2/19/2013. Omega-6, Omega-3 and Omega-9 Fatty Acids: All Good for the Heart?

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1 Omega-6, Omega-3 and Omega-9 Fatty Acids: All Good for the Heart? Professor of Medicine Sanford School of Medicine University of South Dakota President OmegaQuant, LLC Sioux Falls, SD Senior Research Scientist Health Diagnostic Lab, Inc. Richmond, VA Effects on CHD Death or MI of Replacing Saturated Fat with PUFA, Carbohydrates or MUFA Mozaffarian et al. PLoS Med 2010;7:e Meta-analysis of 60 controlled trials on dietary fats and blood lipids Effect of replacing carbohydrate with different fats PUFAs are most beneficial Total/HDL LDL HDL Mensink & Katan. Am J Clin Nutr 2003;77:1146 1

2 Meta-analysis analysis of RCTs Examining the Effects on CHD Death or MI of Replacing Saturated Fat with PUFA Mozaffarian et al. PLoS Med 2010;7:e Linoleic Acid for Secondary Prevention of CHD: Sydney Heart Study Revisited men with recent coronary event Randomized to high n-6 PUFA-low SFA diet or usual care Followed for 5 yr 8% vs 15% en PUFA 13.5% vs 9.3% SFA Total deaths: 27 vs 38 CVD deaths: 25 vs 37 Ramsden et al. BMJ 2013;346:e8707 Usually soybean oil - 50%LA and 7% ALA Whale meat and cod liver oil encouraged Ramsden et al. BMJ 2013;346:e8707 2

3 Sydney Heart Study Revisited Multi-intervention study also were changes in smoking, BMI, alcohol, physical exercise Very small study - only 65 total deaths Extreme intakes of LA (15% en) and virtually no ALA Margarines used were high in trans FA Highly improbable that the ALA in the n6+n3 interventions not only blocked the adverse effects of LA, but went on to actually reduce events Even if 15% LA has adverse effects, this study does not challenge current AHA recommendations of 5%-10% en as LA, and include ALA and marine n-3 FA; nor does it show that LA recommendations should be reduced below 5% en Comments from F. Hu, D. Mozaffarian, W. Willett and P. Zock appreciated Sydney Heart Study Revisited Multi-intervention study also were changes in smoking, BMI, alcohol, physical exercise Very small study - only 65 total deaths Extreme intakes of LA (15% en) and virtually no ALA Margarines used were high in trans FA Highly improbable that the ALA in the n6+n3 interventions not only blocked the adverse effects of LA, but went on to actually reduce events Even if 15% LA has adverse effects, this study does not challenge current AHA recommendations of 5%-10% en as LA, and include ALA and marine n-3 FA; nor does it show that LA recommendations should be reduced below 5% en Comments from F. Hu, D. Mozaffarian, W. Willett and P. Zock appreciated 3

4 Omega-6 Fatty acids and Cardiovascular Health 1. Temporal changes between linoleic acid (LA) intakes and CHD mortality are consistent with causation 2. Higher LA intakes lower LDL-cholesterol levels 3. Higher serum levels of LA are associated with reduced levels of inflammatory markers, and reduced risk for CHD events 4. Both arachidonic acid (AA) and LA give rise to proinflammatory and anti-inflammatory compounds, hence classification of n-6 as pro-inflammatory is inaccurate. 5. Higher LA intakes higher membrane AA levels 6. Meta-analysis of studies in which PUFA (90% LA) replaced saturated fat showed reduced risk for CHD events. Harris et al. Circulation 2009; Rizos E et al. JAMA 2012;308: The Omega-3 and CVD Roller Coaster Fish oil pills with omega-3 don t help against disease (Sept 12, 2012) 4

5 Rizoset The Omega-3 al. Meta-Analysis and CVD Roller of Omega-3 Coaster Supplementation Studies (including open label trials) Conclusion: Omega-3 Supplements reduce risk for cardiac death Critical level set at p=0.006 to control for multiple comparisons Unprecedented and too conservative for a safe agent? Conclusion: Omega-3 supplements have no effect on any CVD endpoint Rizos E et al. JAMA 2012;308: (Sept 11) JAMA Meta-Analyses of 16 Omega-3 and CHD Meta-Analyses 14 of 15 Used 95% CI and none adjusted for multiple comparisons Where do we stand today? It is not unreasonable to conclude that, for patients With dysglycemia, a history of CHD, or recent MI Whose average age is 63 years Who are consuming n-3 FA at > typical US intakes Whose omega-3 biostatus is unknown Who are being treated for CHD per guidelines doses of mg EPA+DHA per day for 2-4 years may not reduce risk for CHD events 5

6 Where do we stand today? However, it is NOT reasonable to conclude that omega-3 fatty acids do not work, in patients Who are noton optimal drug therapy Who take omega-3 supplements for decades Who take >1 g of omega-3 With a low omega-3 index due to eating the typical Western diet Dietary Fat Quality and Sudden Cardiac Death Nurses Health Study Prospective cohort study in 91,981 women yrs of age in 1980 Multiple food frequency questionnaires completed 8 times over 26 yrs 385 sudden cardiac death (SCD) cases documented Risk for SCD by quintile of type of fat (as a % of total fat) was determined Chiuve et al. AJCN 2012;96: Dietary Fat Quality and Sudden Cardiac Death Nurses Health Study 1.2 Protective Neutral Protective Protective P<0.001 P=0.32 P<0.001 P< Relative Risk Q1 Q2 Q3 Q4 Q5 0 Linoleic Arachidonic Plant n3 Marine n3 Chiuve et al. AJCN 2012;96:

7 CVD is not our ONLY problem Omega-3 Biomarkers and Dementia Meta-analysis of 11 Case-Control Studies Demented patients have reduced omega-3 levels vs controls Lin et al. J Clin Psychiat 2012;73: SUMMARY Omega-3 intervention trials show reduced risk for cardiac death and a NS trend towards total mortality and sudden death benefit Epidemiology still strongly favors higher omega-3 intakes/blood levels Risk:Benefitratio for omega-3 supplementation is still favorable There are emerging roles for omega-3 in neurocognitive function THE END 7

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