Thiamine Reduces Breast Cancer Cell Proliferation In Tissue Culture

aguilaroja

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This study was done with tissue culture of breast cancer cells. It used the Hcl form of thiamine, which as @haidut is the form often used in studies showing beneficial thiamine effects and is widely available. The separate thread is started for emphasis, and is a continuation of @haidut’s thread:
Thiamine Acts Similarly To DCA And May Be Helpful In Cancer

The Effects of Thiamine on Breast Cancer Cells
“Thiamine has a distinct advantage over drugs such as dichloroacetate because it is a water-soluble vitamin that is harmless, even in excess. Moreover, we have already shown that administration of thiamine to thiamine-deficient patients can quickly cause a whole-body shift from aerobic glycolysis toward aerobic metabolism”

“Thiamine had a number of effects in MCF7; it (1) reduced extracellular lactate levels in growth media, (2) increased cellular pyruvate dehydrogenase (PDH) activities and the baseline and maximum cellular oxygen consumption rates, and (3) decreased non-glycolytic acidification, glycolysis, and glycolytic capacity.”

“Conclusions: The treatment of MCF7 breast cancer cells with 1 μg/mL and 2 μg/mL of thiamine for 24 h significantly reduced their proliferation. This reduction is associated with a reduction in glycolysis and activation of the PDH complex in breast cancer cells.”
 

yerrag

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“Conclusions: The treatment of MCF7 breast cancer cells with 1 μg/mL and 2 μg/mL of thiamine for 24 h significantly reduced their proliferation. This reduction is associated with a reduction in glycolysis and activation of the PDH complex in breast cancer cells.”
I have trouble understanding dosage of ug/mL. Would appreciate some guidance.
 
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aguilaroja

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I have trouble understanding dosage of ug/mL. Would appreciate some guidance.

To clarify, the concentration given describes part of the composition of a growth medium for tissue culture (in vitro).

I suggest caution about drawing quick conclusions from this single study about equivalent dosing (oral or other routes) for animals or humans. There are papers describing approaches for allometric scaling from in vitro models, but AFAIK making estimates is much less routine than comparing animal trials to human trials. Maybe other readers have direct experience.

For clues about starting points, it might be useful to look at research reviewed by Lu’o’ng and Nguyen:
http://cgp.iiarjournals.org/content/10/4/169.long
Thiamine supplementation for other conditions, discussed in various forum posts, may be another basis.

One microgram per milliliter is equivalent to one mg per liter, used by the Liu/Donnino group for their cell growth broth in the lab.
 

yerrag

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To clarify, the concentration given describes part of the composition of a growth medium for tissue culture (in vitro).

I suggest caution about drawing quick conclusions from this single study about equivalent dosing (oral or other routes) for animals or humans. There are papers describing approaches for allometric scaling from in vitro models, but AFAIK making estimates is much less routine than comparing animal trials to human trials. Maybe other readers have direct experience.

For clues about starting points, it might be useful to look at research reviewed by Lu’o’ng and Nguyen:
http://cgp.iiarjournals.org/content/10/4/169.long
Thiamine supplementation for other conditions, discussed in various forum posts, may be another basis.

One microgram per milliliter is equivalent to one mg per liter, used by the Liu/Donnino group for their cell growth broth in the lab.
Thanks for the clarification. I missed that part about it being an in vitro study. The first link you posted, on the thread of haidut, gave an indication of dosage, and so I continued on the same path. It's interesting as I know quite a few people who have breast cancer, and thiamine seemed like something that could help without so much of the baggage of side-effects.
 

haidut

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Thanks @aguilaroja - that is another great study and another confirmation of the role of suppressed PDH in cancer growth!
As far as dosages that @yerrag is asking about - the 1mg/L corresponds to 3.76 uM/L, which is not high at all and can probably be achieved with oral doses in the 20mg-30mg range. Interestingly, thiamine is also a carbonic anhydrase inhibitor, which is also helpful in cancer, and the IC50 is not far off from the one used in this study. So, the same dosage should work for increasing CO2, which further lowers lactate.
Thiamine Is A Carbonic Anhydrase Inhibitor As Effective As Acetazolamide

Finally, I posted a human study which showed that thiamine administration completely resolved several cancers so the approach seems to have already been validated in vivo too.
Thiamine Treats Cancer In Humans, Its Deficiency May Cause Cancer

I think an oral dose of 50mg-100mg daily is probably enough for most people but higher doses may be needed initially if there is severe thiamine deficiency. I posted another study showing that the regular cheap thiamine Hcl can achieve the same concentrations as an IV dose if it is given over the course of a week. So, 100mg oral thiamine daily for 7 days would achieve the same concentrations on the 7th day as 100mg IV thiamine, and the latter is considered a decent dose even in an ER setting.
 

TreasureVibe

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Thiamine supplementation may contribute to a high rate of tumor cell survival, proliferation and chemotherapy resistance. Thiamine has also been implicated in cancer through its effects on matrix metalloproteinases, prostaglandins, cyclooxygenase-2, reactive oxygen species, and nitric oxide synthase.
http://cgp.iiarjournals.org/content/10/4/169.full
Antithiamine compounds significantly inhibit nucleic acid synthesis and tumor cell proliferation in vitro and in vivo in several tumor models.

The thiamine dependent TK pathway is the central avenue which supplies ribose phosphate for nucleic acids in tumors and excessive thiamine supplementation maybe responsible for failed therapeutic attempts to terminate cancer cell proliferation.
https://www.researchgate.net/public...ation_to_cancer_patients_A_double_edged_sword
Excess Thiamine May Help Tumor Growth, Research Shows

The dichotomous effect of thiamine supplementation on cancer cell growth is characterized by growth stimulation at low doses and growth suppression at high doses. Unfortunately, how thiamine affects cancer cell proliferation is currently unknown. Recent focuses on metabolic targets for cancer therapy have exploited the altered regulation of the thiamine-dependent enzyme pyruvate dehydrogenase (PDH). Cancer cells inactivate PDH through phosphorylation by overexpression of pyruvate dehydrogenase kinases (PDKs). Inhibition of PDKs exhibits a growth suppressive effect in many cancers. Recently it has been shown that the thiamine co-enzyme, thiamine pyrophosphate, can regulate the phosphorylation of PDH. Therefore, we hypothesize that high dose thiamine can normalize glycolysis in cancer cells leading to a cellular apoptosis. We have determined that high dose vitamin B1 reduces cell proliferation in cancer cell lines by a mechanism involving a reduction in PDH phosphorylation. Additionally we have established that thiamine homeostasis is altered in breast cancer cells and in hypoxic microenvironments. Together these findings suggest that using high dose thiamine may provide an important targeting advantage directed towards altering the cancer metabolic phenotype.
https://getd.libs.uga.edu/pdfs/hanberry_bradley_s_201412_phd.pdf
How about the above? Seems like thiamine can be bad too in cancer..

I think I see a pattern, low dose causes growth, high dose causes inhibition. Calcium paradox anyone?
 
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yerrag

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I think an oral dose of 50mg-100mg daily is probably enough for most people but higher doses may be needed initially if there is severe thiamine deficiency.
How does one test for thiamine deficiency?

I've never tested for it, and the one time I think I may be deficient in thiamine was when I took a lot of garlic. I noticed weakness in my legs, and one time when I was boarding a train, I wasn't even able to hold my ground as I was being pushed from behind. At that moment, I felt like a wheelchair is not far behind for me. It was later on that I found that the excess sulfite/sulfate? from garlic was leading to frequent urination, which also less to excretion of vitamins and minerals, among which is potassium and thiamine.

I suppose at that point I could take in 50-100mg doses for a week, and then revert to maintenance dose of thiamine, right? I don't need to continue on high dosage after it because my case does not involve cancer. On the other hand, if I were dealing with cancer, I could continue on with the high dosage until the cancer disappears.
 
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haidut

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How does one test for thiamine deficiency?

I've never tested for it, and the one time I think I may be deficient in thiamine was when I took a lot of garlic. I noticed weakness in my legs, and one time when I was boarding a train, I wasn't even able to hold my ground as I was being pushed from behind. At that moment, I felt like a wheelchair is not far behind for me. It was later on that I found that the excess sulfite/sulfate? from garlic was leading to frequent urination, which also less to excretion of vitamins and minerals, among which is potassium and thiamine.

I suppose at that point I could take in 50-100mg doses for a week, and then revert to maintenance dose of thiamine, right? I don't need to continue on high dosage after it because my case does not involve cancer. On the other hand, if I were dealing with cancer, I could continue on with the high dosage until the cancer disappears.

Elevated lactate could be a sign of thiamine deficiency, as as well as inability to handle a sugary meal and getting sleepy and then stressed as a rebound reaction. I think 50mg can be used for longer periods of time and 100mg+ can be used as that week-long loading dose.
 

yerrag

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Elevated lactate could be a sign of thiamine deficiency, as as well as inability to handle a sugary meal and getting sleepy and then stressed as a rebound reaction. I think 50mg can be used for longer periods of time and 100mg+ can be used as that week-long loading dose.
Yes, elevated lactate would be a giveaway. Thanks!
 

Mito

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How does one test for thiamine deficiency?

Chris Masterjohn sells a Testing Nutritional Status Cheat Sheet (https://chrismasterjohnphd.com/2018/01/02/testing-nutritional-status-ultimate-cheat-sheet/) that provides a wealth of information on how to test for various nutrients. He has several ideas for assessing thiamin status including whole blood thiamin pyrophosphate, erythrocyte transketolase, alanine, lactate, and possibly pyruvate. He also mentions some organic acids that can indicate thiamine deficiencies but organic acid test are relatively expensive.
 

yerrag

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Chris Masterjohn sells a Testing Nutritional Status Cheat Sheet (https://chrismasterjohnphd.com/2018/01/02/testing-nutritional-status-ultimate-cheat-sheet/) that provides a wealth of information on how to test for various nutrients. He has several ideas for assessing thiamin status including whole blood thiamin pyrophosphate, erythrocyte transketolase, alanine, lactate, and possibly pyruvate. He also mentions some organic acids that can indicate thiamine deficiencies but organic acid test are relatively expensive.
I forgot about the cheat sheet, and I already have it. Thanks!
 

yerrag

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I could not sleep the whole of last night. Very odd, as it's been ages since that's happened. I don't know if taking 100mg of thiamine before bed might have anything to do with that. It's the second day of taking 100mg thiamine only. Maybe I'm already sufficient with thiamine, and can't take this high a dose. I'm gonna go down to a regular dosage.
 

yerrag

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I could not sleep the whole of last night. Very odd, as it's been ages since that's happened. I don't know if taking 100mg of thiamine before bed might have anything to do with that. It's the second day of taking 100mg thiamine only. Maybe I'm already sufficient with thiamine, and can't take this high a dose. I'm gonna go down to a regular dosage.
It may not have to do with thiamine. I also had been taking liposomal C, which is made with lots of lecithin, which also has lots of PUFAs. I think the PUFAs interfered with my glucose metabolism. It caused by blood sugar to go up, and with insulin, caused it to go down, disturbing my sleep.

I'll try thiamine again without liposomal C before sleep. I'll probably just take my liposomal C in the morning if I have to.
 

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