Wright A J A, Finglas P M, Dainty J R, Hart D J, Wolfe C A, Southon S, Gregory J F
Nutrition Department, Institute of Food Research, Norwich Research Park, Colney, Norwich NR4 7UA, UK.
Br J Nutr. 2003 Aug;90(2):363-71. doi: 10.1079/bjn2003908.
Single (13)C6-labelled doses of pteroylmonoglutamic acid (PteGlu; 634 nmol) or 5-formyltetrahydrofolic acid (431-569 nmol) were given to fasted adult volunteers, and the rise in total and (13)C-labelled plasma 5-methyltetrahydrofolic acid metabolite monitored over 8 h by HPLC and liquid chromatography-MS. The dose-adjusted area under the curve (AUC) for total (labelled plus unlabelled) plasma 5-methyltetrahydrofolic acid following a 5-formyltetrahydrofolic acid test dose was 155 % that obtained following a PteGlu test dose. Surprisingly, an average 60 and 40 % of the total plasma 5-methyltetrahydrofolic acid response to [(13)C6]PteGlu and [(13)C6]5-formyltetrahydrofolic acid, respectively, was unlabelled; an observation never before reported. Short-term kinetics of plasma [(13)C6]5-methyltetrahydrofolic acid showed a slower initial rate of increase in plasma concentration and longer time to peak following an oral dose of [(13)C6]PteGlu compared with that for an oral dose of [(13)C6]5-formyltetrahydrofolic acid, while the [(13)C6]5-methyltetrahydrofolic acid AUC for [(13)C6]5-formyltetrahydrofolic acid was 221 % that for [(13)C6]PteGlu. These data indicate that PteGlu and 5-formyltetrahydrofolic acid, which are thought to be well absorbed (about 90 %) at physiological doses, exhibit dramatically different rates and patterns of plasma response. A limitation in the rate of reduction of PteGlu before methylation could result in slower mucosal transfer of [(13)C6]5-methyltetrahydrofolic acid derived from [(13)C6]PteGlu into the plasma. This, when coupled with an observed similar plasma clearance rate for [(13)C6]5-methyltetrahydrofolic acid metabolite derived from either folate test dose, would yield a comparatively smaller AUC. These findings suggest potential problems in interpretation of absorption studies using unlabelled or labelled folates where the rate of increase, the maximum increase, or the AUC, of plasma folate is employed for test foods (mainly reduced folates) v. a 'reference dose' of PteGlu.
向空腹的成年志愿者单次给予（13）C6标记的蝶酰单谷氨酸（PteGlu；634纳摩尔）或5-甲酰四氢叶酸（431 - 569纳摩尔），并通过高效液相色谱法（HPLC）和液相色谱 - 质谱联用技术监测8小时内血浆中总5-甲基四氢叶酸代谢物及（13）C标记的5-甲基四氢叶酸代谢物的增加情况。5-甲酰四氢叶酸试验剂量后血浆中总（标记加未标记）5-甲基四氢叶酸的剂量调整曲线下面积（AUC）是PteGlu试验剂量后所得AUC的155%。令人惊讶的是，血浆中5-甲基四氢叶酸对[（13）C6]PteGlu和[（13）C6]5-甲酰四氢叶酸反应的总量中，分别平均有60%和40%是未标记的；这一观察结果此前从未有过报道。与口服[（13）C6]5-甲酰四氢叶酸相比，口服[（13）C6]PteGlu后血浆中[（13）C6]5-甲基四氢叶酸的短期动力学显示，其血浆浓度初始增加速率较慢，达到峰值的时间更长，而[（13）C6]5-甲酰四氢叶酸的[（13）C6]5-甲基四氢叶酸AUC是[（13）C6]PteGlu的221%。这些数据表明，PteGlu和5-甲酰四氢叶酸在生理剂量下被认为吸收良好（约90%），但它们在血浆反应的速率和模式上表现出显著差异。PteGlu甲基化前还原速率的限制可能导致源自[（13）C6]PteGlu的[（13）C6]5-甲基四氢叶酸向血浆的黏膜转运较慢。再加上观察到源自任一叶酸试验剂量的[（13）C6]5-甲基四氢叶酸代谢物的血浆清除率相似，这将产生相对较小的AUC。这些发现提示，在使用未标记或标记叶酸进行吸收研究时，如果以血浆叶酸的增加速率、最大增加量或AUC来衡量受试食品（主要是还原型叶酸）与PteGlu“参考剂量”的差异，可能会在解释上存在潜在问题。
