October 2010 Issue

Thiamine Deficiency — RDs Are Key Players in Prevention and Treatment
By Theresa A. Fessler, MS, RD, CNSC
Today’s Dietitian
Vol. 12 No. 10 P. 78

In 1979, as college undergrads, a friend and I were discussing our chosen majors while walking to the campus bookstore. She made a statement that, although inaccurate, I have not forgotten: “There is no reason to be a dietitian nowadays because there are no deficiencies anymore. The foods are all fortified.”

Of course, we weren’t yet knowledgeable about the myriad disease states and socioeconomic situations that can result in severe nutrient deficiencies. This article highlights one particular vitamin—thiamine—that is of great importance when treating patients who are severely malnourished, even in modern industrialized nations today. RDs can be instrumental in the prevention and treatment of thiamine deficiency by being aware of risk factors, symptoms, physiology, and metabolic functions of thiamine as well as available products.

Background
Thiamine, also known as vitamin B1 and called aneurin, was the first vitamin to be discovered. Intestinal absorption of thiamine occurs mainly in the jejunum, by carrier-mediated active transport at low concentrations, and by passive diffusion at higher concentrations. Past research indicates that intestinal absorption of thiamine occurs for only a small percentage of a high oral dose and declines at intakes above 5 mg. Thiamine is carried in erythrocytes and plasma. The biological half-life is estimated to be nine to 18 days, and the average adult body contains approximately 30 mg. Urinary excretion increases when serum levels elevate and decreases when serum levels are lower.

Thiamine functions chiefly as thiamine pyrophosphate (TPP), sometimes referred to as thiamine diphosphate, a coenzyme in the metabolism of carbohydrates and branched-chain amino acids. TPP functions in decarboxylation of alpha-keto acids and transketolation reactions of hexose and pentose phosphates. For example, it is necessary for the conversion of pyruvate to acetyl coenzyme-A for entry into the Krebs cycle for energy production. Nerve and brain functions depend on thiamine’s metabolic roles in energy synthesis from glucose, production of myelin, and synthesis of amino acids and neurotransmitters.1-4

Symptoms and Complications of Deficiency
Thiamine deficiency has been historically known as the disease beriberi, occurring in areas where food supply is inadequate or of poor quality, such as in regions where the staple of the diet is polished rice. Symptoms include anorexia, weight loss, muscle weakness, an enlarged heart, and mental abnormalities such as decreased short-term memory and confusion. Lactic acidosis, hypotension, and muscle wasting characterize dry beriberi. Heart failure and edema occur in cases of wet beriberi.1-3

Today, thiamine deficiency in industrialized nations can manifest differently and can go unnoticed by some healthcare professionals if they are not familiar with it. Mild thiamine deficiency may be difficult to detect, with symptoms such as headaches, irritability, and fatigue and in children, poor growth. Prolonged mild deficiency can lead to peripheral nerve damage. Severe deficiency can result in structural and functional damage to the brain within two to three weeks.3 Severe thiamine deficiency results in an acute neurologic disorder called Wernicke’s encephalopathy (WE). Symptoms of WE include ophthalmoplegia, ataxia, and confusion. Without prompt treatment, patients with WE can develop irreversible brain damage called Korsakoff psychosis (or syndrome), which may progress to coma or death. Korsakoff syndrome is characterized by a loss of short-term memory, with retention of long-term memory, and confabulation.3

Who Is at Risk?
Severe thiamine deficiency resulting in WE has been most often found in situations of chronic heavy alcohol use along with poor diet. WE has also been reported in malnourished patients, such as those who have undergone gastrointestinal surgery and those with a small-bowel obstruction, hyperemesis gravidarum, anorexia nervosa, and various cancers. In some cancers, thiamine is used up by rapidly growing tumors, and some chemotherapy drugs can interfere with the functions of thiamine. Patients on renal dialysis, if poorly nourished, are also at risk because thiamine is lost in dialysate. Patients with magnesium deficiency (such as can occur with chronic diuretic use and in alcoholics) are at risk because magnesium is a cofactor in transketolase reactions and in the conversion of thiamine to TPP. WE has also been reported in patients on parenteral nutrition (PN) without multivitamins. In these cases, multivitamins were not added to PN due to multivitamin shortages, iatrogenic error and, in a report from Japan, financial issues resulting from a change in the national health insurance policy.3-5

Treatment
Intravenous (IV) or intramuscular (IM) administration of thiamine is advised for those at risk of or diagnosed with WE. Intestinal absorption is limited even in healthy patients and more so in the alcoholic and/or malnourished patient.3 In “The Royal College of Physicians Report on Alcohol: Guidelines for Managing Wernicke’s Encephalopathy in the Accident and Emergency Department,” published in Alcohol and Alcoholism in 2002, Thomson and colleagues explained that IV infusion of thiamine is necessary to achieve the high blood thiamine levels necessary for rapid diffusion and transport across the blood-brain barrier. Oral thiamine would not increase blood levels sufficiently nor quickly enough to treat the emergent condition of WE.

Currently there is not sufficient evidence to guide clinicians on optimum use of thiamine for treatment of WE due to the lack of randomized controlled studies. However, some researchers have recommended specific protocols. Individuals with WE due to chronic excess alcohol use have required larger doses of thiamine and are more likely to develop Korsakoff syndrome than those with WE for other reasons.3 Thomson and colleagues recommend that for any patient in whom WE is suspected or diagnosed, 500 mg of IV thiamine should be given over a period of 30 minutes three times per day for three days. If symptomatic improvement occurs, 250 mg of IV or IM thiamine should be given per day for three to five days or until there is no further clinical response.

Smaller doses of IV thiamine may be sufficient to replete thiamine status for some patients with WE. In a recent study conducted in Italy, eight cases of WE were diagnosed by clinical symptoms and cranial magnetic resonance scans. Seven patients had received PN without added multivitamins (due to iatrogenic error). The patients were given 100 mg of thiamine per day intravenously for three days. In six of the cases, the symptoms of WE disappeared after the first day; in one case, Korsakoff syndrome occurred.4

Treatment with 250 mg/day of IM thiamine has been recommended for patients without signs of WE but in whom thiamine deficiency is suspected3; however, many clinicians use the oral or enteral route and various dosage amounts. According to the American Hospital Formulary Service AHFS Drug Information 2010, a usual recommended adult dose of IV or IM thiamine hydrochloride is 5 to 100 mg three times per day. For critically ill adults who have improved symptomatically or for those who are not critically ill, a typical dosage for oral thiamine hydrochloride is 5 to 30 mg daily given in single or divided doses for one month. A usual dose for children with thiamine deficiency is 10 to 50 mg oral thiamine hydrochloride per day in divided doses and for those who are critically ill, IV or IM doses of 10 to 25 mg per day.

Additional thiamine can easily be added to PN or enteral nutrition regimens. In North America, thiamine hydrochloride is available in a 100 mg/mL injectable form, as oral tablets (25, 50, 100, 250, and 500 mg), and in varying amounts in many different multivitamin products. In the United Kingdom, a product called Pabrinex, a two-ampule mixture containing 250 mg of thiamine along with riboflavin, pyridoxine, nicotinamide, and vitamin C, is used.3 The injectable form of thiamine hydrochloride can be added to IV fluid or PN solutions. The oral tablets can be crushed and mixed with water for administration via an enteral feeding tube. At the author’s institution, patients who are severely malnourished are usually given at least 100 to 200 mg of extra thiamine per day (in addition to the standard multivitamin mixture) added to PN or IV fluid and also as tablets given enterally.

Other Considerations
Malnourished patients should also be treated with complete multivitamin supplementation, as they are most likely deficient in many micronutrients, especially the water-soluble vitamins. Because of thiamine’s role in glucose metabolism, IV glucose or PN infusion can precipitate or worsen thiamine deficiency or WE in susceptible patients, so it is important that IV thiamine be given prior to or concurrent with IV fluids containing glucose. Although there are blood tests for thiamine deficiency, it is not prudent to wait for test results, which may take several days, prior to giving thiamine to a patient who is suspected to have WE, as immediate treatment is crucial.

Malnourished patients are also at risk for refeeding syndrome, so potassium, magnesium, and phosphorus levels should be monitored daily during initial treatment. Magnesium is of particular importance due to its role in thiamine metabolism and as a cofactor of enzymes. There is a low risk of anaphylactic reaction to IV thiamine; thus, dilution in 100 mL of normal saline or 5% glucose and slow infusion over 30 minutes is recommended, and treatment should be done in a facility that can treat anaphylaxis.3

Importance of Ongoing Knowledge
Thiamine deficiency is a current and real problem among patients who are severely malnourished, particularly chronic alcoholics. If untreated, severe thiamine deficiency can progress to permanent brain damage or death. Ongoing knowledge of recent findings regarding thiamine can help RDs to be successful in the prevention of deficiency, identifying those who are at risk, and helping ensure appropriate treatment.

— Theresa A. Fessler, MS, RD, CNSC, is a nutrition support specialist at the University of Virginia Health System in Charlottesville and a freelance writer. She has been an RD for more than 20 years and has specialized in nutrition support for 17 years.

 

References
1. Thiamin. In: Institute of Medicine, Food and Nutrition Board. Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline. Washington, D.C.: National Academies Press; 1998.

2. Otten JJ, Pitzi Hellwig J, Meyers LD, eds. Dietary Reference Intakes: The Essential Guide to Nutrient Requirements. Washington, D.C.: National Academies Press; 2006.

3. Sechi G, Serra A. Wernicke’s encephalopathy: New clinical settings and recent advances in diagnosis and management. Lancet Neurol. 2007;6(5):442-455.

4. Francini-Pesenti F, Brocadello F, Manara R, et al. Wernicke’s syndrome during parenteral feeding: Not an unusual complication. Nutrition. 2009;25(2):142-146.

5. Shikata E, Mizutani T, Kokubun Y, Takasu T. ‘Iatrogenic ‘ Wernicke’s encephalopathy in Japan. Eur Neurol. 2000;44(3):156-161.

 

Recommended Dietary Allowance for Thiamine

Children aged 1 to 3: 0.5 mg/day
Children aged 4 to 8: 0.6 mg/day
Children aged 9 to 13: 0.9 mg/day
Children aged 14 to 18: 1 mg/day (female) and 1.2 mg/day (male)
Adults aged 19 and older: 1.1 mg/day (female) and 1.2 mg/day (male)

— Author compiled information using reference 2

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