How can befothiamine treat Alzheimer's if it doesn't cross the blood brain barrier?

Elie

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Here @haidut posted a study showing 300 mg benforthiamine twice daily was shown to successfully treat diabetes.

Yet, on his recent, and very informative interview (Stuff your Doctor should know, Maintain your brain) he stated that benfothiamin, unlike allithiamine and fursultiamine, doesn't cross the Blood Brain Barrier (BBB). So how can it treat Alzheimer's (dementia / brain diabetes)?

Moreover, this paper here , suggests that even fursultiamine (as benfo) are unable to raise thiamin pyrophosphate (TPP) in the brain??? and yet the fursulthiamine is used to treat dementia in Japan?

so can these precursors of thiamin reach brain cells and convert into TPP or not?

Thiamin experts please weigh in.
 

xeliex

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Here @haidut posted a study showing 300 mg benforthiamine twice daily was shown to successfully treat diabetes.

Yet, on his recent, and very informative interview (Stuff your Doctor should know, Maintain your brain) he stated that benfothiamin, unlike allithiamine and fursultiamine, doesn't cross the Blood Brain Barrier (BBB). So how can it treat Alzheimer's (dementia / brain diabetes)?

Moreover, this paper here , suggests that even fursultiamine (as benfo) are unable to raise thiamin pyrophosphate (TPP) in the brain??? and yet the fursulthiamine is used to treat dementia in Japan?

so can these precursors of thiamin reach brain cells and convert into TPP or not?

Thiamin experts please weigh in.
Elie, that interview was so jam-packed with information.

I could be wrong, but thought the other analog was prosultiamine instead of fursul - these names, man!

I'd love to here what Haidut has to say - yes, benfo has a lot of studies showing benefits in peripheral tissues but it seems like not in the brain.
 

haidut

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Here @haidut posted a study showing 300 mg benforthiamine twice daily was shown to successfully treat diabetes.

Yet, on his recent, and very informative interview (Stuff your Doctor should know, Maintain your brain) he stated that benfothiamin, unlike allithiamine and fursultiamine, doesn't cross the Blood Brain Barrier (BBB). So how can it treat Alzheimer's (dementia / brain diabetes)?

Moreover, this paper here , suggests that even fursultiamine (as benfo) are unable to raise thiamin pyrophosphate (TPP) in the brain??? and yet the fursulthiamine is used to treat dementia in Japan?

so can these precursors of thiamin reach brain cells and convert into TPP or not?

Thiamin experts please weigh in.

Allithiamine and prosultiamine have been shown to raise brain TPP. Not so for many of the other synthetic B1 analogs and (possibly) not so for thiamine Hcl/nitrate unless the latter is given by IV. It could be that some of the synthetic B1 that do not raise TPP raise the levels of a phosphated derivative of the synthetic B1 instead and since the researchers did not test for that derivative molecule but only TPP (derived from regular thiamine) they decided those analogs are ineffective when in fact they may be effective. Just a speculation on my end, but until we get a human trial with benfo, fursultiamine, etc showing they treat Alzheimer's I would try to use allithiamine or prosultiamine if oral route is desired, and regular thiamine if you can convince a doctor to give the patient thiamine Hcl/nitrate by injection/infusion.
 
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Elie

Elie

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Allithiamine and prosultiamine have been shown to raise brain TPP. Not so for many of the other synthetic B1 analogs and (possibly) not so for thiamine Hcl/nitrate unless the latter is given by IV. It could be that some of the synthetic B1 that do not raise TPP raise the levels of a phosphated derivative of the synthetic B1 instead and since the researchers did not test for that derivative molecule but only TPP (derived from regular thiamine) they decided those analogs are ineffective when in fact they may be effective. Just a speculation on my end, but until we get a human trial with benfo, fursultiamine, etc showing they treat Alzheimer's I would try to use allithiamine or prosultiamine if oral route is desired, and regular thiamine if you can convince a doctor to give the patient thiamine Hcl/nitrate by injection/infusion.

Just to clarify...
First, I need to make a correction. I referred to a paper you posted that showed beforthiamine successfully treated Alzheimer's (not diabetes, as I stated), even though, you stated it doesn't reach the brain (cross the BBB), not does it convert to TPP in the brain (according to the paper i cited).

So, to be clear, you are saying that it may convert to other (active?) thiamin derivatives? Do they act as TPP?
I thought TPP is the actual cofactor for thiamin-dependent enzymes.
Is just a matter of not having enough researched / published info?
 
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Elie

Elie

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Elie, that interview was so jam-packed with information.

I could be wrong, but thought the other analog was prosultiamine instead of fursul - these names, man!

I'd love to here what Haidut has to say - yes, benfo has a lot of studies showing benefits in peripheral tissues but it seems like not in the brain.
Yes, fantastic interview.

... Benfothiamin can't reach the brain, and yet, befothiamine can treat Alzheimers.
Vitamin B1 as a potential treatment for Alzheimer's Disease (AD)
 
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