Thiamine Derivatives

[Dwest022]

Why is Thiamine HCL recommended when it does (as far as I know) not pass through the BBB, when other forms of Thiamine (Benfotiamine, Allithiamine and Sulbutiamine) pass through it? I realize there are advantages to each ,but has anyone tried any of the three mentioned above, and what benefits and/or side effects did you receive from it?

[MBAnderson]

Me too, i.e., why are we taking HCL?

[Dwest022 in reply to MBAnderson]

I have to assume the HCL is absorbed better than the Monohydrate.

[MBAnderson in reply to Dwest022]

Does that matter if it doesn't cross the BBB?

[danfitz]

Thiamine HCI does cross the blood brain barrier. It just that other forms cross it more easily because they are fat soluble and the HCI is water soluble.

As to why Dr C uses thiamine HCI you would have to ask him. Maybe it has to do with adjusting the dose. Being water soluble the HCI is excreted much mare rapidly so adjustment can be made more rapidly. Or maybe it is to avoid a build up of the oil soluble thiamine that might create other problems.

Generally it takes 30 days for a fat soluble substance to completely exit the body while a water soluble substance is excreted in just a few days.

[MBAnderson in reply to danfitz]

Thanks. Is there reason I couldn't do half of one and half of the other? I seem to remember reading it or listening to an interview where he said he went to HCl because it cost less to his patients.

[danfitz in reply to MBAnderson]

I don’t know. Maybe Roy does. I am not doing the thiamine therapy myself. I just responded to the BB issue. If you find out the answer please post it.

[Greenday in reply to MBAnderson]

It is also an issue of availability. In US sulbutiamine is available as a supplement and can be purchased online. In Europe this does not appear to be the case. There is a pharmaceutical form called "Arcalion" but it is not widely available and appears to be discontinued lately.

Also consider the following:

- Dr Costantini has registered an application for a patent with thiamine treatment for fatigue in PD and other disorders since 2011 patents.google.com/patent/W...

"Administration of oral vitamin B1 with doses of from 600 to 2400 mg led to complete recovery from fatigue in about 3-5 days of all patients with Parkinson's disease."

- Les Laboratoires Servier holds the patent with Sulbutiamine treatment for certain symptoms in PD and other disorders patents.google.com/patent/U...

"In Parkinson's patients, treated with sulbutiamine, an improvement in the cognitive, executive and mnesic functions was observed, with diminution of the sensation of fatigue."

It appears that different entities hold/applied for patents of different forms of thiamine for the same disease.

Interestingly both patents include fatigue as one of the main treated symptoms.

Regarding Benfotiamine the following study may offer a better insight:

Benfotiamine, a synthetic S-acyl thiamine derivative, has different mechanisms of action and a different pharmacological profile than lipid-soluble thiamine disulfide derivatives ncbi.nlm.nih.gov/pmc/articl...

"Our results show that, though benfotiamine strongly increases thiamine levels in blood and liver, it has no significant effect in the brain.

This would explain why beneficial effects of benfotiamine have only been observed in peripheral tissues, while sulbutiamine, a lipid-soluble thiamine disulfide derivative, that increases thiamine derivatives in the brain as well as in cultured cells, acts as a central nervous system drug"

[MBAnderson in reply to Greenday]

Interesting. Thanks. It seems a bit much to me, offensive actually, that a person can hold a patent, the purpose of which is to provide exclusive dominion, on the use of a vitamin to improve one's health. Rather like being awarded a patent on the use of water to quench one's thirst.

[Namitaytrev]

Great question. I had been on Sulbutiamine for approximately 2 weeks, then contacted Dr. Constantini to tweet my dose and he recommended I discontinue Sulbutiamine and start Thiamine HCL at 2gr, 1 before breakfast, 1 before lunch.

I told him I chose Sulbutiamine since it crossed the BBB and he said Thiamine does cross the BBB too. So I am unsure why he prefers Thiamine HCL.

[Namitaytrev in reply to Namitaytrev]

Tweak

[Dwest022 in reply to Namitaytrev]

Have you noticed any difference?

[Hidden]

Thiamine HCl is ingested and one of its first stops is the liver, which converts some of it to different active forms. The BBB has various means of thiamine transport depending on which form of Thiamine is present

[Dwest022 in reply to Hidden]

Thanks for the information.

[Namitaytrev]

I was only taking 400 mg of Sulbutiamine for approximately 2 weeks so it most likely not enough to feel any immediate difference. When I switched to Thiamine HCL 2 grams/day, within 12 days I had exacerbated symptoms so Dr C recommended I half the dose. (I weigh 110lbs and have SCA3) I am currently completely off the Thiamine until next week and will restart at 1 gram/day.

[Dwest022 in reply to Namitaytrev]

Thanks for the info. I have ordered the 500mg Thiamine HCL caps from Amazon, I also emailed back my weight and height to Dr. Constantini, haven't heard back. I think the Thiamine HCL uses "carriers" to get through the BBB. And because of the massive doses that Dr. Constantini recommends, what is not excreted by the Kidneys is transported through the BBB.

[MBAnderson]

I couldn't get your 2nd or 3rd link to work

[MBAnderson]

So -- let me see if I can figure this out. Person A owns a patent on Sulbutitiame and recommends people only use that derivative and Person B owns the patent on HCL and recommends people only use that product. Hmmmmmm.

The purpose of securing a patent is to make money. I have no problem with doctors or scientists making money off their discoveries, but it it does look like (the prospect of making) money is determining the recommendations.

I'm hoping we can set aside any biases for or against Dr. C and be objective about which derivative we should be taking.

It's still not clear to me.

Has anyone asked Dr. C why he prefers one over the other?

[Gioc in reply to MBAnderson]

This patent story is not clear. Thiamina hcl for what I remember the doctor uses it because it refers to L.Bettendorff researchers that one of thiamina's top experts. In my opinion thiamina hcl has existed for many years and is well known for other uses so it should not present surprises. I personally prefer the water-soluble form because you can feel the immediate effects, its deficiency and excess body perceptions and energy states . This gives me great control and ease of use rather than a different form that could accumulate somewhere and then act uncontrollably.

[Hidden in reply to MBAnderson]

I will.

Art

[tellme]

Hi everybody!

15 days ago, I started taking Thiamine injections (50 mg / week), according to Dr. Costantini's recommendation.

However, this week, results of blood test showed an increase in uric acid level. I'll talk about this with Dr. Costantini.

In the meantime, I found a post here, with interesting additional information, about thiamine derivatives and other important details about thiamine.

For example, I learned that apparently, Thiamine's injections contains aluminum.

Here is the post:

https: //healthunlocked.com/parkinsonsmovement/posts/134902883/more-on-thiamine ....

[tellme in reply to tellme]

healthunlocked.com/parkinso.......

[Greenday]

Regarding the pharmacokinetics in the brain of both Thiamine HCI and Sulbutiamine: Besides personal opinions, I would like to see more reliable references, especially anything that shows that one form is better and safer than the other one, and for a certain disease. I could not find such studies to support any hypothesis... As far as I know, allithiamine is the only bioavailable form of B1 that can be found in nature, and it is highly lipophilic. Thiamine can be a synthetic & natural compound. Sulbutiamine is a synthetic version of two Thiamine molecules chemically bonded together.

[Gioc in reply to Greenday]

These are specialist things, you should look for expert works like L.Bettendorff..

[Greenday in reply to Gioc]

I've extensively read Bettendorff studies... Bettendorff conducted studies on thiamine, benfotiamine, and sulbutiamine. Regarding the pharmacokinetics, in PD I just know an animal study of Bettendorff that investigates the effects of thiamine on DJ-1 which is a causative gene for familial PD ncbi.nlm.nih.gov/pmc/articl... and another one which concludes that plasma thiamine deficiency is not associated with Parkinson's Disease

link.springer.com/article/1... .

There is also a comparative study of Sulbutiamine and Benfotiamine which I’ve already quoted early in the post. Bettendorff is included in the list of authors. Dr Costantini appears to quote this study to exclude Benfotiamine over Thiamine HCl, but didn’t elaborate on Sulbutiamine which exerted superior results in the study.

Benfotiamine, a synthetic S-acyl thiamine derivative, has different mechanisms of action and a different pharmacological profile than lipid-soluble thiamine disulfide derivatives. ncbi.nlm.nih.gov/pmc/articl...

"Sulbutiamine, a lipid-soluble thiamine disulfide derivative, that increases thiamine derivatives in the brain as well as in cultured cells, acts as a central nervous system drug. We propose that benfotiamine only penetrates the cells after dephosphorylation by intestinal alkaline phosphatases."

Another study with Sulbutiamine also from Bettendorff

Injection of sulbutiamine induces an increase in thiamine triphosphate in rat tissues sciencedirect.com/science/a...

“Moreover, after a chronic treatment of rats with sulbutiamine, intracellular thiamine derivatives were increased by respectively 250% (thiamine), 40% (ThMP), 25% (ThDP) and 40% (ThTP) “

However there is no comparative study between Sulbutiamine and Thiamine HCI, therefore I cannot support any hypothesis posted in this forum unless proved/disproved in other studies

.

[Gioc in reply to Greenday]

Perhaps the answer has not been found yet. It seems to me that the buggies of the various forms are a little different from each other, but maybe I'm wrong I did not read them in depth.

[MBAnderson in reply to Greenday]

Is your post in response to tellme's link's referennces to Silvestrov's post, i.e., do you feel Silvestrov's links aren't reliable enough?

From your previous post, you make the case that sulbutiamine is preferable, no?

Or, from your more recent post, are you saying sulbutiamine being synthesized makes it less viable then HCl -- considering virtually all supplements are synthesized?

[Greenday in reply to MBAnderson]

I'm not aware of Silvestrov post could you recite? Personally, I don't bother whether natural or synthetic. I'm only concerned about safety and efficacy.

[MBAnderson in reply to Greenday]

(Credit to tellme)

healthunlocked.com/parkinso.......

[Greenday in reply to MBAnderson]

I think so this is a good question for Dr. Costantini to answer, whether Thiamine injections include aluminum and if it can build up to dangerous levels in the body through time.

[Gioc in reply to Greenday]

Aluminum?,but it should not be written? How is it possible that someone can answer a similar question? the only thing I do not understand about injections is because in Germany they are sold without prescription and in Italy no. Bah all the time ... go to the doctor, do the recipe etc. etc.

[MBAnderson in reply to Greenday]

Good to hear.

[Greenday in reply to MBAnderson]

My concerns are the following:

1) That the double-blind placebo-controlled study with sulbutiamine is part of a patent, unpublished, and not available for peer review

2) That the Dr. Costantini 2015 study is mainly observational

3) Not standard therapeutic dosages / much trial and error for the ideal dosage

4) Safety concerns in long-term

Result: inconclusive

[Hidden in reply to Greenday]

All titrations involving the BBB are trial and error. It’s the same problem with levodopa. You cannot guess from urine or plasma what’s going on in the brain. Hourly lumbar punctures anyone?

[Greenday in reply to Hidden]

Yes, but as with levodopa and any drugs, the titration is usually gradual and upwards not downwards. I see some patients are advised to take a high dose of 3-5g thiamine from the beginning of their treatment and then advised to cut down to half after they experiencing side effects. My opinion, and what is common medical practice, is that patients should start with the lowest dosage possible after consultation with their doctor and slowly titrate the dosage up until they reach therapeutic dosage probably in 1-2 months. No one starts with the highest dose of levodopa from the day 1. I see in some of those overlooked reports with thiamine treatment, many patients experience side effects in few days, weeks or months and have to cut down their dosage. That would be avoided if they were been gradually introduced from a lower to a higher dosage through time, instead of aiming for fast results and possible side effects. Also, intestinal absorption is an issue in water-soluble compounds such as thiamine as opposed to lipophilic compounds, which make it more difficult to calculate the ideal dosage for each patient.

[Hidden in reply to Greenday]

If you don’t accept my summary try Wikipedia

en.m.wikipedia.org/wiki/Thi... . In the doses we are taking the form really doesn’t matter. Enough will get through!

[Hidden]

I am not a clinician so cannot justify high to low for Thiamine except that the body’s buffer stores need to be topped up first. Intramuscular injection use the mass of muscle to control the release into the blood

[Hidden]

Part 2. Oral water soluble thiamine uses the blood as the buffer but it’s not as effective as muscle. Once the buffers are full the demand side in the brain always has some in reserve. Levodopa doesn’t have the buffers it gets converted

[Greenday in reply to Hidden]

There are 2 studies that compare IM & IV and oral thiamine administration:

- Plasma thiamine concentrations after intramuscular and oral multiple dosage regimens in healthy men.

ncbi.nlm.nih.gov/pubmed/161...

- Tissue thiamin levels of hospitalised alcoholics before and after oral or parenteral vitamins.

ncbi.nlm.nih.gov/pubmed/335...

In summary, those studies showed that Oral thiamine hydrochloride when given over a 1-week period produce blood levels that approach those obtained by intramuscular and intravenous administration.

Also another study:

- Pharmacokinetics of high-dose oral thiamine hydrochloride in healthy subjects" ncbi.nlm.nih.gov/pmc/articl...

"High blood levels of thiamine can be achieved rapidly with oral thiamine hydrochloride. Thiamine is absorbed by both an active and unsaturable passive transport mechanism up to 1500 mg."

However what really matters is the bioavailability and pharmacokinetics of thiamine and its derivatives in the brain of patients with PD :

The following study offers a better insight

- Cerebrospinal fluid levels of thiamine in patients with Parkinson's disease.

ncbi.nlm.nih.gov/pubmed/104...

"Thiamine is an essential cofactor for several important enzymes involved in brain oxidative metabolism, such as the alpha-ketoglutarate dehydrogenase complex (KGDHC), pyruvate-dehydrogenase complex, and transketolase.

The activity of alpha-ketoglutarate dehydrogenase complex (KGDHC) is decreased in the substantia nigra or patients with Parkinson's disease (PD).

We measured cerebrospinal (CSF) levels of thiamine-diphosphate, thiamine-monophosphate, free thiamine, and total thiamine, using ion-pair reversed phase high performance liquid chromatography, in 24 PD patients and 40 matched controls.

** The mean CSF levels of thiamine-derivatives did not differ significantly from those of controls, with the exception of lower CSF free thiamine levels in the PD-patient group.

** PD patients under levodopa therapy had significantly higher CSF thiaminediphosphate and total thiamine than those not treated with this drug.

CSF thiamine levels were not correlated with age, age at onset, duration of the disease, scores of the Unified Parkinson Disease Rating Scale of the Hoehn and Yahr staging in the PD group.

These results suggest that low CSF free thiamine levels could be related with the risk for PD."

[Hidden]

Patent Application, Patent Pending, Patent Fatigue, I can say have or not no matter. I am happy my Parkinson progression stopped and symptoms suppressed thanks to Doc Costantini and thiamin HCI

[Greenday in reply to Hidden]

If your symptoms did suppress why do you need to take the same amount of levodopa (3 x day C/L 50-200 ER) as before the thiamine treatment? How did you judge that progression has stopped? You have been only taking thiamine HCI for a few months. What about tremors did thiamine suppress your tremors? What about Benfotiamine? In a former post healthunlocked.com/parkinso... you mentioned that your initial improvement was with Benfotiamine, which according to a study ncbi.nlm.nih.gov/pmc/articl... , that Dr. Costantini also quotes, benfotiamine cannot reach the brain barrier. So I wonder how did you feel that improvement with Benfotiamine initially?

[Gioc in reply to Greenday]

For once, there was a happy person ...

[Greenday in reply to Gioc]

Happy for all those that thiamine treatment turns out to be successful, but cannot overlook all those accounts who report side effects over time, even on lower dosages, or simply that the treatment does not work for them. Example Juliegrace has been taking thiamine injections for 4-1/2 months and reported that gradually dyskinesia got worse without any increase in med healthunlocked.com/parkinso...

[Hidden]

Thanks for that. I think it’s in line with my summary. The csf paper in particular is interesting. The csf is another buffer store for thiamine and derivatives and is separated from the neurones by membrane barrier

[Hidden in reply to Hidden]

An overview of the relationship between csf, BBB and plasma

link.springer.com/article/1...