Acta Diabetol. 2001;38(3):135-8.
Benfotiamine is similar to thiamine in correcting endothelial cell defects induced by high glucose.
Pomero F, Molinar Min A, La Selva M, Allione A, Molinatti GM, Porta M.
WHO Collaborating Centre for Diabetes-Related Blindness, Department of Internal Medicine, University of Turin, Italy.
We investigated the hypothesis that benfotiamine, a lipophilic derivative of thiamine, affects replication delay and generation of advanced glycosylation end-products (AGE) in human umbilical vein endothelial cells cultured in the presence of high glucose. Cells were grown in physiological (5.6 mM) and high (28.0 mM) concentrations of D-glucose, with and without 150 microM thiamine or benfotiamine. Cell proliferation was measured by mitochondrial dehydrogenase activity. AGE generation after 20 days was assessed fluorimetrically. Cell replication was impaired by high glucose (72.3%+/-5.1% of that in physiological glucose, p=0.001). This was corrected by the addition of either thiamine (80.6%+/-2.4%, p=0.005) or benfotiamine (87.5%+/-8.9%, p=0.006), although it not was completely normalized (p=0.001 and p=0.008, respectively) to that in physiological glucose. Increased AGE production in high glucose (159.7%+/-38.9% of fluorescence in physiological glucose, p=0.003) was reduced by thiamine (113.2%+/-16.3%, p=0.008 vs. high glucose alone) or benfotiamine (135.6%+/-49.8%, p=0.03 vs. high glucose alone) to levels similar to those observed in physiological glucose. Benfotiamine, a derivative of thiamine with better bioavailability, corrects defective replication and increased AGE generation in endothelial cells cultured in high glucose, to a similar extent as thiamine. These effects may result from normalization of accelerated glycolysis and the consequent decrease in metabolites that are extremely active in generating nonenzymatic protein glycation. The potential role of thiamine administration in the prevention or treatment of vascular complications of diabetes deserves further investigation.

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Zh Nevrol Psikhiatr Im S S Korsakova. 2001;101(12):32-6.
[Bendotiamine efficacy in alcoholic polyneuropathy therapy] [Article in Russian]
Anisimova EI, Danilov AB.
Benfogamma efficacy in alcoholic polyneuropathy therapy with pain syndrome and other sensor disorders has been studied. Fourteen males with stage II-III chronic alcoholism (mean age 41.2 +/- 9 years, mean alcoholism duration 20.6 +/- 6 years, mean alcoholic polyneuropathy therapy duration 6.8 +/- 4.9 years) have been examined, 93% of the cases having positive family history of alcoholism. Clinical neurophysiological examination was conducted at the beginning and at the end of 6-week therapy, 450 mg/day (2 weeks) and 300 mg/day (4 weeks). During the treatment the regress of algic, other sensor and movement disorders, as well as some neuropathy symptoms has been observed. The evidence of positive dynamics at peripheral and segmental nerve system level was supported by neurophysiological data.

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Scientific report from Medical Clinic V, School of Clinical Medicine, Mannheim, Germany. 2005.
Milgamma (Benfotiamine) blocks three major pathways of hyperglycemic damage and prevents experimental diabetic retinopathy.
Medical Clinic V, School of Clinical Medicine, Mannheim, Germany.
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 (milgamma) 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.

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Arzneimittelforschung. 1999 Mar;49(3):220-4.
Effectiveness of different benfotiamine dosage regimens in the treatment of painful diabetic neuropathy.
Winkler G, Pal B, Nagybeganyi E, Ory I, Porochnavec M, Kempler P.
2nd Department of Internal Medicine, Municipal St. Johns Hospital, Budapest, Hungary.
The therapeutic effectiveness of a benfotiamine (CAS 22457-89-2)-vitamin B combination (Milgamma-N), administered in high (4 x 2 capsules/day, = 320 mg benfotiamine/day) and medium doses (3 x 1 capsules/day), was compared to a monotherapy with benfotiamine (Benfogamma) (3 x 1 tablets/day, = 150 mg benfotiamine/day) in diabetic patients suffering from painful peripheral diabetic neuropathy (DNP). In a 6-week open clinical trial, 36 patients (aged 40 to 70 yrs) having acceptable metabolic control (HbA1c < 8.0%) were randomly assigned to three groups, each of them comprising 12 participants. Neuropathy was assessed by five parameters: the pain sensation (evaluated by a modified analogue visual scale), the vibration sensation (measured with a tuning fork using the Riedel-Seyfert method) and the current perception threshold (CPT) on the peroneal nerve at 3 frequencies: 5, 250 and 2000 Hz). Parameters were registered at the beginning of the study and at the end of the 3rd and 6th week of therapy. An overall bneneficial therapeutic effect on the neuropathy status was observed in all three groups during the study, and a significant improvement in most of the parameters studied appeared already at the 3rd week of therapy (p < 0.01). The greatest change occurred in the group of patients receiving the high dose of benfotiamine (p < 0.01 and 0.05, resp., compared to the othr groups). Metabolic control did not change over the study. It is concluded that benfotiamine is most effective in large doses, although even in smaller daily dosages, either in combination or in monotherapy, it is effective.

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Zh Nevrol Psikhiatr Im S S Korsakova. 1998;98(9):30-2.
Diabetic polyneuropathy treatment by milgamma-100 preparation.
Sadekov RA, Danilov AB, Vein AM.
Efficiency of Milgamma-100 preparation (100 mg of benfothiamine + 100 mg of pyridoxin) was studied in treatment of diabetic polyneuropathy in 14 patients with diabetes mellitus type II (1 dragee 3 times a day, within 6 weeks). After the course of treatment the intensity of pains was decreased according to visual analogous scale on the average from 8.2 to 2.3 scores, the indices of vibratory sensitivity improved significantly as well as the data of cardiovascular tests characterizing parasympathetic control of heart rhythm. Meanwhile latent periods of the evoked sympathetic potentials on arms and legs which were initially lengthened became significantly shorter. A clear-cut tendency was also found to increasing conduction rate for excitation through the motor nerves. The treatment resulted in the improvement of the condition in 93% of the cases. The conclusion was made about efficiency and safety of Milgamma-100 preparation application in therapy of patients with diabetic polyneuropathy.

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Folia Med (Plovdiv). 1997;39(4):5-10.
Therapeutic efficacy of "Milgamma" in patients with painful diabetic neuropathy.
Simeonov S, Pavlova M, Mitkov M, Mincheva L, Troev D.
Endocrinology and Metabolic Disorders Clinic, Higher Medical Institute, Plovdiv, Bulgaria.
Forty-five diabetes patients with painful peripheral polyneuropathy were enrolled in a 3-month observational study comparing the therapeutic efficacy of Milgamma tablets (50 mg benfothiamine and 0.25 mg cyancobalamine) with parallel randomized treatment assignment with the conventional vitamin B complex treatment regimen Neurobex. Thirty patients in group one were randomized to receive two Milgamma tablets qid for three weeks followed by 1 Milgamma tablet tid for 9 weeks. In group two 15 patients received two Neurobex tablets tid for the entire 3-month study period. Therapeutic efficacy was assessed on the basis of within-patient differences in pain severity between Milgamma and Neurobex-treated patients and in vibration perception thresholds using the Rydel-Seiffer biothesiometer at baseline and at the end of the study. Statistically significant relief of both background and peak neuropathic pain was achieved in all of the Milgamma-treated patients and vibration perception thresholds dramatically improved with a median of 1.56 measured on the biothesiometer scale (t = 3.24, P < 0.01). The sensory symptoms improvement was insignificant in the Neurobex-treated patient group and the changes in the vibration perception thresholds failed to reach statistical significance. The therapeutic efficacy of Milgamma was greater in patients with early-stage diabetes as compared with those with advanced diabetic neuropathy. No adverse reactions were observed following the administration of the medication. Our results underscore the importance of Milgamma tablets as an indispensable element in the therapeutic regimen of patients with painful diabetic polyneuropathy.

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Arzneimittelforschung. 1999 Mar;49(3):220-4.
Effectiveness of different benfotiamine dosage regimens in the treatment of painful diabetic neuropathy.
Winkler G, Pal B, Nagybeganyi E, Ory I, Porochnavec M, Kempler P.
2nd Department of Internal Medicine, Municipal St. John's Hospital, Budapest, Hungary.
The therapeutic effectiveness of a benfotiamine (CAS 22457-89-2)-vitamin B combination (Milgamma-N), administered in high (4 x 2 capsules/day, = 320 mg benfotiamine/day) and medium doses (3 x 1 capsules/day), was compared to a monotherapy with benfotiamine (Benfogamma) (3 x 1 tablets/day, = 150 mg benfotiamine/day) in diabetic patients suffering from painful peripheral diabetic neuropathy (DNP). In a 6-week open clinical trial, 36 patients (aged 40 to 70 yrs) having acceptable metabolic control (HbA1c < 8.0%) were randomly assigned to three groups, each of them comprising 12 participants. Neuropathy was assessed by five parameters: the pain sensation (evaluated by a modified analogue visual scale), the vibration sensation (measured with a tuning fork using the Riedel-Seyfert method) and the current perception threshold (CPT) on the peroneal nerve at 3 frequencies: 5, 250 and 2000 Hz). Parameters were registered at the beginning of the study and at the end of the 3rd and 6th week of therapy. An overall bneneficial therapeutic effect on the neuropathy status was observed in all three groups during the study, and a significant improvement in most of the parameters studied appeared already at the 3rd week of therapy (p < 0.01). The greatest change occurred in the group of patients receiving the high dose of benfotiamine (p < 0.01 and 0.05, resp., compared to the othr groups). Metabolic control did not change over the study. It is concluded that benfotiamine is most effective in large doses, although even in smaller daily dosages, either in combination or in monotherapy, it is effective.