Vitamin C (ascorbic acid) recommended dietary ingestion

解释 在2000年之前，维生素C和其他维生素的推荐膳食供给量（RDA）是基于预防缺乏症的安全边际。我们建议，以维生素C为模型的维生素新RDA应基于浓度依赖性维生素功能。我们把这种浓度-功能方法称为原位动力学，包括分子和临床成分。一些原位动力学的原则被美国国家科学院采纳，作为所有维生素摄入量的修订建议的一部分。 原位动力学依赖于表征与人体血液和组织中维生素浓度相关的维生素功能。 对于维生素C，这种方法取决于探索维生素C生物化学和分子生物学;维生素C生理学;和维生素C临床药代动力学。 维生素C的临床药代动力学的目标是了解其浓度如何在人体中作为剂量的函数，并揭示其潜在的机制。为了表征这些关系，在NIH临床中心进行了临床研究。健康的年轻男性和女性住院5-7个月，并收集了广泛的药代动力学数据。其中许多数据已经公布。根据这些临床数据的一部分，美国和加拿大的维生素C的RDA在2000年被美国国家科学院向上修订，德国、奥地利、丹麦、法国、日本和中国也增加了RDA。对这些数据的持续分析正在进行中。 基于这些药代动力学数据，我们观察到口服摄入维生素C的广泛剂量范围导致严格控制的血浆和组织浓度。严格控制似乎是由三个协调的生理过程介导的：肠吸收;组织转运/蓄积;和肾过滤/重吸收。 肾脏滤过和重吸收似乎在严密控制中起着核心作用。因此，我们开发了新的建模技术，使我们能够准确地确定维生素C的肾脏阈值。分析的数据包括数千个血浆和尿液数据点，这些数据点是从20名受试者在7种不同维生素C剂量下进行的36小时稳态生物利用度实验中获得的。此外，我们还收集了30名患有涉及肾功能的罕见遗传性疾病的受试者的数据，作为了解维生素C的肾脏阈值是否可以改变的模型。研究正在进行，以确定是否维生素C肾阈值，计算后，广泛的数据分析，深入研究的受试者，可以确认在其他30个健康的受试者使用简单和快速的采样技术。 当这些分析完成时，我们将能够确定与血浆浓度相关的维生素C肾阈值，以及产生该血浆浓度的相应维生素C剂量。维生素C排泄的肾脏阈值作为剂量的函数的这种确定将为维生素C的RDA提供全新的基础，首先在健康人群中，最终在疾病状态中。

Explanation Prior to 2000, recommended dietary allowances (RDAs) for vitamin C and other vitamins were based on preventing deficiency with a margin of safety. We proposed that new RDAs for vitamins, with vitamin C as a model, should be based on concentration-dependent vitamin functions. We termed this concentration-function approach in situ kinetics, with both molecular and clinical components. Some principles of in situ kinetics were adopted by the National Academy of Sciences as part of revised recommendations for all vitamin intakes. In situ kinetics is dependent on characterizing vitamin function in relation to vitamin concentration in human blood and tissues. For vitamin C, this approach depends on exploring vitamin C biochemistry and molecular biology; vitamin C physiology; and vitamin C clinical pharmacokinetics. Goals of clinical pharmacokinetics for vitamin C are to learn how its concentrations are achieved in humans as a function of dose, and to reveal the underlying mechanisms. To characterize these relationships, clinical studies were undertaken at the NIH Clinical Center. Healthy young men and women were hospitalized for 5-7 months, and extensive pharmacokinetics data were collected. Many of these data have been published. Based on portions of these clinical data, RDAs for vitamin C in the United States and Canada were revised upward in 2000 by the National Academy of Sciences, and were also increased in Germany, Austria, Denmark, France, Japan, and China. Continuing analyses of these data are on-going. Based on these pharmacokinetics data, we observed that orally ingested vitamin C a wide dose range resulted in tightly controlled plasma and tissue concentrations. Tight control appeared to be mediated by three coordinated physiologic processes: intestinal absorption; tissue transport/accumulation; and renal filtration/reabsorption. Renal filtration and reabsorption appeared to have a central role in tight control. We have therefore developed new modeling techniques to allow us to accurately determine the renal threshold for vitamin C. Data analyzed include thousands of plasma and urine data points obtained from 36 hour bioavailability experiments conducted at steady state at each of 7 different vitamin C doses in 20 subjects. In addition, we have collected data on 30 subjects with a rare genetic disease that involves renal function, as a model to learn whether the renal threshold for vitamin C can change. Studies are on-going to determine whether the vitamin C renal threshold, calculated after extensive data analyses of intensely studied subjects, can be confirmed in 30 other healthy subjects using simple and rapid sampling techniques. When these analyses are complete, we will be able to determine the vitamin C renal threshold in relation to plasma concentration, and the corresponding vitamin C dose that produces this plasma concentration. Such determination of the renal threshold for vitamin C excretion as a function of dose will provide an entirely new basis for an RDA for vitamin C, first in healthy people and eventually in disease states.