How Do Nutritional and Hormonal Status Modify the Bioavailability, Uptake, and Distribution of Different Isomers of Lycopene? Dr. John Erdman, University of Illinois-Urbana-Champaign Metabolic/disease factors unrelated to food intake that may affect lycopene absorption and metabolism include: 1) fat malabsorption syndromes and intestinal parasites; 2) some hypolipidemic drugs; 3) liver or kidney disease; 4) hypothyroidism or hyperthyroidism; 5) anorexia nervosa, bulimia, or weight loss; 6) stage of estrous cycle; and 7) androgen status. The isomer composition of lycopene (cis versus trans) in tomato products changes with processing. These differences in isomer composition may have a metabolic impact, affecting factors such as the ability to influence health outcomes, antioxidant properties, susceptibility to oxidation, specificity of enzymatic cleavage and metabolism, and differential uptake and accumulation in tissues. The literature suggests that the differential accumulation of lycopene in tissues may be: 1) correlated to the number of low-density lipoprotein receptors, 2) dependant on the amount of fat in tissues, 3) preferentially taken up by reproductive tissues, 4) dependant on the “metabolic rate” of tissues, 5) dependant on binding/transport proteins within tissues, 6) a result of differences in cis versus trans uptake and metabolism, or 7) related to tissue “needs” of the tissues. Regarding hormonal status, androgen depletion or 20% food restriction has been found to increase hepatic lycopene and vitamin E accumulation. Thus, higher androgen status or greater energy consumption may stimulate lycopene metabolism and degradation. Data on the effects of stage of the estrous cycle on lycopene metabolism are varied, and many of the metabolic effects are not yet well understood. Future research opportunities include an investigation of the following: 1) why cis isomers are differentially taken up by tissues; 2) why tomato carotenoids (lycopene, phytoene, and phytofluene) are either taken up or accumulate in a differential manner tissue to tissue; and 3) why androgen levels appear to affect lycopene accumulation. In addition, work should continue on identifying important tomato components other than lycopene (e.g., phytoene and phytofluene). Discussion There is evidence that lycopene stability and cis and trans isomer levels may be related to the thermodynamic stabilities of the various lycopene forms. Lycopene in solution rapidly isomerizes to form a mixture of isomers (the half-life of lycopene in solution is on the order of hours). It appears that lycopene is stabilized in the chloroplast of the tomato but also in human cells (where lycopene persists for days, not hours). One participant suggested that lycopene might be localized in the lipid bilayers of cells. Dr. Erdman replied that little is known about lycopene localization within cells. The data have shown that the size of the bilayers, as well as the polarity of lycopene, would make it impossible for lycopene to exist perpendicular to the membrane. Lycopene may exist between the bilayers or be associated with lipid droplets or lipids within cells. A participant asked about the evidence that cis isomers are preferentially absorbed, given the short time period (minutes) required for isomerization. Once the lycopene leaves the plant matrix in the gut (where it is stabilized), the lycopene must either come out of solution and quickly isomerize or remain in lipid as it is absorbed. Dr. Erdman replied that artificial micelles, similar in size to micelles of the human gut, were used to explore the solubility of all-trans versus cis isomers. Cis isomers were found to preferentially accumulate in those micelles. The difference between the small intestine contents and mucosal cells in terms of percent cis also suggests that cis forms are absorbed preferentially. A participant commented that, with regard to hormone status, his laboratory observed higher accumulations of lutein and zeaxanthin in female versus male Japanese quail. His laboratory also is working on the NHANES analysis, and their data will include phytoene and phytofluene for the general human population. An immediate precursor to lycopene in biosynthesis is phytofluene, and the immediate precursor to phytofluene is phytoene. The structures of phytoene, phytofluene, and lycopene differ by only one or two saturated double bonds. One participant asked why these small structural differences would have such a significant effect on uptake of the compounds. Dr. Erdman speculated about the existence of preferential transport proteins. Another participant speculated that the higher accumulation of lycopene in the liver could be for storage lycopene, as is the case with other antioxidants. Dr. Erdman stated that he dislikes the word “storage” because a mechanism that blockes movement is implied. He noted, the liver also transports newly absorbed carotenoids out of the liver, so it is possible that there is no storage mechanism keeping lycopene in the liver. Another participant commented that castration is usually associated with changes in lipid metabolism. He asked if the lycopene accumulation could be explained by the fact that castration is modifying lipid metabolism, perhaps via the proportionally higher estradiol concentration. Dr. Erdman replied that this is plausible, but when the testosterone implants are added, lycopene returns to its normal level 2/05 NIH Meeting Remember we are NOT Doctors and have NO medical training. This site is like an Encylopedia - there are many pages, many links on many topics. 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