A recent study by Liu, Lijun and colleagues revealed that folate supplementation reduce the incidence of side-effects of methotrexate therapy in patients with rheumatoid arthritis.

The systematic review was conducted to evaluate whether folic acid supplementation reduces the MTX toxicity or reduces MTX benefits and decided whether a higher MTX dosage is essential. 

Dr Liu, Lijun et al. performed a sensitive search for abstracts from important rheumatology meetings, and major trial registers were also searched to retrieve all randomized controlled trials and database of Medline, Embase, Web of Science and Cochrane Library databases from inception to 2 June 2016 systematically.

A total of 7 studies were included with 709 patients. It was found that RA patients treated with MTX, supplemented with folic acid were less likely to have elevated transaminase (odds ratio [OR] 0.15; 95% confidence interval [95% CI] 0.10, 0.23 [P < 0.00001]) and gastrointestinal side-effects such as nausea and vomiting (OR 0.71; 95% CI 0.51, 0.99 [P = 0.04]).

The folate supplementation reduced patient withdrawal compared to placebo (OR 0.29; 95% CI 0.21, 0.42 [P < 0.00001]). Whereas, no statistical difference for mouth sores between folate and placebo (OR 0.83; 95% CI 0.57, 1.22 [P = 0.35]) were found. The disease activity markers in included trials were not consistent and so it was not possible to decide if folate supplementation reduced MTX efficacy or not.

The scientists also compared the high-dose of folate (≥25 mg per week) with low-dose folate (≤10 mg per week) on MTX efficacy, but no statistical difference (OR 2.07; 95% CI 0.81, 5.30 [P = 0.13]), on MTX toxicity (OR 1.56; 95% CI 0.80,3.04 [P = 0.19]) was observed.