Thiamine Deficiency Impacts in Clinical Neurology

Thiamine (vitamin B1) is indispensable for cerebral energy metabolism, acting as a coenzyme for enzymes in the Krebs cycle and pentose phosphate pathway. Inadequate thiamine impairs oxidative phosphorylation, leading to neuronal energy failure, selective neuronal vulnerability and neuroinflammatory responses. Clinically, deficiency manifests as a spectrum—from subtle cognitive slowing, peripheral neuropathy and mood disturbances to acute Wernicke’s encephalopathy with confusion, ophthalmoplegia and ataxia. If left untreated, this can progress to irreversible Korsakoff’s syndrome, characterised by profound anterograde amnesia and confabulation. In paediatric and tropical settings, infantile beriberi presents with cardiac failure, lactic acidosis and neurological signs. Diagnosis remains challenging due to non-specific presentations and limited access to rapid biomarkers in resource-poor regions. Magnetic resonance imaging aids early detection by revealing characteristic lesions in thalami, mamillary bodies and periaqueductal areas. Prompt high-dose parenteral thiamine reverses acute deficits and prevents chronic sequelae. Globally, thiamine deficiency persists in vulnerable populations—those with malnutrition, malabsorption, hyperemesis or post-bariatric surgery—highlighting the need for improved surveillance, standardised diagnostics and targeted supplementation programmes.

Research from Nature Portfolio

One foundational study has characterised non-coenzyme actions of thiamine in the brain. Investigators demonstrated that thiamine and its phosphorylated derivatives bind directly to mitochondrial dehydrogenases and pyridoxal kinase, exerting allosteric modulation of malate dehydrogenase, glutamate dehydrogenase and related enzymes. Structural analyses revealed how thiamine triphosphate activates glutamate dehydrogenase and how thiamine diphosphate regulates malate dehydrogenase isoforms, linking thiamine beyond its classical role to control of acetyl‐CoA export, protein acetylation and neurotransmitter synthesis. These mechanistic insights broaden the therapeutic potential of thiamine in metabolic and neurodegenerative disorders.

Thiamine Deficiency Impacts in Clinical Neurology publication trend

The graph below shows the total number of articles in thiamine deficiency impacts in clinical neurology across all publications each year (not limited to Nature Index journals).

Technical terms

Thiamine diphosphate: The biologically active coenzyme form of vitamin B1 required for mitochondrial dehydrogenase complexes.

Erythrocyte transketolase activity coefficient (ETKac): A ratio reflecting activation of red-cell transketolase by added thiamine diphosphate, used as an indirect marker of thiamine status.

Allosteric regulation: Modulation of an enzyme’s activity through binding of an effector molecule at a site distinct from its catalytic centre.

Wernicke–Korsakoff syndrome: A neurological disorder featuring acute encephalopathy and chronic amnestic syndrome secondary to severe thiamine deficiency.

Parenteral thiamine: Administration of vitamin B1 by intravenous or intramuscular injection to rapidly restore tissue levels and reverse deficiency symptoms.

References

1. Protocol and application of basal erythrocyte transketolase activity to improve assessment of thiamine status. Annals of the New York Academy of Sciences (2023).
2. Wernicke-Korsakoff syndrome despite no alcohol abuse: A summary of systematic reports. Journal of the Neurological Sciences (2021).
3. Thiamine Deficiency in Tropical Pediatrics: New Insights into a Neglected but Vital Metabolic Challenge. Frontiers in Nutrition (2016).
4. MR Imaging Findings in Alcoholic and Nonalcoholic Acute Wernicke’s Encephalopathy: A Review. BioMed Research International (2014).
5. Molecular mechanisms of the non-coenzyme action of thiamin in brain: biochemical, structural and pathway analysis. Scientific Reports (2015).