 mg Carcinine per day on empty stomach
- 5 Wobenzym pills upon waking
- prayer and pranayama
- watching funny movies, laughing as much as possible

There, you know all my secrets

 

[JasonUT]

@Asklipia
I recommend for those who can afford it the new book by Dr Lonsdale. It is fascinating. The first two chapters are on Googlebooks:
https://books.google.fr/books?id=DLpvDgAAQBAJ&pg=PR13&lpg=PR13&dq=thiamine lonsdale marss&source=bl&ots=92dhpr653M&sig=f1Ew1VAgbF9ddOLZTrZgBMrjqpo&hl=en&sa=X&ved=0ahUKEwjWmfCUgJPVAhUJC8AKHSQXB0IQ6AEILjAB#v=onepage&q&f=false

I shall try to quote from it from time to time, but not sure if what I pick is what you should know!
Be well!
Asklipia

I'd love to hear more about Lonsdale's clinical experience with the "paradox" of replenishing Thiamine. I don't know if the book touches on this in greater details.

 

[Asklipia]

I'd love to hear more about Lonsdale's clinical experience with the "paradox" of replenishing Thiamine. I don't know if the book touches on this in greater details.

Unfortunately since this morning my house is full of guests so I shall have very limited time for PR. Did you read Dr Lonsdale first book, the one which was burnt before diffusion (A Nutritionist's Guide to the Clinical use of Vitamin B-1)? There are a lot of cases in it.
I see that it is also very expensive, but this one is not : https://www.amazon.com/Why-Left-Ort...rd_wg=TO6YB&psc=1&refRID=MD1WJ3FKA6SJXKNPHQST
Good luck!

 

[JasonUT]

@junkcrap50

My deficiencies are based on SpectraCell Micronutrient panel. The SpectraCell Micronutrient test sounds the inverse of the TKA/TPPE test.

This is straight from SpectraCell:

OVERVIEW OF TEST PROCEDURE
1. A mixture of lymphocytes is isolated from the blood.
2. These cells are grown in a defined culture medium containing optimal levels of all essential nutrients necessary to sustain their growth in cell culture.
3. The T-lymphocytes are stimulated to grow with a mitogen (phytohemagglutinin) and growth is measured by the incorporation of tritiated (radioactive) thymidine into the DNA of the cells. The growth response under optimal conditions is defined as 100%, and all other growth rates are compared to this 100% level of growth.

For example – we remove vitamin B6 from the medium and stimulate the cells to grow by mitogen stimulation. Growth is measured by DNA synthesis and the rate of growth is dependent only upon the functional level of vitamin B6 available within the cells to support growth. For Vitamin B6 a growth rate of at least 55% of the growth rate observed in the optimal (100%) media is considered normal. Results less than 55% are considered to indicate a functional deficiency for Vitamin B6. Each nutrient has a different reference range that was established by assaying thousands of apparently healthy individuals.

Lonsdale's write-up on TKA/TPPE test:

One of the best and simplest tests is red cell transketolase (TKA) combined with thiamine pyrophosphate percentage uptake, or effect (TPPE). Transketolase requires TPP as cofactor. After a baseline activity is measured, it is repeated following addition of TPP in vitro. If the baseline activity accelerates, it reveals TPP desaturation of the enzyme. After prolonged deficiency,42 or because of structural defects in the enzyme,43 TKA activity may be Suboptimal. An increase in TPPE of greater than 20 percent is unequivocal evidence of red cell TPP deficiency.

 

[Gondwanaland]

And unrelated (?)
- 4 mg Carcinine per day on empty stomach
...
- watching funny movies, laughing as much as possible

When I was taking Carcinine something happened again after many years: I laughed untill I cried.
For many years in between I had lost the ability to laugh like that.

 

[junkcrap50]

When I was taking Carcinine something happened again after many years: I laughed untill I cried.
For many years in between I had lost the ability to laugh like that.

What exactly is Carcinine? How does it work and what does it work on? Seems I've read it on these forums quite a bit and a lot of people really like it.

 

[Chocolove]

@junkcrap50

What exactly is Carcinine? How does it work and what does it work on? Seems I've read it on these forums quite a bit and a lot of people really like it.

See: http://forums.phoenixrising.me/inde...pps-carnosine-beta-alanine-methylation.50395/

 

[Chocolove]

The most common cause of vitamin B1 deficiency is chronic alcohol abuse, with thiamine vitamin B1 deficiency occurring in up to 80% of alcoholics (Morgan 1982). However, a lot of other conditions such as gastrointestinal surgical procedures as well as chemical therapies have been reported as predisposing factors in thiamine deficiency. Alcoholism is not directly responsible for vitamin B1 deficiency, but its effects are related to complications of liver functioning (Thomson, 2000).

From: http://www.dryoutnow.com/alcohol-info/thiamine/

Magnesium deficiency in alcoholism.
https://www.ncbi.nlm.nih.gov/pubmed/3544909
Significant magnesium deficiency occurs in chronic alcoholism. The evidence depends on a number of related lines of evidence: hypomagnesemia, a number of clinical ...

Vitamin B1: Mg-deficiency interferes with response to thiamine in B1-deficient rats [150-152, 338, 340] and in alcoholic patients, a not surprising finding in view of the Mg-dependence of enzymes requiring B1 (Review: [310]

A genetic metabolic disorder of B1 metabolism, subacute necrotic encephalopathy (SNE) is similar to Wernicke's encephalopathy, and might respond better to Mg plus B1 than to B1 alone.

An infant with this disorder has responded somewhat better to B1 when Mg was added to the regimen (J. Cooper, personal communication). Another infant has been found to have impaired B6 metabolism [78], a further clue to a possible interrelationship with an abnormality in Mg metabolism.

Administration of thiamine to B1 + Mg deficient animals has intensified Mg-deficiency [150, 339, 340] and has increased the blood levels of serotonum [151, 152]. Long-term high dosage B1 therapy is common in chronic alcoholics, who have Mg-deficiency and high Mg-needs, and in those self-medicating themselves with megavitamins, whose Mg-needs might thereby be increased.

From: http://www.mgwater.com/human.shtml

 

[Gondwanaland]

I am enclosing a thorough review on what was known about thiamine experiments in 2009. It includes issues like magnesium role in pyruvate dehydrogenase activation, serotonin uptake (transient improvement with SSRIs - better addressed in the 2nd chapter linked below), brain lactate, ER stress, accumulation of pyruvate intermediates, etc.

Additionally, in the 2nd chapter of the extremely complex new book by Dr. D. Lonesdale there is something about "promiscuity" (genetic and epigenetic alterations) of certain (G and Muscarinic) receptors which I couldn't understand well.

@Lolinda @Asklipia @Sidereal @alicec @alethea @Chocolove @JasonUT

 

[Skippa]

Oh, Hi!

Just stumbled into this thread tum te tum...

Looks like lots of hectic stuff is going on.

Anyways, can anyone suggest (not recommend of course ) a basic list of supplements to try getting onto this bandwagon to see if any improvements come? (At which point I'd read the whole thread and get more supps).

Many thanks

(Eta, having read around a bit, and seeing @Sidereal 's post it's probably not that good an idea for me. Anyone having any success?)

 

[Sidereal]

(Eta, having read around a bit, and seeing @Sidereal 's post it's probably not that good an idea for me. Anyone having any success?)

My posts are not intended to encourage or discourage anyone from trying thiamine. I can say that, without a shadow of a doubt, it was the most effective treatment I've ever tried. Like everything else, it has its side effects. In this instance, refeeding syndrome.

 

[JasonUT]

Does this mean that SSRI's are helpful or harmful for Thiamine deficient patients? I am confused.

... serotonin uptake (transient improvement with SSRIs - better addressed in the 2nd chapter linked below)...

The effect of thiamine deficiency on the neurotransmitter serotonin has been examined (Plaitakis et al., 1978). The rationale was that evidence existed for a possible role of thiamine in nerve conduction, as described above. In this study, both pyrithiamine and a low thiamine diet were used to produce thiamine deficiency. Results showed that other neurotransmitters studied such as GABA, glutamic acid, norepinepherine, and choline were not affected by thiamine deficiency. Serotonin, however, was affected in that synaptosomes from the cerebellum of thiamine-deficient rats showed the Vmax for serotonin uptake was only 50% that of controls.

The decreased uptake of serotonin was limited to the cerebellum; other regions were not affected. Thiamine added in vitro did not restore decreased serotonin uptake; however, when thiamine was added in vivo, reversal of symptoms occurred, as well as reversal of decreased serotonin uptake. Thiamine deficiency in rats produces seizures in some studies, and hypothermia in all studies. These two symptoms alone are associated with decreased serotonin uptake. Serotonon uptake is energy dependent and there are some mild effects of thiamine deficiency on energy metabolism. Taken together, it seems possible that the changes in serotonin in thiamine-deficient rat brain are secondary to some other key changes.

@Gondwanaland

 

[JasonUT]

Anyways, can anyone suggest (not recommend of course ) a basic list of supplements to try getting onto this bandwagon to see if any improvements come? (At which point I'd read the whole thread and get more supps).

@Skippa

Unfortunately, I don't think there is an agreed upon suggestion. This thread seems to be our attempt at figuring it out and everyone is unique. It seems many of us are experimenting with some combination of lipid soluble Thiamine (aka allithiamine, lipothiamine, benfotiamine, fursultiamine and/or sulbutiamine). Quality B-complex, Multi, Magnesium, other electrolytes, and nutrients may be needed to avoid refeeding syndrome. This thread is a good read with a lot of very smart people contributing. It's worth a read when you have time and energy.

I suggest a SpectraCell Micronutrient test or Genova NutraEval test if finances allow. I was pleasantly surprised that my insurance covered SpectraCell testing.

 

[Skippa]

My posts are not intended to encourage or discourage anyone from trying thiamine. I can say that, without a shadow of a doubt, it was the most effective treatment I've ever tried. Like everything else, it has its side effects. In this instance, refeeding syndrome.

But this is good info to know thanks.

@JasonUT thanks, I'm about halfway through now. I'm scared of refeeding syndrome, and some of these supplements have given me funny reactions in the past, so I think I will wait 'til some of you report back some awesome results

 

[Gondwanaland]

'til some of you report back some awesome results

http://forums.phoenixrising.me/inde...pps-carnosine-beta-alanine-methylation.50395/

Does this mean that SSRI's are helpful or harmful for Thiamine deficient patients? I am confused.

There is much more detailed info in the 2nd ch (if I remember right) of the new book of dr. Lonesdale (link above). Like everything else, for some it will be great, for others it will be awful...