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Updated: Jan 18, 2026

Author Spotlight: Understanding Retinal Vessel Resilience and Disease Progression
Published on: January 12, 2024
Benfotiamine blocks three major pathways of hyperglycemic damage and prevents experimental diabetic retinopathy
Hans-Peter Hammes1, Xueliang Du, Diane Edelstein
1Medical Clinic V, School of Clinical Medicine, Mannheim, Germany.
Abstract:
Three of the major biochemical pathways implicated in the pathogenesis of hyperglycemia induced vascular damage (the hexosamine pathway, the advanced glycation end product (AGE) formation pathway and the diacylglycerol (DAG)-protein kinase C (PKC) pathway) are activated by increased availability of the glycolytic metabolites glyceraldehyde-3-phosphate and fructose-6-phosphate. We have discovered that the lipid-soluble thiamine derivative benfotiamine can inhibit these three pathways, as well as hyperglycemia-associated NF-kappaB activation, by activating the pentose phosphate pathway enzyme transketolase, which converts glyceraldehyde-3-phosphate and fructose-6-phosphate into pentose-5-phosphates and other sugars. In retinas of diabetic animals, benfotiamine treatment inhibited these three pathways and NF-kappaB activation by activating transketolase, and also prevented experimental diabetic retinopathy. The ability of benfotiamine to inhibit three major pathways simultaneously might be clinically useful in preventing the development and progression of diabetic complications.
Insights
Benfotiamine, a thiamine derivative, effectively inhibits key pathways contributing to diabetic vascular damage by activating transketolase. This discovery offers a potential therapeutic strategy for preventing diabetic complications.
Area of Science:
- Biochemistry
- Endocrinology
- Pharmacology
Background:
- Hyperglycemia-induced vascular damage involves the hexosamine, advanced glycation end product (AGE), and diacylglycerol (DAG)-protein kinase C (PKC) pathways.
- These pathways are activated by increased glyceraldehyde-3-phosphate and fructose-6-phosphate availability.
Purpose of the Study:
- To investigate the potential of benfotiamine in inhibiting hyperglycemia-induced biochemical pathways and preventing diabetic vascular complications.
- To elucidate the mechanism by which benfotiamine exerts its effects.
Main Methods:
- Utilized animal models of diabetic retinopathy.
- Administered benfotiamine to assess its impact on key biochemical pathways and NF-kappaB activation.
- Measured the activity of transketolase and the levels of pathway metabolites.
Main Results:
- Benfotiamine inhibited the hexosamine, AGE, and DAG-PKC pathways by activating transketolase.
- Benfotiamine reduced hyperglycemia-associated NF-kappaB activation in diabetic animal retinas.
- Benfotiamine treatment prevented experimental diabetic retinopathy in animal models.
Conclusions:
- Benfotiamine demonstrates a multi-targeted inhibitory effect on pathways driving diabetic vascular damage.
- Activation of transketolase by benfotiamine is a key mechanism for its protective effects.
- Benfotiamine holds clinical promise for preventing and managing diabetic complications.
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