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

Abstract

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.

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

“…In these studies ␤-[ 14 C]carotene doses from 6 to 52 Ci were administered to lymph-cannulated patients with reported absorption values of 8-17% and one extreme at 52% (31,32). Our value of 42.6% ␤-carotene bioavailability is consistent with the prevailing concept (33,34) that ␤-carotene absorption is inefficient, even under favorable absorptive conditions. The fecal output of 14 C was biphasic (Fig.…”

“…As regards the first hypothesis, there are several lines of evidence that suggest retinyl ester secretion with hepatic VLDL: i) The observed parallelism between retinyl esters and ␤-carotene concentration-time course for 24 h postdosing suggests similar metabolism; this is significant because ␤-carotene undergoes hepatic resecretion with VLDL (45); ii) experiments in dogs have documented retinyl ester secretion from the liver (46); and iii) approximately 5-10% of the total vitamin A in fasting plasma is present in the form of retinyl esters and several studies have shown that retinyl esters can travel with hepatically derived VLDL and LDL (42,(47)(48)(49)(50). 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.…”

Serum α- and β-Carotene Concentrations Qualitatively Respond to Sustained Carrot Feeding

“…In fact, the highest responder had AUC of 5.20 and 4.18 lmolÁd/L and the lowest responder had AUC of 0.577 and 0.089 lmolÁd/L for the high and low b-carotene muffins, respectively. The phenomenon of low and high responders to b-carotene supplementation is well documented in the literature (27). Further studies should determine if this is due to differences in absorption, altered chylomicron metabolism ( 27), or differences in the ability to cleave b-carotene to vitamin A.…”

Proteins involved in uptake, intracellular transport and basolateral secretion of fat-soluble vitamins and carotenoids by mammalian enterocytes

“…They have also been obtained with very variable doses of FSV&C, which were incorporated into different matrices and ingested in different meals. Knowing that i) FSV&C absorption is affected by numerous factors, including FSV&C dose, food matrix and meal nutrients [19], ii) absorption is probably mediated by intestinal proteins at dietary doses but is probably passive at pharmacological doses, and iii) there is a huge interindividual variability in the absorption efficiency of most FSV&C [62,63], all these factors likely explains the huge variability in published data.…”

“…On the whole, this review of the literature shows that it is difficult to provide a single narrow range for the absorption efficiency of each FSV&C in humans. This is likely because absorption of FSV&C is affected by numerous factors [19], but also because there is a huge inter-individual variability in the absorption efficiency of these molecules [62,63].…”