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Clinical Chemistry 44: 1886-1891, 1998;
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(Clinical Chemistry. 1998;44:1886-1891.)
© 1998 American Association for Clinical Chemistry, Inc.


Opinion

Erythrocyte folate analysis: a cause for concern?

Anthony J. A. Wrighta, Paul M. Finglas, and Susan Southon

a Author for correspondence. Fax 44 1603 255237; e-mail tony.wright{at}bbsrc.ac.uk.

Neural tube defects can be prevented by adequate intake of periconceptional folate, and inverse associations between folate status and cardiovascular disease and various cancers have been noted. Thus, there is renewed interest in the analysis of red cell folate (RCF) as an indicator of folate deficiency risk. Assessment of the assumptions that underpin RCF assays indicates that many are false. Published literature suggests that increased deoxy-hemoglobin (which can bind RCF electrostatically) yields more assayable folate, and increased oxy-hemoglobin (which cannot bind RCF) yields less assayable folate. It is argued that as deoxy-hemoglobin picks up oxygen and switches quaternary structure, any bound folate must, on purely theoretical grounds, become physically "trapped". Venous blood taken for analysis is 65% to 75% saturated with oxygen, and pro-rata "trapping" will lead to serious underestimation of RCF. Hence, doubt is cast over the validity of all previous RCF values. Some strategies for accurately assessing RCF are suggested.


Key Words: RCF, red cell folate • Hb, hemoglobin • MA, microbiological assay • RFPB, radio-folate-binding protein • AA, ascorbic acid • PteGlu, pteroylmonoglutamic acid (folic acid) • 5CH3-H4-PteGlun, 5-methyltetrahydrofolic acid polyglutamates • 5CH3-H4-PteGlu, 5-methyltetrahydrofolic acid monoglutamate • DPG, 2,3-diphosphoglycerate • T-, tense • R-, relaxed.




The following articles in journals at HighWire Press have cited this article:


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Erythrocyte Folate Extraction and Quantitative Determination by Liquid Chromatography-Tandem Mass Spectrometry: Comparison of Results with Microbiologic Assay
Clin. Chem., December 1, 2005; 51(12): 2318 - 2325.
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Am. J. Clin. Nutr.Home page
A. Brevik, S. E. Vollset, G. S Tell, H. Refsum, P. M. Ueland, E. B. Loeken, C. A Drevon, and L. F. Andersen
Plasma concentration of folate as a biomarker for the intake of fruit and vegetables: the Hordaland Homocysteine Study
Am. J. Clinical Nutrition, February 1, 2005; 81(2): 434 - 439.
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J. Nutr.Home page
A. J. Clifford, E. M. Noceti, A. Block-Joy, T. Block, and G. Block
Erythrocyte Folate and Its Response to Folic Acid Supplementation Is Assay Dependent in Women
J. Nutr., January 1, 2005; 135(1): 137 - 143.
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Home page
Clin. Chem.Home page
A. J. A. Wright, P. M. Finglas, and S. Southon
Erythrocyte Folate Analysis: Saponin Added During Lysis of Whole Blood Can Increase Apparent Folate Concentrations, Depending on Hemolysate pH
Clin. Chem., December 1, 2000; 46(12): 1978 - 1986.
[Abstract] [Full Text] [PDF]




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