Vitamin B1NEW2026-09

Clioquinol inactivates thiamine pyrophosphate by increasing cellular oxidative stress.

Fan Zheyu, Yan Xianghui, Zheng Qiaoqiao, Zhu Ziting et al. — Redox biology

Summary

An old antibiotic, clioquinol, previously linked to nerve damage, appears to cause harm by inactivating the active form of vitamin B1 (thiamine) within cells. This inactivation leads to increased cellular stress and problems with cell energy production. The study suggests that supplementing with active vitamin B1 or antioxidants might help protect against this nerve damage.

AI-generated summary — read the original

Key points

An old antibiotic, clioquinol, can cause nerve damage by interfering with active vitamin B1.
It does this by increasing harmful cellular stress, which inactivates vitamin B1's active form.
This interference leads to problems with cell energy production and mitochondrial health.
Supplementing with active vitamin B1 or antioxidants might help protect against this damage.

What the study looked at

What question did this study ask? Researchers wanted to understand how the old antibiotic clioquinol caused nerve damage, specifically investigating its link to vitamin B1 (thiamine) deficiency. How was it studied? The study used advanced laboratory techniques to analyze how clioquinol affected cell metabolism. They examined its impact on thiamine transport, its active form (thiamine pyrophosphate or TPP), and cellular stress levels. They also observed mitochondrial function and damage in cells. Finally, they tested clioquinol's effects in a mouse model of Alzheimer's disease, observing changes in brain TPP levels and neuronal injury, and whether supplementing TPP or an antioxidant could mitigate these effects. What did it find? The study found that clioquinol inactivates active vitamin B1 (TPP) by increasing oxidative stress within cells. This inactivation led to reduced energy production in mitochondria and altered cell metabolism. In mice, clioquinol also caused oxidative stress, lowered brain TPP, and damaged nerve cells. Importantly, providing extra active vitamin B1 or an antioxidant helped reduce this nerve damage and even improved the clearance of amyloid plaques in the Alzheimer's mouse model.

Dietary takeaway

This research highlights the critical role of vitamin B1 (thiamine) in protecting nerve health, especially against cellular stress. While clioquinol is no longer widely used, maintaining adequate vitamin B1 intake through foods like whole grains, pork, and legumes is generally beneficial for overall cellular function and nerve health. Remember, this is one study, and its findings, particularly from animal models, may not directly translate to human dietary recommendations without further research.

Abstract

Clioquinol (CQ), a prescribed oral antibiotic, was withdrawn from use following its association with the incidence of subacute myelo-optic neuropathy (SMON) in Japan. The neurotoxicity associated with CQ may be linked to thiamine deficiency. However, their relationship and underlying mechanisms remain unclear. In this study, we identified thiamine pyrophosphate (TPP) as a key metabolite affected by CQ via metabolomics analysis. Analysis of related thiamine transport, TPP synthesis, and oxidative stress pathways revealed that CQ promoted TPP inactivation through oxidative modification. The Seahorse metabolic analyzer data showed that CQ-induced TPP deficiency led to diminished mitochondrial oxidative phosphorylation, accompanied by enhanced glycolysis. Morphological examination of mitochondria further indicated that CQ elicited mitochondrial damage in a TPP-dependent manner. In an Alzheimer's disease murine model, CQ administration similarly provoked oxidative stress, decreased cerebral TPP concentrations, and induced neuronal injury. Notably, supplementation with TPP or N-acetylcysteine (NAC) mitigated CQ-associated neurotoxicity and potentiated CQ-mediated clearance of amyloid plaques. Our findings elucidate that CQ is involved in mitochondrial dysfunction and metabolic reprogramming by inactivating TPP, providing valuable insights into the neurotoxicity of CQ.

View on PubMed →DOI: 10.1016/j.redox.2026.104258