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

Abstract

We present a sensitive tracer method, suitable for in vivo human research, that uses ␤ -[ 14 C]carotene coupled with accelerator mass spectrometry (AMS) detection. Using this approach, the concentration-time course of a physiological (306 g; 200 nCi) oral dose of ␤ -[ 14 C]carotene was determined for 209 days in plasma. Analytes included ␤ -[ 14 C]carotene, [ 14 C]retinyl esters, [ 14 C]retinol, and several [ 14 C]retinoic acids. There was a 5.5-h lag between dosing and the appearance of 14 C in plasma. Labeled ␤ -carotene and [ 14 C]retinyl esters rose and displayed several maxima with virtually identical kinetic profiles over the first 24-h period; elevated [ 14 C]retinyl ester concentrations were sustained in the plasma compartment for Ͼ 21 h postdosing. The appearance of [ 14 C]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 ␤ -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 ␤ -carotene, with a minimum of 62% of the absorbed ␤ -carotene being cleaved to vitamin A.In summary, AMS is an excellent tool for defining the in vivo metabolic behavior of ␤ -carotene and related compounds at physiological concentrations. Further, our data suggest that retinyl esters derived from ␤ -carotene may undergo hepatic resecretion with VLDL in a process similar to that observed for ␤ -carotene. -

β-Carotene Conversion to Vitamin A Decreases As the Dietary Dose Increases in Humans

“…Plasma kinetic curves observed in this study were in accord with previously published data (12)(13)(14) and with previously proposed mechanisms of b-carotene absorption, metabolism, and distribution. Inspection of individual subject curves showed that, for most participants, b-carotene-d8 produced 2 plasma peaks, as observed previously (15)(16)(17)(18)(19), with the first representing b-carotene being transported by intestinally derived, triglyceriderich lipoproteins and the second peak representing b-carotene primarily in LDL (19,20).…”

New insights and changing paradigms in the regulation of vitamin A metabolism in development

“…[80][81][82] Circulating carotenoids and retinyl esters are also found associated with lipoproteins including very low density lipoproteins. 83,84 Retinyl ester-containing chylomicron remnants are endocytosed by hepatocytes and hydrolysed through the activity of several carboxylesterases and lipases. 84,85 Other ester hydrolases found in target tissues, such as lipoprotein lipase, hydrolyze retinyl esters from chylomicrons and allow cells to take up the free retinol.…”

New chemical evidence for the ability to generate radical molecular ions of polyenes from ESI and HR-MALDI mass spectrometry

“…7 Kinetic studies of carotenoids and retinoids in human and animal systems were traditionally performed using radioisotope labelling, but more recently mass spectrometric analysis has become more frequently applied. 8 Liquid chromatography in combination with tandem mass spectrometry (LC-MS/MS) is a powerful analytical technique for structure determination. Advances in the development of high-resolution MS and the elucidation of gas-phase fragmentation chemistry are now aiding in the characterisation and analysis of new compounds and new chemical reactions.…”