Please correct me if I am wrong.
So both Disulfiram and DCA cause neuropathy. I am trying to dose both.
DCA can cause memory problems and hand tremors and possible Korsakoffs syndrome which could be very serious and what I am worried the most about. Of all the patients treated by Medicore they did not mention that side effect of DCA but in theory it is possible.
So this Korsakoffs is caused by not enough vit B1.
Neuropathy caused by Disulfiram is caused by other mechanism I assume and not by vit B1 depletion. CUSP 9 doctors are not supplementing with B1.
In that case Disulfiram would never cause Krsakoffs or memory problems because it does not deplete vit B1. So dosing Disulfiram even if taken with DCA I wouldn't have to worry about heart failure, or memory problems. So even If vit b1 is low and I stopped DCA I can still give Disulfiram. Is that correct?
Use of DCA is not associated with Korsakoffs syndrome. I only mentioned Korsakoffs to suggest that some of the symptoms following DCA use could be related to decreased levels of B1, but that was not to suggest that DCA could lead to Korsakoffs, which has never been documented.
ReplyDeleteI just uploaded two studies to the Library (folder 1, Therapies - Human studies), which are both phase 1 studies of DCA for brain tumors and solid tumors. The more recent study (Chu 2015) shows a chart (Table 3) of all the toxicity events experience by the 23 patients in this trial. The two most common toxicites at the doses used (6.25-12.5 mg/kg twice daily) were neuropathy (34.8%) and fatigue (34.8%). Confusion was reported in 8.7% and and dizziness in 8.7%. Loss of balance in 4.3%. The extent that low B1 levels contribute to these symptoms is unknown. Another trial in non-cancer patients showed that B1 supplementation did not prevent neuropathy at DCA dose of 12.5 mg/kg twice daily.
You are correct that disulfiram toxicity is unrelated to B1 depletion. DCA is thought to lower overall levels of B1, because several enzymes involved in DCA metabolism involve thiamine (B1) increasing the need for the vitamin.
I wouldn't go so far as to say that disulfiram would never cause memory problems, since there could be multiple causes of that besides B1 deficiency. There have been rare cases of disulfiram-related psychoses, and a member of this blog just reported that her husband experienced confusion which resolved when disulfiram was stopped.
The rare psychotic effects of disulfiram are more likely to do with its inhibition of dopamine-beta-hydroxylase. And other toxicities of disulfiram such as peripheral neuropathy are most likely caused by oxidative stress, lipid peroxidation, and demyelination in peripheral nerves (much of this is related to the copper chelating abililty of disulfiram metabolites, as copper increases oxidative stress, and copper is also necessary for the toxic effects of disulfiram on cancer cells).