Thiamine Is A Carbonic Anhydrase Inhibitor As Effective As Acetazolamide

[DaveFoster]

So you take 2/3 of a bottle of energen a day?

Ethanol potentiates the B-vitamins 15-20x. It's in the first page of the Energin thread.

 

[haidut]

Ethanol potentiates the B-vitamins 15-20x. It's in the first page of the Energin thread.

May be that's also the reason B vitamins go so well with drinking. A shot of Energin and some booze leaves me feeling a lot better than Energin or booze by themselves.

 

[Regina]

May be that's also the reason B vitamins go so well with drinking. A shot of Energin and some booze leaves me feeling a lot better than Energin or booze by themselves.

well duh. rolleyes:

 

[passivity]

Thiamine seems remarkably safe. I'm getting about 1,000 mg thiamine from Energin per day, and I'm going to make my own solution of thiamine HCL in ethanol to try to get up to the 3-5 g range per day.

I'll report back.

So did you take 3g+ a day? if so then did it make any difference?

Ethanol potentiates the B-vitamins 15-20x. It's in the first page of the Energin thread.

I posted another thread on thiamine and acetazolamide reducing cortisol. The scientists were aware of the increased need for electrolytes while on this therapy and had the patients drink 8oz of orange juice daily. It seems that was all the extra potassium people needed.

thanks.

 

[kitback]

So I got my Acetazolamide from Mexico yesterday and I am eager to start taking it, along with my thiamine. I will start with a low dose, 62 mg of Acetazolamide.
I am hoping to avoid the negative effects I have read about some people experiencing with it. Based on my reading, I understand I should not be taking aspirin or baking soda if I am taking Acetazolamide? Are there other things that I should avoid, such as seltzer, other types of soda?

 

[ken]

So why they want to lower carbon dioxide for copd sufferers? PulmoCare | Therapeutic Nutrition for People With COPD

 

[ken]

This is interesting, I know this is an older thread, but my 93 old mother has been hospitalized for three weeks. At the moment they have been trying to wean her off 100 % high flow oxygen. Her diagnosis is copd. Every time they reduce it o2 saturation falls straight into the seventys. To humor me the doctor agreed to give her some thiamine, in the middle of the talk about hospice. So a few minutes ago the nurse calls excitedly to say that when they reduced the flow today her saturation held. I asked him when they would start thiamine and he said" well I gave her a shot a half an hour before this, probably a coincidence ".
If it continues she can go to rehab nursing instead of hospice.

 

[haidut]

This is interesting, I know this is an older thread, but my 93 old mother has been hospitalized for three weeks. At the moment they have been trying to wean her off 100 % high flow oxygen. Her diagnosis is copd. Every time they reduce it o2 saturation falls straight into the seventys. To humor me the doctor agreed to give her some thiamine, in the middle of the talk about hospice. So a few minutes ago the nurse calls excitedly to say that when they reduced the flow today her saturation held. I asked him when they would start thiamine and he said" well I gave her a shot a half an hour before this, probably a coincidence ".
If it continues she can go to rehab nursing instead of hospice.

COPD sufferers do have high CO2 but it is as a result of their lung disease, not the cause of it. Not sure why they try to lower it, I guess another example of treating the symptoms, which in this case could be just protective adaptation.
Fascinating story about the grandmother. Does she have any lung disease? I would push for the B1 therapy to continue, at least 2-3 times weekly as injections and then as maintenance oral therapy of 300mg daily. Most people over age of 40 are thiamine deficient, and it has almost no side effects so no reason not to give it even as general prevention measure.

 

[ken]

The story continues a bit, after 30 hours her ability to maintain saturation fell off a cliff. I asked the nurse what her tsh was and the nurse looks at the computer and says 9. I kind of flip out, demanding t3 treatment. we will talk to doctor tomorrow. So I email peat who responds saying thiamine, niacin amide, acetalamide and 1 t0 2 mcg t3 every 3 hours. A young md friend calls back and says that once mentioned should be obvious treatment. Next day I'm working everyone, doctor is busy, so I see the nurse giving her some pills. What is she getting. This and that and synthroid. When did she start that? 4 days ago. Which is when I had pitched the thiamine and ask what her tsh was. When the the Doctor said 3, its normal. I had responded I would prefer zero. She was released to a nursing rehab today after her oxygen saturation had remained stable for 36 hours on 4 liters of regular. And it's actually my mother.

 

[haidut]

The story continues a bit, after 30 hours her ability to maintain saturation fell off a cliff. I asked the nurse what her tsh was and the nurse looks at the computer and says 9. I kind of flip out, demanding t3 treatment. we will talk to doctor tomorrow. So I email peat who responds saying thiamine, niacin amide, acetalamide and 1 t0 2 mcg t3 every 3 hours. A young md friend calls back and says that once mentioned should be obvious treatment. Next day I'm working everyone, doctor is busy, so I see the nurse giving her some pills. What is she getting. This and that and synthroid. When did she start that? 4 days ago. Which is when I had pitched the thiamine and ask what her tsh was. When the the Doctor said 3, its normal. I had responded I would prefer zero. She was released to a nursing rehab today after her oxygen saturation had remained stable for 36 hours on 4 liters of regular. And it's actually my mother.

Wow, amazing story! So, they refused to give her T3 and still went with T4?

 

[Antonello]

@patchpreset Me too. Took me a long time to figure out what the smell was from. I was also taking Swanson's- so I'm not sure if it's the brand or thiamine in general. If thiamine causes liver problems, it could be that our liver function is sub-optimal.

Where did u read thiamine causes liver problem?

 

[SB4]

Interesting. What is confusing me is I have read that carbonic anhydrase inhibitors cause an increase in mitochondrial respiration by increasing the levels of CO2. This study ( Cyclic AMP produced inside mitochondria regulates oxidative phosphorylation ) says that CAI decrease respiration by stopping bicarbonate from activating sAC -> cAMP -> PKA -> COX.

The only way I can square this hole is by saying that carbonic anhydrase inhibitors mainly work in blood in vivo, where the extra CO2 will increase O2 delivery to cells (Bohr effect); yet have not so much effect in mitochondria.

This study ( Cyclic AMP produced inside mitochondria regulates oxidative phosphorylation ) alludes to this saying both CO2 and Bicarbonate increase respiration despite different pH's but never explains how.

"Addition of the carbonic anhydrase inhibitor (CAI) acetazolamide, diminished COX driven respiration by 10% (p<0.01), indicating that CO2 diffusing through the mitochondrial membranes is converted into bicarbonate that activates sAC and stimulates COX."

"We note that, since OXPHOS activity is increased by both bicarbonate and by exogenously generated CO2, in a carbonic anhydrase dependent manner, these effects cannot be due to pH changes (or ionic strength), because bicarbonate addition increases pH while CO2 addition decreases it."

What am I missing here? Does CAI decrease OXPHOS but increases uncoupling?

 

[ruprmurdoch]

IF it does indeed inhibit carbonic anhydrase, then yes, it will have diuretic effect. Acetazolamide is a diuretic due to the increase in CO2, which extracts water from the cells and sends to the kidneys to excrete together with bicarbonate.

maybe just zinc + soda water is the simpliest substitute of acetalozamide, or my thinking is wrong ?

 

[haidut]

maybe just zinc + soda water is the simpliest substitute of acetalozamide, or my thinking is wrong ?

Zinc activates carbonic anhydrase.

 

[Highserotonin90]

To date, which form of thiamine do you suggest to buy?

 

[Alex Jaramillo]

I got some thiamine for Christmas and have been taking 100-300 milligrams a day. The sedative effects are noticeable for me.

 

[Highserotonin90]

I forgot: in case of PDH (Pyruvate dehydrogenase) deficiency, is it useful to combine B1 with alpha lipoic acid or can it be counterproductive?

 

[Alex Jaramillo]

Another thing I thought I would report is that thiamine has been increasing my libido

 

[Amazoniac]

Spoiler: Toxicology

Spoiler: Fundamentals of Biochemistry

• 043-Enzyme Activity & Rate Equations
• 044-Michaelis-Menten Equation
• 045-Kinetic Constants: Km & Vmax
• 046-Catalytic Efficiency; Lineweaver-Burk Equation
• 047-Non-Michaelis-Menten Kinetics
• 048-Irreversible Enzyme Inhibition
• 049-Competitive Inhibition
• 050-Other Reversible Inhibitors
• 051-Allosteric Regulation; Summary of Enzyme Regulation

- Enzyme inhibitor - Wikipedia

Spoiler: Types of inhibition | AK Lectures

• Competitive, Uncompetitive and Noncompetitive Inhibition (Part I)
• Competitive, Uncompetitive and Noncompetitive Inhibition (Part II)

Spoiler: Lippincott’s Illustrated Reviews: Biochemistry (978-1-60831-412-6)

- Enzyme inhibitors | University College London


- The difference between Ki, Kd, IC50, and EC50 values | The Science Snail
- An Intuitive Look at the Relationship of Ki and IC50: A More General Use for the Dixon Plot

- IC50 - Wikipedia

⬐ [22] Relationship between the inhibition constant (KI) and the concentration of inhibitor which causes 50 per cent inhibition (I50) of an enzymatic reaction

Inhibition of mammalian carbonic anhydrase isoforms I, II and VI with thiamine and thiamine-like molecules

"Carbonic anhydrase (EC 4.2.1.1., CA) has been a well-characterized pH regulatory enzyme in most tissues including erythrocytes[1]. CA catalyzes the reversible hydration of CO2 to HCO3− and H+. At least 16 CA isozymes have so far been described in mammals, the most active ones as catalysts for carbon dioxide hydration being CA-II and CA-IX[2–5]. The first one is primarily found in red blood cells but also in many other secretory tissues of the gastrointestinal tract, kidneys, lungs, eye, central nervous system etc[3,6]., whereas the second one is a tumor-associated isoform[3–7]."

Spoiler: Table 1

Pharmacokinetics of high-dose oral thiamine hydrochloride in healthy subjects

Spoiler: Figure 1

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.

 

[RealNeat]

Spoiler: Toxicology

Spoiler: Fundamentals of Biochemistry

• 043-Enzyme Activity & Rate Equations
• 044-Michaelis-Menten Equation
• 045-Kinetic Constants: Km & Vmax
• 046-Catalytic Efficiency; Lineweaver-Burk Equation
• 047-Non-Michaelis-Menten Kinetics
• 048-Irreversible Enzyme Inhibition
• 049-Competitive Inhibition
• 050-Other Reversible Inhibitors
• 051-Allosteric Regulation; Summary of Enzyme Regulation

- Enzyme inhibitor - Wikipedia

Spoiler: Types of inhibition | AK Lectures

• Competitive, Uncompetitive and Noncompetitive Inhibition (Part I)
• Competitive, Uncompetitive and Noncompetitive Inhibition (Part II)

Spoiler: Lippincott’s Illustrated Reviews: Biochemistry (978-1-60831-412-6)

View attachment 17740


View attachment 17741​

- Enzyme inhibitors | University College London

- The difference between Ki, Kd, IC50, and EC50 values | The Science Snail
- An Intuitive Look at the Relationship of Ki and IC50: A More General Use for the Dixon Plot

- IC50 - Wikipedia

⬐ [22] Relationship between the inhibition constant (KI) and the concentration of inhibitor which causes 50 per cent inhibition (I50) of an enzymatic reaction

"Carbonic anhydrase (EC 4.2.1.1., CA) has been a well-characterized pH regulatory enzyme in most tissues including erythrocytes[1]. CA catalyzes the reversible hydration of CO2 to HCO3− and H+. At least 16 CA isozymes have so far been described in mammals, the most active ones as catalysts for carbon dioxide hydration being CA-II and CA-IX[2–5]. The first one is primarily found in red blood cells but also in many other secretory tissues of the gastrointestinal tract, kidneys, lungs, eye, central nervous system etc[3,6]., whereas the second one is a tumor-associated isoform[3–7]."

Spoiler: Table 1

View attachment 17742

Spoiler: Figure 1

View attachment 17743

1500 at once?