Folate reference interval estimation in the Dutch general population

Vos, M. J., van Pelt, L. J., Kok, M. B., Dijck-Brouwer, D. A. J., Heiner-Fokkema, M. R., Dikkeschei, L. D. & Kootstra-Ros, J. E., Aug-2019, In : Practical Laboratory Medicine. 16, 6 p., 00127.

Research output: Contribution to journalArticleAcademicpeer-review

Background: 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.

Materials and methods: 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.

Results: 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%).

Conclusions: 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

Original languageEnglish
Article number00127
Number of pages6
JournalPractical Laboratory Medicine
Publication statusPublished - Aug-2019


  • Folate, Folic acid, One-carbon metabolism, Homocysteine, Reference interval, HOMOCYSTEINE, PLASMA, VALUES

ID: 112036760