COLTIVAZIONE DELL’OLIVO • Origini: 5000 a.C. (Medio Oriente) • 4500 a.c. Codice di Hammurabi • In Italia: 500 a.c. • 800 milioni di piante nel mondo • 700 milioni di piante nel Mediterraneo Mediterranean Diet Dietary patterns found in olive growing regions of the Mediterranean Countries Basso rischio cardiovascolare Basso rischio di cancro “Vantaggio” Mediterraneo RUOLO DELL’OLIO D’OLIVA IMPORTANZA BIOLOGICA DELL’OLIO D’OLIVA • MUFA - Fluidità di membrana cellulare • ANTIOSSIDANTI - Anti radicali liberi - Anti perossidazione • MALATTIE CARDIOSVACOLARI - LDL - colesterolo - Ipertrigliceridemia IMPORTANZA BIOLOGICA DELL’OLIO D’OLIVA • APPARATO DIGERENTE - attività della colecisti - secrezione pancreatica • CANCRO - > apoptosi - oncogene ras, - < addotti al DNA WITH MEDITERRANEAN DIET: < 10% PROSTATE, PANCREAS, ENDOMETRIUM < 25% COLON < 15% BREAST (Trichopoulou et al., 2000) CANCER RISK FACTORS FATS The issue of fats, and of specific types of fats, on the risk of colorectal and breast cancers, as well as of several other neoplasms, remains a major open question. RRs and 95% CI of selected cancers according to RED MEAT consumption. Italy, 1983-1997 CARNE & CANCRO DEL COLON Meta-analisi, IARC, Lione 2002 Carni lavorate 1.8 1.6 1.2 Pesce 1 0.8 Tutte le carni Carni bianche 1.4 Carni rosse 0.6 Cohort studies Case-control studies All studies GENETICA E DIETA Nei Giapponesi emigrati negli Stati Uniti: Marcato aumento del cancro del colon in soggetti con genotipo rapid NAT2: Ma solo in chi consumava carni rosse molto cotte J Natl Cancer Inst Monogr 1999;(26):101-5 COMBINED INFLUENCE OF GENETIC AND DIETARY FACTORS ON COLORECTAL CANCER INCIDENCE IN JAPANESE AMERICANS. Marchand LL. (Honolulu, USA) Cancer Epidemiol Biomarkers Prev 2002 Jun;11(6):541-8 DIET ACTIVITY, AND LIFESTYLE ASSOCIATIONS WITH P53 MUTATIONS IN COLON TUMORS. Slattery ML, Curtin K et al. (Salt Lake City, USA) P53: tumor suppressor gene Casi con mutazione del gene P53 più frequentemente: consumano una dieta “occidentale” presentano indice glicemico alto seguono una dieta ricca in carni rosse e fast food GRASSI N-6 E N-3 IN RAPPORTO TRA ACIDI VARIE POPOLAZIONI POPOLAZIONI n-6:n-3 Periodo paleolitico 0,79 Grecia prima del 1960 1,00 / 2,00 Stati Uniti 2000 16,74 Regno Unito e Nord Europa 15 Giappone 4 Italia 13 RRs and 95% CI of selected cancers according to FISH consumption. Italy, 1983-1997. N-3 Polyunsaturated fatty acids QUINTILE OF INTAKE CASES/CONTROLS (N) 3RD 5TH (HIGHEST) Oral cavity/pharynx 736/1772 0.7 (0.5-0.9) 0.5 (0.3-0.7) Oesophagus 395/1066 0.7 (0.5-1.1) 0.5 (0.3-0.7) Large bowel 2280/4765 1.0 (0.9-1.2) 0.7 (0.6-0.9) Colon 1394/4765 0.9 (0.8-1.1) 0.7 (0.5-0.8) Rectum 886/4765 1.1 (0.9-1.4) 0.8 (0.6-1.0) Breast 2900/3122 1.0 (0.8-1.1) 0.8 (0.7-1.0) Ovary 1031/2411 0.8 (0.6-1.0) 0.6 (0.4-0.7) CANCER SITE OMEGA-3 & CANCRO (olio di pesce) DHA Riduce l’espressione di COX-2 Induce apoptosi (Da Caterina,01) Olive oil & Colorectal cancer Tertile of intake 2 3 (high) Colorectal 0.78 (0.62-0.99) 0.77 (0.59-0.99) Colon 0.79 (0.59-1.04) 0.82 (0.60-1.12) Rectum 0.79 (0.57-1.11) 0.69 (0.46-1.02) FATS In a large study from Italy, isocaloric substitution of 5% of total calories as saturated fats by unsaturated ones was associated with reductions in breast (OR= 0.67) and colorectal (OR= 0.78) cancer risk FATS DIETARY CHANGE BREAST (OR 95% CI) COLON RECTUM (OR 95% CI) Replacement of saturated fat by complex carbohydrate (10% of cal.) 0.95 (0.73-1.25) 0.96 (0.74-1.24) Replacement of saturated fat by polyunsaturated fat (5% of cal.) 0.67 (0.54-0.83) 0.78 (0.65-0.95) Replacement of complex carbohydrate by polyunsaturated fat (5% of cal.) 0.69 (0.58-0.81) 0.80 (0.69-0.93) FATS DIETARY CHANGE BREAST (OR 95% CI) COLON RECTUM (OR 95% CI) Replacement of saturated fat by monounsaturated fat (5% of cal.) 0.91 (0.73-1.12) 0.89 (0.73-1.09) Replacement of complex carbohydrate by monounsaturated fat (5% of cal.) 0.93 (0.83-1.04) 0.91 (0.82-1.00) Olive oil Oral and pharyngeal cancer UPPER LIMIT - (g per day) INTAKE QUINTILE 1 3 5 3.2 29.5 - OR (95% CI) 1 0.7 (0.5-1.1) 0.4 (0.3-0.7) Vegetable-adjusted OR (95% CI) 1 0.8 (0.5-1.2) 0.6 (0.4-0.9) Mixed seed oils 0.3 2.3 - OR (95% CI) 1 1.0 (0.7-1.4) 1.1 (0.7-1.7) Vegetable-adjusted OR (95% CI) 1 0.9 (0.6-1.4) 1.1 (0.7-1.7) 0.4 1.9 - OR (95% CI) 1 1.3 (0.8-1.9) 2.3 (1.6-3.5) Vegetable-adjusted OR (95% CI) 1 1.3 (0.9-2.0) 2.4 (1.6-3.5) Olive oil Butter FATS Substituting olive oil for other seasoning fats has favourable effects on the risk of oral, laringeal and pharyngeal (OR= 0.7), and oesophageal (OR= 0.4) cancers Mediterranean diet score and cancers of the upper digestive tract An a priori defined score, summarising eight of the major characteristics of the Mediterranean diet, was applied to data of case-control studies of oral (n=599), oesophageal (n=304) and laryngeal (n=460) cancers Diet and cancers of the upper digestive tract CANCER, OR (95% CI) ORAL/PHARYNGEAL OESOPHAGEAL LARYNGEAL Monounsaturated/ saturated fat ratio 0.72 (0.56-0.93) 0.73 (0.51-1.01) 0.97 (0.73-1.28) Alcohol 4.26 (3.11-5.83) 6.04 (3.79-9.62) 2.77 (2.01-3.83) Legumes 1.09 (0.87-1.38) 1.03 (0.74-1.42) 0.75 (0.58-0.98) Cereals 0.77 (0.59-1.00) 0.96 (0.67-1.38) 0.92 (0.68-1.24) Fruit 1.06 (0.83-1.35) 0.95 (0.68-1.31) 0.82 (0.62-1.07) Vegetables 0.79 (0.62-1.01) 0.72 (0.51-1.01) 0.51 (0.39-0.67) Meat and meat products 1.42 (1.11-1.81) 1.50 (1.06-2.13) 1.53 (1.15-2.04) Milk and dairy products 1.09 (0.86-1.40) 1.24 (0.87-1.75) 1.07 (0.81-1.42) Mediterranean diet score and cancers of the upper digestive tract (Bosetti, ‘03) Cancer Mediterranean diet score <3 6 4 Oral/pharyngeal Cases/controls OR (95% CI) 214/241 120/376 41/201 1 0.41 (0.30-0.57) 0.40 (0.26-0.62) 102/147 66/174 14/83 1 0.63 (0.41-0.95) 0.26 (0.13-0.51) 183/225 98/279 19/124 1 0.47 (0.33-0.66) 0.23 (0.13-0.40) Oesophageal Cases/controls OR (95% CI) Laryngeal Cases/controls OR (95% CI) Pizza and cancer risk Pizza is one of the best known and most widespread Italian foods, and it is the most common generic commercial sign worldwide. Investigating the role of pizza on cancer risk may have interesting implications in respect to dietary advice not only in Italy Pizza and cancer risk OR (95% CI) CANCER OCCASIONAL REGULAR ALL EATERS Oral cavity and pharynx 0.76 (0.60-0.95) 0.66 (0.47-0.93) 0.73 (0.59-0.91) Oesophagus 0.57 (0.42-0.78) 0.41 (0.25-0.69) 0.53 (0.39-0.72) Larynx 0.86 (0.66-1.11) 0.82 (0.56-1.19) 0.85 (0.66-1.08) Colon 0.84 (0.72-0.97) 0.74 (0.61-0.89) 0.81 (0.70-0.93) Rectum 0.85 (0.71-1.02) 0.93 (0.75-1.17) 0.88 (0.74-1.04) Cancer Causes Control 2000 Aug;11(7):609-15 MEN WHO CONSUME VEGETABLE OILS RICH IN MONOUNSATURATED FAT: THEIR DIETARY PATTERNS AND RISK OF PROSTATE CANCER (NEW ZEALAND). Norrish AE, Jackson RT et al. (Auckland, New Zealand) 317 prostate cancer cases vs 480 controls. Increasing levels of MUFA-rich vegetable oil intake were associated with a progressive reduction in prostate cancer risk - multivariate relative risk = 0.5 (> 5.5 ml per day vs. nonconsumption - P trend = 0.005) Prostate cancer risk was not associated with intake of total MUFA or the major animal food sources of MUFA CONCLUSION: 1) protective effect of an associated dietary pattern high in antioxidants and fish oils. 2) Independent protective effect of MUFA-rich vegetable oils unrelated to the MUFA component PHENOLIC AND LIPID COMPONENTS OF OLIVE OILS-2: THE CONCENTRATION AND ANTIOXIDANT ACTIVITY OF TOTAL PHENOLS, SIMPLE PHENOLS, SECOIRIDOIDS, LIGNANS AND SQUALENE. Robert W. Owen,1 Attilio Giacosa,2 Walter Mier, Bertold Spiegelhalder1 and Helmut Bartsch1 1German Cancer Research Center, Heidelberg, Germany 2National Institute of Cancer Research, Genoa, Italy TOTAL AND INDIVIDUAL PHENOLIC COMPOUNDS IN OLIVE OIL PHENOLIC COMPOUND mg/kg OLIVE OIL ALL VOQ RVO P value Total 196 19 232 15 62 12 < 0.00001 Hydroxytyrosol 11.66 2.60 14.42 3.01 1.74 0.84 < 0.05 Tyrosol 22.13 3.82 27.45 4.05 2.98 1.33 < 0.01 Total simple phenols (TSP) 33.79 4.48 41.87 6.17 4.72 2.15 < 0.01 SID-1 7.97 2.57 9.62 3.18 2.00 0.87 ns SID-2 15.75 3.54 18.09 4.31 7.30 3.01 ns Total secoiridoids (SID) 23.71 5.61 27.72 6.84 9.30 3.81 ns Lignans 34.09 4.42 41.53 3.93 7.29 2.56 < 0.001 TSP + SID + LIGNANS 91.59 10.57 111.12 9.99 21.31 8.03 < 0.001 POLYPHENOLS 350 300 250 200 150 100 50 0 Extra-vergin Refined Seed oil LIGNANS 90 80 70 60 50 40 30 20 10 0 Extra-vergin Refined Seed oil Eur J Cancer Prev 2002 Aug;11(4):351-8 Cancer chemoprevention by hydroxytyrosol isolated from virgin olive oil through G1 cell cycle arrest and apoptosis. Fabiani R, De Bartolomeo A, Rosignoli P, Servili M, Montedoro GF, Morozzi G. (Perugia, Italy) Hydroxytyrosol inhibited proliferation of both human promyelocytic leukaemia cells HL60 and colon adenocarcinoma cells HT29 At concentrations ranging from 50 to 100 micromol/l, hydroxytyrosol induced an appreciable apoptosis Hydroxytyrosol (50-100 micromol/l) arrested the cells in the G0/G1 phase with a concomitant decrease in the cell percentage in the S and G2/M phases. Scavenging of ROS generated in the faecal matrix by tyrosol isolated from olive oil. Dihydroxy benzoic acids (%) 100 Tyrosol (µ M) 20 0.01 0.1 1 10 100 1000 10000 J Agric Food Chem 2002 Oct 9;50(21):5962-7 Influence of thermal treatments simulating cooking processes on the polyphenol content in virgin olive oil. Brenes M, Garcia A, Dobarganes MC et al. (Sevilla, Spain) • Thermal oxidation: – rapid degradation of alpha-tochopherol – 180°: < tyrosol and tydroxytyrosol for 25 h.: lignans unchanged • Microwave: – for 10 min.: minor losses • Pressure cooker: – for 30 min: losses of polyphenols at ph <6 – alpha-tocopherol: not modified • Lignans: the least affected polyphenols SQUALENE 400 SQUALENE MG/100G 350 300 250 200 150 100 50 0 Extra-vergin Refined Seed oil Squalene: potential chemopreventive agent. Smith TJ. (University of South Carolina, USA), 2000 The average intake: 30 mg/day in the United States 200-400 mg/day in Mediterranean countries (olive oil). Experimental studies have shown that squalene can effectively inhibit chemically-induced colon, lung and skin tumourigenesis in rodents. The mechanisms involved: •inhibition of Ras farnesylation, •modulation of carcinogen activation •anti-oxidative activities. Int J Cancer 2000 Aug 1;87(3):444-51 Diet, metabolic polymorphisms and dna adducts: the EPIC-Italy cross-sectional study. Palli D, Vineis P, Russo A, et al. (Florence, Italy) DNA adducts in peripheral leukocytes: reliable indicator of internal dose exposure to genotoxic agents and cancer risk. EPIC-Italy (section of European prospective study): 47,749 men and women, aged 35-64 years, in 5 centres. Among 309 volunteers, 72.8% had detectable levels of DNA adducts. Strong negative associations emerged with the reported frequency of consumption of fresh fruit and vegetables, olive oil, and the intake of antioxidants. DNA adducts were higher in subjects with GSTT1 null genotype (p = 0.05). Cancer Preventive role of olive oil Study project Italy Greece Spain CASES CONTROLS 12000 10000 1500 1500 ? ? Dieta Mediterranea e prevenzione dei tumori e delle malattie cardiovascolari MICRONUTRIENTI & SOSTANZE BIOATTIVE VIT. C, E, ACIDO FOLICO, SE FRUTTA & VERDURA LUTEINA VEGETALI GIALLI E VERDI LICOPENE POMODORO FLAVONOIDI FRUTTA & VERDURA, THE, VINO CUMARINE AGRUMI DITIOLTIONI ISOTIOCIANATI CRUCIFERE INDOLO-3- CARBINOLO DIALLIL SOLFIDE ALLIL METIL TRISOLFIDE AGLIO FLAVONOIDI * Responsabili dei colori di molti vegetali * Presenti in semi, agrumi, the, vino rosso * Azione antiossidante e antiproliferativa CAROTENOIDI E CANCRO • Luteina • Zeaxantina < incidenza Ca mammella (premenopausa) > apoptosi < Ca mammella (in storia familiare positiva!) Vegetali gialli (arance, carote, pomodori) Spinaci, broccoli, sedano ANTIOSSIDANTI E FRUTTA (Unità ORAC) • • • • • • • • • • • Arancia 1 Succo di arancia 1 bicchiere Fragole una tazza Prugne nere 3 Mirtilli 1 tazza Melone 3 fette Pesca 1 Mela 1 Spinaci cotti 1 tazza Succo di uva nera un bicchiere More 1 tazza 983 unità 1142 unità 1170 unità 1454 unità 3480 unità 197 unità 222 unità 301 unità 2042 unità 5216 unità 1466 unità ANTIOSSIDAN TI E FRUTTA (Unità ORAC) • • • • • • • • • • • Arancia 1 983 unità Succo di arancia 1 bicchiere 1142 unità Fragole una tazza 1170 unità Prugne nere 3 1454 unità Mirtilli 1 tazza 3480 unità Melone 3 fette 197 unità Pesca 1 222 unità Mela 1 301 unità Spinaci cotti 1 tazza 2042 unità Succo di uva nera un bicchiere 5216 unità More 1 tazza 1466 unità IL TUMORE DELLO STOMACO QUANTA FRUTTA E VERDURA ? • • • • • 500 – 600 g al giorno Almeno 5 porzioni al giorno Ogni porzione in più: < 10% rischio di CRC La più ampia varietà possibile Stagionalità, locoregionalità CALORIE ,PESO e SALUTE (?!?) • CALORIE & CANCRO DEL COLON Studio Italiano COLON-RETTO Quintili di Calorie ORs (95% CI) 1 1 2 1.10 (0.92-1.31) 3 1.18 (0.99-1.42) 4 1.16 (0.97-1.39) 5 1.50 (1.25-1.80) Continuous (100 kcal/day) 1.02 (1.01-1.03) (Franceschi ,Giacosa et al, 97) ATTIVITA’ FISICA E CANCRO DEL COLON Rischio relativo 2 1 0.6 0 1 2 3 4 5 Livello di attività fisica Slattery et al, 97 CARBOIDRATI & CANCRO DEL COLON Studio Italiano COLON-RETTO Alimenti ORs in highest vs lowest quintile (95% CI) Pane e farinacei 1.69 (1.36-2.10) Dolci 1.13 (0.93-1.37) Zucchero 1.43 (1.19-1.73) Patate 1.20 (0.96-1.51) (Franceschi ,Giacosa et al, 97) CHO & CANCRO DELLA MAMMELLA Quintile di consumo 1 (basso) 2 3 4 5 (alto) Carboidrati disponibili OR 1 1.05 1.13 1.16 1.29 1 1.05 1.28 1.24 1.39 Amidi OR Lancet, 96 IPOTESI INSULINICA • Le farine raffinate e gli zuccheri possono indurre: - sovraccarico glicemico - resistenza insulinica • Ciò può indurre promozione della crescita cellulare • Attraverso ormoni specifici e fattori di crescita RELAZIONE TRA BMI E RISCHIO DI MORTALITA’ RISCHIO DI MORTALITA’ 2.5 2 1.5 ------------------------------------------------------------------------1 20 25 30 35 40 BODY MASS INDEX (kg/m2) METABOLICHE CARDIOVASCOLARI • DIABETE • DISLIPIDEMIA • GOTTA • IPERTENSIONE • EVENTI COMPLICANZE DELL’OBESITA’ CEREBROVASC. • CORONOPATIA • SCOMPENSO CARDIACO • INSUFFICIENZA VENOSA ALTRE • COLELITIASI • CALCOLOSI RENALE • APNEE NOTTURNE • ARTROSI ERNIA IATALE L’ERNIA IATALE • IL REFLUSSO • IL DOLORE • IL BRUCIORE • MAL DI CUORE ? • ASMA? • TOSSE? Ernia iatale Esofagite Esofago di Barrett • L’ERNIA IATALE Calcolosi della colecisti Calcolosi della colecisti DIETA E PREVENZIONE DEI TUMORI Mantieni attivo il fisico durante tutta la vita, effettuando almeno mezz’ora al giorno di attività fisica intensa, ma adeguando il tipo di esercizio al variare dell’età. Evita il soprappeso e l’obesità e tieni costantemente sott’occhio il peso corporeo, stando attento a ciò che mangi ed evitando la sedentarietà. Assumi spesso alimenti ricchi in fibre Cerca di e prodotti limitare il integrali. consumo di zucchero, dolci e prodotti con farina bianca. Cerca di assumere almeno cinque porzioni al giorno tra frutta e verdura. Modera l’apporto di grassi di origine animale (ad esempio latticini e carni grasse) scegliendo spesso latte e formaggi magri e togliendo il grasso visibile dalla carne e la pelle dal pollo. Per la cottura e per i condimenti, scegli preferibilmente olio extra-vergine d’oliva. Ricordati che il pesce e i legumi sono splendide alternative alla carne. Inoltre, l’olio presente nel pesce è utile per prevenire vari tumori (soprattutto il tumore della mammella) e le malattie cardiovascolari. Bevi acqua in abbondanza e, se assumi alcolici, bevi al massimo due bicchieri al giorno di vino o birra se sei di sesso maschile, uno se sei di sesso femminile. La scelta e lo stoccaggio degli alimenti sono molto importanti. Controlla sempre l’etichetta e, per i vegetali, cerca di preferire prodotti locali, stagionali e freschi o surgelati. Per cucinare in modo salutare, fai uso di piccole quantità di grasso e olio, utilizza basse temperature e riduci il più possibile i tempi di cottura. Mediterranean diet score and cancers of the upper digestive tract This study provides evidence that an a priori defined nutritional pattern, which includes several aspects of the Mediterranean diet, favourably affects the risk of cancers of the upper aerodigestive tract