European Journal of Clinical Nutrition (2018) 72:785–795
The effect of vitamin B12 and folic acid supplementation on routine
haematological parameters in older people: an individual
participant data meta-analysis
Antonia FH Smelt
Lynette W Bermingham
Alan D Dangour
Simone JPM Eussen
Lisette CPGM De Groot
Frans J Kok
Arduino A Mangoni
Ondine Van De Rest
Wendy PJ Den Elzen
Received: 25 August 2017 / Revised: 28 November 2017 / Accepted: 27 December 2017 / Published online: 8 March 2018
© Macmillan Publishers Limited, part of Springer Nature 2018
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
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 haemato-
logical 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.
The prevalence of anaemia in older persons is high (around
10% among people aged ≥65 years) and rises with advan-
cing age [1, 2]. In about one-third of older persons with
anaemia co-incidental nutritional deﬁciencies, such as iron,
vitamin B12 and folate deﬁciency, exist . Among people
aged ≥75 years, the prevalence of both vitamin B12 and
folate deﬁciency is >10% [3–7]. These deﬁciencies are not
only associated with macrocytic anaemia but also with
dementia, peripheral neuropathy, combined degeneration of
the spinal cord and cardiovascular disease [8–11].
As the prevalence of deﬁciencies in vitamin B12 and
folate are high, screening for deﬁciencies in vitamin B12
and folate has been recommended as part of a geriatric
work-up [12, 13]. Guidelines recommend vitamin
B12 supplementation in patients with very low serum
vitamin B12 concentrations due to lack of intrinsic factor
(IF) (pernicious anaemia) or food-vitamin B12 malabsorp-
tion. Several studies have shown signiﬁcant increases in
haemoglobin after vitamin B12 administration in these
patients [14–16]. Thus, when low levels of vitamin B12 and
* Wendy PJ Den Elzen
Extended author information available on the last page of the article
Electronic supplementary material The online version of this article
(https://doi.org/10.1038/s41430-018-0118-x) contains supplementary
material, which is available to authorised users.