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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 Nutrition volume 72, pages 785–795 (2018)Cite this article

Subjects

Abstract

Background/objectives

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).

Subjects/methods

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.

Results

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.

Conclusions

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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Acknowledgements

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

Authors and Affiliations

  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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  1. Antonia FH Smelt
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  14. Eric Seal
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  18. Wendy PJ Den Elzen
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Correspondence to Wendy PJ Den Elzen.

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Smelt, A.F., Gussekloo, J., Bermingham, L.W. et al. The effect of vitamin B12 and folic acid supplementation on routine haematological parameters in older people: an individual participant data meta-analysis. Eur J Clin Nutr 72, 785–795 (2018). https://doi.org/10.1038/s41430-018-0118-x

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  • DOI: https://doi.org/10.1038/s41430-018-0118-x

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