Biomarker responses to folic acid intervention in healthy adults: A meta-analysis of randomized controlled trials

Maresa E. Duffy, Leane Hoey, Catherine F. Hughes, J. J. Strain, Audrey Rankin, Olga W. Souverein, Carla Dullemeijer, Rachel Collings, Lee Hooper, Helene McNulty

Research output: Contribution to journalArticlepeer-review

34 Scopus citations


Background: The task of revising dietary folate recommendations for optimal health is complicated by a lack of data quantifying the biomarker response that reliably reflects a given folate intake. Objective: We conducted a dose-response meta-analysis in healthy adults to quantify the typical response of recognized folate biomarkers to a change in folic acid intake. Design: Electronic and bibliographic searches identified 19 randomized controlled trials that supplemented with folic acid and measured folate biomarkers before and after the intervention in apparently healthy adults aged ≥18 y. For each biomarker response, the regression coefficient (β) for individual studies and the overall pooled β were calculated by using random-effects meta-analysis. Results: Folate biomarkers (serum/plasma and red blood cell folate) increased in response to folic acid in a dose-response manner only up to an intake of 400 μg/d. Calculation of the overall pooled β for studies in the range of 50 to 400 μg/d indicated that a doubling of folic acid intake resulted in an increase in serum/plasma folate by 63% (71% for microbiological assay; 61% for nonmicrobiological assay) and red blood cell folate by 31% (irrespective of whether microbiological or other assay was used). Studies that used the microbiological assay indicated lower heterogeneity compared with studies using nonmicrobiological assays for determining serum/plasma (I 2 = 13.5% compared with I2 = 77.2%) and red blood cell (I2 = 45.9% compared with I2 = 70.2%) folate. Conclusions: Studies administering >400 μg folic acid/d show no dose-response relation and thus will not yield meaningful results for consideration when generating dietary folate recommendations. The calculated folate biomarker response to a given folic acid intake may be more robust with the use of a microbiological assay rather than alternative methods for blood folate measurement.

Original languageEnglish
Pages (from-to)96-106
Number of pages11
JournalAmerican Journal of Clinical Nutrition
Issue number1
StatePublished - 1 Jan 2014
Externally publishedYes


Dive into the research topics of 'Biomarker responses to folic acid intervention in healthy adults: A meta-analysis of randomized controlled trials'. Together they form a unique fingerprint.

Cite this