Applied nutritional investigationω-3 fatty acids as an adjuvant therapy ameliorates methotrexate-induced hepatotoxicity in children and adolescents with acute lymphoblastic leukemia: A randomized placebo-controlled study

- We determined the role of ω-3 fatty acids in patients with acute lymphoblastic leukemia (ALL) receiving methotrexate (MTX).
- A randomized study divided patients with ALL into two groups and followed them for 6 mo.
- MTX use alone led to significant increases in liver enzymes and oxidative stress.
- MTX and ω-3 maintained oxidant-antioxidant levels.
- The study found that ω-3 has protective effects against MTX-oxidative liver injury in patients with ALL.

ObjectivesMethotrexate (MTX)-induced hepatotoxicity is a significant clinical problem that may affect overall prognosis and disease outcome. Oxidative stress is a key player in its pathogenesis. The aim of this study was to investigate the role of ω-3 fatty acids as an adjuvant therapy in children and adolescents with acute lymphoblastic leukemia (ALL) during the maintenance phase of chemotherapy and the effect of ω-3 on MTX-induced hepatotoxicity.MethodsThis randomized, double-blind, placebo-controlled trial included 70 patients with ALL who were in the maintenance phase. The participants were divided into two groups: group A received oral MTX and ω-3 fatty acids (1000 mg/d) and group B (received MTX and placebo). Both groups were followed-up for 6 mo with assessment of liver enzymes, total antioxidant capacity (TAC), uric acid, malondialdhyde, superoxide dismutase (SOD), and glutathione peroxidase. The trial was registered at ClinicalTrials.gov (NCT02373579).ResultsBaseline clinical and laboratory parameters were consistent between the two groups (P > 0.05). After 6 mo, liver enzymes and malondialdhyde increased, whereas TAC, uric acid, SOD, and glutathione peroxidase decreased in group B (MTX and placebo) compared with baseline levels or with group A ALL patients receiving ω-3 fatty acids (P < 0.001). The addition of ω-3 to MTX maintained normal liver function and oxidant-antioxidant levels among group A patients at the end of treatment compared with pretherapy levels (P > 0.05). No adverse reactions due to ω-3 supplementation were reported. ALT was inversely correlated to TAC and SOD in the MTX group.ConclusionsThe study determined that ω-3 fatty acids ameliorated MTX-induced hepatotoxicity and could be safely used during the maintenance phase of ALL.