Volker Böhm Institute of Nutrition, Friedrich Schiller University Jena, Jena, Germany Tomatoes and cardiovascular diseases since 1558

"Tomatoes and cardiovascular diseases", Murcia, Arrangement Introduction Epidemiology Analysis - HPLC separation - antioxidant activity Intestinal absorption of lycopene Conclusions

"Tomatoes and cardiovascular diseases", Murcia, Introduction (1) Press releases TLZ „Healthy Food can protect against Cancer“

"Tomatoes and cardiovascular diseases", Murcia, Introduction (2) Press releases Apotheken-Umschau A 8/98 TLZ „Tomatoes protect the cells“ „Tomatoes against cancer“

"Tomatoes and cardiovascular diseases", Murcia, Introduction (3) Production of tomatoes (1000 t) for processing (WPTC, World Processing Tomato Council, 2003)

"Tomatoes and cardiovascular diseases", Murcia, Epidemiology (1) (modified to E Giovannucci, J. Natl. Cancer Inst. 91 (1999) ) Health Professionals Follow-Up Study ( ) participants, 2481 cases of prostate cancer lycopene intake (high vs. low quintile): RR=0.84 ( ) tomato sauce intake (  2 servings/week vs. <1/month): RR=0.77 ( ) (E Giovannucci et al., J. Natl. Cancer Inst. 94 (2002) )

"Tomatoes and cardiovascular diseases", Murcia, Epidemiology (2) Unexpected negative results with  -carotene ATBC-study in Finland smokers 20 mg/d 18 % increase in lung cancer risk (Heinonen et al. 1994) CARET-study in USA smokers and asbestos workers 30 mg/d IE vitamin A (  7.5 mg Retinol) 28 % increase in lung cancer risk (Omenn et al. 1996)

"Tomatoes and cardiovascular diseases", Murcia, Epidemiology (3) C. Liu et al., Carcinogenesis 21 (2000) “... 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, Lycopene and cardiovasular disease

"Tomatoes and cardiovascular diseases", Murcia, (modified to L Arab and S Steck, Am. J. Clin. Nutr. 71 (2000) 1691S-1695S)

"Tomatoes and cardiovascular diseases", Murcia, (modified to HD Sesso et al., Am. J. Clin. Nutr. 79 (2004) 47-53) Women‘s Health Study (WHS)

"Tomatoes and cardiovascular diseases", Murcia, Kuopio Ischaemic Heart Disease Risk Factor Study (KIHD) (modified to TH Rissanen et al., Br. J. Nutr. 85 (2001) )

"Tomatoes and cardiovascular diseases", Murcia, Kuopio Ischaemic Heart Disease Risk Factor Study (KIHD) (modified to TH Rissanen et al., Am. J. Clin. Nutr. 77 (2003) ) CCA-IMT: intima-media thickness of the common carotid artery

"Tomatoes and cardiovascular diseases", Murcia, 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, 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, Fig. 1: Antioxidant activity (TEAC) of five lycopene isomers compared to that of (E)-  -carotene (V Böhm, NL Puspitasari-Nienaber, MG Ferruzzi, SJ Schwartz, J. Agric. Food Chem. 50 (2002) ) HPLC chromatogram of a tomato paste extract after iodine isomerization. YMC C 30,. 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)

"Tomatoes and cardiovascular diseases", Murcia, Study on intestinal absorption of lycopene (1) Human studies on intestinal absorption of lycopene

"Tomatoes and cardiovascular diseases", Murcia, 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) )

"Tomatoes and cardiovascular diseases", Murcia, Study on intestinal absorption of lycopene (3) Own human study (2003) Characterization of volunteers: Fig. 2: Study design

"Tomatoes and cardiovascular diseases", Murcia, Intervention conditions: Study on intestinal absorption of lycopene (4) Own human study (2003)

"Tomatoes and cardiovascular diseases", Murcia, Fig. 3: HPLC chromatogram (YMC C 30 ) of human plasma extract after intervention with tomato paste Study on intestinal absorption of lycopene (5)

"Tomatoes and cardiovascular diseases", Murcia, Fig. 4: Plasma lycopene concentrations (mean + or - sd) over time in subjects of all three intervention groups Study on intestinal absorption of lycopene (6)

"Tomatoes and cardiovascular diseases", Murcia, 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, 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) ) Fig. 6: Relative portions (mean) of lycopene isomers over time in subjects of the tomato paste group

"Tomatoes and cardiovascular diseases", Murcia, Relative contents (mean) of lycopene isomers over time in subjects of the three intervention groups

"Tomatoes and cardiovascular diseases", Murcia, Fig. 7: Plasma lycopene concentrations (mean + sd) over time in non-smokers and smokers consuming daily portions of tomato paste for 2 weeks after a 2 weeks initial period

"Tomatoes and cardiovascular diseases", Murcia, 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, 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, Acknowledgements Antje Schmid Karin Kaufmann Doreen Reuter Kati Fröhlich Heike Schmidt Irmtraut Schmuck Dr. J. Schlenzka Dr. Th. Sicker Dr. U. Kuhn Dr. Th. Franke Volunteers of the human studies Prof. Steven Schwartz THANK YOU FOR YOUR ATTENTION Dr. Dietmar Breithaupt Dr. Jürgen Conrad