Biomarkers of folate status in NHANES: a roundtable summary123456

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A roundtable to discuss the measurement of folate status biomarkers in NHANES took place in July 2010. NHANES has measured serum folate since 1974 and red blood cell (RBC) folate since 1978 with the use of several different measurement procedures. Data on serum 5-methyltetrahydrofolate (5MTHF) and folic acid (FA) concentrations in persons aged ≥60 y are available in NHANES 1999–2002. The roundtable reviewed data that showed that folate concentrations from the Bio-Rad Quantaphase II procedure (Bio-Rad Laboratories, Hercules, CA; used in NHANES 1991–1994 and NHANES 1999–2006) were, on average, 29% lower for serum and 45% lower for RBC than were those from the microbiological assay (MA), which was used in NHANES 2007–2010. Roundtable experts agreed that these differences required a data adjustment for time-trend analyses. The roundtable reviewed the possible use of an isotope-dilution liquid chromatography–tandem mass spectrometry (LC-MS/MS) measurement procedure for future NHANES and agreed that the close agreement between the MA and LC-MS/MS results for serum folate supported conversion to the LC-MS/MS procedure. However, for RBC folate, the MA gave 25% higher concentrations than did the LC-MS/MS procedure. The roundtable agreed that the use of the LC-MS/MS procedure to measure RBC folate is premature at this time. The roundtable reviewed the reference materials available or under development at the National Institute of Standards and Technology and recognized the challenges related to, and the scientific need for, these materials. They noted the need for a commutability study for the available reference materials for serum 5MTHF and FA.

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From the Office of Dietary Supplements (EAY, RLB, CS, PMC, MFP), Genome Technology Branch, National Human Genome Research Institute (LCB), and Eunice Kennedy Shriver National Institute of Child Health and Human Development (JLM), National Institutes of Health, Bethesda, MD; National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, GA (CMP, ZF); the Analytical Chemistry Division, National Institute of Standards and Technology, Gaithersburg, MD (KWP); National Center for Health Statistics, Centers for Disease Control and Prevention, Hyattsville, MD (DAL, LRC, CLJ); the Haematology Department, United Kingdom National External Quality Assessment Service, Sutton Coldfield, United Kingdom (SB); the Department of Pathology, Stony Brook University Medical Center, Stony Brook, NY (JLB); the Department of Medicine, New York Methodist Hospital, Brooklyn, NY, and Weill Medical College, Cornell University, New York, NY (RC); the Department of Preventive Medicine and Epidemiology, Loyola University Chicago Stritch School of Medicine, Maywood, IL (RAD-A); the Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN (JHE); the Department of Medical Pathology and Laboratory Medicine and Medicine, University of California Davis, Sacramento, CA (RG); the Food Science and Human Nutrition Department, University of Florida, Gainesville, FL (JFG); the Departments of Laboratory Medicine and Medicine, University of Washington, Seattle, WA (ANH); the Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine, Case Western Reserve University, and the Department of Cell Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH (DWJ); Jean Mayer US Department of Agriculture Human Nutrition Research Center on Aging, Tufts University, Boston, MA (PFJ, JS); the Department of Clinical Medicine, School of Medicine, Trinity College, Dublin, Ireland (AMM); the Department of Biostatistics, Boston University School of Public Health, Boston, MA (JM); the Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus, Denmark (EN); the Center for Food Safety and Applied Nutrition, Food and Drug Administration, College Park, MD (JIR); the Department of Nutritional Science and Toxicology, University of California, Berkeley, CA (BS); the Department of Medicine/Division of Hematology, University of Colorado Health Sciences Center, Aurora, CO (SS); the Division of Nutritional Sciences, Cornell University, Ithaca, NY (PS); the Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, AL (TT); Nutrition Science and Delivery, the Department of Health, London, United Kingdom (AT); National Institute for Biological Standards and Control, Herts, United Kingdom (SJT).

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The authors dedicate this article and the roundtable to Mary Frances Picciano, Office of Dietary Supplements, National Institutes of Health, who was the driving force behind this effort prior to her death in August 2010.

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Any opinions, findings, conclusions, or recommendations expressed in this publication are those of the authors and do not necessarily reflect the views of the Centers for Disease Control and Prevention, the National Institutes of Health, the US Department of Health and Human Services, or the National Institute of Standards and Technology, or any of the authors’ related affiliations. Certain commercial equipment, instruments, or materials are identified in this article to specify adequately the experimental procedure. Such identification does not imply recommendation or endorsement by the National Institute of Standards and Technology, the Centers for Disease Control and Prevention, the National Institutes of Health, or the US Department of Health and Human Services, nor does it imply that the materials or equipment identified are necessarily the best available for the purpose.

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Supported by the National Center for Health Statistics, Centers for Disease Control and Prevention, and the Office of Dietary Supplements, NIH.

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Address reprint requests to PM Coates, Director, Office of Dietary Supplements, National Institutes of Health, 6100 Executive Boulevard, Room 3B01, MSC 7517, Bethesda, MD 20892-7517. E-mail: [email protected].

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Address correspondence to EA Yetley (retired), Office of Dietary Supplements, National Institutes of Health, 6100 Executive Boulevard, MSC 7517, Bethesda, MD 20892. E-mail: [email protected].