Folate reference interval estimation in the Dutch general population

• Published in: Practical laboratory medicine Vol. 16; p. e00127
• Main Authors: Vos, Michel J., Joost van Pelt, L., Kok, Maarten B., Dijck-Brouwer, D.A. Janneke, Heiner-Fokkema, M. Rebecca, Dikkeschei, Lambert D., Kootstra-Ros, Jenny E.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.08.2019; Elsevier
• Subjects: Folate; Folic acid; Homocysteine; One-carbon metabolism; Reference interval; One-carbon metabolism; Reference interval; Homocysteine; Folate; Folic acid
• ISSN: 2352-5517; 2352-5517
• DOI: 10.1016/j.plabm.2019.e00127

Folate functions as an enzyme co-factor within the one-carbon metabolic pathway, providing key metabolites required for DNA synthesis and methylation. Hence, insufficient intake of folate can negatively affect health. As correct interpretation of folate status is dependent on a well-established reference interval, we set out to perform a new estimation following the restandardization of the Roche folate assay against the international folate standard. The folate reference interval was estimated using samples obtained from the Dutch population-based Lifelines cohort. The reference interval was estimated using two methods: a nonparametric estimation combined with bootstrap resampling and by fitting the data to a gamma distribution. The lower reference limit was verified in a patient cohort by combined measurement of folate and homocysteine. Dependent on the method used for estimation and in- or exclusion of individuals younger than 21 years of age, the lower reference limit ranged from 6.8 to 7.3 nmol/L and the upper reference limit ranged from 26 to 38.5 nmol/L. Applying a lower reference limit of 7.3 nmol/L resulted in the following percentage of folate deficiencies over a period of 12 months: general practitioner 15.5% (IQR 4.0%), general hospital 12.8% (IQR 5.3%), academic hospital 9.6% (IQR 4.3%). We estimated the folate reference interval in the Dutch general population which is not affected by a folic acid fortification program and verified the obtained lower reference limit by homocysteine measurements. Based on our results, we propose a folate reference interval independent of age of 7.3–38.5 nmol/L