Possible Interaction: Folic Acid and Methotrexate

“OBJECTIVES This study investigated whether: (i) rheumatoid arthritis (RA) patients have more micronuclei (MN) than healthy controls; (ii) methotrexate (MTX) treated RA patients have more MN than those not using MTX, and (iii) folic acid supplementation decreases the number of MN in MTX treated patients.”

“Supplementation with folic or folinic acid reduced the risk of toxicity-related discontinuation of MTX treatment both in patients with and in patients without the mutation.”

“These results reopen the question of whether folic acid should be used immediately in all patients when MTX is begun.”

“Total clearance of MTX and Vd were higher when patients were also receiving folic acid than when they were taking MTX alone (p < 0.02).”

“ Folic acid supplementation has been reported anecdotally to lessen toxicity in patients receiving methotrexate treatment [27, 28].”

“The influence of the folic acid dose on methotrexate toxicity and efficacy remains controversial, and the effects of different doses of folic acid are not known [37, 38].”

“Interestingly, the induction of different sulfotransferases by MTX was inhibited by high doses of folic acid at both protein and mRNA levels in Hep G2 cells.”

“Inhibition studies of human rNAT1 and hamster rNAT2 revealed that folic acid and methotrexate ( MTX ) are competitive inhibitors of both the unacetylated and acetylated forms of the enzymes, with KI values in 50–300 μ range.”

“ MTX , an antagonist of folic acid synthesis, causes apoptosis in activated cells, primarily in the G1 and S phases of the cell cycle.”

“Among the potential safety issues are interaction between folic acid and zinc, interaction between folic acid and drugs (phenytoin, methotrexate etc.)”

“This was true for all methotrexate concentrations examined from 10 μM to 3 mM. The presence of folic acid at concentrations above 0.1 mM and of acidic conditions decreased the uptake of methotrexate into single cells and enhanced tissue penetration.”

“In addition, RA patients with the MTHFR C677T polymorphism who were supplemented with folic acid displayed significantly elevated risk for MTX toxicity.”