Laboratoire de Biochimie et Nutrition HumaineAGROCAMPUS - INRA, Rennes, FRANCE

NUTRITIONAL INTEREST OF CHEESE FAT

A lot of new datas

METABOLISM AND FUNCTIONS OFSATURATED FATTY ACIDS

Pr. Philippe LEGRAND

Montreal, August 2011

SATURATED FATTY ACIDS

- We make them

- We eat them

- Metabolism

- Important specific functions

- Problems with CVD and MS biomarkers

Saturated fatty acids« We do synthesize them» : (human, animals, plants…)

Sugars, starch, alcohol……….

Palmitic acid

18:0

16:0

Stearic acid

synthesis

elongation

In addition,mammary gland synthesizes the short and middle chain saturates (C4-C10), plus lauric (C12) and myristic acid (C14)

Sugars, starch…..

Palmitic acid 16:0

Mammary gland

C4

C6

C8

C10

C12

C14

SATURATED FATTY ACIDS

- We make them

- We eat them

- Metabolism

- Important specific functions

- Problems with CVD and MS biomarkers

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

SATURATED FATTY ACIDS

- We make them

- We eat them

- Metabolism

- Important specific functions

- Problems with CVD and MS biomarkers

Intestine

Long chain fatty acids

Short and middle chain fatty acids Portal vein

Chylomicrons

Lymph

MuscleAdipose

Circulation

Comparative absorption of saturated fatty acids

STORAGE

CATABOLISM(β-oxidation)

Liver

Myristic / Palmitic acid metabolism

Secretion

HEPATOCYTEC14:0

Uptake Incorporation into lipids

β-oxidation

Desaturation

Acylation of proteins (myristoylation)Biosynthesis

C14:0

Gene regulation ?

Elongation

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),

METABOLISM

Ø Short and middle chain SFA have a specific and « safe » metabolism, Ø Myristic acid and palmitic acid have not the same metabolic fate in

the cell :Ø Myristic acid is rapidly β-oxidized, weakly secreted in the form of TG-

VLDL, but strongly elongated into palmitic acid. No accumulation !Ø Palmitic acid is stored and secreted in the form of TG, weakly

elongated into stearic acid. Also main product of de novolipogenesis, palmitic acid accumulates in the cell !

Ø Stearic acid is less synthesized (than palmitic), actively desaturated into oleic acid. No accumulation !

SATURATED FATTY ACIDS

- We make them

- We eat them

- Metabolism

- Important specific functions

- Problems with CVD and MS biomarkers

Saturated fatty acids functions (in addition to energetical function)

C4 butyric

C6 caproïc

C8 caprylic

C10 capric

C12 lauric

C14 myristic

C16 palmitic

C18 stearic

C20 arachidic

C22 behenic

C24 lignoceric

- Inhibition of tumor proliferation in vivo and in vitro- Induction of apoptosis- Colon and smooth muscle cells- Less fat deposition - C8 ê 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

Saturated fatty acids functions (in addition to energetical function)

C4 butyric

C6 caproïc

C8 caprylic

C10 capric

C12 lauric

C14 myristic

C16 palmitic

C18 stearic

C20 arachidic

C22 behenic

C24 lignoceric

- Active desaturation to oleic acid

- Nervous structure (myelinisation)

- Componant of sphingolipids

- « non specific » acylation of some proteins

- Low elongation et β-oxidation 1 / 3 of phospholipids fatty acids : structural role

SATURATED FATTY ACIDS

- We make them

- We eat them

- Metabolism

- Important specific functions

- Problems with CVD and MS biomarkers

Saturated fatty acids functionsProblems ?

C4 butyric

C6 caproïc

C8 caprylic

C10 capric

C12 lauric

C14 myristic

C16 palmitic

C18 stearic

C20 arachidic

C22 behenic

C24 lignoceric

Problem with the CVD risk :Deleterious effects …. in case of excess

Accumulation of palmitic acid : endogenous + exogenous origins

- No problem with the CVD risk !

- No problem with the CVD risk !

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

Epidemiological studies (cohorts)Then

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

Neutral

Association between SFA and CVD risk :

Meta-analysis (Siri-Tarino 2010) : 21 cohorts”Overall, despite the conventional wisdom that reduced dietary saturated fatintake is beneficial for CVD health, there is no significant evidence for concludingthat 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

Recent Intervention studies on SFA More

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

Jebb et al, 2010

Dairy products study : beneficial effects of dairy products ?

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

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

Which saturated fatty acids ?

Short and middle chain fatty acids(C4- C10)

32% energy C8 - C10

Cholesterolemia

§ Non hypercholesterolemic Keys 1957Hashi 1960 (lowering effect)Hegsted 1965Keys 1965Wardlaw 1995 (RCT), 6% energy C8-C10Temme 1997 (RCT), 10% energy C6-C8-C10 (myristic, oleic)

§ HypercholesterolemicMc Candy 1970Swift 1992Cater 1997Tholstrup 2004 53% fat, 43% sat !

45% fat, 70% sat !

CHD risk : NO RISKHu et al., 1999 (Nurse Health Study)

Body weight, Fat mass, Waist circumference, TG : Favorable or neutralTsuji 2001, Nosaka 2003, Kasai 2003, St Onge 2003, Zhang 2010,

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.

CONCLUSION, Take Home Messages

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……..

……….. So, we did it in France throw the

recommandations of the food safety agency (ANSES)

MINIMAL PHYSIOLOGICALREQUIREMENT

ANC

Total lipids 30 35 - 40

Essential FA

C18:2 n-6 2 4

C18:3 n-3 0,8 1

DHA (C22:6 n-3) 250 mg 250 mg

Non essential FA

EPA (C20:5 n-3) - 250 mg

Lauric acid (C12:0) + Myristic acid (C14:0) +Palmitic acid (C16:0)

- ≤ 8

Total saturated fatty acids - ≤ 12Oleic acid (C18:1 n-9) - 15 - 20

Other non essential fatty acids - -

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)

DAIRY SFAs / other sources of SFAs

- 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

C4 butyric

C6 caproic

C8 caprylic

C10 capric

C12 lauric 3,5 %

C14 myristic 10 %

C16 palmitic 23-32 % 46-62 %*.... *

C18 stéaric 13 % 6 %.... *

Dairy SFAs « plant SFAs » ( from palm oil mainly)

13-15 %

SFA qualitative value + + + - - - *

SFA content : 52-70% 52……100%

* Worst if hydrogenation

COMPARATIVE COMPOSITION 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

CONCLUSION FOR DAIRY SOURCES OF SFA

Thanks for your attention