Weekly Folic Acid Supplementation Helps Maintain Folate Levels in IBD Patients


At the 6 month follow-up visit, all participants had stable folic acid levels without macrocytic anemia and the monthly questionnaires showed no increase in symptoms or adverse events reported.

Weekly Folic Acid Supplementation Helps Maintain Folate Levels in IBD Patients

Credit: Polina Tankilevitch

Weekly folic acid supplementation can go a long way toward maintaining normal folate levels in patients with inflammatory bowel disease (IBD).1

A team, led by Tsega Adera Temtem, Department of Pediatrics, Division of Pediatric Gastroenterology, Le Bonheur Children’s Hospital, University of Tennessee Health Science, evaluated the safety and adequacy of once-weekly folic acid supplementation in pediatric patients with IBD who are treated with methotrexate.

Methotrexate and Folic Acid

Methotrexate, a folate analog immunosuppressant, is often used to manage pediatric patients with IBD, along with daily folic acid supplementation in order to prevent folate deficiency and reduce the side effects of methotrexate, including nausea, stomatitis, and hepatotoxicity. The drug mainly targets actively proliferating tissues in IBD by decreasing pro-inflammatory cytokines and inducing lymphocyte apoptosis.

Methotrexate is generally used to treat patients with mild to moderate Crohn’s disease, which are primarily male, or patients with thiopurine ineffectiveness or intolerance.

Folate, the naturally occurring form of folic acid in the reduced form, is a water-soluble B vitamin that is essential for normal cell growth and replication. It is also the main factor in preventing DNA damage and cell injury.

The Study

In the single-arm observational study, the investigators examined 31 patients aged 2-21 years with IBD who were treated witha methotrexate 10-15 mg/m2 dose weekly and 800 mcg of folic acid daily. The patient population included 21 patients with Crohn’s disease, 17 of which had ileal involvement, and 5 patients with ulcerative colitis. Of the 31 patients, 5 withdrew because of poor compliance or transition to adult gastroenterology.

The mean age of the patient population was 15.2 years.

Moreover, 39% (n = 12) patients were treated with methotrexate as a combination therapy with a biologic.

Each participant completed a symptom questionnaire and the investigators measured baseline folate levels, blood counts, and chemistries. The participants were also switched to weekly 800 mcg of folic acid in conjunction with methotrexate and monthly phone calls were conducted with a standardized questionnaire in order to assess compliance and any change in symptoms.


At the 6 month mark, the investigators conducted follow-up blood tests. Finally, normal folate levels was defined as greater than 5.38 ng/mL. No patients withdrew because of symptoms or abnormal folate levels.

Comparing the results, there was no difference in folate levels of patients taking daily versus weekly doses (Mean Difference (MD), 0.81 ng/mL; P = 0.51).

The results show, at the 6 month follow-up visit, all participants had stable folic acid levels without macrocytic anemia. The monthly questionnaires also showed no increase in symptoms with no adverse events reported.

“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,” the authors wrote.


Temtem TA, Vickers M, Whitworth J. Weekly Folic Acid Is a Convenient and Well-Tolerated Alternative to Daily Dosing in Pediatric Patients with Inflammatory Bowel Disease on Methotrexate. Nutrients. 2023; 15(7):1586. https://doi.org/10.3390/nu15071586

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