A few questions about how the B1 Therapy is currently administered, and an idea on how to improve results.

[billbobby]

First question I'm wondering about is those of you who have been experimenting with B1, what methodology have you been using to try to find the correct dosage?

Also, what method does Dr. Constantini recommend for determining the individual dosage amount needed for each person?

A thought I had was if doing pill stops could be an effective tool to help dial in the B1 dosage to the specificity needed for each individual. So perhaps increase the B1 in 200 mg increments for 10 days, and then stopping ingestion of B1 for 2-5 days to see if any significant positive effect is seen at any time period during this pill stop. It's a methodology that works for finding the optimal L-dopa dosage for those that use Mucuna, so perhaps it could be of value in finding the optimal B1 dosage as well.

So if no positive response is observed during the pill stop, you then increase the dosage again, and repeat the process until either a negative response occurs from an increase in B1, which would potentially indicate that the pill stop method doesn't work, or that you jumped over the needed dosage.

So for example lets say your optimal B1 dosage is 850 mg. You take 800 mg for 10 days, do a pill stop, and do not observe any benefit from doing so. Thus, you increase to 1000 mg. At 1000 mg, you begin experiencing negative side effects from the B1 because you have pushed past your therapeutic dosage need of 850 mg. If you can't make it the 10 days because of the severity of side effects of the excess B1, you could decrease it by 100 mg, observe effects, then go from there.

The best way I think to find out whether or not pill stops could work for B1 is to see how consistent blood levels are from concurrent administration of B1. Questions that need to be answered:

What are blood levels of B1 prior to starting B1 intake, i.e. baseline levels?

How many days of concurrent intake of a static dosage are needed for consistent and reliable systemic concentrations of B1 to stabilize? This would be the minimum amount of days needed to stay on a dosage before doing a pill stop.

After this, doing 2-3 tests every day during the pill stop days to see if the blood levels of B1 drop in a reliable and predictable fashion. If they do not, then pill stops probably will not work, but if they do, then it could be a tool that could assist in finding the individualized dosage need for every patient.

Just as people need varying levels of L-dopa to compensate for the dysfunction of the dopaminergic neurons, the same is likely true of Vitamin B1. It's essentially a relative nutritional deficiency of Vitamin B1.

"An absolute nutritional deficiency occurs when nutrient intake is not sufficient to meet the normal needs of the system, and a relative nutritional deficiency exists when nutrient intake and systemic levels of nutrients are normal, while a change occurs in the system that induces a nutrient intake requirement that cannot be supplied from diet alone." Source: ncbi.nlm.nih.gov/pubmed/226...

[Fed1000]

I started with B1 in the form of pills last August with a 300 mg. dose with gradual increases of 100 mg. in 100 mg. every 20/25 days. I am currently taking B1 in the form of injections of 0,70 mg. having started with 0,50 mg. with increments of 0,10 mg. every 20/25 days. I think I stay on this amount because the results are excellent.

The equivalent Intramuscular administration of thiamine would be:

- for 2 grams/day orally = 1 x 100mg. injectable solution per week;

- for 3 grams/day orally = 2 x 75mg. injectable solution per week;

- for 4 grams/day orally = 2 x 100mg. injectable solution per week.

In order to obtain the same effects of the intramuscular dose, the oral dosage should be around 140 times higher. For instance, 100 mg. injected once a week have the same therapeutic effect that 2 grams per day x 7 days (total 14,000mg. thus times 100mg.) have if administrated orally. Dr. Antonio Costantini

[bassofspades]

I think you have to do 30 day pill stops. It takes that long to see a result. L dopa metabolizes much faster.

[billbobby in reply to bassofspades]

Interesting, I wasn't aware of the metabolic rate of B1, but that does make sense. Do you know if it takes 30 days for systemic concentrations to get back to baseline or how much a decrease are we talking about? To give an illustration of what you need to do using numbers. Imagine 200 mg gives a systemic value of 500, 400 mg gives a systemic value of 1000, etc. You don't need the pill stop to drop systemic values all the way back down to baseline of 0, you are just trying to have the systemic values go through the range of 500-1000, which perhaps wouldn't take as long.

[bassofspades in reply to billbobby]

I can't claim to really know exactly how it is stored or how it ebbs and flows throughout the protoplasm. We can think this out together perhaps.

We're using water solvable B1, so im not sure it builds up in the system at all. My theory is that it fuels the mitochondria which makes everything work better (remember, some say pd is a mitochondrial disease as well) then, when the person starts to heal, the required amount is less. Hence, my need to constantly adjust my dose.

I don't know that this is true, just a guess. But I don't think it works the same way as Levadopa, an amino acid precursor to the neurotransmitter dopamine.

[bassofspades]

Just to elaborate, dr costantini costantini started me on 4g per day. After 30 days, to the day, i felt dramatically better. After 6 months i started feeling worse again and dr c said up it to 6g. If that doesn't help, take 30 days off and try 2g. I bounced around for a few months and after a long time of trial and error im back to 4g per day with weekends 0g to 2g per day. This seems to be working for me as i have been doing this for the last 10 months .

Of course there are other factors, such as i feel best when i fast at least 16-24 hours and i also use many other supplements.

I guess it's best to say this is not an exact science. But every pwp should probably at least try thiamine therapy. Its low risk compared to the potential benefits.

[chartist]

billbobby,

I think your dose escalation plan may work for some, but definitely not all. One problem with your dose escalation regimen is that some people have not seen any benefit until after seven months and others have reported no benefit until 3 or 4 months. I refer to these groups as "slow responders" and it would not be practical for these slow responders.

Initially, Dr. Costantini felt that the best way to treat his email patients was to use a few criteria to establish a general idea of what size dose might be best. One criteria was length of time since diagnosis. Another criteria was an approximate idea of how advanced the disease appeared to be based on symptoms. Another consideration was the physical size of the patient. In short, a lengthy duration since diagnosis generally pointed to a higher dose. More advanced symptomatology generally pointed toward a higher dose. A larger person generally may require a higher dose than a smaller person.

With all of the criteria above, he might start a patient at as high a dose as 4 grams total per day and see how they do at that dose. Often times the initial response might be positive followed by a loss of all positive benefits and sometimes a new worsening of symptoms that was worse than any symptom levels previously seen, clearly indicating an over dose of B-1. In such a case, he would have the patient stop B-1 for a week or so and during this time it was helpful for the patient to take precise notes about how they felt each day after stopping B-1. At some point the patient notices that the increased symptoms are now decreasing and knowing how soon that happens, as the notes will precisely determine, made it easier for Dr. C to determine the next dose he would like to try. If the improvement was seen within the first two or three days of stopping B-1, he might feel that you were fairly close to your optimal dose, so he may or may not cut the original dose in half , but with a quick response he was more likely to consider reducing the dose by a quarter, whereas if it takes a full week for increased symptoms to decrease, he would be more likely to suggest halving the original dose and repeating the process.

If your optimal dose is 4 grams, all testing doses short of 4 grams might be likely to have little to no effect, so starting with a relatively low dose of 200 mg/day and going one month at each dose, it could take about 20 months to reach that 4 gram dose! Most people may not be willing to go over a year and half with no apparent benefit and some people would just assume it does not work for them after 1 to 3 months. I think Dr. C was aware of this problem and this may be a partial explanation of why he chose to start at higher dosing in order to potentially reduce the time to see benefit so that patients are not lost to impatience. Only a guess on my part, but I know he wanted as many of his patients as possible to realize the potential benefits of HDT/B-1 and starting with a higher dose as opposed to lower dosing may have been part of the reason for starting higher because there was a better chance to see benefit in the shortest time. Once a patient saw just one good benefit from B-1, he knew that they would likely stick with testing it until they found their optimal dose, but if a patient saw no benefit for many months, chances were greater that they would just assume that B-1 does not work for them and consequently stop testing B-1.

Art

[alaynedellow]

If you read posts Art has collated you can see how others hv monitored B1. Dr C's last recommendations wwere to tirate dose upwards.

Improvents bad or good seem to take 3/4 weeks to sometimes happen. It not a stict length of time thing, some days it absorbed more. As Dr C says video self before n during n keep a log. It very easy to forget what altered otherwise. It , for some of us, not a quick month trial. Took me a year.

[rescuema]

Thiamine has to be attached to transporter to gain entry to cells but some people end up having various transporter issues that require much higher dosage so that even with the deficient transporters the thiamine could pass through the BBB through passive diffusion instead - this could only occur if the B1 concentration is high in the blood.

So while the pill stop method seems logical in majority cases, it does not apply to HDT at least initially. It's better to start high and then taper down. Be sure to supplement magnesium - it's a required co-factor. You may also opt for TTFD - this lipid soluble B1 form does not require transporters to be absorbed, valuable for those who are genetically compromised.

Thiamine blood test may show a normal level but a person can still be deficient due to lack of tansketolase enzyme transporter activity.

[billbobby]

All great replies everyone, thanks! Will do some more research and try to figure out if there is a better way to possibly do this.