Benfotiamine blocks three major pathways of hyperglycemic damage and prevents experimental diabetic retinopathy

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.

Long-Term Cognitive Improvement After Benfotiamine Administration in Patients with Alzheimer’s Disease

“…Here, we present the results of a clinical case study showing the potential of benfotiamine as a disease-modifying drug for AD. As a derivative of thiamine with better bioavailability, benfotiamine has been demonstrated to exert beneficial effects against abnormal glucose metabolism and its consequences via multiple mechanisms, including the elimination of oxidative stress [16,17] and the inhibition of glycogen synthase kinase-3 [18], which are both considered to be major pathogenic factors that cause neurodegeneration in AD. The better bioavailability and the pharmacological effects via multiple mechanisms against abnormal glucose metabolism and its consequences may explain why benfotiamine administration but not thiamine supplementation [24] had a long-term beneficial effect on cognitive ability in AD patients.…”

“…Benfotiamine is a synthetic thiamine derivative with better bioavailability than thiamine and has been shown to prevent abnormal glucose metabolism via multiple pathways [16,17]. Our previous study demonstrated that benfotiamine improves cognitive impairment in a mouse model of AD (amyloid precursor protein/presenilin-1 (APP/PS1) transgenic mice) [18].…”

Effect ofOcimum sanctum (Tulsi) and vitamin E on biochemical parameters and retinopathy in streptozotocin induced diabetic rats

“…Cusick et al (28) has clearly shown that Vitamin E in dietary formulation (in dose of 500 IU daily) could reduce age related eye disease (ARED). Benfotiamine has been shown to block three major pathways of hypoglycemic damage and prevent diabetic retinopathy in experimental animals (29). Beside hypoglycemic control familial and genetic factors have been stressed to take part in the pathogenesis of complications like nephropathy and retinopathy (30).…”

Multiple levels of regulation determine the role of the receptor for AGE (RAGE) as common soil in inflammation, immune responses and diabetes mellitus and its complications

“…In the diabetic retina, RAGE is predominantly upregulated in glia cells [101]. While the understanding of RAGE and its role in retinal dysfunction in diabetes and/or activation of pro-inflammatory pathways is less complete than in other organ systems, increasing evidence indicates that RAGE contributes to cellular perturbations in the retina [102][103][104]. Remarkably, in each of these models, protection from development of the pathological features was more profound in wild-type mice treated with sRAGE than in Rage −/− mice.…”