Thiamine And Cancer

haidut

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Hi all,

There have been many studies on thiamine (vitamin B1) and its effects on cancer. The studies report mixed results, with some studies suggesting thiamine stimulates tumor growth and others saying it retards tumor growth. There has been a recent study (2013), which does a more thorough review on the role of thiamine in cancer and what are the discrepancies. It seems that whether thiamine helps of hinders cancers depends very much on its ability to stimulate pyruvate dehydrogenase and reduce lactate. So, if you are given thiamine and it does those two things for you then it will help with cancer. Otherwise, it may hurt. Well, what determines if thiamine lowers lactate and activates pyruvate dehydrogenase? Individual variability, metabolism, age, exposure to toxins, etc. So, basically everybody's response would be unique. That's pretty bad news from a medical point of view since it means everybody has to be evaluated separately, which pretty much guarantees that no doctor would give thiamine 2 seconds of their time. However, the researchers noticed that at high dosages pretty much everybody started responding to thiamine. Here is an excerpt from the study:

http://cgp.iiarjournals.org/content/10/4/169.full.pdf

"...A metabolic control analysis demonstrated a high stimulatory effect on tumor growth of 164% compared with controls with a thiamine dose of 25-fold the recommended dietary allowance (RDA); however, at very high doses of thiamine, ~2500-fold the RDA, the opposite effect was observed, producing an [haidut note: average] inhibitory effect on tumor growth of 36% compared with control animals (153). The Authors suggested that when thiamine supplementation is necessary for patients with cancer it should be administered at high doses to avoid the tumor-promoting effect of low doses."

So, the above inhibitory effect is an aggregate effect over many types of cancer and many types of patients. Another way to put it would be that high doses of thiamine would reduce tumor growth by 36% on average in most types of cancer. That's a pretty strong statement, and the only one I have ever seen made about a vitamin! Time will tell if it holds true as it has been shown for aspirin.
But more to the point, Ray seems to be once again correct in his assessment that agents that activate pyruvate dehydrogenase (thus kickstarting oxidative metabolism, lowering lactate, and limiting glycolysis), which thiamine does - such agents would be very helpful in the treatment/management of cancer. Palmitic acid is another such agent, and I believe fructose does it as well.
Finally, how much is 2500-fold RDA for thiamine? It is about 3,500mg daily, which suddenly do not seem that high when you take into account the other studies I posted on Chron's, PD, and MS. I think there is method to the madness. Dosages of thiamine that helped with those conditions, and even higher ones, would be helpful in cancer.
Thoughts?
 
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Peata

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Makes me worry about the 250 - 500 mg. I've been taking daily.
 

charlie

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jaa said:
It sure tastes like it's giving me cancer!
:rolling

No kidding. The stuff is pretty stout tasting.
 

Giraffe

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"...A metabolic control analysis demonstrated a high stimulatory effect on tumor growth of 164% compared with controls with a thiamine dose of 25-fold the recommended dietary allowance (RDA); however, at very high doses of thiamine, ~2500-fold the RDA, the opposite effect was observed, producing an [haidut note: average] inhibitory effect on tumor growth of 36% compared with control animals (153). The Authors suggested that when thiamine supplementation is necessary for patients with cancer it should be administered at high doses to avoid the tumor-promoting effect of low doses."
"2500-fold" looks not correct to me. *)

The effect of thiamine supplementation on tumour proliferation

This must be the study where that figure came from. From the full text:
A clear thiamine stimulatory effect on tumour growth was found in a range of thiamine concentrations between 12.5 and 75 times the RDA, with a maximum effect (164% of cell proliferation increase with respect to controls) at a dose of 25 times the RDA.
...

In that study they did not only administer thiamine (as thiamine HCl), but also oxythiamine (never heard of that substance, lol). I googled a bit... It is described as "thiamine analog", "thiamine antagonist", "a toxin that causes functional thiamine deficiency" and as an "irreversible inhibitor of transketolase" and as such a possible chemotherapy drug.

So as other cells, the cancer cells need thiamine to survive. Administration of oxythiamine caused functional thiamine deficiency. Then they supplementented thiamine and checked at which dose the net effect was zero? This is what figure 1 looks like to me.

Am I missing something?

*) Edit to add: Don't know how to interpret a figures for thiamine if a thiamine antagonist was used as well.

-----

Sidenote: Ray Peat mentioned 300 mg thiamine when asked about cancer.
 
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haidut

haidut

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"2500-fold" looks not correct to me. *)

The effect of thiamine supplementation on tumour proliferation

This must be the study where that figure came from. From the full text:

...

In that study they did not only administer thiamine (as thiamine HCl), but also oxythiamine (never heard of that substance, lol). I googled a bit... It is described as "thiamine analog", "thiamine antagonist", "a toxin that causes functional thiamine deficiency" and as an "irreversible inhibitor of transketolase" and as such a possible chemotherapy drug.

So as other cells, the cancer cells need thiamine to survive. Administration of oxythiamine caused functional thiamine deficiency. Then they supplementented thiamine and checked at which dose the net effect was zero? This is what figure 1 looks like to me.

Am I missing something?

*) Edit to add: Don't know how to interpret a figures for thiamine if a thiamine antagonist was used as well.

-----

Sidenote: Ray Peat mentioned 300 mg thiamine when asked about cancer.

It's not a typo. The 2,500 is from the study itself. Look on page 174, bottom left portion of the page. Here is the full quote again:
"...A metabolic control analysis demonstrated a high stimulatory effect on tumor growth of 164% compared with controls with a thiamine dose of 25-fold the recommended dietary allowance (RDA); however, at very high doses of thiamine, ~2500-fold the RDA, the opposite effect was observed, producing an inhibitory effect on tumor growth of 36% compared with control animals (153). The Authors suggested that when thiamine supplementation is necessary for patients with cancer, it should be administered at high doses to avoid the tumor-promoting effect of low doses."

Oxythiamine is a thiamine antagonist. It depletes thiamine in the cell and I would never try it for any disease. The idea of using oxythiamine stems from the idea of starving the cancer of glucose. It does not work, many things like this have been tried with horrible results. Another similar approach that was tried was using 2-DG (a glucose substitute that cannot be metabolized) and fooling the cancer into starvation. Needless to say, that did not work either. If starving therapy works at all it should be aimed at restricting fat supply to the tumor, not glucose. I posted a few articles recently on tumors being addicted to fat and Ray wrote about that too and the role of the enzyme FAS in tumor growth.
The goal should not be to deprive tumor cells of thiamine since the goal is not to try and kill them. When you deprive them of their nutrient they grow and multiply even faster. The goal is to provide a high dose of thiamine to inhibit the excessive glycolysis in the cancer cell AND also inhibit carbonic anhydrase (as thiamine is a CA inhbitor) and thus sending the signal to the cancer cell that things are OK in the environment and there is no need to grow and divide.
 

Giraffe

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@haidut, you quoted from a review. What the reviewers wrote is misleading. Also what the authors of the original study wrote is not quite correct. I don't understand why the authors of the review incluced that study in the first place, and then failed to mention that a thiamine antagonist was used while thiamine was supplemented.

I am not worried of "cancer-promoting properties" of thiamine at doses of 300 mg /day. :wink
 

TubZy

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Hi all,

There have been many studies on thiamine (vitamin B1) and its effects on cancer. The studies report mixed results, with some studies suggesting thiamine stimulates tumor growth and others saying it retards tumor growth. There has been a recent study (2013), which does a more thorough review on the role of thiamine in cancer and what are the discrepancies. It seems that whether thiamine helps of hinders cancers depends very much on its ability to stimulate pyruvate dehydrogenase and reduce lactate. So, if you are given thiamine and it does those two things for you then it will help with cancer. Otherwise, it may hurt. Well, what determines if thiamine lowers lactate and activates pyruvate dehydrogenase? Individual variability, metabolism, age, exposure to toxins, etc. So, basically everybody's response would be unique. That's pretty bad news from a medical point of view since it means everybody has to be evaluated separately, which pretty much guarantees that no doctor would give thiamine 2 seconds of their time. However, the researchers noticed that at high dosages pretty much everybody started responding to thiamine. Here is an excerpt from the study:

http://cgp.iiarjournals.org/content/10/4/169.full.pdf

"...A metabolic control analysis demonstrated a high stimulatory effect on tumor growth of 164% compared with controls with a thiamine dose of 25-fold the recommended dietary allowance (RDA); however, at very high doses of thiamine, ~2500-fold the RDA, the opposite effect was observed, producing an [haidut note: average] inhibitory effect on tumor growth of 36% compared with control animals (153). The Authors suggested that when thiamine supplementation is necessary for patients with cancer it should be administered at high doses to avoid the tumor-promoting effect of low doses."

So, the above inhibitory effect is an aggregate effect over many types of cancer and many types of patients. Another way to put it would be that high doses of thiamine would reduce tumor growth by 36% on average in most types of cancer. That's a pretty strong statement, and the only one I have ever seen made about a vitamin! Time will tell if it holds true as it has been shown for aspirin.
But more to the point, Ray seems to be once again correct in his assessment that agents that activate pyruvate dehydrogenase (thus kickstarting oxidative metabolism, lowering lactate, and limiting glycolysis), which thiamine does - such agents would be very helpful in the treatment/management of cancer. Palmitic acid is another such agent, and I believe fructose does it as well.
Finally, how much is 2500-fold RDA for thiamine? It is about 3,500mg daily, which suddenly do not seem that high when you take into account the other studies I posted on Chron's, PD, and MS. I think there is method to the madness. Dosages of thiamine that helped with those conditions, and even higher ones, would be helpful in cancer.
Thoughts?

Is your view still accurate on thiamine based on this thread, I noticed this thread is 4 years old? If so, you are saying high dose thiamine only is the best way to go?
 
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haidut

haidut

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Is your view still accurate on thiamine based on this thread, I noticed this thread is 4 years old? If so, you are saying high dose thiamine only is the best way to go?

Peat was asked about this recently and he said 300mg up to twice a day is enough for people with cancer. Obviously, measuring lactate and blood B1 levels would be needed to see if the B1 is even absorbed as absorption is low in many sick people, and would show if the dose is enough to have a clinically meaningful effect on lactate and CO2.
 
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haidut

haidut

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Amazoniac

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"The different doses of thiamine tested were 0, 0.25, 0.5, 0.75, 1, 1.5, 2.5, 5, and 50 mg per kg mice per day. As the dietary allowance of thiamine (recommended dietary allowance, RDA) per mouse is 20 µg per kg mice per day [10] the above doses can be expressed as 0, 12.5, 25, 37.5, 50, 75, 125, 250, and 2500 times the mice RDA for thiamine."​
"In each experiment, groups of six mice per dose of thiamine were used. The corresponding thiamine dose was administered by subcutaneous injection daily starting 4 days after tumour implantation and for 4 days. The experiments were carried out three times on different days (18 mice for each thiamine dose in total). Mice were killed 24 h after the last subcutaneous injection of thiamine."​
1633876030261.png
"To further investigate the anti-tumoural effect of thiamine at high doses we changed the pattern of thiamine administration. We performed experiments at two significantly different doses of thiamine (25 and 2500 times the RDA), starting daily administration 7 days before tumour inoculation and continuing until 8 days after tumour implantation. A thiamine dose 25 times the RDA was found to produce a 22% increase in tumour growth when the dose was injected daily 7 days before tumour inoculation. This observed stimulatory effect is much lower than that found when the same dose of thiamine is administered later, starting 4 days after tumour inoculation (compare with data in Fig. 1). Interestingly, when the highest thiamine dose (2500 times the RDA) is administered starting 7 days before tumour inoculation, 36% tumour inhibition is observed. Thus, the effect on tumour inhibition of a high overdose of thiamine is increased when thiamine administration is started early (see Fig. 1)."​

The experiments using deaminated thiamid was separate (hence control groups in respective treatments).

- A simple practice guide for dose conversion between animals and human

0.5 mg/kg ÷ 12.3 ⨯ 70 kg ≈ 3 mg​
2.5 mg/kg ÷ 12.3 ⨯ 70 kg ≈ 14 mg​

- Thiamin | LPI

1.15 mg ⨯ 25 ≈ 30 mg​
1.15 mg ⨯ 125 ≈ 140 mg​
300 mg ÷ 1.15 mg ≈ 260

:hairpull
 

Amazoniac

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Of course pharmacological thiamid use in cancer would be after initiation, where 2500x the RDA was the only tested dose that led to a 10% inhibition. From the numbers above, that would be 30 mg (scaled based on body proportions) or 300 mg (based on RDA).

- Subcutaneous Drug Administration

"The absorption of drugs from a subcutaneous depot of an aqueous solution proceeds rather rapidly."​

1633947508764.png
:smokingcrack

It's not inreasonable ):wave: akgrl( to opt for their high end dose due to liver decontamination after ingestion.
 

Ben.

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Its kinda wierd that dosage alone would determine wether it is good or bad for tumor growth ... even more so that mega doses are inhibiting and low/medium dosages are growth promoting ...
As Haidut mentioned back then, how much is absorbed is a important question too(?).

These high/mega dosages seem to be realy effective due to abnormalities in thiamine-dependent processes that are/may be overcome by a diffusion-mediated transport at elevated thiamine concentrations.
So... the increased intracellular passive transport of the thiamine trough high oral dosages may bring relief, but what is causing the dysfunction in the first place?
While i guess there are worse things than taking thiamine HCL everyday, i still feel there needs to be a puzzle piece missing ... and if its, lets say ...environmental ... how is it that some suffer more from it than others?
 

TranceWax

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How does this translate over to animals? I want to give this to a dog thats 9kg for cancer, 2500 above the RDA based on weight is around 50-60mg, does this sound about right?
 

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