Benfotiamine

Benfotiamine is a lipid-soluble derivative of thiamin that demonstrates improved absorption and duration of activity compared to water-soluble thiamin hydrochloride (HCL). As compared to thiamin HCL administration, maximum plasma levels are approximately five times higher and bioavailability is, at maximum, approximately 3.6 times as high. Its effectiveness, however, has been demonstrated even in low doses (i.e. 150 mg/d) [1].

Pathways of Glucose-Metabolite–Induced Damage: High intracellular sugars can lead to an accumulation of intermediate metabolic products. These metabolic products activate certain pathways [2,3]. These pathways are: (1) polyol pathway flux; (2) increased formation of AGEs (advanced glycation end-products); (3) increased expression of the receptor for AGEs (RAGEs) and its activating ligands; (4) activation of protein kinase C (PKC) isoforms; and (5) over activity of the hexosamine pathway [3]. Together, these mechanisms can impact vascular tissue and target particularly susceptible capillary endothelial cells of the retina, mesangial cells in the renal glomerulus, neuronal cells, and Schwann cells [2-6].

Benfotiamine Supports Diversion to Different Pathway: Benfotiamine was shown to have a positive influence on AGE formation and PKC activity. This research has been supported by a human pilot study wherein subjects given benfotiamine (600 mg/d) plus alpha-lipoic acid (1200 mg/d) demonstrated healthy changes in AGE formation, monocyte hexosamine-modified proteins, and prostacyclin synthase activity [7].

Nerve Tissue Health: Microvasculature feeding peripheral nerves can be affected by the pathways discussed earlier. Furthermore, lower AGE formation is associated with healthier nerve tissue. The role of benfotiamine in diverting glucose metabolites to a less harmful metabolic pathway may well be the underlying reason it has been used successfully in Germany for over a decade to support nerve health. Results suggest that benfotiamine is most effective in large doses (320-600 mg/d), although effectiveness is still achieved in smaller daily dosages (150 mg/d) [1,8,9].

References

1. Winkler G, Pál B, Nagybéganyi E, et al. Effectiveness of different benfotiamine dosage regimens in the treatment of painful diabetic neuropathy. Arzneimittelforschung. 1999 Mar;49(3):220-24. [PMID: 10219465]
2. Brownlee M. The pathobiology of diabetic complications: a unifying mechanism. Diabetes. 2005 Jun;54(6):1615-25. [PMID: 15919781]
3. Giacco F, Brownlee M. Oxidative stress and diabetic complications. Circ Res. 2010 Oct 29;107(9):1058-70. [PMID: 21030723]
4. Hammes HP, Du X, Edelstein D, et al. Benfotiamine blocks three major pathways of  hyperglycemic damage and prevents experimental diabetic retinopathy. Nat Med. 2003 Mar;9(3):294-99. [PMID: 12592403]
5. Balakumar P, Rohilla A, Krishan P, et al. The multifaceted therapeutic potential of benfotiamine. Pharmacol Res. 2010 Jun;61(6):482-88. [PMID: 20188835]
6. Thornalley PJ. The potential role of thiamine (vitamin B1) in diabetic complications. Curr Diabetes Rev. 2005 Aug;1(3):287-98. [PMID: 18220605]
7. Du X, Edelstein D, Brownlee M. Oral benfotiamine plus alpha-lipoic acid normalises complication-causing pathways in type 1 diabetes. Diabetologia. 2008 Oct;51(10):1930-32. [PMID: 18663426]
8. Haupt E, Ledermann H, Köpcke W. Benfotiamine in the treatment of diabetic polyneuropathy—a three-week randomized, controlled pilot study (BEDIP study). Int J Clin Pharmacol Ther. 2005 Feb;43(2):71-77. [PMID: 15726875]
9. Stracke H, Gaus W, Achenbach U, et al. Benfotiamine in diabetic polyneuropathy (BENDIP): results of a randomised, double blind, placebo-controlled clinical study. Exp Clin Endocrinol Diabetes. 2008 Nov;116(10):600-05. [PMID: 18473286]