I see there is growing interest on high dose thiamine on this forum. Sadly, the topic is being driven with lots of information that is either old or from a single source. I want to offer some additional information that people can use to make their own decisions, and I will update the studies I find that are relevant. I also want to emphasize that I believe thiamine is beneficial to neurological disorders, I just want to urge caution, patience, research, and a discussion with one's doctor.
contention number one: benfotiamine does not increase brain thiamine. Early research indicated this was the case.
Comparative Pharmacokinetic Analysis of Thiamine and Its Phosphorylated Metabolites Administered as Multivitamin Preparations
More recent research directly contradicts this belief:
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Powerful beneficial effects of benfotiamine on cognitive impairment and β-amyloid deposition in amyloid precursor protein/presenilin-1 transgenic mice
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"Both benfotiamine and fursultiamine increased levels of thiamine but not its phosphate esters in the brain
Next, we investigated the effects of benfotiamine and fursultiamine on levels of thiamine and its phosphate esters in blood and brain. Using high performance liquid chromatography examination, we found that in adult wild-type mice, both benfotiamine and fursultiamine significantly increased the blood concentrations of free thiamine, thiamine monophosphate (TMP) and thiamine pyrophosphate (TPP) at 1 h after a single administration or a consecutive 10 day administration, at the dose of 100 mg/kg (Fig. 4A). Benfotiamine showed better bioavailability than fursultiamine, as shown by the significantly higher blood concentrations of thiamine and TPP after benfotiamine treatment than fursultiamine (Fig. 4A). However, in the brain, after a single administration or a consecutive 10-day administration, benfotiamine and fursultiamine only elevated the level of free thiamine, but not that of TMP and TDP (Fig. 4B), consistent with the results shown by previous studies (Volvert et al., 2008; Nozaki et al., 2009). Furthermore, the increased thiamine level in the brain did not differ between benfotiamine and fursultiamine after the chronic administration (Fig. 4B), despite the slightly greater effect of benfotiamine than fursultiamine on the brain thiamine level after the single administration (Fig. 4B). Taken together, these results suggest that the beneficial effect of benfotiamine in APP/PS1 mice cannot be solely attributed to the increase in the brain levels of thiamine and/or its phosphate esters."
Thiamine and benfotiamine prevent stress-induced suppression of hippocampal neurogenesis in mice exposed to predation without affecting brain thiamine diphosphate levels.
So far the only "scientific evidence" of the effective oral HCL Thiamine dosage for Parkinson's is based on an email correspondence with Dr C. No any reference in journals or other studies to support that. No reference to other highly biovalable lipid disdulfides that exert specific effects on brain function like Sulbutiamine. I wonder if oral HCL is so effective for Parkinson's why they don't produce a liposomal form to compete the bioavailability of true lipid soluble thiamines like Sulbutiamine and allithiamine.
Here is another human clinical trial that used benfotiamine and had positive results. In this study one key element was a reduction in "anxiety" which is a function of the brain:
Double-blind, randomized placebo-controlled clinical trial of benfotiamine for severe alcohol dependence
Again, please ask yourself, why are serious researchers with peer reviewed HUMAN clinical trials that showed a benefit from thiamine choosing to use benfotiamine. Why did they not use thiamine hcl injections or tablets if that would have been a better form of thiamine? It doesn't make sense.
And another study touting the preferred use of benfotiamine:
Liver, plasma and erythrocyte levels of thiamine and its phosphate esters in rats with acute ethanol intoxication: a comparison of thiamine and benfotiamine administration.
"A comparison between lipophilic thiamine derivatives
and thiamine itself was made based on the results
of both studies. The extent of thiamine absorption
was significantly greater when thiamine was given as a
lipophilic derivative compared with thiamine itself. In
study B (fursultiamine/thiamine), the %GMR (90%
CI) of AUClast of total plasma thiamine was 249.0%
(218.7%–283.5%), whereas this value was 100.3%
(90.5%–111.2%) in study A (fursultiamine/benfotiamine).
The absorption rate was also considered
greater for lipophilic derivatives, based on the lower
median Tmax values (with larger Cmax/dose values),
which were 1 to 1.5, 1.5, and 3 hours after dosing
with fursultiamine, benfotiamine, and thiamine
respectively. These findings suggest that lipophilic
thiamine derivatives have clear benefits for the delivery
of thiamine into the bloodstream, as intended in
the development steps"
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In the 2008 study of thiamine hcl it took 1500 mg of oral dose to reach a plasma level of thiamine of 400 micromoles/l - in the 2016 study a mere 100 mg of benfotiamine achieved the same result.
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So far I can not find any data to support the idea that taking thiamine hcl is the better method for supplementation of thiamine.
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I purchased the rights to the 2016 study if anyone would like to see it.
Dude. Don't pay to read those articles when you can get a full copy of them for FREE. Visit sci-hub.la
Seriously this site will provide you with a PDF of ANY medical or science article that you'd like to read.
FYI you'll get the best results for this site when you enter the DOI for the medical article you're interested in. Simply copy the DOI from the article's entry on pubmed into the sci-hub site and BOOM you'll have a full PDF copy of your article that you can download or save as you wish.
You can also paste in the full title of the article and download it that way, but sometimes this 'search by title' feature doesn't work on some occasions.
And don't feel bad for getting it free, either. The researchers, peer reviewers, and journal editors that worked hard on this research don't get any of your money when you decide to purchase an article. Only publishers get your money, and they are very greedy so they keep it, rather than use it to fund science or other research.
My initial symptoms improvement (before switching to thiamin hcl) is credited to 500mg/day of benfotiamine. I must now reconsider choices.
For some reason I can't find benfotiamine 300 mg by Life Extension, it seems that only Doctor's Best brand has that amount and Bestvite brand which I've never heard of before.
Looks like no thiamine for me. After a week my blood pressure has gone from 110/70 to 140/90. I guess I'll wait to see more research directly tied to ataxia before I try thiamine again.
I was taking 300 mg twice a day of Benfotiamine sold by Life Extension. It's interesting because I've now been off thiamine for 24 hours and my legs feel "heavy" this morning. If it persists I may wait a week and try going back on benfotiamine to see if it changes how I feel. Joe in NY
Great you opened this topic and included all those studies. It is a small oasis within such misinformation surrounding thiamine.
I guess you take the Mega Benfotiamine 250mg/cap. When comes to dosages there is a lack of clinical data for Parkinson’s. However in a small study Alzheimer patients exhibited cognitive improvements after they received Benfotiamine 300mg daily for over 18 months . ncbi.nlm.nih.gov/pubmed/276... . Possibly the drug may show benefits for Parkinson’s after long term administration and at smaller dosage. A new well-organized clinical trial is under way where Alzheimer patients are receiving 300 mg morning & evening nia.nih.gov/alzheimers/clin... . Of course the results may be relevant or irrelevant to the Parkinson’s. I’d really like to see a similar study take place. Personally I always start with a lower dosage and distribute throughout the day to keep AUC levels high and observe for possible side effects before increase. Currently I start with 3x100mg liposomal Benfothiamine.
I see great minds think alike I linked to those studies above as well. Those human clinical trials as well as the completed trial in alcoholics were what convinced me to try 300 mg twice a day. The benfo I was taking came in 100 mg pill form:
Assuming you told the truth that it is proof benfotiamine is dangerous, not acting as b1, and doing things b1 would not do. Taking regular thiamine HCL would not have raised your blood pressure; in fact there is studies showing it lowers blood pressure.
Back again Sunvox. Might get banned, and deleted again.
I suspect benfotiamine does not break down to thiamine in the body. Maybe it goes through unchanged or maybe it breaks down to some metabolites other than thiamine.
What proof do you have that once in the body the benzoyl group breaks off the sulfur atom in benfotiamine, and then the thiazole ring closes up leaving thiamine?
If I get banned again don't worry I wont come back. I can take a hint. I am just genuinely curious about benfotiamine.
I'm happy to discuss science with any and all. I am not a pharmacologist nor a chemist, and I know there are molecular differences between thiamine and it's derivatives, and of course I have no evidence that benfotiamine becomes "pure" thiamine once it enters the body, but as a patient with an illness, I'm no where near interested in the basic chemistry as I am in the results.
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The simple fact is that animal studies and human clinical trials of benfotiamine are finding neuroprotective benefits. Therefore given it's higher proven bio-availability and the fact that it is the choice of numerous respectable research centers including Columbia University, I have to ask why would a patient with SCA (my case) or Parkinson's try thiamine hcl first instead of benfotiamine.
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I, myself, have only just begun to experiment. I tried benfotiamine for a week and found that my blood pressure went up considerably so I stopped for a day, but the very next day I noticed changes in my body so last night I took 300 mg again of benfotiamine and this morning the "heavy" feeling in my legs is once again gone.
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Is benfotiamine chemically identical to thiamine? No, of course not. Is there research demonstrating potential neuroprotective value in thiamine? Yes. Is there research demonstrating neuroprotective value in benfotiamine? Also, yes. Question: As a patient making my own decisions based on the available research which do I want to try first? Me - my answer is benfotiamine. Might thiamine hcl turn out to be a better answer? You bet, but that's what I'm trying to figure out, and for sure, I don't believe the answer is a "slam dunk" either way, but thats the beauty of a website like this. I get to talk to people that are trying thiamine hcl and hear their results. One poster just this morning made me question myself. Her son has FA and has been taking thiamine hcl for months with great results, and she says there are other parents of children with FA who are having the same experience. That's some powerful evidence in favor of thiamine hcl.
Look in the literature on thiamine HCL, and you will see it lowers blood pressure, corrects abnormal lipids/cholesterol, improves circulation, normalizes blood glucose, improves insulin secretion, but your experience with benfotiamine had the opposite happen so it doesn't look good for benfotiamine. And look on amazon reviews at the critical reviews on it not the positive ones. Anyone can fake a positive review to promote a product. The inverse is true yes however I believe the negative reviews are honest.
Thiamine HCL exists in nature well not really but once it is dropped in water it becomes free thiamine, and that exists in nature. Benfotiamine does not. It's a general rule of thumb that naturally occurring= safe, and effective thats why people have success with thiamine HCL. How many Drs actually use benfotiamine to treat their patients Parkinsons, and other disease rather than use thiamine HCL. That would be relevant. Compare the two in the clinical setting.
Now you're talkin' . . . Although I don't agree that just because something is "natural" it is inherently better, I did like your advice of checking Amazon reviews which I just did and found two other people taking Benfo who reported an increase in blood pressure. Now THAT plus the poster from this morning is convincing me I need to try thiamine hcl myself and see if my blood pressure goes back to normal.
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Thank you for patiently discussing the facts.
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I'm leaving for work today and don't expect the thiamine hcl to arrive until next week so it may be a couple weeks before I can report back on changes, but I'll be very interested to see what happens next.
1)Currently no clinical study exists that shows 4,000mg oral HCL/daily for Parkinson’s without side effects in short or long term. It is the intramuscular 100mg injections twice a week which came up without side effects at Dr Constantine study for Parkinson’s. However, though rare, side effects are reported, like heart palpitation, nausea, allergic reactions,urticarial, etc.
2)If HCL is so powerful why there is not available in a liposomal form? The technology is currently inexpensive and widely available. That would considerably increase the low bioavailability of thiamine HCL up to multiple times and minimize the dosage pills and any possible (if any) side effects.
3)According to the study “Plasma thiamine concentrations after intramuscular and oral multiple dosage regimens in healthy men” ncbi.nlm.nih.gov/pubmed/161... : oral thiamine hydrochloride when given over a 1-week period produce blood levels that approach those obtained by intramuscular administration.
Therefore oral administration of 200mg Thiamine HCL for 7 days should produce the same results as 2x100mg intramuscular injections right? i wonder how many (if any) patients of Parkinson’s have been treated with 200mg thiamine HCL/daily. Why a megadose of 2,000-4,000mg of thiamin HCL is the suggested oral dosage (allegedly by Dr C.) in the course of 1-2 months? Possibly the real facts contradict current studies or bioavailability and methods differ for Parkinson’s.
4)The exact mechanism of HCL in the brain of Parkinson’s patients is not investigated and it is currently unknown. A possible explanation is that thiamine may increase the density of the dopaminergic receptors (d1) like Sulbutiamine induced in animal experimental studies ncbi.nlm.nih.gov/pubmed/109... . At the presence of increased dopaminergic receptors levodopa efficacy may be increased as well, therefore the positive effects. Of course the exact mechanism of action may be completely different. However it appears that thiamine HCL is not “the cure”, and possible benefits may start to wean off after the end of treatment. No wonder why Dr ConstantinI suggests that the patients continue their usual medication including levodopa.
5)It is true that Benfotiamine is not a real ‘lipid-soluble' thiamine precursor and it’s not a disulfide but a derivative. Oral administration of benfotiamine is able to cross the plasma membranes but not the cell membranes. Benfotiamine leads to significant increases in thiamine, THMP and THDP levels in blood, liver but not in the brain. Its beneficial effects of concern peripheral tissues but not the central nervous system.
However Parkinson’s, MSA and other Parkinson’s syndromes also affect the peripheral system not just brain. Therefore Benfotiamine may exhibit specific effects (or not) in the peripheral system of those patients. Benfotiamine is discussed at the following paper bmcpharma.biomedcentral.com... .
Roy, a member of this forum, experienced benefits with “mega Benfotiamine” and didn’t report any side effect healthunlocked.com/parkinso... .
6)What about Allithiamine? it is the only natural highly bioavailable lipid disulfide and can be administered at much low dosages. Why HCL is better than Allithiamine for Parkinson’s?
7)Actually (and unfortunately) many neurologists currently don’t consent on the use of parenteral thiamine HCL for Parkinson’s unless a thiamine deficiency is proved. So far oral administration of thiamine in any form has not been documented in any study for Parkinson’s.
I'm at work and on an iPad so this will be relatively brief but I just want everyone to understand where I'm coming from:
A) I have spinocerebellar ataxia type 1; it is very similar to Parkinson's but faster and always fatal
B) I made myself symptom free using a combo of supplements, exercise and diet
C) my interest in thiamine is as an aid to what I am already trying
D) I took benforiamine for a week and I felt it was beneficial to me
E) multiple patients with Friereichs Ataxia are reporting thiamine hcl pills (Benerva) are helping at a dose of 200 mg twice a day
F) i think benfotiamine made my blood pressure rise and I found others online reporting similar adverse reaction to bento so I'm interested to see if thiamine hcl gives me the same improved feeling in my legs without the increase in blood pressure
G) I expect to exercise and take supplements everyday of my life because I do not expect gene therapy will be available during my lifetime.
H) although doctors are not on board yet I think there is ample evidence out there to indicate that thiamine can have neuroprotective benefits. The question for this thread is thiamine or a derivative and why?
My current "stack":
1) trehalose 40 g daily in coffee plus 3 or more squirts of Trehalose infused water in my nose
2)Niagen 500 mg twice a day
3) at the moment 300 mg benfotiamine a day
4) 2000 IU vitamin D daily
5) a B complex vitamin
6) pyrroloquinone quinone 20 mg daily
But I combine that with 30 minutes daily exercise and a mostly vegetarian diet. It is my opinion that this regimen can stop the progression of many neurological disorders like Parkinson's, Huntington's, and Ataxia in people that are either presymptomatic or have only early mild symptoms. If you read my posting history you will see I provide extensive research links for all my reasons. I also believe exercise at least 4 days per week at 80% max heart rate for 30 mins is the most important part of my regimen.
Exercise is the most effective drug to my experience, especially intense exercise with treadmill. There is a large clinical trial under way "Effect of High-Intensity Treadmill Exercise on Motor Symptoms in Patients With De Novo Parkinson Disease: A Phase 2 Randomized Clinical Trial" ncbi.nlm.nih.gov/pubmed/292... .
2x 500 mg Niagen? This is huge dosage! Do you experience any benefits or increase energy with Niagen alone?
Do you still experience high blood pressure with Benfotiamine 3x100mg? Possibly Benfothiamine affects your your disease in a different way. I read accounts of people with Ataxia benefit with Thiamine HCL
Also if you read my previous posts you will find a wealth of information on Niagen and why I take what I take. I realize we all have busy lives and searching takes time so I will summarize - I have been taking Niagen for almost a year. I also have been giving it to my father and my aunt both of whom have SCA1. Niagen is a relatively newly available form of vitamin B3 that does not cause flushing, is more bioavailable than nicotinamide (NAM), and acts as a sirtuin activator and not as a sirtuin inhibitor, and most importantly, there are now 2 completed human clinical trials that have shown NR increase NAD+ dramatically and is safe at doses of 1000 mg a day. Finally over the course of the last year I tried different dose levels and found that at 500 mg daily I did not feel any benefit, but at 1000 mg I felt considerable benefit mostly in the stiffness of my leg muscles. Last - my father and my aunt have been taking 500 mg twice a day for nearly a year although sadly my father entered a nursing home in January and until just this past weekend they stopped giving him NR and his condition immediately worsened in that he became unable to stand on his own in the bathroom. They are just this week restarting his NR, and I have hopes it will prove beneficial once again.
A HUGE thank you for sharing your treatment regimen. I have been diagnosed with ataxia and other neurological dysfunction. Dr's won't give me a disease diagnoses because I have a documented pesticide poisoning (Roundup is not as safe as table salt). I believe I have MSA. Any direction for therapy is sincerely appreciated.
If someone doesn't want to buy thiamine di phosphate or the two forms from garlic then it is possible to make home made liposomal nutrients. I tried it with thiamine HCL however it didn't seem to mix well even though it is highly water soluble maybe to do with the low pH or low density of thiamine HCL. It separated out into phases sometimes after sonicating where as other home made liposomal nutrients I made did not. It might be better to try it with thiamine mononitrate powder which is available from a website in USA.
Here is the recipe
In 100ml water add
8g thiamine mononitrate powder (assuming it is up to 8g/100ml water soluble). Thiamine mononitrate will be pH 6-7 in water, and the optimal pH for liposomes is 6.5 so this is perfect.
8g pure ethanol (grain alcohol from alcohol shops /everclear or 99% ethanol is sold as fire starter gel) or if not ethanol DMSO or isopropyl alcohol or acetone.
8g glycerol aka vegetable glycerin
16g soy or sunflower lecithin granules
Blend well then sonicate in glass jar in water filled jewellery cleaner for one hour. Drink 1g worth a day (divide the final weight of the solution by 8 to figure out how much that is). All those numbers can be changed if wanted.
There is a facebook group called liposomal vitamin c where they discuss how to make home made lipo c, and other nutrients for more info.
I cannot verify by any reliable source that the procedure described above can produce functional and stableThiamine liposomes. The end result will be possibly a mix of thiamine and phospholipids particles or unstable mega-liposomes, not suitable for human use, with degraded thiamine structure. Moreover what applies for vitamin C liposomes does not apply universally for any other compound as factors such as molecular structure, weight, and solubility differ.
The development of functional multi-layer Nano-liposomes is much more complex than homemade recipes which unable to verify the final result. (1) liposome size, 2) actual amount of liposomes, 3) quality, 3) structure, 4) homogeneity, 5) integrity, 6) stability etc).
Home-made manufacturing will require multiple experimentation with a single compound and special equipment to possibly develop stable bi-layer liposomes which would be small enough to qualify for human use. This procedure is difficult to achieve and the end result should be verified with Transmission electron microscopy.
Sonication (which requires equipment) is generally considered a "gross" method of preparation and it may be further damage the structure of the compound to be encapsulated. There are other more reliable methods developed for human use and employed in industrial scale.
The Following from wiki:
Manufacturing
The choice of liposome preparation method depends, i.a., on the following parameters:
1) the physicochemical characteristics of the material to be entrapped and those of the liposomal ingredients;
2) the nature of the medium in which the lipid vesicles are dispersed
3) the effective concentration of the entrapped substance and its potential toxicity;
4) additional processes involved during application/delivery of the vesicles;
5) optimum size, polydispersity and shelf-life of the vesicles for the intended application; and,
6) batch-to-batch reproducibility and possibility of large-scale production of safe and efficient liposomal products
The one suggested it's Fursultiamine (TTFD) (as thiamin tetrahydrofurfuryl disulfide). Natural Allithiamine is from garlic as Thiamine allyl disulfide (TAD). Fursultiamine is missing the Allyl group. I don't see the above company has a functional web site, other than a page with a phone number.
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I linked to those studies above as well. Those human clinical trials as well as the completed trial in alcoholics were what convinced me to try 300 mg twice a day. The benfo I was taking came in 100 mg pill form:
High Dose Thiamine / B1 / Thiamin
PD needs paradigm shift: eg, Alzheimer's, HSV1, P. gingivalis, amyloid-beta and tau are antimicrobial peptides.
