Benfotiamine Inhibits Intracellular Formation of Advanced Glycation End Products in
vivo
JIHONG LIN, ALEX ALT, JUTTA LIERSCH, REINHARD G. BRETZEL,
MICHAEL BROWNLEE, HANS-PETER HAMMES
Third Medical Department,
Justus-Liebig-University Giessen, Germany
Albert-Einstein College of Medicine, New York, USA
Abstract
We have demonstrated previously that intracellular formation of
the advanced glycation end product (AGE) N-epsilon-(carboxymethyl)-lysine (CML) inversely correlates with diabetic vascular
complications independently from glycemia (Diabetologia 42, 603, 1999).Here, we studied the effect of benfotiamine, a lipid-soluble
thiamine derivative with known AGE-inhibiting properties in-vitro on the intracellular
formation of (CML) and methylglyoxal-derived AGE in red blood cells.
Blood was collected from 6 Type 1 diabetic patients(2 m, 4 f, age 31.8 ± 5.5 years; diabetes duration 15.3 ± 7.0
years) before and after treatment with 600 mg/day benfotiamine for 28 days.
In addition to HbA1c (HULK), CML and methylglyoxal were measured using specific antibodies and a quantitative dot
blot technique While treatment with benfotiamine did not affect HbA1c levels
(at entry: 7.18±0.86%; at conclusion 6.88±0.88%; p not significant), levels
of CML decreased by 40 % (737 ± 51 arbitray unit/mg protein (AU) vs. 470 ± 86 AU; p<0.001). The levels of
intracellular methylglyoxal-derived AGE were reduced by almost 70% (1628 ±1136 AU
vs. 500 ± 343 AU; p < 0.01). The data indicate that thiamine derivatives
are effective inhibitors of both intracellular glycoxidation and AGE
formation.
INTRODUCTION
Intracellular formation of the advanced glycation end product (AGE) Ne-(carboxymethyl)lysine
(CML) inversely correlates with diabetic vascular complications independently from glycemia.
(1) Intracellular CML is generated by the oxidation of Amadori products or, alternatively,
by lipid peroxidation (2,3). The dicarbonylmethylglyoxal is formed by
non-oxidative fragmentation of glycolysis-derived triosephosphates and is the most
important intracellular AGE (4,5).
Thiamine is a potent AGE-inhibitor in-vitro (6),
and benfotiamine, the lipid-soluble pro-drug of thiamine was shown to reduce CML and other AGE in
target tissues of diabetic complications in-vivo (7). We studied
the effect of benfotiamine, a lipid-soluble thiamine derivative with known AGE-inhibiting properties in-vitro on the intracellular formation of (CML)
and methylglyoxal-derived AGE in red blood cells of patients with type 1
diabetes.
METHODS
Study group: six patients (2 males, 4 females), age31.8 ± 5.5 years; diabetes duration 15.3 ± 7.0
years. Treatment with 600 mg/day benfotiamine for 28days after informed consent and approval by
the local ethics committee. Venous EDTA-blood (3 ml) drawn before and at
the end of the study, samples lysed and centrifuged, adjusted to identical hemoglobin
concentrations. Quantitative immunoblotting carried out essentially as described before (1). Statistical analysis
was performed using the alternate Welsh t test.
CONCLUSION
Thiamine derivatives, in particular the lipid-soluble pro-drug benfotiamine, are effective inhibitor
of intracellular formation of AGE and CML.
References
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7. Hammes HP et al.: Diabetologia 41, Suppl. 1, A310, 1998
