Long-term kinetic study of β-carotene, using accelerator mass spectrometry in an adult volunteer

We present a sensitive tracer method, suitable for in vivo human research, that uses β-[¹⁴C]carotene coupled with accelerator mass spectrometry (AMS) detection. Using this approach, the concentration-time course of a physiological (306 μg; 200 nCi) oral dose of β-[¹⁴C]carotene was determined for 209 days in plasma. Analytes included β-[¹⁴C]carotene, [¹⁴C]retinyl esters, [¹⁴C]retinol, and several [¹⁴C]retinoic acids. There was a 5.5-h lag between dosing and the appearance of ¹⁴C in plasma. Labeled β-carotene and [¹⁴C]retinyl esters rose and displayed several maxima with virtually identical kinetic profiles over the first 24-h period; elevated [¹⁴C]retinyl ester concentrations were sustained in the plasma compartment for >21 h postdosing. The appearance of [¹⁴C]retinol in plasma was also delayed 5.5 h postdosing and its concentration rose linearly for 28 h before declining. Cumulative urine and stool were collected for 17 and 10 days, respectively, and 57.4% of the dose was recovered in the stool within 48 h postdosing. The stool was the major excretion route for the absorbed dose. The turnover times (1/k(el)) for β-carotene and retinol were 58 and 302 days, respectively. Area under the curve analysis of the plasma response curves suggested a molar vitamin A value of 0.53 for β-carotene, with a minimum of 62% of the absorbed β-carotene being cleaved to vitamin A. In summary, AMS is an excellent tool for defining the in vivo metabolic behavior of β-carotene and related compounds at physiological concentrations. Further, our data suggest that retinyl esters derived from β-carotene may undergo hepatic resecretion with VLDL in a process similar to that observed for β-carotene.