β-Cryptoxanthin modulates the response to phytosterols in post-menopausal women carrying NPC1L1 L272L and ABCG8 A632 V polymorphisms: an exploratory study

Abstract

Phytosterol (PS) intake may be used for hypercholesterolaemia in some groups although the presence of non-responders is well known. Carotenoids and PS/ cholesterol may compete for the same transporters during absorption. As part of a randomized, double-blind, crossover, multiple-dose supplementation study with b-cryptoxanthin (b-Cx) and PS, single and combined, polymorphisms of ABCG8 (A632V) and NCPL1 (L272L) were determined in 19 post-menopausal women. Subjects carrying CC polymorphism for NCP1L1 (L272L) showed a net increase in total cholesterol and LDL after PS intake but, interestingly, displayed a decrease in both lipid fractions after consuming PS plus b-Cx. For the ABCG8 (A632V) gene, CT/TT carriers consuming PS also displayed an increase in total cholesterol and LDL, but this increment was much lower after the intake of PS plus b-Cx. Additionally, in CC carriers for ABCG8 (A632V), a greater decrease in total cholesterol and LDL was found after the intake of PS plus b-Cx compared to that observed after PS alone. Overall, our results suggest that b-Cx improves the response to PS in individuals carrying specific genetic polymorphisms (i.e. non-responders), opening the possibility to modulate the response to PS by food technology. (ClinicalTrials.gov NCT01074723).

Common Genetic Variations Involved in the Inter-Individual Variability of Circulating Cholesterol Concentrations in Response to Diets: A Narrative Review of Recent Evidence

“…It is now well-established that dietary plant sterols (PS) can inhibit intestinal cholesterol absorption through several mechanisms, such as competition for incorporation into mixed micelles, hydrolysis of esters by digestive enzymes, enterocyte uptake by NPC1L1, and incorporation into chylomicrons [ 34 , 37 ]. In a randomized crossover supplementation study involving 19 post-menopausal females, participants carrying the CC genotype at rs2072183 (a synonymous variant with leucine at 272, published as L272L) in NPC1L1 showed significantly different changes in serum TC and LDL-C concentrations (0.38 ± 0.29 and 0.33 ± 0.29 mmol/L, respectively) compared to carriers of the G allele (−0.29 ± 0.10, and −0.18 ± 0.12 mmol/L, respectively) after consuming for four weeks a beverage providing 1.5 g PS/d [ 16 ]. Of note, these differences were no longer significant when an outlier in the participants homozygous for the minor allele was excluded from the statistical analysis.…”

“…These data replicate, to some extent, previous associations described among Spanish children [ 45 ], where male carriers of the ABCG5 rs6720173-G allele had higher plasma TC and LDL-C concentrations with a daily intake of 14.3–34.1 g saturated fatty acids (SFA) compared to CC homozygotes [ 45 ]. Another crossover multiple-dose supplementation study with beta-cryptoxanthin and PS in healthy postmenopausal females showed that carriers of the CC genotype of ABCG8 rs6544718 (published as A632V, a missense variant, as defined by the amino acid change) had lower serum TC concentrations (−0.34 ± 0.09 mmol/L) compared to carriers of the T allele (0.08 ± 0.20 mmol/L) after consuming a beverage providing 1.5 g/d of PS plus 750 µg beta-cryptoxanthin over 4 wk [ 16 ].…”

Carotenoids from Haloarchaea and Their Potential in Biotechnology

“…Some of the most important carotenoids in terms of biotechnological and biomedical uses explored so far are: Astaxanthin (3,3′-dihydroxy-β,β′-carotene-4,4′-dione) [ 36 , 39 , 40 ], β-Carotene (β,β-carotene) [ 38 , 41 , 42 , 43 , 44 ], Canthaxanthin (β,β-carotene-4,4′-dione) [ 45 , 46 , 47 , 48 ], β-Cryptoxanthin (hydroxy-β-carotene) [ 38 , 49 , 50 , 51 , 52 , 53 , 54 ], Fucoxanthin [ 38 , 55 ], Lycopene (ψ,ψ-carotene) [ 33 , 56 , 57 ], Lutein (β,ε-carotene-3,3′-diol) [ 42 , 58 , 59 , 60 , 61 ], Zeaxanthin (β,β-carotene-3,3′-diol) [ 38 , 62 , 63 ], and Violaxanthin (5,6:5′,6′-diepoxy-5,5′,6,6′-tetrahydro-β-carotene-3,3′-diol) [ 64 , 65 , 66 , 67 , 68 ].…”

CYP7A1, NPC1L1, ABCB1, and CD36 Polymorphisms Associated with Coenzyme Q10 Availability Affect the Subjective Quality of Life Score (SF-36) after Long-Term CoQ10 Supplementation in Women

“…As described above, rs3808607, rs2072183, and rs1761667 were associated with increased serum cholesterol levels [30,33,34]. In addition, the mean age of the women included in this study was 64.3 years, suggesting that most were menopausal or postmenopausal.…”

“…CYP7A1 and NPC1L1 are involved in cholesterol metabolism. Both the T-allele of rs3808607 and C-allele of rs2072183, associated with the HR phenotype, were found to be involved in the insensitivity of phytosterol-dependent decrease in serum TC levels [30,31]. In addition, the A-allele of rs1761667, associated with the HR phenotype, increased the ratio of people exhibiting high serum cholesterol levels [32].…”