This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. 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).
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