Many carrot-salads ago, back in ancient pre-pandemic times, I posted a study on high-dose biotin (300mg daily) stopping the so-called primary-progressive multiple sclerosis (PPMS) – the most aggressive variant of this “autoimmune” illness. The proposed mechanism of action for the benefit seen in that human clinical trial was biotin’s effects on restoring oxidative metabolism (OXPHOS) and ATP levels in the myelin-producing cells that are part of the central and peripheral nervous systems. A few years later, another study came out and demonstrated conclusively that all forms of MS are metabolic diseases, and can be successfully treated by reducing fat oxidation and improving glucose oxidation. It is well-known that biotin is one of the key factors in the oxidation of glucose. Vitamins B1 (thiamine) and B3 (niacinamide) are the other major factors controlling glucose oxidation. Thus, the therapeutic effects of high-dose biotin in MS are in all likelihood due to its effects on glucose metabolism.<\/p>\n
Over the last several years, several smaller studies, in both animals and humans, have demonstrated that reduced glucose metabolism is also implicated in a number of other neurological conditions, including Alzheimer’s Disease (AD), Parkinson Disease (PD), ALS, Huntington Disease (HD), etc. Borrowing from the prior discoveries in regards to MS, AD, PD, etc the studies below now claim that not only is reduced glucose metabolism the major driving factor for HD, but that intervention with high doses of thiamine and biotin seems to completely reverse the pathology. The animal study did confirm the thiamine+biotin combo to reverse the HD pathology, but the human clinical trial has not completed yet. Assuming the human clinical trial got the animal dose conversions right, it looks like thiamine in daily doses of 600mg-1,200mg combined with biotin in daily doss of 150mg, taken for up to a year, should be able to put HD in my favorite medical-euphemism state – “permanent remission”. It is the kind of bizarre word gymnastics medicine uses when it does not want to use the word “cure”:-)<\/p>\n
Btw, since the human study states that it is using the thiamine Hcl and\/or thiamine mononitrate salts, which have low absorption and bioactivity, it is plausible that using one of the liphillic thiamine analogs such as allithiamine, sulbutiamine, fursultiamine, prosultiamine, etc may provide both stronger effects while also using much lower doses (e.g. 1\/10 of the daily dose used for the Hcl\/mononitrate salts). Oh, and considering the crucial role of niacinamide in glucose metabolism (as mentioned above) I don’t see why adding niacinamide to the thiamine+biotin combo won’t increase the effectiveness even more.<\/p>\n
https:\/\/clinicaltrials.gov\/ct2\/show\/NCT04478734<\/a><\/p>\n https:\/\/www.science.org\/doi\/10.1126\/scitranslmed.abe7104<\/a><\/p>\n https:\/\/www.nature.com\/articles\/s41467-022-35388-x<\/a><\/p>\n “…Additionally, we show that DAG lipids, which activate PRKCE, were decreased in HD brains. Interestingly, protein kinase C signaling has been shown to be important to OPC differentiation, and myelination66<\/a>,67<\/a>,68<\/a>,69<\/a><\/sup>. We found PRKCE levels to be decreased in HD, and that downregulating\u00a0PRKCE<\/i>\u00a0in OPCs in vitro leads to increased differentiation of OLs. Further determination of the mechanism underlying these findings is the subject of future studies. Moreover, appropriate glucose metabolism is critical for the proper development and function of OLs<\/strong><\/span>, as OPCs transition to myelinating OLs70<\/a>,71<\/a>,72<\/a>,73<\/a><\/sup>. Finally, thiamine metabolism is linked to OL differentiation based on evidence from deficient pyruvate dehydrogenase function in humans, which is known to cause structural white matter abnormalities<\/strong><\/span>74<\/a><\/sup>, and experimental evidence from pyruvate-dehydrogenase deficient mice, which show a reduction of O4-positive OL\/OPCs<\/strong><\/span>75<\/a><\/sup>.”<\/p>\n