THIAMINE DEFICIENCY IN INDIVIDUALS WITH ALCOHOLISM: IMPLICATIONS FOR THE DEVELOPMENT OF WERNICKE-KORSAKOFF SYNDROME

Abstract

Introduction: Chronic alcoholism is a major public health concern and is associated with several neurological complications, among which Wernicke-Korsakoff syndrome (WKS) is the most prominent neuropsychiatric disorder resulting from thiamine deficiency. Although the relationship between alcoholism, vitamin B1 deficiency, and WKS is well established, the pathophysiological mechanisms underlying disease progression remain scattered across the literature, hindering an integrated understanding of the condition. Objective: To analyze the scientific evidence regarding the pathophysiological mechanisms by which thiamine deficiency in individuals with chronic alcoholism contributes to the development and progression of Wernicke-Korsakoff syndrome. Methods: This integrative literature review was conducted using the National Library of Medicine (PubMed), Academic Search Ultimate, and the Virtual Health Library (VHL) databases, employing the descriptors "Korsakoff Syndrome," "Thiamine Deficiency," and "Alcoholism." Studies published between 2016 and 2025, available in full text and free of charge, in English or Portuguese, were included. After applying the eligibility criteria, nine studies comprised the final sample. Results: Most publications were written in English (88%) and included narrative reviews, experimental studies, observational studies, and one case report. The findings showed that thiamine deficiency initially induces alterations in cerebral energy metabolism, characterized by reduced activity of thiamine-dependent enzymes, decreased ATP production, and mitochondrial dysfunction, mechanisms addressed in 55% of the studies. Subsequently, this metabolic impairment promotes neuronal injury through oxidative stress, neuroinflammation, microglial activation, excitotoxicity, and neuronal loss, which were described in 66.6% of the selected articles. In addition, recent evidence suggests that genetic variants related to thiamine transport, particularly in the SLC19A1 gene, may influence individual susceptibility to the development of the syndrome. Discussion: The findings demonstrate that metabolic alterations and neuronal injury mechanisms act in an interdependent manner in the pathophysiology of WKS, with thiamine deficiency representing the central link between chronic alcoholism and neurodegeneration. Despite advances in understanding the molecular mechanisms involved, significant challenges remain regarding the early diagnosis and therapeutic management of the syndrome. Conclusion: Thiamine deficiency resulting from chronic alcoholism is the primary pathophysiological mechanism associated with the development of Wernicke-Korsakoff syndrome, promoting metabolic disturbances that progress to neuronal damage. These findings reinforce the importance of early identification of at-risk individuals and appropriate thiamine replacement as essential strategies to prevent potentially irreversible neurological sequelae.