Physiological compartmental modeling of total lycopene metabolism and its cis/trans isomers in humans

A physiological pharmacokinetic model was developed to describe the disposition of total lycopene and its cis and trans isomers, delivered in a tomato beverage formulation at 5 graded doses (10, 30, 60, 90 or 120 mg), in healthy male subjects (5 per dose). The relationship of triacylglyceride-rich lipoprotein (TGRLP) lycopene concentrations and serum triacylglycerides (TAG) was also investigated to determine if individual differences in lycopene metabolism were related to variations in lipid assimilation.; Blood was collected before dose administration and at scheduled intervals until 672 hours. TGRLP fractions were isolated from the first 12 hour serum samples. Concentrations of carotenoids and vitamins in the serum and TGRLP fractions were measured by HPLC analysis.; The proposed model was comprised of 7 compartments: gastrointestinal tract, enterocytes, chylomicrons, plasma lipoproteins, fast-turnover liver, slow-turnover tissues and a delay compartment before the enterocytes. The predicted percentage absorption at the 10 mg dose (33.9 ± 8.1%) was significantly greater than at the higher doses, however, the amount of lycopene absorbed was not statistically different (mean: 4.69 ± 0.55 mg) between doses, suggesting a possible saturation of absorptive processes. Independent of dose, 80% of the subjects absorbed less than 6 mg of lycopene. This may have important implications for planning clinical trials with pharmacological doses of lycopene in cancer control and prevention.; Pharmacokinetic modeling of lycopene isomers suggested that greater accumulation of cis lycopene in vivo may be related to better absorptive efficiency of cis compared to the trans isomer, greater metabolic loss of trans lycopene, or greater accumulation of cis in the slow-turnover tissue pool compared to trans lycopene.; High interindividual variations in the serum TAG and TGRLP lycopene response were observed. In many subjects hourly changes in TGRLP lycopene and serum TAG concentrations tracked very closely, while in others no associations were observed. Subjects who showed a strong association between serum TAG and TGRLP lycopene displayed a higher rise in serum TAG from baseline, and a larger area-under the concentration time curve for TGRLP lycopene. These findings suggest that individual variations in response to lycopene supplementation may be related to differences in lipid metabolism.