Fumaric Acid

Fumaric Acid

Linear Formula



boletic acid, lichenic acid, donitic acid, trans butenedioic acid, butenedioic acid, trans-1,2-ethylenedicarboxylic acid

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Fumaric acid, or trans butenedioic acid, is one of many organic acids. Fumaric acid is a weak acid that appears as a crystalline powder and is slightly soluble in ethyl ether and acetone. It is one of nine carboxylic acids that take part in the tricarboxylic acid cycle (TCA cycle), a metabolic process that produces energy. In the TCA cycle, the enzyme fumarase converts fumaric acid into malic acid (or maleic acid).

Fumaric acid is used as a food additive and food acidulant, acting as a potent flavoring agent for gelatin desserts, baking powders, and fruit juices. The organic acid also has industrial applications: it is present in coating additives, stain remover, paint additives, printing inks, drying oils, and contact lenses.

The industrial chemistry behind fumaric acid production

Fumaric acid is typically produced from maleic acid and maleic anhydride through isomerization1. However, the process drives substantial carbon emissions. For this reason, scientists have sought more sustainable methods to produce fumaric acid. In turn, researchers have proposed fermentation as an alternative approach2. Many fumaric acid-producing microbes, namely Rhizopus species, exist and can provide similar titers of fumaric acid as conventional production lines3.

Fumaric acid and chemical safety

Despite their health benefits and industrial applications, fumaric acid is a hazardous chemical. The European Commission and the National Institute of Standards and Technology note that the compound can cause severe eye irritation. Upon such exposure, a person must remove contact lenses before washing to prevent serious eye irritation.

Fumaric acid esters and drug development

Fumaric acid is commonly used in cosmetic products. Fumaric acid derivatives such as fumaric acid esters (FAEs) are small molecules that can modulate the immune system and exert anti-oxidative effects4. Multiple clinical trials over the past decades demonstrate FAE’s efficacy in treating psoriasis by reducing pro-inflammatory responses5. This data culminated in a 2015 systematic review which determined that FAEs provide psoriasis relief after 12-16 weeks of treatment6.

FAEs may also reduce the risk of relapsing remitting multiple sclerosis. Phase 3 clinical trial data of dimethyl fumarate, an oral FAE, shows that FAEs can reduce relapse rates7. While scientists do not fully understand its mechanism of action, they do know that FAEs act as a prodrug of monomethylfumarate, the active compound that acts as a receptor agonist8.

Fumaric acid is also used as an ingredient in Ensitrelvir, a formulation for treating mild-to-moderate COVID-19 and asymptomatic SARS-CoV-2 infections9,10. Ensitrelvir fumaric acid has demonstrated favorable clinical outcomes and has a long half-life. Notably, COVID-19 patients taking Ensitrelvir fumaric acid tested negative for SARS-CoV-2 sooner than patients who took a placebo.

Fumaric acid in research

As of July 2023, there are 241 citations for “fumaric acid” in research publications (*excluding books and documents) on PubMed. Because many publications explore the use of fumaric acid in treating psoriasis, any basic or preclinical research program focusing on skin health and disease may benefit from metabolomics analyses to characterize the mechanism of action and inform dosing strategies for existing and novel fumaric acid-based treatments. Because fumaric acid is also a commonly used treatment in multiple sclerosis, studies seeking to understand the molecular mechanisms of the disease and patient response to treatment may consider quantifying fumaric acid and related metabolites.


  1. Felthouse TR, Burnett JC, Horrell B, Mummey MJ, Kuo YJ. Maleic Anhydride, Maleic Acid, and Fumaric Acid. In: Kirk-Othmer Encyclopedia of Chemical Technology. John Wiley & Sons, Ltd; 2001. doi:10.1002/0471238961.1301120506051220.a01.pub2
  2. Roa Engel CA, Straathof AJJ, Zijlmans TW, van Gulik WM, van der Wielen LAM. Fumaric acid production by fermentation. Appl Microbiol Biotechnol. 2008;78(3):379-389. doi:10.1007/s00253-007-1341-x
  3. Roa Engel CA, van Gulik WM, Marang L, van der Wielen LAM, Straathof AJJ. Development of a low pH fermentation strategy for fumaric acid production by Rhizopus oryzae. Enzyme and Microbial Technology. 2011;48(1):39-47. doi:10.1016/j.enzmictec.2010.09.001
  4. Gold R, Linker RA, Stangel M. Fumaric acid and its esters: an emerging treatment for multiple sclerosis with antioxidative mechanism of action. Clin Immunol. 2012;142(1):44-48. doi:10.1016/j.clim.2011.02.017
  5. Mrowietz U, Asadullah K. Dimethylfumarate for psoriasis: more than a dietary curiosity. Trends in molecular medicine. 2005;11(1):43-48.
  6. Balak DM. Fumaric acid esters in the management of psoriasis. Psoriasis (Auckl). 2015;5:9-23. doi:10.2147/PTT.S51490
  7. Gold R, Kappos L, Arnold DL, et al. Placebo-Controlled Phase 3 Study of Oral BG-12 for Relapsing Multiple Sclerosis. New England Journal of Medicine. 2012;367(12):1098-1107. doi:10.1056/NEJMoa1114287
  8. Mrowietz U, Morrison PJ, Suhrkamp I, Kumanova M, Clement B. The Pharmacokinetics of Fumaric Acid Esters Reveal Their In Vivo Effects. Trends in Pharmacological Sciences. 2018;39(1):1-12. doi:10.1016/j.tips.2017.11.002
  9. Mukae H, Yotsuyanagi H, Ohmagari N, et al. A Randomized Phase 2/3 Study of Ensitrelvir, a Novel Oral SARS-CoV-2 3C-Like Protease Inhibitor, in Japanese Patients with Mild-to-Moderate COVID-19 or Asymptomatic SARS-CoV-2 Infection: Results of the Phase 2a Part. Antimicrob Agents Chemother. 2022;66(10):e0069722. doi:10.1128/aac.00697-22
  10. Shimizu R, Sonoyama T, Fukuhara T, Kuwata A, Matsuo Y, Kubota R. Safety, Tolerability, and Pharmacokinetics of the Novel Antiviral Agent Ensitrelvir Fumaric Acid, a SARS-CoV-2 3CL Protease Inhibitor, in Healthy Adults. Antimicrob Agents Chemother. 66(10):e00632-22. doi:10.1128/aac.00632-22