Interconversions of plasma folate species in response to dosing with oral folic acid and 5‐methyltetrahydrofolate: an LC‐MS/MS pilot study

Abstract

Information is sparse on changes in plasma folate species in response to high folic acid (PGA) intake. As part of a pharmacokinetics study, we investigated the conversion of oral PGA (1 and 2.5 mg) and 5‐methyltetrahydrofolate (5MTHF; 5 mg) into plasma folate species (5MTHF, PGA, 5‐formylTHF [5FTHF], THF, and 5,10‐methenylTHF) by LC‐MS/MS in 6 subjects/dose at five time points (0, 1.5, 3.0, 6.5 and 24 h) and compared results to a placebo group. 5,10‐methenyl‐THF was not detectable. At baseline, total folate (TFOL) consisted of 80–97% 5MTHF, 1–7% PGA, 1–14% 5FTHF, and 0–12% THF. In the placebo group, TFOL and folate species remained unchanged over time. In the two PGA dose groups, the highest increases were observed for PGA at 1.5 h; smaller increases (≤5‐fold) were observed for the other folate species. In the 5MTHF dose group, 20‐fold increases were observed for 5MTHF and 5FTHF and < 5‐fold increases for PGA and THF. Changes in folate species pattern generally returned to baseline by 24 h. Preliminary results from this sensitive LC‐MS/MS method show that there are small interconversions of folate species in response to dosing with PGA and 5MTHF. Supported by NIH grant HL068165 to JEA. Folate concentration (nmol/L) at 0 h/x‐fold increase at 1.5 h Placebo 1 mg PGA 2.5 mg PGA 5 mg 5MTHF 5MTHF 19.3/1.0 17.2/1.7 31.5/2.0 20.4/19 PGA 0.5/0.9 0.6/57 0.7/238 0.4/4.4 5FTHF 1.5/1.0 0.6/2.5 1.2/2.1 0.6/18 THF 0.9/0.3 0.3/5.3 0.4/4.4 1.1/2.8