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INTRODUCTION

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Thiamine (vitamin B1) is a water-soluble vitamin found in organ meats, yeast, eggs, and green leafy vegetables that is essential in the creation and utilization of cellular energy. While there is no toxicity associated with thiamine excess, thiamine deficiency is responsible for “wet” beriberi (congestive heart failure) and “dry” beriberi (Wernicke encephalopathy and the Wernicke-Korsakoff syndrome). Patients at risk include those with poor oral intake (HIV-AIDS, cancer, fad diets, anorexia nervosa, bulimia, hyperemesis gravidarum, and following bariatric surgery), those with impaired absorption (alcoholism and bariatric surgery), and those with enhanced elimination (high dose loop diuretic therapy). Typical signs of Wernicke encephalopathy include ataxia, altered mental status, and ophthalmoplegia. Although administration of 100 mg of parenteral thiamine hydrochloride will protect against thiamine deficiency for more than one week, patients with clinical deficiencies may require larger doses for a longer period of time.

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HISTORY

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Kanehiro Takaki, a physician in the Japanese navy, first established the relationship between a nutritional deficiency and beriberi in 1884. It was not until 1901 that Gerrit Grijns determined that the nutrient, as yet unnamed, was contained in the outer coat of rice and was lost during the polishing ­process. Ten years later, Casimir Funk isolated thiamine, and Williams finally determined its structure in 1934. Originally thiamine was called aneurin for “antineuritic vitamin”19 and was ultimately synthesized by Cline, Williams, and Finkeltstein.25 In 1936, Peters demonstrated that thiamine could reverse neurologic disease in nutritionally deprived pigeons and that improvement was coupled to an enhanced ability to metabolize pyruvate.82

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In 1881, Carl Wernicke reported three alcoholic patients who died after developing confusion, ataxia, and ophthalmoplegia.117 Autopsies showed characteristic hemorrhages surrounding the third and fourth ventricles. A few years later, Sergei Korsakoff reported amnesia and confabulation in 30 alcoholics that was preceded in many by the clinical findings reported by Wernicke.125 Today, these two neurologic disorders are often combined and called the Wernicke-Korsakoff syndrome in recognition that they are likely a spectrum of the same disease.

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PHARMACOLOGY

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Biochemistry

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As a coenzyme in the pyruvate dehydrogenase complex, thiamine diphosphate (thiamine pyrophosphate), the active form of thiamine, facilitates the conversion of pyruvate to acetylcoenzyme A (acetyl-CoA). This reaction occurs at the C2 atom of thiamine, which is located between the nitrogen and sulfur atoms on the thiazolium ring.38 In the protein-rich environment of the enzyme complex, this C2 atom is deprotonated to form a carbanion that rapidly attaches to the carbonyl group of pyruvate, thereby stabilizing it for decarboxylation.54 In a series of subsequent reactions, the hydroxyethyl group that remains bound to thiamine diphosphate is transferred to lipoamide, where an acetyl group is later broken off and attached to ­coenzyme A (CoA). This overall process links anaerobic glycolysis to the Krebs cycle, where subsequent aerobic metabolism produces the equivalent of 36 ...

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