Juliegee wrote:I have much more to share on this tomorrow- specifically the importance of a specialized B1, thiamine, to optimize our brain's utilization of glucose. (It looks like Dr. Bredesen is already on to this- phew.)
Did anyone mention sulbutiamine? I have taken it off and on for several years because of its purported nootropic properties due to its ability to shuttle thiamine past the blood-brain barrier. Effects on me are not obvious, but some people swear by it. Lately I have only taken it once in a while - my supply is uncapped, so it can't just go down the hatch with all the other supplements.
I added benfotiamine a couple of months ago because it showed up in the Bredesen protocol - no obvious effects on me.
Anyway, here's a 2008 mouse study that compares the two and casts doubt on benfotiamine's ability to get thiamine to the brain:
Conclusion: Our results show that, though benfotiamine strongly increases thiamine levels in blood and liver, it has no significant effect in the brain. This would explain why beneficial effects of benfotiamine have only been observed in peripheral tissues, while sulbutiamine, a lipid-soluble thiamine disulfide derivative, that increases thiamine derivatives in the brain as well as in cultured cells, acts as a central nervous system drug. We propose that benfotiamine only penetrates the cells after dephosphorylation by intestinal alkaline phosphatases. It then enters the bloodstream as S-benzoylthiamine that is converted to thiamine in erythrocytes and in the liver. Benfotiamine, an S-acyl derivative practically insoluble in organic solvents, should therefore be differentiated from truly lipid-soluble thiamine disulfide derivatives (allithiamine and the synthetic sulbutiamine and fursultiamine) with a different mechanism of absorption and different pharmacological properties.
The researchers learned empirically as they developed their experimental procedure that benfotiamine is not lipophilic as often claimed, and they considered the biochemistry directly and offered a possible explanation for confusion on this point:
Wada et al. already noted that benfotiamine was sparingly soluble in organic solvents such as benzene, chloroform and methanol, but was readily soluble in aqueous media at pH≥8.0. This is not surprising as the phosphoryl group of benfotiamine has two negative charges at alkaline pH. Here, we confirm that benfotiamine is sparingly soluble in water at pH≤7.0 and cannot be dissolved in octanol or oils. Thus benfotiamine should not be classified as a "lipophilic" compound as many authors still do.[10,24,25,38] Indeed, benfotiamine appears unable to diffuse across cell membranes. We have shown here that intracellular thiamine content is not increased in cultured neuroblastoma incubated in the presence of 10 µM benfotiamine, while it was increased ten-fold after incubation with 10 µM sulbutiamine. Moreover, after a chronic treatment of rats with sulbutiamine intracellular thiamine derivatives were increased by respectively 250% (thiamine), 40% (ThMP), 25% (ThDP) and 40% (ThTP).
This is in apparent contradiction with results obtained with cultured cells of endothelial origin,[18-20,39] showing that benfotiamine is able to counteract glucose toxicity in these cells by increasing transketolase activity. However, the benfotiamine concentrations used were 50-100µM, much higher than in our study. Hammes et al. even report that there was no effect on transketolase activity in cultured endothelial cells at 10 or 25µM. In any event, this is no proof that benfotiamine is able to cross the membranes: indeed, cultured endothelial cells seem to possess an ecto-alkaline phosphatase. It is therefore likely that, in these cells, the added benfotiamine is at least partially dephosphorylated to S-benzoylthiamine that can enter the cells as in the case of the intestinal mucosa. The slow dephosphorylation to S-benzoylthiamine might also explain the lag period observed between the addition of benfotiamine to thiamine-depleted Neuro 2a cells and the increase in intracellular thiamine derivatives (Fig. 6). In erythrocytes, it was shown that fursultiamine, a lipophilic disulfide, is rapidly incorporated into the cells while benfotiamine is not. Taken together, these results strongly suggest that benfotiamine is unable to cross plasma membranes unless it is dephosphorylated.
They conclude by speculating that sulbutiamine may even be more effective at benfotiamine's purported sweet spot:
Furthermore our results on cultured neuroblastoma cells show that benfotiamine, in contrast to sulbutiamine, does not easily cross cell membranes (Figs 5 and 6). It would therefore be interesting to test whether a thiamine disulfide compound such as sulbutiamine or fursultiamine, would not be more efficient and act at lower concentrations than benfotiamine in counteracting diabetic complications.