I have posted about this before and even linked to the references that these graphs are from but I think that all of us that are taking high doses try to understand how much of it is in our system
Blood Thiamine levels : I have posted about... - Cure Parkinson's
Blood Thiamine levels
thank you so much Retry, very interesting
How could a chart be if one used 100 mg I.m?
Afraid it can’t it’s oral dosing only
Thanks you very much.
It would have been interesting to see the concentration and the trend with 100 mg of thiamine HCL I.M. every 3/4 days, in my opinion it is quite different and one could emulate with the tablets taking them in high doses in a discontinuous way, one day yes and two no, but I'm not an expert.
Gio,
You might consider asking Dr. Costantini as he may know the answer to your question on IM thiamine since that is his preferred method of delivery.
Art
True I could ask him, but it's not that it makes me crazy with curiosity, just that all this problem on the dosage of the pills with the injections I've never had. The doctor's advice for me has always been 2/3 injections of thiamine hcl 100mg per week and stop. this has always worked very well without particular ups and downs. That's why I wondered if there were any differences. However I know only my experience, the doctor has seen thousands of cases treated with b1 the difference is obviously abysmal, better I ask to him.( next year )
A bit more....
5.2 Pharmacokinetic properties
Absorption: Thiamine is rapidly absorbed in humans, largely in the proximal small intestine. There are two mechanisms, one by a carrier mediated transport at low physiological concentrations (<2μM), one by passive diffusion at higher concentrations. Absorption is typically high, but intestinal absorption in humans is rate limiting.
Distribution: The average total amount of thiamine in an adult is approximately 30mg. In general the heart has the highest concentration (0.28- 0.79mg per 100g), followed by kidney (0.24-0.58mg per 100g), liver (0.20- 0.76mg per 100g), and brain (0.14-0.44mg per 100g). In the spinal cord and the brain, the thiamine level is about double that of peripheral nerves. The whole-blood thiamine content varies from 5 to 12μg per 100 ml, 90% of which is in the red cells and leukocytes. Leukocytes have a 10 fold higher concentration than red cells. Thiamine has a high turnover rate in the body and is not stored in large amounts for any period of time in any tissue. When intake is about 60μg per 100g body weight (or 42mg per 70kg) and the total body thiamine reaches 2μg/g (or 140mg per 70kg), a plateau is reached in most tissues.
Thiamine transport across the blood-brain barrier involves two different mechanisms. The saturable mechanism at the blood-brain barrier, however, differs from the energy-dependent mechanism described in the gut, and from the active transport system described in cerebral cortex cells, which may be dependent upon membrane-bound phosphatases.
The immunohistochemical distribution of TTP (thiamine triphosphate) suggests that it has a role in nerve conduction.
Metabolism: Thiamine is quickly converted to the diphosphate and to a smaller extent the triphosphate esters in the tissues. All thiamine in excess of tissue needs, as well as binding and storage capacity, is rapidly excreted in the urine in the free form. Stimulation of nerves causes the release of thiamine or the monophosphate with a concomitant decrease in the triand diphosphates.
Excretion: Thiamine is excreted in the urine. The half-life of thiamine in the body is 10-20 days. In addition to free thiamine and a small amount of thiamine diphosphate, thiochrome, and thiamine disulfide, about 20 metabolites of thiamine have been reported in the urine of rats and humans but only six have been conclusively identified. The relative proportion of metabolites to thiamine excreted increases with decreasing thiamine intake.
very clear and simple, thank you
the last chapter tells me that the b1 maybe eat the minerals. Better to eat lots of fresh fruit and vegetables.
Retry, What is your point? All these graphs tell me is that "bigger dose, bigger blood levels." Not earth shaking news! Also that the thiamin remains elevated in the blood for about half a day. Is there something else that I am missing? And can you give the link for your earlier post on this topic?
It looks like frequent smaller doses would keep the levels more constant than several large doses if it peaks at 4 hours? Say 500 every 4 hours during the day it would stay constant at the 80mmol/l level and the excess would be excreted? Otherwise two 1500 doses would be quite up and down. I presume that is worse for you?
Or maybe to work it has to be at maximum concentration for a little to get through. If there is a maximum rate it can be excreted rather than a maximum rate it can be absorbed by taking these supersized doses you are forcing the concentration in the brain up higher as it can't be excreted fast enough and you might need that really high concentration to get a little through to the brain. But if you over do it that little becomes a little too much then you feel worse. So you stop and wait until the excretion catches up and the brain concentration drops to the optimal level then start taking it again at a lower level which this time keeps the optimal level in your brain constant. (Just guessing based on people's stories.)
That might explain why lower doses don't seem to work very well. It is excreted as fast as it is taken so never reaches the correct level in the brain.
I think that’s about right. I am trying to build a spreadsheet model but I am short of data.
Even though the half life in the blood is 10-20 days that’s only at the low dose ......
....A large dose 1500 milligrams unless it is topped up is down to small dose levels within 12 hours. But this is only blood levels!!
It is difficult to understand how cellular life interacts with b1, another mine weak hypothesis that interacts with cellular calcium as per this research. But everyone can say his hypothesis. The urine could tell us something. It's enough for me the thiamine work.
ncbi.nlm.nih.gov/pmc/articl...
“The second group of experiments tested whether thiamine alters oxidant-sensitive aspects of calcium regulation including endoplasmic reticulum (ER) calcium stores and capacitative calcium entry (CCE). Thiamin diminished ER calcium considerably, but did not alter CCE. Thiamine did not alter the actions of ROS on ER calcium or CCE. “
Can’t find the original post at the moment here’s the reference for the graphs
What actually are these two graphs saying? What is the detail to the study? I assume these are in human? Are the drop-off when subjects stop taking thiamine? Please provide more detail. Thank you Retry.
Regards,
Mon
The full paper is linked to above. Basically 12 subjects took one dose of 1500 or 500 or 100 milligrams and blood levels were measured over time
The main takeaway is that the high dose is dealt with over 10-12 hours whilst lower doses remain stable and reflect a half life of 10-20 days
Imagine the blood concentration after an injection of 500mg IM as from the research you previously posted here. It would be interesting to know how is gone.
healthunlocked.com/parkinso...
that is
ncbi.nlm.nih.gov/m/pubmed/1...
ncbi.nlm.nih.gov/m/pubmed/8...
also this is interesting