The effects of low-dose weekly folate supplementation versus high-dose daily folate

Year 2015, Volume: 15 Issue: 4, - , 19.03.2015

Aslı Gencay Can , Zafer Günendi Gönen Mengi Özlem Aslan Feride Göğüş

https://doi.org/10.17098/amj.63037

Abstract

Objectives: There is no consensus on the dosage of folic acid required for the prevention of methotrexate (MTX) toxicity in rheumatoid arthritis (RA). The aim of the study was to assess the effects of low-dose weekly folate versus high-dose daily folate on prevention of MTX toxicity in RA patients.

Materials and Methods: Randomized controlled study of rheumatoid arthritis patients who were treated at Department of Rheumatology in Gazi University between October 2009 and February 2010. Thirty-eight RA patients were received 10 mg/week MTX and 5-10 mg/day prednisolon were randomly allocated to receive 5 mg/week folate or 2.5 mg six days/week folate. All patients were evaluated for complete blood cell count, liver function tests, alopecia, stomatitis and gastrointestinal symptoms before and six months after the treatment.

Results: There were no significant differences in the development of stomatitis, alopecia, gastrointestinal symptoms, anemia, leukopenia, erythropenia, thrombocytopenia, elevated liver function tests between the groups at sixth month.

Conclusion: Our results support that 5 mg folate supplementation once a week is adequate in RA patients.

Keywords

Methotrexate; rheumatoid arthritis; folate supplementation

Romatoid Artritli Hastalarda Metotreksat Toksisitesini Önlemede Yüksek Doz Günlük Folat Desteğine Karşın Düşük Doz Haftalık Folat Desteğinin Etkileri

Abstract

Amaç: Romatoid artritte metotreksat toksisitesinin önlenmesinde gerekli folik asit  dozu ile ilgili ortak bir görüş yoktur. Bu çalışmanın amacı romatoid artritli hastalarda metotreksat toksisitesinin önlenmesinde yüksek doz günlük folat  kullanımına karşın düşük doz haftalık folat kullanımının etkilerini değerlendirmekti.            

Materyal ve Metot: Ekim 2009 ile Şubat 2010 tarihleri arasında Gazi Üniversitesi Romatoloji Bölümü'nde tedavi edilen romatoid artritli  hastalarda yapılan randomize kontrollü bir çalışma. 10 mg/hafta ve 5-10 mg/gün prednisolon kullanan 34 romatoid artritli hastaya randomize şekilde 5mg/hafta folat veya 2.5 mg 6 gün/hafta folat verildi. Hastaların tam kan sayımları, karaciğer fonksiyon testleri, alopesi, stomatit ve gastrointestinal semptomları tedaviden önce ve tedaviden 6 ay sonra değerlendirildi.

Bulgular: Tedavinin 6. ayında stomatit, alopesi, gastrointestinal semptomlar, anemi, lökopeni, eritropeni, trombositopeni, eleve karaciğer fonksiyon testleri açısından gruplar arasında fark yoktu.

Sonuç: Sonuçlarımız haftalık 5 mg folat desteğinin romatoid artritli hastalarda yeterli olduğunu desteklemektedir.

Keywords

Metotreksat, romatoid artrit, folat desteği

References

• Whittle SL, Hughes RA. Folate supplementation and methotrexate treatment in rheumatoid arthritis: a review. Rheumatology 2004;43:267-71.
• Cario H, Smith DEC, Blom H et al. Dihydrofolate reductase deficiency due to a homozygous DHFR mutation causes megaloblastic anemia and cerebral folate deficiency leading to severe neurologic disease. Am J Hum Genet 2011;88:226-31.
• Arabelovic S, Sam G, Dallal GE et al. Preliminary evidence shows that folic acid fortification of the food supply is associated with higher methotrexate dosing in patients with rheumatoid arthritis. J Am Coll Nutr 2007;26:453-5.
• Ortiz Z, Shea B, Suarez-Almazor ME, Moher D, Wells GA, Tugwell P. The efficacy of folic acid and folinic acid in reducing methotrexate gastrointestinal toxicity in rheumatoid arthritis: a metaanalysis of randomized controlled trials. J Rheumatol 1998;25:36-43.
• van Ede AE, Laan RFJM, Blom HJ, De Abreu RAD, van de Putte LBA. Methotrexate in rheumatoid arthritis: an update with focus on mechanisms involved in toxicity. Semin Arthritis Rheum 1998;27:277-92.
• van Ede AE, Laan RFJM, Rood MJ et al. Effect of folic or folinic acid supplementation on the toxicity and efficacy of methotrexate in rheumatoid arthritis: A forty-eight–week, multicenter, randomized, double-blind, placebo - controlled study. Arthritis Rheum 2001;44: 1515-24.
• Morgan SL, Baggott JE, Vaughn WH et al. Supplementation with folic acid during methotrexate therapy for rheumatoid arthritis. A double-blind, placebo-controlled trial. Ann Intern Med 1994;121:833-41.
• Prey S, Paul C. Effect of folic or folinic acid supplementation on methotrexate-associated safety and efficacy in inflammatory disease: a systematic review. British J Dermatol 2009; 160:622-8.
• Ortiz Z, Shea B, Suarez-Almazor ME, Moher D, Wells GA, Tugwell P. Folic acid and folinic acid for reducing side effects in patients receiving methotrexate for rheumatoid arthritis (Review). Cochrane Database Syst Rev 2000;2:CD000951.
• Griffith SM, Fisher J, Clarke S et al. Do patients with rheumatoid arthritis established on methotrexate and folic acid 5 mg daily need to continue folic acid supplements long term? Rheumatology 2000;39:1102-9.
• Khanna D, Park GS, Paulus HE et al. Reduction of the efficacy of methotrexate by the use of folic acid: Post hoc analysis from two randomized controlled studies. Arthritis Rheum 2005;52:3030-8.
• Weinblatt ME, Fraser P. Elevated mean corpuscular volume as a predictor of haematologic toxicity due to methotrexate therapy. Arthritis Rheum 1989;32:1592-6.
• van Ede AE, Laan RF, Blom HJ et al. Homocysteine and folate status in methotrexate treated patients with rheumatoid arthritis. Rheumatology 2002;41:658-65.
• Tiftikci A, Ozdemir A, Tarcin O et al. Influence of serum folic acid levels on plasma homocysteine concentrations in patients with rheumatoid arthritis. Rheumatol Int 2006;26: 191-4.
• Morgan SL, Baggot JE, Lee JY, Alarcon GS. Folic acid supplementation prevents deficient blood folate levels and hyperhomocysteinemia during long-term, low dose methotrexate therapy for rheumatoid arthritis: implications for cardiovascular disease prevention. J Rheumatol 1998;25:441-6.