%0 Journal Article
%T Plasma and Red Cell Reference Intervals of 5-Methyltetrahydrofolate of Healthy Adults in Whom Biochemical Functional Deficiencies of Folate and Vitamin B12 Had Been Excluded
%A Agata Sobczy¨½ska-Malefora
%A Dominic J. Harrington
%A Kieran Voong
%A Martin J. Shearer
%J Advances in Hematology
%D 2014
%I Hindawi Publishing Corporation
%R 10.1155/2014/465623
%X 5-Methyltetrahydrofolate (5-MTHF) is the predominant form of folate and a strong determinant of homocysteine concentrations. There is evidence that suboptimal 5-MTHF availability is a risk factor for cardiovascular disease independent of homocysteine. The analysis of folates remains challenging and is almost exclusively limited to the reporting of ¡°total¡± folate rather than individual molecular forms. The purpose of this study was to establish the reference intervals of 5-MTHF in plasma and red cells of healthy adults who had been prescreened to exclude biochemical evidence of functional deficiency of folate and/or vitamin B12. Functional folate and vitamin B12 status was assessed by respective plasma measurements of homocysteine and methylmalonic acid in 144 healthy volunteers, aged 19¨C64 years. After the exclusion of 10 individuals, values for 134 subjects were used to establish the upper reference limits for homocysteine (13£¿¦Ìmol/L females and 15£¿¦Ìmol/L males) and methylmalonic acid (430£¿nmol/L). Subjects with values below these cutoffs were designated as folate and vitamin B12 replete and their plasma and red cell 5-MTHF reference intervals determined, : 6.6¨C39.9£¿nmol/L and 223¨C1041£¿nmol/L, respectively. The application of these intervals will assist in the evaluation of folate status and facilitate studies to evaluate the relationship of 5-MTHF to disease. 1. Introduction 5-MTHF, the predominant form of folate (vitamin B9) in plasma and red cells, is a substrate for the methionine synthase and vitamin B12 (methylcobalamin form¡ªmethyl-Cbl) mediated conversion of homocysteine (tHcy) to methionine (Figure 1). Suboptimal 5-MTHF availability leads to an increase in circulating homocysteine (hyperhomocysteinaemia) which has been associated with many diseases and health complications including cardiovascular disease [1, 2]. There is also evidence to suggest that 5-MTHF deficiency may be a cardiovascular risk factor independent of homocysteine [3, 4]. Figure 1: Homocysteine, folate, and vitamin B 12 metabolism. THF (tetrahydrofolate), 5-MTHF (5-methyltetrahydrofolate), MTHFR (methylene tetrahydrofolate reductase), MS (methionine synthase), CBS (cystathionine beta-synthase), SAM ( S-adenosyl methionine), Cbl (cobalamin), TC II (transcobalamin), holo TC (holotrascobalamin), OH-Cbl (hydroxocobalamin), MMA-CoA (methylmalonyl-CoA), and MMA (methylmalonic acid). In the plasma of healthy humans, 5-MTHF typically constitutes 80¨C90% of total folate [5, 6]. Circulatory concentrations of 5-MTHF are partly dependant on methylenetetrahydrofolate reductase (MTHFR)
%U http://www.hindawi.com/journals/ah/2014/465623/