European Journal of Nutrition

, Volume 53, Issue 7, pp 1445–1456 | Cite as

Three-month B vitamin supplementation in pre-school children affects folate status and homocysteine, but not cognitive performance

  • Astrid Rauh-Pfeiffer
  • Uschi Handel
  • Hans Demmelmair
  • Wolfgang Peissner
  • Mareile Niesser
  • Diego Moretti
  • Vanessa Martens
  • Sheila Wiseman
  • Judith Weichert
  • Moritz Heene
  • Markus Bühner
  • Berthold Koletzko
Original Contribution



Suboptimal vitamin B status might affect cognitive performance in early childhood. We tested the hypothesis that short-term supplementation with folic acid and selected B vitamins improves cognitive function in healthy children in a population with relatively low folate status.


We screened 1,002 kindergarten children for suboptimal folate status by assessing the total urinary para-aminobenzoylglutamate excretion. Two hundred and fifty low ranking subjects were recruited into a double blind, randomized, controlled trial to receive daily a sachet containing 220 μg folic acid, 1.1 mg vitamin B2, 0.73 mg B6, 1.2 μg B12 and 130 mg calcium, or calcium only for 3 months. Primary outcomes were changes in verbal IQ, short-term memory and processing speed between baseline and study end. Secondary outcomes were urinary markers of folate and vitamin B12 status, acetyl-para-aminobenzoylglutamate and methylmalonic acid, respectively, and, in a subgroup of 120 participants, blood folate and plasma homocysteine.


Pre- and post-intervention cognitive measurements were completed by 115 children in the intervention and 122 in the control group. Compared to control, median blood folate increased by about 50 % (P for difference, P < 0.0001). Homocysteine decreased by 1.1 μmol/L compared to baseline, no change was seen in the control group (P for difference P < 0.0001) and acetyl-para-aminobenzoylglutamate was 4 nmol/mmol higher compared to control at the end of the intervention (P < 0.0001). We found no relevant differences between the groups for the cognitive measures.


Short-term improvement of folate and homocysteine status in healthy children does not appear to affect cognitive performance.


B vitamin supplementation Cognition Pre-school children 



We thank the participating families and kindergarten staff for their enthusiastic support of the project. We thank Sabine Eiselen (Dr von Hauner Children’s Hospital, University of Munich Medical Centre, Munich, Germany) for practical organization of the study, Martina Weber (Dr von Hauner Children’s Hospital, University of Munich Medical Centre, Munich, Germany) and Winfried Theis (Unilever R&D, Vlaardingen, Netherlands) for statistical advice, Christian Hellmuth (Dr von Hauner Children’s Hospital, University of Munich Medical Centre, Munich, Germany) for laboratory analyses, and Ingrid Pawellek (Dr von Hauner Children’s Hospital, University of Munich Medical Centre, Munich, Germany) for the evaluation of the food frequency questionnaires. MMA analyses (Institute for Clinical Chemistry, University of Munich Medical Centre, Munich, Germany) were supported by the Hans-Fischer-Gesellschaft, München. This work was supported financially in part by NUTRIMENTHE (Grant Agreement No. 212652). This project was also supported by Unilever R&D, Vlaardingen, The Netherlands.

Conflict of interest

The authors declare that they have no conflict of interest.


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Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Astrid Rauh-Pfeiffer
    • 1
  • Uschi Handel
    • 1
  • Hans Demmelmair
    • 1
  • Wolfgang Peissner
    • 1
  • Mareile Niesser
    • 1
  • Diego Moretti
    • 2
    • 3
  • Vanessa Martens
    • 2
  • Sheila Wiseman
    • 2
  • Judith Weichert
    • 4
  • Moritz Heene
    • 4
  • Markus Bühner
    • 4
  • Berthold Koletzko
    • 1
  1. 1.Dr von Hauner Children’s HospitalUniversity of Munich Medical CentreMunichGermany
  2. 2.Unilever R&DVlaardingenThe Netherlands
  3. 3.Laboratory of Human Nutrition, Institute of Food Science and NutritionETH ZürichZurichSwitzerland
  4. 4.Department of PsychologyUniversity of MunichMunichGermany

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