Possible Interaction: Homocysteine and Methotrexate

“In the univariate linear regression, the global toxicity score was associated with a significant rise in plasma HCY concentrations within 48 h after MTX administration (β = 0.4; R2 = 0.12; p = 0.02).”

“OBJECTIVE Interference of methotrexate (MTX) with the metabolism of homocysteine may contribute to MTX neurotoxicity.”

“In a multiple regression model there was an association between the alteration in Hcy level over 0–12 months and MTX treatment, as well as the alteration in CRP, adjusted for B‐vitamin treatment.”

“In cell culture studies, MTX inhibits Hcy remethylation, leading to increased Hcy export to the medium (6)(7)(8) .”

“Recently, it has been postulated that homocysteine may be a marker of the 'pharmacodynamic effect' of methotrexate , but studies attesting to this role are only now emerging.”

“Although its efficacy is widely attributed to a decrease in nucleotide biosynthesis (1), methotrexate is known to increase homocysteine (2), a compound associated with an elevated risk of heart disease, Alzheimer's disease (3), and neural tube defects (4).”

“Specific clinical conditions like the use of antiepileptic drugs or methotrexate , renal failure, cancer, rheumatoid arthritis, and hypothyroidism may lead to elevated tHcy concentrations.”

“We should keep in mind, for example, that exposure to any folate or vitamin B6 antagonist, such as methotrexate , phenytoin, estrogens, tobacco, or theophylline, could significantly raise blood concentrations of homocysteine thus strongly increasing the risk of arterial and venous thrombotic events.”

“Plasma homocysteine level did significantly increase in AS patients under sulfasalazine or MTX treatment.”

“ Homocysteine concentrations increased after MTX administration by a median of 2.5 mumol/l (range 0.7-5.1).”