Facts on Fats - UniSA...Facts on Fats Ronald P. Mensink Department of Human Biology NUTRIM, School...

Facts on Fats

Ronald P. MensinkDepartment of Human BiologyNUTRIM, School for Nutrition, Toxicology and MetabolismMaastricht UniversityMaastricht The Netherlands

Outline of the Presentation

• Saturated fatty acids and cardiovascular risk- Stearic acid- Triglyceride structure

• N-3 polyunsaturated fatty acids

• Plant stanols

• Conclusions

Summary on the Effects of Fatty Acids on Fasting Plasma Lipoproteins

- compared to carbohydrates -LDL HDL TC/HDL TG

• SAFA =

• MUFAcistrans = =

• PUFAlinoleic acidα-linolenic acidEPA/DHA = = =

Two Meta-analyses on Cohort Studies …

… Two Different Outcomes

What Can We Learn From These Discrepant Findings

• Observational nutritional epidemiology has its proven benefits, but its limitations should be recognized

• Rely on randomized clinical trials, if available

And What Do RCTs Tell Us?

Mozaffarian et al. PloS Med, 2010

The Total to HDL Cholesterol Ratio Largely Explains the Effects of (n-6)-PUFA vs. SAFA

RR: 0.91 RR: 0.90

Mozaffarian et al. PloS Med, 2010

RR decreased when the duration of the study increased

Do (n-6)-PUFAs Affect Other Non-Lipoprotein Related Pathways?

• Systemic inflammation

• Blood pressure

• Endothelial function

• Haemostatic function

• Insulin resistance

• Postprandial metabolism

• Weight gain

Mixed results

What Is the Best Fasting Lipid Marker to Define Cardiovascular Risk?

• The options: LDL cholesterol HDL cholesterol Triacylglycerol

The total to HDL cholesterol ratio

• The options: LDL cholesterol HDL cholesterol Triacylglycerol

The total to HDL cholesterol ratio

For diet-induced changes: comparable risk estimates Total to HDL cholesterol is the most simple one

What Is the Best Fasting Lipid Marker to Define Cardiovascular Risk?

-0.04

-0.02

0

0.02

0.04

Total to HDL cholesterol

Effects of Different Classes of Fatty Acids onTotal to HDL Cholesterol

**

*

SAFA Cis-MUFACis-PUFA Trans-MUFA

Relative to carbohydrates

• SAFA do not• Cis-MUFA favorably• Cis-PUFA favorably• Trans-MUFA adversely

change the total:HDL cholesterol ratio

Effects of trans-MUFA is about7.3 as strong as that of SAFA

Change

Effects on CHD-risk of Consuming 5 En% of the Different FA in place of Carbohydrates

SAFA Cis-MUFACis-PUFA Trans-MUFA

-9

-6

-3

0

3

6

CHD-risk-0.2

-0.1

0

0.1

0.2


% ChangeChange

-0.04

-0.03

-0.02

-0.01

0

0.01


Effects of Individual Saturated Fatty Acids onTotal to HDL Cholesterol

Relative to carbohydrates

• C12:0 (lauric acid)

favorably affects the total toHDL cholesterol ratio

C14:0 (myristic acid) C16:0 (palmitic acid) C18:0 (stearic acid)

have no effectsSAFA C12:0 C14:0

C16:0 C18:0

*

Change

-0.20

-0.15

-0.10

-0.05

0.00

0.05


Effects on CHD-risk of 5 En% of the Individual Saturated FA in Place of Carbohydrates

SAFA C12:0 C14:0C16:0 C18:0

-10

-8

-6

-4

-2

0

2

CHD-risk

% ChangeChange

Fatty Acids and Plasma Markers of Inflammation and Endothelial Function

Fibrinogen CRP IL-6 E-selectin

CHO

OL

TFA

TFA+STE

STE

LMP

Baer et al. Am J Clin Nutr, 2004FA exchange: 8 En%

-3

0

3

6

CHD-risk

Effects on CHD-risk of 5 En% of C18:0 and Trans-MUFA

C18:0 Trans-MUFA

-9

-6

-3

0

CHD-risk

Compared to carbohydrates Replacement of TFA with C18:0

% Change% Change

Interesterification

• Interesterification: re-arrangement of fatty acids over the triacylglycerol molecule

Change in physical characteristics

• Interesterification can be used as an alternative to partial hydrogenation

Structure of Triacylglycerol from Vegetable Oils

Sn-1:Mainly (mono-un)saturated

Sn-2: Mainly polyunsaturated

Sn-3: Mainly (mono-un)saturated

Why Should We Care About the Positional Distribution of Fatty Acids?

Metabolism

• The sn-2 fatty acid is largely preserved, which may have metabolic consequences

• The sn-1 and sn-3 free saturated fatty acids may form calcium soaps in the GI tract

delayed or decreased absorption

Possible Differential Effects of Natural vs. Semisynthetic Fats is Not New …

... But Controversial

Grande et al. Am J Clin Nutr, 1970

Interesterification Does not Change the Effects of Fats on Serum Lipids

• Palmitic acid- Nestel et al. (Am J Clin Nutr 1995; 62:950-5)- Zock et al. (Am J Clin Nutr 1995; 61:48-55)

• Stearic acid- Grande et al. (Am J Clin Nutr 1970; 23:1184-93)- Berry et al. (Am J Clin Nutr 2007; 85:1486-94)

Effects of Interesterified Fat Blends on Fasting Serum Lipids are Highly Controversial

• Meijer and Weststrate (Eur J Clin Nutr 1997; 51: 527-34)

- Native vs. interesterified mixed fat blend providing4 or 8 En%.

- 60 healthy normocholesterolemic men and women- 21 days on diet (cross-over design)

No effects on the serum lipoprotein profile

Effects of Interesterified Fat Blends on Fasting Serum Lipids are Highly Controversial

• Sundram et al. (Nutr Metab 2007;4:3)

- Palm olein vs. partially hydrogenated soy bean oil vs. aninteresterified fat rich in stearic acid providing > 70% oftotal fat intake.

- Total fat intake was 31 En%.- 30 healthy normocholesterolemic men and women- 28 days on diet (cross-over design)

An interesterified fat rich in stearic acid has adverse effects on LDL cholesterol

Test Fats

• Palm olein

• Partially hydrogenated soybean oil (PHSO)

• Interesterified fats (IE) rich in stearic acid- Fully hydrogenated soybean oil- Blended with soybean oil and palm olein- Interesterification

Sundram et al. Nutr Metab, 2007

SAFA C16:0 C18:0 MUFA PUFA Trans

0

5

10

15

20

Palm olein PHSO Interesterified fat

En%

Intakes of Fatty Acids

Sundram et al. Nutr Metab, 2007

-0.40

-0.30

-0.20

-0.10

0.00

0.10

0.20

0.30

Predicted vs. Observed Effects of the Fats on LDL and HDL Cholesterol

-0.15

-0.10

-0.05

0.00

LDL cholesterol HDL cholesterol

Observed PHSOSundram et al. Nutr Metab, 2007Compared to Palm Olein: Observed IE

Predicted IEPredicted PHSO

mmol/L mmol/L

**

*

Conclusions about Saturated Fatty Acids

• Consumption of (n-6)-polyunsaturated fatty acids in place of a mixture of saturated fatty acids lowers cardiovascular risk

• Effects of other macronutrients largely unknown

• Stearic acid and interesterification may be suitable alternatives for trans monounsaturated fatty acids (but more research is needed …)




• Plant stanols

• Conclusions

CH3

CH3

CH3

COOH

COOH

COOH

3

3

3

Alpha-linolenic acid (ALA, C18:3n-3)

Eicosapentaenoic acid (EPA, C20:5n-3)

Docosahexaenoic acid (DHA, C22:6n-3)

first double bond in n-3 or omega-3 position

Intake from fish0.1-0.2 g/day

Intake from plant oils1-2 g/day

What About n-3 or ω-3 Fatty Acids - structures, dietary intakes -

Conversion of 〈−Linolenic Acid into DHA

∆6 desaturationElongation

∆5 desaturation

18:3(n-3)Linolenic acid (ALA)

20:5(n-3)EPA

Elongation22:5(n-3)

DPAElongation∆6 desaturationβ-oxidation 22:6(n-3)

DHA

Can 〈-Linolenic Acid Replace Fish Oil?

〈-Linolenic acid cannot replace fish oil

Can 〈-Linolenic Acid Replace Fish Oil?

• ALA and EPA / DHA have different metabolic effects

• Conversion of α-linolenic acid into EPA is low:

n-3 Fatty Acids and Cardiovascular Disease Outcomes- a systematic review -

Wang et al. Am J Clin Nutr, 2006

Relative Risk of Fatal MI Might Be Lower inMen with a High α-Linolenic Acid Intake

Dolocek & Granditis 1991

Ascherio et al. 1996

Oomen et al. 2001

Pietinen et al. 1997

Hu et al. 1999

Combined RR

0.3 1.20.4 0.650.5 0.8 1 1.5 2.7 3.5 4.52.0Brouwer et al. J Nutr, 2004

The Debate on n-3 Fatty Acids and Cardiovascular Disease Will Continue

Kromhout et al. (New Engl J Med, August 29, 2010) 4837 patients (60-80 yrs), who had had a myocardial infarction and

received good clinical care For 40 months, additional daily intake of 1.9 g ALA OR 376 mg EPA/DHA Conclusion: Low doses of n-3 fatty acids did not reduce cardiovascular

endpoints

Why Do Fish Oil FA Have Beneficial Effects onCardiovascular Disease?

• Lower serum triglycerides

• Lower blood pressure

• Decrease platelet aggregation

• Improve endothelial function?

• Are anti-inflammatory?

• Are anti-arrhythmic

0

5

10

15

20

25

Flaxseed Does not Increase (n-3)-LCPUFA Status in Human Myocardial Phospholipids

Olive oil (28 d) Flaxseed (29 d) Fish oil (33 d)

0

3

6

9%

Metcalf et al. Am J Clin Nutr, 2007

C20:4(n-6) C18:3 C20:5 C22:6

%

n-3 FA intake: 5-6 g

The Omega-3 Index as a Risk Marker for Death from Coronary Heart Disease

• Introduced by Harris and colleagues

• The sum of EPA+DHA in red blood cells

• >8% greatest cardioprotection•

0

2

4

6

Effects of 〈−Linolenic Acid and EPA/DHA on the Omega-3 index

Control ALA-group EPA/DHA group

• Run-in period of 4 weeks• Intervention period of 24 weeks• 10-12 subjects in each group• Additional ALA intake: 3.3 gram• Additional EPA/DHA intake: 0.6 gram

Mensink, Unpublished results

Om

ega-

3 in

dex

*

Conversion of Linoleic Acid and 〈−LinolenicAcid into LCPUFAs

∆6 desaturation (FADS2)Elongation

∆5 desaturation (FADS1)

18:3(n-3)Linolenic acid (ALA)

20:5(n-3)EPA

Elongation22:5(n-3)

DPAElongation∆6 desaturation (FADS2)

β-oxidation 22:6(n-3)DHA

18:2(n-6)Linoleic acid (LA)

20:4(n-6)AA

22:4(n-6)

22:5(n-6)

FADS1 FADS2 Gene Variants Relate to LCPUFA Levels

- Results from the KOALA Birth Cohort Study -

• Fatty acid composition was determined in week 34 of pregnancy and in milk 1 month postpartum

• For 309 women, 3 SNPs from the FADS1 FADS2 gene cluster were analyzed: rs174561, rs3834458, rs174575

• The SNPs were highly linked

• FFQ were determined in week 34 of pregnancy

• Genotype was not related to fatty acid intake

10

15

20

25

Plasma Human milk

The n-6 FA Profile in Plasma and Human Milk is Related to FADS1 Genotype

MM, n=166 Mm, n=125 mm, n=18rs174561: FADS1

0

2

4

6

8

Plasma Human milk

% C18:2(n-6)LA %C20:4(n-6)

AA

P

0.0

0.2

0.4

0.6

Plasma Human milk

The DHA Level in Plasma and Human Milk is Related to FADS1 Genotype


0

1

2

3

4

Plasma Human milk

% C20:5(n-3)EPA %C22:6(n-3)

DHA

P=0.580 P=0.083 P=0.002 P=0.044

Molto-Puigmarti et al. Am J Clin Nutr, 2010

Relation between Fish Intake and DHA in Human Milk Relates to FADS Gene Variants


Molto-Puigmarti et al. Am J Clin Nutr, 2010

Conclusions about (n-3) Polyunsaturated Fatty Acids

• α-Linolenic cannot replace EPA / DHA

Do not use the n-3 / n-6 ratio

• The usefulness of the Omega-3 Index needs to be proven

• FADS genotype variants are important determinants of LCPUFA levels. Studies with functional outcomes are needed




• Plant stanols

• Conclusions

Plant Sterols / Stanols Have a Structure Very Similar to that of Cholesterol

Cholesterol Sitosterol

Sitostanol Sitostanol ester

HO HO

HO R

Questions

• Do effects of plant stanols on LDL cholesterol level off at intakes?

• Do plant stanols only affect LDL cholesterol?

A large proportion of the populations has high TAG and low HDL cholesterol concentrations

Plant Stanol Esters Decrease LDL Cholesterol Dose-Dependently

mmol/L

LDL cholesterol LDL cholesterol

Mensink et al. Am J Clin Nutr, 2010

%

6-g group 9-g group3-g group

0.0

0.5

1.0

1.5

2.0

2.5

Baseline

In Subjects with the Metabolic Syndrome, Plant Stanols Lower Serum Triacylglycerol

-0.3

-0.2

-0.1

0

0.1

0.2

0.3

Change

Plat et al. J Nutr, 2010

ControlPlant stanols (8 weeks, 2 g plant stanols / day as a yogurt drink)

27% reduction by plant stanols versus control

mmol/L mmol/L

Conclusions about Plant Stanols

• Plant stanols lower serum LDL cholesterol dose-dependently at intakes up to 9 g

• Plant stanol esters may lower serum triacylglycerol concentrations, especially in subjects with elevated baseline serum triacylglycerol concentrations

This effect most likely origins from a lowered hepatic production of large TAG-rich VLDL particles




• Plant stanols

• Conclusions

Basis of Dietary Guidelines for Healthy Adults

1. Fat is not necessarily bad, but fatty acids can be bad

SAFA can be replaced by cis-(poly)unsaturated fatty acids (though fat intake should not be unlimited)

2. Functional foods can be helpful

3. There is more than just fat

Basis of Dietary Guidelines for Healthy Adults

• Total fat intake

→ Cardiovascular disease

→ Essential fatty acids→ Cardiovascular disease

• Saturated and trans fatty acids

• Polyunsaturated fatty acids

→ Essential fatty acids, vitamins, energy→ Insulin resistance, energy intake??

Thank You Very Much for Your Kind Attention!

Slide Number 1Outline of the PresentationOutline of the PresentationSummary on the Effects of Fatty Acids on Fasting Plasma Lipoproteins�- compared to carbohydrates -Two Meta-analyses on Cohort Studies …… Two Different OutcomesWhat Can We Learn From These Discrepant FindingsAnd What Do RCTs Tell Us?The Total to HDL Cholesterol Ratio Largely Explains the Effects of (n-6)-PUFA vs. SAFADo (n-6)-PUFAs Affect Other Non-Lipoprotein Related Pathways?What Is the Best Fasting Lipid Marker to Define Cardiovascular Risk?What Is the Best Fasting Lipid Marker to Define Cardiovascular Risk?Effects of Different Classes of Fatty Acids on Total to HDL CholesterolEffects on CHD-risk of Consuming 5 En% of the Different FA in place of CarbohydratesEffects of Individual Saturated Fatty Acids on Total to HDL CholesterolEffects on CHD-risk of 5 En% of the Individual Saturated FA in Place of CarbohydratesFatty Acids and Plasma Markers of Inflammation and Endothelial FunctionEffects on CHD-risk of 5 En% of C18:0 and Trans-MUFAInteresterificationStructure of Triacylglycerol from Vegetable OilsWhy Should We Care About the Positional Distribution of Fatty Acids?MetabolismPossible Differential Effects of Natural vs. Semisynthetic Fats is Not New … ... But ControversialInteresterification Does not Change the Effects of Fats on Serum LipidsEffects of Interesterified Fat Blends on Fasting Serum Lipids are Highly ControversialEffects of Interesterified Fat Blends on Fasting Serum Lipids are Highly ControversialTest FatsIntakes of Fatty AcidsPredicted vs. Observed Effects of the Fats on LDL and HDL CholesterolConclusions about Saturated Fatty AcidsOutline of the PresentationWhat About n-3 or -3 Fatty Acids �- structures, dietary intakes -Conversion of α-Linolenic Acid into DHACan α-Linolenic Acid Replace Fish Oil?Can α-Linolenic Acid Replace Fish Oil?n-3 Fatty Acids and Cardiovascular Disease Outcomes�- a systematic review - Relative Risk of Fatal MI Might Be Lower in Men with a High -Linolenic Acid IntakeThe Debate on n-3 Fatty Acids and Cardiovascular Disease Will ContinueWhy Do Fish Oil FA Have Beneficial Effects on Cardiovascular Disease?Flaxseed Does not Increase (n-3)-LCPUFA Status in Human Myocardial PhospholipidsThe Omega-3 Index as a Risk Marker for Death from Coronary Heart DiseaseEffects of α-Linolenic Acid and EPA/DHA on the Omega-3 indexConversion of Linoleic Acid and α-Linolenic Acid into LCPUFAsFADS1 FADS2 Gene Variants Relate to LCPUFA Levels �- Results from the KOALA Birth Cohort Study - The n-6 FA Profile in Plasma and Human Milk is Related to FADS1 GenotypeThe DHA Level in Plasma and Human Milk is Related to FADS1 GenotypeRelation between Fish Intake and DHA in Human Milk Relates to FADS Gene VariantsConclusions about (n-3) Polyunsaturated Fatty Acids Outline of the PresentationPlant Sterols / Stanols Have a Structure Very Similar to that of CholesterolQuestionsPlant Stanol Esters Decrease LDL Cholesterol Dose-DependentlyIn Subjects with the Metabolic Syndrome, Plant Stanols Lower Serum TriacylglycerolSlide Number 55Outline of the PresentationBasis of Dietary Guidelines for Healthy AdultsBasis of Dietary Guidelines for Healthy AdultsThank You Very Much for Your Kind Attention!Slide Number 60

Facts on Fats - UniSA...Facts on Fats Ronald P. Mensink Department of Human Biology NUTRIM, School...

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