Benfotiamine blocks three major pathways of hyperglycemic damage and prevents experimental
diabetic retinopathy and incipient nephropathy in these models. In cultured vascular cells,
it also reduces aldose reductase gene expression, activity, and sorbitol levels. It does so
by activating the enzyme transketolase. α-lipoic acid, a potent antioxidant, has also been
reported to reduce both diabetic microvascular and macrovascular complications in animal
models. To determine whether benfotiamine in combination with α-lipoic acid would
normalize markers of ROS-induced pathways of complications in humans, we performed a pilot
study in subjects with Type 1 diabetes using one daily dose of benfotiamine in combination
with α-lipoic acid.
The glycemic status of study patients was assessed by measuring baseline values of HbA1c,
fructosamine, and fasting plasma glucose. Mean HbA1c was 8.7+ 0.7%, mean fructosamine was
421+29 mg/dl (normal range 174-286 mg/dl), and mean fasting blood glucose was 198+44
At day 0, subjects levels of markers of two benfotiamine-sensitive pathways were determined:
intracellular advanced glycation endproduct (AGE) formation, as reflected by a marker of
increased intracellular methylglyoxal adducts in endothelial cells, angiopoietin 2 and
hexosamine pathway activity, measured by determination of N-acetylglucosamine-modified
protein in circulating monocytes. PKC activity in circulating monocytes could not be
measured because the amount of blood required exceeded that approved by the Committee on
Clinical Investigations. Serum levels of 6-keto-PGF-1 , a stable product produced by the
nonenzymatic hydration of the antiatherogenic mediator prostacyclin were also determined.
Subjects then took benfotiamine 300 mg twice a day, (Advanced Orthomolecular Research,
Calgary, AB,CANADA) and slow-release α-lipoic acid (600 mg twice a day) (MRI, San
Francisco, CA) for 28 days. Blood was obtained at day 0, day 15, and day 28.
Data were analyzed using 1-factor analysis of variance to compare the means of all the
groups. The Tukey−Kramer multiple comparisons procedure was used to determine which pairs of
means were different.
- Type 1 diabetes duration between zero and fifteen years
- current insulin therapy
- proliferative retinopathy
- symptomatic diabetic neuropathy
- cardiovascular disease
- taking medications