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. 2016 Dec;104(6):1607-1615.
doi: 10.3945/ajcn.116.138529. Epub 2016 Sep 28.

Applying inappropriate cutoffs leads to misinterpretation of folate status in the US population

Christine M Pfeiffer  1 , Maya R Sternberg  2 , Heather C Hamner  3 , Krista S Crider  4 , David A Lacher  5 , Lisa M Rogers  6 , Regan L Bailey  7   8 , Elizabeth A Yetley  8
Affiliations

Applying inappropriate cutoffs leads to misinterpretation of folate status in the US population

Christine M Pfeiffer et al. Am J Clin Nutr. 2016 Dec.

Abstract

Background: Folate cutoffs for risk of deficiency compared with possible deficiency were originally derived differently (experimental compared with epidemiologic data), and their interpretations are different. The matching of cutoffs derived from one assay with population-based data derived from another assay requires caution.

Objective: We assessed the extent of folate-status misinterpretation with the use of inappropriate cutoffs.

Design: In the cross-sectional NHANES, serum and red blood cell (RBC) folate were first measured with the use of a radioprotein-binding assay (RPBA) (1988-2006) and, afterwards, with the use of a microbiologic assay (2007-2010). We compared prevalence estimates for assay-matched cutoffs (e.g., with the use of an RPBA cutoff with RPBA data) and assay-mismatched cutoffs (e.g., with the use of microbiologic assay cutoff with RPBA data) for risk of deficiency on the basis of megaloblastic anemia as a hematologic indicator in persons ≥4 y of age (e.g., serum folate concentration <7 nmol/L and RBC folate concentration <305 nmol/L derived with the use of a microbiologic assay), possible deficiency on the basis of rising homocysteine as a metabolic indicator in persons ≥4 y of age (e.g., serum folate concentration <10 nmol/L and RBC folate concentration <340 nmol/L derived with the use of an RPBA), and insufficiency on the basis of elevated risk of neural tube defects in women 12-49 y old (e.g., RBC folate concentration <906 nmol/L derived with the use of a microbiologic assay).

Results: Pre-folic acid fortification (1988-1994), risks of deficiency for assay-matched compared with assay-mismatched cutoffs were 5.6% compared with 16% (serum folate), respectively, and 7.4% compared with 28% (RBC folate), respectively; risks declined postfortification (1999-2006) to <1% compared with <1% (serum folate), respectively, and to <1% compared with 2.5% (RBC folate), respectively. Prefortification (1988-1994), risks of possible deficiency for assay-matched compared with assay-mismatched cutoffs were 35% compared with 56% (serum folate), respectively, and 37% compared with 84% (RBC folate), respectively; risks declined postfortification (1999-2006) to 1.9% compared with 7.0% (serum folate), respectively, and to 4.8% compared with 53% (RBC folate), respectively. Postfortification (2007-2010), risks of insufficiency were 3% (assay matched) compared with 39% (assay mismatched), respectively.

Conclusions: The application of assay-mismatched cutoffs leads to a misinterpretation of folate status. This confusion likely applies to clinical assays because no comparability data are available, to our knowledge.

Keywords: NHANES; deficiency; insufficiency; microbiologic assay; radioprotein-binding assay.

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References

    1. Institute of Medicine, Food and Nutrition Board. Dietary reference intakes: thiamin, riboflavin, niacin, vitamin B6, folate, vitamin B12, pantothenic acid, biotin, and choline. Washington (DC): National Academy Press; 1998. - PubMed
    1. Yetley EA, Johnson CL.. Folate and vitamin B-12 biomarkers in NHANES: history of their measurement and use. Am J Clin Nutr 2011;94(Suppl):322S–31S. - PMC - PubMed
    1. WHO. Serum and red blood cell folate concentrations for assessing folate status in populations [Internet]. Vitamin and Mineral Nutrition Information System. Geneva (Switzerland): World Health Organization; 2015. [cited 2016 Mar 19]. Available from: http://apps.who.int/iris/bitstream/10665/162114/1/WHO_NMH_NHD_EPG_15.01.....
    1. Bailey LB, Stover PJ, McNulty H, Fenech MF, Gregory JF III, Mills JL, Pfeiffer CM, Fazili Z, Zhang M, Ueland PM, et al. . Biomarkers of nutrition for development – folate review. J Nutr 2015;145:1636S–80S. - PMC - PubMed
    1. Life Sciences Research Office, Center for Food Safety and Applied Nutrition. Assessment of the folate nutritional status of the U.S. population based on data collected in the Second National Health and Nutrition Survey, 1976–1980. Washington (DC): U.S. Food and Drug Administration, Department of Health and Human Services; 1984.

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