Beriberi

Synonyms: Thiamine deficiency, aneurin deficiency, vitamin B1 deficiency

Beriberi is caused by deficiency of thiamine, also called aneurin and vitamin B1. This is a water soluble, heat labile vitamin that acts as a co-enzyme on a number of metabolic pathways. The recommended daily intake is 1.2 mg.¹

The cardiovascular, muscular, gastrointestinal and nervous systems can be affected.

The word beri means weak in Sinhala, a language from Sri Lanka. Beriberi means very weak. Another translation is 'I cannot, I cannot'.²

Beriberi was endemic in some areas of the world and may be related to the consumption of milled rice. The process removes the outer crust that contains the vitamin, and in Indonesia especially, the condition is very common although the World Health Organisation (WHO) claims considerable improvement in the area.³ Worldwide, beriberi is now much less common than it was.The disease tends to affect adults and infants between 1 and 4 months old.

Outbreaks occasionally occur in circumstances in which there are dietary restrictions, and/or intake of thiamine antagonists.^4,5 An outbreak in Israel in 2005 was traced to the use of soy-based milk formula.⁶

Risk factors¹

In western societies predisposing factors to thiamine deficiency include gastrointestinal disease and alcoholism as the latter impairs absorption of the vitamin. Deficiency has been recorded in AIDS, after bariatric surgery and in hyperemesis gravidarum.^7,8 Hypermetabolic states also predispose to deficiency and this includes fever, pregnancy, postoperative state, total parenteral nutrition and renal dialysis.⁹ A loop diuretic can also increase the risk.¹⁰

History

Early features:

• Fatigue and apathy
• Irritability
• Drowsiness, depression poor concentration
• Anorexia, nausea, vomiting, abdominal pain

• Paraesthesia, peripheral neuropathy, depressed tendon reflexes, loss of vibration sense
• Tender leg muscles and muscle cramps
• Congestive heart failure with dyspnoea, orthopnoea and oedema

In infancy beriberi can present as acute fulminating, acute cardiac, aphonic and pseudomeningitic. In the aphonic form there is hoarseness and a weak cry due to paralysis of the laryngeal nerve. In the pseudomeningitic variety there is nystagmus, vomiting and convulsions but normal cerebrospinal fluid.

Examination

Beriberi is often classified as dry beriberi when features are neurological and muscular and wet beriberi when there is predominantly heart failure. Physical findings include:

• Pallor and waxy skin
• Signs of malnutrition and wasting
• Listlessness, weakness
• Tachycardia, hepatomegaly, cardiomegaly and peripheral oedema
• Paraesthesia and peripheral neuropathy including depressed tendon reflexes

Two conditions caused by thiamine deficiency that are usually related to alcohol abuse in western societies are Wernicke's encephalopathy and Korsakoff's psychosis. See article on Wernicke-Korsakoff Syndrome.

A high index of suspicion should be maintained for patients with chronic alcohol abuse, special diets, and malnutrition.
Congestive heart failure may need to be excluded as may other vitamin deficiencies(vitamin B-12, niacin) if neurological symptoms are present.

• Probably the best diagnostic test is a good clinical response to administration of thiamine.
• One of the best laboratory tests is whole blood or erythrocyte transketolase activity. Thiamine diphosphate is added and the activity should increase by at least 15% in deficiency.
• Other tests include blood thiamine level, pyruvate, lactate, alphaketoglutarate and glycosylate.
• In Wernicke's encephalopathy, the CSF is normal or protein is slightly elevated but if left untreated then blood pyruvate and blood transketolase will rise.
• MRI scan has been used to detect brain changes in infants with thiamine deficiency.¹²
• Echocardiogram should be used to assess heart failure.

There is often a deficiency of more than one vitamin and so the patient must be carefully monitored as treatment starts.
Thiamine is available in both oral and parenteral form and the latter may be employed at first with transfer to oral preparations later. However, the Medicines and Healthcare products Regulatory Agency (MHRA) recommends that potentially serious allergic adverse reactions may occur during, or shortly after, parenteral administration. They recommend that:¹³

• Use is restricted to patients in whom parenteral treatment is essential.
• Intravenous injections should be administered slowly over 10 minutes.
• Facilities for treating anaphylaxis should be available.

10 to 25 mg daily is recommended for chronic mild deficiency and 200 to 300 mg daily for more severe deficiency.

Vitamin B deficiency, other than vitamin B12 deficiency, is rare in the UK and should be treated with preparations containing thiamine (B1), riboflavin (B2), and nicotinamide. They do recommend parenteral administration followed by oral treatment for Wernicke's encephalopathy and Korsakoff's psychosis.¹⁴

There is no need for the usual diuretics and ACE inhibitors for heart failure as there is usually improvement in 6 to 24 hours and marked improvement in a few days.¹⁵

If alcoholism is the underlying problem a 3 stage approach is required:

• If alcohol is suddenly stopped a withdrawal syndrome of delirium tremens may result. A reducing dose of benzodiazepine, usually chlordiazepoxide, should therefore be started during the withdrawal process, the starting dose being dependent upon the level of alcohol consumption
• The next stage is to get the patient to admit that there is a problem of alcohol abuse.
• The final stage is to get the patient to enter into long term management of the problem.
  For more information, see Alcoholism and Alcohol Abuse - Management.

• The heart failure of beriberi, if untreated, can be fatal.
• Anaphalaxis can result from parenteral treatment.¹³
• Treatment with thiamine may unmask other deficiencies.¹⁶
• Korsakoff's psychosis is considered more fully elsewhere. The essential features are anterograde and retrograde amnesia, often with disorientation and confabulation. The last usually makes the patient delightful but any check of the authenticity of stories will reveal them as confabulation.
• Wernicke's encephalopathy is also covered elsewhere. Patients are often apathetic and confused. There is ataxia, nystagmus and even coma may result.

Adults or the families of children need education about the cause of the disease and how to prevent recurrence. In third world countries the child may be discharged back to the same environment.

In developed countries the problem is usually one of the very difficult management of alcohol abuse. If there are other reasons such as after bariatric surgery, supplements can be continued.

Good dietary sources of thiamine are whole grains, lean pork, and legumes. Thiamine is not present in fats, oils, and refined sugars and is destroyed by heat, pasteurisation, and ionising radiation. Freezing does not affect thiamin content of foods.

The disease was described by the Chinese around 2700 BC, but the cause was unknown. In the 19th century it was realised that the diet needed protein, fat and most of the calories from carbohydrate but it was not until the late 19th and early 20th century that the need for other nutrients was appreciated. Christiaan Eijkman studied prisoners in the Dutch East Indies who were fed a diet of polished rice and he noted a high incidence of neurological disorders.¹⁷ He also found that either feeding the whole rice or adding the husk would reverse the disorder. In 1911 Funk confirmed such findings in birds and postulated substances called vital amines, later abbreviated to vitamins.¹⁸ Beriberi was not uncommon on long naval voyages and was thought to have much in common with scurvy.

In 1753 Royal Navy Surgeon James Lind demonstrated that the consumption of fresh lemons and oranges cured scurvy.¹⁹ He divided 12 sailors into 4 groups of 3 to try 3 treatments and a control group in what was almost the first randomised controlled trial on record. There was a similar naval controlled trial in the early 1880s. A young Japanese medical officer, Kanehiro Takaki, arranged that 2 ships left Japan on similar voyages, but with different diets. The first ship served the usual fare of rice, with some vegetables and fish. The second also served the crew wheat and milk, in addition to more meat than was served on the first ship. The results were impressive with 25 deaths from beriberi on the first ship and none on the other. The Japanese Admiralty adopted the new diet for the entire navy.

In 1926 two biochemists called Jansen and Donath isolated a tiny amount of a substance they called aneurin but there was too little to be of much value.²⁰ Commercial production did not start until 1937 but it achieved great importance in the 1950s with the demand for the fortification of food.