Compartmental and noncompartmental modeling of 13C-lycopene absorption, isomerization, and distribution kinetics in healthy adults

Moran, Nancy E.; Cichon, Morgan J.; Riedl, Ken M.; Grainger, Elizabeth M.; Schwartz, Steven J.; Novotny, Janet A.; Erdman, John W.; Clinton, Steven K.

doi:10.3945/ajcn.114.103143

Cited by 48 publications

(53 citation statements)

References 51 publications

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“…However, it has also been emphasized that ADME‐related factors, including digestion and matrix release, solubilisation in mixed micelles, epithelial uptake in the (small) intestine, and further bio‐distribution, all prerequisites for exerting potential biological effects, can be different between individuals. This likely results in variable blood/tissue concentrations . However, blood plasma/serum alone may not constitute the best indicator to assess carotenoid status, and additional methods, such as isotopic labelling, similar as for retinoids or easy accessible compartments such as white blood cells or buccal cells , may allow for more insights regarding endogenous carotenoid levels, carotenoid compartments, and turnover .…”

Section: Introductionmentioning

confidence: 99%

Host‐related factors explaining interindividual variability of carotenoid bioavailability and tissue concentrations in humans

Bohn

Desmarchelier

Dragsted

et al. 2017

Molecular Nutrition Food Res

192

159

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Carotenoid dietary intake and their endogenous levels have been associated with a decreased risk of several chronic diseases. There are indications that carotenoid bioavailability depends, in addition to the food matrix, on host factors. These include diseases (e.g. colitis), life‐style habits (e.g. smoking), gender and age, as well as genetic variations including single nucleotide polymorphisms that govern carotenoid metabolism. These are expected to explain interindividual differences that contribute to carotenoid uptake, distribution, metabolism and excretion, and therefore possibly also their association with disease risk. For instance, digestion enzymes fostering micellization (PNLIP, CES), expression of uptake/efflux transporters (SR‐BI, CD36, NPC1L1), cleavage enzymes (BCO1/2), intracellular transporters (FABP2), secretion into chylomicrons (APOB, MTTP), carotenoid metabolism in the blood and liver (LPL, APO C/E, LDLR), and distribution to target tissues such as adipose tissue or macula (GSTP1, StARD3) depend on the activity of these proteins. In addition, human microbiota, e.g. via altering bile‐acid concentrations, may play a role in carotenoid bioavailability. In order to comprehend individual, variable responses to these compounds, an improved knowledge on intra‐/interindividual factors determining carotenoid bioavailability, including tissue distribution, is required. Here, we highlight the current knowledge on factors that may explain such intra‐/interindividual differences.

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Section: Introductionmentioning

confidence: 99%

Host‐related factors explaining interindividual variability of carotenoid bioavailability and tissue concentrations in humans

Bohn

Desmarchelier

Dragsted

et al. 2017

Molecular Nutrition Food Res

192

159

View full text Add to dashboard Cite

show abstract

“…Stable isotope labeling provides an alternative low-risk approach, where 13 C-labeled carotenoids can be consumed at concentrations found in the diet. This strategy has been used to study β-carotene absorption and conversion to vitamin A [ 16 , 17 ], as well as lycopene [ 18 ] and phytoene [ 19 ] pharmacokinetics.…”

Section: Introductionmentioning

confidence: 99%

Identification of an Epoxide Metabolite of Lycopene in Human Plasma Using 13C-Labeling and QTOF-MS

et al. 2018

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The carotenoid lycopene is a bioactive component of tomatoes and is hypothesized to reduce risk of several chronic diseases, such as prostate cancer. The metabolism of lycopene is only beginning to be understood and some studies suggest that metabolites of lycopene may be partially responsible for bioactivity associated with the parent compound. The detection and characterization of these compounds in vivo is an important step in understanding lycopene bioactivity. The metabolism of lycopene likely involves both chemical and enzymatic oxidation. While numerous lycopene metabolites have been proposed, few have actually been identified in vivo following lycopene intake. Here, LC-QTOF-MS was used along with 13C-labeling to investigate the post-prandial oxidative metabolism of lycopene in human plasma. Previously reported aldehyde cleavage products were not detected, but a lycopene 1,2-epoxide was identified as a new candidate oxidative metabolite.

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“…However, there is no evidence to suggest that the cis -lycopene isomer has any additional health benefits over the trans - form. Kinetic studies in adults have shown that the proportion of cis -lycopene isomers increase over time, and trans -lycopene isomers have a shorter half-life than cis -lycopene isomers [ 25 , 26 ]; however, the kinetics of lycopene isomers have not been studied in neonates. Therefore, we could speculate that the beneficial effects of lycopene on growth are more profound after the conversion of trans-lycopene to the more biologically active cis -lycopene, and mechanisms by which this conversion is performed may be immature in a newborn infant.…”

Section: Discussionmentioning

confidence: 99%

“…Improvements in analytical technology in recent years have led to the discovery that lycopene in human blood and tissue is distributed among 10–20 different isomers [ 25 ]. Typical food sources of lycopene contain 60–95% trans -lycopene [ 25 ], however; tissue and plasma have higher concretions of cis -lycopene, possibly due to post-absorptive trans -to- cis -lycopene isomerization [ 26 ]. However, the transfer from mother to fetus of these isomers, or differing impacts on maternal-newborn outcomes, has rarely been investigated.…”

Section: Introductionmentioning

confidence: 99%

Serum Lycopene Concentrations and Associations with Clinical Outcomes in a Cohort of Maternal-Infant Dyads

et al. 2018

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Oxidative stress has been associated with adverse neonatal outcomes, and many carotenoids, including lycopene, potentially have antioxidant properties. The objective of this analysis was to explore the associations between serum lycopene concentrations, including lycopene isomers, and maternal-newborn outcomes. Maternal and cord blood samples were collected in 180 mother-infant pairs. Serum of total lycopene as well as the cis- and trans-isomers concentrations were measured using HPLC (High Performance Liquid Chromatography). Descriptive statistics were calculated; Spearman coefficients were used to assess correlations between maternal and cord concentrations. The relationship between lycopene concentration and outcomes were evaluated with linear and logistic regression models, with adjustment for relevant confounders. A p ≤ 0.05 was considered statistically significant. Maternal and cord serum lycopene concentrations were positively correlated for total lycopene (r = 0.30, p < 0.0001), cis-lycopene (r = 0.29, p = 0.0002); and trans-lycopene (r = 0.32, p < 0.0001). Maternal concentrations of cis-lycopene were significantly lower in mothers whose infants developed respiratory distress syndrome compared to those who did not (0.336 ± 0.171 vs. 0.445 ± 0.238 µmol/L, p = 0.04) and also in mothers whose babies were admitted to the newborn intensive care unit compared to those who were not (0.380 ± 0.202 vs. 0.458 ± 0.244 µmol/L, p = 0.04). Conversely, cord concentrations of trans-lycopene were significantly higher in infants who developed RDS (Respiratory Distress Syndrome) (0.023 ± 0.012 vs. 0.016 ± 0.012, p = 0.007 for RDS vs. no RDS), and a similar pattern was seen NICU admission (0.023 ± 0.016 vs. 0.015 ± 0.009 µmol/L for NICU (Newborn Intensive Care Unit) admission vs. no NICU admission, p = 0.007). Maternal concentrations of total and cis-lycopene were positively associated with infant birth weight, length and head circumference after adjustment for relevant confounders. As serum carotenoids, including lycopene, are modifiable by diet, future research determining the clinical impact of these compounds is warranted.

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Compartmental and noncompartmental modeling of 13C-lycopene absorption, isomerization, and distribution kinetics in healthy adults

Cited by 48 publications

References 51 publications

Host‐related factors explaining interindividual variability of carotenoid bioavailability and tissue concentrations in humans

Host‐related factors explaining interindividual variability of carotenoid bioavailability and tissue concentrations in humans

Identification of an Epoxide Metabolite of Lycopene in Human Plasma Using 13C-Labeling and QTOF-MS

Serum Lycopene Concentrations and Associations with Clinical Outcomes in a Cohort of Maternal-Infant Dyads

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