Methotrexate and folic acid
Methotrexate is an active substance that acts as an antagonist of folic acid in the body (a so-called folic acid antagonist). Folic acid or vitamin B9 is important for cell division, in particular it plays a role in the production of building blocks of the genetic material (DNA). So if the effect of folic acid is inhibited, the cell can no longer multiply.
Cancer cells or cells of the body’s own defense system that are too active and thus trigger a chronic inflammatory rheumatic disease can be prevented from growing and multiplying by the effect of methotrexate. Since methotrexate is an antagonist of folic acid, the administration of folic acid can conversely cancel out the effect of methotrexate and act as an antidote in cases of poisoning. However, undesirable side effects of Methotrexate can also be reduced or avoided altogether by the sensible administration of folic acid, such as nausea, inflammation of the oral mucosa, liver enzyme elevation, hair loss and diarrhea.
The German Society for Rheumatology recommends folic acid supplementation (additional administration of folic acid in addition to the diet) with at least 5 milligrams of folic acid per week. For comparison: the daily dose of folic acid recommended by the German Society for Nutrition is 400 micrograms. However, folic acid should be taken no earlier than 24-48 hours after ingestion or injection of methotrexate.
The largest amount of methotrexate is excreted on the first day after taking or injecting the injection. A smaller amount of methotrexate is first converted in the body into a metabolic product similar to methotrexate and is not excreted until the second day after taking methotrexate. A folic acid supplementation is therefore recommended after 48 hours, since after this time no significant amounts of methotrexate or its metabolic product are left in the body and thus the effect of methotrexate is not significantly weakened.
Nevertheless, a good protection against possible undesirable side effects is achieved.The dosage of folic acid supplementation should be adjusted during the course of therapy if necessary. Dosages of up to 15 milligrams daily, 5 days a week, starting 48 hours after administration of methotrexate are conceivable. This increase in the dose of folic acid should be considered, for example, if undesirable effects occur, especially if liver values increase.
Alternatively, the use of folic acid at a dosage of 2.5 milligrams per week is also possible; there do not seem to be any relevant differences between folic acid or folinic acid supplementation. The intake of folic acid during treatment with methotrexate has been controversially discussed in the past. There are fears that folic acid could weaken or even cancel the effect of methotrexate against rheumatic diseases.
If folic acid is added to a methotrexate therapy, the rate of possible side effects can be reduced. If folic acid is added too early or too much, the effectiveness of Methotrexate may be reduced. However, the mechanism of action of methotrexate in rheumatic diseases is still largely unexplained, so that this connection does not necessarily exist.
Nevertheless, many rheumatologists in Germany and Europe refrain from the general administration of folic acid. In this country, methotrexate therapy is predominantly carried out initially without folic acid supplementation. The additional administration of folic acid is only carried out if methotrexate is not well tolerated or if the blood count shows indications of a folic acid deficiency (macrocytosis = too large blood cells and hyperchromasia = too high a load of the red blood cells with the blood pigment haemoglobin).
A folic acid deficiency also manifests itself through inflammation of the mucous membranes, especially the oral mucosa. If such symptoms occur, methotrexate therapy is briefly interrupted and folic acid is given in high doses until the inflammation of the mucous membranes has subsided. Continued treatment with Methotrexate is followed by additional folic acid supplementation.
