Fumaric Acid Supports Skin Health

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By Kimberly Pryor

Psoriasis is a common, chronic disease of the skin consisting of papules that merge to form plaques with distinct borders. Silvery, yellow-white scales develop over these plaques as the disease progresses.

For anyone who suffers from psoriasis, that clinical description barely touches on the discomfort and embarrassment associated with this condition that can range from a minor cosmetic problem to a life-threatening emergency. Some psoriasis patients (about 5 percent) also will develop mild arthritis. National Psoriasis Awareness Month, observed in August, focuses attention on this common disease.
Many of the skin changes that occur in psoriasis happen as a result of rapid turnover of the epidermis. In normal skin, 27,000 cells produce approximately 1,250 new cells a day per each square centimeter. In people with psoriasis, however, a whopping 52,000 skin cells produce 35,000 new cells each day per each square centimeter. In normal skin, the cell cycle is usually 311 hours, but in people with psoriasis it is reduced to 36 hours.

The cause of psoriasis isn’t known, but genetics may play a role. Infections, some pharmaceuticals, climate, hormonal factors and smoking may trigger attacks. Stress is a major cause of exacerbations. There is no standard treatment that results in more than temporary relief.

Fumaric Acid

Fumaric acid is one of the organic acids in the Krebs cycle known to metabolize fats, carbohydrates and proteins. In some European countries, fumaric acid has been used for decades in the therapy of psoriasis with a great deal of success. A number of studies—both old and new—confirm its benefits in psoriasis patients. One study of 100 psoriasis patients indicated that fumaric acid derivatives significantly control psoriasis.¹

Another multicenter study of 70 psoriasis patients investigated the efficacy of fumaric acid therapy for four months. Fumaric acid was highly effective, with the patients showing an overall 80 percent decrease in the amount and severity of psoriasis.²

On a smaller scale, British researchers used fumaric acid to treat two patients with severe chronic plaque psoriasis, which had been unresponsive to other therapies. Fumaric acid, however, successfully cleared the psoriasis, even at this advanced stage of the disease.³

New Research

Several recent studies confirm past research on fumaric acid’s ability to support skin health. A study published in the April 2004 British Journal of Dermatology investigated whether fumaric acid could be used as adjunctive therapy with anti-psoriasis drugs.

Researchers analyzed the records of patients who had received fumaric acid for severe psoriasis, either alone or combined with other systemic medications. The study authors then reviewed the efficacy of fumaric acid and assessed whether the patients reduced the dose of other systemic anti-psoriasis drugs while taking fumaric acid.

Of 12 patients treated with fumaric acid, one discontinued the natural treatment, due to flushing. The other 11 patients all experienced an improvement in psoriasis after starting fumaric acid. Nine patients received fumaric acid in combination with other systemic therapies including cyclosporin, acitretin, hydroxyurea and methotrexate. Seven of the patients were able to reduce the dosage of the pharmaceuticals while taking fumaric acid. In two patients, severe psoriasis was controlled using fumaric acid alone.

The researchers concluded, “Fumaric acid appears effective and less toxic than other systemic treatments for psoriasis. Fumaric acid esters were used successfully in combination with other systemic agents and generally enabled the doses of the more hazardous drugs to be reduced.” ⁴

Another earlier study published in January 2004 evaluated the efficacy and safety of fumaric acid esters, in particular dimethylfumarate (DMF), in the treatment of moderate to severe plaque psoriasis intolerant and/or resistant to other conventional systemic therapies. Researchers administered a daily dose of 30 mg up to 360 mg of the fumaric acid ester to 40 patients for six months. In follow-up of the subjects, the scientists evaluated the area of the skin covered by the psoriasis, and the severity of the condition.

A total of 33 (82.5 percent) patients achieved complete clinical remission with the fumaric acid ester treatment: eight after three months and 25 after six months. Four of the subjects who experienced side effects, such as intolerable abdominal cramps and diarrhea, stopped therapy.⁵

According to the study authors, “The findings suggest that [the fumaric acid ester] dimethylfumarate is a safe, effective and well-tolerated long-term oral treatment worthy of consideration for selective patients.”

Because psoriasis is a chronic, long-term disease, a treatment that can safely withstand the test of time is important. Many of the earlier studies of fumaric acid were done with limited follow-up periods. But an August 2003 study in the British Journal of Dermatology investigated the safety of fumaric acid esters using follow-up periods of up to 14 years.

The researchers looked at current or past use of fumaric acid in 66 patients with severe psoriasis. Forty-one of the 66 subjects had received fumaric acid esters for at least 1 year, and 12 of these 41 patients had received fumaric acid esters for between 10 and 14 years.

Side effects—mostly mild—were reported in 73 percent of the patients. These side effects consisted of flushing (55 percent), diarrhea (42 percent), nausea (14 percent), tiredness (14 percent) and stomach complaints (12 percent). Lymphocytopenia (a deficiency of lymphocytes in the blood) was observed in 76 percent of patients during therapy with fumaric acid esters. Liver enzymes were moderately raised in 25 percent of patients.⁶ The researchers concluded, “The present study indicates that fumaric acid esters can be considered as a safe, long-term treatment in patients with severe psoriasis.”

References

1. Altmeyer P.J., Matthes U., Pawlak F., Hoffmann K., Frosch P.J., Ruppert P., Wassilew S.W., et al. Antipsoriatic effect of fumaric acid derivatives. Results of a multicenter double-blind study in 100 patients. J Am Acad Dermatol 1994; 30(6):977-81.

2. Mrowietz U., Christophers E., Altmeyer P. Treatment of psoriasis with fumaric acid esters: results of a prospective multicentre study. German Multicentre Study. Br J Dermatol 1998; 138(3):456-60.

3. Ameen M., Russell-Jones R. Fumaric acid esters: an alternative systemic treatment for psoriasis. Clin Exp Dermatol 1999; 24(5):361-4.

4. Balasubramaniam P., Stevenson O., Berth-Jones J. Fumaric acid esters in severe psoriasis, including experience of use in combination with other systemic modalities. Br J Dermatol 2004 Apr;150(4):741-6.

5. Carboni I., De Felice C., De Simoni I., Soda R., Chimenti S. Fumaric acid esters in the treatment of psoriasis: an Italian experience. J Dermatolog Treat. 2004 Jan;15(1):23-6.

6. Hoefnagel J.J., Thio H.B., Willemze R., Bouwes Bavinck J.N. Long-term safety aspects of systemic therapy with fumaric acid esters in severe psoriasis. Br J Dermatol 2003 Aug;149(2):363-9.

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