Thiamine and Dr Costantini, what we know ... - Cure Parkinson's

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Thiamine and Dr Costantini, what we know and don't know

wriga profile image
42 Replies

Sorry this is so long, it is meant to be a summary, but there’s a lot to say.

There is now a wealth of information on the discovery by the Italian neurologist Dr Antonio Costantini that high dose Thiamine can be used to treat a range of neurological diseases including Parkinson’s disease. In Dr Costantini’s own words the conventional medical profession is totally indifferent to his findings even though he has published many scientific papers on the subject over the last 6 years and his team has treated more than 2500 patients often with remarkable results. Moreover Dr Costantini is totally open to consulting with patients who cannot travel to Italy using email and DOES NOT CHARGE for such consultations. I myself have consulted with him and have been very satisfied with his response and the fact that he sent me some 18 publications and files to read knowing that I am a research scientist and could well be critical of what I read.

Here I would like to resume what I understand to be the known facts of this discovery and also give my opinion of what I THINK MAYBE TRUE but for which I don’t yet have the proof.

Much of what I write here can be found in 2 threads on this site

healthunlocked.com/parkinso...

healthunlocked.com/parkinso...

WHAT WE KNOW

Dr Constantini is a clinical neurologist who has discovered that treating Parkinson’s patients (PwP) with high doses of vitamin B1, also known as Thiamine, over a relatively long period (months, years) gives excellent results and progressively relieves the symptoms of Parkinson's. In his clinic, this is done via injections of 100 mg of thiamine twice per week. For patients who cannot go to the clinic, after questioning and/or requesting a short video of the patient’s symptoms, he prescribes a dose of Thiamine HCl tablets to be taken in 2 sessions, one before breakfast and one before lunch. This starting dose is usually about 4 g of thiamine in total, some 40 times higher than the injected dose, presumably because the oral path is less efficient in getting thiamine through the gut and into the brain. This dose may be revised over time.

From the various papers that Dr Costantini has published we can see that this treatment appears to work on a whole range of neurological diseases, which means that there is a common cause of the problems and logically a common mechanism for the way thiamine helps treat the symptoms. As a clinical neurologist, Dr Costantini is primarily interested in finding therapies that work. If it provides a benefit, stay with it. If it doesn’t help, change something until it does. His approach is pragmatic. Most of these papers are online publications and don't have the credibility of peer reviewed professional journals. Nevertheless they are quite convincing.

Parkinson’s disease is known to be caused by the loss of function of certain brain cells that produce dopamine. Dopamine is a hormone and a neuro-transmitter. It is involved in controlling the transmission of nerve signals including those to muscle tissue that control movement. More precisely, dopamine is a neuro-modulator. Its presence is used to stop the transmission of nerve signals. A deficiency of dopamine allows unwanted nerve signals to be transmitted thus causing involuntary muscle tone or involuntary movement. As the disease progresses, a greater proportion of these cells either die or suffer damage causing them to produce less and less dopamine. Symptoms occur when the total production of dopamine falls to a level below that needed to maintain optimum control of the nerves. Dopamine acts by binding to a nuclear (dopamine) receptor in the synapse. Its binding inhibits the transmission of nerve signals, its release enables the signal to pass. There are at least 6 known types of dopamine receptors, depending on the type of synapse. These could be more or less responsive to different degrees of dopamine deficiency depending on their affinity to compete for the same dopamine source.

WHAT WE DON’T KNOW

Where does thiamine come in ? According to Dr Costantini’s publications, the loss of dopamine production is caused by chronic thiamine deficiency which causes damage to some brain cells and cell death.

He quotes “We hypothesize that motor and non-motor symptoms of PD could derive from a chronic intracellular thiamine deficiency, characterized by the following: (1) a severe and focal thiamine deficiency in the substantia nigra pars compacta and in other centers that are typically involved in PD, which could determine a progressive dysfunction and selective neuronal loss, and (2) a mild thiamine deficiency in all other cells, which could determine cell suffering.”

What is known is that thiamine is essential to the proper functioning of all cells and thiamine deficiency causes severe cellular dysfunction. What we don’t know however is whether PD patients actually suffer (or have suffered) from thiamine deficiency IN THE BRAIN. Thiamine levels in the blood are rarely deficient in western countries, except for chronic alcoholics and I have seen no proof of chronically low thiamine levels in (selected parts) of the brain, so as Dr Costantini says, this is purely a hypothesis. Nevertheless, when you massively boost thiamine levels, patients who suffer from PD or other neurological disorders show marked and sustained improvement.

Could thiamine be acting in other ways independent of Parkinson’s disease ?

“Thiamine is known to be involved in several cell functions, including energy metabolism and the degradation of sugars and carbon skeletons. Other roles that are connected to this vitamin are neuronal communication ...” S Manzetti et al. 2014. So giving a big dose of thiamine could affect fatigue/energy and nerve effects independent of PD. This doesn’t mean to say that Dr Costantini’s hypothesis is wrong, it’s just not proven.

If this hypothesis is true, then how does it work ?

The mechanism could be as follows : Some of the thiamine ingested gets into the brain and into the intracellular space of the substantia nigra. It is progressively taken up by the thiamine-deficient cells which gradually recover their good health and, over time, start to produce dopamine once again. This would not take the patient back to pre-Parkinson days. Some cells are dead and will never be regenerated. The mildly damaged cells may recover rapidly but the severely damaged ones would take much longer and may never recover totally.

How could this affect PD symptoms ?

My feeling is that this is a complex and selective process. I will try to propose a simplified story to give an idea of what might be happening.

When the supply of dopamine first starts to diminish, the body (and the affected neurons) will most likely adapt to keep things running as smoothly as possible. Synapses store dopamine for re-use and will use their reserves to try to function properly, so we don’t feel symptoms, at least not the full range of symptoms. Once the shortage of dopamine gets too bad, we will start to have synapses with depleted reserves and as a result they cannot fully shut off the nerve signals. They are leaking electrical signals, like a low-current short circuit. That will give us cramps, tremors and more. We feel the symptoms, but more importantly the synapses are themselves being damaged.

When the revived dopamine cells start to deliver more dopamine, do we go back to pre-symptom conditions ? Probably not. We now have damaged and leaking synapses with no reserves of dopamine. Even with a proper external supply of dopamine, they will take time to build up reserves and recover their proper health and function. This is the famous hysteresis effect I mentioned in an earlier post. The conditions that triggered the onset of symptoms will not be the same as the conditions that trigger removal of the symptoms. Just getting back to the same dopamine level will not be enough.

So now we can see that several time factors will come into play if the hypothesis that thiamine heals damaged dopamine cells is indeed playing out :

1) the time to heal damaged cells depending on the degree of damage sustained,

2) the time to build up a dopamine level well above the level at which symptoms were first felt,

3) the time for the synapses to recover their reserves of dopamine and to repair the damage done by leakage.

I suspect the first timescale will be the longest, although I may be wrong, but you no doubt get the idea.

The point I would like to make is that you must give the process enough time to get through all of these stages before you will see signs of improvement in the symptoms.

Finally, why do some symptoms appear earlier than others or take longer to clear.

I think that this could be related to types of dopamine receptors. There are 6 different types of dopamine receptors known. Each of these will have a different affinity for dopamine but they are all competing for the same supply of dopamine. The synapses having receptors with the lowest affinity will attract less dopamine than the others and will start to dysfunction first. The muscles served by these synapses will feel symptoms early in the process and will probably be the last to feel relief. It would be interesting to compare individual experience on this point.

In my case the use of high dose thiamine had absolutely no effect for three weeks. Then quite suddenly, my intense fatigue went away. One week later my stiffness improves considerably. Right now I’m typing this with painful hands and fingers that are curling up but I’m so much better than before.

So that’s my personal analysis on what we do and don’t know, but also on what might be happening if Dr Costantini is right. Let’s hope he is !

All your comments and criticisms are welcome. This is not my field of expertise.

If this is true think of what happens to the poor suffering synapses when you take L-dopa

Albert

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wriga
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42 Replies
AmyLindy profile image
AmyLindy

Yayyyyy Albert! Reasonable, very thorough review and summary-thank you! Frank Church in NC /usa & Dr Gary Sharpe UK are also scientists & PWP. Google or Facebook them!

wriga profile image
wriga in reply toAmyLindy

Hi Amy, found Frank C Church on Researchgate, He has papers on Parkies, thanks

Gary Sharpe is not there

AmyLindy profile image
AmyLindy in reply towriga

Gary Sharp or Sharpe is in UK. And on Facebook where he submits himself to all sorts of trials and compares against existing research /published papers.

jaybird53 profile image
jaybird53 in reply toAmyLindy

AmyLindy glad I found you on here. Looking to see if there’s a way to transition from Hinz method as this sound much simpler. Funny both deal w B vitamins but I can’t mix Hinz B6 w Costantini ‘s B1(Thiamine) . There had to be a catch.Jaybird

Dee1980 profile image
Dee1980

Thanks for that!

I'm having a bit of a look into thiamine, got my dad on benfotiamine but as I understand it, it doesn't cross the BBB. Looks like Dr Costantini is right about it being used for a lot of neurological disorders:

autismrc.com/2016/04/16/aut...

in reply toDee1980

2 x day (morning 2g and 5 pm 2g) Vitacost vitamin B1 (as thiamin HCL) 500mg, easy swallow capsule

Dee1980 profile image
Dee1980 in reply to

Thanks, I'll try to source some now!

carpark profile image
carpark

Excellent analysis! Thank you for sharing!

Kia17 profile image
Kia17

Great review Albert. Many thanks

wriga profile image
wriga

Small afterthought : Timescale 3 could be very short but complex. When people take L-Dopa the effects are felt in 20 minutes and fall off fast also, so dopamine reserves in the synapses are depleted and filled quickly. Synapse damage could be different, but L-dopa could help since it gives a rest from leaking. Could be useful to take L-dopa with thiamine to help synapse healing if they are indeed damaged by leakiing signals.

in reply towriga

Doc Costantini advises PwP to take L-dopa with thiamine

in reply towriga

"The suspension of ropinirole is necessary because the right dose of thiamine could make no other treatment necessary. We calculate the right dose beyond the improvement of the symptoms also on the reaction to the pull test. The dose we plan to stop the progression of the disease forever will greatly diminish your symptoms. If there is any small thing left we will make it disappear with small doses of levodopa, which will never cause you the late effects that depend not on the duration of the treatment but on the progression of the disease. So in 10 days you will let me know about the suspension of ropirinol and the result of the pull test and we will see how to adjust."

wriga

wriga profile image
wriga in reply to

Thanks for bringing this out again Roy,

That was indeed a very encouraging and brave statement. I hope it ages well.

I couldn't put it in this post as it was already quite long.

Astra7 profile image
Astra7

Thanks for great summary

nellie58 profile image
nellie58

What is the pull test?

wriga profile image
wriga in reply tonellie58

It's described in a reply in the first link above. .. + video posted by kia

nellie58 profile image
nellie58 in reply towriga

Found it! Thanks.

Despe profile image
Despe in reply towriga

Video is not playing on my computer.

Thanks for a JOB WELL DONE, wriga! My husband's symptoms are tremor RH and RF. Lack of energy and brain fog. Has not started any meds as the neurologist at Mayo advised. He is on pelvic floor rehab as the FM physician at Cleveland prescribed.

Shall we suspend this protocol and start Dr. Constantini's?? Should he start levodopa now or after I contact Dr. C? Should it be L/C or only levodopa?

Thanks a million!

wriga profile image
wriga in reply toDespe

Hello Despe.

Obviously I'm not qualified to give you any advice on how you should or should not proceed with medication, so I'm not going to.

I started on 2.5g Thiamine 5 weeks ago. I had practically all the known symptoms : brain fog, disorientation, severe stiffness, terrible leg pains, cramps in feet and hands, curling toes, extreme fatigue, LH tremor, neck and face pain. Today I played a round of golf no problem. Still some cramps in one hand and foot and the tremor. All the rest has gone suddenly in the last week !

What else can I say.

Despe profile image
Despe in reply towriga

I am so happy for you and everyone who gets better on any form of medication, conventional or alternative.

Despe profile image
Despe in reply towriga

Are you on L-dopa? Thank you.

wriga profile image
wriga in reply toDespe

I started on a very low dose of ropinirole and I'm cutting down to zero. No problems.

in reply towriga

Hello Wriga, I am so appreciative of your research and this post. I understand Dr. Constantini hypothesized that the HDT can protect the dopaminergic neurons. I would think whether his hypothesis is true could be determined with the 2,000+ people he helped. If many or most stabilize, that would be strong evidence that the neurons are being protected . Do you believe such evidence exists?

I am trying to determine if I should be taking HDT as a proactive and preventative measure to protect my neurons. I am 46. My symptoms are subtle. I’m not on CL.

Additionally, would the thiamine be compatible with Ambroxol and Exenatide?

Given that the manner by which it works is uncertain, I too am uncertain of this.

On a different subject, I wonder your thoughts on Quercitin which I hear is being trialed at the Mayo Clinic

M1tz1 profile image
M1tz1

Thank you so very much, Wriga, for all the effort that has gone into this on our behalf. Bless you.

wriga profile image
wriga

Today I found some research articles on damage to synapses in Parkinson patients. It seems it occurs at the same time and with the same severity as the damage to dopamine producing cells. This is related to a-synuclein deposits that may block the transport of dopamine across the synapse gap. So there are probably two damage centres to be repaired to make the nerves work properly : dopamine producing cells and synapses that make the nerve connections. These are not in the same place. Does Thiamine manage to repair both ? Now that would be a scoop.

wriga profile image
wriga in reply towriga

So don't forget that these replies I'm giving here still belong to "what we don't know " but are part of a credible hypothesis that needs to be tested.

Having two types of dysfunction fits the hypothesis.

1) loss and damage to dopamine producing cells in the substancia nigra causes a reduction of dopamine available to all neurons in the brain. This will affect all neurons that use dopamine as their neurotransmitter in their synapses, It's a general dysfunction that can be resolved by providing extra dopamine by meds like L dopamine.

2) damage to synapses is much more specific. Each type of synapses connects nerve signals to different parts of the body. Some use dopamine as neurotransmitter, many use other neurotransmitters. For the dopamine synapses there are different receptors for different nerves. You see where I'm leading ? Damaged synapses will cause different types of symptoms. This fits our experience as PwP. We all have different symptoms at different times.

We need a solution that repairs or improves both of these types of damage centres. Current meds only target the first one.

Erniediaz1018 profile image
Erniediaz1018

Thank you for the detailed breakdown.

Greenday profile image
Greenday

Wriga, possibly the answer of thiamine as a treatment for PD can be found next to your doorstep from LES LABORATOIRES SERVIER in France who developed the medicine Arcalion Subultiamine, a highly bioavailable Thiamine derivative; the Labs hold multiple patents and studies patents.google.com/patent/U... since 1997 for the treatment of PD and other disorders with a dose of 400-800mg Subultiamine. As a former chemist in France it would be easier for you to contact the labs and ask for more information regarding their studies on PD. The same medicine has been used for many years for the treatment of fibromyalgia, asthenia and fatigue. The medicine is currently sold as Arcalion in France and Europe. Dr Costantini possibly didn't bother with sulbutiamine since its use for the treatment of PD is patented or for other reasons I am not aware of.

"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." According to the patent the study included a placebo group.

Can you post a link to the reference on synaptic damage please?

Any thoughts about the interaction of Tyrosine hydroxylase and Thiamine?

tbirchf profile image
tbirchf

Thank you for your very informative post. My husband started Dr. Constatini's protocol about a week ago and we were a little discouraged because we haven't seen any significant improvements yet, so I was thankful and encouraged to read your results came after 3 weeks of thiamine!

in reply totbirchf

It is said it takes up to four months to be fully effective. Quoting Doc. Constatini. But for me and I read others testimonies some results in a matter of weeks. Keep the faith as the alternative is progression of Parkinson

wriga profile image
wriga

Think of Parkinson's like a poor ficus that has been neglected for years with not enough water and light in the doctors waiting room. Now you're going to take care of it. Make sure that you give it enough water (thiamine) and light (love) every day. This ficus is suffering, everything hurts. First its roots need to get well. Later small green shoots will appear and maybe some branches will never recover but with care and time it will no longer suffer.

Gioc profile image
Gioc in reply towriga

Bellisssssssima!

VERy VERY BEATIFULL!

:-)

To answer my own question

unboundmedicine.com/medline...

wriga profile image
wriga in reply to

I'm away this weekend, will try to reply to you in a few days. Thanks

wriga profile image
wriga

Retry,

I read on another post that you have some neuroscience knowledge, certainly more than mine so any exchange would be useful.

The ref to synapses damage is here.

frontiersin.org/articles/10...

He concentrates on damage to synapses In dopamine producing neurons and asks the " chicken/ egg question. Are PD symptoms caused by these cells dying or is their death caused by damage to their axon synapses that then blocks the release of dopamine.

My question goes one stage further ... There are neurones in the brain that use dopamine as a transmitter but do not make it. what happens to their synapses when they receive a signal to release dopamine to the synapse cleft, but non is available ? Surely such synapses are stressed. This happens frequently to those on prescription drugs. Does this stress cause damage or some kind of compensation in the long run ?

in reply towriga

The quick answer is I don’t think anybody knows. I’ve a feeling that it might be sites like this that work out some of answers.I am working on a different type of model for idiopathic Parkinson’s

.. This model has a series of conceptual blocks Which can then be populated by various disciplines such as biochemistry,neuroanatomy physiology and pharmacology. We start simple and see what happens happens

The synapse damage paper is very interesting and deserves serious study

wriga profile image
wriga

The critical event in Parkinsons is when dopamine is In short supply at the terminal synapse of the axon. This is dopamine depletion and will cause stress in the synapses. How will the synapses respond? The answer is called neuron plasticity, a means to adapt to the lack of dopamine. It involves physical changes to the synapse including perforation ! That's real damage that will take time to heal on the condition that the dopamine depletion is permanently stopped. This does not happen with short term acting prescription drugs but may be the case if thiamine actually repairs neurons.

The following paper gives some insight into the subject.

ncbi.nlm.nih.gov/pubmed/252...

and another

researchgate.net/publicatio...

There are plenty of recent papers on this "novel concept"

ncbi.nlm.nih.gov/pubmed/243...

LAJ12345 profile image
LAJ12345

Can people please list the brand names of the thiamine they are taking orally? Where do you buy such high concentration doses?

Has anyone tried Benfotiamine natural source which is more bioavailable at lower doses instead of the stronger synthetic form? As it is fat soluble does it build up in the body ?

Kia17 profile image
Kia17 in reply toLAJ12345

Thiamine HCI ,Solgar brand from iherb.com

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