!!Διατροφή!και!αθηροσκλήρωση!!ίσως!το! καλύτερο!φάρμακο

Dietary!Fats!and!LDLCCholesterol! 0,18 0,14 0,10 β=0.032*& SFA! Change!in! LDLCC! (mmol/l)! 0,06 0,02-0,02-0,06-0,10 β=c0.009*& β=c0.019*& 0 1% 2% 3% 4% 5% percentage!of!calories!vs.!carbohydrate! MUFA! PUFA! Based&on&Mensink&&&Katan&2003.&&Figure&from&Micha&&&Mozaffarian,&Lipids&2010!

Dietary!Fats!and!Triglycerides! 0,00 Change!in! Triglycerides! (mmol/l)! -0,05-0,10-0,15 β=0.019*& β=c0.021*& β=c0.026*& 0 1% 2% 3% 4% 5% percentage!of!calories!vs.!carbohydrate! MUFA! SFA! PUFA! Based&on&Mensink&&&Katan&2003.&&Figure&from&Micha&&&Mozaffarian,&Lipids&2010!

Dietary!Fats!and!HDLCCholesterol! 0,05 β=0.01*& SFA! 0,04 β=0.008*& MUFA! Change!in! HDLCC! (mmol/l)! 0,03 0,02 β=0.006*& PUFA! 0,01 0,00 0 1% 2% 3% 4% 5% percentage!of!calories!vs.!carbohydrate! Based&on&Mensink&&&Katan&2003.&&Figure&from&Micha&&&Mozaffarian,&Lipids&2010!

Dietary!Fats!and!Total:HDLCCholesterol!Ra\o! 0,04 0,00 β=0.003& SFA! Change!in! Total:HDL! Ra\o! -0,04-0,08-0,12-0,16-0,20 β=c0.026*& β=c0.032*& 0 1% 2% 3% 4% 5% percentage!of!calories!vs.!carbohydrate! MUFA! PUFA! Based&on&Mensink&&&Katan&2003.&&Figure&from&Micha&&&Mozaffarian,&Lipids&2010!

Cohort!Studies:!!SFA!and!Heart!Disease!Events! No Significant Effect (!) MetaCanalysis&of&16&cohorts,&including&214,182! parocipants&and&8,644!chd&events& SiriCTarino&et&al,& AJCN&2010&

Saturated!Fat!and!CHD!C!RCT!Evidence! Women s!health!ini\a\ve!(whi)!rct! 48,835 women of various race/ethnicity, randomized to low fat diet vs. control. Total fat reduction: 9% lower at 7 years. Saturated fat reduction: nearly 3% lower at 7 years. Unequal intensity of intervention would bias toward intervention group. Followed for average of 7.5 years (up to 9 years). Howard et al, JAMA 2006

Total!Fat!and!CHD!C!RCT!Evidence! HR = 0.97 (95% CI = 0.90, 1.06) Women's Health Initiative (WHI), Howard et al, JAMA 2006

Pooled Analysis of 11 Major Cohort Studies Change in CHD Risk for Each 5% Energy -20-10 0 10 20 SFA PUFA *& SFA Carb SFA MUFA *& Total&of&344,696&individuals&with&5,249&CHD&events.&&*p<0.05& Jakobsen&et&al,&AJCN&2009!

Replacing SFA with PUFA: Randomized Trials PUFA n6 n6 Consumption (% energy) label ev n con Rx Clinical Trial Events n Control Rx 8 randomized trials, 13,614 participants, 1,042 CHD events % RR (95% CI) Weight RR (95% CI) % Weight LA Veterans 124 846 4.0 14.9 0.74 (0.53, 1.03) 13.44 MRC soy 96 393 4.4 20.4 0.86 (0.61, 1.22) 12.48 Oslo Diet-Heart 142 412 5.2 20.7 0.75 (0.57, 0.99) 16.87 Finnish - Men 72 461 4.3 12.9 0.55 (0.34, 0.88) 8.19 Finnish - Women 73 357 4.3 12.9 0.64 (0.41, 1.00) 8.69 Minnesota CS 252 9057 5.2 14.7 1.08 (0.84, 1.37) 18.79 DART 276 2033 6.4 8.9 0.91 (0.73, 1.14) 20.60 STARS 7 55 5.2 8.0 0.41 (0.09, 1.96) 0.94 Overall Overall Pooled Effect 0.81 (0.70, 0.95) 100.00 Overall Pooled Effect (per 5% energy) 0.90 (0.83, 0.97) NOTE: Weights are from random effects analysis.33.5 1 2 3 Rela%ve'Risk'of'Coronary'Heart'Disease' Mozaffarian, Micha et al, PLoS Med 2010

Saturated Fat vs. Carbohydrate Quality Change in CHD Risk for Each 5% Energy -20-10 0 10 20 30 40 SFA Low GI Carb SFA Med GI Carb SFA High GI Carb *& Risk&of&CHD&among&53,644&adults&followed&for&12&years.&&*p<0.05& Jakobsen&et&al,&AJCN&2010!

Makers! Dietary Change (each 5% energy) RR (95% CI) Polyunsaturated Fat Replacing Saturated Fat Predicted Effect from TC:HDL-C Change Meta-Analysis of 8 RCTs Pooled Analysis of 11 Observational Cohorts 0.91 (0.87, 0.95) 0.90 (0.83, 0.97) 0.87 (0.77, 0.97) Carbohydrate Replacing Saturated Fat Predicted Effect from TC:HDL-C Change 1.01 (0.98, 1.04) Women's Health Initiative RCT 0.98 (0.88, 1.09) Pooled Analysis of 11 Observational Cohorts 1.07 (1.01, 1.14) Monounsaturated Fat Replacing Saturated Fat Predicted Effect from TC:HDL-C Change 0.93 (0.89, 0.96) RCTs None -- Pooled Analysis of 11 Observational Cohorts 1.19 (1.00, 1.42) 0.7 1.0 1.5 Relative Risk of CHD for Each 5% Energy Intake Mozaffarian,&Micha&et&al.,&PLoS&Med&2010&

- : Κρεατικά! RR of CHD per 100 g/day of unprocessed red meats Study& RR!(95%!CI)& %!Weight& Whiteman&(1999) & Ascherio&(1994) & &&&&0.51&(0.22,&1.20)& 1.03&(0.80,&1.33)& 14.20& 38.20& Pooled RR=1.00 (0.81-1.23) Burke&(2007) & 0.69&(0.39,&1.22)& 23.20& MarOnezCGonzalez&(2002) & 1.60&(0.94,&2.74)& 24.40& Overall!(oneCstage!es\ma\on)& 1.00!(0.81,!1.23)& 100.00& Weights&are&from&random&effects&analysis&.25& && 1& && 4& RR of CHD per 50 g/day of processed meats Study& RR!(95%!CI)& %!Weight& Pooled RR=1.42 (1.07-1.89) Whiteman&(1999) & Burke&(2007) & Liu&(2003) & MarOnezCGonzalez&(2002) & Sinha&(2009)& &men *&& Sinha&(2009)& &women * && Overall!(oneCstage!es\ma\on)& Weights&are&from&random&effects&analysis&.25& && 1& && 4& 1.27&(0.36,&4.44)& 11.4&(1.1,&115.3)& 2.14&(1.25,&3.68)& 1.06&(0.28,&3.98)& 1.15&(1.08,&1.22)& 1.42&(1.29,&1.56)& *assessed total cardiovascular mortality (CHD and stroke) only 2.62& 0.80& 11.10& 2.34& 42.68& 40.45&!1.42!(1.07,!1.89)& 100.00& Για&κάθε&50&γρ&κατανάλωσης& επεξεργασμένου&κρέατος,& 42%&αύξηση&CHD&&& Micha R et al., Circulation 2010;121:2271-83

Average Constituents of Meats in the US Per 50g of meat Red meats Processed meats mean (SE) mean (SE) Energy (kcal) 123 (0.7) 138 (2.0) Total fat (% E) 50 (0.3) 58 (0.6) SFA (% E) 19 (0.1) 19 (0.3) MUFA (% E) 21 (0.1) 25 (0.3) PUFA (% E) 3 (0.0) 6 (0.1) Protein (% E) 46 (0.3) 35 (0.5) Sodium (mg)* 154.8 (3.4) 621.7 (7.6) Potassium (mg) 161.0 (0.8) 170.2 (1.9) Cholesterol (mg) 41.9 (0.2) 34.1 (0.3) Iron (mg) 1.1 (0.0) 0.6 (0.0) Nitrates (mg)* 3.3 (0.0) 4.6 (0.1) Nitrites (mg)* 0.5 (0.0) 0.8 (0.0) Nitrosamines (µg)* 0.1 (0.0) 0.3 (0.0) * Processed meats have higher preservative levels Micha&et&al.,&CirculaOon&2010&

Baseline!and!followCup!dietary!data!in!SDHS,!for!426!par\cipants! with!baseline!and!at!least!one!followcup!dietary!record!! Ramsden&CE&et&al&BMJ&2013&

KaplanCMeier!es\mates!of!5! yr!cumula\ve!death!rates! ater!randomiza\on!to!the! interven\on!or!control! group.!results!of!cox! propor\onal!hazards!model! include!all!followcup!data! (<83!months)!on!an! inten\on!to!treat!basis! Ramsden&CE&et&al&BMJ&2013&

Serum&Cholesterol&Regulated&by&Intracellular&Free&& &&&&&&&&Cholesterol&&&AcOvity&of&LDL&Receptors& Serum!LDL!! Liver!Cell! HMGCoA&Reducase& Acetate& Free!Cholesterol! Y! Y! Y! Y! Y! LDL!!!!!!LDL! Receptors! +& NCSREBP& LDL&receptor&protein& TranscripOon&LDL&receptor&gene&+&

Dietary Fatty Acids Influence Serum Cholesterol through Differential Effects on Free Cholesterol & LDL Receptor Activity &&Intracellular& Pool&free&chol& ACAT! Cholesterol Esters LDL!receptors!!!!!!!!Blood!LDLCC! Saturated and trans fatty acids (c12-16) Intracellular& pool&of&free& cholesterol& ACAT! Cholesterol Esters!!!!!!!!!!!MUFA!&!nC6!PUFA!

Schema'of'Physiologic'Effects'of'n43'PUFA'Consumption' Mozaffarian)D)Int)J)Environ)Res)Public)Health)2009;6:1894C1916))

N-3 fatty acids and cardiovascular events after myocardial infarction The Alpha Omega Trial 40 months intervention A margarine supplemented with a combination of EPA and DHA (with a targeted additional daily intake of 400 mg EPA-DHA) A margarine supplemented with ALA (with a targeted additional daily intake of 2 g of ALA) A margarine supplemented with EPA-DHA and ALA Placebo margarine Kromhout D et al N Engl J Med 2010;363:2015-26

Kromhout D et al N Engl J Med 2010;363:2015-26

Are!nC3!faky!acids!s\ll!cardioprotec\ve?! Harris!WS!Curr!Opin!Clin!Nutr!Metab!Care!2013,!16:141 149!

Key!Messages! Recent&nC3&fa{y&acid&intervenOon&studies&have&been&unable&to&detect&a&beneficial& effect&of&these&nutrients&on&cardiovascular&outcomes,&perhaps&due&to&a& combinaoon&of&low&doses&administered,&short&followcup,&high&background&nc3& fa{y&acid&intake,&frequent&use&of&modern&pharmacotherapy,&relaovely&lowcrisk& paoent&populaoons,&and/or&small&sample&sizes.& &The&latest&of&15&metaCanalyses&of&nC3&fa{y&acids&in&cardiovascular&disease&found& a&significant&benefit&on&cardiac&death&using&the&standard&rules&of&evidence,&but& concluded&no&benefit&when&applying&a&higher&standard.& &The&riskCbenefit&raOo&of&nC3&fa{y&acids&for&reducing&risk&for&cardiovascular& disease&remains&favorable.&

Γαλακτοκοµικά και καρδιαγγειακά νοσήµατα Nurses&Health&Study&έδειξε ότι η κατανάλωση γαλακτοκοµικών πλούσιων σε λιπαρά vs. µειωµένων σχετίζεται µε κίνδυνο CHD Συστάσεις για προτίµηση σε γαλακτοκοµικά µειωµένα σε λιπαρά Αντικρουόμενα&αποτελέσματα&σε&επιδημιολογικές&μελέτες& Κλινικές&μελέτες&δείχνουν&ουδέτερη&ή&θετική&επίδραση&στα&επίπεδα&TG,& HDL,&γλυκόζη& Μέτριας&ισχύς&αποτελέματα&δείχνουν&πιθανή&προστατευτική&επίδραση& έναντι&του&διαβήτη&και&καρδιαγγειακών&νοσημάτων& & Hu et al., Am J Clin Nutr 1999

Food!Sources!of!Saturated!Fat:!!Milk/Dairy! MetaCAnalyses!of!Milk/Dairy!Consump\on!and!Risk!of!CHD,!Stroke,!and!Diabetes! Mul\variableCadjusted!RR! comparing!the!highest!to!the!lowest!intake! Mozaffarian&D.&NutriOon&and&Cardiovascular&Disease.&Chapter&48.& In:&Braunwald's!Heart!Disease;!A!Textbook!of!Cardiovascular!Medicine,'9th!EdiAon.&2011&

Dietary!intake!of!saturated!fat!by!food!source!and!incident! cardiovascular!disease:!the!mul\cethnic!study!of!atherosclerosis!,&& Design:&ParOcipants&who&were&45 84&y&old&at&baseline&(n&=&5209)&were&followed& from&2000&to&2010.&diet&was&assessed&by&using&a&120citem&ffq.&cvd&incidence& (316&cases)&was&assessed&during&followCup&visits.&& Results:&A&higher&intake&of&dairy&SF&was&associated&with&lower&CVD&risk&[HR&(95%& CI)&for&+5&g/d&and&+5%&of&energy&from&dairy&SF:&0.79&(0.68,&0.92)&and&0.62&(0.47,& 0.82),&respecOvely].&In&contrast,&a&higher&intake&of&meat&SF&was&associated&with& greater&cvd&risk&[hr&(95%&ci)&for&+5&g/d&and&a&+5%&of&energy&from&meat&sf:&1.26& (1.02,&1.54)&and&1.48&(0.98,&2.23),&respecOvely].&& Marcia!C!de!Oliveira!Oko!Am!J!Clin!Nutr!2012;96:397C404!

Marcia!C!de!Oliveira!Oko!Am!J!Clin!Nutr!2012;96:397C404!

Γαλακτοκοµικά Πιθανοί µηχανισµοί Περιεκτικότητα!σε!βιταμίνη!D!(εμπλουτισμένα!τρόφιμα)! C C C Ρύθμιση&ομοιόστασης&γλυκόζης/ινσουλίνης& Ομοιόσταση&ασβεστίου& Πιθανή&θετική&επίδραση&στην&αρτηριακή&πίεση& Ασβέστιο! C C C Υπολογίζετε&οτι&το&50%&του&διατροφικού&ασβεστίου&προέρχεται&από&τα& γαλακτοκομικά&προϊόντα& Θετική&επίδραση&στην&αρτηριακή&πίεση& Πιθανή&αρνητική&συσχέτιση&πρόσληψης&ασβεστίου&και&σωματικού&λίπους& ( ενδοκυτταρικού&ασβεστίου&&&&&&&&&&&αυξημένη&λιπόλυση)& Κάλιο!και!μαγνήσιο! C Πιθανή&θετική&επίδραση&στην&αρτηριακή&πίεση&

150C250mg&Cholesterol&/&yolk& Dietary!Cholesterol!!

!!Consensus!on!Effect!of!Dietary!Cholesterol!on! Serum!Cholesterol!!!!!!!!Δ!Dietary!cholesterol!!!!!!!!100!mg/day!(~0.5!egg!yolk) Clinically no!effect!on!coronary!heart!disease!risk!!!!!!!!!!!!!δ!serum!cholesterol&& &&&&&&&&&&&&<&0.10!mol/l!(4C5mg/dl)

Spence&et&al.&tried&to&invesOgate&associaOons&in&paOents&with&exisOng&CVD.& The&results&are&extremely&interesOng&but&they&lack&adjustments&for&crucial& confounders.&& It&becomes&increasingly&clearer&that,&eggs&consumpOon&is&not&associated&with& CVD&risk&in&healthy&populaOons,&the&evidence&cannot&be&considered&as& conclusive&in&high&risk&populaoons.&& Eggs&consumpOon&may&increase&the&size&of&low&density&lipoprotein&(LDL)& parocles,&making&them&less&atherogenic,&and&they&are&also&major&dietary& sources&of&lutein&and&zeaxanthin,&two&potent&anooxidants,&which&may&reduce& LDL&oxidaOon.&

MetaCAnalysis!Comparing!Mediterranean!to!LowCFat!Diets! for!modifica\on!of!cardiovascular!risk!factors& Nordman!AJ!et!al!The!Am!J!Med!2011;124:! 841C51!

MetaCAnalysis!Comparing!Mediterranean!to!LowCFat!Diets! for!modifica\on!of!cardiovascular!risk!factors& Nordman!AJ!et!al!The!Am!J!Med!2011;124:!841C51!

Accruing!evidence!on!benefits!of!adherence!to!the! Mediterranean!diet!on!health:!an!updated!systema\c!review! and!metacanalysis! Sofi!F!et!al!Am!J!Clin!Nutr!2010;92:1189C96!