Here is some article about thiamine, that it influences cancer growth both ways depending on the dose. Since we are supplementing dca with it I am wondering what dosages should we use and if it should be thiamine or benfotiamine.
http://www.ncbi.nlm.nih.gov/pubmed/23893925
I'm interested in this too. It looks to me like Benfotiamine is the better of the two? I think we'll start with that. Anders took 1000mg a day so I'll try for 3 of the 300mg capsules daily with the DCA.
ReplyDeleteI've read that Medicor Cancer Centre supplements DCA with benfotiamine 80 mg twice daily (among other supplements, see Toxicities page above). It's probably best to be conservative with thiamine dosing given the study Anna mentioned and other studies like it. This is being added to my list of things I need to look into further.
DeleteDoses of thiamine and benfotiamine are not equivalent as benfotiamine is better absorbed.
Seems like a jump in logic to assume befotiamine is better than thiamine, if in fact thiamine is a problem. Benfotiamine as I understand it is a fat soluble form of thiamine. Seems to me a fat soluble form would have greater access to the CNS given the high lipid content of the brain and therefore CNS tumors. Thoughts?
ReplyDeletehttp://www.medscape.com/viewarticle/583556_3
DeleteThere is some good info in here. Too late for me to delve into right now, but will do tomorrow.
We may need to rethink our use of thiamine/benfotiamine. I haven't seen any conclusive evidence that thiamine actually does prevent DCA-induced neuropathy or other toxicities in humans. In one human trial 10 mg/kg thiamine did not prevent neuropathy from DCA doses of 25 mg/kg/d.
ReplyDeleteI think much of the idea that thiamine prevents DCA toxicity comes from rat studies.
http://www.ncbi.nlm.nih.gov/pubmed/2318357
I haven't seen any comparable studies in humans, showing protective effects of thiamine combined with DCA. I'm not sure if Medicor has ever demonstrated this.
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ReplyDelete2018 https://www.ncbi.nlm.nih.gov/pubmed/29914147
ReplyDeletehttp://sci-hub.tw/https://doi.org/10.3390/molecules23061464
A great, but very interesting, excerpt about thiamine and DCA. Your opinion? Maybe it's worth combining a large dose of thiamine and DCA?
"First described by Otto Warburg in 1956, it has long been known that that cancer cells favor anaerobic over aerobic metabolism to produce energy to fuel tumor growth. Now termed the Warburg effect, this effect appears to hold true whether or not oxygen is present, and can thus be termed aerobic glycolysis [1]. Overall, this metabolic shift causes cancer cells to have a higher rate of glucose metabolism, greater lactate production, and an enhanced biosynthesis of lipids and other macromolecules [1,2].
Thiamine (vitamin B1), an essential cofactor for several key enzymes, is responsible for metabolic processes including biomass generation, amino acid catabolism, and the generation of energy [3]. Most notably, thiamine acts as an effective gatekeeper of aerobic metabolism in its role as cofactor for pyruvate dehydrogenase, the enzyme that allows pyruvate to enter the Krebs cycle. The role of thiamine in cancer has been debated for years. Tsao et al. recognized a substantial reduction of thiamine pyrophosphate in whole blood from patients diagnosed with advanced stages of non-small cell lung cancer [4]. A 2001 study by Comin-Anduix et al. showed a biphasic effect of thiamine when administered to mice injected with Ehrlich’s ascites tumor cells. They reported increased tumor proliferation when mice were given lower doses of thiamine and decreased tumor proliferation when mice were given 2500 times the recommended daily allowance (RDA) of thiamine for mice for eight days [5]. Interestingly, the proliferative effect of low doses of thiamine was diminished, and the anti-proliferative effect of high doses of thiamine was increased if the mice were pretreated with either low or high does thiamine for seven days prior to the introduction of tumor cells. However, this same study, as well as others, found inconsistent results when trying to associate cancer with dietary intake of thiamine [5–9]. For example, a 2008 study following a large cohort of women over 16 years found no link between the intake of B vitamins and cancer [7]. In contrast, other animal and human studies imply that thiamine deficiency is related to tumor growth [8,9].
When pyruvate dehydrogenase (PDH) activity is depressed due to thiamine deficiency or high phosphorylation by the overexpression of pyruvate dehydrogenase kinase (PDK) [10,11], aerobic glycolysis will be employed in the place of failed aerobic metabolism. When thiamine is administered to severely deficient patients, aerobic metabolism is rapidly restored, and the clearance of lactate and reversal of shock can occur within hours. Since tumor cells prefer aerobic glycolysis for tumor growth, the restoration of aerobic metabolism could theoretically slow the growth of the tumor. This hypothesis has been tested previously with dichloroacetate, which is another regulator of PDH. Dichloroacetate was found to attenuate glycolysis and increase aerobic metabolism, resulting in the reduction of colorectal cancer cell growth [12]. However, dichloroacetate also has some potentially toxic effects, including significant neuropathy, which may make it unsuitable for use in cancer patients. In this study, we hypothesized that the administration of thiamine to breast cancer cells would convert their metabolic phenotype from aerobic glycolysis to aerobic metabolism, and thus reduce cellular proliferation. 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 [13]."
"While the literature on this topic has shown mixed results, we believe that our findings and those of others may be reconciled by considering the level of thiamine in cancerous cells and the dose of thiamine used in prior experiments. Trebukhina et al. found that tumor growth resulted in tissue vitamin store depletion [19], and that during tumor growth, cancer cells kept a constant level of TPP, while host liver tissue exhibited a continuous decline [20]. Another study, analyzing post-surgical or autopsy tissues, found that thiamine levels increased 2.5-fold in colon adenocarcinomas relative to uninvaded control tissue [21]. These studies strongly suggest preferential thiamine accrual in cancer cells. This accumulation of thiamine may account for the effectiveness of a low dose of thiamine supplementation in promoting cancer growth, which has been shown in an animal study [5]. We hypothesize that a low dose may only be enough to provide only the basic cellular building blocks for assembling new cells; however, a high dose of exogenous thiamine may provide not just the cellular building blocks, but may preferentially shift metabolism from glycolytic to aerobic via reactant loading. By promoting aerobic mitochondrial metabolism, fewer glycolytic intermediates and micronutrient building blocks are generated, and cancer cell proliferation is thus stunted. This theory is supported by Hanberry et al., who found that a high dose of thiamine reduces cancer cell proliferation at a level similar to dichloroacetate by reducing PDH phosphorylation, glucose consumption, lactate production, and mitochondrial membrane potential [22]. Our findings of slightly increased PDH activity, decreased lactate, and more aerobic energy phenotype mapping in cancer cells treated with thiamine further support this hypothesis."
ReplyDeleteAnd another article about similar effects of DCA and thiamine:
ReplyDeletehttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3963161/
" Inhibition of PDKs by dichloracetate (DCA) exhibits a growth suppressive effect in many cancers. Recently it has been shown that the thiamine co-enzyme, thiamine pyrophosphate reduces PDK mediated phosphorylation of PDH. Therefore, the objective of this study was to determine if high dose thiamine supplementation reduces cell proliferation through a DCA like mechanism...
...Our findings suggest that high dose thiamine reduces cancer cell proliferation by a mechanism similar to that described for dichloroacetate."
I want to find research on the penetration of thiamine into the brain after pre-oral administration, but I cannot yet (
By the way, the DCA study, which I have not seen before and which upset me very much:
ReplyDeletehttps://www.ncbi.nlm.nih.gov/pubmed/16476929
http://sci-hub.tw/https://doi.org/10.1212/01.wnl.0000196641.05913.27
"We conclude that DCA at 25 mg/kg/day is not efficacious in the treatment of patients with MELAS because of the documented peripheral nerve toxicity and the lack of proof that the drug is effective. Based on our results, all MELAS A3243G subjects are at
risk for this toxic effect, and oral thiamine supplementation at 10 mg/kg/day does not prevent this complication. Our data show that the therapeutic benefit of DCA at 25 mg/kg/day, under the experimental conditions of our study design, is negligible, whereas the toxicity is significant, resulting in an unfavorable therapeutic index."
"Presenting symptoms were distal limb paresthesias (n 14), pain (n 5), distal numbness (n 8), falls (n 7), or subacute gait disturbance (n 16), alone or in combination."