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Tomatoes and cardiovascular diseases

since 1558. Tomatoes and cardiovascular diseases. Volker Böhm Institute of Nutrition, Friedrich Schiller University Jena, Jena, Germany (Volker.Boehm@uni-jena.de). Arrangement. Introduction. Epidemiology. Analysis - HPLC separation - antioxidant activity.

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Tomatoes and cardiovascular diseases

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  1. since 1558 Tomatoes and cardiovascular diseases Volker Böhm Institute of Nutrition, Friedrich Schiller University Jena,Jena, Germany (Volker.Boehm@uni-jena.de)

  2. Arrangement • Introduction • Epidemiology • Analysis - HPLC separation - antioxidant activity • Intestinal absorption of lycopene • Conclusions "Tomatoes and cardiovascular diseases", Murcia, 14.10.2004 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29

  3. Introduction (1) Press releases „Healthy Food can protect against Cancer“ TLZ 24.11.1994 "Tomatoes and cardiovascular diseases", Murcia, 14.10.2004 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29

  4. Introduction (2) „Tomatoes protect the cells“ Press releases „Tomatoes against cancer“ TLZ 07.03.2002 Apotheken-Umschau A 8/98 "Tomatoes and cardiovascular diseases", Murcia, 14.10.2004 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29

  5. Introduction (3) Production of tomatoes (1000 t) for processing (WPTC, World Processing Tomato Council, 2003) "Tomatoes and cardiovascular diseases", Murcia, 14.10.2004 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29

  6. Epidemiology (1) Health Professionals Follow-Up Study (1986-1998) 47365 participants, 2481 cases of prostate cancer lycopene intake (high vs. low quintile): RR=0.84 (0.73-0.96) tomato sauce intake (2 servings/week vs. <1/month): RR=0.77 (0.66-0.90) (E Giovannucci et al., J. Natl. Cancer Inst. 94 (2002) 391-398) (modified to E Giovannucci, J. Natl. Cancer Inst. 91 (1999) 317-331) "Tomatoes and cardiovascular diseases", Murcia, 14.10.2004 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29

  7. Epidemiology (2) Unexpected negative results with -carotene • ATBC-study in Finland • 29133 smokers • 20 mg/d • 18 % increase in lung cancer risk (Heinonen et al. 1994) • CARET-study in USA • 18314 smokers and asbestos workers • 30 mg/d + 25.000 IE vitamin A ( 7.5 mg Retinol) • 28 % increase in lung cancer risk (Omenn et al. 1996) "Tomatoes and cardiovascular diseases", Murcia, 14.10.2004 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29

  8. Epidemiology (3) C. Liu et al., Carcinogenesis 21 (2000) 2245-2253 “... In contrast with a pharmacological dose of -carotene, a physiological dose of -carotene in smoke-exposed ferrets has no potentially detrimental effects and may afford weak protection against lung damage induced by cigarette smoke.” - instability of the -carotene molecule in the free radical rich antioxidant poor environment - increased levels of oxidative metabolites of -carotene "Tomatoes and cardiovascular diseases", Murcia, 14.10.2004 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29

  9. Lycopene and cardiovasular disease "Tomatoes and cardiovascular diseases", Murcia, 14.10.2004 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29

  10. (modified to L Arab and S Steck, Am. J. Clin. Nutr. 71 (2000) 1691S-1695S) "Tomatoes and cardiovascular diseases", Murcia, 14.10.2004 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29

  11. Women‘s Health Study (WHS) (modified to HD Sesso et al., Am. J. Clin. Nutr. 79 (2004) 47-53) "Tomatoes and cardiovascular diseases", Murcia, 14.10.2004 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29

  12. Kuopio Ischaemic Heart Disease Risk Factor Study (KIHD) (modified to TH Rissanen et al., Br. J. Nutr. 85 (2001) 749-754) "Tomatoes and cardiovascular diseases", Murcia, 14.10.2004 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29

  13. Kuopio Ischaemic Heart Disease Risk Factor Study (KIHD) CCA-IMT: intima-media thickness of the common carotid artery (modified to TH Rissanen et al., Am. J. Clin. Nutr. 77 (2003) 133-138) "Tomatoes and cardiovascular diseases", Murcia, 14.10.2004 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29

  14. Analysis (1) Antioxidant activity (1) • interactions with free radicals • stop of radical chain reactions • singlet oxygen quencher • formation of stable radical cations • formation of stable radical adducts "Tomatoes and cardiovascular diseases", Murcia, 14.10.2004 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29

  15. Analysis (2) Antioxidant activity (2) • Lipophilic TEAC assay • TEAC: Trolox equivalent antioxidant capacity • ABTS: 2,2‘-azinobis-(3-Ethylbenzothiazoline-6-sulfonate) • oxidation of ABTS with manganese dioxide • photometrically measurable radical cation ABTS•+, =734 nm • reduction of the radical cation by carotenoids • Trolox equivalents (1 mmol/L Carotenoid  x mmol/L Trolox) "Tomatoes and cardiovascular diseases", Murcia, 14.10.2004 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29

  16. HPLC chromatogram of a tomato paste extract after iodine isomerization. YMC C30,. 1 = lycopene (Z)-isomer no. 1; 2 = lycopene (Z)-isomer no. 2; 3 = lycopene (Z)-isomer no. 3; 4 = (E)-lycopene; 5 = lycopene (Z)-isomer no. 4. Analysis (3) Antioxidant activity (3) Fig. 1: Antioxidant activity (TEAC) of five lycopene isomers compared to that of (E)-b-carotene(V Böhm, NL Puspitasari-Nienaber, MG Ferruzzi, SJ Schwartz, J. Agric. Food Chem. 50 (2002) 221-226) "Tomatoes and cardiovascular diseases", Murcia, 14.10.2004 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29

  17. Study on intestinal absorption of lycopene (1) Human studies on intestinal absorption of lycopene "Tomatoes and cardiovascular diseases", Murcia, 14.10.2004 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29

  18. Study on intestinal absorption of lycopene (2) Own human study (1998) • physiologically relevant doses of lycopene (5 mg/d, 4 w) are better available from tomato juice and lycopene capsules compared to raw tomatoes • no interactions with other carotenoids • no alterations of antioxidant capacity of plasma • no effect on lipid status parameters • (V Böhm, R Bitsch, Eur. J. Nutr. 38 (1999) 118-125) "Tomatoes and cardiovascular diseases", Murcia, 14.10.2004 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29

  19. Study on intestinal absorption of lycopene (3) Own human study (2003) Characterization of volunteers: Fig. 2: Study design "Tomatoes and cardiovascular diseases", Murcia, 14.10.2004 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29

  20. Study on intestinal absorption of lycopene (4) Own human study (2003) Intervention conditions: "Tomatoes and cardiovascular diseases", Murcia, 14.10.2004 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29

  21. Study on intestinal absorption of lycopene (5) Fig. 3: HPLC chromatogram (YMC C30) of human plasma extract after intervention with tomato paste "Tomatoes and cardiovascular diseases", Murcia, 14.10.2004 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29

  22. Study on intestinal absorption of lycopene (6) Fig. 4: Plasma lycopene concentrations (mean + or - sd) over time in subjects of all three intervention groups "Tomatoes and cardiovascular diseases", Murcia, 14.10.2004 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29

  23. Differences in the lycopene isomer pattern between tomato products (A) and human plasma (B) Hypothesis 1: (Z)-isomers are preferred in absorption Hypothesis 2: (Z)-isomers are formed after absorption within the body "Tomatoes and cardiovascular diseases", Murcia, 14.10.2004 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29

  24. Human intervention study with lycopene (23-35 mg/d, 15 d) comprised in tomato products (juice and soup):- after a 7 days depletion period, the relative content of (E)-lycopene decreased from 44.4 % to 39.6 % while the content of (Z)-isomers increased from 55.6 % to 60.4 %  isomerization of (E)-lycopene and/or biological preservation of (Z)-isomers(CW Hadley, SK Clinton, SJ Schwartz, J. Nutr. 133 (2003) 727-732) Fig. 6: Relative portions (mean) of lycopene isomers over time in subjects of the tomato paste group "Tomatoes and cardiovascular diseases", Murcia, 14.10.2004 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29

  25. Relative contents (mean) of lycopene isomers over time in subjects of the three intervention groups "Tomatoes and cardiovascular diseases", Murcia, 14.10.2004 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29

  26. Fig. 7: Plasma lycopene concentrations (mean + sd) over time in non-smokers and smokers consuming daily portions of tomato paste for 2 weeks aftera 2 weeks initial period "Tomatoes and cardiovascular diseases", Murcia, 14.10.2004 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29

  27. Fig. 8: Relative portions (mean) of lycopene isomers over time in smokers consuming daily portions of tomato paste for 2 weeks after a 2 weeks initial period "Tomatoes and cardiovascular diseases", Murcia, 14.10.2004 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29

  28. Conclusions • Lycopene (Z)-isomers might be formed after absorption within the body • Smokers showed a different absorption time course for lycopene and a different isomer pattern compared to non-smokers • Further ongoing studies will look on the metabolism of lycopene more in detail (kinetic studies, oxidation products, etc.) "Tomatoes and cardiovascular diseases", Murcia, 14.10.2004 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29

  29. Acknowledgements THANK YOU FOR YOUR ATTENTION Antje SchmidKarin KaufmannDoreen Reuter Kati Fröhlich Heike SchmidtIrmtraut Schmuck Dr. J. Schlenzka Dr. Th. Sicker Dr. U. Kuhn Dr. Th. Franke Dr. Dietmar Breithaupt Volunteers of the human studies Dr. Jürgen Conrad Prof. Steven Schwartz "Tomatoes and cardiovascular diseases", Murcia, 14.10.2004 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29

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