Weekly Folic Acid Is a Convenient and Well-Tolerated Alternative to Daily Dosing in Pediatric Patients with Inflammatory Bowel Disease on Methotrexate

Nutrients. 2023 Mar 24;15(7):1586. doi: 10.3390/nu15071586.


Tsega Adera Temtem 1 2Maggie Vickers 1John Whitworth 1


Author information

1Department of Pediatrics, Division of Pediatric Gastroenterology, Le Bonheur Children's Hospital, University of Tennessee Health Science Center, 50 North Dunlap, Memphis, TN 38103, USA.

2Department of Pediatrics, Division of Pediatric Gastroenterology, University of Louisville, Louisville, KY 40202, USA.


Background: Inflammatory bowel disease (IBD) is a chronic autoimmune disorder that affects the gastrointestinal tract. Methotrexate is a folate analog immunosuppressant used in the management of pediatric IBD. Daily folic acid supplementation is currently recommended to prevent folate deficiency and reduce the side effects of methotrexate such as nausea, stomatitis, and hepatotoxicity. The aim of this study was to evaluate the safety and adequacy of once-weekly folic acid supplementation in pediatric inflammatory bowel disease patients taking methotrexate.

Methods: In this single-arm observational study, we included subjects aged 2-21 years old with inflammatory bowel disease who were receiving a standard oral methotrexate dose of 10-15 mg/m2weekly and 800 mcg of folic acid daily. Baseline folate level, blood counts and chemistries, and a symptom questionnaire were completed. Subjects were switched to weekly 800 mcg of folic acid to be taken in conjunction with methotrexate. Monthly phone calls with a standardized questionnaire were used to assess compliance and any change in symptoms. Follow-up blood tests were obtained 6 months after enrollment. Normal folate level was defined as >5.38 ng/mL.

Results: Thirty-one subjects were enrolled. Five subjects were withdrawn due to poor compliance or transition to adult gastroenterology. Twenty-one (81%) subjects had Crohn's disease (17 with ileal involvement) and five (19%) had ulcerative colitis. Twelve (39%) subjects were on methotrexate as a combination therapy with a biologic agent. At the 6-month follow-up visit, all subjects had stable folic acid levels (>5.38 μg/L) without macrocytic anemia. Monthly questionnaires found no increased symptoms, and there were no adverse events.

Conclusions: Once weekly folic acid supplementation at a dose commonly found in a multivitamin may be sufficient to maintain normal folate levels without the development of adverse symptoms in pediatric patients with inflammatory bowel disease on methotrexate therapy.



© Copyright 2013-2024 GI Health Foundation. All rights reserved.
This site is maintained as an educational resource for US healthcare providers only. Use of this website is governed by the GIHF terms of use and privacy statement.