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

• Published in: Nutrition (Burbank, Los Angeles County, Calif.) Vol. 32; no. 1; pp. 41 - 47
• Main Authors: Elbarbary, Nancy Samir, M.D, Ismail, Eman Abdel Rahman, M.D, Farahat, Reham Kamel, M.Sc, El-Hamamsy, Manal, Ph.D
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.01.2016
• Subjects: Acute lymphoblastic leukemia; Adolescent; Antioxidants - metabolism; Antioxidants - pharmacology; Antioxidants - therapeutic use; Chemical and Drug Induced Liver Injury - metabolism; Child; Child, Preschool; Double-Blind Method; Fatty Acids, Omega-3 - pharmacology; Fatty Acids, Omega-3 - therapeutic use; Female; Gastroenterology and Hepatology; Glutathione Peroxidase - metabolism; Hepatotoxicity; Humans; Liver - drug effects; Liver - metabolism; Male; Malondialdehyde - metabolism; Methotrexate; Methotrexate - adverse effects; Methotrexate - therapeutic use; Oxidative stress; Oxidative Stress - drug effects; Precursor Cell Lymphoblastic Leukemia-Lymphoma - drug therapy; Superoxide Dismutase - metabolism; ω-3 fatty acids; Oxidative stress; ω-3 fatty acids; Acute lymphoblastic leukemia; Methotrexate; Hepatotoxicity
• ISSN: 0899-9007; 1873-1244
• DOI: 10.1016/j.nut.2015.06.010

Abstract Objectives Methotrexate (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. Methods This 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 ). Results Baseline 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. Conclusions The study determined that ω-3 fatty acids ameliorated MTX-induced hepatotoxicity and could be safely used during the maintenance phase of ALL.