Effects of thiamine and benfotiamine on intracellular glucose metabolism and relevance in the prevention of diabetic complications. Acta Diabetol

Department of Internal Medicine, University of Turin, Corso AM Dogliotti, 14, 10126, Turin, Italy.
Acta Diabetologica (Impact Factor: 2.4). 07/2008; 45(3):131-41. DOI: 10.1007/s00592-008-0042-y
Source: PubMed


Thiamine (vitamin B1) is an essential cofactor in most organisms and is required at several stages of anabolic and catabolic intermediary metabolism, such as intracellular glucose metabolism, and is also a modulator of neuronal and neuro-muscular transmission. Lack of thiamine or defects in its intracellular transport can cause a number of severe disorders. Thiamine acts as a coenzyme for transketolase (TK) and for the pyruvate dehydrogenase and alpha-ketoglutarate dehydrogenase complexes, enzymes which play a fundamental role for intracellular glucose metabolism. In particular, TK is able to shift excess fructose-6-phosphate and glycerhaldeyde-3-phosphate from glycolysis into the pentose-phosphate shunt, thus eliminating these potentially damaging metabolites from the cytosol. Diabetes might be considered a thiamine-deficient state, if not in absolute terms at least relative to the increased requirements deriving from accelerated and amplified glucose metabolism in non-insulin dependent tissues that, like the vessel wall, are prone to complications. A thiamine/TK activity deficiency has been described in diabetic patients, the correction of which by thiamine and/or its lipophilic derivative, benfotiamine, has been demonstrated in vitro to counteract the damaging effects of hyperglycaemia on vascular cells. Little is known, however, on the positive effects of thiamine/benfotiamine administration in diabetic patients, apart from the possible amelioration of neuropathic symptoms. Clinical trials on diabetic patients would be necessary to test this vitamin as a potential and inexpensive approach to the prevention and/or treatment of diabetic vascular complications.

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    • "Thiamine acts as a coenzyme for enzymes (transketolase, pyruvate dehydrogenase, and alpha-ketoglutarate dehydrogenase complexes), which contribute in intracellular glucose metabolism. Hence, glucose intolerance and diabetes might be the result of a thiamine-deficient state.[131] This difference between our results and other reports could be due to differences in the type of study and individuals that had been investigated. "
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    ABSTRACT: Dietary micronutrients have been proposed to protect against oxidative damage and related clinical complications. We aimed to compare the micronutrient intake between individuals with and without metabolic syndrome (MS). This cross-sectional study included 3800 men and women who were aged between 35 and 65 years. The diagnosis of the MS was based on International Diabetes Federation criteria. Dietary intake of participants was assessed using a questionnaire for 24 h dietary recall. Student's t-test and Mann-Whitney U-tests were used for comparing the micronutrient intake of subjects with or without the MS and the odds ratio for the presence of the MS was calculated for each micronutrient by control for total energy intake adjusted by the residue method. The mean age of MS subjects and the control group was 48.8 ± 7.9 years and 47.6 ± 7.6 years, respectively. Energy-adjusted intake of vitamin E (P < 0.05), B2 (P < 0.01), and B12 (P < 0.05) was higher in normal women compared with women with MS. Energy-adjusted intake of vitamin B1 was significantly higher in women with MS. After logistic regression analysis, no significant association between micronutrient intake and MS was shown. We found no significant association between micronutrient intake and MS.
    North American Journal of Medical Sciences 06/2013; 5(6):377-85. DOI:10.4103/1947-2714.114171
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    • "Although, at present no mechanism is known that links TPP with nitric oxide synthesis, recent evidences have shown that the administration of thiamine or benfotiamine inhibits apoptosis (event associated with an impaired mitochondrial activity) [42], hyperfiltration [43], and normalizes TK activity [14] [15]. Interestingly , some evidences revealed that the administration of thiamine attenuates the endothelial dysfunction observed in high glucose concentrations [44] [45]. However, it is relevant to underline that thiamine needs to change at its active metabolite (TPP) to be able to perform this function. "
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    ABSTRACT: Thiamine (Vitamin B1) is considered an essential micronutrient for humans; its deficient intake brings about the Wernicke-Korsakoff syndrome (encephalopathy and psychosis) or beriberi (a neurological and cardiovascular disease). Once thiamine enters the cells it is phosphorylated by thiamine pyrophosphokinase (TPPK), and converted into the coenzyme thiamine pyrophosphate (TPP), the active form of thiamine. TPP is a relevant cofactor for transketolase (TK), α-ketoglutarate dehydrogenase (αKDH), and pyruvate dehydrogenase (PDH), all these enzymes are fundamental for glucose metabolism. Diabetes mellitus (DM), however, is considered both a deficient thiamine and deficient energy state, as a consequence of the limited TPP synthesis. Recent evidences have shown that the administration of thiamine or lipid-soluble derivatives, such as benfotiamine (developed to improve the bioavailability of thiamine), has positive effects in the diabetic patient (after thiamine is transformed into TPP). For this reason, administration of supplements with TPP in the diabetic patients is recommended to avoid complications, like neuropathy and nephropathy. It has been suggested that these beneficial effects are a consequence of the activation of TK (pentose pathway) or the PDH complex in mitochondria. Nitric oxide (NO) is synthesized by the endothelial cell and is also an important element for the viability and functionality of this cell type. However, in the DM patient, a deficient synthesis of NO has been reported. It is relevant to mention that recent evidences have led to propose mitochondrial activity as an important regulator of nitric oxide synthesis (ON). We consider that the exogenous administration of TPP facilitates the utilization of this molecule, regulating some metabolic processes such as phosphorylation of thiamine by TPPK, energy consumption (ATP), as well as mitochondrial activity, inducing eventually NO synthesis. If this is confirmed, the administration of TPP to the diabetic patient would provide additional protection to endothelial cells, reducing the risk of vascular damage, to which the diabetic patient is highly susceptible.
    Medical Hypotheses 05/2011; 76(5):629-31. DOI:10.1016/j.mehy.2011.01.015 · 1.07 Impact Factor
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    • "Further, benfotiamine has been shown to reduce the oxidative stress and genomic damage caused by the mutagenic model compound NQO, the uremic toxin indoxyl sulfate and the peptide hormone angiotensin II in renal cells indicating its direct antioxidant capacity [67]. During hyperglycemia benfotiamine has been shown to regulate the activity of glycolytic enzyme transketolase and divert glucose utilization via pentose phosphate pathway [20] [59]. This could prevent the excessive ROS production due to glucose over-utilization by mitochondria which depends on glycolysis for reducing intermediates, NAD(P)H. "
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    ABSTRACT: This study was designed to investigate the molecular mechanisms by which benfotiamine, a lipid-soluble analogue of vitamin B1, affects lipopolysaccharide (LPS)-induced inflammatory signals leading to cytotoxicity in the mouse macrophage cell line RAW264.7. Benfotiamine prevented LPS-induced apoptosis, expression of the Bcl-2 family of proapoptotic proteins, caspase-3 activation, and PARP cleavage and altered mitochondrial membrane potential and release of cytochrome c and apoptosis-inducing factor and phosphorylation and subsequent activation of p38-MAPK, stress-activated kinases (SAPK/JNK), protein kinase C, and cytoplasmic phospholipase A2 in RAW cells. Further, phosphorylation and degradation of inhibitory kappaB and consequent activation and nuclear translocation of the redox-sensitive transcription factor NF-kappaB were significantly prevented by benfotiamine. The LPS-induced increased expression of cytokines and chemokines and the inflammatory marker proteins iNOS and COX-2 and their metabolic products NO and PGE(2) was also blocked significantly. Thus, our results elucidate the molecular mechanism of the anti-inflammatory action of benfotiamine in LPS-induced inflammation in murine macrophages. Benfotiamine suppresses oxidative stress-induced NF-kappaB activation and prevents bacterial endotoxin-induced inflammation, indicating that vitamin B1 supplementation could be beneficial in the treatment of inflammatory diseases.
    Free Radical Biology and Medicine 02/2010; 48(10):1423-34. DOI:10.1016/j.freeradbiomed.2010.02.031 · 5.74 Impact Factor
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