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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. Although there is no toxicity associated with thiamine excess, thiamine deficiency is responsible for “wet” beriberi high output (congestive heart failure) and “dry” beriberi (Wernicke encephalopathy and the Wernicke-Korsakoff syndrome). Patients at risk include those with malnutrition (HIV/AIDS, cancer, end-stage kidney disease, fad diets, anorexia nervosa, bulimia, cyclic vomiting, hyperemesis gravidarum, and after bariatric surgery), those with impaired absorption (alcoholism, sepsis, bariatric surgery, inflammatory bowel disease), 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 protects against thiamine deficiency for more than 1 week, patients with clinical deficiencies require larger doses for a longer period of time.

HISTORY

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”22 and was ultimately synthesized by Cline, Williams, and Finkelstein.28 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.109

In 1881, Carl Wernicke reported 3 patients with alcoholism who died after developing confusion, ataxia, and ophthalmoplegia.149 Autopsies showed characteristic hemorrhages surrounding the third and fourth cerebral ventricles. A few years later, Sergei Korsakoff reported amnesia and confabulation in 30 individuals with alcoholism and 16 without alcoholism that was preceded in many by the clinical findings reported by Wernicke.157 Today, these 2 neurologic disorders are often combined and called the Wernicke-Korsakoff syndrome in recognition that they are a spectrum of the same disease.

PHARMACOLOGY

Biochemistry

As a coenzyme in the pyruvate dehydrogenase complex, thiamine diphosphate (thiamine pyrophosphate), the active form of thiamine, facilitates the conversion (with bound lipoamide and magnesium as cofactors) 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.53 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.73 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). ...

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