levoleucovorin and 5-methyltetrahydrohomofolic-acid

Folate deficiency increases the risk of several human diseases. Likewise, high intakes of folate, particularly synthetic folic acid intake, may be associated with adverse health outcomes in humans. A more comprehensive understanding of the "input side" of folate nutrition may help to set dietary recommendations that strike the right balance between health benefits and risks. It is well known that the microflora in the colon produce large quantities of folate that approach or exceed recommended dietary intakes; however, there is no direct evidence of the bioavailability of this pool in humans.. The objective was to determine whether, and to what extent, the natural folate vitamer 5-formyltetrahydrofolic acid is absorbed across the intact colon of humans.. During screening colonoscopy, 684 nmol (320 microg) [(13)C]glutamyl-5-formyltetrahydrofolic acid was infused directly into the cecum of 6 healthy adults. Three or more weeks later, each subject received an intravenous injection of the same compound (172 nmol). Blood samples were collected before and after each treatment. The ratio of labeled to unlabeled folates was determined in plasma by tandem mass spectrometry.. The apparent rate of folate absorption across the colon of a bolus dose of [(13)C]5-formyltetrahydrofolic acid infused into the cecum was 0.6 +/- 0.2 nmol/h, as determined by the appearance of [(13)C(5)]5-methyltetrahydrofolic acid in plasma. In comparison, the rate of appearance of [(13)C(5)]5-methyltetrahydrofolic acid after an intravenous injection of [(13)C(5)]5-formyltetrahydrofolate was 7 +/- 1.2 nmol/h.. Physiologic doses of natural folate are absorbed across the intact colon in humans.

Topics: Adult; Carbon Isotopes; Cecum; Colon; Colonoscopy; Female; Folic Acid; Formyltetrahydrofolates; Genotype; Humans; Intestinal Absorption; Leucovorin; Male; Methylenetetrahydrofolate Reductase (NADPH2); Middle Aged

Chromatographic conditions for the determination of 5-methyltetrahydrofolic acid in plasma and spinal fluid are described, involving simple pretreatment of the sample. Electrochemical detection was used. The linear range of the method is more than 10(3). Recovery from plasma and spinal fluid is 100%, and the detection limit of the method is 2.10(-9) M, sufficient for the detection of endogenous plasma and spinal fluid levels. The detection conditions are discussed. Endogenous concentrations of the compound in plasma and spinal fluid were determined and correlated with a folate bioassay. Plasma concentrations have been shown after the administration of leucovorin which is used in anticancer therapy.

Topics: Animals; Biological Assay; Chromatography, High Pressure Liquid; Folic Acid; Humans; Leucovorin; Methotrexate; Rats