Skip to main content

Advertisement

Log in

A longitudinal study of the association of the eicosapentaenoic acid/arachidonic acid ratio derived from fish consumption with the serum lipid levels: a pilot study

  • Short Communication
  • Published:
Heart and Vessels Aims and scope Submit manuscript

Abstract

It has been demonstrated that regular fish consumption is associated with a reduced mortality from atherosclerotic cardiovascular disease (ASCVD). However, data are scarce regarding the correlation between the changes in the serum eicosapentaenoic acid/arachidonic acid (EPA/AA) ratio associated with regular fish consumption and the changes in the serum lipid profile variables. This study was designed as a hospital-based longitudinal study to investigate the relationship between the changes in the serum EPA/AA ratio and changes of the serum lipid levels in patients with one or more risk factors for ASCVD. In 475 patients followed-up for at least 1 year, univariable and multivariable regression analyses conducted after adjustments for the risk factors of ASCVD revealed that the absolute change of the EPA/AA ratio (∆EPA/AA ratio) was independently and significantly associated with the changes of the serum levels of low-density lipoprotein cholesterol (LDL-C) (β = − 0.129, p = 0.005), triglyceride (TG) (β = − 0.108, p = 0.019), non-high-density lipoprotein cholesterol (non-HDL-C) (β = − 0.149, p = 0.001), and TG/HDL-C ratio, a marker of the LDL particle size (β = − 0.104, p = 0.02), while not being correlated with any other lipid parameters. On the other hand, while the ∆ docosahexaenoic acid (DHA)/AA ratio was inversely correlated with the changes of the serum HDL-C level and positively correlated with the changes of the TG/HDL-C ratio, possibly serving to promote development of atherosclerosis. The results suggest that an increase of the EPA/AA ratio might be associated with decrease of the serum levels of LDL-C, TG and non-HDL-C levels, as well as with an increase of the TG/HDL-C ratio, which represents increased LDL particle size, all of which play a role in the development of ASCVD. A high EPA/AA ratio, but not DHA/AA ratio, derived from fish consumption might reduce the risk of ASCVD through reducing the risk of development of atherosclerosis.

Clinical Trial Registration Information: UMIN (http://www.umin.ac.jp/), Study ID: UMIN000010603.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1

References

  1. http://www.jfa.maff.go.jp/j/kikaku/wpaper/h22_h/trend/1/t1_2_1_1.html. Accessed 11 July 2014

  2. Kromhout D, Bosschieter EB, de Lezenne Coulander C (1985) The inverse relation between fish consumption and 20-year mortality from coronary heart disease. N Engl J Med 312:1205–1209

    Article  CAS  PubMed  Google Scholar 

  3. Iso H, Kobayashi M, Ishihara J, Sasaki S, Okada K, Kita Y, Kokubo Y, Tsugane S, JPHC Study Group (2006) Intake of fish and n3 fatty acids and risk of coronary heart disease among Japanese: the Japan Public Health Center-based (JPHC) Study Cohort I. Circulation 113:195–202

    Article  CAS  PubMed  Google Scholar 

  4. Mozaffarian D, Wu JH (2011) Omega-3 fatty acids and cardiovascular disease: effects on risk factors, molecular pathways, and clinical events. J Am Coll Cardiol 58:2047–2067

    Article  CAS  PubMed  Google Scholar 

  5. Tani S, Matsuo R, Kawauchi K, Yagi T, Atsumi W, Hirayama A (2018) A cross-sectional and longitudinal study between association of n-3 polyunsaturated fatty acids derived from fish consumption and high-density lipoprotein heterogeneity. Heart Vessels 33:470–480

    Article  PubMed  Google Scholar 

  6. Yokoyama M, Origasa H, Matsuzaki M, Matsuzawa Y, Saito Y, Ishikawa Y, Oikawa S, Sasaki J, Hishida H, Itakura H, Kita T, Kitabatake A, Nakaya N, Sakata T, Shimada K, Shirato K, Japan EPA lipid intervention study (JELIS) Investigators (2007) Effects of eicosapentaenoic acid on major coronary events in hypercholesterolaemic patients (JELIS): a randomised open-label, blinded endpoint analysis. Lancet 369:1090–1098

    Article  CAS  PubMed  Google Scholar 

  7. Itakura H, Yokoyama M, Matsuzaki M, Saito Y, Origasa H, Ishikawa Y, Oikawa S, Sasaki J, Hishida H, Kita T, Kitabatake A, Nakaya N, Sakata T, Shimada K, Shirato K, Matsuzawa Y, Investigators JELIS (2011) Relationships between plasma fatty acid composition and coronary artery disease. J Atheroscler Thromb 18:99–107

    Article  CAS  PubMed  Google Scholar 

  8. Ohnishi H, Saito Y (2013) Eicosapentaenoic acid (EPA) reduces cardiovascular events: relationship with the EPA/arachidonic acid ratio. J Atheroscler Thromb 20:861–877

    Article  CAS  PubMed  Google Scholar 

  9. Hashimoto T, Ako J, Nakao K, Ozaki Y, Kimura K, Noguchi T, Yasuda S, Suwa S, Fujimoto K, Nakama Y, Morita T, Shimizu W, Saito Y, Hirohata A, Morita Y, Inoue T, Okamura A, Uematsu M, Hirata K, Tanabe K, Shibata Y, Owa M, Tsujita K, Funayama H, Kokubu N, Kozuma K, Uemura S, Toubaru T, Saku K, Ohshima S, Nakai M, Nishimura K, Miyamoto Y, Ogawa H, Ishihara M, J-MINUET investigators (2018) A lower eicosapentaenoic acid/arachidonic acid ratio is associated with in-hospital fatal arrhythmic events in patients with acute myocardial infarction: a J-MINUET substudy. Heart Vessels 33:481–488

    Article  PubMed  Google Scholar 

  10. Tani S, Nagao K, Hirayama A (2015) Association of atherosclerosis-related markers and its relationship to n-3 polyunsaturated fatty acids levels with a prevalence of coronary artery disease in an urban area in Japan. Heart Vessels 30:9–19

    Article  PubMed  Google Scholar 

  11. Tani S, Takahashi A, Nagao K, Hirayama A (2015) Association of fish consumption-derived ratio of serum n-3 to n-6 polyunsaturated fatty acids and cardiovascular risk with the prevalence of coronary artery disease. Int Heart J 56:260–268

    Article  CAS  PubMed  Google Scholar 

  12. Imai E, Horio M, Nitta K, Yamagata K, Iseki K, Hara S, Ura N, Kiyohara Y, Hirakata H, Watanabe T, Moriyama T, Ando Y, Inaguma D, Narita I, Iso H, Wakai K, Yasuda Y, Tsukamoto Y, Ito S, Makino H, Hishida A, Matsuo S (2007) Estimation of glomerular filtration rate by the MDRD study equation modified for Japanese patients with chronic kidney disease. Clin Exp Nephrol 11:41–50

    Article  PubMed  Google Scholar 

  13. Sniderman AD, Blank D, Zakarian R, Bergeron J, Frohlich J (2003) Triglycerides and small dense LDL: the twin Achilles heels of the Friedewald formula. Clin Biochem 36:499–504

    Article  CAS  PubMed  Google Scholar 

  14. Ueshima H (2007) Explanation for the Japanese paradox: prevention of increase in coronary heart disease and reduction in stroke. J Atheroscler Thromb 14:278–286

    Article  PubMed  Google Scholar 

  15. Itakura H, Yokoyama M, Matsuzaki M, Saito Y, Origasa H, Ishikawa Y, Oikawa S, Sasaki J, Hishida H, Kita T, Kitabatake A, Nakaya N, Sakata T, Shimada K, Shirato K, Matsuzawa Y (2012) The change in low-density lipoprotein cholesterol concentration is positively related to plasma docosahexaenoic acid but not eicosapentaenoic acid. J Atheroscler Thromb 19:673–679

    Article  CAS  PubMed  Google Scholar 

  16. Davidson MH, Maki KC, Kalkowski J, Schaefer EJ, Torri SA, Drennan KB (1997) Effects of docosahexaenoic acid on serum lipoproteins in patients with combined hyperlipidemia: a randomized, double-blind, placebo-controlled trial. J Am Coll Nutr 16:236–243

    Article  CAS  PubMed  Google Scholar 

  17. Leigh-Firbank EC, Minihane AM, Leake DS, Wright JW, Murphy MC, Griffin BA, Williams CM (2002) Eicosapentaenoic acid and docosahexaenoic acid from fish oils: differential associations with lipid responses. Br J Nutr 87:435–445

    Article  CAS  PubMed  Google Scholar 

  18. Harris WS, Ginsberg HN, Arunakul N, Shachter NS, Windsor SL, Adams M, Berglund L, Osmundsen K (1997) Safety and efficacy of Omacor in severe hypertriglyceridemia. J Cardiovasc Risk 4:385–491

    Article  CAS  PubMed  Google Scholar 

  19. Innes JK, Calder PC (2018) The differential effects of eicosapentaenoic acid and docosahexaenoic acid on cardiometabolic risk factors: a systematic review. Int J Mol Sci. https://doi.org/10.3390/ijms19020532

    Article  PubMed  PubMed Central  Google Scholar 

  20. Maruyama C, Imamura K, Teramoto T (2003) Assessment of LDL particle size by triglyceride/HDL-cholesterol ratio in non-diabetic, healthy subjects without prominent hyperlipidemia. J Atheroscler Thromb 10:186–191

    Article  CAS  PubMed  Google Scholar 

  21. Quispe R, Manalac RJ, Faridi KF, Blaha MJ, Toth PP, Kulkarni KR, Nasir K, Virani SS, Banach M, Blumenthal RS, Martin SS, Jones SR (2015) Relationship of the triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio to the remainder of the lipid profile: the very large database of lipids-4 (VLDL-4) study. Atherosclerosis 242:243–250

    Article  CAS  PubMed  Google Scholar 

  22. Gabbs M, Leng S, Devassy JG, Monirujjaman M, Aukema HM (2015) Advances in our understanding of oxylipins derived from dietary PUFAs. Adv Nutr 6:513–540

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Leaf DA, Hatcher L (2009) The effect of lean fish consumption on triglyceride levels. Phys Sportsmed 37:37–43

    Article  PubMed  Google Scholar 

  24. Tørris C, Molin M, Cvancarova MS (2016) Lean fish consumption is associated with lower risk of metabolic syndrome: a Norwegian cross sectional study. BMC Public Health 16:347

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Oscarsson J, Hurt-Camejo E (2017) Omega-3 fatty acids eicosapentaenoic acid and docosahexaenoic acid and their mechanisms of action on apolipoprotein B-containing lipoproteins in humans: a review. Lipids Health Dis 16:149

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Iso H (2011) Lifestyle and cardiovascular disease in Japan. J Atheroscler Thromb 18:83–88

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

This work was supported by KAKENHI Grant Number 16K09045 of the Japan Society for the Promotion of Science (JSPS). The authors would like to thank International Medical Information Center (http://www.imic.or.jp/services/translation.html) for the English language review. The authors would also like to thank Mr. Gary Cooper for his help in editing the English manuscript.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Shigemasa Tani.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Tani, S., Matsuo, R. & Matsumoto, N. A longitudinal study of the association of the eicosapentaenoic acid/arachidonic acid ratio derived from fish consumption with the serum lipid levels: a pilot study. Heart Vessels 34, 189–196 (2019). https://doi.org/10.1007/s00380-018-1226-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00380-018-1226-1

Keywords

Navigation