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

该子项目是利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得主要资金， 因此可以在其他CRISP条目中表示。列出的机构是 研究中心，而研究中心不一定是研究者所在的机构。 赞比亚6个月至5岁的儿童目前计划接受高剂量维生素A补充剂（6个月至12个月的婴儿为100，000 IU（30 mg），>/= 13个月至60个月的儿童为200，000 IU（60 mg）），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，高剂量胶囊给药对该人群的血清视黄醇浓度几乎没有影响。 血清视黄醇浓度低（<0.70微摩尔/升）的儿童比例仍然很高（约55%），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解释是：1）高剂量补充剂吸收不良，2）吸收后高剂量补充剂迅速排出（保留不良），3）每日维生素A利用率高，或4）高剂量补充剂被吸收并保留在肝脏中，但未被肝外组织动员使用。 为了研究这些可能性，我们进行了一项研究：1）估计3-4岁赞比亚儿童对高剂量维生素A补充剂的吸收和保留，2）估计每日维生素A利用率，3）估计全身维生素A库的大小，以及在施用高剂量维生素A补充剂后30天，以评估补充的维生素A是否对全身维生素A储备具有持续影响。 由于感染可能对维生素A的吸收、保留和/或利用产生不利影响，并且由于膳食维生素A摄入量影响维生素A库的大小，因此我们还收集了研究期间含维生素A食物摄入的发病率和频率的信息。 为了估计高剂量补充剂中维生素A的吸收和保留，以及每日维生素A利用率，我们将示踪剂量的14 C标记的维生素A（25 nCi）与高剂量维生素A补充剂（60 mg）共同给药，并分别收集3天和7天的24小时粪便和尿液样本，通过加速器质谱法（AMS）测量14 C含量。 AMS是一种非常灵敏的分析方法，可检测阿摩尔浓度（10 18)生物样品中标记底物的14 C水平。 由于分析方法的高灵敏度，可以将示踪剂剂量（低纳居里（nCi）量）的14 C标记底物安全地给予健康人体。 没有其他现有的技术来估计人体对维生素A的吸收和保留。 此后，在另外4个时间点（间隔约7-12天）采集24小时尿样。 粪便和尿液中回收的14 C量将用于估计补充剂量的维生素A被吸收和保留的量; 14 C的长期尿排泄率将提供维生素A每日利用率（系统分解代谢率）的估计值。

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).