Does Benfotiamine Neutralize Advanced Glycation End-Products?
Benfotiamine does not directly neutralize or break down existing AGEs, but it reduces the formation of new AGEs by activating transketolase and redirecting glucose metabolites away from AGE-forming pathways. 1
Mechanism of Action
Benfotiamine works through a preventive rather than neutralizing mechanism:
- Benfotiamine increases intracellular thiamine diphosphate levels, which activates the enzyme transketolase 1
- Transketolase redirects AGE precursors (glucose metabolites) into the pentose phosphate pathway, thereby reducing the substrate available for AGE formation 1
- This represents a preventive strategy rather than direct AGE neutralization or breakdown 1
The compound does not function as an AGE "breaker" (like alagebrium) that cleaves existing AGE cross-links, nor does it directly scavenge reactive dicarbonyl compounds like methylglyoxal (MGO) or glyoxal (GO) that form AGEs 2, 3
Clinical Evidence: Mixed and Unconvincing
Animal Studies Show Promise
- In diabetic rats, benfotiamine completely prevented diabetes-induced glycoxidation products (CML) and caused major inhibition of neural imidazole-type AGE formation when administered preventively 4
- Motor nerve conduction velocity was nearly normalized after six months of benfotiamine treatment in diabetic rats 4
- One study found benfotiamine alleviated cerebral oxidative stress in diabetic mice, but this occurred independent of AGE levels, suggesting alternative mechanisms 5
Human Studies Are Disappointing
The most rigorous human trial found that benfotiamine for 12 weeks did not significantly reduce plasma or urinary AGEs (CML, CEL, or MG-H1) in patients with type 2 diabetes and nephropathy 6. This randomized controlled trial directly contradicts the animal data and represents the highest quality clinical evidence available.
A comprehensive 2013 review concluded that clinical evidence on benfotiamine's AGE-inhibiting effects is "limited, weak and unconvincing" 3
Important Caveats
- The disconnect between animal and human studies is substantial - what works in diabetic rats does not translate reliably to human patients 6, 4
- Benfotiamine may have beneficial effects through non-AGE-dependent mechanisms, including direct antioxidant effects 5
- The timing matters: benfotiamine appears more effective when started early (prevention) rather than after AGE accumulation has occurred 4
- Alternative strategies for reducing AGE burden include dietary modification, cooking methods (steaming/poaching vs frying/grilling), and polyphenol-rich foods which have better-established effects on reducing AGE formation and accumulation 2
Clinical Bottom Line
For patients concerned about AGE accumulation, prioritize proven dietary strategies over benfotiamine supplementation 2. These include consuming fresh vegetables and fruits, avoiding high-temperature cooking methods, and incorporating polyphenol-rich beverages like green tea that can trap reactive dicarbonyl species 2. If benfotiamine is considered, set realistic expectations: it may prevent future AGE formation in early diabetes but will not "neutralize" existing AGEs 1, 6.