Carotenoids in biological emulsions: solubility, surface-to-core distribution, and release from lipid droplets

119

The aim of this study was to assess the interindividual variability of chylomicron ␤ -carotene response to a pharmacological load of ␤ -carotene in the population, to identify the mechanisms responsible for this variability, and to evaluate its consequences on ␤ -carotene status and metabolism. The variability, as estimated by the 3-h chylomicron ␤ -carotene response to 120 mg ␤ -carotene in 79 healthy male volunteers, was high (CV ‫؍‬ 61%), but it was unimodal and all the subjects had detectable chylomicron ␤ -carotene. In 16 subjects randomly selected among the 79, the interindividual variability of the triglyceride-adjusted chylomicron ( ␤ -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 ␤ -carotene. The chylomicron ␤ -carotene response was correlated ( r ‫؍‬ 0.50, P Ͻ 0.05) with the chylomicron triglyceride response. The ␤carotene status, as assessed by ␤ -carotene concentration in buccal mucosal cells, was correlated ( r ϭ 0.73, P Ͻ 0.05) with the triglyceride-adjusted chylomicron ␤ -carotene response, i.e., with the ability to respond to ␤ -carotene. The triglyceride-adjusted chylomicron retinyl-palmitate response was correlated ( r ‫؍‬ 0.55, P Ͻ 0.05) with the triglycerideadjusted chylomicron ␤ -carotene response. Plasma all-trans retinoic acid slightly, but significantly, increased ( ؉ 40%) 3 h after the ␤ -carotene load, but this increase was not related to the triglyceride-adjusted ␤ -carotene response. In conclusion, the ability to respond to ␤ -carotene is highly variable, but there is probably a very small proportion of true non-responders to pharmacological doses of ␤ -carotene in the healthy population. This variability is apparently mainly due to interindividual differences in the efficiency of intestinal absorption of ␤ -carotene and in chylomicron metabolism. The ability to respond to ␤ -carotene can affect the ␤carotene status and the provitamin A activity of ␤ -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 ␤ -carotene.

Section: Discussionmentioning

confidence: 83%

Low and high responders to pharmacological doses of β-carotene: proportion in the population, mechanisms involved and consequences on β-carotene metabolism

Borel¹,

Grolier²,

Mekki

et al. 1998

119

“…The second hypothesis of multiple inputs of ␤-carotene from the intestine due to a subsequent meal(s) and/or irregular secretion of lipid has been previously suggested (11,34). This phenomenon has been attributed to the relatively poor solubility of ␤-carotene in triglyceride (51,52), which leads to significant deposition of ␤-carotene within the enterocyte membrane. The ␤-carotene is then released and incorporated into newly synthesized chylomicrons with subsequent fat intake (10).…”

Section: Discussionmentioning

confidence: 97%

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

Dueker

Lin

Buchholz

et al. 2000

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. -

“…As the phenoxyl radical must also terminate itself, it could instead react with a molecule of unoxidized lipid to propagate the chain of lipid oxidation. Perhaps in enriching the LDL in vitro we have incorporated carotenoid only near the surface and not necessarily where they might normally be located (39). Similar to ␣-tocopherol, the carotenoid radical intermediate formed from reaction with an initiating species in the aqueous phase might also react to propagate the chain (pro-oxidation) rather than break the chain (antioxidation).…”

Section: Discussionmentioning

confidence: 99%

Impact of LDL carotenoid and α-tocopherol content on LDL oxidation by endothelial cells in culture

Dugas

Morel

Harrison

1998

Carotenoids and ␣ -tocopherol are dietary, lipophilic antioxidants that may protect plasma lipoproteins from oxidation, a process believed to contribute to atherogenesis. Previous work demonstrated that after the Cu(II)initiated oxidation of human low density lipoprotein (LDL) in vitro, carotenoids and ␣ -tocopherol were destroyed before significant lipid peroxidation took place, and that ␣tocopherol was destroyed at a much faster rate than were the carotenoids. Additionally, in vitro enrichment of LDL with ␤ -carotene, but not with lutein or lycopene, inhibited LDL oxidation. In the present studies the impact of LDL carotenoid and ␣ -tocopherol content on LDL oxidation by human endothelial cells (EaHy-1) in culture was assessed. LDL isolated from 11 individual donors was incubated at 0.25 mg protein/mL with EaHy-1 cells in Ham's F-10 medium for up to 48 h. Formation of lipid hydroperoxides was assessed by chemical analysis and the contents of lutein, ␤cryptoxanthin, lycopene, ␤ -carotene and ␣ -tocopherol were determined by high performance liquid chromatography. The extent of lipid peroxidation correlated with the endogenous ␣ -tocopherol content of the LDL but not with its content of carotenoids. As in the Cu(II)-initiated system, carotenoids and ␣ -tocopherol were destroyed before significant peroxidation took place, but, in the cell-mediated system, ␣ -tocopherol and the carotenoids were destroyed at comparable rates. Also, like the Cu(II)-initiated oxidation, enrichment of the LDL with ␤ -carotene protected it from oxidation by the endothelial cells. However, enrichment with either lutein or lycopene actually enhanced the cell-mediated oxidation of the LDL. Thus, the specific content of carotenoids in low density lipoprotein (LDL) clearly modulates its susceptibility to oxidation, but individual car otenoids may either inhibit or promote LDL oxidation.-