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The effect of vitamin B12 and folic acid supplementation on routine haematological parameters in older people: an individual participant data meta-analysis

European Journal of Clinical Nutritionvolume 72pages785795 (2018) | Download Citation



Low vitamin B12 and folate levels in community-dwelling older people are usually corrected with supplements. However, the effect of this supplementation on haematological parameters in older persons is not known. Therefore, we executed a systematic review and individual participant data meta-analysis of randomised placebo-controlled trials (RCTs).


We performed a systematic search in PubMed, EMBASE, Web of Science, Cochrane and CENTRAL for RCTs published between January 1950 and April 2016, where community-dwelling elderly (60+ years) who were treated with vitamin B12 or folic acid or placebo. The presence of anaemia was not required. We analysed the data on haematological parameters with a two-stage IPD meta-analysis.


We found 494 full papers covering 14 studies. Data were shared by the authors of four RCTs comparing vitamin B12 with placebo (n = 343) and of three RCTs comparing folic acid with placebo (n = 929). We found no effect of vitamin B12 supplementation on haemoglobin (change 0.00 g/dL, 95% CI: −0.19;0.18), and no effect of folic acid supplementation (change −0.09 g/dL, 95% CI: −0.19;0.01). The effects of supplementation on other haematological parameters were similar. The effects did not differ by sex or by age group. Also, no effect was found in a subgroup of patients with anaemia and a subgroup of patients who were treated >4 weeks.


Evidence on the effects of supplementation of low concentrations of vitamin B12 and folate on haematological parameters in community-dwelling older people is inconclusive. Further research is needed before firm recommendations can be made concerning the supplementation of vitamin B12 and folate.

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We thank Anne-Mette Hvas and Ebba Nexo for sharing study data for this project. We thank Jan Schoones from the Walaeus Library of the Leiden University Medical Center for constructing and performing the electronic search strategies.

Author information


  1. Department of Public Health and Primary Care, Leiden University Medical Center, Leiden, The Netherlands

    • Antonia FH Smelt
    • , Jacobijn Gussekloo
    • , Lynette W Bermingham
    •  & Wendy PJ Den Elzen
  2. Faculty of Epidemiology and Population Health, London School of Hygiene & Tropical Medicine, London, UK

    • Elizabeth Allen
    •  & Alan D Dangour
  3. Department of Epidemiology, School for Cardiovascular Diseases – CARIM, Maastricht University, Maastricht, The Netherlands

    • Simone JPM Eussen
  4. Department of Ambulatory Care and Community Medicine, University of Lausanne, Lausanne, Switzerland

    • Bernard Favrat
  5. Division of Human Nutrition, Wageningen University, Wageningen, The Netherlands

    • Lisette CPGM De Groot
    • , Frans J Kok
    •  & Ondine Van De Rest
  6. Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, NT, Hong Kong

    • Timothy Kwok
  7. Department of Clinical Pharmacology, School of Medicine, Flinders University, Adelaide, SA, Australia

    • Arduino A Mangoni
  8. Department of Medicine, University of Thessaly, Larissa, Greece

    • George Ntaios
  9. Royal Melbourne Hospital, The University of Melbourne, Melbourne, VIC, Australia

    • Eric Seal
  10. School of Health Sciences Fribourg, HES-SO University of Applied Sciences and Arts Western Switzerland, Fribourg, Switzerland

    • Paul Vaucher
  11. Unilever R&D Vlaardingen, Vlaardingen, The Netherlands

    • Petra Verhoef
  12. Department of Medical Statistics, Leiden University Medical Center, Leiden, The Netherlands

    • Theo Stijnen
  13. Department of Clinical Chemistry and Laboratory Medicine, Leiden University Medical Center, Leiden, The Netherlands

    • Wendy PJ Den Elzen


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Conflict of interest

The authors declare that they have no conflict of interest.

Corresponding author

Correspondence to Wendy PJ Den Elzen.

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