Journal of Lipid Research, Vol. 23, 480-489, March 1982
Copyright © 1982 by Lipid Research, Inc.

Further validation of the plasma isotope ratio method for measurement of cholesterol absorption in man

Paul Samuel , Donald J. McNamara , E. H. Ahrens Jr. , John R. Crouse , and Thomas Parker

The Rockefeller University, New York, NY 10021

Recently we evaluated an isotope ratio method (IRM) for measurement of cholesterol absorption in 14 patients (15 experiments) hospitalized in the metabolic ward by comparing it to simultaneous measurements with a fecal radioactivity method (FRM) and found good to excellent agreement between two procedures (Samuel, P., J. R. Crouse, and E. H. Ahrens, Jr. 1978 J. Lipid Res. 19: 82-93). This comparison has now been extended to additional studies carried out in eight hospitalized patients (19 experiments). Of the 34 comparisons between the IRM and the FRM in our hands, 29 were technically acceptable (chromic oxide fecal recovery ≥80%): percent cholesterol absorption was 43.1 ± 12% by the FRM and 46.0 ± 11% by the IRM, exhibiting an accuracy within 3.5% at the 95% and 4.7% at the 99% confidence levels. In addition, various procedural modifications of the IRM were studied in out-patients. The measurement of isotope ratios in a single blood sample (analyzed in sextuplicate) on the third day (or later) following the tests gave identical results to those obtained from six to eight daily blood samplings. Blood samples drawn at any time during the day gave cholesterol absorption values similar to those obtained from samples drawn following an overnight fast. Absorption tests carried out before and 1 hr after breakfast, lunch, or dinner, or giving the oral isotope in three divided daily doses all yielded identical results with tests carried out in the am in the fasting state. Cholesterol absorption was markedly reduced when the oral radiolabeled cholesterol was administered in orange juice vs. liquid formula, milk or a solution of glucose and amino acids, consistent with the well-known fact that gallbladder contraction is a critical requirement of cholesterol absorption. A meal high in cholesterol consumed on the day of the test did not influence the results of the absorption measurements. Furthermore, addition of three eggs per day (~750mg cholesterol) for 3 weeks to a low-cholesterol poly-unsaturated fat diet caused no significant change in percent cholesterol absorption in any of eight patients. We conclude that the isotope ratio method accurately and precisely measures cholesterol absorption in man, and that it is suitable not only for in- but also for out-patient studies.—Samuel, P., D. J. McNamara, E. H. Ahrens, Jr., J. R. Crouse, and T. Parker. Further validation of the plasma isotope ratio method for measurement of cholesterol absorption in man.

Supplementary key words dietary cholesterol • fecal neutral steroids • chromic oxide recovery • plasma cholesterol

Submitted on September 1, 1981
Revised on December 16, 1981

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