AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Background

Thiamine deficiency or beriberi refers to the lack of thiamine pyrophosphate, the active form of the vitamin known as thiamine or vitamin B-1. Thiamine pyrophosphate acts as a coenzyme in carbohydrate metabolism through the decarboxylation of alpha-ketoacids and in the formation of glucose by acting as a coenzyme for the transketolase in the pentose monophosphate pathway. Persons may become deficient in thiamine either by not ingesting enough vitamin B-1 through the diet or by excess use, which may occur in hyperthyroidism, pregnancy, lactation, or fever. Prolonged diarrhea may impair the body's ability to absorb vitamin B-1, and severe liver disease impairs its use.

Thiamine is a water-soluble vitamin. Once it is absorbed; thiamine mostly concentrates in the muscle tissues. It is not easily stored in the body. It is excreted by the kidney.

Pathophysiology

In healthy individuals who are deprived of thiamine, thiamine stores are depleted in approximately 1 month. However, within a week of no thiamine intake, healthy people develop a resting tachycardia, weakness, and decreased deep tendon reflexes and some people develop a peripheral neuropathy.

Nervous system involvement is termed dry beriberi. Usually this presentation  occurs when poor caloric intake and relative physical inactivity are present. The neurologic findings can be peripheral neuropathy characterized by symmetric impairment of sensory, motor, and reflex functions of the extremities, especially in the distal lower limbs. Through histological analysis, the lesions comprise a degeneration of the myelin in the muscular sheaths without inflammation. Another presentation of neurologic involvement is Wernicke encephalopathy, in which an orderly sequence of symptoms occurs, including vomiting, horizontal nystagmus, palsies of the eye movements, fever, ataxia, and progressive mental impairment leading to Korsakoff syndrome. Improvement can be achieved at any stage by the addition of thiamine, unless the patient is in frank Korsakoff syndrome. Only half of patients treated at this stage recover significantly.

Wet beriberi is the term used for the cardiovascular involvement of thiamine deficiency. The chronic form of wet beriberi consists of 3 stages. In the first stage, peripheral vasodilation occurs, leading to a high cardiac output state. This leads to salt and water retention mediated through the renin-angiotensin-aldosterone system in the kidneys. As the vasodilation progresses, the kidneys detect a relative loss of volume and respond by conserving salt. With the salt retention, fluid is also absorbed into the circulatory system. The resulting fluid overload leads to edema of the dependent extremities.

By the time significant edema occurs, the heart has been exposed to a severely high workload to pump the required cardiac output needed to satisfy end organ requirements. Parts of the heart muscle undergo overuse injury, which results in the physical symptoms of tachycardia, edema, and high arterial and venous pressures. These changes can lead to myocardial injury, expressed as chest pain.

A more rapid form of wet beriberi is termed acute fulminant cardiovascular beriberi or Shoshin beriberi. The predominant injury is to the heart, and the rapid deterioration follows the inability of the heart muscle to satisfy the body's demands because of its own injury. In this case, edema may not be present. Instead, cyanosis of the hands and feet, tachycardia, distended neck veins, restlessness, and anxiety occur. Treatment with thiamine causes a low output cardiac failure as the systemic vasoconstriction is reinstated before the heart muscle recovers. Support of the heart function is an added requirement at this stage, and recovery is usually fairly quick and complete if treatment is initiated promptly. However, if no treatment is available, death occurs just as rapidly.

Frequency

United States

Beriberi is observed in developed nations in persons with alcoholism, people on fad diets, persons on long-term peritoneal dialysis without thiamine replacement, persons undergoing long-term starvation, or persons receiving intravenous fluids with high glucose concentration. No accurate statistics are available on the incidence of this condition.

International

Developing countries are known to have more vitamin deficiency problems in general, but no accurate statistics for thiamine deficiency are available.

Beriberi has been reported among refugees who are relying on emergency food aids. This is due to the lack of available micronutrition supplementation.

Mortality/Morbidity

This disease can be quickly fatal or can slowly rob an individual of almost all energy for even the simplest of daily activities. However, it is one of the most easily treatable conditions, with remarkable recoveries possible even in severe cases.

In cases of wet beriberi, clinical improvement can be observed within 12 hours of treatment, with normalization of heart function and size in 1 or 2 days. The recovery is so dramatic that treatment with thiamine is a diagnostic test, which can be used in cases of acute heart failure and insidious peripheral neuropathy.

Race

Vitamin deficiency has no racial predilection.

Sex

Vitamin deficiency has no sex predilection.

Age

No age predilection exists. Infantile beriberi occurs in infants aged 2-4 months who are fed only breast milk and whose mothers are thiamine deficient.

CLINICAL

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

History

Most patients have no symptoms and signs of thiamine deficiency; therefore, it must be suspected in the appropriate clinical setting.

Early symptoms and signs are often nonspecific and vague, such as fatigue.
Other common symptoms and signs are listed under the major organs that are affected.

Neurologic symptoms are as follows:

• Poor memory, irritability, sleep disturbance



• Wernicke encephalopathy, Korsakoff syndrome



• Bilateral symmetric lower extremities paresthesias, burning pain



• Muscle cramps



• Decreased vibratory position sensation



• Absent knee and ankle jerk



• Muscle atrophy



• Foot drop (late stage)

Cardiovascular symptoms are as follows:

• Tachycardia



• Chest pain



• Wide pulse pressure



• Heart failure (orthopnea with or without edema, warm skin due to vasodilation)



• Hypotension, shock

Gastroenterologic symptoms are as follows:

• Anorexia



• Abdominal discomfort



• Constipation

Infantile beriberi symptoms are as follows:

• Congestive heart failure



• Aphonia



• Absent deep tendon reflex

Persons with chronic alcoholism have low thiamine intake, impaired thiamine uptake and storage, accelerated destruction of thiamine diphosphate, and varying degrees of energy expenditure. Alcohol is a direct neurotoxin. The effects on the body's supply of thiamine and on the brain tissue are detrimental. Persons with known alcoholism should be administered parenteral thiamine as a routine action when they present to a medical facility.

Fad diets often do not contain necessary amounts of thiamine.

Dialysis also robs thiamine from the circulation.

Persons with history of gastric bypass may also have beriberi. For bariatric surgery, it is believed that deficiency can occur most during the first 6 months after surgery, where there is the most rapid weight loss.

States of high energy consumption, such as hyperthyroidism, pregnancy, or severe illness, require more thiamine and other nutrients.

Physical

High output cardiac failure should prompt investigation of thiamine deficiency as a cause. The same applies to neuropathic symptoms, particularly in the distal extremities.

Causes

• Lack of thiamine intake
  
  
  • Diets consisting mainly of the following:
    
    
    • Food containing high level of thiaminases-milled rice, raw fresh water fish, raw shellfish, ferns
    
    
    
    • Food high in anti–thiamine factor, such as tea, coffee, betel nuts
    
    
    
    • Processed food with contents high in sulfite, which destroys thiamine
       
  • Alcoholic state
  
  
  
  • Starvation state
     
• Increased consumption states
  
  
  • Diets high in carbohydrate or saturated fat intake
  
  
  
  • Pregnancy
  
  
  
  • Hyperthyroidism
  
  
  
  • Lactation
  
  
  
  • Fever- severe infection
  
  
  
  • Increased physical exercise
     
• Increased depletion
  
  
  • Diarrhea
  
  
  
  • Diuretic therapies
  
  
  
  • Peritoneal dialysis
  
  
  
  • Hemodialysis
  
  
  
  • Hyperemesis gravidarum
     
• Decreased absorption
  
  
  • Chronic intestinal disease
  
  
  
  • Alcoholism
  
  
  
  • Malnutrition
  
  
  
  • Gastric bypass surgery
  
  
  
  • Malabsorption syndrome - Celiac and tropical sprue
  
  
  
  • Folate deficiency, for example, in patients undergoing chemotherapy with high-dose methotrexate
    
    
    • Thiamine serves as a coenzyme in a variety of metabolic processes as thiamine pyrophosphate. In these processes, thiamine pyrophosphate is regenerated via the donation of a proton from the reduced form of nicotinamide adenine dinucleotide (NADH).
    
    
    
    • Folic acid is essential to having enough dihydrofolate reductase to regenerate NADH from its oxidative form so that NADH continues to be present to regenerate thiamine pyrophosphate without being consumed in the process.
    
    
    
    • If folic acid is deficient in the cells, then it causes an indirect thiamine deficiency because thiamine is present but cannot be activated.

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Other Problems to be Considered

• Alcoholic cirrhosis



• Hyperthyroidism, thyrotoxicosis, or both
  
  
  • When examining a patient with high output cardiac failure, thyrotoxicosis is an important differential diagnosis to consider and treat, although no definite clinical correlation has been found between thiamine and thyroid disease. Only animal studies suggest any benefit in administering thiamine to treat patients with thyrotoxicosis.
  
  
  
  • If thyrotoxicosis is suspected, the treatment must be directed at protecting the heart from the thyroid storm, as opposed to supporting the cardiac output while increasing the thiamine level. However, because no damage is expected from administering supplemental thiamine to patients with thyrotoxicosis, the addition of thiamine in their treatment is innocuous and may be helpful.
  
  
  
  • In laboratory studies, thiamine appears to inhibit formation of monoiodotyrosine (MIT) and diiodotyrosine (DIT). No clinical correlation has been reported.

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Lab Studies

• For practical reasons, replacing thiamine as an initial test may be most feasible. If the patient responds to treatment, a safe assumption is that a measure of thiamine deficiency was responsible for the condition. Thiamine is not toxic in high levels; thus, this route carries little risk and time is saved in treating the patient and money is saved in testing.



• If laboratory confirmation is needed, measure blood thiamine, pyruvate, alpha-ketoglutarate, lactate, and glyoxylate levels. Also, measure urinary excretion of thiamine and its metabolites. The scarcity of any of these chemicals strongly suggests thiamine deficiency.



• In conjunction with whole blood or erythrocyte transketolase activity preloading and postloading, a thiamine loading test is the best indicator of thiamine deficiency. An increase of more than 15% in enzyme activity is a definitive marker of deficiency. However, this test is expensive and time consuming and is only performed for criterion standard proof of deficiency.



• Measure urinary methylglyoxal.



• Measure serum thyroid-stimulating hormone (TSH) to rule out thyrotoxicosis-induced high output heart failure, if applicable.

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical Care

In suspected cases, prompt administration of parenteral thiamine is indicated. The recommended dose is 50 mg intramuscularly for several days. The duration of therapy depends on the symptoms, and therapy is indicated until all symptoms have disappeared. Maintenance is recommended at 2.5-5 mg per day orally, unless a malabsorption syndrome is suspected.

Support for other cardiac function is necessary in cases of wet beriberi because lack of cardiac function support leads to low output cardiac failure when the thiamine deficiency is corrected.

Thiamine, even at high concentrations, is not toxic in a person with normal renal function. No cases of thiamine toxicity have been reported from its use at the dosages indicated even in patients in critical condition.

Diet

Thiamine-containing foods include all vegetables and the outer layer of grains. Thiamine is not present in fats or highly refined sugars and is present sparingly in cassava. Factors in the diet that decrease absorption are the presence of foods containing thiaminases, such as milled rice, shrimp, mussels, clams, fresh fish, and raw animal tissues.

Cassava is a staple in many developing countries and has been used in a variety of high-energy diets. Although it contains thiamine (0.05-0.225 mg of thiamine per 100 g of cassava, depending on the crop), the high carbohydrate load of a diet rich in cassava actually consumes more thiamine than it offers the body and can result in thiamine deficiency from the same mechanism as administering dextrose to a person with limited supplies of the vitamin.

Table. Nutritional Needs for Specific Age Groups

Activity

The level of activity and high-energy consumption states (eg, hyperthyroidism, pregnancy, lactation, severe disease) increase the daily requirements of thiamine.

MEDICATION

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

The goals of pharmacotherapy are to correct the vitamin deficiency, reduce morbidity, and prevent complications.

Drug Category: Vitamins

Vitamins are essential for normal DNA synthesis.

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Further Inpatient Care

• Depending on the cause of the vitamin deficiency, a referral to an alcohol dependency clinic may be needed.



• Follow-up care until delivery of current pregnancy, intensive care of advanced cardiomyopathy, definitive care for hyperthyroidism, or further workup of intestinal derangement may be warranted.



• An optimal method for delivering the needed thiamine in a bioavailable form must be determined for long-term treatment of each patient.

Further Outpatient Care

• Most outpatient care is targeted at delivering thiamine in a bioavailable form to rehabilitated patients. Clinic follow-up with measurement of thiamine diphosphate activity may be warranted if relapse or noncompliance is suspected.

Prognosis

• The patient prognosis for beriberi is usually good, unless patients have established Korsakoff syndrome. When patients have progressed to this stage, the degree of damage is only minimally reversible.

Patient Education

• Include education regarding Korsakoff syndrome for patients being treated for alcohol dependency. As with any substance abuse treatment program, education needs to be combined with a serious multidisciplinary team approach to have any chance of success.



• With other causes of beriberi, once the primary problem has been addressed, an appropriate diet should provide thiamine levels that are more than adequate.

MISCELLANEOUS

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical/Legal Pitfalls

• Thiamine deficiency is an easily treatable condition, and adverse effects of treatment are minimal. Failure to recognize and treat thiamine deficiency can result in litigation.

Special Concerns

• Clinical response to thiamine administration remains the least expensive and easiest form of testing; however, clinicians usually miss the subclinical forms of beriberi.

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

• Merck Research Laboratories. Beers MH, Berkow R, Bogin RM, eds. The Merck Manual. 17^th ed. Whitehouse Station, NJ: Merck & Co; 1999:45-46.
• Angstadt JD, Bodziner RA. Peripheral polyneuropathy from thiamine deficiency following laparoscopic Roux-en-Y gastric bypass. Obes Surg. Jun-Jul 2005;15(6):890-2. [Medline].
• Braverman LE, Utiger RD. Werner and Ingbar's The Thyroid: A Fundamental and Clinical Text. 7^th ed. Baltimore, Md: Lippincott Williams & Wilkins; 1996:694, 864.
• Cole PD, Kamen BA. "Beriber" interesting!. J Pediatr Hematol Oncol. Dec 2003;25(12):924-6. [Medline].
• Indraccolo U, Gentile G, Pomili G, Luzi G, Villani C. Thiamine deficiency and beriberi features in a patient with hyperemesis gravidarum. Nutrition. Sep/2005;21(9):967-8. [Medline].
• Isselbacher KJ, Braunwald E, Wilson JD. Harrison's Principles of Internal Medicine. 13^th ed. New York, NY: McGraw-Hill; 1994:474-475.
• Koike H, Iijima M, Mori K, Hattori N, Ito H, Hirayama M, et al. Postgastrectomy polyneuropathy with thiamine deficiency is identical to beriberi neuropathy. Nutrition. Nov-Dec 2004;20(11-12):961-6. [Medline].
• McCormick DB. Shils ME, Young V.R. Modern nutrition and health and disease. Philadelphia, Pa: Lea and Febiger; 1988:355-361.
• Dietary reference intakes: Vitamins. Available at www.nal.usda.gov/fnic/etext/000105.html. Accessed April 6,2004.
• Thiamine Deficiency and Dependency. Available at www.merck.com/mrkshared/nmanual/section1/chapter3/3j.jsp.
• Thiamine. Available at http://en.wikipedia.org/wiki/Thiamine.
• Thiamine. Monograph. Altern Med Rev. Feb/2003;8(1):59-62. [Medline].
• Rosen P, Barkin R. Emergency Medicine: Concepts and Clinical Practice. 4^th ed. St. Louis, Mo: Mosby Year Book; 1998:2138-2140.
• Shenoy VV, Patil PV, Nagar VS, Deshpande AK, Shedge RT, Badiye AP, et al. Congestive cardiac failure and anemia in a 15-year-old boy. J Postgrad Med. Jul-Sep/2005;51(3):225-7. [Medline].
• Weise Prinzo Z, de Benoist B. Meeting the challenges of micronutrition deficiencies in emergency-affected population. Proc Nutr Soc. May/2002;61(2):251-7. [Medline].

Article Last Updated: Nov 15, 2006