From the Guidelines
Metronidazole inhibits thiamine by blocking its absorption and metabolism in the body, and patients requiring extended metronidazole treatment should be considered for thiamine supplementation, typically 100 mg daily, to prevent neurological complications. When metronidazole is administered, it can interfere with thiamine pyrophosphokinase, the enzyme responsible for converting thiamine to its active form, thiamine pyrophosphate (TPP) 1. This inhibition occurs because metronidazole's chemical structure allows it to compete with thiamine at binding sites. Additionally, metronidazole may accelerate thiamine breakdown in the gut and reduce its intestinal absorption.
The provided evidence from the ESPEN micronutrient guideline 1 highlights the importance of thiamine supplementation in various clinical situations, including patients at risk of deficiency due to malnutrition, poor oral intake, chronic alcohol consumption, and critical illness. The guideline recommends thiamine supplementation, typically 100-300 mg/day, for patients admitted to emergency or intensive care, as well as those with suspicion of reduced food intake or high alcohol consumption 1.
Key points to consider:
- Thiamine deficiency can lead to severe neurological complications, including Wernicke's encephalopathy 1
- Metronidazole therapy can increase the risk of thiamine deficiency, particularly in patients with risk factors such as alcoholism or malnutrition 1
- Thiamine supplementation can be administered orally, enterally, or IV, with the IV route being the most efficient in acute deficiency symptoms 1
- The recommended dose of thiamine supplementation varies depending on the clinical situation, but typically ranges from 100-300 mg/day 1
In clinical practice, it is essential to consider thiamine supplementation for patients requiring extended metronidazole treatment, especially those with risk factors for thiamine deficiency, to prevent neurological complications and improve patient outcomes.
From the Research
Mechanism of Metronidazole Inhibition of Thiamine
- Metronidazole is converted to a thiamine analog, which acts as a vitamin B1 antagonist, inhibiting thiamine pyrophosphokinase in vitro 2.
- The thiamine analog is a close structural analog of thiamine and is an effective inhibitor of thiamine pyrophosphokinase, leading to thiamine deficiency 2.
- Enzymatic alkylation reactions, such as those effected by thiaminase, may increase the electrophilicity and/or reduction potential of metronidazole, contributing to its inhibition of thiamine 2.
Effects of Metronidazole on Thiamine Levels
- Prolonged metronidazole therapy can lead to thiamine deficiency, which may contribute to its side effects of neurotoxicity and infertility in experimental animals 3.
- Metronidazole use has been associated with decreased thiamine levels, which may be related to its mechanism of action as a thiamine antagonist 3.
Clinical Implications of Metronidazole-Induced Thiamine Deficiency
- Thiamine deficiency can lead to a range of clinical manifestations, including lactic acidosis, peripheral neuropathy, ataxia, and ocular changes 4.
- Metronidazole-induced thiamine deficiency may contribute to its side effects of neurotoxicity, including peripheral neuropathy, optic neuropathy, and encephalopathy 5, 3.