ABSORPT, RETENT & LONG-TERM IMPACT OF VIT A SUPPLEMENTS IN ZAMBIAN CHILDREN

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 赞比亚6个月至5岁的儿童目前计划接受大剂量维生素A补充(6个月至12个月的婴儿为100,000国际单位(30毫克)或儿童为200,000国际单位(60毫克)；=至13个月至60个月)，大约每4-6个月一次，以改善他们的维生素A状况，降低与维生素A缺乏有关的疾病的风险。然而，最近的数据表明，服用高剂量胶囊对这一人群的血清视黄醇浓度影响很小。血清视黄醇浓度低的儿童比例仍然很高(~55%)，这表明维生素A缺乏是一个持续存在的公共卫生问题。 补充计划明显缺乏效果的可能原因是1)高剂量补充剂没有被很好地吸收，2)高剂量补充剂在吸收后迅速排出(保留不良)，3)每日维生素A利用率很高，或4)高剂量补充剂被吸收并保留在肝脏中，但没有动员起来供肝外组织使用。为了调查这些可能性，我们进行了一项研究，以：1)估计3-4岁赞比亚儿童对大剂量维生素A补充剂的吸收和保留，2)估计每日维生素A的利用率，以及3)估计服用大剂量维生素A补充剂之前和之后30天的全身维生素A池大小，以评估补充维生素A是否对身体总维生素A储备有持续的影响。由于感染可能会对维生素A的吸收、滞留和/或利用产生不利影响，而且由于膳食中维生素A的摄入量影响维生素A池的大小，我们还收集了研究期间含维生素A食物的发病率和摄取频率的信息。 为了评估高剂量补充剂对维生素A的吸收和保留，以及每日维生素A的利用率，我们联合服用示踪剂量的14C标记维生素A(25NCI)和高剂量维生素A补充剂(60 Mg)，并分别收集24小时的大便和尿样3天和7天，用于加速器质谱仪(AMS)测量14C含量。AMS是一种极其灵敏的分析方法，可以从生物样品中标记的底物中检测大摩尔(10 18)水平的14C。由于分析方法的高灵敏度，有可能对健康人体安全地给予示踪剂剂量(低纳米库仑(NCI)量)的14C标记底物。目前还没有其他现有的技术来估计人体对维生素A的吸收和滞留。此后，在大约相隔7-12天的另外四个时间点收集24小时尿样。从粪便和尿液中回收的14C量将被用来估计补充剂量的维生素A被吸收和保留了多少；而较长期的14C尿排泄率将提供对维生素A每日利用率(系统分解代谢率)的估计。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Zambian children 6 months to 5 years of age are currently scheduled to receive high-dose vitamin A supplements (100,000 IU (30 mg) for infants 6 mo-12 mo of age or 200,000 IU (60 mg) for children >/= to13 mo-60 mo of age), approximately once every 4-6 months to improve their vitamin A status and lower their risk of diseases associated with vitamin A deficiency. However, recent data indicate that administration of high-dose capsules has little impact on serum retinol concentrations in this population. The proportion of children with low serum retinol concentrations (<0.70 micromol/L) remains high (~55%), indicating a persistent public health problem of vitamin A deficiency. Possible explanations for this apparent lack of effect of the supplementation program are 1) the high-dose supplement is not well-absorbed, 2) the high-dose supplement is rapidly excreted (poorly retained) after absorption, 3) the daily vitamin A utilization rate is high, or 4) the high-dose supplement is absorbed and retained in the liver, but is not mobilized for use by extra-hepatic tissue. To investigate these possibilities, we conducted a study to: 1) estimate absorption and retention of the high dose vitamin A supplement in 3-4 year-old Zambian children, 2) estimate the daily vitamin A utilization rate, and 3) estimate total body vitamin A pool size before, and 30-d after administration of the high-dose vitamin A supplement to assess whether the supplemental vitamin A has a sustained impact on total body vitamin A reserves. Because infection may have an adverse effect on absorption, retention and/or utilization of vitamin A, and because dietary vitamin A intake affects vitamin A pool size, we also collected information on morbidity and frequency of intake of vitamin A-containing foods during the study period. To estimate absorption and retention of vitamin A from the high-dose supplement, and the daily vitamin A utilization rate, we co-administered a tracer dose of 14C-labeled vitamin A (25 nCi) with the high-dose vitamin A supplement (60 mg) and collected 24-hr stool and urine samples for 3 and 7 days, respectively, for measurement of the 14C content by accelerator mass spectrometry (AMS). AMS is an extremely sensitive analytical method that detects attomolar (10 18) levels of 14C from labeled substrates in biological samples. Because of the high sensitivity of the analytical method, it is possible to administer tracer doses (low nanoCuries (nCi) quantities) of 14C labeled substrates safely to healthy humans. There are no other existing techniques for estimating vitamin A absorption and retention in humans. Thereafter, 24-hr urine samples were collected at four additional time points approximately 7-12 days apart. The amount of 14C recovered in stool and urine will be used to estimate how much of the supplemental dose of vitamin A is absorbed and retained; and the longer-term urinary excretion rate of 14C will provide an estimate of the daily utilization rate of vitamin A (system fractional catabolic rate).