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Supplement: Promises and Perils of Lycopene/Tomato Supplementation and Cancer Prevention

How Can the Metabolomic Response to Lycopene (Exposures, Durations, Intracellular Concentrations) in Humans Be Adequately Evaluated?¹

Department of Food Science and Interdisciplinary Graduate Program in Nutrition, The Ohio State University, Columbus, OH 43210

²To whom correspondence should be addressed. E-mail: schwartz.177{at}osu.edu.

KEY WORDS: • lycopene • exposure • bioavailability • tomato • isomers

	EXPANDED ABSTRACT

TOP EXPANDED ABSTRACT CONCLUSIONS LITERATURE CITED

 
Lycopene, the carotenoid present at high concentrations in tomatoes and tomato products, has attracted considerable attention because epidemiological evidence continues to suggest that this compound may provide protection against cancer and other degenerative diseases. Although this antioxidant serves as a useful blood and tissue biomarker uniquely indicative of tomato-product consumption, the array of other phytochemicals in tomato products must also be the focus of additional research. Estimates of lycopene consumption do not necessarily provide an accurate measure of biological exposure. Studies of blood-lycopene concentrations and estimated lycopene intake may show correlations in the range of 0.21 to 0.47, suggesting that our ability to estimate biological effects of lycopene will require additional insight into bioavailability and metabolism based on carefully controlled clinical studies. Many questions remain regarding lycopene bioavailability from food sources, effects of food processing, the influence of other dietary constituents (such as fat or fiber), and the role of food preparation (1). Additional research to define the relations among carotenoid intake, absorption, tissue distribution, and biological effects is clearly necessary to address the potential health benefits of tomato products and lycopene consumption. Among the many poorly understood complexities of lycopene are the issues of cis-isomer formation in vivo, metabolism and interconversion of isomers, and the biological effects or functions of specific isomers (2). Analytical technology improvements in recent years have provided tools to separate and detect several different isomers of lycopene in human blood and tissue.

At Ohio State University, we have conducted several pilot clinical studies to further our understanding of lycopene absorption, distribution, and clearance. Standard-size portions of tomato products were found to increase plasma and breast-milk lycopene concentrations in lactating woman and therefore could increase the lycopene status of nursing infants. Results suggest that consumption of tomato sauce increases milk-lycopene concentrations more effectively than consumption of fresh tomatoes (3). In a separate study of healthy adults consuming single daily servings of processed tomato products, blood and buccal mucosal cell lycopene concentrations increased after a 4-wk intervention after washout. As expected, lycopene levels in blood decreased during the 2-wk washout period, reducing to 50% from baseline levels. The estimated half-life for lycopene in these subjects was 10–14 d. Blood lycopene levels ranged from 0.5 to 1.5 µmol/L, with the highest concentrations obtained for those individuals consuming tomato sauce. The plasma response data generated in this study suggest that the bioavailability of lycopene differs among commercial tomato products available to consumers. Buccal mucosa cell lycopene deposition was found in greater amounts for those individuals consuming tomato sauce, reflecting the lycopene plasma response (4). To detect lycopene in small quantities of buccal cells, an HPLC procedure using electrochemical detection was used to enhance the sensitivity for this analysis, allowing measurement of low quantities of lycopene deposited in this tissue (nmoles/µg protein). In a similarly designed study, both lycopene concentration and isomer patterns were observed to change rapidly with variation in dietary intake. Increases in plasma total antioxidant capacity were also observed. In addition, a Cu⁺² mediated oxidation lag phase of lipoproteins increased significantly from washout through treatment during tomato product consumption, suggesting that these interventions may reduce susceptibility of lipoproteins to oxidative stress (5).

A pilot clinical trial with prostate cancer patients (28 men, 7 per group) was conducted. Subjects were placed on a lycopene-free diet (washout) for 1 wk and then randomized to consume 1 of 3 tomato products (juice, soup, or sauce) daily for 3 wk. A control group consumed a soy protein supplement daily for the 21-d period before surgery. Blood levels of those subjects consuming tomato products increased significantly for all 3 groups. The control group consuming the soy protein supplement showed a significant decrease in lycopene blood concentrations relative to baseline (after washout). Prostate tissue from all 28 subjects was collected and analyzed for carotenoid content. Although a number of prostate carotenoids were detected, only lycopene levels were significantly higher in men consuming tomato-based products when compared with concentrations in men consuming soy. No significant difference in prostate lycopene was noted among the 3 tomato product interventions; however, greater deposition of lycopene in those subjects consuming the more thermally processed tomato sauce and soup was noted relative to juice. Interestingly, the percentage of prostate all-trans-lycopene (20%) and total cis-lycopene (80%) was not different among the tomato-based product and soy groups after the treatment phase.

Postprandial experiments monitoring newly absorbed carotenoids present within the lipoprotein chylomicron fraction provide another means to evaluate lycopene absorption from specific food products or formulated meals. In collaboration with Iowa State University, we conducted a study where salads containing tomatoes were consumed with full-fat, reduced-fat, and fat-free dressings. Area under the curve measurements of carotenoids were determined. A marginal postprandial response was observed for lycopene when a no-fat dressing was added; however, a significant enhancement was observed when the salad was consumed with a full-fat dressing. This approach was used to show the importance of co-consumed lipid to efficiently absorb lycopene and other carotenoids from a meal (6).

Although dietary lipids are hypothesized to be an important factor for carotenoid bioavailability, most carotenoid-rich fruits and vegetables are low in lipids. The objective of this latter study was to assess whether avocado addition as a lipid source enhances carotenoid and lycopene absorption in humans after salsa consumption both with and without avocado. Healthy subjects were recruited for this crossover postprandial study (n = 11 per study). The effect of avocado addition (150 g) to salsa on lycopene and ß-carotene absorption was examined. Intact carotenoids were quantified in plasma triacylglycerol-rich lipoprotein fraction over 9.5 h after test meal consumption and expressed as baseline-corrected area under the concentration-vs.-time curve (AUC). Salsa consumption with avocado significantly enhanced lycopene and ß-carotene absorption (P < 0.003), resulting in 4.4 and 2.6 times the mean AUC of avocado-free salsa, respectively. In conclusion, avocado can significantly enhance carotenoid absorption from salsa, which can be attributed primarily to the lipids present in avocado (7).

Lastly, postprandial studies indicated that cis-lycopene isomers present in differently processed tomato sauces were absorbed to a greater extent than all-trans-lycopene. In addition, area under the curve measurements of lycopene isomers present in unique tomato varieties also indicated enhanced uptake of cis-lycopene relative to all-trans-lycopene.

	CONCLUSIONS

TOP EXPANDED ABSTRACT CONCLUSIONS LITERATURE CITED

 
In summary, a few considerations from this research are highlighted.

1. The physical state of lycopene within the plant tissue, crystalline, amorphous, or soluble within lipid phase affects uptake from the matrix that will influence blood and tissue levels.
   
2. Concentrations of lycopene in blood and tissues can be altered after consumption of typical commercial tomato products within relatively short intervention periods.
   
3. Processing through physical and thermal treatments has the potential to enhance absorption by disruption of the plant-tissue matrix, disassociation of carotenoid-protein complexes, enhanced surface area, and increases in solubility.
   
4. Structural considerations influencing solubility, molecular size, and geometrical isomerization to cis-lycopene isomers can enhance bioavailability.
   
5. Relative to other carotenoids in the diet, lycopene is poorly absorbed; however, co-consumed lipid is critical and enhances absorption from the tomato matrix.
   

	FOOTNOTES

 
¹ Presented as part of the conference "Promises and Perils of Lycopene/Tomato Supplementation and Cancer Prevention," February 17–18, 2005, Bethesda, MD. This conference was sponsored by the Division of Cancer Prevention, Division of Cancer Epidemiology and Genetics, Center for Cancer Research, National Cancer Institute (NCI), National Institutes of Health (NIH), Department of Health and Human Services (DHHS); Office of Dietary Supplements (ODS), NIH, DHHS; and the Agricultural Research Services (ARS), USDA. Guest editors for the supplement publication were Cindy D. Davis, NCI, NIH; Johanna Dwyer, ODS, NIH; and Beverly A. Clevidence, ARS, USDA.

	LITERATURE CITED

TOP EXPANDED ABSTRACT CONCLUSIONS LITERATURE CITED

 

1. Gärtner, C., Stahl, W. & Sies, H. (1997) Lycopene is more bioavailable from tomato paste than from fresh tomatoes. Am. J. Clin. Nutr. 66:116-122.[Abstract/Free Full Text]

2. Clinton, S. K., Emenhiser, C., Schwartz, S. J., Bostwick, D. G., Williams, A. W., Moore, B. J. & Erdman, J. W. (1996) Lycopene stereoisomers, carotenoids and retinol in the human prostate. Cancer Epidemiol. Biomark. Prev. 5:823-833.[Abstract]

3. Allen, C. M., Smith, A. M., Clinton, S. K. & Schwartz, S. J. (2002) Tomato consumption increases lycopene isomer concentrations in breast milk and plasma of lactating women. J. Am. Diet. Assoc. 102:1257-1262.[Medline]

4. Allen, C. M., Schwartz, S. J., Craft, N. E., Giovannucci, E. L., DeGroff, V. L. & Clinton, S. K. (2003) Changes in plasma and oral mucosal lycopene isomer concentrations in healthy adults consuming standard servings of processed tomato products. Nutr. Cancer 47:48-56.[Medline]

5. Hadley, C. W., Schwartz, S. J. & Clinton, S. K. (2003) The consumption of processed tomato products enhances plasma lycopene concentrations in association with a reduced lipoprotein sensitivity to oxidative damage. J. Nutr. 133:727-732.[Abstract/Free Full Text]

6. Brown, M. J., Ferruzzi, M. G., Nguyen, M. L., Cooper, D. A., Eldridge, A. L., Schwartz, S. J. & White, W. S. (2004) Carotenoid bioavailability from salads ingested with full-fat than with fat-reduced salad dressing as measured with electrochemical detection. Am. J. Clin. Nutr. 80:396-403.[Abstract/Free Full Text]

7. Unlu, N. Z., Bohn, T., Clinton, S. K & Schwartz, S. J. (2005) Enhanced carotenoid absorption in humans from salad and salsa with addition of avocado or avocado oil. J. Nutr. 135:431-436.[Abstract/Free Full Text]

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