Nutr Res Pract.  2025 Feb;19(1):107-116. 10.4162/nrp.2025.19.1.107.

Association of dietary intake of total fat and fatty acids with the Omega-3 Index: a cross-sectional analysis of NHANES 2011–2012

• Jin Y
• Hong H
• Tintle NL
• Harris WS
• Park Y

• KMID: 2565388
• DOI: http://doi.org/10.4162/nrp.2025.19.1.107

Abstract

BACKGROUND/OBJECTIVES
The Omega-3 Index (O3I), which is the total eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in erythrocytes as a percentage of total fatty acids (FAs), is associated with fish intake. O3I also varies with body mass index, age, sex, and dietary factors other than the intake of n-3 polyunsaturated fatty acids (PUFAs). This study examined the relationship between the dietary intake of total fat and FA classes, and O3I, specifically regarding EPA+DHA intake.
SUBJECTS/METHODS
Data on dietary intake and serum FAs from 2,370 participants (1,192 males and 1,178 females) aged 18–79 yrs, collected during the 2011–2012 National Health and Nutrition Examination Survey, were used in this study. The O3I was estimated from the serum EPA+DHA content.
RESULTS
In the total population, O3I showed an inverse correlation with the intake of total fat (r = -0.417), saturated FAs (SFAs; r = -0.423), and monounsaturated fatty acids (MUFAs; r = -0.412) (P < 0.01). Similar relationships were observed among males. However, in females, only SFA intake was correlated with O3I (r = -0.386, P < 0.05). In contrast, no correlation was observed between n-6 PUFA intake and O3I. Multivariable regression analysis also showed that a 1% increment in energy provided by total fat, SFA, and MUFA corresponded to reductions of 0.019, 0.055, and 0.035 units in O3I, respectively (P < 0.01). Both SFA and MUFA intakes mediated the negative relationship between total fat intake and O3I in the total population and males. However, MUFA were not significant mediators in women.
CONCLUSION
The intakes of total fat, SFA, and MUFA negatively influenced O3I, independent of n-3 PUFA intake.

Keyword

Dietary fats; fatty acids; fatty acids, monounsaturated; fatty acids, omega-3

Figure

• 

  Fig. 1 Mediation effects of mediating variable (SFA, MUFA, and n-6 PUFA) intake on the association between fat intake (independent variable) and the Omega-3 Index (dependent variable) by Sobel tests adjusting factors. (A) Total population, (B) male, and (C) female; (a) path: effect of fat intake on SFA, MUFA, and n-6 PUFA intake; (b) path: effect of SFA, MUFA and n-6 PUFA intake on the Omega-3 Index; (c) path: indirect effect in total; Z: For statistically significant indirect effects in each variable.SFA, saturated fatty acid; MUFA, monounsaturated fatty acid; PUFA, polyunsaturated fatty acid.*P < 0.05; **P < 0.01; ***P < 0.001.

Reference

1. Harris WS, Von Schacky C. The Omega-3 Index: a new risk factor for death from coronary heart disease? Prev Med. 2004; 39:212–220. PMID: 15208005.

2. Cao J, Schwichtenberg KA, Hanson NQ, Tsai MY. Incorporation and clearance of omega-3 fatty acids in erythrocyte membranes and plasma phospholipids. Clin Chem. 2006; 52:2265–2272. PMID: 17053155.

3. Jackson KH, Polreis JM, Tintle NL, Kris-Etherton PM, Harris WS. Association of reported fish intake and supplementation status with the Omega-3 Index. Prostaglandins Leukot Essent Fatty Acids. 2019; 142:4–10. PMID: 30773210.

4. Howe PR, Buckley JD, Murphy KJ, Pettman T, Milte C, Coates AM. Relationship between erythrocyte omega-3 content and obesity is gender dependent. Nutrients. 2014; 6:1850–1860. PMID: 24803096.

5. Wagner A, Simon C, Morio B, Dallongeville J, Ruidavets JB, Haas B, Laillet B, Cottel D, Ferrières J, Arveiler D. Omega-3 Index levels and associated factors in a middle-aged French population: the MONA LISA-NUT study. Eur J Clin Nutr. 2015; 69:436–441. PMID: 25335443.

6. Childs CE. Sex hormones and n-3 fatty acid metabolism. Proc Nutr Soc. 2020; 79:219–224. PMID: 31416488.

7. Zhang M, Li CC, Li F, Li H, Liu XJ, Loor JJ, Kang XT, Sun GR. Estrogen promotes hepatic synthesis of long-chain polyunsaturated fatty acids by regulating ELOVL5 at post-transcriptional level in laying hens. Int J Mol Sci. 2017; 18:1405. PMID: 28665359.

8. Simopoulos AP. An increase in the omega-6/omega-3 fatty acid ratio increases the risk for obesity. Nutrients. 2016; 8:128. PMID: 26950145.

9. Raatz SK, Bibus D, Thomas W, Kris-Etherton P. Total fat intake modifies plasma fatty acid composition in humans. J Nutr. 2001; 131:231–234. PMID: 11160538.

10. Raatz SK, Young LR, Picklo MJ Sr, Sauter ER, Qin W, Kurzer MS. Total dietary fat and fatty acid content modifies plasma phospholipid fatty acids, desaturase activity indices, and urinary prostaglandin E in women. Nutr Res. 2012; 32:1–7. PMID: 22260857.

11. Kim D, Choi JE, Park Y. Low-linoleic acid diet and oestrogen enhance the conversion of α-linolenic acid into DHA through modification of conversion enzymes and transcription factors. Br J Nutr. 2019; 121:137–145. PMID: 30507367.

12. Valenzuela R, Barrera C, Espinosa A, Llanos P, Orellana P, Videla LA. Reduction in the desaturation capacity of the liver in mice subjected to high fat diet: relation to LCPUFA depletion in liver and extrahepatic tissues. Prostaglandins Leukot Essent Fatty Acids. 2015; 98:7–14. PMID: 25910408.

13. Walker RE, Parkhomenko V, Ying Y, Urrutia N, Harvatine KJ. Dietary SFAs and omega-6 fatty acids alter incorporation of omega-3 fatty acids into milk fat of lactating CD-1 mice and tissues of offspring. J Nutr. 2021; 151:1834–1843. PMID: 33982073.

14. Hanke D, Zahradka P, Mohankumar SK, Clark JL, Taylor CG. A diet high in α-linolenic acid and monounsaturated fatty acids attenuates hepatic steatosis and alters hepatic phospholipid fatty acid profile in diet-induced obese rats. Prostaglandins Leukot Essent Fatty Acids. 2013; 89:391–401. PMID: 24140006.

15. Picklo MJ, Murphy EJ. A high-fat, high-oleic diet, but not a high-fat, saturated diet, reduces hepatic alpha-linolenic acid and eicosapentaenoic acid content in mice. Lipids. 2016; 51:537–547. PMID: 26694605.

16. Johnson CL, Dohrmann SM, Burt VL, Mohadjer LK. National health and nutrition examination survey: sample design, 2011-2014. Vital Health Stat 2. 2014; 1–33.

17. U.S. Department of Agriculture Agricultural Research Service. USDA food and nutrient database for dietary studies [Internet]. Beltsville (MD): USDA Agricultural Research Service;2024. cited 2024 December 12. Available from: https://www.ars.usda.gov/northeast-area/beltsville-md-bhnrc/beltsville-human-nutrition-research-center/food-surveys-research-group/docs/fndds.

18. Harris WS, Jackson KH, Carlson H, Hoem N, Dominguez TE, Burri L. Derivation of the Omega-3 Index from EPA and DHA analysis of dried blood spots from dogs and cats. Vet Sci. 2022; 10:13. PMID: 36669014.

19. Saylor J, Friedmann E, Lee HJ. Navigating complex sample analysis using national survey data. Nurs Res. 2012; 61:231–237. PMID: 22551998.

20. Montgomery DC, Peck EA, Vining GG. Introduction to Linear Regression Analysis. Hoboken (NJ): John Wiley & Sons;2021.

21. Greenland S, Pearce N. Statistical foundations for model-based adjustments. Annu Rev Public Health. 2015; 36:89–108. PMID: 25785886.

22. Sobel ME. Asymptotic confidence intervals for indirect effects in structural equation models. Sociol Methodol. 1982; 13:290–312.

23. Stark KD, Van Elswyk ME, Higgins MR, Weatherford CA, Salem N Jr. Global survey of the omega-3 fatty acids, docosahexaenoic acid and eicosapentaenoic acid in the blood stream of healthy adults. Prog Lipid Res. 2016; 63:132–152. PMID: 27216485.

24. Harika RK, Eilander A, Alssema M, Osendarp SJ, Zock PL. Intake of fatty acids in general populations worldwide does not meet dietary recommendations to prevent coronary heart disease: a systematic review of data from 40 countries. Ann Nutr Metab. 2013; 63:229–238. PMID: 24192557.

25. Eilander A, Harika RK, Zock PL. Intake and sources of dietary fatty acids in Europe: are current population intakes of fats aligned with dietary recommendations? Eur J Lipid Sci Technol. 2015; 117:1370–1377. PMID: 26877707.

26. Micha R, Khatibzadeh S, Shi P, Fahimi S, Lim S, Andrews KG, Engell RE, Powles J, Ezzati M, Mozaffarian D, et al. Global, regional, and national consumption levels of dietary fats and oils in 1990 and 2010: a systematic analysis including 266 country-specific nutrition surveys. BMJ. 2014; 348:g2272. PMID: 24736206.

27. Schuchardt JP, Cerrato M, Ceseri M, DeFina LF, Delgado GE, Gellert S, Hahn A, Howard BV, Kadota A, Kleber ME, et al. Red blood cell fatty acid patterns from 7 countries: focus on the Omega-3 Index. Prostaglandins Leukot Essent Fatty Acids. 2022; 179:102418. PMID: 35366625.

28. Sala-Vila A, Harris WS, Cofán M, Pérez-Heras AM, Pintó X, Lamuela-Raventós RM, Covas MI, Estruch R, Ros E. Determinants of the Omega-3 Index in a Mediterranean population at increased risk for CHD. Br J Nutr. 2011; 106:425–431. PMID: 21450116.

29. Richardson CE, Krishnan S, Gray IJ, Keim NL, Newman JW. The Omega-3 Index response to an 8 week randomized intervention containing three fatty fish meals per week is influenced by adiposity in overweight to obese women. Front Nutr. 2022; 9:810003. PMID: 35187036.

30. Sands SA, Reid KJ, Windsor SL, Harris WS. The impact of age, body mass index, and fish intake on the EPA and DHA content of human erythrocytes. Lipids. 2005; 40:343–347. PMID: 16028715.

31. Degirolamo C, Rudel LL. Dietary monounsaturated fatty acids appear not to provide cardioprotection. Curr Atheroscler Rep. 2010; 12:391–396. PMID: 20725810.

32. National Cancer Institute. Identification of top food sources of various dietary components [Internet]. Bethesda (MD): National Cancer Institute;2019. cited 2024 March 23. Available from: https://epi.grants.cancer.gov/diet/foodsources.

33. Zong G, Li Y, Sampson L, Dougherty LW, Willett WC, Wanders AJ, Alssema M, Zock PL, Hu FB, Sun Q. Monounsaturated fats from plant and animal sources in relation to risk of coronary heart disease among US men and women. Am J Clin Nutr. 2018; 107:445–453. PMID: 29566185.

34. Bezerra IN, Goldman J, Rhodes DG, Hoy MK, Moura Souza A, Chester DN, Martin CL, Sebastian RS, Ahuja JK, Sichieri R, et al. Difference in adult food group intake by sex and age groups comparing Brazil and United States nationwide surveys. Nutr J. 2014; 13:74. PMID: 25047421.

35. Schmitz G, Ecker J. The opposing effects of n-3 and n-6 fatty acids. Prog Lipid Res. 2008; 47:147–155. PMID: 18198131.

36. Kris-Etherton P, Fleming J, Harris WS. The debate about n-6 polyunsaturated fatty acid recommendations for cardiovascular health. J Am Diet Assoc. 2010; 110:201–204. PMID: 20102846.

37. Block RC, Harris WS, Pottala JV. Determinants of blood cell omega-3 fatty acid content. Open Biomark J. 2008; 1:1–6. PMID: 19953197.

38. Harris WS. The omega-6/omega-3 ratio and cardiovascular disease risk: uses and abuses. Curr Atheroscler Rep. 2006; 8:453–459. PMID: 17045070.

39. Harris WS. The omega-6:omega-3 ratio: a critical appraisal and possible successor. Prostaglandins Leukot Essent Fatty Acids. 2018; 132:34–40. PMID: 29599053.

40. Nelson JR, Raskin S. The eicosapentaenoic acid:arachidonic acid ratio and its clinical utility in cardiovascular disease. Postgrad Med. 2019; 131:268–277. PMID: 31063407.