Original Article | Published:

Lipids and cardiovascular/metabolic health

Effects of dietary saturated and n-6 polyunsaturated fatty acids on the incorporation of long-chain n-3 polyunsaturated fatty acids into blood lipids

European Journal of Clinical Nutrition volume 70, pages 812818 (2016) | Download Citation

Abstract

Background/Objectives:

Omega-3 polyunsaturated fatty acids (n-3PUFA) are better absorbed when they are combined with high-fat meals. However, the role of different dietary fats in modulating the incorporation of n-3PUFA in blood lipids in humans has not been previously explored. Omega-6 polyunsaturated fatty acids (n-6PUFA) are known to compete with n-3PUFA in the metabolic pathways and for the incorporation into phospholipids, whereas saturated fats (SFA) may enhance n-3PUFA incorporation into tissues.

Subjects/Methods:

In a randomized parallel-design trial, we aimed to investigate the long-term effects of n-3PUFA supplementation in subjects consuming a diet enriched with either SFA or n-6PUFA on fatty acid incorporation into plasma and erythrocytes and on blood lipid profiles (total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and triglycerides).

Results:

Dietary supplementation with n-3PUFA co-administered with SFA for 6 weeks resulted in a significant rise in total cholesterol (0.46±0.60 mmol/L; P=0.020) and LDL-C (0.48±0.48 mmol/L; P=0.011) in comparison with combination with n-6PUFA. The diet enriched with SFA also induced a greater increase in eicosapentaenoic acid (2.07±0.79 vs 1.15±0.53; P=0.004), a smaller decrease in docosapentaenoic acid (−0.12±0.23 vs −0.30±0.20; P=0.034) and a similar increase in docosahexaenoic acid (3.85±1.14 vs 3.10±1.07; P=0.128) percentage in plasma compared with the diet enriched with n-6PUFA. A similar effect was seen in erythrocytes. N-3PUFA supplementation resulted in similar changes in HDL-C and triglyceride levels.

Conclusions:

The results suggest that dietary substitution of SFA with n-6PUFA, despite maintaining low levels of circulating cholesterol, hinders n-3PUFA incorporation into plasma and tissue lipids.

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References

  1. 1.

    , , , , , et al. Dietary saturated and trans fatty acids and cholesterol and 25-year mortality from coronary heart disease: The Seven Countries Study. Prev Med. 1995; 24: 308–315.

  2. 2.

    , , . Plasma fatty acid composition and incident heart failure in middle-aged adults: The Atherosclerosis Risk in Communities (ARIC) Study. Am Heart J 2008; 156: 965–974.

  3. 3.

    , , , , , et al. Intake of saturated and trans unsaturated fatty acids and risk of all cause mortality, cardiovascular disease, and type 2 diabetes: systematic review and meta-analysis of observational studies. BMJ 2015; 02: 04.

  4. 4.

    , , . Effects on coronary heart disease of increasing polyunsaturated fat in place of saturated fat: a systematic review and meta-analysis of randomized controlled trials. PLoS Med 2010; 7: e1000252.

  5. 5.

    , , , . Meta-analysis of prospective cohort studies evaluating the association of saturated fat with cardiovascular disease. Am J Clin Nutr 2010; 91: 535–546.

  6. 6.

    , , , , , et al. Diet, serum cholesterol, and death from coronary heart disease. N Engl J Med 1981; 304: 65–70.

  7. 7.

    , , . Combined effects of saturated fat and cholesterol intakes on serum lipids: Tehran Lipid and Glucose Study. Nutrition 2009; 25: 526–531.

  8. 8.

    , , , . Dietary fat intake in healthy adolescents: inverse relationships between the estimated intake of saturated fatty acids and serum cholesterol. Br J Nutr 2001; 85: 333–341.

  9. 9.

    , , , , , et al. Biomarkers of dairy fatty acids and risk of cardiovascular disease in the multi‐ethnic study of atherosclerosis. J Am Heart Assoc 2013; 2: e000092.

  10. 10.

    , , , , , et al. Milk-derived fatty acids are associated with a more favorable LDL particle size distribution in healthy men. J Nutr 2004; 134: 1729–1735.

  11. 11.

    , , , , . Consumption of dairy products and associations with incident diabetes, CHD and mortality in the Whitehall II study. Br J Nutr 2013; 109: 718–726.

  12. 12.

    , , . Interactions of saturated, n-6 and n-3 polyunsaturated fatty acids to modulate arachidonic acid metabolism. J Lipid Res 1990; 31: 271–277.

  13. 13.

    , . Incorporation of n-3 Fatty Acids into Plasma and Liver Lipids of Rats: Importance of Background Dietary Fat. Lipids 2004; 39: 545–551.

  14. 14.

    , , . Prediction of serum-cholesterol responses of man to changes in fats in the diet. Lancet 1957; 273: 959–966.

  15. 15.

    , , , , , . The influence of dietary fats on serum lipid levels in man. Lancet 1957; 1: 944–953.

  16. 16.

    , , , , , et al. Effects of saturated and polyunsaturated fat diets on the chemical composition and metabolism of low density lipoproteins in man. J Lipid Res 1980; 21: 91–99.

  17. 17.

    , , , , , et al. Use of dietary linoleic acid for secondary prevention of coronary heart disease and death: evaluation of recovered data from the Sydney Diet Heart Study and updated meta-analysis. BMJ 2013; 346.

  18. 18.

    , . Dietary linoleic acid has no effect on arachidonic acid, but increases n-6 eicosadienoic acid, and lowers dihomo-γ-linolenic and eicosapentaenoic acid in plasma of adult men. Prostaglandins Leukotrienes Essent Fatty Acids 2009; 80: 201–206.

  19. 19.

    , , . High dietary ω-6 fatty acids contribute to reduced docosahexaenoic acid in the developing brain and inhibit secondary neurite growth. Brain Res 2008; 1237: 136–145.

  20. 20.

    . Dietary n-6 and n-3 polyunsaturated fatty acids: from biochemistry to clinical implications in cardiovascular prevention. Biochem Pharmacol 2009; 77: 937–946.

  21. 21.

    , . The modification of mammalian membrane polyunsaturated fatty acid composition in relation to membrane fluidity and function. Biochim Biophys Acta 1984; 779: 89–137.

  22. 22.

    , , , , . Benefits of fish oil supplementation in hyperlipidemia: a systematic review and meta-analysis. Int J Cardiol 2009; 136: 4–16.

  23. 23.

    , , , , , et al. Randomized placebo-controlled intervention with n-3 LC-PUFA supplemented yoghurt: Effects on circulating eicosanoids and cardiovascular risk factors. Clin Nutr 2013; 32: 686–696.

  24. 24.

    , . Direct trans-esterification of all classes of lipid in an onestep reaction. J Lip Res 1986; 27: 114–120.

  25. 25.

    , , , , . Increased plasma fatty acid concentrations after respiratory exacerbations are associated with elevated oxidative stress in cystic fibrosis patients. Am J Clin Nutr 2002; 75: 668–675.

  26. 26.

    , . The lipid-lowering effects of phytosterols and (n-3) polyunsaturated fatty acids are synergistic and complementary in hyperlipidemic men and women. J Nutr 2008; 138: 1086–1090.

  27. 27.

    , , , . Dietary saturated fat level alters the competition between α-linolenic and linoleic acid. Lipids 1989; 24: 334–339.

  28. 28.

    , , , , , . Effects of varying dietary fat, fish, and fish oils on blood lipids in a randomized controlled trial in men at risk of heart disease. Am J Clin Nutr 1994; 59: 1060–1068.

  29. 29.

    , , , , , et al. Effects of dietary saturated, monounsaturated and n-3 fatty acids on fasting lipoproteins, LDL size and post-prandial lipid metabolism in healthy subjects. Atherosclerosis 2003; 167: 149–158.

  30. 30.

    , . Mechanisms by which dietary fatty acids modulate plasma lipids. J Nutr 2005; 135: 2075–2078.

  31. 31.

    , , , , , et al. Long-chain omega-3 fatty acids eicosapentaenoic acid and docosahexaenoic acid dose-dependently reduce fasting serum triglycerides. Nutr Rev 2010; 68: 155–167.

  32. 32.

    , , , , . Dose-dependent effects of docosahexaenoic acid-rich fish oil on erythrocyte docosahexaenoic acid and blood lipid levels. Br J Nutr 2008; 99: 1083–1088.

  33. 33.

    , , , , , et al. Purified eicosapentaenoic and docosahexaenoic acids have differential effects on serum lipids and lipoproteins, LDL particle size, glucose, and insulin in mildly hyperlipidemic men. Am J Clin Nutr 2000; 71: 1085–1094.

  34. 34.

    , , , , . Dietary linoleic acid increases and palmitic acid decreases hepatic LDL receptor protein and mRNA abundance in young pigs. J Lipid Res 1996; 37: 2310–2323.

  35. 35.

    , , , . Dietary fish oils modify the assembly of VLDL and expression of the LDL receptor in rabbit liver. Arterioscler Thromb Vasc Biol 1998; 18: 1490–1497.

  36. 36.

    , , , , , et al. Distinct regulation of plasma LDL cholesterol by eicosapentaenoic acid and docosahexaenoic acid in high fat diet-fed hamsters: participation of cholesterol ester transfer protein and LDL receptor. Prostaglandins Leukotrienes Essent Fatty Acids 2013; 88: 281–288.

  37. 37.

    . The effect of n−3 fatty acids on low density lipoprotein subfractions. Lipids 2001; 36: S91–S97.

  38. 38.

    , , , , . Saturated fat-induced changes in Sf 60–400 particle composition reduces uptake of LDL by HepG2 cells. J Lipid Res 2006; 47: 393–403.

  39. 39.

    , , , , , et al. Contribution of apolipoprotein E genotype and docosahexaenoic acid to the LDL-cholesterol response to fish oil. Atherosclerosis 2010; 209: 104–110.

  40. 40.

    , , , , , et al. Beneficial effects of Omega-3 fatty acids on low density lipoprotein particle size in patients with type 2 diabetes already under Statin Therapy. Diabetes Metab J 2013; 37: 207–211.

  41. 41.

    , . Small dense LDL: an emerging risk factor for cardiovascular disease. Clin Chim Acta 2012; 414: 215–224.

  42. 42.

    , , , , , et al. LDL particle subclasses, LDL particle size, and carotid atherosclerosis in the Multi-Ethnic Study of Atherosclerosis (MESA). Atherosclerosis 2007; 192: 211–217.

  43. 43.

    , . Influence of diets rich in saturated and Omega-6 polyunsaturated fatty acids on the postprandial responses of apolipoproteins B-48, B-100, E, and lipids in triglyceride-rich lipoproteins. Arterioscler Thromb Vasc Biol 1995; 15: 2111–2121.

  44. 44.

    , , , , , et al. Effects of n−6 PUFAs compared with SFAs on liver fat, lipoproteins, and inflammation in abdominal obesity: a randomized controlled trial. Am J Clin Nutr 2012; 95: 1003–1012.

  45. 45.

    , , , . Saturated fat consumption may not be the main cause of increased blood lipid levels. Med Hypotheses 2014; 82: 187–195.

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Acknowledgements

This study was supported by a research grant from the Hunter Medical Research Institute. We are grateful to EPAX Norway AS (Norway) for providing the fish oil concentrate capsules; Ms Melissa Fry for assistance with the fatty acid analysis; and the volunteers from the Hunter Medical Research Institute (HMRI) research register. CBD was supported by a scholarship from Coordenação Nacional de Desenvolvimento Científico e Tecnológico-CNPq.

Author information

Affiliations

  1. Nutraceuticals Research Group, School of Biomedical Sciences and Pharmacy, University of Newcastle, Callaghan, New South Wales, Australia

    • C B Dias
    •  & M L Garg
  2. Centre for Asthma and Respiratory Disease, School of Biomedical Sciences and Pharmacy, University of Newcastle, Callaghan, New South Wales, Australia

    • L G Wood

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Competing interests

The authors declare no conflict of interest.

Corresponding author

Correspondence to M L Garg.

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DOI

https://doi.org/10.1038/ejcn.2015.213

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