Effect of olive oils on biomarkers of oxidative DNA stress in Northern and Southern Europeans Anja Machowetz * ,1 , Henrik E. Poulsen † ,1 ,2 , Sindy Gruendel * , Allan Weimann † , Montserrat Fitó ‡ , Jaume Marrugat ‡ , Rafael de la Torre § , Jukka T. Salonen || , Kristiina Nyyssönen || , Jaakko Mursu || , Simona Nascetti ¶ , Antonio Gaddi ¶ , Holger Kiesewetter †† , Hans Bäumler †† , Hany Selmi †† , Jari Kaikkonen ‡‡ , Hans-Joachim F. Zunft * , Maria-Isabel Covas ‡ and Corinna Koebnick * * German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany; † Department of Clinical Pharmacology, Rigshospitalet, Copenhagen, Denmark; ‡ Lipids and Cardiovascular Epidemiology Unit, Institut Municipal d'Investigació Mèdica, Barcelona, Spain; § Pharmacology Research Unit, Institut Municipal d'Investigació Mèdica, Barcelona, Spain; || Research Institute of Public Health, University of Kuopio, Kuopio, Finland; ¶ Centro per lo Studio dell’Arteriosclerosi e delle Malattie Dismetaboliche "GC Descovich," Dipartimento di Medicina Clinica e Biotecnologia Applicata, Policlinico S. Orsola-Malpighi, Bologna, Italy; †† Institute of Transfusion Medicine, Charité-Universitätsmedizin Berlin, Germany; and ‡‡ Oy Jurilab, Kuopio, Finland 2 Correspondence: Department of Clinical Pharmacology Q7642, Rigshospitalet, Copenhagen University Hospital, 9 Blegdamsvej, DK-2100 Copenhagen, Denmark. E-mail: hepo@rh.dk High consumption of olive oil in the Mediterranean diet has been suggested to protect DNA against oxidative damage and to reduce cancer incidence. We investigated the impact of the phenolic compounds in olive oil, and the oil proper, on DNA and RNA oxidation in North, Central, and South European populations. In a multicenter, double-blind, randomized, controlled crossover intervention trial, the effect of olive oil phenolic content on urinary oxidation products of guanine (8-oxo-guanine, 8-oxo-guanosine and 8-oxo-deoxyguanosine) was investigated. Twenty-five mililiters of three olive oils with low, medium, and high phenolic content were administered to healthy males ( n =182) daily for 3 wk. At study baseline the urinary excretion of 8-oxo-guanosine (RNA oxidation) and 8-oxo-deoxyguanosine (DNA oxidation) was higher in the Northern regions of Europe compared with Central and Southern European regions ( P =0.035). Urinary excretion of the 8 hydroxylated forms of guanine, guanosine, deoxyguanosine and their nonoxidized forms were not different when comparing olive oils with low, medium, and high phenolic content given for 2 wk. Testing the effect of oil from urinary 8-oxo-deoxyguanosine changes from baseline to post-treatment showed a reduction of DNA oxidation by 13% ( P =0.008). These findings support the idea that ingestion of olive oil is beneficial and can reduce the rate of oxidation of DNA. This effect is not due to the phenolic content in the olive oil. The higher DNA and RNA oxidation in Northern European regions compared with that in Central and Southern regions supports the contention that olive oil consumption may explain some of the North-South differences in cancer incidences in Europe.—Machowetz, A., Poulsen, H. E., Gruendel, S., Weimann, A., Fitó, M., Marrugat, J., de la Torre, R., Salonen, J. T., Nyyssönen, K., Mursu, J., Nascetti, S., Gaddi, A., Kiesewetter, H., Bäumler, H., Selmi, H., Kaikkonen, J., Zunft, H. J-F., Covas, M-I., Koebnick, C. Effect of olive oils on biomarkers of oxidative DNA stress in Northern and Southern Europeans. Key Words: phenolic compounds • DNA and RNA damage

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