Pyruvate dehydrogenase function depends on thiamine (B1)

[Asklipia]

@JasonUT Yes! Thank you very much for joining us and taking the time and effort to share your results.
I have read your posts yesterday and was impressed by your efforts to share, efforts which will bear fruit I am sure.
In the meantime I wish you a complete and happy recovery!
What we suffered has taught us a lot, and I for one, never dreamt of being in such good shape as I am now. all because I researched my problems.
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=DL...VAhUJC8AKHSQXB0IQ6AEILjAB#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

 

[Chocolove]

@JasonUT Thought you might find these of interest.

http://www.stewartnutrition.co.uk/nutritional_emergencies/acute_thiamine_deficiency.html

Treatment of Severe Thiamine Deficiency
Oral thiamine in low doses is well absorbed but the mechanism, which is an active rate-limited process. is easily saturated and it is considered that it is impossible to absorb more than approximately 4.5 mg from a single oral dose. For patients who are not vomiting, are without malabsorption, have not consumed excess alcohol, which inhibits thiamine absorption, and are not severely ill oral supplements are likely to be adequate.

Oral doses of thiamine of 5-10 mg three times per day are probably adequate for mild deficiency however because of the possible co-existence of other B vitamin deficiencies for which amounts greater than 5 mg per day are usually required it is often prudent to use vitamin B complex 50 mg three times per day which is widely available in health food shops and some pharmacies.

Parenteral forms of vitamin B1 are required by all seriously ill patients especially those with Wernicke’s Encephalopathy, WE. Pabrinex, a prescription only preparation of several B vitamins, is available for intravenous and intramuscular administration; however it may very rarely precipitate anaphylactic shock and should only be administered in a situation where there are facilities for coping with such a possibility. Pabrinex is usually administered as two pairs of ampoules every 8 hours for the first 48 hours of alcohol withdrawal.

It is prudent to regard that all poorly nourished patients and alcoholics are likely to be deficient and may need to be given parenteral thiamine and other B vitamins particularly before receiving IV glucose. Stores of magnesium, which is needed for the activation of thiamine and other B vitamins, are likely to be inadequate in those with malabsorption, diarrhoea, muscle wasting or chronic alcohol excess and supplementation may be required, which should be intravenous if hypomagnesaemia is present. See above article for full details of treatment of acute thiamine deficiency.

http://www.todaysdietitian.com/newarchives/100610p78.shtml

Malnourished patients are also at risk for refeeding syndrome, so potassium, magnesium, and phosphorus levels should be monitored daily during initial treatment. Magnesium is of particular importance due to its role in thiamine metabolism and as a cofactor of enzymes.

http://www.practicalgastro.com/arti...sser-Known-Side-Effect-of-Thiamine-Deficiency

There is large variability in thiamine prescribing practices, most revolving around the treatment of alcoholics. Only one randomized, double blind study using different doses of parenteral thiamine exists to date.10 ...Thiamine is both inexpensive and safe. Because of the potentially devastating effects of undertreating thiamine deficiency, recommendations of higher doses have appeared in the literature.11 In the United Kingdom, 500 mg IV thiamine 3 times daily is prescribed followed by 250 mg IV or IM for 5 days.12 The European Guidelines suggest 200 mg IV three times daily until symptoms resolve.13 American guidelines suggest the lowest amounts of thiamine, ranging from 50-100 mg IV daily for a period of at least 3 days.11 (see Table 3).

 

[Asklipia]

I have my doubts about thiamine deficiency created only by a few cups of tea or coffee. To result in thiamine deficiency, this habit is supposed to need a co-factor : a deficiency in vitamin C.

On the other hand, I found this extremely interesting in Lonsdale's book p. 16 :

About 80% of thiamine in nervous tissue is TPP. About 5%-15% is in the form of TTP, and the remainder is free thiamine and thiamine monophosphate. Thiamine triphosphatase, diphosphatase, and monophosphatase catalyze the respective hydrolysis reactions from TTP to free thiamine. All require magnesium.

The original observations of Minz concerning the release of thiamine into the medium after electrical stimulation of a nerve have been confirmed by other investigators. This release coincides with a shift of the thiamine phosphate esters to a more dephosphorylated form (39). A similar release occurs after the use of a variety of neuroactive agents, (62, 63) so it appears that any condition that results in a change in ion movements dephosphorylates the vitamin and permits its efflux.

(39) Collins GH, Webster HDF, Victor, M. The ultrastructure of myelin and axonal alterations in sciatic nerves of thiamin deficient and chronically starved rats, Acta Neuropathol 1964; 3(5):511-521
(62) Itokawa Y, Cooper JR. Ion movements and thiamine in nervous tissue ---I Intact nerve preparations, Biochem Pharmacol 1970, 19: 985-92
(63) Itokawa Y, Cooper JR. Thiamine release from nerve membranes by tetrodotaxin, Science 1969; 166(3906) 759-60

This is what is discussed in the ebook that I had quoted in my previous post
http://forums.phoenixrising.me/inde...te-inhibiting-thiamine-b-1.23392/#post-357739

If nerve stimulation wastes thiamine by dephosphorylation, just think of the amount of activities in your day that do so! Mainly activities where you are not active, but a passive subject of visual/audio stimulation for example. Or stimulation by chemical exciting agents like MSG or others.
THIAMINE EFFLUX

 

[Asklipia]

Video games > thiamine efflux > death by shoshin

 

[JasonUT]

@Chocolove
@Asklipia

Dr. Lonsdale suggests that Thiamine deficiency depends on 3 factors: stress, nutrients, and genetics.

Interesting research study comparing Allithiamine to parenterally administered Thiamine HCl and TPP.

This article, by Chanlder Marrs, is what spawned my interest in Thiamine deficiency.

 

[Asklipia]

Interesting research study comparing Allithiamine to parenterally administered Thiamine HCl and TPP.

I like that part :
Healthy volunteers ingesting 50mg THCI had a slight increase in circulating thiamine.
Thiamine-deficient alcoholics who were ingesting alcoholic beverages showed little or no increase in circulating thiamine.
Both normal and thiamine-deficient subjects showed significant increases in circulating thiamine activity after ingestion of TPD (thiamine propyl disulfide); circulating thiamine was increased after oral TPD in the deficient alcoholics even while they were ingesting alcoholic beverages.

This article by, Chanlder Marrs, is what spawned my interest in Thiamine deficiency.

Yes, especially the black line and the 6% offer a lot of hope.

 

[JasonUT]

Reading on a screen costs more thiamine than reading from paper!
Throwing the glance costs thiamine but it seems that if the object looked at is blue, it costs more thiamine that if it is red!

Interesting. I find LCD screens tire me which are high in blue light emission. I can't watch my big screen 60" LED TV anymore. When I use my phone or tablet I install a blue light filter and that seems to help a lot. I thought I was crazy. Maybe I am crazy, but at least I know I am not alone.

 

[Asklipia]

I solved this a couple of years ago by watching my films on a white wall with a projector. There are very good and powerful ones now for a reasonable price. The image is sent from my computer. No problem.
Also, if not watching, the thing disappears from sight. Very satisfying, I hate plastic stuff sitting round.
You are not crazy and you are not alone.
God bless.

 

[JasonUT]

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).

This is interesting to me. I had taken AlliMed 450 mg BID for possible prostate/bladder infection in Nov 2016. It helped and also relieved many of my other symptoms. I wonder if my body was creating Allithiamine during digestion. Maybe I was unknowingly solving my B1 deficiency?

Fermentation increases some vitamin B levels (Uzogara et al,1990) and has been reported that a thiamine-deficient diet when supplemented with milk curds appears to increase the intestinal synthesis of thiamine as shown by an increase in urinary and faecal thiamine excretions (Bhuvaneswaran and Sreenivasan, 1962).

I wonder if Kefir, Sauerkraut, Kimchi, etc. would help?

 

[Chocolove]

@JasonUT I use f.lux on my computer to adjust or totally remove the blue light. When blue light is totally removed the screen looks like a traditional dark room for photography with red light against black. It has helped me a lot. The download is free. See: https://justgetflux.com/

 

[Chocolove]

I have my doubts about thiamine deficiency created only by a few cups of tea or coffee. To result in thiamine deficiency, this habit is supposed to need a co-factor : a deficiency in vitamin C.

Incidentally, two years ago I had an ongoing problem for months. Daily after meals my bowels would violently flush everything they could. I began the rounds of dietary and supplement removal to see what the offender could be. It turned out to be the black tea I was consuming - several glasses with a meal. Now I don't mean the normal quickening of bowels, triggered by caffeine. The total bowel flushes finally and completely stopped when I stopped drinking the black tea. I strongly suspect the tannins in the tea of causing this daily dump and the loss of nutrients. The tea was a bit puckery which is an indicator of tannins probably increased by steeping too long.

At the time, I was getting a considerable amount of vitamin C at the time through supplements and food. However my body clearly and desperately was trying to rid itself of that tea.

 

[Chocolove]

@JasonUT While your wife and others may not appreciate the smell, transdermal application appears to be the way to go for some of our members, and perhaps you if you are not seeing oral results?

http://forums.phoenixrising.me/inde...ermal-thiamine-comparable-to-injection.47588/

As per @Sidereal

Transdermal allithiamine is the most effective intervention I have found for my ME/CFS. Noticeable increase in energy and cognitive clarity within 15-20 mins. I open the capsules and mix them with hand lotion and apply to skin.... I went as high as 300-400 mg per day....It's really messy and smelly but it works. Swallowing any form of thiamine - and I've tried them all - has little to no effect.

As per @Lolinda
I corrobate the that there are issues:

• I used one single time 75mg of B1 orally and it badly increased my neuropathy, I felt almost nothing in my soles. This is why I am now that careful to take such minimal doses as described above.
• On google scholar, you find reports on patients who died from thiamine injections...

Still, I started taking some thiamine, because I tested as deficient as in full-blown beri-beri and my symptoms match, too.

 

[Chocolove]

@JasonUT In consideration of using thiamine injections:
Antonio Constantini M.D. has recently had some remarkable results treating patients using thiamine, including patients with Parkinson's Disease. You may be interested in the 13 free PubMed articles:
https://www.ncbi.nlm.nih.gov/pubmed/?term=Thiamine Antonio Costantini

And a news interview with Dr. Constantini and videos of his patients:
http://www.ultimaedizione.eu/costan...-thiamine-parkinson-suffers-a-terrible-strik/
http://www.ultimaedizione.eu/costantinis-patients-tell-of-their-victories-over-parkinsons-disease/
http://www.ultimaedizione.eu/videos-parkinsons-patients-treatment/

In conclusion, we found that the long-term treatment with the intramuscular administration of thiamine has led to a significant improvement of motor and non-motor symptoms of the patients with PD; this improvement was stable during time and without side effects.

 

[JasonUT]

New article by Lonsdale. I haven't read it yet.

https://www.hormonesmatter.com/navigating-thiamine-supplements/

Is there a way to find slc19 in 23andme raw data? If not how would it be tested?

 

[Chocolove]

Benfotiamine may penetrate the brain after all.
There is an ongoing clinical trial using benfotiamine on Alzheimer's patients.
http://burke.weill.cornell.edu/gibs...e-alzheimers-disease-pilot-study-benfotiamine
It does not appear from study description that they are also supplementing the patients with magnesium, so I wonder whether the benfotiamine will be effective without first repleting magnesium..... since it appears magnesium is so commonly deficient and especially in Alzheimer's.

That body requirement to have magnesium onboard to utilize thiamine is imperative.
See below:

Brain. 2010 May;133(Pt 5):1342-51. doi: 10.1093/brain/awq069. Epub 2010 Apr 12.
Powerful beneficial effects of Benfotiamine on cognitive impairment and beta-amyloid deposition in amyloid precursor protein/presenilin-1 transgenic mice.
Pan X1, Gong N, Zhao J, Yu Z, Gu F, Chen J, Sun X, Zhao L, Yu M, Xu Z, Dong W, Qin Y, Fei G, Zhong C, Xu TL.Author information
1
Department of Neurology, Zhongshan Hospital & Shanghai Medical College, State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai 200032, China.
Abstract
Reduction of glucose metabolism in brain is one of the main features of Alzheimer's disease. Thiamine (vitamin B1)-dependent processes are critical in glucose metabolism and have been found to be impaired in brains from patients with Alzheimer's disease. However, thiamine treatment exerts little beneficial effect in these patients.

Here, we tested the effect of benfotiamine, a thiamine derivative with better bioavailability than thiamine, on cognitive impairment and pathology alterations in a mouse model of Alzheimer's disease, the amyloid precursor protein/presenilin-1 transgenic mouse. We show that after a chronic 8 week treatment, benfotiamine dose-dependently enhanced the spatial memory of amyloid precursor protein/presenilin-1 mice in the Morris water maze test.

Furthermore, benfotiamine effectively reduced both amyloid plaque numbers and phosphorylated tau levels in cortical areas of the transgenic mice brains.

Unexpectedly, these effects were not mimicked by another lipophilic thiamine derivative, fursultiamine, although both benfotiamine and fursultiamine were effective in increasing the levels of free thiamine in the brain.

Most notably, benfotiamine, but not fursultiamine, significantly elevated the phosphorylation level of glycogen synthase kinase-3alpha and -3beta, and reduced their enzymatic activities in the amyloid precursor protein/presenilin-1 transgenic brain.

Therefore, in the animal Alzheimer's disease model, benfotiamine appears to improve the cognitive function and reduce amyloid deposition via thiamine-independent mechanisms, which are likely to include the suppression of glycogen synthase kinase-3 activities.

These results suggest that, unlike many other thiamine-related drugs, benfotiamine may be beneficial for clinical Alzheimer's disease treatment.

PMID: 20385653
DOI: 10.1093/brain/awq069
************************************************

Altered ionized magnesium levels in mild-to-moderate Alzheimer’s disease
Mario Barbagallo, Mario Belvedere, Giovanna Di Bella, Ligia J. Dominguez Chair of Geriatrics, Department of Internal Medicine and Medical Specialties (DIMIS), University of Palermo, Italy Correspondence: M. Barbagallo, MD, Ph.D, Professor of Geriatrics, University of Palermo, Via F. Scaduto 6/C, Italy
Abstract.
Magnesium deficiency is present in several chronic, age-related diseases, including cardiovascular, metabolic and neurodegenerative diseases. Alzheimer’s disease (AD) is the most common cause of dementia. The aim of the present study was to study magnesium homeostasis in patients with mild to moderate AD. One hundred and one elderly (≥65 years) patients were consecutively recruited (mean age: 73.4±0.8 years; M/F: 42/59). In all patients, a comprehensive geriatric assessment was performed including cognitive and functional status. Admission criteria for the AD group (diagnosed according to the DSM-IV and the NINCDS-ADRDA criteria) included: mild to moderate cognitive impairment (MMSE score: 11–24/30, corrected for age and education). Blood samples were analyzed for serum total magnesium (Mg-tot) and serum ionized magnesium (Mg-ion).

AD patients had significantly lower MMSE scores (20.5±0.7 vs 27.9±0.2; p<0.001), and for the physical function tests. Mg-ion was significantly lower in the AD group as compared to age-matched control adults without AD (0.50±0.01 mmol/L vs 0.53±0.01 mmol/L; p<0.01). No significant differences were found in Mg-tot between the two groups (1.91±0.03 mEq/L vs 1.95±0.03 mEq/L; p=NS). For all subjects, Mg-ion levels were significantly and directly related only to cognitive function (Mg-ion/MMSE r=0.24 p<0.05), while no significant correlations were found in this group of patients between magnesium and ADL or IADL.

Our results show the presence of subclinical alterations in Mg-ion in patients with mild to moderate AD.
Full article here:
http://www.jle.com/download/mrh-290...mer_s_disease--WXO5HH8AAQEAAB3rAyoAAAAD-a.pdf

 

[junkcrap50]

I have come back to this reread this thread and the commenters and conversation in last 3 pages interests me.

I am wondering, does anyone knows if there is a lab in the US that does the functional thiamine test, aka erythrocyte transketolase activity test (TKA) and with the thiamine pyrophosphate effect (TPPE), as recommended by Dr. Lonsdale? SEE EDIT

I am having a difficult time finding a lab in the US that does. It seems like it is still done frequently in the UK and Europe, but according to Mayo Clinic Labs:

Transketolase determination, once considered the most reliable means of assessing thiamine status, is now considered an inadequate method.... However, the test is somewhat nonspecific, as other factors may decrease transketolase activity. Transketolase is less sensitive than liquid chromatography-tandem mass spectrometry (LC-MS/MS) [of thiamine diphosphate in whole blood], has poor precision, and specimen stability concerns. (Source)

Dr. Lonsdale replied in a comment to one off his articles that Mayo's explanation is nonsense and not true.

These two blog posts (here and here) mention King James Medical Laboratory and Metametrix (now Genova Diagnostics) as the only places that do the Transketolase test. However, King James Medical Labs is now out of business, referring you to TMI Trace Minerals International Laboratory. I have an email in to them if they do the Transketolase test and am waiting for a reply. Also, as of writing this, Genova's website is under maintenance, so I can't see if they provide the test.

Thanks if anyone has any information!

EDIT: DOH! I missed a comment in the same aricle I linked where Dr. Lonsdale replied. Yes. TMI Trace Mineral International Laboratory does do the Transketolase test, as of January 2016 as one commenter found out for $25.

 

[JasonUT]

It appears that the half-life of TTFD (aka Lipothiamine, Allithiamine, Fursultiamine) is 4 hours [Source]. I think this must be why Lonsdale recommends taking it twice per day.

The apparent biological half-life of thiamine from TTFD was more than 4 hours compared to 35 min for parent drug Thiamine.

 

[Asklipia]

It appears that the half-life of TTFD (aka Lipothiamine, Allithiamine, Fursultiamine) is 4 hours [Source]. I think this must be why Lonsdale recommends taking it twice per day.

We take some kind of thiamine approximately every 3 hours and found this the most helpful.

 

[Eastman]

...
There is an ongoing clinical trial using benfotiamine on Alzheimer's patients...

Have you seen this study?

Safety Study of Nicotinamide to Treat Alzheimer's Disease

The result of the study was apparently not published but according to a member of another forum who contacted the lead investigator, "the results went way beyond the simple toxicity study he aimed for this to be" and that "UCI is working on a patentable niacinamide version".

 

[JasonUT]

We take some kind of thiamine approximately every 3 hours and found this the most helpful.

@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