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. 2016 Jun;38(2):e84-97.
doi: 10.1093/pubmed/fdv087. Epub 2015 Jul 9.

Systematic review of adverse health outcomes associated with high serum or red blood cell folate concentrations

Cynthia K Colapinto  1 , Deborah L O'Connor  2 , Margaret Sampson  3 , Brock Williams  4 , Mark S Tremblay  1
Affiliations

Systematic review of adverse health outcomes associated with high serum or red blood cell folate concentrations

Cynthia K Colapinto et al. J Public Health (Oxf). 2016 Jun.

Abstract

Background: To examine the relationship between reported high serum or red blood cell (RBC) folate status and adverse health outcomes.

Methods: We systematically searched PubMed/Medline and EMBASE (to May 2013), with no limits by study type, country or population, to identify studies reporting high folate concentrations in association with adverse health outcomes. Two reviewers screened studies and extracted data. Study quality was assessed.

Results: We included 51 articles, representing 46 studies and 71 847 participants. Quantiles were used by 96% of studies to identify high folate concentrations. Eighty-three percent of serum folate and 50% of RBC folate studies reported a high folate cutoff that corresponded with a clinically normal concentration. Increasing values of reported high folate concentration did not demonstrate a consistent association with risk of adverse health outcomes. Overall, reported high folate concentrations appeared to be associated with a decreased risk of adverse health outcomes, though substantial methodological heterogeneity precluded complex analyses.

Conclusions: Our interpretation was complicated by methodological variability. High folate cutoffs varied and often corresponded with normal or desirable blood concentrations. In general, a negative association appeared to exist between reported high folate status and adverse health outcomes. Consistent methods and definitions are needed to examine high folate status and ultimately inform public health interventions.

Keywords: health; high folate status; red blood cell folate; serum folate; systematic review.

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Figures

Fig. 1
Fig. 1
Flowchart of study selection process.
See this image and copyright information in PMC

References

    1. McNulty H, Pentieva K. Folate bioavailability. In: Bailey L. (ed). Folate in Health and Disease, 2nd edn Boca Raton, FL: Taylor & Francis Group, L.L.C., 2010.
    1. Goh YI, Koren G. Folic acid in pregnancy and fetal outcomes. J Obstet Gynaecol 2008;28(1):3–13. - PubMed
    1. Institute of Medicine. DRI Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline. Washington, DC: National Academies Press, 1998. - PubMed
    1. MRC Vitamin Study Research Group. Prevention of neural tube defects: results of the Medical Research Council Vitamin Study. Lancet 1991;338(8760):131–7. - PubMed
    1. Czeizel AE, Dudas I. Prevention of the first occurrence of neural-tube defects by periconceptional vitamin supplementation. N Engl J Med 1992;327(26):1832–5. - PubMed

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