Amazoniac
Member
To take? I would compare with the lower dose because it might suffice, or renewing more often. In the experiment it was a single time.1500 at once?
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To take? I would compare with the lower dose because it might suffice, or renewing more often. In the experiment it was a single time.1500 at once?
I wonder if thiamine would work for ulcers and h. pylori similar to famotidine if you think the mechanism of action is the same, or if thiamine or famotidine would interfere with stomach acid and digestion since they inhibit CA.After findings the studies on synergism between thiamine and acetazolamide, and their combined use in a number of diseases I became intrigued. Then the wild thought just came out of nowhere - what if thiamine was also a carbonic anhydrase inhibitor but at different isoenzymes and with different effectiveness.
It looks like my hunch was correct. Plain old vitamin B1 (thiamine) is not only a carbonic anhydrase inhibitor, but it is about as effective as acetazolamide on average, and more effective at certain isoenzymes of CA. Since thiamine and acetazolamide have about the same effectiveness, this may explain why similar doses of the two substances were used in the studies I posted earlier today.
Inhibition of mammalian carbonic anhydrase isoforms I, II and VI with thiamine and thiamine-like molecules - PubMed
"...Here we determined the in vitro inhibitory effects of 5-(2-hydroxyethyl)-3,4-dimethylthiazolium iodide (1), 3-Benzyl-5-(2-hydroxyethyl)-4-methylthiazolium chloride (2) and thiamine (3) on human erythrocyte carbonic anhydrase I, II isozymes (hCA I and hCA II) and secreted isoenzyme CA VI. K(I) values ranged from 0.38 to 2.27 µM for hCA I, 0.085 to 0.784 µM for hCA II and 0.062 to 0.593 µM for hCA VI, respectively. The compounds displayed relatively strong actions on hCA II, in the same range as the clinically used sulfonamidesethoxzolamide, zonisamide and acetazolamide."
"...the slow cytosolic isozyme hCA I, compound 1 behaves as a moderate inhibitor, with a KI value of 2.27 μM. Compound 2 and thiamine 3 showed better inhibitory activity when compared to the previously mentioned compound 1, with KI values of 1.15 and 0.38 μM (Table 1). Thus, the 4-amino-2-methyl-pyrimidin-5-yl moiety improves hCA I inhibitory activity. AZA is also a strong hCA I inhibitor with this assay and KI of 0.27 μM, whereas thiamine, ZNA and EZA were more powerful inhibitors than AZA (Table 1). A better inhibitory activity has been observed with compounds 2 and 3 for the inhibition of the rapid cytosolic isozyme hCA II (Table 1). Compound 1 showed moderate hCA II inhibitory activity with a KI value of 0.784 μM (Table 1), whereas thiamine was quite an effective hCA II inhibitor, with a KI value of 0.085 μM, (Table 1). Similar to hCA I, 4-amino-2 -methyl-pyrimidin-5-yl moiety strongly influences hCA II inhibitory activity as well. Compounds 1 and 2 were relatively weak inhibitors for hCA VI, whereas, 3, EZA and ZNA were moderate inhibitors of the secreted isozyme, with KI of 0.050–0.095 μM. A better inhibitory activity has been observed with AZA for the inhibition of the secreted isozyme hCA VI (Table 1)."
So, I think this is a pretty important find for several reasons:
1. Thiamine activates pyruvate dehydrogenase and inhibits pyruvate dehydrogenase kinase. This optimizes glucose metabolism into CO2.
2. Thiamine inhibits carbonic anhydrase about as effectively as acetazolamide, which means that not only it stimulates CO2 production but it also inhibits its degradation. I don't know of another drug that does both of these things.
3. In similar doses, thiamine can substitute for acetazolamide in those people that do not have access to acetazolamide or are unwilling to take a prescription drug. In addition, thiamine and acetazolamide are synergistic as mentioned in the studies on mental health I posted earlier today, so in theory one could get away with much lower doses when using both substances together. For instance, there is some data showing that 250mg acetazolamide + 300mg thiamine is as effective as 750mg - 1,000mg acetazolamide in terms of raising CO2.
4. The highest concentration of thiamine is required to inhibit hCA I and it is 380nM/L. This figure from a human study on the pharmacokinetics of thiamine shows that this concentration is achievable using a 1,500mg dose. Th concentration required to inhibit the other isoenzymes of hCA were 85nM and 62nM, which are easily achieved with a thiamine dosage of 300mg - 500mg. In order for acetazolamide to inhibit hCA I, the concentration required is not far off of that for thiamine. This would explain that doses of 2g acetazolamide daily, which given the long half life of the drug will likely reach the concentrations required to inhibit hCA I. But more importantly, a 1,500mg of oral thiamine has been shown to be well tolerated and without any serious side effects. In fact, an human study on Alzheimer treatment with thiamine used 1,500mg doses up to 5 times a day and did not observe any toxicities. But given the synergism of thiamine and acetazolamide, one can probably get the full effects by taking lower doses of both substances together. Alternatively, if only partial inhibition of hCA is OK for your goals then 300mg - 500mg of thiamine should suffice. These lower doses are in line with Peat's recommendations of taking 300mg thiamine every 4 hours if a person has degenerative conditions.
Thoughts?
The reason is probably that acetazolamide is associated with increased levels of ammonia. At least, that the official data. So, in people with bad liver function and inability to convert ammonia to urea this can become an issue. I would like to hear Ray's take on it since he says increased CO2 is the primary way to dispose of ammonia by converting it to urea. This means that if acetazolamide is bad for liver it could be due to something specific that the drug does to the liver and nor its CO2-increasing effects.
High dose thiamine hcl resolves ammonia, so perhaps Acetazolamide does also.Are they saying now that Acetazolamide inhibit Ammonia ?
Blossom, Eight years on, are you still taking high dose thiamine hcl?I'm liking the thiamine better than acetazolamide. Thanks haidut, such_saturation and aguilaroja for your contributions to this thread.
No, I no longer seem need it fortunately.Blossom, Eight years on, are you still taking high dose thiamine hcl?