Patients taking a drug commonly prescribed for rheumatoid arthritis can lower their risk for drug-related liver damage by taking folate supplements.

The investigators found that patients who took folic acid or folinic acid supplements along with the arthritis drug methotrexate were less likely to have a malfunctioning liver than those taking just methotrexate. As a result, patients taking the folate supplements were able to continue their drug therapy for longer periods.

The folate supplements did not affect the incidence, severity and duration of methotrexate's other side effects, such as nausea, dizziness, diarrhea and fatigue.

Rheumatoid arthritis is an autoimmune disease that most often strikes people in their 30s and 40s, especially women. The illness causes the immune system to attack tissues that line the joints, which can cause pain, inflammation and joint destruction. Methotrexate is a common drug used to treat the condition, but about 30% of patients discontinue treatment early due to toxicity.

To investigate whether folic acid and folinic acid could decrease the drug's toxic side effects, the researchers gave more than 400 patients methotrexate in addition to either 1 milligram (mg) daily of folic acid, 2.5 mg weekly of folinic acid, or an inactive placebo. Doses of methotrexate began at 7.5 mg weekly and increased to a maximum of 25 mg a week.

After 48 weeks, 38% of patients taking the placebo had stopped treatment with methotrexate, compared with 17% of patients taking folic acid and 12% of patients taking folinic acid. Patients taking the placebo had higher levels of liver enzymes than patients taking folate supplements, the report indicates. High levels of liver enzymes indicate toxicity to the liver.

The researchers add that any possible negative effect of folate supplementation on the efficacy of the drug can be overcome by increasing the dosage. Indeed, by the end of the study, patients taking folate needed higher amounts of methotrexate to achieve the same impact on their arthritis as patients taking methotrexate with placebo.

Arthritis & Rheumatism July 2001;44:1515-1524

Dr. Mercola's Comments:

I have treated thousands of rheumatoid arthritis patients with my revision of Dr. Thomas Brown's antibiotic protocol to treat a mycoplasma infection. My major addition to his protocol was development of the eating plan, which will frequently clear up the arthritis, especially if it is early on, without the need for the antibiotics. I have subsequently modified the protocol to incorporate NST which has even further improved our results and ability to relieve RA without the need for the antibiotic protocol. I never put patients on methotrexate but patients will frequently come in on this drug which works by impairing folate synthesis. I was always perplexed on whether or not these patients should be placed on folate as it would appear to reduce the effectiveness of the drug. However this study makes it quite clear that while the folate does appear to partially lower the effectiveness of the drug it more than compensates for the damage it causes on the liver. Take home message: If you or anyone you know is taking methotrexate have them take a folic acid supplement and also be sensitive to the need for possibly increasing the dose of the methotrexate. Related Articles: Rheumatoid Arthritis Patients Not Living Longer Rheumatoid Arthritis Has Been Around for Centuries -- How Best to Treat It If You Have Rheumatoid Arthritis You Need To Consider NST