Folic Acid Supplementation vs Placebo

Published Date: 19th July 2016

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Abstract

Methotrexate (MTX) is the first-line systemic agent in the treatment of chronic plaque psoriasis (CPP). We undertook a prospective, double-blind, randomized controlled trial in CPP patients treated with MTX to examine the effects of daily folic acid supplementation vs. placebo on MTX efficacy, nausea and serum homocysteine levels. Fifty patients with CPP were randomized to two groups of 25; one group received weekly MTX with 5 mg of folic acid a day and the other group weekly MTX with placebo for a 12-week period.

We had 80% power (as determined by a two-sided t-test at the 5% significance level) to detect differences in both overall Psoriasis Area Severity Index (PASI) change and homocysteine level in the two groups. Eight patients in the folate group and five in the placebo group did not complete the study. MTX dosage was commenced at 5 mg a week and the dose titrated up until clinical improvement was noted. Full blood count, urea and electrolytes, and liver function tests were repeated every 2 weeks for the duration of the study. Homocysteine, folate, vitamin B6 and B12 levels were performed at weeks 0, 2, 4 and 12. PASI was assessed at week 0, 4 and 12. A visual analogue score (VAS) to estimate nausea experienced by patients was done at baseline and then every 2 weeks to week 12. Mean homocysteine levels (normal range < 15 lmol L^-1) at week 0, 2, 4 and 12 were 10.9, 9, 7.5 and 7.3 lmol L^-1 in the folic acid supplementation group vs. 11, 11.8, 11.6 and 11.2 lmol L^-1 in the placebo group; the difference being highly significant, P < 0.0001, by week 12. Mean PASI scores showed no significant difference between the groups at any time point, indicating that folic acid supplementation did not have an effect on MTX efficacy. Determination of VAS at week 0, 2, 4, 6, 8, 10 and 12 showed no statistical difference in the two cohorts, suggesting that folic acid did not reduce MTX related nausea. This study has not shown a significant benefit of supplementary folic acid vs. no folic acid on MTX related efficacy or nausea in a cohort of CPP. However, a powerful effect of folic acid in reducing homocysteine levels was demonstrated. As hyperhomocysteinemia is known to increase the risk of coronary artery disease, any intervention that results in its decrease may be beneficial. Larger studies are required to assess these data further.

Yesudian, PD; Hashim, N; Bharati, A; Alkali, A; Warren, RB; Cox, T; Parslew, RAG. (2013). P88  A prospective, double-blind, randomized controlled trial of folic acid supplementation vs. placebo in patients with chronic plaque psoriasis treated with methotrexate and effects on serum homocysteine . British Journal of Dermatology. 169 (Suppl S1), 59

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