Acute Thiamine (Vitamin B1) Deficiency

Acute severe deficiency of thiamine is one of the most important medical problems that hospital doctors and GPs can deal with.  Chronic alcohol excess is the main but not only cause.  Experts acknowledge that it may not be properly recognised or adequately treated with very significant health consequences for the individual.  There is much the patient and their carers can do to prevent its development.

Thiamine Functions

Most of the information in this section is taken from the detailed article The Royal College of Physicians Report on Alcohol: Guidelines for Managing Wernicke’s Encephalopathy in the Accident and Emergency Department.  Thomson AD, Cook CCH, Touquet R, Henry JA.  Alcohol and Alcoholism Vol 37, No. 6, pp513-521, 2002.  All doctors involved in the acute care of emergency patients should read the entire article.

Thiamine is a cofactor for several enzymes involved in energy release from carbohydrate and its requirement is related to the dietary intake of carbohydrate.  There are not significant stores of thiamine and deficiency can develop within two weeks of a poor intake especially if some of the other causative factors, most often alcohol excess or vomiting, are present. 

One of the first features of thiamine deficiency is a rise in lactic acid and then other changes including decline in the activity of dependent enzyme transketolase, which is needed for carbohydrate as well as lipid and amino acid metabolism and the maintenance of the protective myelin nerve sheaths. 

The mineral magnesium is an important co-factor for thiamine-dependent enzymes and nerve conduction and sometimes co-existing deficiency limits the response to the correction of thiamine deficiency.  

Clinical Picture of Deficiency in Adults

There are several distinct clinical pictures that can result from thiamine deficiency.  They include:

• Muscle pain – typically in the calves due to rapid accumulation of lactic acid after slight physical activity
• Congestive cardiac failure – shortness of breath, fluid retention and a rapid and sometimes bounding pulse
• Peripheral neuropathy – loss of sensation and sometimes strength in the hands or lower limbs
• Wernicke’s Encephalopathy – ataxia (unsteadiness), impaired consciousness and problems of eye movement
• Korsakoff’s Psychosis – loss of memory for both new (anterograde) and past (retrograde) events together with confabulation, making up a version of events to cover for the loss of memory
• Other features – hypothermia, hypotension (low blood pressure) and autonomic neuropathy

Wernicke’s Encephalopathy, WE, can lead to the development of Korsakoff’s psychosis with loss of short term memory, development of confabulation and permanent mental and social handicap.  In one Scottish study of patients with Korsakoff’s psychosis nearly all the subjects were unemployed and over half were divorced. (Ramayya A, Jauhar P.  Increasing incidence of Korsakoff’s Psychosis in the East end of Glasgow.  Alcohol and Alcoholism Vol 22 No. 3 pp281-5. 1997)

Experts now recognise that the majority of episodes of WE go unrecognised or, if recognised, inadequately treated.  Post-mortem studies in Australia have revealed that this preventable syndrome is only diagnosed in 10% of sufferers before death.  Part of the difficulty is that acute episodes of WE are often precipitated by alcohol excess and will be indistinguishable from acute alcohol intoxication.  The attending doctor or Accident and Emergency staff may simply ascribe the person’s confusion and unsteadiness to the acute effects of alcohol and not recognise the part also played by an underlying thiamine deficiency.

Causes of Thiamine Deficiency

The causes of thiamine deficiency may overlap and if several are present a severe deficiency may result

• Very poor dietary intake (missed meals, lack of bread and over-reliance upon processed meals and beef as opposed to other types of meat)
• Excessive intake of carbohydrate-rich foods that are low in thiamine  e.g. white rice, sugar, glucose including IV glucose or feeding given to patients in hospital
• Chronic alcohol excess, which is often the commonest and most serious cause
• High dietary intake of thiaminases (enzymes that destroy thiamine) from betel nuts and raw fish
• Malnutrition resulting in weight loss >10% of premorbid weight or low BMI
• Persistent vomiting
• Increased urinary losses due to: chronic renal failure, type I or type II diabetes and increasing age
• Hyperalimentation, AIDs and drug misuse
• Genetic variations in thiamine metabolism (rare)

Tests of Thiamine Deficiency

The most widely used test of thiamine status is measurement of the activity of the dependent enzyme transketolase in red cells and its increase when additional thiamine is added.  From these two measures an activation coefficient can be calculated the normal range for erythrocyte transketolase activation coefficient, ETKAC, is <1.25.

Other tests of thiamine include red cell thiamine pyrophosphate, RBCTPP and the normal range is 165 – 286 nmol/l.

However these tests may not identify all of those with or at risk of severe deficiency and in the emergency situation thiamine should be administered according to the clinician’s judgement.  According to expert guidance “..it is more important to make a presumptive diagnosis of WE and to treat the patient as soon as possible”.

The National Diet and Nutrition Surveys assessed thiamine status by measurement of both intake as well as red cell transketolase activation coefficient, ETKAC.  Inadequate intake is considered to be one that is below the Lower Reference Nutrient Intake, LRNI, and biochemical deficiency is considered to be an ETKAC greater than 1.25. 

Thiamine Status in the British Population                                                                

It should be noted that not all of those who are biochemically deficient will have significant clinical effects of deficiency and that the tests will not detect all of those who are clinically deficient.

Treatment of Severe Thiamine Deficiency

Oral thiamine in low doses is well absorbed but the mechanism, which is an active rate-limited process. is easily saturated and it is considered that it is impossible to absorb more than approximately 4.5 mg from a single oral dose.  For patients who are not vomiting, are without malabsorption, have not consumed excess alcohol, which inhibits thiamine absorption, and are not severely ill oral supplements are likely to be adequate. 

Oral doses of thiamine of 5-10 mg three times per day are probably adequate for mild deficiency however because of the possible co-existence of other B vitamin deficiencies for which amounts greater than 5 mg per day are usually required it is often prudent to use vitamin B complex 50 mg three times per day which is widely available in health food shops and some pharmacies.

Parenteral forms of vitamin B1 are required by all seriously ill patients especially those with Wernicke’s Encephalopathy, WE.  Pabrinex, a prescription only preparation of several B vitamins, is available for intravenous and intramuscular administration; however it may very rarely precipitate anaphylactic shock and should only be administered in a situation where there are facilities for coping with such a possibility.  Pabrinex is usually administered as two pairs of ampoules every 8 hours for the first 48 hours of alcohol withdrawal.

It is prudent to regard that all poorly nourished patients and alcoholics are likely to be deficient and may need to be given parenteral thiamine and other B vitamins particularly before receiving IV glucose.  Stores of magnesium, which is needed for the activation of thiamine and other B vitamins, are likely to be inadequate in those with malabsorption, diarrhoea, muscle wasting or chronic alcohol excess and supplementation may be required, which should be intravenous if hypomagnesaemia is present.  See above article for full details of treatment of acute thiamine deficiency.

Reference:

The Royal College of Physicians Report on Alcohol: Guidelines for Managing Wernicke’s Encephalopathy in the Accident and Emergency Department.  Thomson AD, Cook CCH, Touquet R, Henry JA.  Alcohol and Alcoholism Vol 37, No. 6, pp513-521, 2002.  See report here. All doctors involved in the acute care of emergency patients should read the entire article.