Thiamine Deficiency

OVERVIEW

• Thiamine Deficiency = Beri-Beri (wet or dry)
• lack of thiamine pyrophosphate or Vitamin B1
• can progress slowly or quickly and be fatal
• water-soluble vitamin
• limited storage in body (30mg)
• stores of thiamine last around 1 month

ACTIONS

• acts as a co-enzyme in carbohydrate metabolism through the decarboxylation of alpha ketoacids
• co-enzyme for transketolase in pentose monophosphate pathway (formation of glucose)
• co-enzyme for conversion of pyruvate into acetyl-CoA (if blocked leads to lactate production)

CAUSES

• inadequate intake (alcoholics, diet, starvation)
• decreased absorption (intestinal disease, alcoholism, malnutrition, gastric bypass, folate deficiency)
• increased consumption (hyperthyroidism, pregnancy, lactation, fever)
• increased depletion (diarrhoea, diuretics, dialysis)
• severe liver disease (impairs its use)
• folate deficiency (thiamine regenerated via proton donation from NADH -> folate required to have enough dihydrofolate reductase to regenerate NADH)

CLINICAL FEATURES

Dry Beri-Beri

• bilateral, peripheral sensory and motor neuropathy with weakness and hyporeflexia

Wernicke encephalopathy

• altered mental state
• ophthalmoplegia with horizontal nystagmus
• ataxia and vestibular dysfunction
• fever and vomiting may be present

Korsakoff encephalopathy

• progressive mental impairment characterised by short-term memory loss and confabulation
• chronic and irreversible

Wet Beri-Beri

• tachycardia
• vasodilation
• high cardiac output
• fluid overload
• cardiac failure

INVESTIGATIONS

• lactic acidosis
• echocardiography
• blood thiamine, pyruvate, alpha-ketoglutarate and glyoxylate levels
• thiamine loading test erythrocyte transketolase activity preloading and post-loading is the best indicator of thiamine deficiency (look for  increase of >5% in enzyme activity
• urinary thiamine and methylglyoxal

MANAGEMENT

Prevention and treatment of thiamine deficiency

• thiamine 100 mg orally daily

Prevention and treatment of thiamine deficiency in severe alcoholics

• thiamine 100 to 200 mg IV daily for 3 days
• then thiamine 100 mg orally daily

Treatment of Wernicke encephalopathy

• thiamine 500 mg IV infusion over 30 minutes, 3 times daily for 3 days
• then thiamine 250 mg IV or IM, daily for 3 to 5 days or until clinical improvement ceases

Supportive care monitoring

• optimise nutrition
• treat underlying cause, e.g. chronic alcoholism with liver disease
• treat complications e.g. heart failure

SHOULD THIAMINE BE GIVEN BEFORE GLUCOSE IN HYPOGLYCAEMIA?

• Traditional teaching is to never treat hypoglycaemia prior to giving thiamine due to risk of precipitating Wernicke encephalopathy – this is a myth – never delay treatment of hypoglycemia
• The concern is that an excessive carbohydrate load will lead to the build up of toxic metabolites when the activity of these enzymes is reduced because of thiamine deficiency
• There are no reported instances of a single bolus of glucose precipitating Wernicke encephalopathy
• Prolonged carbohydrate administration (e.g. from total parenteral nutrition) without thiamine supplementation has been reported to precipitate Wernicke’s encephalopathy

References and Links

LITFL

• Critical Care Drug Manual — Thiamine
• Toxicology Conundrum 037 — Hypoglycaemia, but how? (includes discussion of need to replace thiamine prior to treatment)

Journal articles and textbooks

• Donnino MW, Vega J, Miller J, Walsh M. Myths and misconceptions of Wernicke’s encephalopathy: what every emergency physician should know. Ann Emerg Med. 2007 Dec;50(6):715-21. PMID: 17681641
• Hack JB, Hoffman RS. Thiamine before glucose to prevent Wernicke encephalopathy: examining the conventional wisdom. JAMA. 1998 Feb 25;279(8):583-4. PMID: 9486750