Methotrexate, or MTX, is a pharmaceutical drug used as a therapy for rheumatoid arthritis, RA. Both folic acid and folinic acid supplements have been shown to diminish the toxicity of MTX when used in RA treatment. The effectiveness of folate supplementation on MTX toxicity still needs to be studied, but addition of folic acid to the diet has been found to have a beneficial effect and may thwart the formation of metabolites of MTX that lead to toxicity. However, consult a rheumatologist before supplementing with folic acid in the treatment of RA.
Rheumatoid Arthritis
Rheumatoid arthritis is an unceasing inflammatory disorder that affects many tissues and organs, but primarily attacks synovial joints. The disease often leads to the destruction of cartilage and can also produce diffuse inflammation in the pericardium, the tissue surrounding the heart, as well as the pleura, the tissue surrounding the lungs. The cause of rheumatoid arthritis is unknown, but autoimmunity has been shown to have a crucial role in its progression.
Folic with Folinic Acid Supplementation
An article appearing in the July 2001 issue of "Arthritis and Rheumatism" studied the effect of folates to determine which adverse reactions are reduced to investigate the effects on the effectiveness of MTX and to contrast folic with folinic acid supplementation in a 48-week, placebo-controlled trial. The researchers assigned patients with active RA to receive MTX plus either a placebo, folic acid at 1mg per day, or folinic acid at 2.5mg per week. The initial MTX dosage was 7.5mg per week, and dosage increases were allowed up to a maximum of 25mg per week. The study found that toxicity of MTX, shown by decreased concentrations of elevated liver enzymes, occurred in 38 percent of the placebo group, 17 percent of the folic acid group, and 12 percent of the folinic acid group. The study concluded that both folate supplements decreased the occurrence of elevated liver enzyme levels during MTX therapy, and as a consequence, MTX had to be discontinued less often in these patients.
Fortification of Food
Since the addition of folic acid to food to reduce the frequency of neural tube defects was initiated, several other countries have considered whether to adopt the same policy. A commentary in the March 2008 issue of the "American Journal of clinical Nutrition" stated that when fortification is introduced in food stuffs, millions of people are exposed to an increased intake of folic acid for each neural tube defect that is prevented and asked whether the benefits to the few outweigh the potential harm to some of the many exposed. The authors pointed out that in animals, a folic acid-rich diet can influence DNA, which leads to changes in following generations and in humans, increased folic acid intake leads to elevated blood concentrations of normally occurring folates and of unmetabolized folic acid. They further stated that elevated concentrations of folic acid may be related to decreased activity of immune and increased folate may reduce the response to anti-folate drugs used against malaria, rheumatoid arthritis, psoriasis and cancer. The article concluded that a high folic acid intake may be unsafe for some people and other nations considering fortification should be cautious and develop correct strategies for the populace as a whole.
Supplementation and the Use of MTX
A letter to the editor appearing in the August 2008 issue of the "American Journal of Clinical Nutrition" commented on folic acid fortification and supplementation and the use of MTX in the treatment of autoimmune diseases including rheumatoid arthritis RA. The authors stated that folic acid supplements are routinely used to reduce the toxicity of low-dose MTX so that patients may experience the effects of this drug without its toxicity because a key reason for stopping low-dose MTX therapy is drug toxicity, not a lack of effectiveness. The authors confirmed that using MTX can develop conditions such as stomatitis, elevated concentrations of liver function enzymes, and cytopenias, even though arthritic conditions are greatly reduced. The article concluded that rheumatologists have become more confident in the use of MTX, especially because its related toxicity is manageable with folic acid supplements. Therefore, it can be used at higher doses to achieve potentially better responses.
References
- American Journal of Clinical Nutrition: Is Folic Acid Good for Everyone?
- American Journal of Clinical Nutrition: Folic Acid Supplements Are Good (Not Bad) for Rheumatoid Arthritis Patients Treated with Low-dose Methotrexate
- Arthritis and Rheumatism: Effect of Folic or Folinic Acid Supplementation on the Toxicity and Efficacy of Methotrexate in Rheumatoid Arthritis: A Forty-eight Week, Multicenter, Randomized, Double-blind, Placebo-controlled Study
- Clinical and Experimental Rheumatology: Folate Supplementation During Methotrexate Therapy for Rheumatoid Arthritis
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