Milgamma scientific update |
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Diabetologia. 2006 Feb;49(2):405-20. Epub 2006 Jan 17.
Gadau S, Emanueli C, Van Linthout S, Graiani G, Todaro M, Meloni M, Campesi I, Invernici G, Spillmann F, Ward K, Madeddu P.
Experimental Medicine and Gene Therapy, National Institute of Biostructures and Biosystems (INBB), Osilo, Italy.
Benfotiamine accelerates the healing of ischaemic diabetic limbs in mice through protein kinase B/Akt-mediated potentiation of angiogenesis and inhibition of apoptosis.
AIMS/HYPOTHESIS: Benfotiamine, a vitamin B1 analogue, reportedly prevents diabetic microangiopathy. The aim of this study was to evaluate whether benfotiamine is of benefit in reparative neovascularisation using a type I diabetes model of hindlimb ischaemia. We also investigated the involvement of protein kinase B (PKB)/Akt in the therapeutic effects of benfotiamine. METHODS: Streptozotocin-induced diabetic mice, given oral benfotiamine or vehicle, were subjected to unilateral limb ischaemia. Reparative neovascularisation was analysed by histology. The expression of Nos3 and Casp3 was evaluated by real-time PCR, and the activation state of PKB/Akt was assessed by western blot analysis and immunohistochemistry. The functional importance of PKB/Akt in benfotiamine-induced effects was investigated using a dominant-negative construct. RESULTS: Diabetic muscles showed reduced transketolase activity, which was corrected by benfotiamine. Importantly, benfotiamine prevented ischaemia-induced toe necrosis, improved hindlimb perfusion and oxygenation, and restored endothelium-dependent vasodilation. Histological studies revealed the improvement of reparative neovascularisation and the inhibition of endothelial and skeletal muscle cell apoptosis. In addition, benfotiamine prevented the vascular accumulation of advanced glycation end products and the induction of pro-apoptotic caspase-3, while restoring proper expression of Nos3 and Akt in ischaemic muscles. The benefits of benfotiamine were nullified by dominant-negative PKB/Akt. In vitro, benfotiamine stimulated the proliferation of human EPCs, while inhibiting apoptosis induced by high glucose. In diabetic mice, the number of circulating EPCs was reduced, with the deficit being corrected by benfotiamine. CONCLUSIONS/INTERPRETATION: We have demonstrated, for the first time, that benfotiamine aids the post-ischaemic healing of diabetic animals via PKB/Akt-mediated potentiation of angiogenesis and inhibition of apoptosis. In addition, benfotiamine combats the diabetes-induced deficit in endothelial progenitor cells.
Endocrinology and Metabolic Disorders Clinic, Higher Medical Institute,
Simeonov S, Pavlova M, Mitkov M, Mincheva L, Troev D
Folia Med (Plovdiv). 1997;39(4):5-10. Bulgaria
Therapeutic efficacy of
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
Scientific report from Medical Clinic V, School of Clinical Medicine, Mannheim, Germany. 2005.
Medical Clinic V, School of Clinical Medicine, Mannheim, Germany.
Milgamma (Benfotiamine) blocks three major pathways of hyperglycemic damage and prevents experimental diabetic retinopathy.
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.
Zh Nevrol Psikhiatr Im S S Korsakova. 2001;101(12):32-6.
Anisimova EI, Danilov AB.
[Bendotiamine efficacy in alcoholic polyneuropathy therapy] [Article in Russian]
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.
Acta Diabetol. 2001;38(3):135-8.
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.
Benfotiamine is similar to thiamine in correcting endothelial cell defects induced by high glucose.
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.
Milgamma description...
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Drug category:Antidiabetic agents
 Milgamma scientific update
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