Dual isotope test for assessing beta-carotene cleavage to vitamin A in humans.
BACKGROUND
The ability of beta-carotene to deliver bioactive retinoids to tissues is highly variable. A clearer understanding of the environmental and genetic factors that modulate the vitamin A potential of beta-carotene is needed.


OBJECTIVE
Assess the vitamin A value of orally administered beta-carotene relative to a co-administered reference dose of preformed vitamin A.


METHODS
Equimolar doses (30 micromol) of hexadeuterated D6 beta-carotene and D6 retinyl acetate were orally co-administered in an emulsified formulation to a male subject. The plasma concentration time courses of D6 retinol (derived from D6 retinyl acetate) and bioderived D3 retinol (from D(6) beta-carotene) were determined for 554 h postdosing using gas chromatography/mass spectrometry. Intact D6 beta-carotene plasma concentrations were determined by high-pressure liquid chromatography. The ratio of the two forms of vitamin A, D6 retinol/D3 retinol, at any single time point is postulated to reflect the quantity of vitamin A derived from beta-carotene relative to preformed vitamin A. Additionally, a minute amount of 14C beta-carotene (50 nCi; 0.27 microg) was included in the oral dose and cumulative 24-h stool and urine samples were collected for two weeks to follow absorption and excretion of the b-carotene. The 14C nuclide was detected using accelerator mass spectrometry (AMS). Results During the absorption/distribution phase (3-11 h) the D6/D3 ratio of the two retinols was not stable and ranged between a value of 3 and 16. Between 11 and 98 h postdosing the ratio was relatively stable with a mean value of 8.5 (95 % CI: 7.5, 8.7). These data suggest that in this subject and under these conditions, 8.5 moles of beta-carotene would provide a vitamin A quantity equivalent to 1 mole of preformed vitamin A. On a mass basis, 15.9 microg of beta-carotene was equivalent to 1 microg of retinol. The total administered beta-carotene was found to be 55 % absorbed by AMS analysis of cumulative stool.


CONCLUSIONS
The co-administration of D6 beta-carotene and D6 retinyl acetate provides a technique for assessing individual ability to process beta-carotene to vitamin A. The results indicate that a single time point taken between 11-98 h after dose administration may provide a reliable value for the relative ratio of the two forms of vitamin A. However, results from more subjects are needed to assess the general utility of this method.
Hickenbottom
Sabrina J
SJ
3217A Meyer Hall, Department of Nutrition, University of California, Davis, One Shields Ave, Davis, CA 95616, USA.
Lemke
Shawna L
SL
Dueker
Stephen R
SR
Lin
Yumei
Y
Follett
Jennifer R
JR
Carkeet
Colleen
C
Buchholz
Bruce A
BA
Vogel
John S
JS
Clifford
Andrew J
AJ
D000328:Adult; D001682:Biological Availability; D002250:Carbon Radioisotopes; D003903:Deuterium; D004224:Diterpenes; D005243:Feces / Q000737:chemistry; D006801:Humans; D007700:Kinetics; D008297:Male; D000084562:Retinyl Esters; D014801:Vitamin A / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism* / Q000493:pharmacokinetics; D019207:beta Carotene / Q000097:blood / Q000378:metabolism* / Q000493:pharmacokinetics*
D002250:Carbon Radioisotopes; D004224:Diterpenes; D000084562:Retinyl Esters; D019207:beta Carotene; D014801:Vitamin A; C009166:retinol acetate; D003903:Deuterium