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Although the actual mechanisms of MTX-induced liver and kidney damage are unknown, one of the hypotheses is the breakdown in cellular antioxidant defences, which increases the production of reactive oxygen species and nitrogen species, inhibits cytosolic NADP-dependent dehydrogenase and NADP malic enzyme, lowers glutathione (GSH), superoxide dismutase (SOD) and catalase levels and reduces the effectiveness of the antioxidant defence system protecting the cell against reactive oxygen species (Reference Savran, Cicek and Doguc7)

The European recommended daily intake also varies by age, beginning at 1.5 g for infants and increasing to 4 g for adults, with slightly higher requirements during pregnancy and lactation (4.5 g and 5 g, respectively