KINETIC MODELING OF FOLATE METABOLISM THROUGH USE OF CHRONIC ADMINISTRATION OF DEUTERIUM-LABELED FOLIC-ACID IN MEN

This study was conducted as an initial investigation of in vivo folate kinetics in healthy men (n = 4) and made use of a chronic-administrat ion protocol with stable-isotope labeling. Subjects were given 0.453 m u mol (200 mu g) total folic acid in aqueous solution daily throughout the 18-wk study while they consumed self-selected folate-adequate die ts. After a 2-wk pretrial period with unlabeled folic acid, subjects w ere given 0.227 mu mol (100 mu g) pteroyl-L-[H-2(4)]glutamic acid/d ([ H-2(4)]folic acid) combined with 0.227 mu mol nonlabeled folic acid or [H-2(2)]pteroylhexaglutamic acid/d for the next 8 wk; then for the ne xt 8 wk the [H-2(4)]folic acid was withdrawn and the subjects received only nonlabeled folic acid. Little unmetabolized folic acid was excre ted in urine. Isotopic enrichment of urinary folate during [H-2(4)]fol ic acid administration and withdrawal was consistent with a kinetic mo del having a rapid turnover pool and a slow turnover pool. In contrast with previous two-pool models, provisions were made for folate turnov er by urinary folate excretion (as measured here) and by fecal excreti on and catabolic processes. The precision of modeling will be improved in future studies by measurement of enrichment of additional pools. H owever, this study shows clearly the slow turnover of the whole-body f olate pool (less than or equal to 1% per day) and the feasibility of f urther long-term kinetic analysis.