ASSESSING HIGH DIETARY VITAMIN A

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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. Publications are pending.