Stable isotopic abundances as reflections of ingestion practices

The proportions of stable isotopes found in biological tissues (e.g., 13C/12C, 15N/14N, or 18O/16O) are constant only on a macroscopic scale. Sensitive mass spectrometric measurements of the isotope ratio or isotopic abundance for each element show that the tissue (and organism) displays small excursions in these abundances, which are reflections of isotope fractionations that occur in prior stages of the food chain. These excursions can be detected in respiratory CO2 in urine, and in stool, with changes over time intervals as short as 2 hours or as long as 6-12 months. Perturbation of these stable isotopic abundances has been used to demonstrate phenomena as gross as the change in carbon sources of milk proteins when cows are moved from winter silage to summer pastures, or as subtle as the utilization of a single feeding of complex carbohydrates by infants by measuring the isotopic abundance of their respiratory CO2. The use of marker molecules enriched with 13C, 15N, or 18O thus provides a nonpharmacological, nonradioactive, and under ideal conditions, noninvasive procedure to document the ingestion of single or multiple doses of the pharmacological agent being tested. Such generic markers are potentially suitable for all study populations, regardless of developmental age, reproductive activity, or degree of compliance.