ASSESSING HIGH DIETARY VITAMIN A

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。 目的：进一步明确长期高维生素A饮食对人体的影响。 最近对被用作人类生物医学研究模型的恒河猴(Macaca Mulatta)的维生素A(VA)状况的研究揭示了肝脏VA的亚毒性浓度。他们食用的普通研究饮食提供的VA量是NRC推荐的四倍。为了进一步确定恒河猴的VA状态，使用雄性恒河猴进行了一项涉及稳定同位素和肝脏活检的研究。我们在16只雄性恒河猴中的8只(11.9±2.9岁)的化学筛查资料中发现了“异常”的乳酸脱氢酶。LDH升高是令人担忧的，因为它是肝病或功能障碍的标志，这是维生素A中毒的直接结果。此外，由于致畸方面的考虑，怀孕期间禁止摄入过多的预制维生素A。为了探讨过量摄入维生素A对早期胎肝维生素A储存的影响，对35~93d龄猴胎肝中维生素A(n=19)和维甲酸(n=9)进行了分析。在所有的胎儿肝脏中都发现了视黄酸酯，而视黄醇作为百分比在较年轻的胎儿中更为明显。肝脏VA含量随胎龄增加而升高(r=0.98P 0.0001)，最小胎龄(35d)和最大胎龄(93d)分别为0.0011~0.26m ol/g。妊娠早期肝脏VA浓度为0.023±0.008摩尔/克，中期为0.19±0.008摩尔/克。妊娠早期全反式维甲酸浓度(99.2±57.0pmol/g，n=6)高于孕中期(18.2±6.1pmol/g，n=3)，但差异有统计学意义。妊娠中期的胎儿肝脏中的VA浓度高于发育后期的人和猴的肝脏，后者被认为是生长和VA积累率最高的阶段。因此，母亲摄入过多的预制维生素A会导致早期胎儿肝脏视黄酸酯的储存被放大。 这项研究使用了WNPRC Research Services。 出版物： 作者：Dever JT，Tanumihardjo SA.实验非人类灵长类动物中的维生素A过多：证据、原因和康复之路。我是J普利马托尔。2009年10月；71(10)：813-6。

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. Objective: To further define the effects of chronically high dietary vitamin A. Recent work examining the vitamin A (VA) status of rhesus monkeys (Macaca mulatta) used as models for human biomedical research revealed subtoxic hepatic VA concentrations. They consume common research diets that provide up to four times the amount of VA recommended by the NRC. To further define VA status in rhesus monkeys, male rhesus monkeys were used for a study that involved stable isotopes and liver biopsies. We found "abnormal" lactate dehydrogenase values in the chemistry screening profiles in 8 of the 16 male rhesus monkeys (11.9 ¿ 2.9 y). Elevation of LDH is cause for concern as it is a marker of liver disease or malfunction, which is a direct outcome of vitamin A toxicity. Furthermore, excessive preformed VA intake is contraindicated during pregnancy due to teratogenic concerns. To investigate overconsumption of preformed VA on early fetal liver VA storage, monkey fetal livers ranging from 35 to 93 d gestational age were analyzed for VA (n = 19) and retinoic acid (n = 9). Retinyl esters were identified in all fetal livers, and retinol, as a percentage, was more pronounced in younger fetuses. Liver VA concentration increased with gestational age (r = 0.98, P 0.0001), ranging from 0.0011 to 0.26 ¿mol/g in the youngest (35 d) and oldest fetuses (93 d), respectively. Liver VA concentrations were 0.023 ¿ 0.008 ¿mol/g in early gestation and 0.19 ¿ 0.06 ¿mol/g in mid-gestation fetuses. All-trans retinoic acid concentrations were higher in early gestation (99.2 ¿ 57.0 pmol/g, n = 6) than in mid-gestation (18.2 ¿ 6.1 pmol/g, n = 3), but were variable. Liver VA concentrations from mid-gestation fetuses were higher than those observed in fetal human and monkey livers from later stages of development, when growth and VA accumulation rates are assumed to be highest. Thus, excessive intake of preformed VA by the mothers results in amplified early fetal liver retinyl ester storage. This research used WNPRC Research Services. PUBLICATION: Dever JT, Tanumihardjo SA. Hypervitaminosis A in experimental nonhuman primates: evidence, causes, and the road to recovery. Am J Primatol. 2009 Oct;71(10):813-6.