Benfotiamine Overview

Benfotiamine Research Summary

Benfotiamine, a lipid-soluble thiamine analogue, is absorbed significantly better than water-soluble thiamine salts when taken orally. The compound shows superior absorption compared to other lipophilic thiamine derivatives, with plasma levels of thiamine from benfotiamine being approximately 5 times higher, and its bioavailability up to 3.6 times greater than thiamine hydrochloride. This excellent absorption and bioavailability profile suggests that benfotiamine should be the preferred choice for thiamine supplementation in conditions that require it.

Benfotiamine is used to prevent diabetic complications by increasing tissue levels of thiamine diphosphate and enhancing transketolase activity. However, while it significantly increases thiamine levels in the blood and liver, it does not do so in the brain. This may explain why benefits are observed in peripheral tissues but not in the central nervous system. In contrast, another lipid-soluble thiamine disulfide derivative, sulbutiamine, does increase thiamine levels in the brain and acts as a central nervous system drug.

Solid dispersions of benfotiamine created with hydrophilic polymers PVP K-30 and HPMC E4 using a kneading method have been shown to effectively increase the dissolution rate of benfotiamine, suggesting a potential enhancement in the solubility of poorly water-soluble drugs.

Benfotiamine's ability to reduce advanced glycation end products (AGEs) makes it a promising treatment for diabetic complications such as neuropathy, nephropathy, and retinopathy. Moreover, it has been found to improve spatial memory and reduce amyloid plaque numbers and phosphorylated tau levels in an Alzheimer's disease mouse model, indicating a potential treatment for AD.

The pentose phosphate pathway, activated by benfotiamine, plays a role in preventing oxidative stress in the brain caused by diabetes, and the compound has shown synergistic effects with resveratrol in reducing neurogenic pain in mice. High glucose levels promote the production of beta-amyloid in cells, and benfotiamine can prevent this increase, suggesting a therapeutic role in conditions associated with elevated beta-amyloid production, such as Alzheimer's disease.

In clinical trials, benfotiamine has demonstrated effectiveness in improving symptoms of diabetic polyneuropathy, with the potential to influence glucose metabolism. It has also shown protective effects against diabetic cardiomyopathy by inhibiting the interaction between AGEs and their receptor (RAGE). Additionally, benfotiamine has been found to inhibit protein phosphatase activation induced by high glucose, preventing endothelial cell death and correcting other metabolic defects.

Benfotiamine treatment has been shown to completely prevent the vascular dysfunction and oxidative stress caused by AGE-rich meals in individuals with type 2 diabetes, and to protect against DNA damage in hemodialysis patients. Furthermore, benfotiamine has demonstrated anti-inflammatory effects by suppressing oxidative stress and inhibiting the activation of enzymes and transcription factors involved in inflammation.

References:

1. Pharmacokinetics of thiamine derivatives especially of benfotiamine
2. A new thiamine derivative, S-benzoylthiamine O-monophosphate
3. Solubility enhancement of benfotiamine, a lipid derivative of thiamine by solid dispersion technique
4. Benfotiamine, a synthetic S-acyl thiamine derivative, has different mechanisms of action and a different pharmacological profile than lipid-soluble thiamine disulfide derivatives
5. Prostatic acid phosphatase is required for the antinociceptive effects of thiamine and benfotiamine
6. Bioavailability assessment of the lipophilic benfotiamine as compared to a water-soluble thiamin derivative
7. The multifaceted therapeutic potential of benfotiamine
8. Powerful beneficial effects of benfotiamine on cognitive impairment and beta-amyloid deposition in amyloid precursor protein/presenilin-1 transgenic mice
9. Benfotiamine prevents increased β-amyloid production in HEK cells induced by high glucose
10. Benfotiamine alleviates diabetes-induced cerebral oxidative damage independent of advanced glycation end-product, tissue factor and TNF-alpha
11. Antinociceptive interaction between benfotiamine and resveratrol in capsaicin-induced licking
12. Benfotiamine relieves inflammatory and neuropathic pain in rats
13. Benfotiamine in diabetic polyneuropathy (BENDIP): results of a randomised, double blind, placebo-controlled clinical study
14. Advanced glycation endproduct (AGE) accumulation and AGE receptor (RAGE) up-regulation contribute to the onset of diabetic cardiomyopathy
15. High-dose benfotiamine rescues cardiomyocyte contractile dysfunction in streptozotocin-induced diabetes mellitus
16. Vitamin B1 analog benfotiamine prevents diabetes-induced diastolic dysfunction and heart failure through Akt/Pim-1-mediated survival pathway
17. PP2A contributes to endothelial death in high glucose: inhibition by benfotiamine
18. Benfotiamine prevents macro- and microvascular endothelial dysfunction and oxidative stress following a meal rich in advanced glycation end products in individuals with type 2 diabetes
19. Adiponectin decreases postprandially following a heat-processed meal in individuals with type 2 diabetes: an effect prevented by benfotiamine and cooking method
20. Advanced glycation end-products inhibition improves endothelial dysfunction in rheumatoid arthritis
21. Normalizing mitochondrial superoxide production blocks three pathways of hyperglycaemic damage
22. Benfotiamine blocks three major pathways of hyperglycemic damage and prevents experimental diabetic retinopathy
23. Aldose reductase, oxidative stress, and diabetic mellitus
24. Properties and functions of the thiamin diphosphate dependent enzyme transketolase
25. Blood thiamine levels in outpatients with diabetes mellitus
26. The potential role of thiamine (vitamin B1) in diabetic complications
27. Benfotiamine exhibits direct antioxidative capacity and prevents induction of DNA damage in vitro
28. Benfotiamine counteracts glucose toxicity effects on endothelial progenitor cell differentiation via Akt/FoxO signaling
29. Boosting the pentose phosphate pathway restores cardiac progenitor cell availability in diabetes
30. Oral benfotiamine plus alpha-lipoic acid normalises complication-causing pathways in type 1 diabetes
31. Effect of benfotiamine on advanced glycation endproducts and markers of endothelial dysfunction and inflammation in diabetic nephropathy
32. The effects of long-term oral benfotiamine supplementation on peripheral nerve function and inflammatory markers in patients with type 1 diabetes: a 24-month, double-blind, randomized, placebo-controlled trial
33. Comment on: Fraser et al. The effects of long-term oral benfotiamine supplementation on peripheral nerve function and inflammatory markers in patients with type 1 diabetes: a 24-month, double-blind, randomized, placebo-controlled trial. Diabetes Care 2012;35:1095-1097
34. Benfotiamine increases glucose oxidation and downregulates NADPH oxidase 4 expression in cultured human myotubes exposed to both normal and high glucose concentrations
35. Diabetes mellitus induces bone marrow microangiopathy
36. Inhibition of macrophage oxidative stress prevents the reduction of ABCA-1 transporter induced by advanced glycated albumin
37. Advanced glycation end product precursors impair ABCA1-dependent cholesterol removal from cells
38. AGE-BSA decreases ABCG1 expression and reduces macrophage cholesterol efflux to HDL
39. Protective role of benfotiamine, a fat-soluble vitamin B1 analogue, in lipopolysaccharide-induced cytotoxic signals in murine macrophages
40. Anti-inflammatory effects of benfotiamine are mediated through the regulation of the arachidonic acid pathway in macrophages
41. Benfotiamine reduces genomic damage in peripheral lymphocytes of hemodialysis patients
42. Antioxidant supplementation reduces inter-individual variation in markers of oxidative damage
43. Benfotiamine counteracts smoking-induced vascular dysfunction in healthy smokers
44. Benfotiamine protects against peritoneal and kidney damage in peritoneal dialysis
45. Increased protein damage in renal glomeruli, retina, nerve, plasma and urine and its prevention by thiamine and benfotiamine therapy in a rat model of diabetes
46. A double-blind, randomized, placebo-controlled clinical trial on benfotiamine treatment in patients with diabetic nephropathy
47. Thiamine and benfotiamine prevent apoptosis induced by high glucose-conditioned extracellular matrix in human retinal pericytes
48. A study of capillary pericyte viability on extracellular matrix produced by endothelial cells in high glucose
49. Pericyte adhesion is impaired on extracellular matrix produced by endothelial cells in high hexose concentrations
50. Different apoptotic responses of human and bovine pericytes to fluctuating glucose levels and protective role of thiamine
51. Pericytes in the microvasculature
52. Effects of thiamine and benfotiamine on intracellular glucose metabolism and relevance in the prevention of diabetic complications