Effect of Folic Acid on Primary Folate Forms in Relation to MTHFR


The common polymorphism in MTHFR gene (C677T) has a significant effect on (6S)-5-CH3-H4folate after folic acid supplementation. For example, post supplementation differences in (6S)-5-CH3-H4folate between CC and TT are above 30%.

Full Title of Study: “Effect of Mild Increase in Folic Acid Intake on the Distribution of Folate Forms in Relation to a Common Polymorphism in One Folate Catabolising Enzyme”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Basic Science
    • Masking: Double (Participant, Outcomes Assessor)
  • Study Primary Completion Date: December 2012

Detailed Description

The investigators aim to test the effect of low doses of folic acid with or without B6 and B12 on folate forms in relation to polymorphisms in folate catabolising enzymes in elderly people. Our hypothesis is that differences in folate forms after folic acid supplementation might be due to polymorphisms in folate catabolising enzymes. Therefore, folic acid might be retained by people with certain genotypes.


  • Dietary Supplement: folic acid plus B6 and B12
    • folic acid 400 µg plus vitamin B12 plus B6
  • Dietary Supplement: folic acid
    • folic acid 400 µg

Arms, Groups and Cohorts

  • Active Comparator: folic acid plus B6 and B12
    • folic 400 µg plus vitamin B12 plus B6
  • Placebo Comparator: Folic acid
    • folic acid alone

Clinical Trial Outcome Measures

Primary Measures

  • blood metabolic markers
    • Time Frame: 18 months
    • we will measure primary folate forms after folic acid supplement

Participating in This Clinical Trial

Inclusion Criteria

  • Males and females
  • Age > 65 years.

Exclusion Criteria

  • Renal dysfunction
  • Recent stroke, or coronary event (within the last 3 months)
  • Current cancer treatment
  • Antifolate (e.g. methotrexate) treatment
  • Ileum resection
  • Current B-vitamin supplement
  • Epilepsy medications
  • Megaloblastic anemia or other indications for treatment with high doses of folate or vitamin B12.

Gender Eligibility: All

Minimum Age: 65 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: Accepts Healthy Volunteers

Investigator Details

  • Lead Sponsor
    • Saarland University
  • Provider of Information About this Clinical Study
    • Principal Investigator: Rima Obeid, Prof. Dr. – Saarland University
  • Overall Official(s)
    • Rima Obeid, PhD, Principal Investigator, Department of Clinical Chemistry, University of Saarland

Citations Reporting on Results

Obeid R, Kirsch SH, Dilmann S, Klein C, Eckert R, Geisel J, Herrmann W. Folic acid causes higher prevalence of detectable unmetabolized folic acid in serum than B-complex: a randomized trial. Eur J Nutr. 2016 Apr;55(3):1021-8. doi: 10.1007/s00394-015-0916-z. Epub 2015 May 6.

Clinical trials entries are delivered from the US National Institutes of Health and are not reviewed separately by this site. Please see the identifier information above for retrieving further details from the government database.

At TrialBulletin.com, we keep tabs on over 200,000 clinical trials in the US and abroad, using medical data supplied directly by the US National Institutes of Health. Please see the About and Contact page for details.