1

SpecialArticle1

Evaluating and adapting the Mediterranean diet for non­Mediterranean2

populations­acriticalappraisal3

4

Authors5

R.Hoffman(correspondingauthor)6

SchoolofLifeandMedicalSciences,UniversityofHertfordshire,Hatfield,AL107

9AB,UK8

Tel.01707284526;Fax017072850469

E‐Mail:R.Hoffman@herts.ac.uk10

11

M.Gerber12

CancerResearchCenter,INSERM‐CRLC,34298,Montpellier,cedex5,France13

14

Keywords15

Mediterraneandiet;Mediterraneandietscore;confoundingfactors16

17

Abstract18

This review discusses the limitations of current techniques for evaluating the19

Mediterranean diet in non‐Mediterranean populations, and how differences20

between theeatingand lifestylehabitsof these twopopulationsmay influence21

2

the implementationofaMediterraneandiet innon‐Mediterraneanpopulations.22

Food groups may vary significantly between Mediterranean and non‐23

Mediterraneanpopulationsdue to theprecise foodswithin the foodgroupand24

due to aspects of foodproduction andpreparation.Examples includeMUFA in25

relationtoitssource(meatversusoliveoil),vegetablesinrelationtotheamount26

consumedandhowtheyareprepared,alcohol in termsof itspatternof intake27

and source (wine versus other sources), and the nature of meat and dairy28

produce. Lifestyle factors such asmeal patterns and exposure to sunlightmay29

also act as confounding factors when assessing the overall benefits of a30

Mediterraneandiet.ImprovingMediterraneandietscoresandmeasuringplasma31

nutrient levels may help mitigate the effects of these confounders. These32

considerations may have important health implications when implementing a33

Mediterraneandietinnon‐Mediterraneanpopulations.34

35

3

35

Introduction......................................................................................................................................336

DietaryassessmentsofadherencetoaMeddiet .............................................................637

Aprioridietarypatterns ........................................................................................................638

CorrelatingandconfoundingfactorsassociatedwithaMeddiet..................... 1039

Comparisonbetween foodsand theirpreparationmethods inMediterranean40

andnon‐Mediterraneancountries....................................................................................... 1141

Oliveoil ....................................................................................................................................... 1242

Vegetables.................................................................................................................................. 1243

FruitsandNuts ........................................................................................................................ 1644

Cereals......................................................................................................................................... 1945

Legumes...................................................................................................................................... 1946

Fish ............................................................................................................................................... 2047

Dairyproduce .......................................................................................................................... 2248

Meat.............................................................................................................................................. 2449

Otherfoods................................................................................................................................ 2550

Alcohol ........................................................................................................................................ 2651

Discussion....................................................................................................................................... 2852

Conclusions.................................................................................................................................... 3153

Acknowledgements .................................................................................................................... 3154

55

Introduction56

DespitethemultipleformsoftheMediterraneandiet(Meddiet)thathavearisen57

asaconsequenceofthediversefoodhabitsacrosstheregion,nutritionistshave58

neverthelessestablishedamodelMeddiet.ThismodelMeddietischaracterised59

byalargequantityanddiversityofplant‐derivedfoods(wholegraincereals,raw60

andcookedvegetables,freshanddryfruits,legumesandnuts),fish,amoderate61

intakeofmeatanddairyproduce(bothpreferablyfromgoatsandsheep),olive62

oil as added fat, and amoderate intake of wine duringmeals. 1,2 This dietary63

4

pattern typically represented the food habits of Southern Italy and Greece64

(especially Crete) around the 1970s. These countries were part of the “Seven65

CountriesStudy”,whichwasthefirststudytodemonstratethehealthbenefitsof66

a Med diet with regard to all‐cause mortality, and especially cardiovascular67

mortality, when comparing a traditional Med diet with diets from the US and68

NorthEuropeancountries.3Later,thehealtheffectsoftheMeddietwerestudied69

within a single population by classifying the subjects into groups according to70

theiradherencetoaMeddiet, 4andbyevaluating theirdiseaseriskrelativeto71

how far their food habits were from the traditional Med diet. 5 Both of these72

studies were conducted within Mediterranean populations and used a priori73

dietarypatternsthatwerebasedonthemaincharacteristicsoftheMeddiet.74

75

Subsequently, itwas proposed to applyMeddiet scores to non‐Mediterranean76

populations.However,thereareanumberofdifferencesbetweentheeatingand77

lifestylehabitsofMediterraneanandnon‐Mediterraneanpopulationsthatmake78

usingtheoriginalMeddietscoreseitherimpossible(forexample,whentheMed79

dietscoreincludesoliveoil,sinceonlyafewpopulationsintheworlduseolive80

oil), or misleading (for example if the foods of the score have different81

compositions in Mediterranean and non‐Mediterranean countries). This latter82

pointcouldpotentiallyinfluencetheevaluationoftheeffectivenessofaMeddiet83

fornon‐Mediterraneanpopulations.Analysingtheresultsofvariousstudiesthat84

haveappliedaMeddietscore(eithertheoriginalone,oraderivedormodified85

score),itispossibletopinpointthosefeaturesoftheMeddietthatappearmost86

stringent.This is importantbecauseof the interest inusingaMeddiet innon‐87

5

Mediterraneanpopulations tomanagecoronaryheartdisease (CHD)andother88

chronicdiseases.6,789

90

This reviewdiscusses someof thedifferencesbetween the eating and lifestyle91

habits of Mediterranean and non‐Mediterranean populations that could92

potentially impacton thehealthbenefitsofaMeddiet.Weaddress threemain93

issues:94

1. Are the a priori Med diet scores that have been constructed from95

literature data or dietary assessment obtained in Mediterranean96

populations appropriate for evaluating adherence to aMed diet and its97

healtheffectsinnon‐Mediterraneancountries?98

2. Arethere factorsassociatedwithaMeddiet inMediterraneancountries99

butnotpresentinnon‐Mediterraneancountriesthatmayaffectthehealth100

benefits obtained from aMed diet (eg differences in lifestyle andmeal101

structure)?102

3. Coulddifferencesinthetypesandvarietiesoffoodsconsumedandtheir103

methodsofpreparationalsoplayarole?104

105

Theseissueswillbeillustratedbycomparingthewesterndiet,andespeciallythe106

UKdiet,withthedietinMediterraneancountries.107

108

6

DietaryassessmentsofadherencetoaMeddiet109

Aprioridietarypatterns110

By the 1990s, nutritional epidemiology had foreseen the limits of using an111

assessment system based on nutrient intake. The ability to understand the112

relationshipbetweenfoodandhealthwasrestrictedbecauseofincompletefood113

compositiontablesandbecauseofthedifficultyinascertainingthespecificityof114

a given nutrient, or even a given food, to an observed health effect. It became115

evident that aholistic approach shouldbeused innutritional epidemiology, 8,9116

and this especially applied to theMed diet, a dietary patternwhose beneficial117

effects were becoming widely acknowledged. 10 Several Med diet scores were118

thereforedesigned.5,11,12OnlytheMeddietscoresofTrichopoulouetal,referred119

tohereasMDS,willbediscussedherebecause it is theonemostwidelyused,120

andalsobecauseithasbeenmodifiedtofitvariouspopulations.121

122

IntheoriginalMDS,theauthorstookadvantageofthefoodconsumptionpattern123

of an elderly Greek populationwho hadmaintained a traditionalMed diet up124

untilthe1990s.5Anutritionalsurveyofthispopulationprovidedaquantitative125

assessment of the characteristic foods of the Med diet. A point scale was126

established to assess the degree of adherence to the traditionalMed diet. The127

authors arbitrarily decided that the median sex‐specific value of the128

consumptionofnineselectedcharacteristiccomponentsof theMeddietwould129

bethecut‐offdeterminingadherence.Avalueof0or1wasassignedforeachof130

thefivepresumedbeneficialfoodgroupsievegetables,legumes,fruitsandnuts,131

cerealsandfish.Avalueof0wasassignedifconsumptionwasbelowthemedian,132

7

and a value of 1 was assigned if consumption was above the median. It was133

decided to replace olive oil with the ratio of monounsaturated fatty acids134

(MUFAs)tosaturatedfattyacids(SFAs)becauseAncelKeyshadestablishedthat135

this ratio was the main factor contributing to the low cardiovascular disease136

(CVD)mortality.3Thusavalueof1wasassignedtoindividualswithaMUFA:SFA137

ratioatorabovethemedianobserved inthepopulation,andavalueof0 fora138

ratio less than the median. For dairy products, and meat and meat products139

(whoseconsumptionistypically lowormoderateintheMeddiet),avalueof0140

was assigned for consumption at or above the median, and a value of 1 was141

assignedforconsumptionbelowthemedian.Withregardtothemoderateintake142

ofethanolintheMeddiet,avalueof1wasassignedtomenconsumingbetween143

10gand<50gperdayandtowomenconsumingbetween5gand<25gper144

day. Thus, the final MDS ranged from 0 (minimal adherence) to 9 (maximal145

adherence).146

147

ThispatternwasperfectlyadaptedtotheGreekpopulationandconformedwith148

previous results on the benefits of aMed diet onmortality. 5 Itwas therefore149

proposed to apply it to other populations, e.g. populations in the EPIC study.150

However,afewmodificationswerenecessaryinordertoadapttheMDStoother151

Europeanpopulations.ThescorefortheEPICstudyhadtwomajoradaptations152

13:153

(1) In theoriginal score, themajor sourceofMUFAs isoliveoil and the154

high MUFA:SFA ratio reflects a high consumption of olive oil and a low155

consumption of animal products. Because relatively few people in Northern156

8

Europeuseoliveoil,itwasnecessarytomodifythescoreusinganothermarker157

for vegetable oil consumption.Hence theMUFA:SFA ratio becameunsaturated158

fat:SFA. This had two consequences. Firstly, it did not take into consideration159

substancesinthenon‐saponifiablefractionofoliveoil(especiallythetriterpene160

squaleneandthephenoliccompoundshydroxytyrosolandoleocanthal),manyof161

which have antioxidant and anti‐inflammatory actions and are potentially162

beneficialagainstchronicdegenerativediseases,andhencemortality.Secondly,163

MUFAsare,toalargeextent,markersofoliveoilintheoriginalMDSsinceitwas164

applied to a populationmainly consuming olive oil for cooking and as a salad165

dressing.ButwhenappliedtoNorthernEuropeanpopulations,MUFAsreflect,to166

alargeextent,theconsumptionofanimalfat,andithasbeendemonstratedthat167

these MUFAs are associated with CVD 14 and breast cancer, 15 as further168

discussed by Gerber and Richardson. 16 It is interesting to note that in an “a169

posteriori”adaptationoftheMDS,oliveoilreplacedtheratioMUFA:SFA.17170

(2) A significant difference between Greek and North European171

populationsisintheirintakeofplant‐derivedfoods.RetainingtheGreeklevelof172

consumption would have resulted in the majority of North European people173

scoring0forvegetablesandlegumes.Hence,itwasdecidedtouseasacut‐offthe174

median of the consumption of the nine components of the MDS in each175

population. Under these conditions, the value of the cut‐off differedmarkedly176

among the EPIC populations. For example, the median Greek consumption of177

vegetables(excludingpotatoes)intheEPICstudywas500g/dformenand550178

g/dforwomen,5whereasthemedianvaluesforallpopulationsoftheEPICstudy179

were157g/dayformenand184g/dforwomen.13Asmightbeanticipated,such180

amodifiedMDSwasnot associatedwitha reducedmortality risk in theNorth181

9

Europeanpopulationsanalysed.13TheaposterioriadaptationoftheMDSofSofi182

etalproposedabsolutevalues for foodconsumption tobe reached inorder to183

describe adherence to a Med diet. 17 These values were derived from a184

segmentedregressionanalysisofeachfoodconsumptionoftheMDSandoverall185

mortalityoftheGreekEPICcohort.The“change‐point”onthesegmentprovided186

forthefoodcut‐offtobeusedintheMDS.Thusforvegetablesthe“change‐point“187

is >500 g, very close to what could be deduced from the literature, and the188

amountthatisgenerallyproposedinpublichealthrecommendations.189

190

SeveralothermodifiedMeddietscoreshavesubsequentlybeenproposed.Inthe191

US, Fung and colleagues excluded potato products from the vegetable group,192

separated fruit and nuts into two groups, eliminated the dairy group because193

low‐fat milk is predominantly used in the US, included whole‐grain products194

only,includedonlyredandprocessedmeatsinthemeatgroup,andallocated1195

pointforalcoholintakebetween5and15g/d.18ItwascalledthealternateMDS196

(aMDS)andwasnotassociatedwithoverallpost‐menopausalbreastcancerrisk,197

but only in sub‐classes of this disease. In 2010, another modification was198

developed and applied to the EPIC cohorts. 19 Each component (apart from199

alcohol)wascalculatedasafunctionofenergydensity(g/1000Kcal/d)andwas200

thendividedintotertilesofintake.Ascoreof0,1or2wasassignedtothefirst,201

second,andthirdtertilesof intake for the fivecomponentspresumedto fit the202

Med diet, namely fruit (including nuts and seeds), vegetables (excluding203

potatoes), legumes, fish(freshorfrozen,excludingfishproductsandpreserved204

fish), andcereals.Thescoringwas inverted for the twocomponentspresumed205

10

not to fit the Med diet, namely total meat and dairy produce. This scoring206

recognizedthe importanceofoliveoil:0wasassignedtonon‐consumers,1 for207

subjects consuming below the median (calculated only within olive oil208

consumers), and2 for subjects consumingequalorabove thismedian.Alcohol209

wasassignedeither2formoderateconsumers(range:5–25g/dforwomenand210

10–50g/d formen)or0 forsubjectsoutside(aboveorbelow) thesex‐specific211

range. This modification was called the relative Med diet (rMED). The rMED212

scoreswerethengroupedintolow(0–6),medium(7–10),andhigh(11–18).This213

scorecompensatedforthedifferenceinfoodconsumptionamongthecohortsby214

usingenergydensityandtookintoconsiderationthespecificityofoliveoil.The215

resultsarenotshownbycohorts,buttheoverallresultsshowedariskreduction216

forgastricadenocarcinomaof33%withincreasingadherencetotherMED.217

218

CorrelatingandconfoundingfactorsassociatedwithaMeddiet219

Ithasbeenshownthattheorderofcourses inamealandthepatternofmeals220

through the day are strong characteristics of aMed diet. 20 Lunch is themain221

meal, providing not only the required energy but also a sufficient quantity of222

plant‐derivednutrients,iefibre,micronutrientsandphytochemicals.Inaddition,223

besides the expected typical food intake, sharing of meals with family or224

colleagues and an absence of snacking were found to be major features in225

Sardinia,wherethereishighadherencetoatraditionalMeddiet,comparedwith226

Malta, where many traditional features have been lost. 20 Although these227

differentfactorsmightplayanadditionalroletofoodcomponentsinpreserving228

11

health, they are not currently assessed in dietary questionnaires and hence229

cannotbecontrolledforbystatisticaltechniques.230

231

Severalotherfactorsmaybereducedorabsentinthelifestylesofpeoplelivingin232

non‐Mediterranean countries. A healthy energy balance derived from physical233

activity was an intrinsic part of the Med diet in Mediterranean populations234

following a traditional lifestyle. Also, taking a siesta ‐ still current in some235

Mediterraneancountries ‐hasbeenassociatedwitha lowerriskofCVD, 21but236

this is rarely considered in epidemiological studies. Another potentially237

confounding factor in relation to several chronic degenerative disorders is the238

possibleprotectiveeffectsconferredbyvitaminD.22,23Becauseofmoreintense239

sunlight, the UV‐induced synthesis of vitamin D will supplement nutritional240

intaketoagreaterextentformanypeopleinMediterraneancountries,compared241

tomorenortherlycountries.242

243

Comparison between foods and their preparation methods in244

Mediterraneanandnon­Mediterraneancountries245

246

The precise composition of a food and how it is produced and prepared can247

differ significantly between Mediterranean and non‐Mediterranean countries.248

ThesedifferencesmayimpactontheoverallhealthbenefitsofaMeddietinnon‐249

Mediterraneancountries.250

251

12

Oliveoil252

ThemajordifferencebetweennorthernandMediterraneancountriesinrelation253

tooliveoilissimplywhetherornotitisconsumed,andthishasbeendiscussed254

earlier. However, the quality of olive oil and its culinary use may also be255

importantwith regard to its health benefits. AlthoughMUFA content does not256

varysignificantlybetweendifferentqualitiesofoliveoil,oliveoilalsocontainsa257

"non‐saponifiable" fraction comprising various triterpenes (mostly squalene),258

phytosterols(mostlyβ‐sitosterol),tocopherols(mostlyvitaminE)andphenolics,259

and these may vary between various types of olive oil and be influenced by260

culinarypractices.Levelsofsqualene,aputativeprotectivefactoragainstbreast261

cancer,24phytosterolsandtocopherolsarereducedwithincreasingrefinement262

ofvirginoliveoil.Inaddition,phenolicsareonlypresentinsignificantquantities263

invirginoliveoilandsotheirhealthbenefitswillbelostwhennon‐virginolive264

oils are consumed. Potentially important phenolics in virgin olive oil include265

lignans, which are associated with reduced breast cancer risk,25,26266

hydroxytyrosol, which has cardioprotective and anticancer activity in267

experimental systems, 27 and the anti‐inflammatory substance oleocanthal.268

Fryingwithvirginoliveoil reduces thephenolic content, 28 and thishighlights269

thepotentiallyimportantrolethatconsumptionofrawvirginoliveoilmayplay270

intheMeddiet.271

272

Vegetables273

Populations inMediterraneanandnon‐Mediterraneancountriescanhavequite274

differentpreferencesfortypesofvegetablesandtheirpreparationmethods,and275

13

this may influence health outcomes in relation to vegetable consumption. 29276

Dutchuniversitystudentswerereportedtoprefer"Brusselssprouts,greenpeas277

andcarrotsoftenwithapplesauce"whereasGreekstudentschose"mostlyfresh278

saladsoftomatoes,cucumber,cabbage,rocket,radishes,spinachandlettucewith279

olive oil, vinegar or balsamic vinegar and herbs, or green vegetables in baked280

pies (spinachpie, leakpie, etc.)". 30 Saladswere found tobe consumedseveral281

timesaweekinananalysisofthetraditionalCretanMeddiet.31InEPICcohorts282

fromnortherncountries,consumptionofrawvegetablesasaproportionoftotal283

vegetable consumption was reported to be lower compared to their southern284

counterparts. 32Thiswasparticularly striking forUKmenwhoconsumedonly285

half asmuch rawvegetables as cookedvegetables,whereas theproportionsof286

rawandcookedvegetableswerefairlysimilarinMediterraneancountries.Data287

fromtheUKLivingCostsandFoodSurveyindicatethatthemainpurchasedfresh288

vegetables in the UK in 2010 included cabbages, brussel sprouts, cauliflower,289

saladleaves,carrots,alliumsandtomatoes.33290

291

Thesewide variations in preferred types of vegetablesmay have a significant292

impactonphytochemical intake andhenceonany correlateddisease risk.The293

lowconsumptionofdarkgreenleafyvegetables(egbroccoli,spinach,kale)inthe294

UK32 isnoteworthysincetheserepresentamajordietarysourceofvitaminsC295

andK,folate,β‐carotene,lutein+zeaxanthinandflavones.34Garlicconsumption,296

commoninMediterraneancountries,islowintheUK,andtheWCRF/AICR2007297

reportconsideredit"probable"thatgarlicconsumptioncontributestoprotective298

effects against stomach and colorectal cancers. 35 Differences in the299

14

phytochemicalcontentbetweendifferentvarietiesofthesamevegetablecanbe300

substantial. For example, flavonol content of lettuce varieties ranged from 0.5301

µg/g freshweight for iceberg lettuce ‐avarietycommonlypurchased inNorth302

Europeancountries‐to207µg/gfreshweightfortheItalianvarietylollorosso.303

36DietaryflavonolintakeislinkedtoadecreasedriskofCVD,includingstroke.37304

Of course, low consumption of one vegetable may be compensated for by305

consumptionofanothervegetablecontainingthesamebeneficialnutrients,and306

moreovermany phytochemicals present in vegetables are also found in fruits.307

Thus, amixed and diverse diet can help ensure an optimum intake of a wide308

rangeofhealthyphytochemicals.Thepotential importanceofavarieddietwas309

highlightedinanEPICstudywhichshowedthatdiversityoffruitandvegetables310

consumptionwasassociatedwithadecreasedriskoflungcancer,aneffectover311

and above the inverse association with quantity. 38 It is noteworthy that a312

traditional Med diet includes a particularly wide diversity of fruits and313

vegetables.314

315

Preparation method can influence both nutrient levels and nutrient316

bioavailability. Consumption of raw vegetables preserves heat labile nutrients317

suchasvitaminsAandCandfolatesthatotherwisecanbelostwhenvegetables318

are cooked. Also, using an oil‐based dressing ‐ olive oil is traditional in319

Mediterranean countries ‐ was shown to increase the bioavailability of320

carotenoidsfromsaladingredients.39Breakingdownthefoodmatrixbycooking321

orpureeingcanalso increase thebioavailabilityof carotenoids.40Thecommon322

practice inNorth European countries of boiling a single type of vegetable and323

15

discarding the cooking water can result in significant nutrient loss due to324

leaching ofwater soluble nutrients such as folates and glucosinolates into the325

cooking water. 41,42 This practice is less common in Mediterranean countries,326

where soups and stews arepreferred, and since these cookingmethods retain327

the cooking medium, there is no loss of water soluble nutrients. Frying328

vegetables can lead to significant losses of fat soluble nutrients such as329

carotenoids, probably into the cooking fat, 43 but this practice is not very330

commonintheMeddiet.Ontheotherhandwhentheentirecontentsofthepan331

areconsumed,forexampleinMediterraneanstews,theoverallnutritionalvalue332

ofthedishwillnotbecompromised.333

334

The emphasis in a traditionalMeddiet is for seasonal, field‐grown vegetables,335

whereas for a North European market "Mediterranean" vegetables are336

frequently grown under glass. This latter cultivation practice reduces UV‐B337

exposuredue to the limited light absorbingproperties of glass. It is also often338

accompaniedbyincreasedfertiliseruse.Bothofthesefactorscanhaveadverse339

effects on phytochemical production, although this appears to dependboth on340

thetypeofvegetableandthespecificphytochemical.44341

342

In conclusion, the nutritional benefits that different populations receive from343

consuming vegetables may vary widely, and is not accounted for by simply344

determiningabsolutelevelsofconsumption.345

346

16

FruitsandNuts347

TotalfruitconsumptionintheUKislowcomparedtoMediterraneancountries,348

and across Europe there is a North South gradient for total consumption. 32349

Apples,bananasandcitrusfruitstogetheraccountedforabouttwo‐thirdsofall350

fresh fruitpurchased in2010byUKhouseholds,andprocessed fruitsand fruit351

products(excludingfruitjuices)accountedforathirdoftotalfruitpurchases.33352

Consumption of summer fruits popular in Mediterranean countries ‐ such as353

pomegranates,figs,grapesand"orangefruits"(egapricots,peaches,nectarines,354

cantaloupemelons)‐isrelativelylowintheUK.355

356

When eaten raw,many fruits are a good source of vitamin C. By contrast, the357

relative amounts of various phytochemicals can vary widely: citrus fruits are358

good sources of flavanones and flavones, berries are rich in anthocyanins and359

flavan‐3‐ols, and Mediterranean "orange" fruits are important sources of α‐360

carotene and β‐carotene. Due to the difficulty for epidemiological studies to361

identify the effects of individual nutrients within a diet, it is unclear if the362

particularnutrientcontentofaspecific fruitaffectshealthoutcomes.However,363

Chong et al concluded that therewas some limited evidence that fruits rich in364

flavonols,anthocyaninsandprocyanindins,suchaspomegranate,purplegrapes365

andberries,aremoreeffectiveatreducingCVDrisk.45366

367

Fruit isatypicalwaytoendamealinMediterraneancountries.Attheendofa368

meal there is a rise inpro‐oxidant andpro‐inflammatoryprocesses and this is369

linked to increased cardiovascular damage. Postprandial hyperlipidaemia and370

17

hyperglycaemia are also risk factors for a number of metabolic disorders371

including type 2 diabetes, CVD and metabolic syndrome. Some studies have372

shown that consumption of phenolic‐rich fruits during the postprandial phase373

increases the antioxidant capacity of the blood46Hence consuming fruit at the374

endofamealisaprudentstrategyforhealthyeating.375

376

In conclusion, consumption of awide range of fruits is advisable, especially if377

phytochemical intake from vegetables is limited. Eating fruit, rather than a378

pastry, at theendof amealnotonly reduces calorie intakebut fruitphenolics379

mayalsohelpcounteractoxidativestressandotherpathologicaleventsduring380

thepostprandialphase.381

382

AnanalysisofnutconsumptionintheEPICstudyfoundthatcohortsfromcentral383

European countries (North of France, Germany, Netherlands, UK) and384

Mediterranean countries (South of France, Greece, Italy, Spain) had similar385

overall levels of consumption. 47 However, a higher proportion of peanuts386

relativetotreenuts(mainlywalnuts,almondsandhazelnuts)wereconsumedin387

the central European countries. For example in the UK, peanuts and tree nuts388

constituted 40.4% and 36.4% respectively of total nuts and seeds consumed,389

whereasinSpainthesefigureswere26.8%and54.9%respectively.390

391

AlltypesofnutshavebeenshowntoreducetheriskofCHD,althoughonlyvery392

limiteddataisavailableforpeanuts.48Nutshavehypocholesterolaemiceffects,393

andanumberof intervention studieshavedemonstrated thatnuts lowerboth394

18

LDL‐cholesterol and the ratio of LDL‐cholesterol to HDL‐cholesterol. 48395

Participants of the PREDIMED study (a multi‐centre intervention study) who396

consumednutsaspartofaMeddiethadastatisticallysignificantreduction(p<397

0.05) in LDL‐cholesterol and the LDL/HDL‐cholesterol ratio. 49 The398

cardioprotectiveeffectsofnutsmayberelatedtotheirrelativelyhighproportion399

of unsaturated fatty acids such as MUFA and linoleic acid. 50 The400

hypocholesterolaemiceffectsofnutsmayalso, inpart,berelatedto theirquite401

high phytosterol content. Pistachio nuts ‐ a common aperitif nut in402

Mediterraneancountries‐havethehighestphytosterolcontentofallnuts(279403

mg/100 g), and oil‐ and dry‐roasted peanuts and peanut butter also contain404

moderate levelsofphytosterols (135mg/100g inoil‐roastedpeanuts). 51Tree405

nuts,which constitute a higherproportionof nuts inMediterranean countries,406

haveadditionalnutrientsincluding:ahighvitaminEcontentinalmonds,52high407

levels ofα‐linolenic acid in walnuts,50 and, when eaten with their skins, high408

levelsofphenolicantioxidants.53409

410

In conclusion, although there is good evidence that tree nuts have411

hypocholesterolaemic properties, there is currently no strong evidence for412

hypocholesterolaemic properties for peanuts. Moreover, high levels of salt in413

many peanut products preclude high intake, especially in subjects with high414

blood pressure, and peanuts are also relatively high in saturated fat including415

palmiticacid.416

417

19

Cereals418

It is difficult to appropriately assess the effects of cereals from a nutritional419

questionnaire,sincecerealscanberefinedorwholegrain,saltedorsweetened,420

all factors that strongly influencehealth. InoneMDSwhereneithersweetened421

cereals nor bread from fast‐food were scored for, it was still not possible to422

clearlyevaluatetheeffectsofcereals.11Wholegraincerealsareverylikelytobe423

abettermarkerforhealthbenefits,butthisevaluationcanonlybeappliedwhen424

whole grain cereals are consumed by a high percentage of the subjects under425

study.54Anotherapproachistoscorerefinedcerealsnegatively.55426

427

Legumes428

Legume consumption excluding peas and green beans (ie pulses) showed a429

gradient of consumption in cohorts from the EPIC study,with higher levels of430

consumptioninsoutherncountriesandlowerlevelsinnortherncountries.32As431

well as quantitative differences, the preferred types of legumes in these two432

regions also differs. Commonly consumed legumes inMediterranean countries433

include chickpeas, lentils and fava (broad) beans, although there are national434

differencesegchickpeaconsumptionishighinSpainandintakeoffavabeansis435

highinEgypt.IntheUK,chickpeas,favabeansandlentilsaremainlyconsumed436

byethnicminorities,andthemajortypesof legumes intheUKdietarecanned437

"bakedbeansinsauce"andgardenpeas.33438

439

LegumeconsumptionisassociatedwithadecreasedriskofCHDandCVD,56and440

consumptionofvarious legumes, includingbakedbeans (whicharemade from441

20

haricotbeans),57hasbeenfoundinarecentmeta‐analysistolowercholesterol442

levels. 58 Legumes have excellent nutritional value and were ranked as an443

important source in the US diet for fibre, phytosterols, folate, vitamin B6,444

flavonols, favan‐3‐olsandvariousminerals. 34Both fibreandphytosterolsmay445

belinkedtothehypocholesterolaemiceffectsoflegumes.59InrelationtotheUK446

diet,gardenpeascontain134mg/100gphytosterols,60whichiscomparableto447

amountsfoundinotherpulses,andharicotbeansareagoodsourceoffibre.This448

suggests that legumes commonly consumed in the UK may have some of the449

cardioprotective effects of the pulses more commonly associated with a Med450

diet.29451

452

Fish453

There isgoodevidencethat fishconsumption lowerstheriskofcardiovascular454

mortality. 61 The most important bioactive nutrients in fish are generally455

considered to be the n‐3 LC‐PUFAs EPA and docosahexaenoic acid (DHA). A456

recent systematic review concluded thatmarine n‐3 LC‐PUFAs are effective in457

preventingcardiovascularevents,cardiacdeathandcoronaryevents,especially458

inpersonswithhighcardiovascular risk. 62There is lessevidence fora roleof459

LC‐PUFAsinthepreventionofcancer.63460

461

Levelsofn‐3LC‐PUFAsareconsiderablyhigherinoilyfishthanwhitefish.Since462

there isvariability intherelativeproportionsofoilyandnon‐oily fishbetween463

countries,measuringtotalfishintakemaynotreflecttheintakeofn‐3LC‐PUFAs464

for a givenpopulation.The relative amountsof oily andnon‐oily fishdoesnot465

21

followanorthsouthgradientsinceconsumptionof"veryfattyfish",definedby466

Welchetalasincludingherrings,kippersandmackerel,ishighinScandinavian467

countries. 64Bycontrast, theproportionof these typesof fishconsumed in the468

UK isrelatively low,andso in theUKtotal fishconsumptionwillbeassociated469

withaproportionallylowerintakeofn‐3LC‐PUFAsfromfishthanisthecasein470

someothercountries.471

472

Awide rangeof factors including the fish’s food source influence theLC‐PUFA473

contentofoily fish,andthis isparticularly importantwhenconsideringfarmed474

fish,anincreasinglyimportantdietarysource.Farmedsalmonisamajorsource475

ofn‐3PUFAsintheUKdiet.Salmon,likeothersalt‐waterfish,hasonlyalimited476

capacity to synthesise LC‐PUFAs and instead obtains LC‐PUFAs from its feed.477

Whenfedfishoils,farmedsalmonareanexcellentsourceofLC‐PUFAs,butthere478

are increasing environmental and commercial pressure on fish farmers to use479

non‐marinesourcesofoils.ThispracticecandrasticallyreduceDHAlevels.For480

example, levelsof17gDHA/100gtotal fattyacidsweredeterminedinsalmon481

thatwere fed fishoils,whereas levels of5 gDHA/100g total fatty acidswere482

found in salmon fed plant oils. 65 Feeding fish oils during the last fewmonths483

beforemarketingthefishisonetechniquethatcanrestoreEPAandDHAtofish484

fed a diet that has been predominantly vegetable‐based. 66 Hence, the food485

supplyof farmed fish is an important considerationwhenassessing thehealth486

benefitsofoilyfish.487

488

22

Pan fryingwith olive oil is one of themost popularways of preparing fish in489

Mediterranean countries and fish fried in virgin olive oil has been found to490

absorbsignificantquantitiesofantioxidantphenolics,terpenicacidsandvitamin491

Efromtheoil.67Hence,theremaybeincidentalbenefitsoffryingfishinoliveoil.492

Ontheotherhand,therecanalsobeanexchangeoffattyacidsbetweenthosein493

thefishwiththoseinthefryingoil.N‐3fattyacids insardinesfellbetween2‐3494

foldwhentheywerefriedineithersunfloweroiloroliveoilandtherewasarise495

inn‐6fattyacids.68496

497

Inconclusion, the typeof fish, itsdiet, andhow it ispreparedcontribute to its498

nutritional content, and these factors may vary significantly between499

Mediterraneanandnon‐Mediterraneancountries.500

501

Dairyproduce502

The preferred types of dairy produce consumed in many Mediterranean503

countries are significantly different to those consumed in non‐Mediterranean504

countries. In most Mediterranean countries, Spain being the main exception,505

proportionally less milk and milk beverages and more cheese and yogurt are506

consumedthaninNorthEuropeancountries.69Significantly,a largenumberof507

the cheeses in Mediterranean countries are made from sheep's milk (eg508

Roquefort and tomme from the Pays Basque region of Southern France,509

manchego fromSpain,and feta fromGreece)andgoat'smilk (suchas thewide510

rangeofchevresfromSouthernFrance).Bycontrast,themaindairyproducein511

23

Northern Europe is cow'smilk and cow'smilk cheese such as "cheddar type"512

hardcheeseintheUK.513

514

Althoughcheesesmadefromgoatandsheepmilkhaveasimilartotalsaturated515

fatcontentascheesesmadefromcowmilk,thecompositionofthesaturatedfats516

is different since goat and sheep milk are richer in medium chain fatty acids517

(MCFAs)ie<12carbonatoms(<12C).TheseMCFAsincludecaproicacid(C6:0),518

caprylic(C8:0)andcapric(C10:0)(thenamesarederivedfromtheLatincaper519

foragoat)(Table1).70Forexample, freshgoatcheesewith40%fatcomprises520

15%<12CFAswhereastheseFAsonlyconstitute7%inacomparablecow’smilk521

cheese.Similarly, thefatcontentofRoquefortcheesecomprises15%<12CFAs522

and23%palmiticacid.Bycomparison,acow’smilkfattycheesecomprises33%523

palmitic acid (16C), themost atherogenic SFA. 71 MCFAs are non‐atherogenic,524

andaredirectlyoxidisedintheliverthusreducingtheiraccumulationinadipose525

tissue.SomeepidemiologicalevidencesupportingthebeneficialeffectsofMCFAs526

camefromtheNurses'HealthStudy(aprospectivecohortstudyincludingmore527

than 80,000 US females) which showed that in contrast to LCFAs, intake of528

MCFAswasnotsignificantlyassociatedwiththeriskofCHD.72529

530

The composition of milk is influenced by the animal's diet and this can have531

beneficial effects. Goats and sheep aremore likely than cows to be raised on532

naturalpasture.Pasture isrich inALAandgivesrisetohigher levelsofALAin533

theanimal'slipidswhichcanbedesaturatedtoEPA,ann‐3LC‐PUFAwithanti‐534

inflammatoryproperties.535

24

536

HighconsumptionofdairyproducewasconsideredtobedetrimentalintheMDS537

devisedbyTrichopoulouandcolleagues.Thisisbecausethedairyproducewas538

rarely low‐fat and longer chain SFAs have detrimental effect on cholesterol539

levels.Thereisnowatrendinmanycountriestowardslow‐fatdairyproduce.In540

theUK,weekly purchases ofwholemilk have steadily decreased year on year541

(2655ml/weekin1974downto352ml/weekin2010)withaconcomitantrise542

in the purchase of skimmed milk (mostly semi‐skimmed). 33 Similarly, milk543

consumption in the US is mostly low‐fat. However, not all saturated fats are544

harmful.Myristicacid (14C),present in themilkof ruminants, isnecessary for545

the myristoylation of several functional proteins, 73 and it is not atherogenic546

whentheexogenoussourceis<2%ofthetotalenergyintake.Also,thenatural547

trans‐FAtrans‐palmitoleicacid(cis‐16:1n‐7), levelsofwhichcorrelatestrongly548

with whole fat dairy consumption, was shown to be associated with lower549

metabolicriskfactors.74Theseobservationsquestiontherelevanceofthelow‐550

fatmilkrecommendationsinmanycountries.551

552

Meat553

Arecentmeta‐analysisconcludedthatredmeatconsumptionisassociatedwith554

asmallincreaseintheriskforcolorectalcancer,75althoughotheranalyseshave555

concludedthatbecauseofpossibleconfoundingthecurrentevidenceforsuchan556

associationisweak.76Ithasbeensuggestedthatthepro‐carcinogeniceffectsof557

haem iron, a putative carcinogen in red meat, can be suppressed by various558

dietaryconstituentssuchaschlorophyll,calciumandantioxidantvitamins(Cand559

25

E), 77,78 although the possible relevance of these interactions in relation to the560

Med diet is not known. Marinating, a technique traditionally used in561

Mediterranean cuisine to tenderise cheap cuts, may also potentially have562

beneficialhealtheffects.Cookingmeatathightemperatures,suchasfryingand563

grilling, generates carcinogenic heterocyclic aromatic amines (HA), and564

marinades that contain virgin olive oil, onions, garlic, herbs or redwine have565

highantioxidantcapacityandhavebeenshowntoinhibitHAformation.79‐81566

567

The geographical characteristics of the Mediterranean favour small livestock568

withspecialisedfeedinghabits:sheepandgoatscantakeadvantageofthehilly569

landscapeandofMediterraneangrazing,whereaspigspreferopenwildspaces570

suchasinholm‐oakforest.BecausethepastureofMediterraneananimalsused571

toproducedairyandmeatisricherinPUFAsthanthatoftheequivalentanimal572

givenanimal feeds, theirFAprofile ishealthier.This is especially true forpigs573

running inopenspaces inCorsicaandSardinia‐ theirmeat is leaner,andtheir574

fat consists of 40 to 50%MUFA. Togetherwith the higher content of LA, this575

resultsinlessSFAinthefatcomposition(Table2).71,82576

577

Otherfoods578

Anumber of other foodsnot generally scored for inMDSmayhave important579

healthbenefits foraMeddiet.These includeherbs (also takenasherbal teas),580

wild greens, and pumpkin, sunflower and other types of seeds. Local581

consumption of these can be high, and many are very rich sources of582

26

phytochemicals(forexample,pumpkinseedscontainhighlevelsofphytosterols)583

andothernutrients.2584

585

Notable by their absence in a traditional Med diet aremodern fast foods and586

sugar‐sweeteneddrinks.20Fastfoodscanbeamajorsourceofsaltandtransfats587

‐bothwell‐knownriskfactorsforCVD,andbothfastfoodsandsugar‐sweetened588

drinksarepositivelyassociatedwithlong‐termweightgain.83Anevaluationof589

fast foods and sugar‐sweetened drinks is only rarely included inMDS. In one590

such study from rural Lebanon it was found that when food consumption591

deviated from a traditionalMed diet by including refined cereals and pastries592

and sugar‐sweetened drinks, there was an increase in obesity and visceral593

adiposity.55594

595

Alcohol596

Moderatealcoholconsumption(definedasmenconsuming10gto<50gperday597

andwomenconsuming5gto<25gperday)isassumedtobebeneficialinMDS5.598

This is most strongly linked to a reduced risk of CVD. The most compelling599

mechanism to explain the cardioprotective effects of moderate alcohol600

consumptionistheincreaseinlevelsofHDL‐cholesterol;beneficialeffectsonthe601

vasculaturemayalsobeinvolved.602

603

A number of studies fromnon‐Mediterranean countries have shown that even604

moderatealcoholconsumptionincreasestheriskofcanceratsomesites,suchas605

27

thebreast.84,85Bycontrast,aMeddietreducesoverallcancerrisk,andthereis606

noevidencefromspecificanalysisofthealcoholcomponentthatmoderatelevels607

of consumption in the context of a Med diet increases cancer risk. 86 One608

important factor that might contribute to these disparities between609

Mediterranean and non‐Mediterranean countries with regard to the risk of610

cancerwithmoderatealcohol consumption isdrinkingpattern. 87Whereas the611

custom in Mediterranean countries is to drink in moderation with a meal,612

drinking outside mealtimes and binge drinking are more prevalent in North613

European countries. 88,89 Drinkingwith ameal slows the rate of absorption of614

alcohol from thegutwhereasdrinkingonanempty stomach raisesabsorption615

rates, and may increase blood alcohol concentrations to levels that saturate616

alcohol metabolic pathways resulting in the production of carcinogenic617

metabolites. Dietary folates may also possibly influence the cancer risks of618

drinking. Some studies, 90 but not all, 84 have shown that folates reduce the619

cancer‐associatedeffectsofmoderatealcoholconsumption.Itisnoteworthythat620

theMed diet has particularly high levels of folate consumption, and there is a621

goodcorrelationbetweenfolateconsumptionandadherencetoaMeddiet.91622

623

Alcohol consumption in Mediterranean countries is typically associated with624

wine, mostly red which is drunk with a meal, whereas beer and spirits are625

consumedingreaterquantitiesinsomenon‐Mediterraneancountries.88Thereis626

someevidencethatoverandabovetheeffectsofalcohol,phenolicsthatoccurin627

redwinemayhavespecificcardioprotectiveeffects.Distinguishingbetweenthe628

effects of alcohol and phenols in wine can be undertaken using dealcoholised629

28

wine.Forexample,dealcoholisedredwineretainedtheabilityofcompletewine630

tomodulatedleucocyteadhesionmolecules,importantinflammatorybiomarkers631

relatedtoatherosclerosisinsubjectsathighriskofCVD.92Studiesalsosuggest632

thatdrinkingwinewithamealmayconferadditionalcardioprotectiveeffects.93633

A large number of studies have shown that dealcoholised wine increases634

postprandial total antioxidant capacity and reduces postprandial rises in635

oxidisedLDL‐cholesterol,animportantriskfactorforCVD.46,94,95636

637

In summary, drinking moderate amounts of red wine with a meal may have638

superior health benefits compared to other types of drinking, and this is not639

assessed when measuring consumption of alcohol in MDS. Hence, factors not640

monitoredinMDS‐suchasdrinkingpattern,otherdietaryconstituentsandtype641

of alcohol ‐ are important factors to considerwhenweighing up the risks and642

benefitsassociatedwithmoderatealcoholconsumption.643

644

Discussion645

In the traditional concept of the Med diet, there are various food habits and646

lifestyleaspectsthatmaybeabsentinnon‐Mediterraneanpopulations.Wehave647

describedhowtheaprioriMDSfirstdescribedbyTrichopoulouandcolleagues648

in2003thereforeneededtobeadaptedforspecificpopulations;butineffectitis649

nolongerMediterraneansincethereareanumberofnutritionalcharacteristics650

which are different from the typical Mediterranean diet. Determining if these651

adaptationsinfluencehealthoutcomesisimportantwhenapplyingaMeddietto652

populations in non‐Mediterranean countries. One lifestyle factor that may be653

29

important is physical activity, and in fact this is generally taken into654

consideration in questionnaires. But for others, such as meal structure, the655

organisationofmealsduringtheday,conviviality,andtakingasiesta,itwouldbe656

necessarytoextendthescopeofquestionnairesundertakenaspartofevaluating657

theMDS.Althoughmoretimeconsuming,informationonthesourceofmeatand658

dairy products would also be helpful by assessing the importance of specific659

categories of SFA, and the level of PUFAs. This could be supported with660

biomarkermeasurementsoffattyacidsandothernutrients.11Anotherbiological661

measurementofinterestisvitaminDstatus.662

663

It became evident during the early development of MDS that the first MDS,664

originallydevelopedforaMediterraneanpopulation,wouldhavetobeadapted665

for non‐Mediterranean populations in order to take into consideration the666

genuineeatinghabitsofnon‐Mediterraneanpopulations.19,54,55Infact,takinga667

nutritional survey aposteriori in order to identify dietary patterns is the best668

way to reveal the healthiest type of diet among the eating habits of this669

population.ThesepatternscouldthenbecomparedtotheoriginalMeddiet,and670

differencesbetween the twopatterns canbe identified.Using this approach to671

adapting theMDS, some important featureshavebeen identified. For example,672

therMed‐score19andthenewaposterioriMDS17 identified the importanceof673

taking olive oil consumption into account, and for the latter the necessity of674

consideringanabsoluteamountoffoodinrelationtoitsbeneficialeffect.675

676

30

Measuringplasmalevelsofselectednutrientsthatarespecifictoauniquesource677

orclassof food(e.g.LCn‐3PUFAand fish)mayofferamoreprecisewaythan678

FoodFrequencyQuestionnairesofassessingtheroleofspecificnutrientsforthe679

healthbenefitsofthetraditionalMeddiet.WhenapplyingtheMeddiet innon‐680

Mediterraneanpopulations,particularlyrelevantnutrientsarethoselinkedwith681

healthwhose levels are likely tobe influencedby culinaryand lifestyle factors682

that vary significantly between Mediterranean and non‐Mediterranean683

populations. One candidate nutrient is folate, since dietary intake of folate is684

associated with a reduced risk of a range of chronic disorders such as colon685

cancer. 96Folate levels in foodsare influencedbyculinarypractices: it iswater686

soluble and heat labile and boiling results in leaching of folate into cooking687

water.41Moreover,folatelevelsvarywidelybetweenvegetablessinceitoccurs688

mainly in green leafy vegetables and so will not be specifically assessed by689

quantifying total vegetable intake. Hence, folate plasma levels may not690

necessarilybereflectedinMDS.691

692

SufficientplasmalevelsofothernutrientsthatarelinkedtoadherencetoaMed693

dietmayalsobe important inorder fornon‐Mediterraneans toachieve the full694

benefits of a traditional Med diet. Gerber et al. found a significant correlation695

betweenplasmalevelsofα‐tocopherol,β‐carotene,EPAandDHAwiththeMed696

dietqualityindex,especiallywhenthesenutrientswerecombinedinacomposite697

index, thus establishing that plasma values of these nutrients correlated with698

goodadherencetoaMeddiet.11SubjectsinNorthernSpainwithhigherMeddiet699

adherence,asmeasuredbytwodietaryindexes,hadsignificantlyhigherplasma700

31

concentrations of β‐carotene, folates, vitamin C, α‐tocopherol and HDL701

cholesterol. 91 Carotenoids may also be useful biomarkers because of their702

associationwithriskofcanceratcertainsitesandbecausefoodpreparationcan703

influence bioavailability. However, correlating plasma concentrations of a704

particular nutrient with disease reduction is not straightforward since food705

plantscontainmanynutrients thatareconsumedat thesametimee.g.mostof706

thefruitandvegetablescontainingcarotenoidscontainalsolignans.707

708

Conclusions709

Although there is extensive epidemiological evidence supporting the health710

benefitsofaMediterraneandiet,thisismostlyderivedfromMediterraneandiet711

scoresthatdonotfullytakeintoconsiderationthemanypotentiallyconfounding712

factors between Mediterranean and non‐Mediterranean populations. We have713

identifiedanumberof factors thatmayconfound theassessmentof thehealth714

benefitsofaMeddietinMediterraneancountries,bothbecauseofthenatureof715

the food itself and also due to aspects of food production and preparation.716

Lifestylefactorssuchasmealpatternsandexposuretosunlightmayalsoactas717

confounders. Improving Mediterranean diet scores and measuring plasma718

nutrient levelsmayhelpmitigate the effects of these confounders. Taking into719

considerationtheseconfoundersmayhave importanthealth implicationswhen720

implementingaMediterraneandietinnon‐Mediterraneanpopulations.721

722

Acknowledgements723

Theauthorshavenorelevantintereststodeclare724

32

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1003Table1Mediumchainfattyacidcontentofsheep,goatandcowmilk701004

Fattyacid Fattyacidcomposition(%total)

Sheep Goat Cow

CaproicC6:0 2.9 2.4 1.6

CaprylicC8:0 2.6 2.7 1.3

CapricC10:0 7.8 10.0 3.0

Total 13.3 15.1 5.9

1005

1006

Table2Fatcompositionofvariousmeats(basedon71,82)1007

45

Meat Fattyacids(%totalfat)

Saturatedfattyacids

Monounsaturatedfattyacids

Totalpolyunsaturatedfattyacids

Linoleicacid

Alpha‐linolenicacid

Lamb 52.1 40.5 5.8 5.0 0.8

Pork 43.2 47.6 9.2 8.6 0.6

Beef 56.4 40.3 3.2 2.5 0.7

1008

1009

1010