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. A steady supply of dietary micronutrients (vitamins) is needed to maintain normal biochemical reactions within humans. Folate is needed to maintain purine and pyrimidine synthesis, and metabolism of homocysteine to methionine. Carotene is a commonly consumed plant pigment (polyene) that is a biological antioxidant and a nutritional precursor of vitamin A. These and other micronutrients have generally been studied within humans at high, non-physiologic, doses in the past using stable or radioactive isotopes. While safe for use in humans, stable isotopes produce kinetic signals that quickly approach natural isotopic levels after a single dose. Radioisotopic labels are sufficicently distinct to provide traceable levels for longer periods, but the risks of radiation exposure limit such uses to populations that are less concerned with possible damage, such as elderly or infirm men. Accelerator mass spectrometry has such high sensitivity for quantifying long-lived isotopes that 14C-labeled micronutrients can now be traced in healthy young people, including particularly women of child-bearing age. Volunteers are given microgram doses of 14C-labeled compounds at radiative doses of 100-200 nCi (6-12 kBq). Blood is frequently collected from an indwelling catheter in the arm during the first day or two to provide high density data reflecting the absorption and initial metabolism phases of the pharmacokinetics. Urinary and fecal collections are made daily during the first two weeks past exposure to provide the quantitative bioavailability of the compound. Blood is then collected occasionally by venipuncture over the next 4-7 months post exposure. Circulating metabolites of the labeled nutrient are seprarted by HPLC. All samples are quantified for 14C concentration by AMS measurement of at least 0.5 mg carbon from the sample. Studies have been performed to examine the metabolism of various nutients including: beta-carotene, folate and vitamin E. Compartmental models are devised for the nutrient based on present best understanding of the absorption, metabolism, and elimination processes. The models are then modified to fit the dense data set of AMS measurements. Such models provide insight into the slowest turning ( and thus the most sustained) pools of nutrients in the volunteers.
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