NUTRITIONAL INTEREST OF CHEESE FAT. A lot of new datas

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Philippe LEGRAND Laboratoire de Biochimie et Nutrition

1 NUTRITIONAL INTEREST OF CHEESE FAT A lot of new datas METABOLISM AND FUNCTIONS OF SATURATED FATTY ACIDS Pr. Philippe LEGRAND Laboratoire de Biochimie et Nutrition Humaine AGROCAMPUS - INRA, Rennes, FRANCE Montreal, August 2011

2 SATURATED FATTY ACIDS - We make them - We eat them - Metabolism - Important specific functions - Problems with CVD and MS biomarkers

3 Saturated fatty acids «We do synthesize them» : (human, animals, plants ) Sugars, starch, alcohol. synthesis Palmitic acid 16:0 elongation Stearic acid 18:0

4 In addition,mammary gland synthesizes the short and middle chain saturates (C4-C10), plus lauric (C12) and myristic acid (C14) Sugars, starch.. Mammary gland C4 C6 C8 C10 C12 C14 Palmitic acid 16:0

5 SATURATED FATTY ACIDS - We make them - We eat them - Metabolism - Important specific functions - Problems with CVD and MS biomarkers

6 CONSUMPTION IN FRANCE Men Women Total Lipids (g/day) 103,0 81,6 91,8 Lipids (%Energy) 38,8 39,8 39,3 Saturated Fatty Acids (%En) 15,8 15,9 15,9 AET : Apport énergétique total Source: INCA 2

7 SATURATED FATTY ACIDS - We make them - We eat them - Metabolism - Important specific functions - Problems with CVD and MS biomarkers

8 Comparative absorption of saturated fatty acids Intestine Long chain fatty acids Lymph Circulation Chylomicrons Adipose Muscle STORAGE Liver Short and middle chain fatty acids Portal vein CATABOLISM (β-oxidation)

9 Myristic / Palmitic acid metabolism C14:0 Secretion HEPATOCYTE Uptake C14:0 Incorporation into lipids β-oxidation Elongation Biosynthesis Gene regulation? Rioux et al. (2000), Rioux et al. (2002), Legrand et al. (2002), Rioux et al. (2003), Jan et al. (2004), Rioux et al. (2005), Rioux et al. (2006), Rioux et al. (2007), Rioux et al. (2008), Desaturation Acylation of proteins (myristoylation)

10 METABOLISM Short and middle chain SFA have a specific and «safe» metabolism, Myristic acid and palmitic acid have not the same metabolic fate in the cell : Myristic acid is rapidly β-oxidized, weakly secreted in the form of TG- VLDL, but strongly elongated into palmitic acid. No accumulation! Palmitic acid is stored and secreted in the form of TG, weakly elongated into stearic acid. Also main product of de novo lipogenesis, palmitic acid accumulates in the cell! Stearic acid is less synthesized (than palmitic), actively desaturated into oleic acid. No accumulation!

11 SATURATED FATTY ACIDS - We make them - We eat them - Metabolism - Important specific functions - Problems with CVD and MS biomarkers

12 Saturated fatty acids functions (in addition to energetical function) C4 butyric C6 caproïc C8 caprylic C10 capric C12 lauric C14 myristic C16 palmitic - Inhibition of tumor proliferation in vivo and in vitro - Induction of apoptosis - Less fat deposition Colon and smooth muscle cells - C8 VLDL secretion (inhibition of apo B synthesis) - Hypocholesterolemic effect (C8, C10) - Antiviral role - Specific acylation of proteins - Activation of conversion from C18:3 n-3 towards EPA + DHA - Activation of sphingolipids synthesis C18 stearic C20 arachidic C22 behenic C24 lignoceric

13 Saturated fatty acids functions (in addition to energetical function) C4 C6 C8 butyric caproïc caprylic C10 capric C12 lauric C14 myristic C16 palmitic C18 stearic - Componant of sphingolipids - 1 «/ non 3 of specific phospholipids» acylation fatty of acids some : structural proteins role - Active Low elongation desaturation et β-oxidation to oleic acid C20 arachidic C22 behenic - Nervous structure (myelinisation) C24 lignoceric

14 SATURATED FATTY ACIDS - We make them - We eat them - Metabolism - Important specific functions - Problems with CVD and MS biomarkers

15 Saturated fatty acids functions Problems? C4 C6 C8 butyric caproïc caprylic - No problem with the CVD risk! C10 capric C12 lauric C14 myristic C16 palmitic C18 stearic Problem with the CVD risk : Deleterious effects. in case of excess Accumulation of palmitic acid : endogenous + exogenous origins - No problem with the CVD risk! C20 arachidic C22 behenic C24 lignoceric

16 Saturated fatty acids and health At the beginning : association with CHD risk Keys 1966, Kato 1973 But : ecological studies (7 countries study) NEVER CONFIRMED BY COHORT STUDIES

17 Then Epidemiological studies (cohorts) Association between SFA and CVD risk : Neutral Garcia 1980 Mc Gee 1984 Esrey 1996 Boniface 2002 Jakobsen 2004 Xu 2006 Gillman 1997 Mozzafarian 2004 Jakobsen 2009 Yamagashi 2009 Jakobsen 2010 (MI) Shekelle 1981 Kushi 1985 Posner 1991 Ascherio 1996 Pietinen 1997 Tucke 2005 Leosdottir 2007 Meta-analysis (Siri-Tarino 2010) : 21 cohorts Overall, despite the conventional wisdom that reduced dietary saturated fat intake is beneficial for CVD health, there is no significant evidence for concluding that dietary saturated fat is associated with an increased risk of CHD or CVD For dairy products specifically, see works by Elwood et al : no risk association

18 More Recent Intervention studies on SFA Lipgene study : a european randomized dietary intervention study on SFA No effect of reducing SFA (16% to 8%) on parameters of metabolic syndrome (insulin sensitivity, blood pressure), inflammation, LDL-C Diets including dairy products (full-fat vs low-fat), 12 weeks. Tierney et al, 2011 The RISK trial : replacement of SFAs by MUFAs or Carbohydrates No favorable effects on insulin sensitivity, reduction of TC/HDL-C ratio No dairy products included inthe intervention Dairy products study : beneficial effects of dairy products? Jebb et al, 2010 No effect (but no adverse effect!!), except positive effect on waist circumference despite higher energy intake (related to the presence of short chain FA?) Diets with 3-5 portions of dairy products (cheese), 6 months Wennersberg et al, 2009

19 Which saturated fatty acids? Stearic acid (C18:0) Neutral on cholesterolemia Yu 1995, Kelly 2001, Mensink 2005, Huster 2010 (review) Neutral on arterial diameter Mozzafarian 2004 Not thrombogenic Sanders 2001, Tholstrup 2003, Thijssen 2005 NO PROBLEM

20 Cholesterolemia Which saturated fatty acids? Short and middle chain fatty acids(c4- C10) Non hypercholesterolemic Keys 1957 Hashi 1960 (lowering effect) Hegsted 1965 Keys 1965 Wardlaw 1995 (RCT), 6% energy C8-C10 Temme 1997 (RCT), 10% energy C6-C8-C10 (myristic, oleic) Hypercholesterolemic Mc Candy 1970 Swift % energy C8 - C10 Cater 1997 Tholstrup % fat, 43% sat! CHD risk : NO RISK Hu et al., 1999 (Nurse Health Study) 45% fat, 70% sat! Body weight, Fat mass, Waist circumference, TG : Favorable or neutral Tsuji 2001, Nosaka 2003, Kasai 2003, St Onge 2003, Zhang 2010,

21 CONCLUSION, Take Home Messages No reason for considering SFA en bloc anymore, - in term of structure and metabolism, - in term of functions - in term of deleterious effect as well.

22 CONCLUSION, Take Home Messages No reason for considering SFA en bloc anymore, in term of structure and metabolism, in term of functions and in term of deleterious effect as well. - Need of more precise epidemiological studies (different saturated fatty acids, dose-effects approach, controls ) for evaluating the levels and sources where C12, C14, C16 FA are deleterious - Time for up to date recommendations without caricatural old statements of toxicity or eviction..

23 .. So, we did it in France throw the recommandations of the food safety agency (ANSES)

24 Adequate Intake (ANC :Apport Nutritionnel Conseillé) Values expressed in % of total energy intake except for DHA and EPA (in mg) for an adult (at 2000 kcal/day) MINIMAL PHYSIOLOGICAL REQUIREMENT ANC Total lipids Essential FA C18:2 n C18:3 n-3 0,8 1 DHA (C22:6 n-3) 250 mg 250 mg EPA (C20:5 n-3) mg Non essential FA Lauric acid (C12:0) + Myristic acid (C14:0) + Palmitic acid (C16:0) - 8 Total saturated fatty acids - 12 Oleic acid (C18:1 n-9) Other non essential fatty acids - -

25 DAIRY SFAs / other sources of SFAs

26 - Dairy products account for 34% total SFA (only!!!) (France) - SFA from dairy sources have an interesting composition (13% short and middle chain) - SFA from plant origin have a poor composition (long chain) - SFA from plant origin are less «visible» and cheaper - The health concern is the excess of C12, C14, C16

27 COMPARATIVE COMPOSITION OF SFA Dairy SFAs «plant SFAs» ( from palm oil mainly) C4 C6 C8 butyric caproic caprylic % C10 capric C12 lauric 3,5 % C14 myristic 10 % C16 palmitic % %*... * C18 stéaric 13 % 6 %... * SFA qualitative value * SFA content : 52-70% % * Worst if hydrogenation

28 CONCLUSION FOR DAIRY SOURCES OF SFA IF THE TOTAL SFA INTAKE SHOULD BE REDUCED, OR MORE SERIOUSLY IF THE ATHEROGENIC (when in excess) SFA SHOULD BE REDUCED THEN : 1) CONSIDER THE DAIRY / PLANT ORIGIN OF SFA. 2) DAIRY PRODUCTS ARE NOT THE GOOD TARGET QUALITATIVELY 3) DAIRY PRODUCTS ARE NOT THE UNIC TARGET QUANTITATIVELY

29 Thanks for your attention

SATURATED FATTY ACIDS A new paradigm is necessary. Nutrients before all.

SATURATED FATTY ACIDS A new paradigm is necessary Nutrients before all. Pr. Philippe LEGRAND Laboratoire de Biochimie et Nutrition Humaine AGROCAMPUS - INRA, Rennes, FRANCE EFSA Conference 2018, Parme