Olive Oil & Health;Olive Oil & Health;Olive Oil & Health;Olive Oil & Health;Food LabelFood LabelFood LabelFood LabelDr Yahya LALELIDr Yahya LALELIDr. Yahya LALELIDr. Yahya LALELI

IX. Beslenme ve Metabolizma Kongresi,IX. Beslenme ve Metabolizma Kongresi,2007 Istanbul.

www.lalelioliveoil.com

Oli e Oil & HealthOlive Oil & HealthHi t f Oli Oil• History of Olive Oil

• Accepted health effects of Olive Oil.p• Other beneficial effects of Olive Oil

f di l j lfrom medical journals,• Obesity in World, Control of Obesity,y , y,• What fraction if Olive oil, other than Oleic acid,

had positive effect on health and how?(Trans Fat.?, testing…fraying???)(Trans Fat.?, testing…fraying???)

The greatest exponent of olive The greatest exponent of olive g pg poil is monounsaturated fatoil is monounsaturated fat..

Olive oil is the only vegetable Olive oil is the only vegetable oil that can be consumed as it oil that can be consumed as it isis freshl pressed from thefreshl pressed from theis is –– freshly pressed from the freshly pressed from the

fruit.fruit.

Olive oil is a natural juice which Olive oil is a natural juice which preserves the taste, aroma, preserves the taste, aroma,

vitamins and properties of the vitamins and properties of the olive fruit.olive fruit.

Primary component of the Primary component of the Mediterranean Diet.Mediterranean Diet.

St i id Ol i id d• Stearic acid ------- Oleic acid donusumu

A photo from Klazomenai – near İzmir, TURKEY

Stack of baskets filled with olive pulp is being pressed by a stone-weighted beam.

Olive oil is considered a gift of god ina gift of god in

regions where it is used in are part of the p

world. Kings and priests were anointed

with olive oil and royal scepters were

d f limade from olive wood.

A photo from Klazomenai – near İzmir, TURKEY

Olive oil was used not only for cooking/lighting but also asOlive oil was used not only for cooking/lighting but also as

medicine, mainly basic ingredient for ointment by Hippocrates,

Pliny Galen Dioscorides and AverroesPliny, Galen, Dioscorides, and Averroes.

In antiquity olive oil was the base for all cosmetics The Egyptians used it forIn 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.

Olive oil has Olive oil has b d fb d fbeen used for been used for

nutrition of hair nutrition of hair since the since the

ancient timesancient timesancient times.ancient times.It is used in It is used in

t diti I dit diti I ditradition Indian tradition Indian for hair for hair

massagemassage..

Olive leaves also have beneficial properties, d h h b f f hand 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 stimulatethe natural immune reaction that accelerates cellular regeneration, and act as a fungicide

and detoxifier.

Types of Dietary FatTypes of Dietary Fat

h i

Dietary Fat

More Atherogenic Less Atherogenic

Saturated Fatty Acids Unsaturated Fatty Acids

Dietary Fat

Trans Fatty Acids

Beef, Pork,Veal, Lamb

HydrogenatedVegetable Oils

Cocoa ButterCoconut Oil

Palm Oil

O 6 O 3

PolyunsaturatedFatty Acids

Oli Oil

MonounsaturatedFatty Acids

Trans Fatty AcidsMargarine,Shortening

Corn Safflower

Omega-6

Fish Flaxseed

Omega-3 Olive Oil,Canola Oil,

Nuts, Avocado

Corn, Safflower,Sunflower.Soybean

Fish, Flaxseed,Soybean,

Marine Vegetation

http://www.feinberg.northwestern.edu/nutrition/tools-resources/sbm-files/SBM-BloodLipidsPressure.ppt

Furthermore, recent research into the effects of diet onFurthermore, recent research into the effects of diet on cardiovascular diseasescardiovascular diseases, , enflamationenflamation, cancer,, cancer,, , osteoporosis and agingosteoporosis and aging has shown that olive oil, p g gp g g ,

contains elements that are useful for preventing those conditions.

Limited and not conclusive scientific evidence suggests that eating about 2 tablespoons (23 grams) of olive oilthat eating about 2 tablespoons (23 grams) of olive oil daily may reduce the risk of coronary heart disease due to the monounsaturated fat in olive oil. To achieve this to t e o ou satu ated at o e o o ac e e t spossible 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."

8 66 cal/gr8.66 cal/gr

BIOACTIVE CONTENTS IN OLIVE OILBIOACTIVE CONTENTS IN OLIVE OIL

Vitamin AOleic Acid

Linoleic Acid

Beta Carotens

Monounsaturated

Vitamin EAlpha-Oliveopherol

Linoleic AcidLinolenic AcidPalmitic Acid

Monounsaturated Fatty Acids &

Essential Fatty Acids

TocopherolBeta-Citosterol5 A t l

Hexanal3 Metil Butanal1-Pentan-3-En

3 H lTocopherol

Squalene

Sterols

5-AnemosterolCampesterolStigmasterol

3-HexanalOctan-3-en

3 Hexanil AcetatNonanal Vanilin

Aromatic Substances

Phospholipid

P l h l

Orto-difenolVanilic Acid

Polyphenol

Terpenic AcidPhosphotidil-ColinPhosphotidil-

Para Hydroxybenzoic AcidSiringic AcidCafeic Acid

Para-Cumarik AcidEthanolamin

Phosphotidil-SerinPhosphotidil-Inozitol

Sinopic AcidSinamic Acid

Trolox:

A cell-permeable, water-soluble derivative of vitamin E with potent antioxidant properties.p p

Prevents peroxynitrite-mediated oxidative stress and apoptosis in rat thymocytesstress and apoptosis in rat thymocytes.

Alpha-Linolenic AcidLinoleic Acid

MONOUNSATURATEDPOLYUNSATURATEDSATURATEDNAME OF FAT/OIL

6110227Canola Oil

Alpha Linolenic Acid(Omega 3)

Linoleic Acid(Omega 6)

14trace7610Safflower Oil

18551710Flaxseed Oil

1225558Hempseed

2915713Corn Oil

1617112Sunflower Oil

48trace3319Peanut Oil

2385415Soybean Oil

751915Olive Oil

471943Lard

19trace5427Cottonseed Oil

8ce339e u O

281368Butterfat

39trace1051Palm Oil

491248Beef Tallow

70291Coconut Oil

281368Butterfat

users.wfu.edu/clagra2/nutrition/powerpoint.ppt

Doymuş yağ asitleri

Stearik asit

Tekli doymamış

(18:0)

y ş

Oleik asit(18:1Δ9)

∆9

Çoklu doymamış Linoleik asit(18:2Δ9, 12)cis9cis12

Bitkiler Hayvanlar

18:2 n(ω)-6( )

∆9∆12

ift b ğ

ω6

cis9cis12

Linolenik asit(18:3Δ9, 12)

C Sayısı X:Y Δn Çift bağların posizyonu

çift bağ sayısı cis 9, cis 12 LinoleikAsid

X:Y n-Z [n = ω, omega]

ESSENTIAL FATTY ACIDSESSENTIAL FATTY ACIDS

• Fatty acids that the body cannot synthesizeFatty acids that the body cannot synthesize• Therefore, must be through diet

Oli il h 2 ti l f tt id• Olive oil has 2 essential fatty acids:-• Linoleic Acid (polyunsaturated)• Linolenic Acid (polyunsaturated)

• Linolenic acid (an Omega-3 fatty acid)• Abundant in cold water fish• Helps dissolve blood clotsHelps dissolve blood clots• Lowers blood pressure• Dilate arteries• Dilate arteries

Mediterranean diet good for the heart

Ad i M di l di hi h i i h i h l i f i liAdopting a Mediterranean style diet, which is rich in whole grains, fruit, olive oil, vegetables and red wine, can reduce the risk of heart disease by 15%.

This was confirmed in a new study carried out by researchers from the Faculty ofThis was confirmed in a new study carried out by researchers from the Faculty of Medicine Timone in Marseille, France. 2006The study which is published in November 2006 issue of the American Journal of Clinical Nutrition examined the diets of 212 volunteer subjects all of whomof Clinical Nutrition, examined the diets of 212 volunteer subjects, all of whom had a moderate risk for heart disease.

To investigate the value of a Mediterranean diet, subjects were split into two g , j pgroups, 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 inResults 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%. Researchers concluded that these results translated into a 15% fall in overallResearchers 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 among those who were given the low-fat diet.

Olive Oil Evidence

http://www.crmef.org/lipids/LipidsTx%20Lifestyles.ppt

High–monounsaturated fatty acid diets lower both plasmah l t l d t i l l l t ticholesterol and triacylglycerol concentrations

•Step I or Step II diets are for lowering bloodfor 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).

St I di t l t t l•Step I diet lowers total cholesterol and LDL cholesterol by 5–7%

•Step II diet can lower total cholesterol and LDLcholesterol and LDL cholesterol an additional 3–7%

•In these diets, saturated fat energy is replaced byenergy 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 = 0.005. Values are least-squares means ± SEs.American Journal of Clinical Nutrition, Vol. 70, No. 6, 1009-1015, December 1999 © 1999 American Society for Clinical Nutrition

http://academic.brooklyn.cuny.edu/health/rschnoll/HNS251/PowerPoint/phytonutrients_files/frame.htm#slide0068.htm

Types of Dietary Fat and Risk of Coronary Heart Disease: A Critical ReviewHeart 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 on total cholesterol (TC) LDL cholesterol (LDL C) and HDL cholesterol (HDL C)linoleic (18:2n-6) acids on total 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)

Yüksek oranda mısır dieti DMBA gradeYüksek oranda mısır dieti, DMBA grade sıçanlarda dimetilbenz(A)anthracene bağlı

d k i d l k di tadeno karsinomaya neden olurken diete, aynı oranda ilave edilen zeytinyağı promotor inhibitörü olarak davranmaktadır. Breast Cancer Research and Treatment 2004; 86. 225-236.

Zeytinyağı(MUFA): Her 2/neu ifadesiniZeytinyağı(MUFA): Her-2/neu ifadesini baskılar. Herceptin Tm nin büyüme kısıtlatıcı etkisineHerceptin Tm nin büyüme kısıtlatıcı etkisine sinerjistir. Annals of Oncology 2005 ; 16. 359-371.Annals of Oncology 2005 ; 16. 359 371.

Salvestrols:Salvestrols:are a new class of natural anticancer chemicals, which arefound in plants and safely eaten in the diet. Initially non‐toxic to the body's normal cells,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 , pgrowing or die, without harming normal cells.This specificity of action is possible because CYP1B1 is an intrinsic component of cancer cells and occurs inall of the wide range of different types of cancer thathave been studied to date,but is to all intents and purposes absent from normal cells.Olives are also a good source of Salvestrols. Several herbscontain appreciable levels of Salvestrols, including basil,

l      th   i t   ti h kparsley, sage, rosemary, thyme, mint, artichoke,scutellaria and the roots of milk thistle and dandelion.Un proses Olive oil often has higher levels of Salvestrols thanclear oil produced using modern methodsclear oil produced using modern methods.

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

Effect of replacing mixed fat in the average American diet with p g gcarbohydrate or various fat sources at 10% of total energy

Source: Mensink et. al. Am. J. Clin. Nutr. 77:1146 (2003)

Olive Oils High in Phenolic Compounds ModulateOxidative/Antioxidative Status in Men

FIGURE 1 The percentage change in plasma oxidized LDL (A), 8-oxo-dG in mitDNA (B), and urine (C), malondialdehyde in i (D) l GSH P ti it (E) d HDL C (F) i ft 4 d f t i d ti f li il ith lurine (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.

Weinbrenner et al, J. Nutr. 134:2314-2321, September 2004

Other compounds found in olive oil are:Palmitic acid which can raise cholesterol levels but olive oilPalmitic acid, which can raise cholesterol levels, but olive oil

seems to protect rather than damage.Stearic acid, which neither raises or lowers cholesterol.Small amounts of lecithin.Beta carotene and Vitamin E, known antioxidants.Chlorophyll known to be a good source of magnesiumChlorophyll, known to be a good source of magnesium.Squalene, a precursor of phytosterols, which protects against

cholesterol absorption from foods.Modified sterols known as triterpenic substances, which

seem to benefit the cardiovascular system and have healing and anti-inflammatory propertiesanti-inflammatory properties.

Triterpenic acids (oleanolic and maslinic) found only in olive oil stimulate pancreatic enzymesolive oil, stimulate pancreatic enzymes.

Polyphenols, with one such being oleoeuropein, known to lower blood pressure.

Pl th 100 th d th t i fl dPlus more than 100 other compounds that give flavor and aroma that have been identified but not studied. http://www.innvista.com/health/nutrition/fats/olive.htm

Some minor components of olive oil that can have major effects:Beta-sitosterol lowers high cholesterol levels.Caffeic and gallic acids stimulate bile flow Gallic acid alsoCaffeic and gallic acids stimulate bile flow. Gallic acid also

inhibits lactic dehydrogenase activity, which is a sign of liver malfunction.malfunction.Phenolic compounds protect against peroxidation of fatty

acids and cholesterol.2-phenylethanol, present in many unrefined oils, stimulates

production of fat-digesting enzymes in the pancreas.Cycloartenol which is stored in the liver lowers the amountCycloartenol, which is stored in the liver, lowers the amount

of circulating cholesterol and increases bile excretion.A combination of Triterpenic acids and 2-phenylethanolA combination of Triterpenic acids and 2 phenylethanol

slows down cholesterol digestion and its absorption from foods.

http://www.innvista.com/health/nutrition/fats/olive.htm

What are Flavonoids?What are Flavonoids?• The family of polyphenolic substances• The family of polyphenolic substances.• There are 4000-5000 different flavanoid types

in nature.• They are found in fruits the vegetables and inThey are found in fruits, the vegetables and in

the roots of plants.• They provide resistance for the defence to

bacterial diseases, parasites and oxidationp• Some flavanoids have relatively high color

magnitutesmagnitutes

FREE RADICALSTOXIC SUBSTANCES THAT ARE CONTINUOUSLY PRODUCED BY ALL CELLS OF THE HUMAN BODY

FREE RADICALS

PRODUCED BY ALL CELLS OF THE HUMAN BODY.FREE RADICALS CAN BE PRODUCED BY TRAUMA, INJURY, SUNLIGHT, POLLUTION, EXPOSURE TO , , ,

TOXINS, ALCOHOL AND CIGARETTE CONSUMPTION, AND SOME FOODS. THEY ARE ALSO A BY PRODUCT OF MANY OF THE BODY'SALSO A BY PRODUCT OF MANY OF THE BODY'S

NATURAL PROCESSES.

• Oils (Lipid peroxidation)Fatty acidsPhospholipidsTriglycerides

• Proteins• Proteins• Nucleic Acids (RNA, DNA)

ANTIOXIDANTSANTIOXIDANTS

Any substance or mixture h i th i flhaving the influence on affecting the oxidationaffecting the oxidation process of an other psubstance.

Antioxidant

Free Radical

Nucleus

HYDROXYBENZOIC ACIDSHYDROXYBENZOIC ACIDSR2 R1

COOHR3

RR4

R =R =R =H R =OH p-Hydroxybenzoic acidR1=R2=R4=H , R3=OH p Hydroxybenzoic acid

R2=R3=R4=H , R1=OH Salicylic acid

R1=H, R2=R3=R4=OH Gallic acid

R1=R4=H, R2=R3=OH Gentisic acid1 4 , 2 3

Dietary Fat Intake and Obesity (US 1955-1990)

3542t

3240

ght

om F

at % Dietary Calories as Fat

2938

erw

eig

ries

fro

26

2334

36

% O

ve

f Cal

or % Overweight

23

20

34

32

% o

f

1955 1962 1969 1976 1983 199032

Yearfrom Amer Dietetic Assoc 95 417-420(1995)

http://www.gen.cam.ac.uk/iabg10/ppts/Heward.ppt

Overweight in Malaysia by age and ethnic backgroundOverweight in Malaysia by age and ethnic background

MalayChinese

IndianOther IndigenousBMI

26

27

MEN WOMEN

24

25MEN WOMEN

22

23

20

21

20-2

425

-29

30-3

435

-39

40-4

445

-49

50-5

455

-59

60-6

465

-69

70+

20-2

425

-29

30-3

435

-39

40-4

445

-49

50-5

455

-59

60-6

465

-69

70+

19

Ismail & James, 2001.AGE (YRS)

http://www.nao.org.uk/conferences/obesity/presentations/james.ppt

Prevalance Population Frequency

Metabolic Syndrome Prevalence As of Year 2005p q y

Germany 20,606,152

82,431,390

0,2500

Italy 14,514,369 58,103,033

0,2498

Greece 2,661,882

10,668,354

0,2495

Malaysia 5,880,620 23,953,136

0,2455

Spain 10,070,195

40,341,462

0,2496

Switzerland 1,862,716

7,489,370

0,2487

Austria 2,043,690

8,184,691

0,2497

United Kingdom 15,067,677

60,441,457

0,2493

Netherlands (Holland) 4,079,549

16,407,491

0,2486

Turkey

17,223,479 69,660,559

0,2472

France 15,106,053

60,656,178

0,2490

Footnotes:1. US Census Bureau, Population Estimates, 20041. US Census Bureau, Population Estimates, 20042. US Census Bureau, International Data Base, 2004http://www.wrongdiagnosis.com/m/metabolic_syndrome/stats-country.htmlhttp://www.infoplease.com/ipa/A0004379.html

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. Howitzprovide 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 , p pp y y ,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.

S f D Si l i d hi ll h h l th t t l th h i l f d iSo far Dr. Sinclair and his colleagues have shown only that 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 h i l b t i l l l ''Wi d d i l i ithchemical, cabernet sauvignon lower levels. ''Wines produced 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 saidflavones, found abundantly in olive oil, Dr. Howitz said.

Under normal conditions in a yeast cell, the

longevity protein Sir2longevity protein Sir2uses NAD as a cofactor

to produce nicotinamide whichnicotinamide, which

then inhibits Sir2 in a negative feedback loop.

But when the cell isBut when the cell is exposed to

environmental stresses like calorie restriction,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

http://www.hms.harvard.edu/news/releases/0503sinclair.html

becomes more active and yeast live longer.

Calorie restriction and aging could becould be

controlled bby some specific genetic

pathways.p y

http://www.sciam.com/article.cfm?chanID=sa006&colID=1&articleID=000B73EB-3380-13F6-B38083414B7F0000

Leptin is produced in and secreted by the Adipocyte. It enters circulation and travels to the central nervous system where it acts oncirculation 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.

Neuropeptide-YHypothalamus

••Decreases HungerDecreases Hunger•• Increases ActivityIncreases Activity•• Increases ThermogenesisIncreases ThermogenesisAdipocyte

http://origin.www.fda.gov/ohrms/dockets/ac/05/slides/2005-4179s1_04_Hassink_FDA.ppt

www.nature.com

Phytochemistry: Ibuprofen-like activity in extra-virgin olive y y p y goil

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, 45-46 (1 September 2005

Extra virgin olive oil has similar activity to ibuprofenExtra-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 profile and potency 'strikingly' similar to the nonsteroidal antianti-inflammatory profile and potency strikingly similar to the nonsteroidal anti-inflammatory drug ibuprofen. Although the two molecules are structurally dissimilar, they both produce a strong stinging sensation in the throat, and inhibit the same cyclo-oxygenase (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),

d th th th t It i d ti i i th th t i il tmay do rather more than that. Its pungency induces a stinging in the throat similar 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?

Table 1. Selective inhibition of COX enzymes byoleocanthal enantiomers.

Agent Concentration ( M) COX-1 (%) COX-2 (%) 15-LO (%)

P t i hibiti f l 1 d 2 (COX 1 COX 2) d 15 li (15 LO) bPercentage inhibition of cyclooxygenases 1 and 2 (COX-1, COX-2) and 15-lipoxygenase (15-LO) bythree different concentrations of oleocanthal and of ibuprofen are presented as mean s.e.m. forthree independent experiments. ND, not determined. Indomethacin was used as a positive(inhibitory) control in the cyclooxygenase assays and nor-dihydroguaiaretic acid (NDGA) andcaffeic acid were used as positive (inhibitory) controls in the lipoxygenase assay. Theconcentrations for 50% inhibition (IC50; calculated by least-squares regression analysis ofconcentrations for 50% inhibition (IC50; calculated by least squares regression analysis ofinhibition versus concentration) for the natural (-) oleocanthal are 23 M and 28 M for COX-1and COX-2, respectively; IC50 values for (+) oleocanthal are 25 M and 40 M for COX-1 and COX-2, respectively; IC50 values for ibuprofen are 5 M and 223 M for COX-1 and COX-2,respectively13.

Agent Concentration ( M) COX-1 (%) COX-2 (%) 15-LO (%)

(-)Oleocanthal 100 83.5 3.5 70.9 8.6 0.4 0.825 56.1 3.2 56.6 9.5 0.0 0.0

7 24.6 7.3 14.5 2.3 0.0 0.0

(+)Oleocanthal 100 68.0 15.2 69.6 3.9 3.5 5.5

25 54.5 4.6 41.3 15.9 0.7 1.0

7 24 6 7 5 6 1 4 2 0 0 0 07 24.6 7.5 6.1 4.2 0.0 0.0Ibuprofen 25 17.8 2.3 12.7 3.6 0.2 0.3

7 0.0 1.3 NDIndomethacin 25 90.1 89.8 0.1 0.9

7 86 6 66 3 0 5 0 17 86.6 66.3 0.5 0.1

NDGA 25 ND ND 63.1 0.87 ND ND 52.5 1.1

caffeic acid 25 ND ND 25.2 2.27 ND ND 19 8 1 37 ND ND 19.8 1.3

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 methodg