Thiamine Normalizes Pyruvate / Lactate Levels In Rats With Cancer

[haidut]

Russian study, so I can't get the actual paper and see route of administration, but it was likely oral or intraperitoneal. Human equivalent dosage is 100mg - 150mg daily.

http://www.ncbi.nlm.nih.gov/pubmed/664448

 

[aguilaroja]

... can't get the actual paper and see route of administration, but it was likely oral or intraperitoneal. Human equivalent dosage is 100mg - 150mg daily.

Velichko and Terbukhina use subcutaneous delivery (to mouse subjects) in a later experiment studying thiamine-dependent enzymes. PubMed links to the free full English text:

http://www.ncbi.nlm.nih.gov/pubmed/6864328

J Nutr. 1983 Jul;113(7):1285-91.
Transketolase, pyruvate and oxoglutarate dehydrogenase activities and [14C]thiamin turnover in tissues of mice fed thiamin-deficient diet.
Trebukhina RV, Ostrovsky YM, Mikhaltsevich GN, Velichko MG, Tumanov VN.

 

[haidut]

... can't get the actual paper and see route of administration, but it was likely oral or intraperitoneal. Human equivalent dosage is 100mg - 150mg daily.

Velichko and Terbukhina use subcutaneous delivery (to mouse subjects) in a later experiment studying thiamine-dependent enzymes. PubMed links to the free full English text:

http://www.ncbi.nlm.nih.gov/pubmed/6864328

J Nutr. 1983 Jul;113(7):1285-91.
Transketolase, pyruvate and oxoglutarate dehydrogenase activities and [14C]thiamin turnover in tissues of mice fed thiamin-deficient diet.
Trebukhina RV, Ostrovsky YM, Mikhaltsevich GN, Velichko MG, Tumanov VN.

Good to know, thanks.

 

[lollipop]

@haidut here is a study released yesterday 16 Mar 2016 showing that a supplementation of pyruvate in mice showed anti aging results. Why might this be? A stress response?

https://www.sciencedaily.com/releases/2016/03/160316194205.htm

 

[jb116]

@lisaferraro I'm confused by your question since anti-aging is a good thing, why are you relating to a stress response?

 

[lollipop]

Thank you for asking @jb116!

I remembered the PHD was used to decrease concentrations of pyruvate and assumed that a build up was undesirable. I can be completely be misunderstanding lol. Obviously reaching out here for more clarity...

 

[jb116]

Thank you for asking @jb116!

I remembered the PHD was used to decrease concentrations of pyruvate and assumed that a build up was undesirable. I can be completely be misunderstanding lol. Obviously reaching out here for more clarity...

ok, do you mean the dehydrogenase? If so that is an enzymatic component to break it down to carbon fragments for creating atp. I see the confusion now. In this case
it is the utilization of pyruvate that is a good thing therefore supplementing these mice with it was like adding direct energy for their brain.

 

[ecstatichamster]

pyruvate is fuel. It's good! I think the title refers to ratio of pyruvate and lactate. Lactate builds, and pyruvate has to clean up the mess. Thiamine can be useful in this regard apparently.

 

[haidut]

@haidut here is a study released yesterday 16 Mar 2016 showing that a supplementation of pyruvate in mice showed anti aging results. Why might this be? A stress response?

https://www.sciencedaily.com/releases/2016/03/160316194205.htm

If the pyruvate is metabolized by PDH then it would be good since it will end up increasing CO2. But in cancer, PDH is strongly suppressed, so adding pyruvate to a mouse with cancer will nto work since there is an excess of NADH and PDH is not working well. So, the mousels LDH enzyme will use the extra pyruvate as an oxidant to oxidize NADH back NAD and in this process will create lactate. Somebody asked Peat in an email is supplementing with pyruvate is OK. He said something along the lines of "as long as it is metabolized through the Krebs cycle and does not build up then yes".

 

[jb116]

If the pyruvate is metabolized by PDH then it would be good since it will end up increasing CO2. But in cancer, PDH is strongly suppressed, so adding pyruvate to a mouse with cancer will nto work since there is an excess of NADH and PDH is not working well. So, the mousels LDH enzyme will use the extra pyruvate as an oxidant to oxidize NADH back NAD and in this process will create lactate. Somebody asked Peat in an email is supplementing with pyruvate is OK. He said something along the lines of "as long as it is metabolized through the Krebs cycle and does not build up then yes".

Its good you brought up the aspect of cancer because I wanted to reconcile the idea of using b1 and for example b3 as supplements for cancer patients. But it occurred to me the thiamin would be increasing pyruvate. So if the pdh is the limiting factor then b1 wouldn't be great to use, no? Unless thiamine also helps with pdh metabolism as well.

 

[haidut]

Its good you brought up the aspect of cancer because I wanted to reconcile the idea of using b1 and for example b3 as supplements for cancer patients. But it occurred to me the thiamin would be increasing pyruvate. So if the pdh is the limiting factor then b1 wouldn't be great to use, no? Unless thiamine also helps with pdh metabolism as well.

You already guessed it - thiamine is the main cofactor for PDH:) So, yes, it would help with PDH functionality and also thiamine inhibits PDK. PDK inhibits PDH and PDK is overexpressed in cancer cells. The chemical DCA used for cancer does the same - it activates PDH and inhibits PDK. Unfortunately, in higher doses DCA is itself carcinogenic.
Thiamine acts similarly to DCA and may be helpful in cancer

Thiamine and biotin seem to be able to do the same as DCA without the carcinogenicity.
Biotin as a treatment for multiple sclerosis (MS)

 

[jb116]

You already guessed it - thiamine is the main cofactor for PDH:) So, yes, it would help with PDH functionality and also thiamine inhibits PDK. PDK inhibits PDH and PDK is overexpressed in cancer cells. The chemical DCA used for cancer does the same - it activates PDH and inhibits PDK. Unfortunately, in higher doses DCA is itself carcinogenic.
Thiamine acts similarly to DCA and may be helpful in cancer

Thiamine and biotin seem to be able to do the same as DCA without the carcinogenicity.
Biotin as a treatment for multiple sclerosis (MS)

Ah excellent, now it is totally clear. Man b1 really should be considered indispensible in the cancer world.

 

[ecstatichamster]

Haidut, do you recommend a particular book on biochemistry? Man you are amazing.

 

[haidut]

Haidut, do you recommend a particular book on biochemistry? Man you are amazing.

I personally read this one:
Marks' Essentials of Medical Biochemistry: A Clinical Approach: 9781451190069: Medicine & Health Science Books @ Amazon.com

I managed to read all of it without much background in biochemistry, so I think other people will be able as well. There may be a better book as an intro, so if somebody has a recommendation please chime in.

 

[ecstatichamster]

thank you -- ordered a copy...

 

[haidut]

thank you -- ordered a copy...

It's available for free on the Internet. Google this "Marks' Essentials of Medical Biochemistry: A Clinical Approach pdf" (without quotes) and look for the result coming from the URL "biology.krc.karelia.ru:8080". You can download the complete book from that link. For me, it is the 3rd result when I perform the search.

 

[ecstatichamster]

thanks! Worked a treat.

It's really good, thanks!

 

[lollipop]

Thank you @haidut and @jb116 - all a bit clearer now! Sooo fascinating actually. Thank you for the book reference - getting it now