Fumaric Acid: Function & Diseases

The remedy fumaric acid has been known since ancient Greece. The active ingredient occurs naturally and can also be produced synthetically. It is mainly used in industry and also in medicine. There, fumaric acid is used to treat psoriasis and a certain form of multiple sclerosis. It inhibits specific immune cells.

What is fumaric acid?

Fumaric acid is an organic and at the same time chemical substance that belongs to the class of fruit acids and is also called trans-ethylenedicarboxylic acid. The salts of fumaric acid are called fumarates. The acid is found in plants, fungi and lichens. It can also be produced in the laboratory. As food additive E 297, it is used to preserve food. The industry produces the plastic polyester from it. In animal husbandry, it is used as a food additive to prevent infections. The salts of fumaric acid fumaric acid ester, fumaric acid monoethyl ester and fumaric acid dimethyl ester are used to treat patients with skin diseases and multiple sclerosis. They are applied topically as ointments or administered orally in the form of capsules and tablets and as injections. 60% of the active ingredient is later excreted via respiration, the rest via urine. Side effects, which are rather rare, can be reduced by having the patient take the medication with meals.

Function, effects, and roles

Fumaric acid primarily has an immunosuppressive effect. This creates a balance between different groups of immune cells. For example, fumaric acid drugs affect B and T lymphocytes as well as Th1 cells by inhibiting the action of Th1 cells with the help of Th2 cells. This is necessary because patients with psoriasis have an excess of Th1 cells. All three fumarates are used in the long-term treatment of psoriasis and, since 2014, also in relapsing remitting multiple sclerosis. Psoriasis is a chronic, non-contagious skin disease. Fumarate ointments, capsules and tablets curb the inflammation that leads to the formation of the scaly skin rashes. Fumaderm therapy is successful in about 90 percent of patients. As early as the 1970s, physicians were treating their psoriasis patients with fumaric acid preparations. Dimethyl fumarate (DMF) was also approved for the treatment of relapsing remitting multiple sclerosis following a positive decision by the European Medicines Agency (EMA) in 2013. The drug is administered as capsules and tablets and replaces the previously used beta interferon injection, which many patients found burdensome. In this particular form of multiple sclerosis, which is based on a disruption of Th1 cells, it inhibits inflammation of the nerve fibers of the brain and spinal cord by releasing the cell protection factor Nrf2. Because it simultaneously interferes with cytokine production – blocking HCA2 receptors – it reduces the frequency of relapses by up to 50%. This delays the progression of the disease. In the treatment of psoriasis, the fumaric acid drugs are administered in lower doses than in the specific form of multiple sclerosis.

Formation, occurrence, properties, and optimal values

Fumaric acid forms colorless, almost odorless, flammable crystals at room temperature and sublimes at approximately 299 °C. The fruit acid is highly irritant and dissolves poorly in water. It has been known since ancient times, where it was used in folk medicine, especially for the treatment of skin diseases. Fumaric acid occurs naturally in some lichens, plants and fungi and was named after the common fumitory (Fumaria officinalis), a red-flowering weed. In 1832, it was isolated from the plant for the first time. Naturopathy also calls the plant “ground fumitory” because it was applied in the form of tea poultices to areas of the body affected by skin rashes. The common fumitory contains a lot of fumaric acid. To produce fumaric acid in the laboratory, maleic acid is heated to at least 150 degrees, irradiated with UV light, or dissolved in water. In non-plant organisms, fumaric acid is produced by the hydrolytic breakdown of the amino acids tyrosine and phenylalanine, among others.

Diseases and disorders

Side effects sometimes occur with the use of fumaric acid preparations, especially at the beginning of treatment.Most frequently observed side effects (more than one in 10 patients) are gastrointestinal problems such as diarrhea, bloating, flatulence, nausea, and abdominal pain, as well as a feeling of excessive heat. These disorders continue to occur occasionally later. In rarer cases, skin allergies associated with itching, flushing (redness of the skin), elevated liver enzymes, drowsiness, fatigue, headache, reduced lymphocyte count in the blood, and increased protein excretion through the urine have been noted. If increased protein is excreted, this indicates the presence of kidney disease and should be investigated more closely immediately. Treatment with fumaric acid can also occasionally lead to the occurrence of progressive multifocal leukoencephalopathy (a brain disease), Kaposi’s sarcoma and lymphopenia. Medical experts assume that the immunosuppressive effect of fumarates is causative for these diseases. Patients with acute severe infection, severe kidney problems, ventricular ulcer, duodenal ulcer, severe liver disease and hypersensitivity to the active ingredient should not consume fumaric acid preparations. This also applies to pregnant women, nursing mothers, and children and adolescents under 18 years of age, as there is as yet no firm evidence on their effects in these patient groups. In addition, fumaric acid medications should not be taken if the patient is also receiving preparations with similar side effects (ciclosporin, retinoids, etc.), as fumaric acid may impair renal function.