ZEYTİNYAĞ. Tali Bileşenleri. Dr. Yahya Laleli. Taylıeli Zeytin ve Zeytinyağı İşletmesi. 20 Mart 2009, Cuma H.Ü. Merkez Kampusu Konferans Salonu

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1 ZEYTİNYAĞ Tali Bileşenleri Ve Sağlık Dr. Yahya Laleli Taylıeli Zeytin ve Zeytinyağı İşletmesi 20 Mart 2009, Cuma H.Ü. Merkez Kampusu Konferans Salonu

2 Sunu Kapsamı Zeytinyağ Sağlık İlişkisinde Genel Bilgi, Bileşenleri, Zeytin, zeytinyağ tarihi/kullanımı, Zeytin yağın sağlık etkilerinin, Akdeniz tipi beslenmenin pozitif iifetkilerine i yönelik yayınlar, Zeytin yağının pozitif etkilerinin bileşenleriyle y y ğ p ş y ilişkisi.

3 Limited and not conclusive scientific evidence suggests that eating about 2 tablespoons (23 grams) of olive oil daily may reduce the risk of coronary heart disease due to the monounsaturated ou ated fat in olive oil. To achieve e this possible benefit, olive oil is to replace a similar amount of saturated fat and not increase the total number of calories you eat in a day. One serving of this product. contains. grams of olive oil." 866cal/gr 8.66

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5 Types of Dietary Fat More Atherogenic Less Atherogenic Dietary Fat Saturated Fatty Acids Unsaturated Fatty Acids Beef, Pork, Hydrogenated Cocoa Butter Veal, Lamb Vegetable Oils Coconut Oil Palm Oil Polyunsaturated Fatty Acids Monounsaturated Fatty Acids Trans Fatty Acids Margarine, Shortening Omega-6 Omega-3 Olive Oil, Canola Oil, Nuts, Avocado Corn, Safflower, Sunflower. Soybean Fish, Flaxseed, Soybean, Marine Vegetation resources/sbm files/sbm BloodLipidsPressure.ppt

6 Zeytinyağı Bileşenleri, içerik olarak Alkoller Alifatik ve triterpene alkoller Polifenoller Lipofilik fenolikler (Vitamin E, Alfa tokoferol) Hidrofilik fenolikler (Hidroksitirozol, Tirozol vb.) Sabunlaşan, Steroller Beta-Sitosterol 5-Anemosterol Kampesterol Estigmasterol Δ 7 -Estigmasterol Δ 5 - Avehasterol Δ 7 --Avenasterol Pigmentler Klorofil (a ve b) ve yıkım ürünü Feofitinler Gliserid Fraksiyonu (Triaçilgliserol) Tekli doymamış coklu doymamis (esansiyel ) ve doymus yağ asitleri. Oleik Asit Linoleik asit Linolenik asit Palmitik asit Stearik Asit Aldehidler Ketonlar : Alkoller : Asidler : Hidrokarbonlar Skualen β-karoten Likopen Aromatik Bileşikler Asit aldehid propanol 2 ve 3 sis ve trans-hekzenallar Pentan -3- on 1-penton 3-on- 1-octan-3-on on Etanol, Pentan, Hekzan Metil Propan, Metilbutan v.s. Asetik asit, Propanoik asit 2-3 Metilbutirik asit v.s. Sabunlaşmayan Non-Gliserid Fraksiyonu

7 Zeytinyağı y ğ minor (Tali) bileşenleri ş ve bu bileşenlerin bilinen sağlık etkileri Alifatik alkoller ( mg/kg) Uzun zincirli (C18 C10) doymuş alkollerden oluşur. Sağlık etkisi bilinmemektedir. Non gliserid esterler ( mg/kg) β sitosterol, Kampesterol, stigmasterol belirler. Antikanserojen etki ile ilişkilendirilir. Yağın kendisine has yöresel karakterlerini verir. Triterpen alkoller ( mg/kg) Sikloarterenol, 24 metilen hidroarterenol ve 2 feniletanol Kolesterol esteraz aktivitesinin inhibitörüdürler. Oleanolik asit ve eritrodiol ün vazodilidatör etkisi vardır. Dihidroksi triterpen (Uvaol, eritrodiol ve oleanolik asit), IL 1β ve IL 6 sentezini inhibe eder. Steroller ( mg/kg) Kampesterol, stigmasterol, 7 stigmasterol, 5 avenasterol, 7 avenasterol ve β sitosterol Serum kolesterol düzeyini ve diyetle alınan kolesterolün barsaktan emilimini azaltır. β sitosterollerin t i anti tümoral tü etkisi i vardır.

8 Zeytinyağı minor (Tali) bileşenleri ve bu bileşenlerin bilinen sağlık etkileri Hidrokarbonlar ( mg/kg) Fenantren, pyren, fluroanten gibi polisiklik aromatik hidrokarbonlar, skualen, β-karoten ve likopen karotenoidlerdir. Diyetle alınan skualen kolesterol geri emilimini kontrol eder. Kan seviyesini artırmaz. Derinin fonksiyonu için koruyucu yenileyici özelliği vardır. Meme ve prostat kanserlerine karşı koruyucu etkisi bildirilmiştir. Pigmentler (Klorofiller 1 10 mg/kg, Feofitinler 0,2 24 mg/kg ) Klorofil A ve Klorofil B ve bunların oksidasyon ürünü feofitin a ve b zeytinyağına rengini verir. Aflatoksin ile oluşanş DNA hasarını önlediği, ğ karaciğer, ğ deri ve kalın barsak kanserlerinde korunma sağladığı! Fenoller (Lipofilik ve Hidrofilik Fenoller) Tokoferoller ve tokotrienoller (E vitamini). Trombosit agregasyonunu önleyici etkisi Tromboksan B 2 salınımını azaltarak prostanoid sentezini azaltmasına bağlıdır. Reaktif oksijen salınımında, lipid peroksidasyonunda ve interleukin-1b salınımında azalma yapar. Hidroksifenoller, kaffeik asit, vanillik asit, (+)-1-asetoksipinorezinol ve oleuropein sadece iyi korunmuş erken hasat zeytinyağında yeterli miktarda bulunur. Ksantin oksidaz enzimi üzerinden anti kanseröjen etki gösterir. Uçucu Maddeler Uçucu Maddeler Karbonil, alkol, ester ve hidrokarbon fonksiyonel grupları içerir. Üretim esnasında ısıyla uçar. Önemli antimikrobiyal etkileri belirtilmiştir.

9 DİYET VE GEN İFADESİ Diyet (A) Besinler Metabolizma (B) Gen İfadesi İşarete Uyum Sağlama (C) Normal Hücre Büyümesi (A) Besin ile gen ifadesi arasındaki direkt ilişki (B) ve (C) Besin ile gen ifadesi arasındaki dolaylı ilişki den adapte edilmisdir.

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11 Acetate Stearic acid Oleic acid Acetate Stearic acid Oleic acid dönüşümü

12 Akdeniz Diyeti: Akdeniz diyetine yakınlık derecesi, koroner kalp hastalığı, kanser ve ölümle ters orantılıdır. Avrupa Birliği toplumunun beslenme rejiminin Akdeniz diyetine çevrilmesiyle ve uyum derecesine paralel olarak ölüm oranları azalmaktadır. Bu azalma koroner riski olan toplumda da görülmektedir (Trichoponlou, 2005). Tansiyon yüksekliği (veya ilaç ihtiyacı) diyetteki zeytin yağ ile ters orantılıdır. Akdeniz diyeti şişmanlıkla vücut kitlesiyle ilgili değildir. Şişmanlık alınan kalori fazlalığına bağlıdır. Randomize çalışmalar sadece Yunanistan da değil İspanya, Fransa ve İtalya da da Akdeniz diyetinin pozitif etkilerini net olarak göstermektedir (Estruch 2006, Fito2007)

13 The greatest exponent of olive oil is monounsaturated fat. Olive oil is the only vegetable oil that can be consumed as it is freshly pressed from the fruit. Olive oil is a natural juice which preserves the taste, aroma, vitamins and properties of the olive fruit. Primary component of the Mediterranean Diet.

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16 A photo from Klazomenai near İzmir, TURKEY Stack of baskets filled with olive pulp is being pressed by a stone-weighted beam.

17 Yağ Ve Su

18 Yağ Yağ Su

19 Olive oil is considered a gift of god in regions where it is used in are part of the world. Kings and priests were anointed with olive oil and royal scepters were made from olive wood. A photo from Klazomenai near İzmir, TURKEY

20 Olive oil was used not only for cooking/lighting but also as medicine, mainly basic ingredient for ointment by Hippocrates, Pliny, Galen, Dioscorides, and Averroes.

21 In antiquity olive oil was the base for all cosmetics The Egyptians used it for In antiquity olive oil was the base for all cosmetics. The Egyptians used it for the heat extraction and collection of fragrant essences. Massage the body following a bath, often cold, so skin would be scented.

22 Olive oil has been used for nutrition of hair since the ancient times. It is used in tradition Indian for hair massage.

23 Olive leaves also have beneficial properties, and they have been a feature of the pharmacopoeia since antiquity. As with olive oil, they are enjoying a new popularity in health care today. Extremely rich in fatty acid, olive leaves have antioxidant properties that protect the epidermis against free radicals, the major cause of aging in the skin. They also stimulate the natural immune reaction that accelerates cellular regeneration, and act as a fungicide and detoxifier.

24 Furthermore, recent research into the effects of diet on cardiovascular diseases, enflamation, cancer,, osteoporosis and aging g has shown that olive oil, contains elements that are useful for preventing those conditions.

25 A.Trichopoulou, BJM, 2005

26 A.Trichopoulou, BJM, 2005

27 A.Trichopoulou, BJM, 2005

28 Mediterranean diet good for the heart Adopting a Mdi Mediterranean style diet, which h is rich ihin whole grains, fruit, olive oil, vegetables and red wine, can reduce the risk of heart disease by 15%. This was confirmed in a newstudy carried outby researchers fromthe Faculty of Medicine Timone in Marseille, France The study which is published in November 2006 issue of the American Journal ofclinical Nutrition, examined thediets of212volunteersubjects subjects, allofwhom had a moderate risk for heart disease. To investigate the value of a Mediterranean diet, subjects were split into two groups, one to consume a low fat diet and the other to take a Mediterranean diet. Results found that those who had taken the low fat diet reported a drop in cholesterol of 4.5%. The group who had consumed the Mediterranean diet had a cholesterol reduction of 7.5%. 75% Researchers concluded that these results translated into a 15% fall in overall cardiovascular risk for those who adopted the Mediterranean diet. A 9% fall was registered it among those who were given the low fat ftdiet.

29 NAME OF FAT/OIL SATURATED POLYUNSATURATED MONOUNSATURATED Linoleic Acid (Omega 6) Alpha Linolenic Acid (Omega 3) Canola Oil Hempseed Flaxseed Oil Safflower Oil trace 14 Sunflower Oil Corn Oil Olive Oil Soybean Oil Peanut Oil trace 48 Cottonseed Oil trace 19 Lard Beef Tallow Palm Oil trace 39 Butterfat Coconut Oil users.wfu.edu/clagra2/nutrition/powerpoint.ppt

30 Effect of replacing mixed fat in the average American diet with carbohydrate or various fat sources at 10% of total energy Source: Mensink et. al. Am. J. Clin. Nutr. 77:1146 (2003)

31 Olive Oil Evidence

32 High monounsaturated fatty acid diets lower both plasma cholesterol l and triacylglycerol l l concentrations ti Step I or Step II diets are for lowering blood cholesterol concentrations. The primary objective of these diets is to lower saturated fat (8 10% and <7% of energy, respectively), cholesterol (300 or 200 mg/d), and total fat (<30% of energy). Step I diet lowers total t cholesterol and LDL cholesterol by 5 7% Step II diet can lower total cholesterol and LDL cholesterol an additional 3 7% In these diets, saturated fat energy is replaced by carbohydrate, resulting in a low-fat, high-carbohydrate diet. FIGURE 3. Effects of LDL cholesterol, HDL cholesterol, and triacylglycerol (TG) concentrations on cardiovascular disease (CVD) risk reduction in response to Step II, olive oil (OO), peanut oil (PO), and peanut and peanut butter (PPB) diets (n = 22). * Significantly different from the other 3 diets, P = Values are least squares means ±SEs. American Journal of Clinical Nutrition, Vol. 70, No. 6, , December American Society for Clinical Nutrition

33 Types of Dietary Fat and Risk of Coronary Heart Disease: A Critical Review Fig. 2. Effects of lauric (12:0), myristic (14:0), palmitic (16:0), elaidic (trans 18:1), stearic (18:0), oleic (cis 18:1), and linoleic (18:2n 6) acids ontotal cholesterol (TC), LDL cholesterol (LDL C) and HDL cholesterol (HDL C). (Reproduced from [15] with permission of the American Society for Clinical Nutrition.) Journal of the American College of Nutrition, Vol. 20, No. 1, 5 19 (2001)

34 Olive oil, lipid profile, and blood pressure. J. Nutr. 137: 84 87, 2007.

35 Olive oil, lipid profile, and blood pressure. J. Nutr. 137: 84 87, 2007.

36 Olive oil, lipid profile, and blood pressure. J. Nutr. 137: 84 87, 2007.

37 PowerPoint/phytonutrients_files/frame.htm#slide0068.htm

38 FIGURE 1 The percentage change in plasma oxidized LDL (A), 8 oxo dg in mitdna (B), and urine (C), malondialdehyde in urine (D), plasma GSH Px activity (E), and serum HDL C (F) in men after 4 d of sustained consumption of olive oil with low (LPC), moderate (MPC), and high (HPC) phenolic content. Values are means ±SEM, n = 12. J. Nutr. 134: , September 2004

39 Ann Intern Med. 2006;145:

40 FIGURE 4 Postprandial concentrations of tyrosol (A), hydroxytyrosol (B), and MHT (C) at baseline (0 h), 1, 2, 4, and 6 h in men after intake of a single dose (25 ml) of olive oil with low (LPC, closed triangle), moderate (MPC, closed square), and high (HPC, closed circle) phenolic content at d 1 and 4 of treatment. Values are means ±SEM, n = 12. *Different from 1, 2, 4, and 6 h for MPC and HPC olive oils, P < J. Nutr. 134: , September 2004

41 FIGURE 3 Absolute urinary concentrations of tyrosol (A), hydroxytyrosol (B), and MHT (C) in men at d 1 and 4, respectively, after 25 ml olive oil intake with low (LPC), moderate (MPC), and high (HPC) phenolic content. Values are means ±SEM, n = 12. Concentrations of tyrosol, hydroxytyrosol, and MHT increased both at d 1 and 4 in a significant linear trend (P < 0.01). Difference from LPC olive oil, P < 0.05; different frommpc olive oil, P < J. Nutr. 134: , September 2004

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43 Phytochemistry: y Ibuprofen-like activity in extra-virgin olive oil Gary K. Beauchamp, Russell S. J. Keast, Diane Morel, Jianming Lin, Jana Pika, Qiang Han, Chi-Ho Lee, Amos B. Smith and Paul A. S. Breslin Nature 437, (1 September 2005 Extra-virgin olive oil has similar activity to ibuprofen. A recent study has shown that oleocanthal, a component of extra-virgin olive oil, has an anti-inflammatory inflammatory profile and potency 'strikingly' similar to the nonsteroidal antiinflammatory drug ibuprofen. Although the two molecules are structurally dissimilar, they both produce a strong stinging sensation in the throat, and inhibit the same cyclooxygenase (COX) enzymes in the prostaglandin biosynthesis pathway. Phenol compounds in newly pressed olive oils contribute to a unique balance of flavours. One, an aldehyde derivative of deacetoxy-ligstroside aglycone (oleocanthal), may do rather more than that. t Its pungency induces a stinging i in the throat t similar il to that caused by the non-steroidal anti-inflammatory drug (NSAID) ibuprofen. Now it seems that this similar perception also indicates a shared pharmacological activity. Oleocanthal acts as a natural anti-inflammatory compound with a potency and profile very like that of ibuprofen. Is it coincidence that some of the health benefits claimed for a Mediterranean diet, rich in olive oil, overlap with those attributed to NSAIDs?

44 Table 1. Selective inhibition of COX enzymes by oleocanthal enantiomers. Agent Concentration ( M) COX-1 (%) COX-2 (%) 15-LO (%) Percentage inhibition of cyclooxygenases 1 and d2(cox1 (COX-1, COX-2) COX2) and d15li 15-lipoxygenase (15-LO) by three different concentrations of oleocanthal and of ibuprofen are presented as mean s.e.m. for three independent experiments. ND, not determined. Indomethacin was used as a positive (inhibitory) control in the cyclooxygenase assays and nor-dihydroguaiaretic acid (NDGA) and caffeic acid were used as positive (inhibitory) controls in the lipoxygenase assay. The concentrations for 50% inhibition (IC 50 ; calculated by least-squaressquares regression analysis of inhibition versus concentration) for the natural (-) oleocanthal are 23 M and 28 M for COX-1 and COX-2, respectively; IC 50 values for (+) oleocanthal are 25 M and 40 M for COX-1 and COX- 2, respectively; IC 50 values for ibuprofen are 5 M and 223 M for COX-1 and COX-2, respectively 13. Agent Concentration ( M) COX-1 (%) COX-2 (%) 15-LO (%) (-)Oleocanthal (+)Oleocanthal Ibuprofen ND Indomethacin NDGA 25 ND ND ND ND caffeic acid 25 ND ND ND ND

45 Biologists have therefore been hoping to find some chemical or drug that would mimic caloric restriction in people by tripping the same genetic circuitry that a reduced-calorie diet does and provide the gain without the pain. Dr. Sinclair and his chief co-author, Dr. Konrad T. Howitz of Biomol Research Laboratories in Plymouth Meeting, Pa., say they have succeeded in finding a class of drugs that mimic caloric restriction in two standard laboratory organisms, yeast and fruit flies. Mice and humans have counterpart genes that are assumed to work in a similar way, though this remains to be proved. The new development has roused the enthusiasm of many biologists who study aging because caloric restriction, the process supposedly mimicked by the chemicals, is the one intervention known to increase longevity in laboratory animals. A calorically restricted diet -- including all necessary nutrients but 30 percent fewer calories than usual -- has been found to extend the life span of rodents by 30 to 50 percent. Scientists hope, but do not yet know, that the same will be true in people.

46 So far Dr. Sinclair i and his colleagues have shown only that t resveratrol, the chemical found in red wine, prolongs life span in yeast, a fungus, by 70 percent. But a colleague, Dr. Mark Tatar of Brown University, has shown, in a report yet to be published, that the compound has similar effects in fruit flies. The National Institute of Aging, which sponsored Dr. Sinclair's research, plans to start a mouse study later in the year. According to ''The Oxford Companion to Wine,'' pinot noir tends to have high levels of the chemical, cabernet sauvignon lower levels. l ''Wines produced d in cooler regions or areas with greater disease pressure such as Burgundy and New York often have more resveratrol,'' the book says, whereas wines from drier climates like California or Australia have less. Besides resveratrol, another class of chemical found to mimic caloric restriction is that of the flavones, found abundantly in olive oil, Dr. Howitz said.

47 Under normal conditions in a yeast cell, the longevity protein Sir2 uses NAD as a cofactor to produce nicotinamide, which then inhibits Sir2 in a negative feedback loop. But when the cell is exposed to environmental stresses like calorie restriction, heat shock, or osmotic stress (top), PNC1 gets switched on. The Pnc1 protein converts nicotinamide to nicotinic acid, a molecule that has no effect on Sir2. No longer inhibited by nicotinamide, Sir2 becomes more active and yeast live longer.

48 monounsaturated fatty acids (such as those of olive oil) have been associated with greater longevity and a high h degree of protection against age-related cognitive decline in humans Volume 64, Supplement 1, October 2006, pp (9)

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51 Yüksek orandamısır dieti, DMBA grade sıçanlarda dimetilbenz(a)anthracene bağlı adeno karsinomaya neden olurken diete, aynı oranda ilave edilen zeytinyağı promotor inhibitörü olarak davranmaktadır. Breast Cancer Research and Treatment 2004; Zeytinyağı (MUFA): Her 2/neu ifadesini baskılar. Herceptin Tm ninbüyüme kısıtlayıcı etkisine sinerjistir. Annals of Oncology 2005 ;

52 OA synergistically enhances trastuzumab induced apoptotic cell death in Her 2/neu overexpressing breast cancer cells. J.A.Menendez, Ann.of Oncology, 2005

53 British Naturopathic Journal, Vol. 23, No. 1, 2006

54 Salvestrols: are a new class of natural anticancer chemicals, which are found in plants and safely eaten in the diet. Initially non toxic to the body's normal cells, Salvestrols, become activated inside human cancer cells by an enzyme, CYP1B1. The activated Salvestrols, then cause the cancer cells to stop growing or die, without harming normal cells. This specificity of action is possible because CYP1B1 is an intrinsic component of cancer cells and occurs in all of the wide range of different types of cancer that have been studied to date, but is to all intents and purposes absent from normal cells. Olives are also a good source of Salvestrols. Several herbs contain appreciable levels of Salvestrols, including basil, parsley, sage, rosemary, thyme, mint, artichoke, scutellaria and the roots of milk thistle and dandelion. Un proses Olive oil often has higher levels of Salvestrols than clear oil produced using modern methods.

55 According to Cancer Research UK, more than one in three of us will develop cancer at some time in our lifetime. This scary prediction reflects the rapid rise in cancer rates over the last few decades, as 270,000 people in the UK are being newly diagnosed with cancer each year. Although we still don t know the precise causes of most types of cancer, an unhealthy and unbalanced diet is considered the second biggest risk factor after smoking. CYP1B1 protein is over expressed in human tumours and is not specific to any particular type of cancer it seems to be a feature of all cancer cells. Fig 1. Molecular structures of resveratrol, piceatannol, oestradiol and 4 hydroxyoestradiol: a) the conversion of resveratrol to piceatannol catalysed by CYP1B1; b) mapping of the phytoestrogen on to the steroid framework of oestradiol; and c) the CYP1B1 catalysed aromatic hydroxylation of oestradiol to 4 hydroxyoestradiol hd dil(reprinted by permission from Macmillan Publishers: Br J Cancer 2002; 86; ).

56 Fenolik Maddelerin MMP Üzerine Regülatör Etkisi Kaffeik asit, MMP 2 ve MMP 9 üzerine inhibitor TIMP1 2 ün; a. Sekresyonu, b. Transkripsiyonu, c. Regülasyonu üzerinden selektif, etkin inhibitor etki gösterir. (fibrosarkom,hwang 2006), (hepatocarsinoma, Chung 2004, Jin,U.H.2005), (Akciğeringiant cell karsinomasi, Xu 2004) (CT26 kolon adenokarsinoma, Liao 2006)

57 Zeytinyağında bulunan nonfenolik asit Cinnamic asit; Glioblastoma, Ml Melanoma, Prostate t ve akciğer kiğ karsinoma hücrelerinde MMP ve TIMP 2 Eksperyonunu değiştirir, (Liu 1995). Vanilik asidin ise fare meme hücreleri üzerinde karsinogenesis yönünden etkisi görülmemiştir (Lirdprapamongkol, 2005).

58 Leptin is produced in and secreted by the Adipocyte. It enters circulation and travels to the central nervous system where it acts on the hypothalamus to decrease the excretion of Neuropeptide Y. This serves to down regulate Neuropeptide Y causing a decrease in hunger, increase in activity, and increase in Thermogenesis, reducing energy storage and fat accumulation. Hypothalamus Neuropeptide Y Adipocyte Decreases Hunger Increases Activity Increases Thermogenesis s1_04_Hassink_FDA.ppt

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61 HYDROXYBENZOIC ACIDS R 2 R 1 R 3 COOH R 4 R 1 =R 2 =R 4 =H, R 3 =OH R 2 =R 3 =R 4 =H, R 1 =OH R 1 =H, R 2 =R 3 =R 4 =OH R 1 =R 4 =H, R 2 =R 3 =OH 1 4, 2 3 p Hydroxybenzoic acid Salicylic acid Gallic acid Gentisic acid

62 The quantitative and qualitative aspects of olive oil are attributable to the following factors; Region the olive trees are grown Method of Harvesting Processing techniques Storage condition Bottling g method

63 Calorie restriction and aging could be controlled by some specific genetic pathways F6 B B7F0000