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

M.E. Duffy, L. Hoey, C.F. Hughes, J.J. Strain, A. Rankin, O.W. Souverein, C. Dullemeijer, R. Collings, L. Hooper, H. McNulty

Research output: Contribution to journalArticleAcademicpeer-review

25 Citations (Scopus)


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 (beta) for individual studies and the overall pooled beta 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 mu g/d. Calculation of the overall pooled beta for studies in the range of 50 to 400 mu g/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 I-2 = 77.2%) and red blood cell (I-2 = 45.9% compared with I-2 = 70.2%) folate. Conclusions: Studies administering >400 mu g 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
JournalAmerican Journal of Clinical Nutrition
Issue number1
Publication statusPublished - 2014


  • plasma homocysteine concentrations
  • neural-tube defects
  • folate status
  • older-adults
  • dose-response
  • blood folate
  • serum folate
  • young-women
  • stroke risk
  • supplementation

Fingerprint 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