Thiamin deficiency and toxicity Domina Petric, MD

Thiamin deficiency I. November 10, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

General signs of thiamin deficiency Organ system/function Signs Appetite Severe decrease, anorexia Growth Decreased Dermatologic Edema Muscular Cardiomyopathy, bradycardia, heart failure, weakness Gastrointestinal Inflammation, ulcer Vital organs Hepatic steatosis Nervous Peripheral neuropathy, opisthotonus November 10, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Beriberi This disease is prevalent in Southeast Asia, where polished rice is the dietary staple. It appears to be associated with the consumption of diets high in highly digestible carbohydrates but marginal or low in micronutrients. November 10, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

General symptoms of beriberi Anorexia Cardiac enlargement Lassitude Muscular weakness (with resulting ataxia) Paresthesia Loss of knee and ankle jerk responses (with subsequent foot and wrist droop) Dyspnea on exertion November 10, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Dry (neuritic) beriberi Occurs primarily in adults. It is characterized by peripheral neuropathy consisting of symmetrical impairment of sensory and motor nerve conduction affecting the distal (more than proximal) parts of the arms and legs. It usually does not have cardiac involvement. November 10, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Medscape.com November 10, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Wet (edematous) beriberi Involves as its prominent signs edema, tachycardia, cardiomegaly and congestive heart failure. In severe cases, heart failure is the outcome. The onset of this form of beriberi can vary from chronic to acute, in which case it is called shoshin beriberi and is characterized by greatly elevated lactic acid concentrations in the blood. November 10, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Staywellworld.org November 10, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Infantile (acute) beriberi Occurs in breastfed infants of thiamin-deficient mothers, most frequently at 2–6 months of age. It has a rapid onset and may have both neurologic and cardiac signs, with death due to heart failure, usually within a few hours. Affected infants are anorectic and milk is regurgitated. Other symptoms are vomiting, diarrhea, cyanosis, tachycardia and convulsions. Their mothers may show no signs of thiamin deficiency. November 10, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Wernicke-Korsakoff syndrome Owing to the fortification of rice and wheat with thiamin, frank thiamin deficiency is rare in industrialized countries but continues to be prevalent in countries without such fortification programs. Subclinical thiamin insufficiency appears to occur in industrialized countries. When such conditions are associated with excessive alcohol consumption, they produce an encephalopathy called the Wernicke–Korsakoff syndrome. November 10, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Wernicke-Korsakoff syndrome The signs of this syndrome range from mild confusion to coma: ophthalmoplegia with lateral or vertical nystagmus cerebellar ataxia psychosis confabulation severely impaired retentive memory and cognitive function The pathology is limited to the central nervous system. November 10, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Chronic alcohol consumption can lead to thiamin deficiency in several ways: Reduced thiamin intake due to the displacement of foods rich in thiamin (and other nutrients) by alcohol. Impaired absorption of thiamin from the small intestine. Impaired cellular uptake and utilization of thiamin. November 10, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Wernicke-Korsakoff syndrome The risk of Wenicke-Korsakoff syndrome is not limited to heavy alcohol users. The thiamin responsive syndrome has been diagnosed in nonalcoholic patients with hyperemesis gravidarum or undergoing dialysis. November 10, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Wernicke-Korsakoff syndrome Patients with Wernicke-Korsakoff syndrome frequently have a transketolase that has an abnormally low binding affinity for TPP. In most cases, it appears that this low affinity can be overcome by using high intramuscular doses of thiamin, to which most affected patients respond. Those patients who fail to respond may have yet another aberrant transketolase (or other TPP-dependent enzyme) incapable of binding TPP. TPP: thiamin diphosphate Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Epidemic neuropathy Widespread thiamin depletion in Cuba in 1992–1993 was reported during an epidemic of optic and peripheral neuropathy that affected some 50,000 people in a population of some 11 million. November 10, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Alzheimer’s disease 55% less α-ketoglutaric dehydrogenase Comparisons of Alzheimer’s disease patients and healthy controls have revealed modest (20%) reductions in the TPP contents of patients’ brains, but dramatic differences in the brain activities of TPP-dependent enzymes: 55% less α-ketoglutaric dehydrogenase 70% less pyruvic dehydrogenase markedly reduced transketolase November 10, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Parkinson’s disease Limited studies have suggested that patients with Parkinson’s disease may have lower cerebrospinal fluid levels of free thiamin (but not TPP or TMP) and reduced activities of less α-ketoglutaric dehydrogenase. In addition, α-ketoglutaric dehydrogenase was found to be inhibited by dopamine oxidation products, which are known to be elevated in Parkinson’s disease. November 10, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Thiamin-Responsive Megaloblastic Anemia (TRMA) Thiamin-responsive megaloblastic anemia with diabetes and deafness is a rare, autosomal recessive disorder reported in fewer than three dozen families. The disorder presents early in childhood with anemia, diabetes and/or deafness plus optic atrophy, cardiomyopathy and stroke-like episodes. The anemia responds to high doses of thiamin. November 10, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

TRMA Defects in thiamin transport were reported in TRMA patients. These have been found to be due to mutations of the SLC19A2 gene encoding the high-affinity thiamin transporter. November 10, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

A few cases of apparent thiamin dependency have been reported. These have involved cases of intermittent episodes of cerebral ataxia, pyruvate dehydrogenase deficiency, branched chain ketoaciduria and abnormal transketolase, all of which responded to very high doses of thiamin. November 10, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Other Thiamin deficiency has been reported in more than a fifth of nonalcoholic HIV-positive or AIDS patients. Pregnant women with hyperemesis gravidarum are known to be at risk of developing low thiamin status. In women with gestational diabetes, maternal thiamin deficiency correlates with macrosomia (abnormally high infant body weight). November 10, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Thiamin toxicity II. November 10, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Thiamin toxicity Parenteral doses of thiamin at 100-fold the recommended intake have been found to produce headache, convulsions, weakness, paralysis, cardiac arrhythmias and allergic reactions. November 10, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Literature Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008. November 10, 2018