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

吸收、保留

• 批准号: 7359017
• 负责人: MARJORIE J HASKELL
• 金额: $ 1.47万
• 依托单位: UNIVERSITY OF CALIF-LAWRNC LVRMR NAT LAB
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-01 至 2007-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7359017
• 关键词: ABSORPT; RETENT; LONG; TERM; IMPACT

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 ?13 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 ?mol/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).

该子项目是利用 NIH/NCRR 资助的中心拨款提供的资源的众多研究子项目之一。子项目和研究者 (PI) 可能已从另一个 NIH 来源获得主要资金，因此可以在其他 CRISP 条目中得到体现。列出的机构是中心的机构，不一定是研究者的机构。目前，赞比亚 6 个月至 5 岁的儿童计划大约每 4-6 个月接受一次大剂量维生素 A 补充剂（6 个月至 12 个月的婴儿为 100,000 IU（30 毫克），13 个月至 60 个月的儿童为 200,000 IU（60 毫克）），以改善维生素 A 状况并降低患维生素 A 缺乏相关疾病的风险。然而，最近的数据表明，服用高剂量胶囊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（<0.70μmol/L）的儿童比例仍然很高（~55%），表明维生素A缺乏的公共健康问题持续存在。 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好，2）高剂量补充剂吸收后迅速排泄（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，但没有被肝外组织动员利用。为了调查这些可能性，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) 估计服用高剂量维生素 A 补充剂之前和之后 30 天的全身维生素 A 库大小，以评估补充维生素 A 是否对全身维生素 A 具有持续影响 储备。由于感染可能会对维生素 A 的吸收、保留和/或利用产生不利影响，并且膳食维生素 A 摄入量会影响维生素 A 库的大小，因此我们还收集了研究期间含维生素 A 食物的发病率和摄入频率的信息。 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，我们将示踪剂剂量的 14C 标记维生素 A (25 nCi) 与高剂量维生素 A 补充剂 (60 mg) 共同服用，并分别收集 3 天和 7 天的 24 小时粪便和尿液样本，通过加速器质量测量 14C 含量 光谱测定（AMS）。 AMS 是一种极其灵敏的分析方法，可从生物样品中的标记底物中检测阿托摩尔 (10 ¿18) 水平的 14C。由于分析方法的高灵敏度，可以安全地将 14C 标记底物的示踪剂剂量（低纳居里 (nCi) 量）给予健康人体。没有其他现有技术可以估计人类维生素 A 的吸收和保留。此后，在大约相隔 7-12 天的另外四个时间点收集 24 小时尿液样本。粪便和尿液中回收的 14C 量将用于估计补充剂量的维生素 A 有多少被吸收和保留； 14C 的长期尿排泄率将提供维生素 A 每日利用率（系统分数分解代谢率）的估计。