Dr. Kumar of the Mayo Clinic and the Mayo College of Medicine has no relevant financial relationships to disclose.)
Dr. Lanska of the University of Wisconsin School of Medicine and Public Health, the Medical College of Wisconsin, and IM Sechenov First Moscow State Medical University has no relevant financial relationships to disclose.)
This article includes discussion of thiamine deficiency, vitamin B1 deficiency, and thiamin deficiency. The foregoing terms may include synonyms, similar disorders, variations in usage, and abbreviations.
The best characterized human neurologic disorders related to thiamine deficiency are beriberi, Wernicke encephalopathy, and Korsakoff syndrome. Thiamine deficiency is increasingly being recognized in nonalcoholics. Some neurologic complications following bariatric surgery are related to thiamine deficiency. The classic Wernicke encephalopathy triad of ocular abnormalities, gait ataxia, and mental status changes is infrequently seen. Prompt recognition and adequate therapy are key factors in improving prognosis.
• The best characterized human neurologic disorders related to thiamine deficiency are beriberi, Wernicke encephalopathy, and Korsakoff syndrome.
• Thiamine deficiency is increasingly being recognized in non-alcoholics.
• Some neurologic complications following bariatric surgery are related to thiamine deficiency.
• The classic Wernicke encephalopathy triad of ocular abnormalities, gait ataxia, and mental status changes is infrequently seen.
• Prompt recognition and adequate therapy are key factors in improving prognosis.
Historical note and terminology
The best characterized human neurologic disorders related to thiamine deficiency are beriberi, Wernicke encephalopathy, and Korsakoff syndrome (also referred to as Korsakoff psychosis). Because of the close relationship between Wernicke encephalopathy and Korsakoff syndrome, the term Wernicke-Korsakoff syndrome is commonly used.
Beriberi has the distinction of being the first-identified human nutritional deficiency disorder. During the industrial revolution of the nineteenth century, introduction of milled rice was accompanied by epidemics of beriberi. Milling removes the husk, which is a rich source of thiamine; therefore, polished white rice is deficient in thiamine. A connection between the consumption of polished rice and beriberi was shown in the latter part of the nineteenth century. In the 1950s, universal thiamine enrichment of rice, grains, and flour products was undertaken. Wernicke encephalopathy was first described in 1881 by Carl Wernicke who described it as an acute superior hemorrhagic polioencephalitis (“polioencephalitis hemorrhagica superioris”) in two alcoholic men and a woman who developed recurrent vomiting due to pyloric stenosis related to sulphuric acid ingestion. In the 1940s it was established that Wernicke encephalopathy is caused by thiamine deficiency. The historical aspects of thiamine deficiency have been reviewed in detail in a publication (Pearce 2008).
. The highest concentrations of thiamine are found in yeast and in the pericarp of grain. Most cereals and breads are fortified with thiamine. Organ meats are a good source of thiamine; dairy products, seafood, and fruits are poor sources. Preterm breast milk is poorer in thiamine as compared to term breast milk (Ford et al 1983). Cow's milk and infant formula have a higher level of thiamine than human milk or evaporated milk formula (Friel et al 1997). Prolonged cooking of food, baking of bread, and pasteurization of milk are all potential causes of thiamine loss. Thiamine does not occur in fats and oils.
. Thiamine requirement is related to the total caloric intake and proportion of calories provided as carbohydrates (Sauberlich et al 1979). A high caloric and high carbohydrate diet increases the demand for thiamine. According to the Food and Agriculture Organization and the World Health Organization, the recommended intake is 0.4 mg of thiamine per 1000 kcal; the Food and Nutrition Board recommends a daily allowance of 0.5 mg per 1000 kcals. The median intake of thiamine from food in the United States is approximately 2 mg/day. Thiamine requirement is also dependent on the body's metabolic rate with the requirement being the greatest during periods of high metabolic demand. Thiamine requirements increase in children, during pregnancy and lactation, and with vigorous exercise. Increased requirements are also seen in hyperthyroidism, malignancy, systemic infections, and in the critically ill. In patients with a marginal nutritional status, the increased metabolic demand associated with these conditions can precipitate symptoms of thiamine deficiency.
. The terms vitamin B1 and thiamine are used interchangeably. At low concentrations, thiamine is absorbed in jejunum and ileum by an active, carrier-mediated, rate-limited process (Thomson et al 2002). At higher concentrations, absorption takes place by passive diffusion. Adequate blood thiamine levels can be rapidly achieved with high-dose oral thiamine (Smithline et al 2012). After gastrointestinal uptake, thiamine is transported by portal blood to the liver. Transport of thiamine across the blood-brain barrier occurs by both active and passive mechanisms (Thomson et al 2002; Lockman et al 2004). Thiamine functions as a coenzyme in the metabolism of carbohydrates, lipids, and amino acids. It has a role in energy production by adenosine triphosphate synthesis, in myelin sheath maintenance, and in neurotransmitter production. Following cellular uptake, thiamine is phosphorylated into thiamine diphosphate, the metabolically active form that is involved in several enzyme systems (Butterworth 1986; Manzo et al 1994). Thiamine diphosphate is a cofactor for the pyruvate dehydrogenase complex, alpha-ketoglutarate dehydrogenase, and transketolase (Butterworth 1986). Pyruvate dehydrogenase and alpha-ketoglutarate dehydrogenase are involved in the tricarboxylic acid cycle in oxidative decarboxylation of alpha-ketoacids such as pyruvate and alpha-ketoglutarate to acetyl CoA and succinate, respectively. Transketolase transfers activated aldehydes in the hexose monophosphate shunt (pentose-phosphate pathway) in the generation of nicotinamide adenine dinucleotide phosphate (NADPH) for reductive biosynthesis. Thiamine diphosphate may be further phosphorylated to thiamine triphosphate, which may activate high-conductance chloride channels and have a role in regulating cholinergic and serotonergic neurotransmission (Bettendorff 1994).
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