University of Wisconsin-Madison, Interdepartmental Graduate Program in Nutritional Sciences, Department of Nutritional Sciences, Madison, WI.
J Nutr. 2018 Aug 1;148(8):1387-1396. doi: 10.1093/jn/nxy095.
Retinol isotope dilution (RID) indirectly estimates vitamin A (VA) status. Multicompartment modeling of RID data is used to refine study designs and equations to calculate VA stores. Previous studies suggest that VA in slowly turning over pools is not traced if follow-up is not long enough; however, shorter RID studies are being investigated. Few long-term models have been published.
We determined the effect of time on mathematical models of VA kinetics, model parameters, and outcomes.
In this longitudinal study, women (mean ± SD age: 22 ± 3 y; n = 7) were given 2.0 µmol [14,15]-13C2-retinyl acetate. Blood samples were staggered from 4 h to 152 d; the fraction of dose in serum was modeled with compartmental models. Four model-time categories were created: full models that used all data (median: 137 d; range 97-152 d) and truncated shorter studies of 14, 27, and 52 d (range: 42-62 d). Outcomes included number of compartments to adequately model serum data, kinetic parameters, total traced VA mass, and time-to-dose equilibration. To gain insight into longer follow-up, an additional participant was given 17.5 µmol 13C4-VA, and data were modeled as long as enrichment was above baseline (5 y).
Longer follow-up times affected kinetic parameters and outcomes. Compared with the 14-d models, long-term full models required an additional compartment for adequate fit (14.3% compared with 100%; P = 0.0056) and had longer [median (quartile 1, quartile 3)] whole-body half-life [15.0 d (10.5, 72.6 d) compared with 135 d (115, 199 d); P = 0.0006], time-to-dose equilibration [3.40 d (3.14, 6.75 d) compared with 18.9 d (11.2, 25.7 d); P < 0.0001], and total traced mass [166 µmol VA (162, 252 µmol VA) compared with 476 µmol VA (290, 752 µmol VA); P = 0.0031].
Extended RID sampling alters numerous mathematically modeled, time-dependent outcomes in women. Length of study should be considered when using mathematical models for calculating total-body VA stores or kinetic parameters related to VA turnover. This study is registered at www.clinicaltrials.gov as NCT03248700.
视黄醇同位素稀释（RID）间接估计维生素 A（VA）状态。RID 数据的多室模型用于改进研究设计和计算 VA 储存的方程。先前的研究表明，如果随访时间不够长，缓慢转化池中的 VA 不会被追踪；然而，正在研究更短的 RID 研究。已经发表了很少的长期模型。
我们确定时间对 VA 动力学数学模型、模型参数和结果的影响。
在这项纵向研究中，给 7 名女性（平均年龄±标准差：22±3 岁；n=7）2.0 µmol [14,15]-13C2-视黄基醋酸酯。血液样本从 4 小时到 152 天错开采集；用房室模型对血清中的剂量分数进行建模。创建了四个模型时间类别：使用所有数据的完整模型（中位数：137 天；范围 97-152 天）和 14、27 和 52 天的截断较短研究（范围：42-62 天）。结果包括充分建模血清数据、动力学参数、总追踪 VA 质量和达到剂量平衡所需的时间的所需房室数量。为了深入了解更长的随访，另一名参与者给予 17.5 µmol 13C4-VA，只要丰度高于基线（5 年），数据就会被建模。
较长的随访时间影响了动力学参数和结果。与 14 天模型相比，长期完整模型需要额外的房室才能充分拟合（14.3%比 100%；P=0.0056），并且具有更长的半衰期[中位数（四分位 1，四分位 3）] [15.0 d（10.5，72.6 d）比 135 d（115，199 d）；P=0.0006]，达到剂量平衡的时间[3.40 d（3.14，6.75 d）比 18.9 d（11.2，25.7 d）；P<0.0001]，以及总追踪质量[166 µmol VA（162，252 µmol VA）比 476 µmol VA（290，752 µmol VA）；P=0.0031]。
RID 采样时间延长会改变女性中许多与时间相关的数学建模结果。在使用数学模型计算全身 VA 储存或与 VA 周转相关的动力学参数时，应考虑研究的长度。本研究在 www.clinicaltrials.gov 上注册为 NCT03248700。
