eMedicine Specialties > Endocrinology > Metabolic Disorders

Beriberi (Thiamine Deficiency)

Author: Dieu-Thu Nguyen-Khoa, MD, Assistant Professor, University of California Los Angeles Residency Program; Physician Specialist, Valley Care-Olive View Medical Center
Coauthor(s): Dennis W Cope, MD, FACP, Emeritus Professor of Clinical Medicine, University of California Los Angeles School of Medicine; Chief, Department of Internal Medicine, Olive View-University of California Los Angeles Medical Center; Ginette V Busschots, MD, Staff Physician, Assistant Professor, University of Michigan, Department of Emergency Medicine, Foote Hospital; Phyllis A Vallee, MD, Associate Program Director, Department of Emergency Medicine, Henry Ford Hospital; Assistant Professor, Department of Internal Medicine, Case Western Reserve University
Contributor Information and Disclosures

Updated: May 20, 2008

Introduction

Background

Thiamine deficiency, or beriberi, refers to the lack of thiamine pyrophosphate, the active form of the vitamin known as thiamine (also spelled thiamin), or vitamin B-1. Thiamine pyrophosphate acts as a coenzyme in carbohydrate metabolism through the decarboxylation of alpha ketoacids; it also takes part 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.^1,2

Thiamine is a water-soluble vitamin. The body cannot produce thiamine and can only store up to 30 mg of thiamine in its tissues. Thiamine is mostly concentrated in the skeletal muscles. Other organs that it is found in are the brain, heart, liver and kidneys. The half-life of thiamine is 9-18 days. It is excreted by the kidney.^3,4,5,6

Related eMedicine topic:
Beriberi [Pediatrics: General Medicine]

Pathophysiology

When healthy individuals are deprived of thiamine, thiamine stores are depleted within 1 month. However, within a week after thiamine intake stops, healthy people develop a resting tachycardia, weakness, and decreased deep tendon reflexes; some people develop a peripheral neuropathy.

Nervous system involvement is termed dry beriberi.⁷ This presentation usually 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 arise from 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.^8,9 Improvement can be achieved at any stage by the addition of thiamine, unless the patient is in frank Korsakoff syndrome. Only half of the 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 in order 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 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 low-output cardiac failure, because systemic vasoconstriction is reinstated before the heart muscle recovers. Support of 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 (within hours or days).

Related eMedicine article:
Wernicke Encephalopathy

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 those refugees who are relying on emergency food aid.¹⁰ 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 a remarkable recovery being 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 occurring 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.¹¹

Clinical

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,⁹  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 failure¹² (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 follows¹¹ :

• Congestive heart failure (CHF)
• 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 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 the necessary amounts of thiamine.

Dialysis also robs thiamine from the circulation.

Persons with a history of gastric bypass may also have beriberi.^13,14  For bariatric surgery, it is believed that deficiency can occur most during the first 6 months after surgery, when 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 a high level of thiaminases, including milled rice, raw freshwater fish, raw shellfish, and ferns
    • Food high in anti-thiamine factor, such as tea, coffee, and betel nuts
    • Processed food with a content high in sulfite, which destroys thiamine
  • Alcoholic state
  • Starvation state
• Increased consumption states
  • Diets high in carbohydrate or saturated fat intake
  • Pregnancy
  • Hyperthyroidism¹⁵
  • Lactation
  • Fever - severe infection
  • Increased physical exercise
• Increased depletion
  • Diarrhea
  • Diuretic therapies
  • Peritoneal dialysis
  • Hemodialysis
  • Hyperemesis gravidarum⁸

One cross-sectional observational study showed that up to 33% of patients admitted with a diagnosis of CHF had a thiamine deficiency due to chronic loop diuretic use, usually for more than 1 month.¹⁷

Risk factors for the development of thiamine deficiency in the study's patients consisted of the following:

• Normal renal function
• Lack of thiamine supplementation (as little as 1.5 mg thiamine/day has been effective in the prevention thiamine deficiency)
• Preadmission spironolactone therapy (indicating more advanced disease)

Repletion of thiamine in patients with CHF has been shown to improve left ventricular function.

• 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 the form of thiamine pyrophosphate) in a variety of metabolic processes. 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. This regeneration allows NADH to continue to be present to regenerate thiamine pyrophosphate without being consumed in the process.
    • If folic acid is deficient in cells, it causes an indirect thiamine deficiency, because thiamine is present but cannot be activated.

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