Ingredient Spotlight: Benfotiamine


For decades, European doctors have prescribed diabetic patients benfotiamine to treat neuropathies and to help prevent complications such as blindness, kidney failure, heart attack, and limb amputation.

Thiamine is a water-soluble vitamin required for numerous biochemical reactions in the body. Allithiamines are a group of fat-soluble thiamine derivatives, so-called because they are abundant in the Allium family of vegetables (e.g., onions, garlic, and shallots). Benfotiamine is the most effective and safe of all allithiamine compounds. It is a fat-soluble, bioavailable form of thiamine whose unique chemical structure allows it to more readily pass through the cell membrane.(1,2) Oral administration of benfotiamine has been shown to increase plasma concentrations of thiamine to levels five times greater than achieved with an equivalent dose of thiamine.(3)

Benfotiamine blocks destructive biochemical pathways that enable high blood sugar levels to damage nerves and small blood vessels and has been used to successfully treat complications associated with diabetes. For decades, European doctors have prescribed diabetic patients benfotiamine to treat neuropathies and to help prevent complications such as blindness, kidney failure, heart attack, and limb amputation.

Benfotiamine also inhibits the formation of advanced glycation end products (AGEs) in both diabetic and normal aging organisms. Glycation, also known as glycosylation, is a process whereby glucose is bonded to proteins and lipids that comprise various tissues/organs causing cellular damage, oftentimes irreversible. Studies show that prolonged healthy tissue exposure to elevated glucose levels results in the production of AGEs. AGEs are well known for their destructive activities in diabetes, where they contribute to vascular disease, kidney failure, eye damage, and other kinds of dysfunction, including the nerve damage known as diabetic peripheral neuropathy.(8-11) In patients with this kind of neuropathy, AGEs directly damage vital components of nerve cells, insidiously reducing their ability to conduct warning sensations such as pain and pressure.

Let’s explore some significant benefits of benfotiamine for diabetes-related conditions.

Mechanism of Action

Benfotiamine has shown to impact glucose metabolism through various mechanisms.

It helps to reduce the excess biosynthesis and accumulation of a variety of glucose metabolites, including glyceraldeyde-3-phosphate and dihydroxyacetone phosphate. Increased concentrations of these glucose intermediates serve as a trigger to many of the mechanisms responsible for hyperglycemia-induced cell damage.(4) Benfotiamine increases tissue levels of thiamine diphosphate, in turn increasing transketolase activity and resulting in a significant reduction in glucose metabolites and precursors to AGEs.(5)

Benfotiamine also helps reduce the activity of aldose reductase, which in turn helps limit tissue accumulation of sorbitol and glucose, helping to reduce endothelial cell damage.(6)

In addition, benfotiamine has been shown to reduce NF-kB activity, thereby limiting the overproduction of the damaging superoxide free radical. Excess superoxide production may partially inhibit a key enzyme in glucose metabolism, glyceraldehyde-3-phosphate dehydrogenase, diverting glucose metabolites from glycolysis into the major glucose-driven signaling pathways that lead to hyperglycemic damage.(7)


Benfotiamine has been shown to improve pain associated with diabetic peripheral neuropathy (DPN) and to improve nerve conduction velocity in conjunction with vitamins B6 and B12.(12-14)

Stracke H et al. performed a double-blind, placebo-controlled, phase III study in which 165 patients with symmetrical, distal DPN were randomized to one of three treatment groups: benfotiamine 600 mg/day (n=47 [intent-to-treat]/43 [per protocol]), benfotiamine 300 mg/day (n=45/42), or placebo (n=41/39). After six weeks of treatment, the primary outcome parameter Neuropathy Symptom Score differed significantly between the treatment groups in the per-protocol population, with the treatment group showing improved results. In the Total Symptom Score (TSS), best results were obtained for the symptom “pain.”(15)

Diabetic retinopathy is a major cause of blindness, and its prevalence is growing worldwide. Administering high-dose benfotiamine prevented the development of retinopathy by halting AGEs formation.(16) Benfotiamine helps decrease retinal capillary changes, and high-dose benfotiamine therapy increases the activity of transketolase in the retina, helping to prevent the development of retinopathy. Also, benfotiamine was shown to block three major pathways of hyperglycemic damage, including AGEs, protein kinase C (PKC), and hexosamine pathways, to prevent the progression of diabetic retinopathy.(17)

Researchers also showed that a heat-treated, high AGEs–content meal induces endothelial dysfunction and oxidative stress and increases serum AGEs and MG concentration-effects that are prevented by benfotiamine.(8)

Diabetic nephropathy is a major cause of end-stage renal failure and is characterized by significant structural changes in the kidney. Hyperglycemia results in accumulation of triosephosphates arising from high glucose concentrations that leads to biochemical dysfunction in the renal cells, ultimately leading to the development of diabetic nephropathy.(18) Benfotiamine in high doses prevented the development of diabetic nephropathy by increasing transketolase expression in renal glomeruli, triggering the conversion of triosephosphates to ribose-5-phosphate and inhibiting the incidence of microalbuminuria, which is associated with decreased activation of PKC and reduced occurrences of protein glycation and oxidative stress.(8)


Several studies support the use of benfotiamine in conditions related to the damaging effects caused by diabetes and/or hyperglycemia. Benfotiamine is one of a few compounds that have been well studied (others include alpha-lipoic acid) using randomized, placebo-controlled studies. Given the scientific evidence supporting the use of benfotiamine, and the lack of natural therapies for diabetes-related conditions (e.g., neuropathy, retinopathy, nephropathy), physicians should consider this inexpensive and safe compound as an adjunct to current diabetes treatment.


  1. Bitsch R, et al. Bioavailability assessment of the lipophilic benfotiamine as compared to a water- soluble  thamine derivative.  Ann Nutr Metab  1991:35:292-296.   
  2. Loew D.  Pharmacokinetics of thiamine derivatives especially of benfotiamine.  Int J Clin Pharmacol Ther  1996:34:47-50. 
  3. Gleiter C, Shreeb K, Freudenthaler S.  Comparative bioavailability of two vitamin B1 preparations:benfotiamine and thiamine mononitrate. In Gries FA, Federlin K, editors.  Benfotiamine in the therapy of polyneuropathy.  New York: Georg Thieme Verlag: 1998. P. 29-33.
  4. Tilton R, et al,  Diabetes-induced glomerular dysfunction: links to a more reduced cytosolic ratio of NADH/NAD+ .  Kidney Int  1992;41:778-788.
  5. Lin J, et al.  Benfotiamine inhibits intracellular formation of advanced glycation end products in vivo.  Diabetes  2000;49:p583.
  6. Beltramo E, el al.  Regulation of intracellular glucose and polyol pathway by thiamine and benfotiamine in vascular cells cultured in high glucose.  J Biol Chem  2006;281:9307-9313.
  7. Nishikawa T, et al.   Normalizing mitochondrial superoxide production blocks three pathways of hyperglycemic damage.  Nature  2000;404:787-70 
  8. Stirban A, et al.  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.  Diabetes Care  2006;29:2064-2071.   
  9. Basta G, et al.  Advanced glycation end products and vascular inflammation: implications for accelerated atherosclerosis in diabetes.  Cardiovasc Res  2004;63:582-592.
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  11. Shimoike T, et al.  The meaning of serum levels of advanced glycosylation end products in diabetic  nephropathy.  Metabolism  2000;49:1030-1035.           
  12. Haupt E, et al.  Benfotiamine in the treatment of diabetic poly neuropathy: a three-week randomized, controlled pilot study (BEDIP study).  Int J Clin Pharmacol Ther  2005;43:71-77.
  13. Stracke H, et al.  Benfotiamine vitamin B combination in treatment of diabetic polyneuropathy.  Exp Clin Endocrinol Diabetes  1996;104:311-316.
  14. Winkler G, et al.   Effectiveness of different benfotiamine dosages regimens in the treatment of painful diabetic neuropathy.  Arzneimittelforschung  1999;49:220-224.
  15. Stracke H, et al.  Benfotiamine in diabetic polyneuropathy (BENDIP): results of a randomized, double-blind, placebo-controlled clinical study.  Exp Endocrin Diabetes  2008;116:600-605.
  16. Obrenovich ME, Monnier VM. Vitamin B1 blocks damage caused by hyperglycemia. Sci Aging Knowledge Environ 2003;6.
  17. Hammes HP, Du X, Edelstein D, Taguchi T, Matsumura T, Ju Q, et al. Benfotiamine blocks three   major pathways of hyperglycemic damage and prevents experimental diabetic retinopathy. Nat Med 2003;294–299.
  18. Babaei-Jadidi R, et al.  Prevention of incipient diabetic nephropathy by high-dose thiamine and benfotiamine.  Diabetes 2003;52:2110–2120.
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