AUTHOR AND EDITOR INFORMATION

Section 1 of 11  

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

INTRODUCTION

Section 2 of 11  

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

Background

In 1630 a Dutch physician, Jacobus Bonitus, observed in Java, "a very troublesome affliction, ...called by the inhabitants Beri-beri (which means sheep), those, whom this same disease attacks, with their knees shaking and the legs raised up, walk like sheep." 

In the last 100 years, the cause of beriberi was determined to be deficiency of thiamine (vitamin B1), a water-soluble and heat-labile vitamin required for carbohydrate metabolism. Thiamine is essential for most vertebrates and some microorganisms. Beriberi has 2 main forms in humans, depending on the system of maximum involvement: wet beriberi (edematous cardiovascular dysfunction) and dry beriberi (multifocal peripheral and/or central neurologic dysfunction). Often times, patients present with features of both. 

How a single vitamin deficiency can have such diverse patterns of presentation is not fully understood. Possible explanations include the coexistence of other vitamin or dietary deficiencies; simultaneous comorbidities, simultaneous stressors, or both; individual genetic differences among the various enzymes that have thiamine as their cofactor; and variations in tissue stores or turnover of the vitamin.

In the Western world, beriberi is usually seen in patients in defined situations outside of the normal protective measures of modern society. Also, unusual physiologic conditions in which beriberi could have been predicted are recognized. Finally, chance circumstances in which thiamine deficiency is fully unanticipated are also recognized. Dietary thiamine deficiency can be caused by an overall poor nutritional intake, by dietary customs that rely heavily on inadequate food sources (eg, milled rice), and, rarely, by consuming foods that contain thiaminases or antithiamine compounds. A cohort at particularly high risk are individuals with alcoholism with poor nutrition because alcohol also impairs thiamine absorption.

In 1998, the Institute of Medicine of the National Academies published the recommended dietary intake of thiamine and other B vitamins for males and females (from infants to the elderly).¹ Also, a comprehensive monograph on beriberi was commissioned by the World Health Organization; it recommends that the term beriberi be replaced by thiamine deficiency.²

For more information regarding the cardiovascular and neurologic manifestations encountered in adult patients, see the eMedicine article Beriberi (Thiamine Deficiency).

Pathophysiology

Thiamine mainly functions as thiamine pyrophosphate (TPP), which serves as a prosthetic group or cofactor for several enzymes in carbohydrate metabolism. These enzymes all use thiamine's thiazole ring to activate and transfer a 2-carbon unit (aldehyde). They catalyze decarboxylation of pyruvate, ketoglutarate, and the transketolation reaction in the pentose phosphate pathway. 

Thiamine is also believed to have a role in nerve conduction through the synthesis of acetylcholine. An impairment in the decarboxylation pathway causes a decrease in ATP (energy) synthesis. A reduction of transketolase activity compromises the hexose monophosphate shunt and yields decreases in nicotinamide adenine dinucleotide phosphate (NADPH) formation, in electron transport, and in ATP synthesis.³

Impaired energy production, increased manufacturing of free radicals, and possible N-methyl-D-aspartate (NMDA) receptor–mediated toxicity have been hypothesized to yield neuronal injury (dry beriberi). The exact biochemical defect responsible for the clinical manifestations of cardiac beriberi (wet beriberi) or its acute form, Shoshin beriberi (from the Japanese, meaning "sudden collapse"), is not yet fully elucidated. Cardiac dysfunction may simply be compromised by myocardial tissue edema and energy depletion.

Thiamine is not widely distributed in high concentrations; consequently, many foods are now routinely fortified with it. Rich natural sources include whole grains, lean pork, peas, spinach, and legumes. Very little thiamine is present in fats, oils, and refined sugars. It is destroyed by heat, pasteurization, and ionizing radiation. Freezing does not affect the bioavailability of thiamine; however, it is insoluble in alcohol. The risk of beriberi increases in individuals who consume a diet high in thiaminase rich foods (eg, raw freshwater fish or shellfish, ferns), a diet high in antithiamine factors (eg, tea, coffee, betel nuts), or both.

Deficiency of thiamine affects the cardiovascular, muscular, nervous, and GI systems. The body stores of thiamine are minimal, and the duration of thiamine reserves is unknown. In one study, deficiency was detected after approximately 6 weeks without thiamine. In another study of healthy young men who consumed less than 0.2 mg of thiamine daily, urinary excretion of thiamine stopped within 18 days. Case studies have suggested that fatal deficiency can develop in as little as 3 weeks without thiamine intake.

Despite the widespread fortification of many foods and infant formulas with thiamine, clinicians must remain aware of the signs and symptoms of beriberi, a life-threatening, but rapidly reversible, condition.

Frequency

United States

The incidence of beriberi is unknown. Although all of the following published cohorts were not been based on American patients, they could have occurred within the United States.

• Besides individuals with alcoholism, beriberi outbreaks have been described in other poorly nourished cohorts. East Asian immigrants who maintain their typical diet are particularly vulnerable.
• Beriberi has been described in patients with GI diseases that include malnutrition, malabsorption syndromes (eg, human immunodeficiency virus [HIV] enteropathy⁴), and hyperemesis gravidarum.⁵ It has also been reported in hypermetabolic conditions such as lymphoma.
• In the late 1980s, a shortage of multivitamin infusion occurred in the United States due to reduced production.⁶ As a result, numerous patients dependent on total parenteral nutrition (TPN) developed beriberi, which was rapidly reversed by intravenous thiamine. Ironically, thiamine was readily available despite the multivitamin shortage.
• More recently, several case reports have described thiamine deficiency after bariatric surgery for morbid obesity.⁷ Deficiency is secondary to marked emesis, altered absorption, or both following the reconfiguration of the GI tract.
• In late 2003, a beriberi outbreak was seen among normal Israeli infants.⁸ The cause of the deficiency was a manufacturing omission of thiamine in a brand of soy-based formula exclusively marketed in Israel. Tragically, 2 of the earliest-affected infants died before the etiology was recognized.   
• An intriguing hypothesis that has recently been published by several groups links subclinical or unrecognized thiamine deficiency to adult congestive heart failure. Diuretics were found to result in increased thiamine excretion and to predispose to a relative deficient state. In a study from Toronto, one third of adults hospitalized with congestive heart failure had thiamine deficiency, compared with 12% of controls.⁹

International

• The prevalence of beriberi is much higher in East Asian countries because of the consumption of milled rice. Thiamine is contained in the outer coat of rice, and polishing destroys it. In the same countries, the custom of eating raw fish further increases the potential for deficiency.
• Breastfed infants whose mothers have thiamine deficiency develop an infantile form of beriberi.
• The same socioeconomic factors that yield beriberi in the West do so with much greater prevalence in East Asia. A study done in Indonesia revealed the prevalence of thiamine deficiency among low-income families to be as high as 66%.¹⁰ A study conducted in a group of Karen women from a refugee camp on the Thailand-Burma border revealed that up to 58% of these women were thiamine deficient 3 months postpartum, despite what appeared to be adequate dietary thiamine supplements.¹¹
• Outbreaks have been described in prisons,¹² drug rehabilitation centers,¹³ rural, agrarian communities, and in ships kept out at sea too long.
• A familial form of thiamine deficiency with mitochondrial myopathy has been described in Japan.¹⁴

Mortality/Morbidity

Mortality is rare and is usually restricted to wet beriberi (cardiac) that goes undiagnosed for too long and, hence, can not be treated. Morbidity is also rare and is usually seen in dry beriberi (neurologic) that is treated so late in the course of the illness that some residual neurologic deficits remain. In both situations, the timely recognition of the signs and symptoms of beriberi can result in thiamine replacement, which rapidly reverses the cardiovascular and neurologic dysfunction.

Race

The prevalence is highest in cultures that depend on a high proportion of their calories from foods that have poor thiamine content, such as milled rice. 

Sex

Beriberi can affect both genders, although alcoholism (a major risk factor) is more prevalent in males.

Age

Beriberi is predominantly observed in adults and infants aged 1-4 months (infantile beriberi).

CLINICAL

Section 3 of 11  

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

History

Thiamine deficiency has a wide range of clinical presentations. Although clinical overlap is common, the basic phenotypes are as follows:

• Wet beriberi
• • This phenotype affects the cardiovascular system and is divided into acute and chronic forms.
  • In acute wet beriberi or Shoshin beriberi, the predominant injury is to the heart, and rapid deterioration occurs because of the heart's inability to maintain function.
  • Presenting symptoms include tachycardia, low diastolic pressure, cardiomegaly, pulmonary edema, and cyanosis. Wet beriberi is characterized by elevated lactic acid levels. This condition can be readily reversed with thiamine infusion, if administered early.
  • Chronic wet beriberi with high-output cardiac failure has 3 stages.
  • • Initially, peripheral vasodilatation occurs, yielding high-output cardiac failure. 
    • Then, the progression of vasodilatation is perceived by the kidney as a relative loss of volume. The ensuing activation of the renin angiotensin system produces greater salt and water retention.
    • Consequently, further fluid overload results in peripheral edema and pulmonary effusions. 
  • Cardiac overuse injury that occurs in the above setting results in tachycardia, hypertension, and chest pain.
  • Thyrotoxicosis, a more common cause of high-output cardiac failure, is always among the differential diagnoses.
• Dry beriberi
• • This phenotype affects the neuromuscular system.
  • Polyneuritis and symmetric, ascending paralysis of the peripheral nerve systems predominate.
  • The sensory system is affected first, followed by the motor and autonomic systems.
  • Typically, tactile sensation is the first to be lost, followed by pain, and, finally, temperature.
  • Paresthesia and hyperesthesia usually begin with the lower extremities and gradually involve the upper extremities and perioral area.
  • Deep tendon reflexes are lost, calf muscles become painful, and foot drop and, eventually, wrist drop occur.
  • If untreated, progressive weakness, wasting of muscles, and, ultimately, complete paralysis occur. 
  • Encephalopathy is an alternative mode of presentation, with vomiting, disorientation, horizontal nystagmus, palsies of the eye movements (ophthalmoplegia), ataxia, and progressive mental impairment.
  • Korsakoff syndrome is a more ominous condition that usually precludes complete recovery. Confusion is followed by the loss of recent memory and confabulation, which is the creation of accounts of events to cover up the loss of memory. 
• Infantile thiamine deficiency
• • This occurs in various forms and typically affects breastfed infants whose mothers had beriberi.
  • Early on, the infant is constipated, crying, restless, and has emesis.
  • Three forms are recognized: 
  • • The pure cardiologic or pernicious form is common in infants aged 1-3 months. They present with cyanosis and features of acute cardiac failure. Infants usually die within 2-4 hours, but this type of deficiency responds very rapidly to thiamine.
    • The aphonic form is seen in infants aged 4-6 months. This milder form causes loss of voice due to paralysis of the vocal cords.
    • The pseudomeningitic form is encountered in infants aged 7-9 months. It presents with clinical signs of meningitis, but cerebrospinal fluid findings exclude infection. Vomiting, sweating, and seizures may be present. 
• Wernicke-Korsakoff syndrome
• • This is an autosomal recessive genetic disease seen most often in Europeans.
  • Affected patients have transketolases that bind thiamine pyrophosphate 10 times less frequently than normal. Patients with Wernicke-Korsakoff are much more sensitive to less severe thiamine deficiency.
  • This syndrome occurs most often in individuals with alcoholism who are malnourished. It is often precipitated by administration of glucose because excessive carbohydrate metabolism exacerbates a subclinical thiamine deficiency. Clinically, it combines features of both Wernicke encephalopathy and Korsakoff psychosis. 
• Subclinical thiamine deficiency
• • This deficiency is seen in people with high carbohydrate intake and low thiamine intake. 
  • Other at-risk groups include those with increased thiamine requirements because of raised physiological or metabolic demands. Clinical scenarios include pregnancy and lactation, heavy physical exertion, intercurrent illness (eg, cancer, liver diseases, infections, hyperthyroidism), and surgery.
  • This deficiency is rarely encountered in patients with increased losses, such as those seen with dialysis, chronic diuretic use, and malabsorption.
  • Symptoms are usually mild, with anorexia often the presenting symptom. Anorexia is regarded to be a protective phenomenon because continued intake of a high-carbohydrate diet could be detrimental.
  • Other early symptoms include weakness, aching, burning sensation in the hands and feet, indigestion, irritability, and depression. After 6-8 weeks, the only objective signs at rest may be a slight fall in blood pressure and moderate weight loss. After 2-3 months, apathy and weakness become extreme and calf muscle tenderness develops. Also, loss of recent memory, confusion, ataxia, and, sometimes, persistent vomiting occur.
  • Pediatric associations include growth restriction and sudden infant death syndrome (SIDS).

Physical

• Wet beriberi (cardiac)
• • Edema
  • Waxy skin
  • Vomiting
  • Widened pulse pressure
  • Systolic flow murmur
  • Gallop rhythm (third heart sound); best heard in left-lateral position during inspiration
  • Jugular venous distension
  • Tachycardia
  • Cardiomegaly
  • Pallor
  • ECG changes (prolonged QT, T-wave inversion, low voltage)
• Acute fulminant cardiovascular beriberi (Shoshin beriberi or occidental beriberi)
• • Breathlessness, cyanosis
  • Wet crackles in lower lung fields
  • Classic heart failure
• Dry beriberi (paralytic or nervous)
• • Pallor
  • Wasting
  • Listlessness
  • Tachycardia
  • Hepatomegaly
  • Symmetric peripheral neuropathy
  • Symmetric paresthesias, especially of the distal extremities, with diminished touch sensation
  • Weakness (starting with feet)
  • Loss of ankle and knee reflexes
  • Normal vibration and pain sensation
• Wernicke disease
• • Irritability, forgetfulness
  • Ataxia
  • Mental confusion
  • Nystagmus (horizontal more common than vertical)
  • Ptosis
  • Ophthalmoplegia
  • Delirium
  • Coma
• Korsakoff psychosis
• • Retrograde amnesia
  • Inability to learn
  • Confabulation
• Wernicke-Korsakoff syndrome - Combined features of both Wernicke disease and Korsakoff psychosis
• Infantile beriberi
• • Physical findings depend on the form but usually begin with nonspecific early findings, including the following:           
  • • Fatigue
    • Anorexia
    • Headaches
    • Irritability, fatigue
  • The physical findings in acute cardiac infantile beriberi are similar to those found in Shoshin beriberi, often with cyanosis.
  • The physical findings in aphonic infantile beriberi include hoarseness that progresses to a complete loss of crying.
  • The physical findings in pseudomeningeal infantile beriberi include nystagmus, muscle twitching, bulging fontanelle, convulsions and coma.

Causes

• Beriberi is caused by thiamine deficiency, which can be the result of different physiologic, dietary, and environmental factors. 
• Frequently, more than one risk factor is present.

DIFFERENTIALS

Section 4 of 11  

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

Other Problems to be Considered

• The differential diagnosis is very wide because different organ systems can be affected in different individuals.
• Other vitamin deficiencies (vitamin B-12, niacin) can coexist with beriberi and can also contribute to the neurologic symptoms.
• In cardiac failure, the differential diagnosis varies depending on the age group; congential diseases and infections are most important in infants and children.
• A high index of suspicion is needed for patients with chronic alcohol abuse, special diets, malabsorption, malnutrition, chronic dialysis, and diuretic use.

WORKUP

Section 5 of 11  

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

Lab Studies

• The most rapid, and thus the best diagnostic test in urgent situations, is observing a clinical response to administration of intravenous thiamine (few hours duration).¹⁵
• The most reliable in vitro laboratory tests involve measurement of whole blood or erythrocyte transketolase activity.
• • An enhancement of enzymatic activity from the in vitro addition of TPP is referred to as the TPP effect.
  • An increase in the enzymatic activity of more than 15% strongly supports the diagnosis of thiamine deficiency.
  • A depressed blood level of thiamine can be seen. 
• Elevated measurements of the following substances are characteristically noted because their metabolism depends on enzymes that have thiamine as their cofactors:
• • Pyruvate
  • Alpha-ketoglutarate
  • Lactate
  • Glycosylate
• Additional investigations that have been proposed as diagnostic tests include the following:
• • Urinary thiamine
  • Thiamine metabolites (thiazole or pyrimidine)
  • Methylglyoxal values
• Unexplained lactic acidosis that persists after fluid bolus should prompt consideration of beriberi.

Imaging Studies

• In infants, thiamine deficiency is characterized by involvement of the frontal lobes and basal ganglia, in addition to lesions present in the periaqueductal region, thalami, and the mammillary bodies that have been described in adults.¹⁶
• MR spectroscopy (MRS) reveals a characteristic lactate peak.

Other Tests

• Diffuse slowing of the EEG can be observed.

Procedures

• An intravenous push of thiamine is recommended in a deteriorating patient who has features suggestive of beriberi. 

Histologic Findings

• The histologic lesions of wet beriberi have been reported to be due to degeneration of myelin in the muscular sheaths without inflammation.

TREATMENT

Section 6 of 11  

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

Medical Care

• Monitor patients with cardiac failure in an intensive care unit.
• Because beriberi often presents with other vitamin B deficiencies, administer a complete vitamin B complex.
• After the high-output state has been addressed with thiamine, patients can go into standard congestive heart failure and, thus, may require ongoing cardiology consultation, possibly remaining in an intensive care unit.

Consultations

• Cardiologic evaluation with 2-dimensional echocardiography is necessary.
• • Essential for diagnosis and management of beriberi
  • Reveals congestive heart failure and the poor ventricular function observed in beriberi
  • Assists in cardiac dysfunction that remains after thiamine administration.
• Neurologic and psychiatric consultations are usually necessary. If dry beriberi has progressed, ongoing care is required.
• Nutritional consultation should be aimed at preventing a recurrence of the deficiency.
• For psychosocial causes, support counseling is essential to avoid recurrence. Specialized multidisciplinary teams are advisable for patients with chronic alcoholism to monitor their future course. Comprehensive follow-up programs are necessary to minimize recidivism in most cases of nutritional beriberi.

Diet

• Patients with lethargy, confusion, and severe heart failure need to be kept on a diet of nothing by mouth (NPO) to prevent aspiration. 
• Dietary sources of thiamine must be emphasized along with ongoing supplementation.

Activity

• Patients who present with congestive heart failure should have activity restricted.

MEDICATION

Section 7 of 11  

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

The treatment of choice is thiamine hydrochloride (ie, aneurine hydrochloride, vitamin B-1). In a prospective study of the safety of thiamine hydrochloride, Wrenn et al evaluated 989 patients (1070 doses of 100 mg).¹⁷ A total of 12 adverse reactions (1.1%) were reported. Minor reactions consisting of transient local irritation were observed in 11 patients (1.02%), and only one major reaction occurred (0.093%), consisting of generalized pruritus.

Several thiamine derivatives (eg, thiamine propyl disulfide [TPD], thiamine tetrahydrofurfuryl disulfide [TTFD]) have also been used to treat beriberi. These compounds are barely soluble in water. Even when orally administered, TPD and TTFD produce a higher thiamine level in the blood than thiamine hydrochloride.

If beriberi occurs in a breastfed infant, both the mother and child should be treated with thiamine. The physician should also be aware that thiamine deficiency can occur concurrently with other water soluble vitamin deficiencies.

Drug Category: Vitamins

These agents are organic substances required by the body in small amounts for various metabolic processes. Vitamins may be synthesized in small or insufficient amounts in the body or may not be synthesized at all, thus requiring supplementation.

FOLLOW-UP

Section 8 of 11  

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

Further Inpatient Care

• In the course of treatment for high-output cardiac failure, care must be taken that other supportive cardiac medications are continued in parallel with thiamine infusion. Failure to do so could precipitate low-output cardiac failure.
• Physicians must be able to elucidate risk factors surrounding the presenting patient in order to prevent recurrence.

Further Outpatient Care

• Preventive therapy should be used in patients with malabsorption problems, patients with decreased intake, patients on long-term TPN,¹⁸ and patients with increasing demand that lasts for more than 2 weeks.
• In specific cohorts (eg, patients with alcoholism), rehabilitation and support therapy must be incorporated into the treatment regimen.

In/Out Patient Meds

• In mild deficiency states, including a breast-feeding mother, a daily oral dose of 10 mg of thiamine during the first week, followed by 3-5 mg daily orally for 6 weeks, helps prevent deficiency.
• After infantile thiamine deficiency with acute heart failure is treated with parenteral therapy, the patient is then placed on oral thiamine, 3-5 mg daily for at least 6 weeks.

Transfer

• Patients with chronic alcoholism should be transferred to a facility with structured programs in place for treating substance abuse.

Deterrence/Prevention

• Physicians in the United States, especially those caring for Asian immigrants, must be able to recognize the various cultural and dietary customs that surround their particular patient population that place them at high risk.
• Internationally, subtle thiamine deficiency should be identified early, especially when dealing with populations at risk (eg, refugees, institutionalized persons, breastfed infants whose mothers are thiamine deficient).

Complications

• GI complaints, including constipation and colicky abdominal pain
• Muscle wasting
• Vision or hearing impairment
• Complete paralysis
• Ataxia
• Profound loss of recent memory with active imagination
• Delirium
• Death

Prognosis

• In patients with wet beriberi, improvement is observed in the first 6-24 hours after thiamine administration.
• • Cyanosis disappears.
  • The heart rate reduces.
  • The respiratory rate reduces.
  • Diuresis and reduction in heart size may be apparent within 1-2 days.
• In patients with dry beriberi, the complete resolution of the peripheral neurologic symptoms can take weeks to months.
• In patients with Wernicke encephalopathy, the ocular symptoms resolve within hours to days, and the confusional state subsides in days to weeks.  
• Korsakoff syndrome resolves over months, and residual deficits are often reported.

Patient Education

• Population at risk must be educated regarding the diversification of diet, the incorporation of foods high in thiamine, proper food preparation (shorter cooking time for vegetables, reduction in amount of rice washing prior to cooking), the value of whole grains, avoidance of alcohol, and thiamine supplementation, if that is necessary to maintain thiamine status.

MISCELLANEOUS

Section 9 of 11  

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

Medical/Legal Pitfalls

• Failure to consider the diagnosis may lead to severe congestive heart failure and death or permanent neurologic disability.
• Failure to recognize that patients with high-output states relieved by intravenous thiamine may remain in cardiac failure that can lead to morbidity.
• Failure to recognize early manifestations of Korsakoff syndrome often leads to residual impairments.

ACKNOWLEDGMENTS

Section 10 of 11  

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

The authors would like to thank Dori Harasek for her assistance in the preparation of this chapter.

REFERENCES

Section 11 of 11

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

1. Institute of Medicine of the National Academies. Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin and Choline. Washington DC: National Academy Press; 1998:[Full Text].
2. World Health Organization. Thiamine Deficiency and its prevention and control in major emergencies. 1999. [Full Text].
3. McCandless DW, Schenker S, Cook M. Encephalopathy of thiamine deficieny: studies of intracerebral mechanisms. J Clin Invest. Oct 1968;47(10):2268-80. [Medline].
4. Muri RM, Von Overbeck J, Furrer J, Ballmer PE. Thiamin deficiency in HIV-positive patients: evaluation by erythrocyte transketolase activity and thiamin pyrophosphate effect. Clin Nutr. Dec 1999;18(6):375-8. [Medline].
5. Indraccolo U, Gentile G, Pomili G, et al. Thiamine deficiency and beriberi features in a patient with hyperemesis gravidarum. Nutrition. Sep 2005;21(9):967-8. [Medline].
6. Centers for Disease Control and Prevention. Lactic acidosis traced to thiamine deficiency related to nationwide shortage of multivitamins for total parenteral nutrition--United States, 1997. JAMA. Jul 9 1997;278(2):109, 111. [Medline].
7. 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].
8. Fattal-Valevski A, Kesler A, Sela BA, et al. Outbreak of life-threatening thiamine deficiency in infants in Israel caused by a defective soy-based formula. Pediatrics. Feb 2005;115(2):e233-8. [Medline].
9. Hanninen SA, Darling PB, Sole MJ, Barr A, Keith ME. The prevalence of thiamin deficiency in hospitalized patients with congestive heart failure. J Am Coll Cardiol. Jan 17 2006;47(2):354-61. [Medline].
10. Djoenaidi W, Notermans SL, Verbeek AL. Subclinical beriberi polyneuropathy in the low income group: an investigation with special tools on possible patients with suspected complaints. Eur J Clin Nutr. Aug 1996;50(8):549-55. [Medline].
11. McGready R, Simpson JA, Cho T, et al. Postpartum thiamine deficiency in a Karen displaced population. Am J Clin Nutr. Dec 2001;74(6):808-13. [Medline].
12. Ahoua L, Etienne W, Fermon F, et al. Outbreak of beriberi in a prison in Cote d'Ivoire. Food Nutr Bull. Sep 2007;28(3):283-90. [Medline].
13. Fozi K, Azmi H, Kamariah H, Azwa MS. Prevalence of thiamine deficiency at a drug rehabilitation centre in Malaysia. Med J Malaysia. Dec 2006;61(5):519-25. [Medline].
14. Morovvati S, Nakagawa M, Sato Y, Hamada K, Higuchi I, Osame M. Phenotypes and mitochondrial DNA substitutions in families with A3243G mutation. Acta Neurol Scand. Aug 2002;106(2):104-8. [Medline].
15. Shivalkar B, Engelmann I, Carp L. Shoshin syndrome: two case reports representing opposite ends of the same disease spectrum. Acta Cardiol. 1998;53(4):195-9. [Medline].
16. Kornreich L, Bron-Harlev E, Hoffmann C, et al. Thiamine deficiency in infants: MR findings in the brain. AJNR Am J Neuroradiol. Aug 2005;26(7):1668-74. [Medline].
17. Wrenn KD, Murphy F, Slovis CM. A toxicity study of parenteral thiamine hydrochloride. Ann Emerg Med. Aug 1989;18(8):867-70. [Medline].
18. Kitamura K, Yamaguchi T, Tanaka H, et al. TPN-induced fulminant beriberi: a report on our experience and a review of the literature. Surg Today. 1996;26(10):769-76. [Medline].
19. Lehninger, Albert L. Vitamins and Coenzymes. In: Biochemistry. 2^nd ed. New York, NY: Worth Publishers; 1977:337-9.
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21. Suter PM, Vetter W. Diuretics and vitamin B1: are diuretics a risk factor for thiamin malnutrition?. Nutr Rev. Oct 2000;58(10):319-23. [Medline].
22. Weise Prinzo Z, de Benoist B. Meeting the challenges of micronutrient deficiencies in emergency- affected populations. Proc Nutr Soc. May 2002;61(2):251-7. [Medline].

Article Last Updated: Apr 23, 2008