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
Patients with Parkinson’s disease (PD) report a strong craving for sweets
Clinical severity in PD is determined by decline in cortical compensation
To speed up research and trials, we require financial support 
