Results of the Copenhagen Cheese Studies: Importance of the matrix

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2 Results of the Copenhagen Cheese Studies: Importance of the matrix Tanja Kongerslev Thorning, Post doc Arne Astrup, Professor MD University of Copenhagen World Dairy Summit 2016

3 Saturated fat SF has for decades been considered being the bad guy Known to increases LDL-cholesterol Also SF increases HDL-cholesterol and reduces TG Humans does not eat groups of fatty acids but complex foods with mixtures of fatty acids Micha & Mozaffarian, Lipids (2010)

4 Saturated fat Is saturated fat independent on the food matrix?

5 Prospective studies of cheese intake and risk of CVD, CHD and stroke Favors a high cheese intake Chen et al. (2016) Eur J Nutr., Aug 12

6 Intervention studies on cheese intake and LDL-cholesterol = correct? De Goede et al. Nutrition Reviews (2015)

7 High content of active components in cheese Calcium * Phosphate * Fermented MFGM ** Whey/casein (per 100 g) (per 100 g) (+/-) (per 100 g) Cheese (25%) 659 mg 510 mg g casein Milk (skimmed) 124 mg 96.8 mg g whey/casein Milk (whole) 116 mg 93 mg g whey/casein Yoghurt (low fat) 136 mg 99 mg + ~ g whey/casein Cream (38%) 67 mg 57 mg g - Butter 15 mg 24 mg DTU ** Dewettinck et al. (2008), International Dairy Journal vol 18, Conway et al (2014), Animal Frontiers, Vol. 4, No. 2 The cheese-matrix may modulate the effect of saturated fat on LDL-cholesterol

8 We need to study foods rather than nutrients! Possible mechanisms of cheese Milk fat globule membrane - polar lipids Fermentation and ripening - bacteria Minerals - calcium and phosphate Reduce hepatic de novo FA synthesis Modulate expression of genes in lipid metabolism Inhibit intestinal cholesterol absorption Change gut microbiota composition Generate bioactive components

9 Amorphous calcium-phosphate

10 Chylomicron TG (mmol/l) Calcium fatty acid soaps Favors long chain saturated fatty acids Lorenzen and Astrup, Am. J. Clin. Nutr. (2007) Christensen et al., obesity reviews (2009)

11 Dairy calcium from milk and cheese Am J Clin Nutr 2014;99:

12 The Copenhagen Cheese Project (4 studies) The aim was to examine the effects of Cheese fat content Cheese ripening duration Cheese saturated fatty acid composition on Fecal fat excretion Markers of cardiovascular disease Markers of type 2 diabetes

13 Study I: Fat within cheese-matrix vs. outside cheese-matrix (porcine) 14-day parallel intervention in 36 pigs Study diets Three iso-caloric macronutrient-matched intervention diets REG: diet with regular-fat cheese RED: diet with reduced-fat cheese + butter BUT: control diet with butter

14 Importance of the location of dairy-fat? r=0.86 (P< ) Strong correlation!

15 Results of the Copenhagen Cheese Studies: Importance of the matrix Lack of difference in LDL-cholesterol may be due to balancing diets with potato protein

16 Study II: Regular-fat vs. reduced-fat cheese vs. CHO (Humans) (AJCN, 2016, in press) Parallel study in 139 free-living subjects with metabolic syndrome 3-months equal intake of regular-fat cheese to reduced-fat cheese or an isocaloric amount of carbohydrate-rich foods

17 Study II: Regular-fat vs. reduced-fat cheese vs. CHO (Humans) Blood lipids No difference in LDL-cholesterol concentrations between regular- or reduced-fat cheese Despite significant differences in dietary fat E% and saturated fat intake Tendency to an increase in HDL-cholesterol concentration by regular-fat cheese Currently awaiting particle size data Body weight No difference in body weight ~200 kj/d lower energy supply with the reduced-fat cheese May support an importance of the fat excretion (stronger with regular-fat cheese) Fat excretion not measured

18 Study III: Cheese ripening time (porcine) McSweeney (2004)

19 Study III: Cheese ripening time (porcine) 21-day parallel intervention in 36 pigs Isocaloric diets with equal amounts of cheese (35g cheese/100g diet) 4-MRC: 4-month ripened cheddar 14-MRC: 14-month ripened cheddar 24-MRC: 24-month ripened cheddar 4-MRC 14-MRC 24-MRC Casein % Peptides % Free amino acids %

20 Study III: Cheese ripening time (porcine) No differences in TC, LDL, HDL, or TG after intake of the cheeses Long-term ripened cheddar may improve insulin sensitivity No difference in plasma glucose after intake of the cheeses

21 Study IV: Saturated fat in cheese vs. meat vs. CHO (humans) 14-day 3-period cross-over study 14 overweight, postmenopausal women with slightly increased cholesterol

22 Study IV: Saturated fat in cheese vs. meat vs. CHO (humans) Fecal fat excretion depends on: the dietary fat content the calcium content

23 Apo A-1 (g/l) HDL-C (mmol/l) Study IV: Saturated fat in cheese vs. meat vs. CHO (humans) 1,8 1,6 1,4 1,2 1 0,8 0,6 0,4 0,2 0 a CHEESE diet CARB diet MEAT diet b P diet= a HDL response depends on the dietary fat content a b P diet= a Surprisingly, no difference in LDL-cholesterol CHEESE diet CARB diet MEAT diet

24 Study IV: Saturated fat in cheese vs. meat vs. CHO (humans) Carbohydrates expected to reduce LDLcholesterol compared to saturated fat Explained by the higher fecal bile acid excretion with cheese and meat?

25 Conclusions Fecal fat excretion Cheese increases fecal fat excretion compared to carbohydrates, butter, and meat The effect may be strongest for fat imbedded in the cheese-matrix (porcine) Fecal fat excretion is not affected by the ripening duration (porcine) Blood lipids Cheese causes less increase in LDL-cholesterol compared to butter, but similar LDL-cholesterol as a diet with a high meat or carbohydrate content Regular-fat cheese seems to have a distinct effect on HDL-cholesterol but equal effect on LDL-cholesterol compared to reduced-fat cheese A long-term ripened cheese (cheddar) causes lower NEFA concentration than short-term ripened cheese (in porcine) Insulin sensitivity Long-term ripened cheese (cheddar) improves HOMA-IR (in porcine)

26 Future perspectives More research in whole foods Moving towards food based dietary guidelines Studies including a broader range of cardiovascular risk markers One diet does not fit all moving towards personalized nutrition True?

27 Acknowledgements Colleagues Arne Astrup, UCPH Anne Raben, UCPH Farinaz Raziani, UCPH Tine Tholstrup, UCPH Nathalie Bendsen, UCPH Janne Lorenzen, UCPH Pia Kiilerich, UCPH Ylva Ardö, UCPH Henry Jörgensen, AU Søren Krogh Jensen, AU Study participants Funding Danish Dairy Research Foundation Dairy Research Institute (USA) Dairy farmers of Canada National Interprofessional Center for Dairy Economy (France) Dairy Australia Dutch Dairy Association