56 replies to this topic

[Michael]

All:

I came to this conclusion last week, and have been doing my usual thing of putting off posting until I have the time to go into it properly, which of course I never do ... and this is too important.

(1) has been posted both here and on sci.l-e, in the context of debating which forms of thiamine are superior to others and whether very-high-dose thiamine can exert similar effects as benfotiamine. But the actual, central import of the study was basically ignored or downplayed by everyone (myself included) in the context of the debate:

The effect of thiamine supplementation on tumour proliferation was demonstrated by in vivo experiments in mice with the ascites tumour. Thiamine supplementation in doses between 12.5 and 250 times the recommended dietary allowance (RDA) for mice were administered starting on day four of tumour inoculation. We observed a high stimulatory effect on tumour growth of 164% compared to controls at a thiamine dose of 25 times the RDA. This growth stimulatory effect was predicted on the basis of correction of the pre-existing level of thiamine deficiency (42%) [which evidently results from the cancer's gobbling up of high levels of thiamine, and "which has been observed for decades in cancer patients"] , as assayed by the cofactor/enzyme ratio.

My attention was drawn back to this study when listening to an episode of CBC's Ideas podcast entitled "Science at the Summit," featuring prominent Canadian scientists, including Tak Mak, discoverer of the T-cell receptor. Beginning at about 0:24:30, Mak explained (in very simple terms) how and why his team is now going after novel cancer therapeutics on the basis of the new understanding of the "Warburg effect" -- the well-known phenomenon that many cancers are hypoxic, engaged in furious non-oxidative metabolism at the expense of oxidative phosphorylation as their energy source. This observation is consistently invoked by a variety of sales people and/or cultish devotees of various pseudoscientific diets, supplements, and quack cancer cures, as proof that cancer is caused by or relies upon either an acid metabolism or a lack of oxygen in the circulation -- which, of course, their supplement/therapy can reverse (for which assertion, in turn, they offer no good evidence).

Instead, Mak briefly explained that, rather than somehow preferring to use the very inefficient lactic acid pathway as their route to generate ATP instead of OXPHOS, these cancers are instead stuck using it, because of what they really need: they are trading off the wasted energetic potential of glucose, in favor of feeding glucose carbon into the pentose phosphate pathway to maximize nucleic acid ribose synthesis, and thereby maintain the massive production of proteins, DNA, and "novel fatty acids" that they need to maintain their runaway proliferation.

Of course, activation of the pentose phosphate shunt is exactly the route by which benfotiamine reduces the formation of intracellular oxoaldehydes -- and thereby, AGE -- in diabetes.

Without analyzing this in detail, I'll point everyone to the references appended. Several lines of evidence -- the high activity of thiamin-dependent, pentose-phosphate-activating transketolase-1 in many cancers, and its predictive role in poor disease prognosis; the efficacy of antithiamin chemotherapeutic agents against a range of cancers; weak evidence showing an apparent link between thiamin insufficiency and reduced cancer risk; and the supplementation study (1) -- all support this idea, and therefore suggest that, while you clearly don't want to go around frankly thiamine deficient in order to avoid cancer, having a chronic oversupply of bioactive thiamine (from benfotiamine, or any other source) likely creates a permissive environment for these cancers.

By strange coincidence, I see that Kismet has just very intelligently raised the question of the evidence basis for benfotiamine supplementation in normal, healthy people. The answer, of course, is that ultimately there isn't one: indeed, there is no really good evidence for any kind of supplementation in normal, healthy people, except for correction of frank nutrient deficiency. In my 2004 CR Society Conference lecture on supplementation, I classified benfotiamine as a 'Tier III' supplement: one for which there was some limited, speculative evidence of possible anti-aging benefit (in this case, based on the results of studies in diabetic animals and humans, and the speculation that it might have similar benefits in healthy folk during postprandial glucose surges, in response to dietary AGE, or in other risky metabolic states), and reasonably good evidence for lack of harm (based on extensive animal studies, some limited human clinical trials, and decades of use as a regulated and monitored 'drug' in Europe).

This was enough for me to take it, and to think it reasonable for others to do so, too; indeed, some of you are likely aware that I am the single person most logistically responsible for the initial availability of benfotiamine as a dietary supplement in North America, and (with the likely de facto exception of Michael Brownlee) for its promotion (starting with this) and its subsequent success and widespread availability from other sources.

Surprise! It now looks like a bad bet. Benfotiamine's speculative ability to lower AGE in normal, healthy people cannot outweigh the (also still-unproven) risk that it may promote the growth and survival of nascent cancers.

Yes, I've also seen this:

Interestingly, at very high overdoses of thiamine, approximately 2500 times the RDA, thiamine supplementation had the opposite effect and caused 10% inhibition of tumour growth.(1)

So, are you going to gamble on the notion, based on this one study, performed in one particular cancer model, that you're safe if you just take even more of the stuff? My friend, please think twice. You are sowing the wind, and I fear the whirlwind to come.

And remember: there is orders of magnitude more evidence for the safety of this molecule in humans than for any other hot dietary supplement you care to mention, with (again) the exception of essential nutrients taken at doses tailored to the correction of frank deficiency. Show me, most notably, the long-term safety record for taking various phytochemicals at doses multiple times more than is present in a normal, healthy diet, such as resveratrol at more than the ~5 mg you'd get from a few glasses of red wine, or more than a hundred or so milligrams of curcumin.

Remember the concerns about a potential cancer-promoting effect of folic acid, and further worries about supra-RDA intake of selenium. Look at the metabolic mess created by just a little too much zinc. Remember the results of the trials with alpha-tocopherol for heart disease ... or antioxidants for cancer ... or the epidemiology on high-potency multivitamin use and prostate cancer ... or preformed vitamin A (retinol -- not carotenoids) and fracture risk ...Hell, even supra-RDA vitamin D supplementation is only strictly speaking evidence-based practice in osteoporotic menopausal women -- though I want to be clear that I still practice and preach this last. I'm just putting it out on the table for the plain fact that it is.*

The days of "supplements are harmless; it can't hurt, and it might help" are over, people.

-Michael

*"So what the hell do you think is sound supplementation practice, Michael??" For some ideas, see here.

1 The effect of thiamine supplementation on tumour proliferation. A metabolic control analysis study.
Comín-Anduix B, Boren J, Martinez S, Moro C, Centelles JJ, Trebukhina R, Petushok N, Lee WN, Boros LG, Cascante M.
Eur J Biochem. 2001 Aug;268(15):4177-82.
PMID: 11488910 [PubMed - indexed for MEDLINE]

2 Population thiamine status and varying cancer rates between western, Asian and African countries.
Boros LG.
Anticancer Res. 2000 May-Jun;20(3B):2245-8. Review.
PMID: 10928186 [PubMed - indexed for MEDLINE]

3 Role of thiamin (vitamin B-1) and transketolase in tumor cell proliferation.
Cascante M, Centelles JJ, Veech RL, Lee WN, Boros LG.
Nutr Cancer. 2000;36(2):150-4. Review.
PMID: 10890024 [PubMed - indexed for MEDLINE]

4 Thiamine supplementation to cancer patients: a double edged sword.
Boros LG, Brandes JL, Lee WN, Cascante M, Puigjaner J, Revesz E, Bray TM, Schirmer WJ, Melvin WS.
Anticancer Res. 1998 Jan-Feb;18(1B):595-602. Review.
PMID: 9568183 [PubMed - indexed for MEDLINE]

5 [Effect of thiamine and its antimetabolite oxythiamine on the proliferative activity of carcinosarcoma Walker 256 cells]
Trebukhina RV, Kravchuk RI, Mikhal'tsevich GN, Petushok VG, Nikitin VS.
Eksp Onkol. 1987;9(2):60-3. Russian.
PMID: 3582243 [PubMed - indexed for MEDLINE]

6 [Level of thiamine diphosphate in the liver of tumor-bearing animals kept on a diet including an excessive amount of vitamin B 1]
Trebukhina RV, Petushok VG, Tumanov VN, Mikhal'tsevich GN.
Vopr Pitan. 1986 Jan-Feb;(1):63-5. Russian.
PMID: 3962272 [PubMed - indexed for MEDLINE]

7 Turnover of [14C]thiamin and activities of thiamin pyrophosphate-dependent enzymes in tissues of mice with Ehrlich ascites carcinoma.
Trebukhina RV, Ostrovsky YM, Shapot VS, Mikhaltsevich GN, Tumanov VN.
Nutr Cancer. 1984;6(4):260-73.
PMID: 6545581 [PubMed - indexed for MEDLINE]

8 Glycolytic metabolism in cultured cells of the nervous system. IV. The effects of thiamine deficiency on thiamine levels, metabolites and thiamine-dependent enzymes on the C-6 glioma and C-1300 neuroblastoma cell lines.
Schwartz JP, McCandless DW.
Mol Cell Biochem. 1976 Oct 30;13(1):49-53.
PMID: 1004496 [PubMed - indexed for MEDLINE]

9 Synthesis, in vitro and in vivo activity of thiamine antagonist transketolase inhibitors.
Thomas AA, Le Huerou Y, De Meese J, Gunawardana I, Kaplan T, Romoff TT, Gonzales SS, Condroski K, Boyd SA, Ballard J, Bernat B, DeWolf W, Han M, Lee P, Lemieux C, Pedersen R, Pheneger J, Poch G, Smith D, Sullivan F, Weiler S, Wright SK, Lin J, Brandhuber B, Vigers G.
Bioorg Med Chem Lett. 2008 Mar 15;18(6):2206-10. Epub 2007 Dec 3.
PMID: 18267359 [PubMed - indexed for MEDLINE]

10 Expression of transketolase-like 1 and activation of Akt in grade IV glioblastomas compared with grades II and III astrocytic gliomas.
Völker HU, Hagemann C, Coy J, Wittig R, Sommer S, Stojic J, Haubitz I, Vince GH, Kämmerer U, Monoranu CM.
Am J Clin Pathol. 2008 Jul;130(1):50-7.
PMID: 18550470 [PubMed - indexed for MEDLINE]

11 TKTL1 is overexpressed in a large portion of non-small cell lung cancer specimens.
Schultz H, Kähler D, Branscheid D, Vollmer E, Zabel P, Goldmann T.
Diagn Pathol. 2008 Aug 12;3:35.
PMID: 18700018 [PubMed - in process]

12 Overexpression of transketolase protein TKTL1 is associated with occurrence and progression in nasopharyngeal carcinoma: a potential therapeutic target in nasopharyngeal carcinoma.
Zhang S, Yue JX, Yang JH, Cai PC, Kong WJ.
Cancer Biol Ther. 2008 Apr;7(4):517-22. Epub 2008 Jan 2.
PMID: 18296915 [PubMed - indexed for MEDLINE]

13 Synthesis, in vitro and in vivo activity of thiamine antagonist transketolase inhibitors.
Thomas AA, Le Huerou Y, De Meese J, Gunawardana I, Kaplan T, Romoff TT, Gonzales SS, Condroski K, Boyd SA, Ballard J, Bernat B, DeWolf W, Han M, Lee P, Lemieux C, Pedersen R, Pheneger J, Poch G, Smith D, Sullivan F, Weiler S, Wright SK, Lin J, Brandhuber B, Vigers G.
Bioorg Med Chem Lett. 2008 Mar 15;18(6):2206-10. Epub 2007 Dec 3.
PMID: 18267359 [PubMed - indexed for MEDLINE]

14 Prodrug thiamine analogs as inhibitors of the enzyme transketolase.
Le Huerou Y, Gunawardana I, Thomas AA, Boyd SA, de Meese J, Dewolf W, Gonzales SS, Han M, Hayter L, Kaplan T, Lemieux C, Lee P, Pheneger J, Poch G, Romoff TT, Sullivan F, Weiler S, Wright SK, Lin J.
Bioorg Med Chem Lett. 2008 Jan 15;18(2):505-8. Epub 2007 Dec 3.
PMID: 18083562 [PubMed - indexed for MEDLINE]

15 Overexpression of transketolase TKTL1 is associated with shorter survival in laryngeal squamous cell carcinomas.
Völker HU, Scheich M, Schmausser B, Kämmerer U, Eck M.
Eur Arch Otorhinolaryngol. 2007 Dec;264(12):1431-6. Epub 2007 Jul 18.
PMID: 17639446 [PubMed - indexed for MEDLINE]

16 Transketolase protein TKTL1 overexpression: A potential biomarker and therapeutic target in breast cancer.
Földi M, Stickeler E, Bau L, Kretz O, Watermann D, Gitsch G, Kayser G, Zur Hausen A, Coy JF.
Oncol Rep. 2007 Apr;17(4):841-5.
PMID: 17342325 [PubMed - indexed for MEDLINE]

17 Expression of the mutated transketolase TKTL1, a molecular marker in gastric cancer.
Staiger WI, Coy JF, Grobholz R, Hofheinz RD, Lukan N, Post S, Schwarzbach MH, Willeke F.
Oncol Rep. 2006 Oct;16(4):657-61.
PMID: 16969476 [PubMed - indexed for MEDLINE]

18 Expression of transketolase TKTL1 predicts colon and urothelial cancer patient survival: Warburg effect reinterpreted.
Langbein S, Zerilli M, Zur Hausen A, Staiger W, Rensch-Boschert K, Lukan N, Popa J, Ternullo MP, Steidler A, Weiss C, Grobholz R, Willeke F, Alken P, Stassi G, Schubert P, Coy JF.
Br J Cancer. 2006 Feb 27;94(4):578-85.
PMID: 16465194 [PubMed - indexed for MEDLINE]

19 In situ localization of transketolase activity in epithelial cells of different rat tissues and subcellularly in liver parenchymal cells.
Boren J, Ramos-Montoya A, Bosch KS, Vreeling H, Jonker A, Centelles JJ, Cascante M, Frederiks WM.
J Histochem Cytochem. 2006 Feb;54(2):191-9. Epub 2005 Aug 22.
PMID: 16116031 [PubMed - indexed for MEDLINE]

20 Identification of novel small-molecule inhibitors for human transketolase by high-throughput screening with fluorescent intensity (FLINT) assay.
Du MX, Sim J, Fang L, Yin Z, Koh S, Stratton J, Pons J, Wang JJ, Carte B.
J Biomol Screen. 2004 Aug;9(5):427-33.
PMID: 15296642 [PubMed - indexed for MEDLINE]

21 Role of thiamin (vitamin B-1) and transketolase in tumor cell proliferation.
Cascante M, Centelles JJ, Veech RL, Lee WN, Boros LG.
Nutr Cancer. 2000;36(2):150-4. Review.
PMID: 10890024 [PubMed - indexed for MEDLINE]

22 [Glucose-6-phosphate dehydrogenase and transketolase activity in the blood of neurological oncologic patients preoperatively and in the dynamics of the postoperative period]
Brodskaia NI, Iansken LI, Kudriavtseva GV.
Vopr Med Khim. 1979 Nov-Dec;25(6):687-90. Russian.
PMID: 516529 [PubMed - indexed for MEDLINE]

23 [Activities of dehydrogenases of the pentose phosphate pathway and transketolase in transplanted mouse hepatomas with different growth rates and in organs of tumor carriers]
Birk RV, Shapot VS.
Biokhimiia. 1979 May;44(5):892-6. Russian.
PMID: 454718 [PubMed - indexed for MEDLINE]

24 Behavior of transaldolase (EC 2.2.1.2) and transketolase (EC 2.2.1.1) Activities in normal, neoplastic, differentiating, and regenerating liver.
Heinrich PC, Morris HP, Weber G.
Cancer Res. 1976 Sep;36(9 pt.1):3189-97.
PMID: 10080 [PubMed - indexed for MEDLINE]

[FunkOdyssey]

Thanks for the sobering warning Michael. This begs the question though, if we are going to decide what to consume or not to consume based on what seems to fuel the growth of cancers, where do we draw the line? Cancer gobbles up all of the resources required for cell proliferation. However, our healthy cells need these same resources for the same reasons. Taken to the extreme, you could provide none of the resources required by cancer, which would surely interfere with its growth, but at the unfortunate expense of killing the host.

Take protein for example. You personally practice and advocate a relatively high protein diet which has the additional effect of maintaining high IGF-1 levels. This would turbocharge the growth of any tissue or cells, including cancer. How do you reconcile the benefits and the risks?

[neogenic]

Isn't this debate similar to using antioxidants or anything anabolic/enhancing protein synthesis with cancer present...beta-carotene and all the others.

Anything that promotes growth or protects cells could promote tumor growth or protect cancer cells. But the downsides would only be in the presence of A TUMOR...right? When one doesn't have Cancer these are positive things. The only issue is if you have subacute Cancer (asymptomatic), in which it would potentially accelerate your symptoms and eventual diagnosis. I think we could find data like this on many supplements though.

I could be missing something, but I've seen these studies countless times with many supplements and it hasn't changed my supplementation one bit. I am anxious to here others thoughts on this. Maybe I am off-base.

[wydell]

The posts on this site over the years had previously led me to believe that this was a somewhat safe supplement. Of course, I realize everything has risks despite what people post. It will be interesting to see additional posts on this topic.

[kismet]

Bumped thread 'cause it's an important warning

Yes, I've also seen this:

Interestingly, at very high overdoses of thiamine, approximately 2500 times the RDA, thiamine supplementation had the opposite effect and caused 10% inhibition of tumour growth.(1)

I guess this at leats merits further investigation. If it can be replicated and high dose thiamine is otherwise safe, this could make thiamine (and benfotiamine?) an ever better life extension supplement? Otherwise it's not worth it in my opinion.

neogenic, the only problem is that there is no proven benefit of high dose B/T in healthy people, whereas the risk is real. We do not even have sufficently convincing mechanistic data for the use of B, which I've criticized in my last thread, much less any kind of long-term results.

However, the issue you describe is a real problem, because unfortunately most things require some kind of trade-off. Some trade-offs are better than others, though. And some substances, as of now, do not have been shown to produce any drawbacks (for life extensionists at least) e.g. CR or epidemiologically proven super foods like cocoa and green tea (not megadosed).
Many substances producing a somewhat "anabolic" environment (e.g. protein) could be expected to aid recovery, tissue repair and such, but on the other hand they'd also be able to increase tumor growth. I just think that high protein diets are backed up by much more convincing science than thiamine derivatives are.
Every drug has side-effects, considering the difference between "drug" and "supplement" is arbitrary and only based on perceived risks or frank politics, I'm sure most - if not all - supplements that mess with metabolism have side-effects. Ever so subtle side-effects, but in the end they could shorten your life span...
I don't know if it's possible to change any parameter X in metabolism, without negatively affecting some other parameter Y, because our metabolism is incredibly well tweaked for what it does. We just need to hope that parameter Y is a negligible problem in this day and age, even CR, for example, produces life extension benefits at the cost of reduced fitness (strength, speed, resistance to cold, starvation, etc).

Edited by kismet, 05 December 2008 - 10:29 PM.

[sUper GeNius]

Show me, most notably, the long-term safety record for taking various phytochemicals at doses multiple times more than is present in a normal, healthy diet, such as resveratrol at more than the ~5 mg you'd get from a few glasses of red wine, or more than a hundred or so milligrams of curcumin.

What exactly is the safety record of 5mg of resveratrol? Just because we don't have people drooping dead after ingesting it doesn't mean it's safe. Is baked bread my wheaties in the morning safe? I think so, but course, I'm told they might give me cancer from acrylamide.

[kismet]

I think it's derived from the epidemiological data on wine consumption. There's zero epidemiological data on long term high-dose resveratrol intake.
5mg may be not completely safe, but certainly safer than high doses?

Edited by kismet, 06 December 2008 - 02:22 PM.

[neogenic]

Isn't this debate similar to using antioxidants or anything anabolic/enhancing protein synthesis with cancer present...beta-carotene and all the others.

Anything that promotes growth or protects cells could promote tumor growth or protect cancer cells. But the downsides would only be in the presence of A TUMOR...right? When one doesn't have Cancer these are positive things. The only issue is if you have subacute Cancer (asymptomatic), in which it would potentially accelerate your symptoms and eventual diagnosis. I think we could find data like this on many supplements though.

I could be missing something, but I've seen these studies countless times with many supplements and it hasn't changed my supplementation one bit. I am anxious to here others thoughts on this. Maybe I am off-base.

Funk, or anyone else...what do you think of this train of thought?

[wayside]

Isn't this debate similar to using antioxidants or anything anabolic/enhancing protein synthesis with cancer present...beta-carotene and all the others.

Anything that promotes growth or protects cells could promote tumor growth or protect cancer cells. But the downsides would only be in the presence of A TUMOR...right? When one doesn't have Cancer these are positive things. The only issue is if you have subacute Cancer (asymptomatic), in which it would potentially accelerate your symptoms and eventual diagnosis. I think we could find data like this on many supplements though.

I could be missing something, but I've seen these studies countless times with many supplements and it hasn't changed my supplementation one bit. I am anxious to here others thoughts on this. Maybe I am off-base.

Funk, or anyone else...what do you think of this train of thought?

One theory I've heard is that we are all constantly getting cancers, but that the vast majority of the time our bodies' immune systems eliminate it (it's an argument used against using full-body scans as a preventative - they show stuff our bodies will deal with on its own but that we might feel compelled to do something about if we know it is there).

If you are ingesting something that is really pro-tumor, then it might be harder for your body to clean up the micro-cancers on its own, and one might develop into a more serious cancer that ordinarily wouldn't have.

[Brainbox]

One theory I've heard is that we are all constantly getting cancers, but that the vast majority of the time our bodies' immune systems eliminate it (it's an argument used against using full-body scans as a preventative - they show stuff our bodies will deal with on its own but that we might feel compelled to do something about if we know it is there).

I had the same impression as well, but it's hard to find evidence.

The following, although a bit OT, might be pointing in this direction.

The dynamics of the inflammatory response to cancer
Mikala Egeblad, Bryan Welm, Hosein-Kouros Mehr, *Matthew F. Krummel and Zena Werb
Departments of Anatomy and *Pathology, University of California, San Francisco, CA, USA
In 1863, Virchow hypothesized that the cancer originated at sites of chronic tissue injury and that the ensuing
inflammation they cause enhances cell proliferation. While it is now clear that proliferation of cells alone does
not cause cancer, sustained cell proliferation in an environment rich in inflammatory cells, growth factors, activated
stroma, and DNA damage promoting agents, certainly potentiates and/or promotes neoplastic risk. The causal
relationship between inflammation, innate immunity and cancer is now widely accepted. Indeed, modifying the
inflammatory response decreases tumor development and progression.We used genetic and in vivo imaging
techniques to study the interaction between leukocytes and epithelial cancer cells during tumor progression by
crossing transgenic tumor-prone mice with mice expressing enhanced green fluorescent protein under general
and inflammatory cell-specific promoters and with mice lacking specific matrix metalloproteinases (MMPs).We
visualized the behavior of the cancer cells and leukocytes in living, anaesthetized mice using a novel four-color
spinning disk confocal microscope.We found that developing tumors undergo an inflammatory switch. The
leukocytes observed at the tumor-stroma interface are very motile whereas those within the tumor are relatively
immotile. The motility of the inflammatory cells is regulated by hypoxia and phagocytosis. These studies show
the dynamic behavior and interactions of cancer cells and leukocytes during mammary carcinoma progression.
Our data support the hypothesis that that inflammatory cells both enhance tumor growth or inhibit tumor
progression.The challenge is to determine which cellular interactions are pro-tumor, and thus should be inhibited,
and which ones inhibit tumors and should be enhanced.

source.

[Skötkonung]

What I have heard about Benfotiamine's connection to cancer:

Note From Benfotiamine.Org:

A knowledgeable benfotiamine user has offered the following response to this article:

"I have searched through the publications of Laszlo Boros on the connection between thiamine and cancer and can report that he has developed so far no evidence that there is a link in humans. In laboratory rats, however, he showed that if they were initially deficient in thiamine, then thiamine supplementation improved the growth of advanced tumors, which are typically thiamine deficient. There was no evidence that thiamine supplementation encouraged the initial appearance of tumors or the increased growth of non-advanced tumors. Interestingly, extremely high megadoses of thiamine were found to have the opposite effect, reducing the growth of advanced tumors."

[FunkOdyssey]

Isn't this debate similar to using antioxidants or anything anabolic/enhancing protein synthesis with cancer present...beta-carotene and all the others.

Anything that promotes growth or protects cells could promote tumor growth or protect cancer cells. But the downsides would only be in the presence of A TUMOR...right? When one doesn't have Cancer these are positive things. The only issue is if you have subacute Cancer (asymptomatic), in which it would potentially accelerate your symptoms and eventual diagnosis. I think we could find data like this on many supplements though.

I could be missing something, but I've seen these studies countless times with many supplements and it hasn't changed my supplementation one bit. I am anxious to here others thoughts on this. Maybe I am off-base.

Funk, or anyone else...what do you think of this train of thought?

This is basically what I said in the post that precedes yours.

[sUper GeNius]

Okay, so what're everyones plans here? To take or not to take?

[kismet]

Personally: don't take. Too expensive in Europe and am going to research more promising supplements. Waiting until cancer issue gets resolved, in theory it could slow cancer.
If you are young and your regimen otherwise protects against cancer (e.g. CR) you might still want to take the gamble. Maybe you could take further precautions, cancer early detection?
But if you really like to take risks you could try 2500 times the RDA if there are no other side-effects. Are there any known side-effects from super high doses? I've read some members have taken up to 1000mg, you'd need to take way over 2500mg to get in the 2500RDA range I guess.
I hope this only applies to IV thiamine, otherwise it could get pretty ugly: "Symptoms of a thiamine overdose may include a feeling of warmth, weakness, sweating, nausea, restlessness, difficulty breathing, tightness of the throat, bluish colored skin, and death."

Okay, so what're everyones plans here? To take or not to take?

[sUper GeNius]

Personally: don't take. Too expensive in Europe and am going to research more promising supplements. Waiting until cancer issue gets resolved, in theory it could slow cancer.
If you are young and your regimen otherwise protects against cancer (e.g. CR) you might still want to take the gamble. Maybe you could take further precautions, cancer early detection?
But if you really like to take risks you could try 2500 times the RDA if there are no other side-effects. Are there any known side-effects from super high doses? I've read some members have taken up to 1000mg, you'd need to take way over 2500mg to get in the 2500RDA range I guess.
I hope this only applies to IV thiamine, otherwise it could get pretty ugly: "Symptoms of a thiamine overdose may include a feeling of warmth, weakness, sweating, nausea, restlessness, difficulty breathing, tightness of the throat, bluish colored skin, and death."

Okay, so what're everyones plans here? To take or not to take?

it's dirt cheap in the US.

[pycnogenol]

Okay, so what're everyones plans here? To take or not to take?

Well, I'm gonna keep taking it only because I'm an old obstreperous bastard that can use all the help I can get!

[neogenic]

What I have heard about Benfotiamine's connection to cancer:

Note From Benfotiamine.Org:

A knowledgeable benfotiamine user has offered the following response to this article:

"I have searched through the publications of Laszlo Boros on the connection between thiamine and cancer and can report that he has developed so far no evidence that there is a link in humans. In laboratory rats, however, he showed that if they were initially deficient in thiamine, then thiamine supplementation improved the growth of advanced tumors, which are typically thiamine deficient. There was no evidence that thiamine supplementation encouraged the initial appearance of tumors or the increased growth of non-advanced tumors. Interestingly, extremely high megadoses of thiamine were found to have the opposite effect, reducing the growth of advanced tumors."

That's an interesting post and backs up my original thoughts. That said wayside and brainbox posted good points I hadn't thought of and give an opposing view. Funk, I am sorry I missed that post. Your contribution is one I always look for (along with Krillin and Edward)...Thanks!

I still side mostly with the data above here and feel the same way about selenium as well. But that's another thread entirely. One study to me, especially one that shows correlation (selenium) and not necessarily causality doesn't show me a whole lot. Like I said its a call to do more research. Although in this case vs. selenium there isn't a wealth of data on this "nutrient". It is engineered with limited information. So I do see it both ways certainly. I am surprised there hasn't been the naturalist argument yet...much like using natural vs. synthetic E...is there any concern of benfotiamine an issue due to it unnaturalness? Don't know.

[mikeinnaples]

Regarding this subject ....there has been so much positive information on Benfotiamine, that I think its silly to stop a supplement because Michael found some bad information. Putting it into perspective, water can kill you at the right doseage, but does that mean we should stop drinking it?

[kismet]

All things are subjective aren't they? I've not found nor heard of "so much positive information" on benfotiamine/thiamine even compared to such simple substances like green tea, cocoa, creatine, etc - at least as of yet. On the other hand being somewhat optimistic, the cancer risk in the young may be not that high anyway, assuming the carcinogenic effect is real to begin with, so one could get away with supplemental B/T.

Edited by kismet, 12 December 2008 - 02:38 PM.

[NDM]

what keeps me away from all thiamine products is not cancer but acne ... Thiamine does a great job at breaking my forehead with pimples, 48 ho after taking it.

[allenallen]

2 thoughts:

1) "pre-existing level of thiamine deficiency " Like saying that cancer cells grow better with a high percenate more X when they are low on X, where X is a normal chemical, helpful for both cancer and normal cells. I'd like to know what is the rate when a normal (100%) supply of thiamine.

2) I would think that in countries where benfotiamine is given as an Rx (and it is my understanding this is over 10 years... yes?) that a pattern of increased cancers (if 2X normal!) would have shown up.

My conclusion is that, with the little knowledge we have, the cleanest supposition is to say it is safe, unless someone who has a cancer tumor is already deficient in thiamine, in which case any X will feed the tumor.

What would sway my opinion would be a longitudinal study of people taking benfo which showed abnormal problems in those people greater than a similar population (benfo given to alcoholics in Spain... yes?).

[niner]

2) I would think that in countries where benfotiamine is given as an Rx (and it is my understanding this is over 10 years... yes?) that a pattern of increased cancers (if 2X normal!) would have shown up.

My conclusion is that, with the little knowledge we have, the cleanest supposition is to say it is safe, unless someone who has a cancer tumor is already deficient in thiamine, in which case any X will feed the tumor.

What would sway my opinion would be a longitudinal study of people taking benfo which showed abnormal problems in those people greater than a similar population (benfo given to alcoholics in Spain... yes?).

The number of people getting it as a prescription drug is not that huge, and 2X isn't that much of an effect; it would take a large number of subjects to see that reliably. This would be a very expensive study. I'm not at all surprised that it hasn't been done. No one will stop you from taking benfotiamine, certainly not the people who sell it, but just assuming something is safe until proven dangerous is not a path everyone will want to take.

[kismet]

My conclusion is that, with the little knowledge we have, the cleanest supposition is to say it is safe, unless someone who has a cancer tumor is already deficient in thiamine, in which case any X will feed the tumor.

Clearly your conclusion is not based on a good understanding of biology 101. Benfotiamine has never been proven to do anything in the healthy and the data in diabetic animals and humans is somewhat lackluster. So both benefit and harm are speculative at this point in time, but cancer is a death sentence and its impact on longevity (or lack thereof) is well-established, while the influence of glycation isn't.

I just don't get why people want to take drugs without any meaningful research? That's not how medicine works: every exogenous (unphysiologic) substance is guilty until proven innocent. Time and time again this approach has proven superior to mega-dosing random stuff.

Edited by kismet, 18 August 2009 - 09:32 PM.

[JLL]

I just don't get why people want to take drugs without any meaningful research?

Because we've all seen what happens to people who don't take drugs: they die of old age, eventually.

Of course, taking the drugs probably won't help, but people take them because they might help. The roulette is spinning, time is running out, some people are betting, others aren't.

EDIT: This is not something I encourage people to do; I just think it answers your question.

Edited by JLL, 30 August 2009 - 09:45 AM.

[kismet]

I know that most people will answer that way, but it doesn't change the fact that most of them are wrong. If supps might help, they also might hurt and a simple implication of biology 101 is that statistically most supplements are going to hurt. Mindless supplementation will kill you faster and make your last days more miserable (we've all seen what happened to the pill-popping old school life extensionists, today they're dead or suffering from old age).
Now taking benfotiamine is not the most egregious error, if you are aware of the risks (and only then). But there are still no supplements showing life span extension in any long lived animals and very few supplements showing (or suggestive of) benefits in healthy humans while most people assessing the risks lack the expertise and time to balance them (remember: most supplements will hurt them). Therefore the odds are against you, if you don't stay with honest, interventional and proven science.

If taking benfo one must assign a probability to both options "it will hurt" and "it will help". Neither has ever been proven in healthy people after all. The probabilities are unkown, but what are the implications of the underlying diseases? Well, I'd say that cancer is obviously more important than glycation (then there's also the question of timing if the risk only applies to existing cancers for instance; then benfo would be safer in the young, although, then again the immediate benefits could be bigger in the elderly if they suffer from blood sugar problems).

Edited by kismet, 30 August 2009 - 12:09 PM.

[immortali457]

I know that most people will answer that way, but it doesn't change the fact that most of them are wrong. If supps might help, they also might hurt and a simple implication of biology 101 is that statistically most supplements are going to hurt. Mindless supplementation will kill you faster and make your last days more miserable (we've all seen what happened to the pill-popping old school life extensionists, today they're dead or suffering from old age).
Now taking benfotiamine is not the most egregious error, if you are aware of the risks (and only then). But there are still no supplements showing life span extension in any long lived animals and very few supplements showing (or suggestive of) benefits in healthy humans while most people assessing the risks lack the expertise and time to balance them (remember: most supplements will hurt them). Therefore the odds are against you, if you don't stay with honest, interventional and proven science.

If taking benfo one must assign a probability to both options "it will hurt" and "it will help". Neither has ever been proven in healthy people after all. The probabilities are unkown, but what are the implications of the underlying diseases? Well, I'd say that cancer is obviously more important than glycation (then there's also the question of timing if the risk only applies to existing cancers for instance; then benfo would be safer in the young, although, then again the immediate benefits could be bigger in the elderly if they suffer from blood sugar problems).

Who are these dead old school life extensionists you refer to?

[kismet]

Who are these dead old school life extensionists you refer to?

The same dead people JLL refers to, i.e. just a general example. The point being that the first wave of pill-popping life extensionists also died and suffered just like everyone else because a. supplements are generally useless (compared to the possibilities of biomedical interventions) and b. because their gamble probably turned out not so well.

[immortali457]

Who are these dead old school life extensionists you refer to?

The same dead people JLL refers to, i.e. just a general example. The point being that the first wave of pill-popping life extensionists also died and suffered just like everyone else because a. supplements are generally useless (compared to the possibilities of biomedical interventions) and b. because their gamble probably turned out not so well.

O.k thanks....I'll keep popping my pills.

[niner]

The point being that the first wave of pill-popping life extensionists also died and suffered just like everyone else because a. supplements are generally useless (compared to the possibilities of biomedical interventions) and b. because their gamble probably turned out not so well.

Supplements might be generally useless for lengthening Maximum lifespan, but that's a figure of merit that I don't care about. I care about mean lifespan, because that is far more likely to have an impact on my own lifespan. I also don't care about how supplements do or don't affect animals that are perfectly husbanded, because I am not perfectly husbanded. My diet is imperfect and, like Mick Jagger, I got nasty habits. (I take tea at three...) The evidence that certain supplements can improve the health, and thus increase mean lifespan, of typical humans is overwhelming. There's a real danger here of conflating things like vitamin D and Magnesium with the latest whacko herb because they all fall under the broad heading of "supplements".

[kismet]

Ok, but there's no such evidence for benfo. I would love to dispute those other points too (at least to some degree), but I'll do it another time.