That’s disappointing. But this is a review, so how much can they screw up - I guess you have to follow all their references to see if they are distorting things; that’s a lot of work just to look at case reports. In general, the benfo excitement has kind of died down a bit. About 16 months ago I heard some rumors that people in Japan have been looking at benfotiamine and PD, but then nothing happened since. But like I said before, I’m very tired with papers that focus on a single molecule. No single molecule is going to “solve” PD, and constantly reading papers with such “findings” just makes me feel hopeless. We need a comprehensive approach starting with fundamentals, otherwise PD will turn into another “cure cancer” dynamic with no end in sight. So, some time ago I decided to just select one area and do a deep dive as far as I possibly can without having a lab. I want to become actually “specialist” (at least by absorbing the literature), in that one part. I selected calcium handling, because it seems to be such a basic part in NDDs in general.
Insofar as single molecules, I try to look at the broader context. For example, I am now convinced that statins are actually a negative for PD. But why? First you have disentangle the effect from the mechanism. The effect is lower LDL (or ApoB) - is that part of the chain? Or is it the mechanism of statins that’s the issue. Focusing on mechanism, as an example, I posted a study about how pitavastatin compared to other statins doesn’t deplete plasma CoQ10. If statins in general deplete CoQ10, is that going to factor into why they’re bad for PD? So it’s not just focusing on a single molecule - as an example of such:
Coenzyme Q10 and Parkinsonian Syndromes: A Systematic Review
So, would that mean that say, pitavastatin - unlike other statins - might not be a PD negative? There’s not enough in the literature to determine much. Exposure in early stages of PD (including before any symptoms), full blown PD, early onset vs late onset.
If you look at supplementing with CoQ10, this doesn’t do anything for PD - but what about supplementing for people who take statins? That has generally been underwhelming too.
So CoQ10 levels are lower in people with PD - but what do we do with that information? That’s the problem with single molecules being measured - because serum CoQ10 levels in PD are normal (or close to), the depletion is in various tissues, lympocytes etc. You don’t know why levels are lower in those tissues - is it downstream of some pathology, is causative itself or merely a marker etc. - that’s why I was interested to see if pitavastatin would exacerbate PD as well, since it doesn’t affect CoQ10 as much, but that’s again a tissue vs plasma thing. If you want to see how crazy these effects are of various statins, look at this (rat) study (free paper):
Influence of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors on ubiquinone levels in rat skeletal muscle and heart: relationship to cytotoxicity and inhibitory activity for cholesterol synthesis in human skeletal muscle cells
“This study sought to evaluate and compare the cytotoxicity of statins (cerivastatin, pitavastatin, fluvastatin, simvastatin, atorvastatin and pravastatin) in cultured human skeletal muscle cells (HSkMCs) and the effects on ubiquinone levels in statin-treated rat skeletal muscle and heart. Cerivastatin, the most potent inhibitor of HMG-CoA reductase, showed the strongest cytotoxicity (over 10-fold) among the statins examined, while the effects of the others were in a similar range. In rat experiments, neither pitavastatin nor cerivastatin decreased ubiquinone levels in skeletal muscle, but both dose-dependently lowered ubiquinone levels in the heart. As the rates of reduction by pitavastatin (9.6% at 30 mg/kg) and cerivastatin (9.7% at 0.3 mg/kg) were almost equal, it was estimated that cerivastatin reduced ubiquinone levels in the rat heart approximately 100-fold more strongly than pitavastatin, based on the effective doses. We found that cerivastatin showed the most potent cytotoxicity in HSkMCs and strongly lowered ubiquinone levels in the rat heart.”
So, CoQ10 levels in skeletal muscle tissue (where people complain about myalgia) were not affected by either cerivastatin or pitavastatin, both lowered levels in the heart, but cerivastatin reduced levels 100-fold more strongly than pitavastatin dose effectively?! And cerivastatin was vastly more cytotoxic.
Bottom line, you have to measure the levels of any single molecule in every tissue and you might find that the effects even in the same class of medications (say, statins), to be dramatically different.
Anyhow, it’s nice to come up for air from all these mechanistic studies and into the calm waters of outcome studies, where you just have to battle confounders. And in outcomes, benfotiamine is not shining - of course, maybe in combination with other stuff it might be of help.
