Ben Sloan

Introduction. Wernicke Encephalopathy (WE) is a two-part syndrome widely associated with chronic alcohol abuse. WE alone is 10 times more prevalent in chronic alcohol abusers compared with the general population.¹ WE is caused by a thiamine deficiency (TD) resulting in a triad of clinical symptoms: altered mental status, gait ataxia, and ophthalmoplegia.¹ Thiamine is an important cofactor in numerous metabolic reactions thus TD can result in oxidative stress, Endoplasmic Reticulum (ER) stress, and autophagy which associated with TD-induced neurodegeneration.³ In addition, there have been several prescription drugs shown to implicate the thiamine transporter resulting in presentation of WE.⁶ Methods. Mice were subjected to chronic alcohol consumption to determine the effects of alcohol on thiamine levels.⁵ Researchers investigated the result of ethanol induced TD on ER and oxidative stress and neuronal damage.⁴ Immunoreactive staining and western blotting were utilized to determine the impact of ethanol on the thiamine transporters (THTR1 and THTR2) and levels of important metabolic ennzymes.⁵ Results. Alcohol exposure in mice reduced the brain thiamine levels by 42%.⁴ TD decreases the bioavailability of thiamine pyrophosphate (TPP), a cofactor in essential energy producing reactions. Ethanol induced TPP deficiency results in inactivation of PDHE1α via phosphorylation. Alcohol intake impairs neuronal mitochondrial respiration via TPP-mediated PDHE1α dysfunction, a likely mechanism of Wernicke-neuropathy.⁵ Chronic alcohol consumption increased the expression of ER and oxidative stress biomarkers resulting in an increase in caspase-3 activity.⁴ Pharmaceuticals have been shown to interact with the thiamine transporter. Fedratinib, a late stage therapy developed for treatment of myelofibrosis, showed to have a 4-fold uptake compared to thiamine at the thiamine transporter.⁶ Conclusions. Research shows that ethanol consumption impairs thiamine absorption by implicating the thiamine transporter in the gut (THTR2).⁵ A decrease in thiamine absorption results in TPP deficiency, an essential cofactor in many mitochondrial reactions, which is necessary to maintain cerebral energy homeostasis.⁵  Ethanol induced TD has shown to increase levels of cellular stress resulting in damage to sensitive neuronal tissue leading to the clinical symptoms typically seen in patients.⁴ Furthermore, several prescription drugs have been shown to interact with the thiamine transporter resulting in impairment of thiamine absorption. Clinicians should re-evaluate and closely monitor thiamine levels in patients placed on these select therapies to avoid development of WE.⁷ WE requires prompt treatment with parenteral thiamine. Delay in treatment, especially to pursue diagnostic testing, can be fatal, with a 20% mortality.¹

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