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

ABSTRACT: BACKGROUND:Lycopene, which is a red carotenoid in tomatoes, has been hypothesized to mediate disease-preventive effects associated with tomato consumption. Lycopene is consumed primarily as the all-trans geometric isomer in foods, whereas human plasma and tissues show greater proportions of cis isomers. OBJECTIVE:With the use of compartmental modeling and stable isotope technology, we determined whether endogenous all-trans-to-cis-lycopene isomerization or isomeric-bioavailability differences underlie the greater proportion of lycopene cis isomers in human tissues than in tomato foods. DESIGN:Healthy men (n = 4) and women (n = 4) consumed (13)C-lycopene (10.2 mg; 82% all-trans and 18% cis), and plasma was collected over 28 d. Unlabeled and (13)C-labeled total lycopene and lycopene-isomer plasma concentrations, which were measured with the use of high-performance liquid chromatography-mass spectrometry, were fit to a 7-compartment model. RESULTS:Subjects absorbed a mean ± SEM of 23% ± 6% of the lycopene. The proportion of plasma cis-(13)C-lycopene isomers increased over time, and all-trans had a shorter half-life than that of cis isomers (5.3 ± 0.3 and 8.8 ± 0.6 d, respectively; P < 0.001) and an earlier time to reach maximal plasma concentration than that of cis isomers (28 ± 7 and 48 ± 9 h, respectively). A compartmental model that allowed for interindividual differences in cis- and all-trans-lycopene bioavailability and endogenous trans-to-cis-lycopene isomerization was predictive of plasma (13)C and unlabeled cis- and all-trans-lycopene concentrations. Although the bioavailability of cis (24.5% ± 6%) and all-trans (23.2% ± 8%) isomers did not differ, endogenous isomerization (0.97 ± 0.25 ?mol/d in the fast-turnover tissue lycopene pool) drove tissue and plasma isomeric profiles. CONCLUSION:(13)C-Lycopene combined with physiologic compartmental modeling provides a strategy for following complex in vivo metabolic processes in humans and reveals that postabsorptive trans-to-cis-lycopene isomerization, and not the differential bioavailability of isomers, drives tissue and plasma enrichment of cis-lycopene. This trial was registered at clinicaltrials.gov as NCT01692340.

SUBMITTER: Moran NE

PROVIDER: S-EPMC4658456 | biostudies-literature | 2015 Dec

REPOSITORIES: biostudies-literature

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

Moran Nancy E NE Cichon Morgan J MJ Riedl Kenneth M KM Grainger Elizabeth M EM Schwartz Steven J SJ Novotny Janet A JA Erdman John W JW Clinton Steven K SK

The American journal of clinical nutrition 20151111 6

<h4>Background</h4>Lycopene, which is a red carotenoid in tomatoes, has been hypothesized to mediate disease-preventive effects associated with tomato consumption. Lycopene is consumed primarily as the all-trans geometric isomer in foods, whereas human plasma and tissues show greater proportions of cis isomers.<h4>Objective</h4>With the use of compartmental modeling and stable isotope technology, we determined whether endogenous all-trans-to-cis-lycopene isomerization or isomeric-bioavailability ...[more]

PMID: 26561629

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Project description:Phytoene is a tomato carotenoid that may contribute to the apparent health benefits of tomato consumption. Although phytoene is a less prominent tomato carotenoid than lycopene, it is a major carotenoid in various human tissues. Phytoene distribution to plasma lipoproteins and tissues differs from lycopene, suggesting the kinetics of phytoene and lycopene differ.The objective of this study was to characterize the kinetic parameters of phytoene absorption, distribution, and excretion in adults, to better understand why biodistribution of phytoene differs from lycopene.Four adults (2 males, 2 females) maintained a controlled phytoene diet (1-5 mg/d) for 42 d. On day 14, each consumed 3.2 mg (13)C-phytoene, produced using tomato cell suspension culture technology. Blood samples were collected at 0, 1-15, 17, 21, and 24 h and 2, 3, 4, 7, 10, 14, 17, 21, and 28 d after (13)C-phytoene consumption. Plasma-unlabeled and plasma-labeled phytoene concentrations were determined using ultra-HPLC-quadrupole time-of-flight-mass spectrometry, and data were fit to a 7-compartment carotenoid kinetic model using WinSAAM 3.0.7 software.Subjects were compliant with a controlled phytoene diet, consuming a mean ± SE of 2.5 ± 0.6 mg/d, resulting in a plasma unlabeled phytoene concentration of 71 ± 14 nmol/L. A maximal plasma (13)C-phytoene concentration of 55.6 ± 5.9 nM was achieved 19.8 ± 9.2 h after consumption, and the plasma half-life was 2.3 ± 0.2 d. Compared with previous results for lycopene, phytoene bioavailability was nearly double at 58% ± 19%, the clearance rate from chylomicrons was slower, and the rates of deposition into and utilization by the slow turnover tissue compartment were nearly 3 times greater.Although only differing from lycopene by 4 double bonds, phytoene exhibits markedly different kinetic characteristics in human plasma, providing insight into metabolic processes contributing to phytoene enrichment in plasma and tissues compared with lycopene. This trial was registered at clinicaltrials.gov as NCT01692340.

Project description:ObjectiveBoron neutron capture therapy (BNCT) is a noninvasive radiation therapy method for cancer treatment. In BNCT, 4-borono-2-[18F]-fluoro-L-phenylalanine (18F-FBPA) PET has been employed to estimate 10B accumulation in target tumors and normal tissues if 10B borono-L-phenylalanine (10B-BPA) is used as a boron carrier. The purpose of the current study was to evaluate the total distribution volume (Vt) of 18F-FBPA in normal organs of healthy volunteers by kinetic analysis and to estimate boron concentration in normal organs for the therapeutic dose of 10B-BPA using obtained Vt values.MethodsSix healthy volunteers were injected with 18F-FBPA (3-5 MBq/kg), and 7 PET-CT scans were performed subsequently. 18F-FBPA radioactivity in whole blood and plasma was measured before, and eight times after the injection. PET images were analyzed by PMOD software. Twelve volumetric regions of interest including the brain, heart, right lung, spleen, liver, parotid salivary glands, esophagus, stomach, pancreas, intestines, and bone marrow were drawn manually for each subject and analyzed with the Logan plot and two Ichise multilinear analyses (MA1 and MA2). The better model was defined by several goodness-of-fit parameters and residual distribution. After Vt values had been derived, boron concentration was estimated in ppm for the 10B-BPA-fructose (10B-BPA-fr) dose 30 g 1 and 2 h post-injection using Vt and interpolated plasma activity data.ResultsThe Ichise MA2 model showed the best fit among all models. Akaike Information Criterion (AIC) was the lowest for the Ichise's MA2 in all regions (mean AIC value - 14.0) comparing to the other models (Logan plot mean AIC 31.4; Ichise MA1 model mean AIC - 4.2). Mean Vt values of the Ichise MA2 model ranged from 0.94?±?0.14 ml/ml in the pancreas to 0.16?±?0.02 ml/ml in the right lung. Estimated boron concentration for 10B-BPA-fr had the highest value in the pancreas (14.0?±?1.9 ppm 1 h after, and 5.7?±?1.7 ppm 2 h after the 18F-FBPA administration) and the lowest value in the right lung (2.4?±?0.3 ppm 1 h, and 1.0?±?0.3 ppm 2 h post-injection).ConclusionThe 10B concentration in normal tissues was best estimated using Vt values of 18F-FBPA with the Ichise multilinear analysis 2 (MA2).Trail registryThe UMIN clinical trial number: UMIN000022850.

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

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

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