Evidence for a central cholinergic effect of high-dose thiamine

In vitro animal studies have suggested that thiamine is involved in the presynaptic release of acetylcholine. Total thiamine content in cholinergic nerve terminals is comparable with that of acetylcholine, and the phosphorylation state of thiamine changes with release of acetylcholine. Thiamine binds to nicotinic receptors and may exhibit anticholinesterase activity. Based on these observations, we investigated the effects of pharmacological doses of thiamine on the cognitive deficits induced by the anticholinergic scopolamine in healthy young adults using a randomized, double-blind, placebo-controlled, double-crossover design. Drug effects were assessed by P3 event-related potential, quantitated electroencephalography, and free recall memory. Conditions included (1) baseline, (2) thiamine 5 gm p.o. and scopolamine 0.007 mg/kg IM, and (3) lactose PO and scopolamine 0.007 mg/kg IM. Thiamine significantly reduced adverse effects of scopolamine on P3 latency, spectral components of electroencephalography, and memory recall. The results are consistent with a cholinomimetic effect of thiamine in the central nervous system. Additional studies are needed to delineate the basic mechanisms and possible therapeutic efficacy of thiamine at pharmacological dosages.