Low and high responders to pharmacological doses of beta-carotene: proportion in the population, mechanisms involved and consequences on beta-carotene metabolism.
The aim of this study was to assess the interindividual variability of chylomicron beta-carotene response to a pharmacological load of beta-carotene in the population, to identify the mechanisms responsible for this variability, and to evaluate its consequences on beta-carotene status and metabolism. The variability, as estimated by the 3-h chylomicron beta-carotene response to 120 mg beta-carotene in 79 healthy male volunteers, was high (CV = 61%), but it was unimodal and all the subjects had detectable chylomicron beta-carotene. In 16 subjects randomly selected among the 79, the interindividual variability of the triglyceride-adjusted chylomicron (beta-carotene + retinyl palmitate) response (0-12.5 h area under the curve) was high (CV = 54%), suggesting that there is a high interindividual variability in the efficiency of intestinal absorption of beta-carotene. The chylomicron beta-carotene response was correlated (r = 0.50, P < 0.05) with the chylomicron triglyceride response. The beta-carotene status, as assessed by beta-carotene concentration in buccal mucosal cells, was correlated (r = 0.73, P < 0.05) with the triglyceride-adjusted chylomicron beta-carotene response, i.e., with the ability to respond to beta-carotene. The triglyceride-adjusted chylomicron retinyl-palmitate response was correlated (r = 0.55, P < 0.05) with the triglyceride-adjusted chylomicron beta-carotene response. Plasma all-trans retinoic acid slightly, but significantly, increased (+40%) 3 h after the beta-carotene load, but this increase was not related to the triglyceride-adjusted beta-carotene response. In conclusion, the ability to respond to beta-carotene is highly variable, but there is probably a very small proportion of true non-responders to pharmacological doses of beta-carotene in the healthy population. This variability is apparently mainly due to interindividual differences in the efficiency of intestinal absorption of beta-carotene and in chylomicron metabolism. The ability to respond to beta-carotene can affect the beta-carotene status and the provitamin A activity of beta-carotene, but it has apparently no effect on the amount of retinoic acid appearing in the plasma after the ingestion of a pharmacological dose of beta-carotene.
Borel
P
P
Unité des Maladies Métaboliques et des Micronutriments, INRA Clermont-Ferrand 63000, France.
Grolier
P
P
Mekki
N
N
Boirie
Y
Y
Rochette
Y
Y
Le Roy
B
B
Alexandre-Gouabau
M C
MC
Lairon
D
D
Azais-Braesco
V
V
D000284:Administration, Oral; D000328:Adult; D000975:Antioxidants / Q000494:pharmacology*; D002914:Chylomicrons / Q000097:blood; D004305:Dose-Response Relationship, Drug; D002149:Energy Intake; D005247:Feeding Behavior; D006801:Humans; D015474:Isotretinoin / Q000097:blood; D008297:Male; D014212:Tretinoin / Q000097:blood; D019207:beta Carotene / Q000008:administration & dosage / Q000494:pharmacology*
D000975:Antioxidants; D002914:Chylomicrons; D019207:beta Carotene; D014212:Tretinoin; D015474:Isotretinoin