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Folate concentrations in serum and whole blood

Serum concentration of folates range between ~10 – 50 nmol/L, with 5-methylTHF predominating (82 – 93% of total folate in serum) (1;2). Most of the blood folate is unspecifically bound to proteins (e.g. α2-macroglobulin, albumin, and transferrin) with a low affinity. Folate-binding proteins (FBPs) bind a small amount of blood folate with high affinity.

Folates are incorporated into the RBCs during erythropoiesis. FBPs are expressed on early stage hematopoietic cells and are involved in the folate uptake. Under normal conditions, RBC folate is 30fold higher than the serum folate concentration ranging from 140 – 450 ng/mL packed cells. Similar to serum, the RBC folates are unspecifically bound to proteins such as hemoglobin. Matured erythrocytes are impermeable for folylpolyglutamates (3). This leads to an intracellular retention of the folates with a half-life of about 100 days (the life span of the erythrocytes). Therefore, RBC folate represents a long-term marker for folate status (4). This marker is not affected by recent changes in the dietary intake.


Folate deficiency in adults

In countries without mandatory FA fortification, the dietary intakes are often insufficient to cover the daily requirements. Flynn et al. summarized the intake of selected nutrients from foods, supplementation, and fortification in European countries (5). The median folate intake in German adults was below the recommended 300 µg/day. This suggests that folate deficiency is common even in wealthy countries. Folate deficiency causes HHCY, an independent risk factor for age-associated diseases. In addition, folate deficiency is associated with many age-related diseases such as stroke, dementia, cancer, and cardiovascular disease (CVD) (6).



1.     Pfeiffer CM, Fazili Z, McCoy L, Zhang M, Gunter EW. Determination of folate vitamers in human serum by stable-isotope-dilution tandem mass spectrometry and comparison with radioassay and microbiologic assay. Clin Chem 2004;50:423-32.
2.     Kirsch SH, Knapp JP, Herrmann W, Obeid R. Quantification of key folate forms in serum using stable-isotope dilution ultra performance liquid chromatography-tandem mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci 2010;878:68-75.
3.     Lucock M. Folic acid: nutritional biochemistry, molecular biology, and role in disease processes. Mol Genet Metab 2000;71:121-38.
4.     Hoffbrand AV, Newcombe FA, Mollin DL. Method of assay of red cell folate activity and the value of the assay as a test for folate deficiency. J Clin Pathol 1966;19:17-28.
5.     Flynn A, Hirvonen T, Mensink GB, Ocke MC, Serra-Majem L, Stos K et al. Intake of selected nutrients from foods, from fortification and from supplements in various European countries. Food Nutr Res 2009;53.
6.     Herrmann W, Herrmann M, Obeid R. Hyperhomocysteinaemia: a critical review of old and new aspects. Curr Drug Metab 2007;8:17-31.