nephrotoxic after long-term use. Medicine Fumaric acid was developed as a medicine to treat the autoimmune condition psoriasis in the 1950s in Germany as a tablet containing 3 esters, primarily dimethyl fumarate, and marketed as Fumaderm by Biogen Idec in Europe. Biogen would later go on to develop the main ester, dimethyl fumarate, as a treatment for multiple sclerosis. In patients with relapsing-remitting multiple sclerosis, the ester dimethyl fumarate (BG-12, Biogen) significantly reduced relapse and disability progression in a phase 3 trial. It activates the Nrf2 antioxidant response pathway, the primary cellular defense against the cytotoxic effects of oxidative stress. Other uses Fumaric acid is used in the manufacture of polyester resins and polyhydric alcohols and as a mordant for dyes. When fumaric acid is added to their feed, lambs produce up to 70% less methane during digestion. Safety It is "practically non-toxic" but high doses are probably nephrotoxic after long-term use. Synthesis and reactions Fumaric acid was first prepared from succinic acid. A traditional synthesis involves oxidation of furfural (from the processing of maize) using chlorate in the presence of a vanadium-based catalyst. Currently, industrial synthesis of fumaric acid is mostly based on catalytic isomerisation of maleic acid in aqueous solutions at low pH. Maleic acid is accessible in large volumes as a hydrolysis product of maleic anhydride, produced by catalytic oxidation of benzene or butane. The chemical properties of fumaric acid can be anticipated from its component functional groups. This weak acid forms a diester, it undergoes additions across the double bond, and it is an excellent dienophile. Fumaric acid does not combust in a bomb calorimeter under conditions where maleic acid deflagrates smoothly. For teaching experiments designed to measure the difference in energy between the cis- and trans- isomers, a measured quantity of carbon can be ground with the subject compound and the enthalpy of combustion computed by difference. See also Citric acid cycle (TCA cycle) Photosynthesis Maleic acid, the cis isomer of fumaric acid References External links International Chemical Safety Card 1173 Dicarboxylic acids Food additives Food acidity regulators Urea cycle Citric acid cycle compounds Nephrotoxins E-number additives Alkene derivatives