Continuing Education Activity

Vitamin B1 is one of the eight B vitamins, also known as thiamin (thiamine). Because thiamin can only be stored in the body for a short time before it is readily excreted, a regular dietary intake of thiamin is necessary to maintain proper blood levels. The recommended daily intake (RDI) for adults over age eighteen is 1.2 mg/day for men and 1.1 mg/day for women. For children, adequate intake levels are lower. Women of any age who are pregnant should increase their daily intake of thiamin to 1.4 mg/day. This activity outlines the indications, mechanism of action, methods of administration, significant adverse effects, contraindications, and monitoring of vitamin B1 so providers can direct patient therapy in treatment or supplementation where it is indicated as part of the interprofessional team.

Objectives:

• Identify the physiological role/mechanism of action of thiamine (vitamin B1).
• Describe the signs and symptoms of thiamine deficiency.
• Review appropriate dosing of thiamine for patients exhibiting deficiency.
• Outline interprofessional team strategies for improving care coordination and communication to properly use vitamin B1 to improve patient outcomes for indicated deficiencies.

Indications

Thiamin (or thiamine) is also known as vitamin B1. It is one of the water-soluble B vitamins. Thiamin is present naturally in some diets or added to some food products and provided in the form of dietary supplements. During energy metabolism, thiamin plays a critical role in the human body. Thiamin is actively absorbed and passively diffused by the small intestine at nutritional and pharmacological doses, respectively.[1]

The intestinal enzyme phosphatase hydrolyzes thiamin into a free form which is then absorbed by the small intestine. The phosphorylated form of thiamin gets stored in the heart, kidneys, liver, and brain. It has a short half-life of 14 to 18 days; therefore, regular dietary intake of thiamin is necessary.[1][2]  In the human body, thiamin exists mainly in the form of thiamin diphosphate (TDP), also known as thiamin pyrophosphate (TPP). This is the main metabolic form of thiamin and serves as a cofactor for many enzymes during the metabolism of glucose, proteins, and lipids.[3] Foods rich in thiamin include whole grains, brown rice, pork, poultry, soybean, nuts, dried beans, peas, and fortified or enriched grain products such as cereals, infant formulas, and bread.[4][5][6] Multivitamins will provide an additional 1.5 mg of thiamin on top of a diet rich in thiamin.[7]

Thiamin (vitamin B1) deficiency occurs if the recommended daily intake (RDI) is not maintained. However, deficiency may also occur due to impaired intestinal absorption or high excretion rates, such as in people with alcohol dependency, acquired immunodeficiency syndrome (AIDS), and malnutrition.[8][9] Individuals with certain medical and non-medical conditions are more susceptible to vitamin B1 deficiency, e.g., alcohol dependency, older age, diabetes, post-bariatric surgery, malignant disease, gastrointestinal disease, pregnancy, lactation, fasting, starvation, use of unbalanced diets, hyperthyroidism, renal failure on hemodialysis, and systemic infections.[10][11]

Vitamin B1 deficiency may present with early or advanced symptoms. Early symptoms mainly arise from neurological, cardiac, and gastrointestinal systems, where patients may experience weight loss, anorexia, confusion, short-term amnesia, malaise, muscle weakness, and cardiac symptoms.

Beriberi is a disorder caused by vitamin B1 deficiency which can present as wet or dry types. Wet beriberi presents as a high-output cardiac failure with signs of edema, an enlarged heart, warm extremities, tachycardia, and respiratory distress. Dry beriberi is predominantly a neurological complication involving the peripheral nervous system and presents with peripheral neuropathy, malaise, muscle weakness, seizures, or brisk tendon reflexes.[10] Infants and children are susceptible to vitamin B1 deficiency as well, presenting as infantile or childhood beriberi. Usually, infants present with edema, ill-looking appearance, pallor, anorexia, coffee ground vomiting, and diarrhea. Neurological signs include a hoarse cry due to vocal cord paralysis, head lag, seizures, coma, and sudden infant death syndrome. Juvenile beriberi is uncommon and often misdiagnosed due to overlapping symptoms of meningitis.[3]

If vitamin B1 deficiency is prolonged or left untreated, an individual is at risk of advanced-stage symptoms. This condition is called Wernicke-Korsakoff syndrome (WKS). It is more common in the United States and 8 to 10 times more common among people with chronic alcohol consumption/misuse, severe gastrointestinal disorders, malignancies, drug use, and AIDS. It presents in two phases. Wernicke encephalopathy (WE) occurs early and presents with polyneuropathy, ataxia, ophthalmoplegia, and gait abnormalities. If left untreated, it can eventually evolve into Korsakoff psychosis (KS) with signs of severe short-term amnesia, disorientation, confabulation, and hallucinations.[12][13][14]

Mechanism of Action

Thiamin is a water-soluble vitamin and is absorbed into the blood from the gastrointestinal tract. It then circulates in the blood and ultimately gets excreted in the urine. Small amounts of thiamin are stored in the liver, heart, kidney, and brain, but only for a short duration.

In blood, the thiamin diphosphokinase enzyme converts thiamin into its active form, thiamin pyrophosphate (TPP). TPP plays different roles during different steps of metabolism, glycolysis, Krebs cycle, and pentose phosphate pathway.[1]

1. TPP works with enzyme functions during the metabolism of carbohydrates, lipids, and branched-chain amino acids.[1]
2. TPP acts as a cofactor at several steps during glycolysis and oxidative decarboxylation of carbohydrates.[1][15][16]
3. TPP acts as a coenzyme for the mitochondrial enzyme complexes such as α-ketoglutarate dehydrogenase and pyruvate dehydrogenase. These enzymes have a critical role in the Krebs cycle and tricarboxylic acid cycle. Thiamin deficiency decreases the activity of these enzymes, which impairs the conversion of lactate into pyruvate, leading to the accumulation of lactic acid. Lactic acidosis may cause focal damage to certain brain structures, such as mamillary bodies and the posteromedial thalamus, which can be seen on MRI.[1]

The presence of TPP is required by the erythrocyte transketolase enzyme during the pentose phosphate pathway of nucleotide synthesis and provides reduced nicotinamide adenine dinucleotide phosphate for several synthetic pathways.[15]

Administration

The RDI of thiamin for adults is 1.2 mg/day for men and 1.1 mg/day for women. For children, the RDI of thiamin is 0.2 mg/day during early infancy and then steadily increases with age. Pregnant women should increase their daily intake of thiamin to 1.4 mg/day. In the US, the average daily thiamin intake among children from the food itself is 1.27 mg, 1.54 mg, and 1.68 mg among individuals of 2 to 5 years, 6 to 11 years, and 12 to 19 years of age, respectively. Among men and women ages 20 years and above, the average daily intake of thiamin is 1.95 mg and 1.39 mg, respectively. Parenteral multivitamins contain 3 to 3.5 mg of thiamin; the adult enteral formula contains 2.2 to 2.9 mg per 1500 kcal/day of feed. The American Society for Parenteral and Enteral Nutrition recommends thiamine intake of 1.2 mg to a max of 10 mg per day.[1][17]

Thiamin can be administered by enteral, intravenous (IV), or intramuscular (IM) routes. The oral route is indicated in patients who do not have IV access. At present, the thiamin hydrochloride form has been used for the prevention and treatment of Wernicke encephalopathy (WE). However, there is a lack of evidence to suggest the route, dose, and duration of treatment for Wernicke encephalopathy. For patients at risk of deficiency or with confirmed deficiency, parenteral thiamin of 100 mg and 200 mg 3 times a day has been used, respectively, in clinical practice.[18] It should be given before food, and a nutritionally appropriate diet should be initiated after recommended thiamin supplementation. Once clinical symptoms improve, supplementation can switch to the oral route with a dose range of 50 to 100 mg per day.[1] Individuals with thiamin deficiency also require other nutrient supplementation, such as magnesium, vitamin B2 (riboflavin), B3 (nicotinamide), B6 (pyridoxine), B12, vitamin C, potassium, and phosphate.

Adverse Effects

Thiamin supplementation is reported to be well-tolerated and safe to use. A retrospective study on adverse effects of thiamin supplementation among more than 300,000 patients found no serious side effects. [19] However, some commonly reported adverse effects include nausea, urticaria, lethargy, ataxia, and impaired gut motility.[1] 

Contraindications

There have been no absolute contraindications against taking vitamin B1 reported in the literature. However, individuals with a history of allergic reactions to vitamin supplements should avoid taking thiamin supplements.

Monitoring

The serum level of thiamin is not a reliable indicator of thiamin status. However, thiamin function can be measured by erythrocyte transketolase activity (ETKA). An EKTA of 0 to 15% is considered adequate, 15 to 25% is considered a moderate risk, and 25% or higher is considered high risk for thiamin deficiency.[20][21] Direct measurement of erythrocyte TPP can be done using whole-blood testing and has more sensitivity, specificity, precision, and robustness.[20] The concentration of TPP in the whole blood ranges from 70 to 180 nmol/L.[10] Urinary thiamin excretion can be used to measure adequate dietary intake. However, it does not reflect the thiamin stores in the body. In adults, thiamin excretion of <100 mcg/day suggests inadequate intake, and less than 40 mcg/day suggests thiamin deficiency.[22]

Toxicity

The human body excretes excess thiamin in the urine. There is a lack of evidence of toxicity from high thiamin intake from food or supplements. Food and Nutrition Board (FNB) concluded that excessive consumption of thiamin might cause adverse effects despite a lack of any strong evidence of toxicity. Per the Institute of Medicine, there is no established upper limit of thiamin intake reported in the literature to cause any toxicity.

Enhancing Healthcare Team Outcomes

All interprofessional healthcare team members (clinicians, nurses, dieticians, pharmacists) should encourage healthy nutrition for their patients. Thiamin deficiency is not common in North America but can occur in certain high-risk populations, and the interprofessional team needs to be alert to the signs of potential thiamin deficiency. Thiamin plays a very critical role in the human body. Therefore, deficiency can lead to a very serious, life-threatening clinical condition, including irreversible brain damage.

Thiamin therapy should be recommended by interprofessional healthcare teams. The outcome of patients with thiamin deficiency can be improved by early recognition of the disease and early initiation of the treatment before severe neurological and cardiac manifestations develop.