Blatt David H, Pryor William A, Mata John E, Rodriguez-Proteau Rosita
Biodynamics Institute, Louisiana State University, Baton Rouge, LA 70803, USA.
J Nutr Biochem. 2004 Jul;15(7):380-95. doi: 10.1016/j.jnutbio.2003.12.011.
Nutritionists generally consider all-rac-alpha-tocopherol and RRR-alpha-tocopherol equivalent in vitamin E activity but disagree whether equivalency requires a dosage ratio of 1.36:1 or 2:1. In contrast, we hypothesize that all-rac- and RRR-alpha-tocopherols are not equivalent in any dosage ratio. Previous observations that all-rac- and RRR-alpha-tocopherols are distributed and eliminated via saturable and stereospecific pathways imply that their relative bioavailability varies with the saturation of these pathways and therefore varies with dosage. Indeed, previous studies observed that the relative bioavailability of all-rac- and RRR-alpha-tocopherols varies between tissues as well as with dose, time after dosing, and duration of dosing. This non-constant relative bioavailability predicts non-constant relative activity (i.e., non-parallel dose-concentration curves predict non-parallel dose-effect curves). Non-constant relative bioavailability suggests that a fixed dosage ratio of all-rac- and RRR-alpha-tocopherols cannot produce a fixed ratio of effects on all processes in all tissues at all times after all dosages. However, previous studies suggest that all-rac- and RRR-alpha-tocopherols have equivalent effects (parallel dose-effect curves) in vitamin E-deficient animals and non-vitamin E-deficient humans. We re-evaluate the data from these animal studies and find non-parallel dose-effect and concentration-effect curves. We discuss pharmacokinetic and pharmacodynamic reasons why previous studies in non-vitamin E-deficient humans did not find non-parallel dose-effect curves for all-rac- and RRR-alpha-tocopherols. We note that saturable elimination predicts that all-rac- and RRR-alpha-tocopherols might inhibit and/or induce elimination of other compounds (including 30-40% of prescription drugs) eliminated via the same saturable pathways, and stereospecific elimination predicts that all-rac- and RRR-alpha-tocopherol have non-parallel dose-effect curves for these interactions.
营养学家一般认为全消旋-α-生育酚和RRR-α-生育酚在维生素E活性方面相当，但对于这种等效性是否需要1.36:1或2:1的剂量比存在分歧。相比之下，我们假设全消旋-α-生育酚和RRR-α-生育酚在任何剂量比下都不等效。先前的观察表明，全消旋-α-生育酚和RRR-α-生育酚通过可饱和的和立体特异性的途径进行分布和消除，这意味着它们的相对生物利用度会随着这些途径的饱和度而变化，因此也会随剂量而变化。事实上，先前的研究观察到，全消旋-α-生育酚和RRR-α-生育酚的相对生物利用度在不同组织之间以及随剂量、给药后时间和给药持续时间而变化。这种非恒定的相对生物利用度预示着非恒定的相对活性（即，非平行的剂量-浓度曲线预示着非平行的剂量-效应曲线）。非恒定的相对生物利用度表明，全消旋-α-生育酚和RRR-α-生育酚的固定剂量比在所有剂量后的所有时间内，都不能对所有组织中的所有过程产生固定比例的效应。然而，先前的研究表明，全消旋-α-生育酚和RRR-α-生育酚在维生素E缺乏的动物和非维生素E缺乏的人类中具有等效的效应（平行的剂量-效应曲线）。我们重新评估了这些动物研究的数据，发现了非平行的剂量-效应和浓度-效应曲线。我们讨论了药代动力学和药效学方面的原因，解释了为什么先前在非维生素E缺乏的人类中的研究没有发现全消旋-α-生育酚和RRR-α-生育酚的非平行剂量-效应曲线。我们注意到，可饱和消除预示着全消旋-α-生育酚和RRR-α-生育酚可能会抑制和/或诱导通过相同可饱和途径消除的其他化合物（包括30-40%的处方药）的消除，而立体特异性消除预示着全消旋-α-生育酚和RRR-α-生育酚在这些相互作用中具有非平行的剂量-效应曲线。
