Benfotiamine (rINN, or S-benzoylthiamine O-monophosphate) is a synthetic S-acyl derivative of thiamine (vitamin B1). It is marketed as a dietary supplement in most of the developed world, and as a pharmaceutical drug in some countries for treating diabetic neuropathy under the trade name Milgamma and others. Combination drugs with pyridoxine or cyanocobalamin are also marketed in a few countries. Benfotiamine is primarily marketed as an antioxidant dietary supplement. In some countries it is marketed as a drug to treat diabetic neuropathy;[1] clinical trials results are mixed, finding it mildly useful or no different from placebo.[2][3] There is little published data on adverse effects; in one study of a combination drug of benfotiamine, pyridoxine, and cyanocobalamin, around 8% of people taking the drug experienced nausea, dizziness, stomach ache and weight gain.[4] Benfotiamine is more bioavailable than thiamine salts, providing higher levels of thiamine in muscle, brain, liver, and kidney.[4] Benfotiamine is dephosphorylated to S-benzoylthiamine by ecto-alkaline phosphatases present in the intestinal mucosa, and is then hydrolyzed to thiamine by thioesterases in the liver.[5] Benfotiamine mainly acts on peripheral tissues through an increase in transketolase activity.[5][4][6] Benfotiamine is a synthetic S-acyl Vitamin B1 analogue; its chemical name is S-benzoylthiamine O-monophoshate.[7] Benfotiamin is a lipid derivative of thiamine vitamin. It has very low solubility in water or other aqueous solvents. .[5] As of 2017, benfotiamine was marketed as a pharmaceutical drug in Argentina, Bosnia & Herzegowina, Bulgaria, Colombia, Czech Republic, Estonia, Georgia, Germany, Hong Kong, Hungary, India, Indonesia, Japan, Latvia, Lithuania, Poland, Portugal, Romania, Serbia, Slovakia, Slovenia, Russian Federation, Taiwan, and Vietnam under the following brand names: Benalgis, Benfogamma, Benforce, Benfotiamina, Biotamin, Biotowa, Milgamma, and Vilotram.[8] It was also marketed in some jurisdictions as a combination drug with cyanocobalamin as Milgamma, in combination with pyridoxine as Milgamma, in combination with metformin as Benforce-M, and with thiamine as Vitafos.[8] Benfotiamine has been studied in laboratory models of diabetic retinopathy, neuropathy, and nephropathy,[9] As of 2015 there had been one clinical study of benfotiamine in diabetic nephropathy.[10] Administration of benfotiamine may increase intracellular levels of thiamine diphosphate, a cofactor of transketolase,[9] and based on metabolic theories of Alzheimers, it has been studied in preclinical models of Alzheimers disease.[11]