Nehring
Member
- Joined
- Aug 17, 2018
- Messages
- 7
Hey guys,
Actively reading Peat's work and subsequently the forum for the last 5 years has (like prob. most of us) inspired me to drastically re-evaluate my understanding of health, biology as well as development through the journey of perceive-think-act.
I really want to thank everyone in this community for their interesting perspectives on the above and most of all for a less authoritarian approach to learning and thought exchange, which seems to be unfortunately perpetually atrophying in “modern” society.
----------------------------------->
While venturing into the world of Allithiamine since about a half a year + reading “Thiamine Deficiency Disease, Dysautonomia, and High Calorie Malnutrition”, I stumbled upon the study “Thiamine mimetics sulbutiamine and benfotiamine as a nutraceutical approach to anticancer therapy”, which was already mentioned by Broken man on May 8th 2020:
Thiamine mimetics sulbutiamine and benfotiamine as a nutraceutical approach to anticancer therapy - ScienceDirect
The study from Jan 2020 compares the anti-cancer potential of thiamine (T), sulbutiamine (SLBT) and benfotiamine (BNFO) with DCA in an in vitro human colon cancer cell model (HCT116) and finally shows intriguing IN VIVO data from a mouse study.
Since I was quite fascinated with this study, I thought I’d share a couple of conclusions which might be worth considering.
First off, the authors speculate this study provide one of the first / if not the first “in vivo evidence for the anticancer effect of a commercially available thiamine analog”.
Part I - In vitro
Part II - In vivo
It should be acknowledged, that this study was co-financed by the American Cancer Society and that the authors are initiating their conclusion with “Considering their presumable safety and notable pre-clinical anticancer effects, exploiting pharmacologic doses of nutraceutical compounds (i.e. vitamins) provides a promising strategy for cancer therapy” and even go on acknowledging Pauling as well as pharmacologic treatment with ascorbate!
This makes one hope for the exploration of actually sane anti-cancer approaches, though unfortunately I'm pessimistic, and you guys know the reasons….
Parting thoughts on the relevance of the study to TTFD (Allithiamine) supplementation
As per Dr. Lonsdale’s and Chandler Marrs’s book “Thiamine Deficiency Disease, Dysautonomia, and High Calorie Malnutrition” (really worth a read!), TTFD enters the cell as normal thiamine after its prosthetic group has been removed. This mechanism supposedly drastically improves bio-availability. TTFD could therefore mimic the benchmark effects of plain thiamine as per the above study, though theoretically much lower dosages would be required due to superior absorption through the gut. Also, TTFD apparently crosses the blood brain barrier, whereas benfotiamine dose not, so one can only speculate about the possible superior anti-tumor growth effects in a brain cancer model.
As to the superiority of TTFD over thiamine hydrochloride, Chandler and Dr. Lonsdale provide some context. In their perspective in case of metabolic derangement and thus down-regulation of key enzymes and transporters (for the non-Lings under us), synthetic thiamine mimetics like TTFD can provide relief where salt forms of thiamine don’t seem to be able to revive oxidative metabolism.
The proof for the justification of substantially higher prices is in the pudding but anecdotally I can attest to the fact that I had superior results specifically on digestion with TTFD.
Actively reading Peat's work and subsequently the forum for the last 5 years has (like prob. most of us) inspired me to drastically re-evaluate my understanding of health, biology as well as development through the journey of perceive-think-act.
I really want to thank everyone in this community for their interesting perspectives on the above and most of all for a less authoritarian approach to learning and thought exchange, which seems to be unfortunately perpetually atrophying in “modern” society.
----------------------------------->
While venturing into the world of Allithiamine since about a half a year + reading “Thiamine Deficiency Disease, Dysautonomia, and High Calorie Malnutrition”, I stumbled upon the study “Thiamine mimetics sulbutiamine and benfotiamine as a nutraceutical approach to anticancer therapy”, which was already mentioned by Broken man on May 8th 2020:
Thiamine mimetics sulbutiamine and benfotiamine as a nutraceutical approach to anticancer therapy - ScienceDirect
The study from Jan 2020 compares the anti-cancer potential of thiamine (T), sulbutiamine (SLBT) and benfotiamine (BNFO) with DCA in an in vitro human colon cancer cell model (HCT116) and finally shows intriguing IN VIVO data from a mouse study.
Since I was quite fascinated with this study, I thought I’d share a couple of conclusions which might be worth considering.
First off, the authors speculate this study provide one of the first / if not the first “in vivo evidence for the anticancer effect of a commercially available thiamine analog”.
Part I - In vitro
- Thiamine mediated increased pyruvate dehydrogenase (PDH) activity might actually be the result of thiamine pyrophosphate (TPP) mediated over-expression of pyruvate dehydrogenase kinase (PDK)
- When administered in vitro, the concentration of thiamine analogs are not increased, while the intracellular thiamine concentration increases approx. 500-fold through administration of SLBT and BNFO and approx. 3000-fold through administration of thiamine directly
- The thiamine dosage needed to be 100 times greater than SLBT/BNFO dosage to achieve this effect, showing a relative superior delivery through the mimetic forms (Fig 3)
- Interestingly, the subsequent increase in TPP is about the same for all 3 thiamine types and surprisingly only shows a modest 2-fold incline
- Comparing the thiamine induced surge of TPP concentration with the profound effects of DCA shows a similar reduction in phosphorylated PDH and thus greater PDH activity (Fig 4)
- The TPP transporter SLC44A4 “demonstrates strong up-regulation in malignant cells”, whereas healthy tissue doesn’t seem to express this up-regulation.
--> I found this very interesting and in my point of view this could be taken as an argument for both sides of the “evil cancer vs. stressed cell” debate.- On the one hand, one could argue that this is yet another vicious attempt of the evil cancer to gain more access to TPP floating around in the extracellular space (e.g. produced by microbiota) in order to further fuel its demonic ever increasing proliferation.
- On the other hand this could be interpreted as a “cry” for help of the stressed cell, which is not able to resuscitate proper OXPHOS of glucose by itself and thus over-expresses the ability to externally assist in PDK inhibition -> revive the glycolysis - TCA link reaction
Part II - In vivo
- The in vivo results show a reduction in tumor growth of both SLBT and BNFO, though BNFO shows a remarkable higher tumor growth reduction than SLBT and it looks like (chart B) between days 35 and 40 tumor growth in the SLBT treated group is stunted!
- What seems inconsistent with the in vitro findings is the fact that “Neither sulbutiamine nor benfotiamine significantly changed PDH phosphorylation or lactate levels measured in tumor tissue isolated” though the anti-proliferative effects where still induced. The authors speculate that “the increase in TPP achieved by our in vivo dosing paradigm may not have been substantial enough to sufficiently inhibit PDK”.
--> Still trying to wrap my head around this, especially the non-significant lactate inhibition.
It should be acknowledged, that this study was co-financed by the American Cancer Society and that the authors are initiating their conclusion with “Considering their presumable safety and notable pre-clinical anticancer effects, exploiting pharmacologic doses of nutraceutical compounds (i.e. vitamins) provides a promising strategy for cancer therapy” and even go on acknowledging Pauling as well as pharmacologic treatment with ascorbate!
This makes one hope for the exploration of actually sane anti-cancer approaches, though unfortunately I'm pessimistic, and you guys know the reasons….
Parting thoughts on the relevance of the study to TTFD (Allithiamine) supplementation
As per Dr. Lonsdale’s and Chandler Marrs’s book “Thiamine Deficiency Disease, Dysautonomia, and High Calorie Malnutrition” (really worth a read!), TTFD enters the cell as normal thiamine after its prosthetic group has been removed. This mechanism supposedly drastically improves bio-availability. TTFD could therefore mimic the benchmark effects of plain thiamine as per the above study, though theoretically much lower dosages would be required due to superior absorption through the gut. Also, TTFD apparently crosses the blood brain barrier, whereas benfotiamine dose not, so one can only speculate about the possible superior anti-tumor growth effects in a brain cancer model.
As to the superiority of TTFD over thiamine hydrochloride, Chandler and Dr. Lonsdale provide some context. In their perspective in case of metabolic derangement and thus down-regulation of key enzymes and transporters (for the non-Lings under us), synthetic thiamine mimetics like TTFD can provide relief where salt forms of thiamine don’t seem to be able to revive oxidative metabolism.
The proof for the justification of substantially higher prices is in the pudding but anecdotally I can attest to the fact that I had superior results specifically on digestion with TTFD.
Last edited: