Omega-3 Index Beyond Heart Health

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Omega-3 Index Beyond Heart Health Peter Howe 1,2, Alison Coates 2, Jon Buckley 2 1 Clinical Nutrition Research Centre, University of Newcastle 2 Nutritional Physiology Research Centre, University of South Australia Newcastle 7 th November, 2013

Omega-3 Index - a new risk factor for death from coronary heart disease? - a biomarker of cardiovascular health EPA + DHA % total fatty acids in red blood cells 10% 8% Greatest cardiovascular protection GISSI-P 2 : 9-10% CHS 3 : 8.8% Australians ~5% Least Protection PHS 6 : 3.9% SCIMO 5 : 3.4% Seattle 7 : 3.3% 6% 4% DART 4 : 8-9% SCIMO 5 : 8.3% 5 epi. studies: 8% PHS 6 : 7.3% Seattle 7 : 6.5% 8.1% 1 Nilsen. AJCN. 74:50, 2001; 2 Marchioli. Circulation. 105:1897, 2002; 3 Mozaffarian. Circulation.107:1372, 2003; 4 Burr. Lancet. 2:757, 1989; 5 von Schacky Ann Intern Med 130:554, 1999; 6 Albert. NEJM. 346:1113, 2002; 7 Siscovick. JAMA. 274:1363, 1995 Harris & von Schacky, Preventive Medicine 2004

Effects of consuming fish or fish-oil on Omega-3 Index Omega - 3 Index (%) 7 6 Harris WS et al, Am J Clin Nutr 2007 5 4 3 Fish (salmon/tuna): 485 mg EPA+DHA/d (95+390mg, respectively) Fish Oil Capsules: 482 mg EPA+DHA/d (104+378mg, respectively) 0 2 4 6 8 10 12 14 16 Weeks 10 Consuming LC n-3 enriched foods (~800mg/d) increases Omega-3 Index % of total fatty acids 8 6 0 mths 6 mths 4 2 0 LNA EPA DPA DHA EPA+DHA EPA+DPA+DHA Murphy KJ et al Br J Nutr 2007

Could the Omega-3 Index concept be applied more broadly? In addition to cardiovascular protection, increased consumption of LC n3 PUFA may also deliver anti-inflammatory, metabolic and mental health benefits, e.g. Polyunsaturated fatty acid status in attention deficit hyperactivity disorder, depression, and Alzheimer's disease: towards an omega-3 index for mental health? Milte CM, Sinn N, Howe PRC. Nutr Rev 2009;67:573 Association between erythrocyte n-3 PUFA and biomarkers of inflammation and oxidative stress in patients with (n=80) and without (n=80) depression. Baek D & Park Y. PLEFA 2013 Omega-3 Index: 8.62 ± 0.24% 9.48 ± 0.20% P<0.006 The association between n-3 polyunsaturated fatty acid levels in erythrocytes and the risk of rheumatoid arthritis in Korean women. Lee AL & Park Y. Ann Nutr Metab 2013;63:88 n = 100 n = 100

Relationship between omega-3 intake and body composition In the Health Professionals Follow up Study (>40 000 men), higher fish intake was associated with a lower incidence of overweight (He K et al. JAMA 2002;288:3130) In the Nurses Health Study (>79 000 women), higher fish intake and higher n-3 intake were associated with higher body mass index (BMI) (Iso H et al. JAMA 2001;285:304). Such studies are limited by crude estimations of n-3 intake (FFQ). Biomarkers of intake may be more reliable. In a small study (124 adults) Micallef et al showed that plasma n-3 levels were inversely related to BMI and waist circumference (Br J Nutr 2009; 102:1370).

BMI (kg/m2) Waist circumference (cm) Can the Omega-3 Index predict body composition? Higher erythrocyte LCn-3 PUFA content is associated with a healthier body composition Coates A, PettmanT, Murphy K, Milte C, Buckley J, Howe P. Proc Nutr Soc Aust 2009;33:35 Aim: to investigate relationships between Omega-3 Index, BMI and body composition Study Design: opportunistic cross-sectional analysis of baseline measurements of erythrocyte fatty acids, BMI, waist circumference and body fat (DEXA) from 476 adults participating in 5 dietary intervention trials. 36 a 120 a b P<0.001 a b b b 32 110 P<0.001 b b 28 3.9 4.7 5.4 6.6 100 4.0 4.8 5.5 7.0 Omega-3 Index Quartiles Omega-3 Index Quartiles

Body Fat (%) Body fat (%) waist circumference (cm) waist circumference (cm) BMI (kg/m 2 ) BMI (kg/m2) Body Composition and Omega-3 Status - split by gender Men: median Omega-3 Index = 5.0 Male Female Women: median Omega-3 Index =5.1 BMI (kg/m 2 ) 32 31.7 31.7 31.1 31.3 40 37.3 P<0.001 35 34.2 32.2 32.6 Waist (cm) 30 115 110 105 male Omega-3 Index Quartiles 112.0 110.5 109.2 108.1 30 120 115 110 105 100 female Omega-3 Index Quartiles 114.3 108.4 98.7 P<0.001 100.6 95 Body Fat (%) 100 36 35 34 33 32 male Omga-3 Index Quatiles 35.4 35.7 34.1 33.0 90 52 51 50 49 48 47 female Omega-3 Index Quartiles 51.2 P<0.001 48.3 46.7 46.6 31 46 30 Omega-3 Omega-3 Index Quartiles quartiles 45 Omega-3 Index Quartiles quartiles

Linear Correlations BMI WC % Body Fat EPA -0.08-0.16 * -0.17 ** DPA -0.05-0.13-0.14 * n = 476 DHA -0.28 ** -0.35 ** -0.33 ** Omega 3 Index -0.24 ** -0.32 ** -0.31 ** BMI WC % Body Fat EPA -0.08-0.16* -0.17** DPA -0.05-0.13-0.14* DHA -0.28** -0.35** -0.33** n = 291 Omega -3 Index -0.24** -0.32** -0.31** BMI WC % Body Fat EPA 0.09-0.06-0.15 DPA -0.02-0.20* -0.23** n = 185 DHA -0.08-0.14-0.19* Omega -3 Index -0.04-0.13-0.19* * P<0.05 ** P<0.01

Curvilinear Regression analyses This analysis demonstrates a possible sigmoidal relationship between the Omega-3 Index and markers of adiposity, particularly in women, indicating that there is less influence around the median level of the Index but larger effects at the lower and possibly upper ends of the range. Women (291) Men (185) BMI (kg/m 2 ) Waist circumference (cm) Body fat (%) r= -0.26 P<0.0001 r= -0.10 P> 0.05 r= -0.36 P<0.0001 r= -0.18 P> 0.05 r= -0.37 P<0.0001 r= -0.23 P> 0.05 2 4 6 8 10 Omega-3 Index 2 4 6 8 10 Omega-3 Index 2 4 6 8 10 Omega-3 Index

Gender difference: is DHA more efficacious in women? Changes in platelet aggregation in 41 men and 53 women after 4 weeks supplementation with placebo, EPA or DHA Phang et al J Nutr 2013

Clinical correlates and heritability of erythrocyte eicosapentaenoic and docosahexaenoic acid content in the Framingham Heart Study Harris WS et al Atherosclerosis 2012;225:425-431 3196 Framingham Study participants (2005-8); mean Omega-3 Index = 5.6%. In multivariable regression models, age, female gender, higher education, dietary EPA+DHA intake, fish oil supplementation, aspirin use, LDL cholesterol and lipid lowering drugs were directly associated with Omega-3 Index. Heart rate, waist girth, triglycerides and smoking were inversely associated with Omega-3 Index. The total explained variability in the Omega-3 Index for the fully adjusted model was 73%, which included major components due to heritability (24%), EPA+DHA intake (25%), and fish oil supplementation (15%). Erythrocyte omega-3 fatty acids increase and linoleic acid decreases with age: observations from 160,000 patients Harris WS et al PLEFA 2013;88:257 women men

Conclusions A higher Omega-3 Index is associated with a healthier body composition DHA appears to be a more significant predictor than EPA or DPA This relationship appears to be stronger in women than men Influences of omega-3 fatty acids on other health parameters are likely to be specific for individual fatty acids, gender and possibly age Such information should be forthcoming from large databases of erythrocyte fatty acid analyses Routine measures of omega-3 fatty acids in erythrocytes could provide a future guide to health status However, causality must be established