What is the recommended dose of thiamine (Vitamin B1) for patients with Non-Alcoholic Steatohepatitis (NASH)-related cirrhosis?

Thiamine Dosing in NASH-Related Cirrhosis

Patients with NASH-related cirrhosis should receive thiamine supplementation at 200-300 mg daily orally, or parenterally if Wernicke's encephalopathy is suspected, based on the high prevalence of thiamine deficiency in all forms of cirrhosis regardless of etiology.

Evidence for Thiamine Deficiency in Cirrhosis

• Thiamine deficiency occurs equally in both alcoholic and non-alcoholic (including HCV-related) cirrhosis, with prevalence rates of approximately 58% in chronic liver disease patients. 1

• The deficiency is specifically associated with cirrhosis itself rather than the underlying etiology, as patients with chronic hepatitis C without cirrhosis showed no thiamine deficiency, while those with HCV-related cirrhosis had similar deficiency rates to alcoholic cirrhosis. 1

• NASH-related cirrhosis should be treated with the same thiamine supplementation approach as other forms of cirrhosis, since the deficiency mechanism relates to the cirrhotic state rather than alcohol exposure. 1

Recommended Dosing Regimens

For Routine Supplementation in Cirrhosis

• Oral thiamine 200-300 mg daily is the standard dose for patients with cirrhosis who have confirmed or suspected thiamine deficiency. 2, 3

• This high-dose supplementation (200 mg/day for one week) has been shown to restore thiamine pyrophosphate (TPP) levels to normal in all cirrhotic patients and stimulate synthesis of TPP-dependent enzymes. 2

• Lower maintenance doses of 50-100 mg/day orally may be used after deficiency resolution, though continued monitoring is warranted. 4

For Suspected Wernicke's Encephalopathy

• If Wernicke's encephalopathy is suspected in a cirrhotic patient, large doses of thiamine should be given parenterally (200-500 mg three times daily for 3-5 days) before any glucose administration. 5

• This parenteral approach is critical in the context of hepatic encephalopathy or when patients cannot take oral nutrition reliably. 5

• Following the initial parenteral course, transition to oral thiamine 250-300 mg/day for maintenance. 6

For Patients Requiring Parenteral Nutrition

• Thiamine should be administered as a first dose before commencing parenteral nutrition in cirrhotic patients to prevent Wernicke's encephalopathy or refeeding syndrome. 5

• Minimum parenteral thiamine dosing should be 2.5 mg/day for maintenance nutrition, with therapeutic doses of 100-300 mg/day IV for suspected deficiency. 7

Clinical Considerations

Metabolic Benefits Beyond Neurological Protection

• Thiamine supplementation (50 mg/day for 30 days) significantly reduces blood glucose levels in cirrhotic patients with hyperglycemia, improving glucose utilization. 8

• The essential role of TPP as a cofactor in intermediary metabolism supports routine high-dose thiamine supplementation in severe chronic liver disease. 2

Route of Administration

• Oral thiamine is generally well-absorbed and preferred in stable patients, while parenteral administration is reserved for acute deficiency, severe symptoms, or inability to take oral medications. 3

• The phosphorylation of thiamine to its active form (TPP) is not impaired in cirrhotic patients, making oral supplementation effective. 1, 9

Safety Profile

• Thiamine has no established upper toxicity limit, with excess being excreted in urine. 3, 4

• Doses exceeding 400 mg may cause mild side effects such as nausea, anorexia, and mild ataxia, but these are uncommon. 3, 4

• High intravenous doses rarely cause anaphylaxis. 3

Monitoring Recommendations

• Measuring red blood cell (RBC) or whole blood thiamine diphosphate (ThDP) is recommended for patients with suspected thiamine deficiency, particularly those with neurological symptoms. 3, 7

• Erythrocyte transketolase activity and TPP effect can also be used to assess thiamine status. 2, 1

Integration with Nutritional Management

• Thiamine supplementation should be part of comprehensive nutritional therapy for cirrhotic patients, which includes daily energy intake of 35-40 kcal/kg ideal body weight and protein intake of 1.2-1.5 g/kg/day. 5

• A multivitamin is generally recommended for all cirrhotic patients, though specific micronutrient replacement (including thiamine) should be given when deficiencies are confirmed or suspected. 5

• Small meals distributed throughout the day with a late-night snack should be encouraged to avoid fasting, which depletes glycogen stores and worsens metabolic status. 5