Facts on Fats. Ronald P. Mensink

Size: px

Start display at page:

Download "Facts on Fats. Ronald P. Mensink"

Adrian Jordan
5 years ago
Views:

1 Facts on Fats Ronald P. Mensink Department of Human Biology NUTRIM, School for Nutrition, Toxicology and Metabolism Maastricht University Maastricht The Netherlands

2 Outline of the Presentation Saturated fatty acids and cardiovascular risk - Stearic acid - Triglyceride structure N-3 polyunsaturated fatty acids Plant stanols Conclusions

3 Outline of the Presentation Saturated fatty acids and cardiovascular risk - Stearic acid - Triglyceride structure N-3 polyunsaturated fatty acids Plant stanols Conclusions

4 Summary on the Effects of Fatty Acids on Fasting Plasma Lipoproteins - compared to carbohydrates - LDL HDL TC/HDL TG SAFA = MUFA cis trans = = PUFA linoleic acid α-linolenic acid EPA/DHA = = =

5 Two Meta-analyses on Cohort Studies

6 Two Different Outcomes

7 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

8 Mozaffarian et al. PloS Med, 2010 And What Do RCTs Tell Us?

9 The Total to HDL Cholesterol Ratio Largely Explains the Effects of (n-6)-pufa vs. SAFA Mozaffarian et al. PloS Med, 2010 RR: 0.91 RR: 0.90 RR decreased when the duration of the study increased

10 Do (n-6)-pufas Affect Other Non-Lipoprotein Related Pathways? Systemic inflammation Blood pressure Endothelial function Haemostatic function Mixed results Insulin resistance Postprandial metabolism Weight gain

11 What Is the Best Fasting Lipid Marker to Define Cardiovascular Risk? The options: LDL cholesterol HDL cholesterol Triacylglycerol The total to HDL cholesterol ratio

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

Effects of Different Classes of Fatty Acids on Total to HDL Cholesterol 0.04 0.02 0-0.02-0.

13 Effects of Different Classes of Fatty Acids on Total to HDL Cholesterol Change * * * Total to HDL cholesterol SAFA Cis-MUFA Cis-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 about 7.3 as strong as that of SAFA

14 Effects on CHD-risk of Consuming 5 En% of the Different FA in place of Carbohydrates 0.2 Change 6 % Change Total to HDL cholesterol -9 CHD-risk SAFA Cis-PUFA Cis-MUFA Trans-MUFA

15 Effects of Individual Saturated Fatty Acids on Total to HDL Cholesterol Change Relative to carbohydrates C12:0 (lauric acid) favorably affects the total to HDL cholesterol ratio * Total to HDL cholesterol SAFA C12:0 C14:0 C16:0 C18:0 C14:0 (myristic acid) C16:0 (palmitic acid) C18:0 (stearic acid) have no effects

16 Effects on CHD-risk of 5 En% of the Individual Saturated FA in Place of Carbohydrates 0.05 Change 2 % Change Total to HDL cholesterol CHD-risk SAFA C12:0 C14:0 C16:0 C18:0

17 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, 2004 FA exchange: 8 En%

18 Effects on CHD-risk of 5 En% of C18:0 and Trans-MUFA 6 % Change 0 % Change CHD-risk -9 CHD-risk Compared to carbohydrates Replacement of TFA with C18:0 C18:0 Trans-MUFA

19 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

20 Structure of Triacylglycerol from Vegetable Oils Sn-1:Mainly (mono-un)saturated Sn-2: Mainly polyunsaturated Sn-3: Mainly (mono-un)saturated

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

22 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

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

24 Grande et al. Am J Clin Nutr, But Controversial

25 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: ) - Berry et al. (Am J Clin Nutr 2007; 85: )

26 Effects of Interesterified Fat Blends on Fasting Serum Lipids are Highly Controversial Meijer and Weststrate (Eur J Clin Nutr 1997; 51: ) - Native vs. interesterified mixed fat blend providing 4 or 8 En% healthy normocholesterolemic men and women - 21 days on diet (cross-over design) No effects on the serum lipoprotein profile

27 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. an interesterified fat rich in stearic acid providing > 70% of total fat intake. - Total fat intake was 31 En% 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

28 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

29 Intakes of Fatty Acids En% Palm olein PHSO Interesterified fat Sundram et al. Nutr Metab, 2007 SAFA C16:0 C18:0 MUFA PUFA Trans

30 Predicted vs. Observed Effects of the Fats on LDL and HDL Cholesterol mmol/l * mmol/l LDL cholesterol * HDL cholesterol * Compared to Palm Olein: Sundram et al. Nutr Metab, 2007 Predicted PHSO Observed PHSO Predicted IE Observed IE

31 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 )

32 Outline of the Presentation Saturated fatty acids and cardiovascular risk - Stearic acid - Triglyceride structure N-3 polyunsaturated fatty acids Plant stanols Conclusions

33 What About n-3 or ω-3 Fatty Acids - structures, dietary intakes - CH3 3 first double bond in n-3 or omega-3 position COOH Alpha-linolenic acid (ALA, C18:3n-3) Intake from plant oils 1-2 g/day 3 CH3 Eicosapentaenoic acid (EPA, C20:5n-3) 3 COOH COOH Intake from fish g/day CH3 Docosahexaenoic acid (DHA, C22:6n-3)

34 Conversion of Linolenic Acid into DHA 6 desaturation Elongation 5 desaturation Elongation Elongation 6 desaturation β-oxidation 18:3(n-3) Linolenic acid (ALA) 20:5(n-3) EPA 22:5(n-3) DPA 22:6(n-3) DHA

35 Can -Linolenic Acid Replace Fish Oil? -Linolenic acid cannot replace fish oil

36 Can -Linolenic Acid Replace Fish Oil? ALA and EPA / DHA have different metabolic effects Conversion of α-linolenic acid into EPA is low: <10% Conversion of EPA into DHA is even lower: <1% Conversion of ALA into EPA is slightly inhibited by linoleic acid The ALA/LA ratio is not important Do not use the n-3 / n-6 ratio for dietary recommendations

37 n-3 Fatty Acids and Cardiovascular Disease Outcomes - a systematic review - Wang et al. Am J Clin Nutr, 2006

38 Relative Risk of Fatal MI Might Be Lower in Men with a High α-linolenic Acid Intake Dolocek & Granditis 1991 Ascherio et al Pietinen et al Hu et al Oomen et al Combined RR Brouwer et al. J Nutr,

39 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

40 Why Do Fish Oil FA Have Beneficial Effects on Cardiovascular Disease? Lower serum triglycerides Lower blood pressure Decrease platelet aggregation Improve endothelial function? Are anti-inflammatory? Are anti-arrhythmic

41 Flaxseed Does not Increase (n-3)-lcpufa Status in Human Myocardial Phospholipids 25 % n-3 FA intake: 5-6 g 9 % C20:4(n-6) C18:3 C20:5 C22:6 Olive oil (28 d) Flaxseed (29 d) Fish oil (33 d) Metcalf et al. Am J Clin Nutr, 2007

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%

42 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 <4% least cardioprotection To reach an omega-3 index of 8%, the intake of EPA/DHA should be at least 1 g (but probably higher)

Effects of Linolenic Acid and EPA/DHA on the Omega-3 index 6 * Omega-3 index 4 2 Run-in period of 4 weeks Intervention period of 24 weeks 10-12

43 Effects of Linolenic Acid and EPA/DHA on the Omega-3 index 6 * Omega-3 index 4 2 Run-in period of 4 weeks Intervention period of 24 weeks subjects in each group Additional ALA intake: 3.3 gram Additional EPA/DHA intake: 0.6 gram 0 Control ALA-group EPA/DHA group Mensink, Unpublished results

44 Conversion of Linoleic Acid and Linolenic 18:2(n-6) Linoleic acid (LA) 20:4(n-6) AA 22:4(n-6) 22:5(n-6) Acid into LCPUFAs 6 desaturation (FADS2) Elongation 5 desaturation (FADS1) Elongation Elongation 6 desaturation (FADS2) β-oxidation 18:3(n-3) Linolenic acid (ALA) 20:5(n-3) EPA 22:5(n-3) DPA 22:6(n-3) DHA

45 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, rs , rs The SNPs were highly linked FFQ were determined in week 34 of pregnancy Genotype was not related to fatty acid intake

46 The n-6 FA Profile in Plasma and Human Milk is Related to FADS1 Genotype 25 % 20 C18:2(n-6) LA 8 % 6 C20:4(n-6) AA P<0.001 P<0.001 P<0.001 P< Plasma Human milk Plasma Human milk (*10) MM, n=166 Mm, n=125 mm, n=18 Molto-Puigmarti et al. Am J Clin Nutr, 2010 rs174561: FADS1

47 The DHA Level in Plasma and Human Milk is Related to FADS1 Genotype 0.6 % 0.4 C20:5(n-3) EPA 4 % 3 C22:6(n-3) DHA P=0.580 P=0.083 P=0.002 P= Plasma Human milk Plasma Human milk Molto-Puigmarti et al. Am J Clin Nutr, 2010 MM, n=166 Mm, n=125 mm, n=18 rs174561: FADS1

48 Relation between Fish Intake and DHA in Human Milk Relates to FADS Gene Variants Molto-Puigmarti et al. Am J Clin Nutr, 2010 MM, n=168 Mm, n=126 mm, n=15 rs174575: FADS2

49 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

50 Outline of the Presentation Saturated fatty acids and cardiovascular risk - Stearic acid - Triglyceride structure N-3 polyunsaturated fatty acids Plant stanols Conclusions

51 Plant Sterols / Stanols Have a Structure Very Similar to that of Cholesterol HO HO Cholesterol Sitosterol HO Sitostanol R Sitostanol ester

52 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

53 Plant Stanol Esters Decrease LDL Cholesterol Dose-Dependently mmol/l % LDL cholesterol 3-g group LDL cholesterol 6-g group 9-g group Mensink et al. Am J Clin Nutr, 2010

54 In Subjects with the Metabolic Syndrome, Plant Stanols Lower Serum Triacylglycerol 2.5 mmol/l 0.3 mmol/l % reduction by plant stanols versus control Baseline Change Control Plant stanols (8 weeks, 2 g plant stanols / day as a yogurt drink) Plat et al. J Nutr, 2010

55 Conclusions about Plant Stanols Plant stanols lower serum LDL cholesterol dosedependently 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

56 Outline of the Presentation Saturated fatty acids and cardiovascular risk - Stearic acid - Triglyceride structure N-3 polyunsaturated fatty acids Plant stanols Conclusions

57 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

58 Basis of Dietary Guidelines for Healthy Adults Saturated and trans fatty acids Cardiovascular disease Polyunsaturated fatty acids Essential fatty acids Cardiovascular disease Total fat intake Essential fatty acids, vitamins, energy Insulin resistance, energy intake??

59 Thank You Very Much for Your Kind Attention!

Composition and Structure of Oil and Fats and its Relationship to Health and Nutrition

Composition and Structure of Oil and Fats and its Relationship to Health and Nutrition SB Neoh* & K. Sundram** * Managing Director, Soon Soon Oilmills Sdn Bhd, Malaysia **Deputy CEO and Director, Science