Blood Pressure Modulating Properties of Omega-3 Polyunsaturated Fatty Acids (PUFA)

Another PUFA Heart Protective Effect?
Review Article


Omega-3 polyunsaturated fatty acids (ω-3 PUFAs) from fish and fish oils appear to protect against coronary heart disease: their dietary intake is in fact inversely associated to cardiovascular disease morbidity/mortality in population studies. Recent evidence suggests that at least a part of their heart protective effect is mediated by a relatively small but significant decrease in blood pressure level. In fact, ω-3 PUFAs exhibit wide-ranging biological actions that include regulating both vasomotor tone and renal sodium excretion, partly competing with ω-6 PUFAs for common metabolic enzymes and thereby decreasing the production of vasoconstriction rather than vasodilating and anti-inflammatory eicosanoids. PUFAs also reduce angiotensin-converting enzyme activity, angiotensin II formation and tumour growth factor-β expression, enhance endothelial nitric oxide generation and activate the parasympathetic nervous system. The final results are an improved vasodilation and arterial compliance of both small and large arteries. Preliminary clinical trials involving patients with dyslipidaemia, patients with diabetes mellitus and elderly subjects, as well as normotensive and hypertensive subjects, confirm this working hypothesis: two meta-analyses suggest that PUFA are able to slightly, but significantly improve arterial hypertension. Future research will clarify whether PUFA supplementation could improve the antihypertensive action of specific blood-pressure-lowering drug classes and of statins.

Key words

fish fish oil omega 3 fatty acids polyunsaturated fatty acids PUFA eicosapentaenoic acid EPA docosahexaenoic acid DHA blood pressure hypertension 


  1. 1.
    Dyerberg J, Bang HO, Hjorne N. Fatty acid composition of the plasma lipids in Greenland Eskimos. Am J Clin Nutr 1975; 28: 958–66PubMedGoogle Scholar
  2. 2.
    Ebbesson SO, Risica PM, Ebbesson LO, et al. Omega-3 fatty acids improve glucose tolerance and components of the metabolic syndrome in Alaskan Eskimos: the Alaska Siberia project. Int J Circumpolar Health 2005; 64(4): 396–408PubMedGoogle Scholar
  3. 3.
    Skerrett PJ, Hennekens CH. Consumption of fish and fish oils and decreased risk of stroke. Prev Cardiol 2003; 1: 38–41CrossRefGoogle Scholar
  4. 4.
    Mozaffarian D, Longstreth WT Jr, Lemaitre RN, et al. Fish consumption and stroke risk in elderly individuals: the cardiovascular health study. Arch Intern Med 2005; 165(2): 200–6PubMedCrossRefGoogle Scholar
  5. 5.
    Morris MC, Evans DA, Tangney CC, et al. Fish consumption and cognitive decline with age in a large community study. Arch Neurol 2005; 62(12): 1849–53PubMedCrossRefGoogle Scholar
  6. 6.
    Brouwer IA, Heeringa J, Geleijnse JM, et al. Intake of very long-chain n-3 fatty acids from fish and incidence of atrial fibrillation: the Rotterdam Study. Am Heart J 2006; 151(4): 857–62PubMedCrossRefGoogle Scholar
  7. 7.
    Kris-Etherton PM, Taylor DS, Yu-Poth S, et al. Polyunsaturated PUFAs in the food chain in the United States. Am J Clin Nutr 2000; 71: 179S–188SPubMedGoogle Scholar
  8. 8.
    Njelekela M, Ikeda K, Mtabaji J, et al. Dietary habits, plasma polyunsaturated fatty acids and selected coronary disease risk factors in Tanzania. East Afr Med J 2005; 82(11): 572–8PubMedGoogle Scholar
  9. 9.
    Marcelo CL, Dunham WR. Fatty acid metabolism studies of human epidermal cell cultures. J Lipid Res 1993; 34(12): 2077–90PubMedGoogle Scholar
  10. 10.
    Gebauer SK, Psota TL, Harris WS, et al. n-3 fatty acid dietary recommendations and food sources to achieve essentiality and cardiovascular benefits. Am J Clin Nutr 2006; 83(6 Suppl.): 1526S–35SPubMedGoogle Scholar
  11. 11.
    Engler MM, Engler MB. Omega-3 fatty acids: role in cardiovascular health and disease. J Cardiovasc Nurs 2006; 21(1): 17–24PubMedGoogle Scholar
  12. 12.
    Gaddi A, Cicero AFG, Pedro E. Clinical perspectives of anti-inflammatory therapy in the elderly: the Lox-/Cox- inhibition concept. Arch Geriatr Gerontol 2004; 38(3): 201–12CrossRefGoogle Scholar
  13. 13.
    Francois H, Coffman TM. Prostanoids and blood pressure: which way is up? J Clin Invest 2004; 114(6): 757–9PubMedGoogle Scholar
  14. 14.
    Wolf G. Free radical production and angiotensin. Curr Hypertens Res 2000; 2: 167–73CrossRefGoogle Scholar
  15. 15.
    On YK, Kim CH, Oh BH, et al. Effects of angiotensin converting enzyme inhibitor and calcium antagonist on endothelial function in patients with essential hypertension. Hypertens Res 2002; 25: 365–71PubMedCrossRefGoogle Scholar
  16. 16.
    Bhatnagar D, Durrington PN. Omega-3 fatty acids: their role in the prevention and treatment of atherosclerosis related risk factors and complications. Int J Clin Pract 2003; 57: 305–514PubMedGoogle Scholar
  17. 17.
    Kumar KV, Das UN. Effect of cis-unsaturated fatty acids, prostaglandins, and free radicals on angiotensin converting enzyme activity in vitro. Proc Exp Biol Med 1997; 214: 331–6Google Scholar
  18. 18.
    Mohan IK, Das UN. Effect of L-arginine-nitric oxide system on the metabolism of essential fatty acids in chemical induced diabetes mellitus in experimental animals by polyunsaturated fatty acids. Nutrition 2001; 17: 126–51CrossRefGoogle Scholar
  19. 19.
    Taddei S, Virdis A, Ghiadoni L, et al. Restoration of nitric oxide availability after calcium antagonist treatment in essential hypertension. Hypertension 2001; 37: 943–8PubMedCrossRefGoogle Scholar
  20. 20.
    Singhal A, Cole TJ, Lucas A. Early nutrition in preterm infants and later blood pressure: two cohorts after randomised trials. Lancet 2001; 357: 413–9PubMedCrossRefGoogle Scholar
  21. 21.
    Jensen CL. Effects of n-3 fatty acids during pregnancy and lactation. Am J Clin Nutr 2006; 83(6 Suppl.): 1452S–7SPubMedGoogle Scholar
  22. 22.
    Das UN. Long-chain polyunsaturated fatty acids interact with nitric oxide, superoxide anion, and transforming growth factor-beta to prevent human essential hypertension. Eur J Clin Nutr 2004; 58(2): 195–203PubMedCrossRefGoogle Scholar
  23. 23.
    Borghi C, Dormi A, Veronesi M, et al. Association between different lipidlowering treatment strategies and blood pressure control in the Brisighella Heart Study. Am Heart J 2004; 148: 285–92PubMedCrossRefGoogle Scholar
  24. 24.
    Arita M, Bianchini F, Aliberti J, et al. Stereochemical assignment, antiinflammatory properties, and receptor for the omega-3 lipid mediator resolvin E1. J Exp Med 2005; 201: 713–22PubMedCrossRefGoogle Scholar
  25. 25.
    Bannenberg GL, Chiang N, Ariel A, et al. Molecular circuits of resolution: formation and actions of resolvins and protectins. J Immunol 2005; 174: 4345–55PubMedGoogle Scholar
  26. 26.
    Serhan CN, Arita M, Hong S, et al. Resolvins, docosatrienes, and neuroprotectins, novel omega-3-derived mediators, and their endogenous aspirin-triggered epimers. Lipids 2004; 39: 1125–32PubMedCrossRefGoogle Scholar
  27. 27.
    Alexander Aguilera A, Hernandez Diaz G, Lara Barcelata M, et al. Induction of Cd36 expression elicited by fish oil PUFA in spontaneously hypertensive rats. J Nutr Biochem 2006; 17(11): 760–5CrossRefGoogle Scholar
  28. 28.
    Aguila MB, Pinheiro AR, Aquino JC, et al. Different edible oil beneficial effects (canola oil, fish oil, palm oil, olive oil, and soybean oil) on spontaneously hypertensive rat glomerular enlargement and glomeruli number. Prostaglandins Other Lipid Mediat 2005; 76(1-4): 74–85PubMedCrossRefGoogle Scholar
  29. 29.
    Deckelbaum RJ, Worgall TS, Seo T. n-3 fatty acids and gene expression. Am J Clin Nutr 2006; 83(6 Suppl.): 1520S–5SPubMedGoogle Scholar
  30. 30.
    Goodfellow J, Bellamy MF, Ramsey MW, et al. Dietary supplementation with marine omega-3 fatty acids improve systemic large artery endothelial function in subjects with hypercholesterolemia. J Am Coll Cardiol 2000; 35: 267–70CrossRefGoogle Scholar
  31. 31.
    Nestel P, Shige H, Pomeroy S, et al. The n-3 fatty acids eicosapentaenoic acid and docosahexaenoic acid increase systemic arterial compliance in humans. Am J Clin Nutr 2002; 76(2): 326–30PubMedGoogle Scholar
  32. 32.
    Tomiyama H, Takazawa K, Osa S, et al. Do eicosapentaenoic acid supplements attenuate age-related increases in arterial stiffness in patients with dyslipidemia? A preliminary study. Hypertens Res 2005; 28(8): 651–5CrossRefGoogle Scholar
  33. 33.
    Grimsgaard S, Bonaa KH, Hansen JB, et al. Effects of highly purified eicosapentaenoic acid and docosahexaenoic acid on hemodynamics in humans. Am J Clin Nutr 1998; 68: 52–9PubMedGoogle Scholar
  34. 34.
    Engler MM, Engler MB, Pierson DM, et al. Effects of docosahexaenoic acid on vascular pathology an reactivity in hypertension. Exp Biol Med 2003; 228: 299–307Google Scholar
  35. 35.
    Bao DQ, Mori T, Burke V, et al. Effects of dietary fish and weight reduction on ambulatory blood pressure in overweight hypertensives. Hypertension 1998; 32: 710–7PubMedCrossRefGoogle Scholar
  36. 36.
    Christensen JH, Skou HA, Madsen T, et al. Heart rate variability and n-3 polyunsaturated fatty acids in patients with diabetes mellitus. J Intern Med 2001; 249: 545–52PubMedCrossRefGoogle Scholar
  37. 37.
    Mori TA, Bao DQ, Burke V, et al. Docosahexaenoic acid but not eicosapentaenoic acid lowers ambulatory blood pressure and heart rate in humans. Hypertension 1999; 34: 253–60PubMedCrossRefGoogle Scholar
  38. 38.
    Geleijnse JM, Giltay EJ, Grobbee DE, et al. Blood pressure response to fish oil supplementation: metaregression analysis of randomized trials. J Hypertens 2002; 20: 1493–9PubMedCrossRefGoogle Scholar
  39. 39.
    Sanders TA, Gleason K, Griffin B, et al. Influence of an algal triacylglycerol containing docosahexaenoic acid (22: 6n-3) and docosapentaenoic acid (22: 5n-6) on cardiovascular risk factors in healthy men and women. Br J Nutr 2006; 95(3): 525–31PubMedCrossRefGoogle Scholar
  40. 40.
    Rasmussen BM, Vessby B, Uusitupa M, et al. Effects of dietary saturated, monounsaturated, and n-3 fatty acids on blood pressure in healthy subjects. Am J Clin Nutr 2006; 83(2): 221–6PubMedGoogle Scholar
  41. 41.
    Damsgaard CT, Schack-Nielsen L, Michaelsen KF, et al. Fish oil affects blood pressure and the plasma lipid profile in healthy Danish infants. J Nutr 2006; 136(1): 94–9PubMedGoogle Scholar
  42. 42.
    Kris-Etherton PM, Harris WS, Appel LJ, et al. AHA scientific statement. Fish consumption, fish oil, omega-3 fatty acids, and cardiovascular disease. Circulation 2002; 106: 2747–57PubMedCrossRefGoogle Scholar
  43. 43.
    Nettleton JA, Katz R. n-3 long-chain polyunsaturated fatty acids in type 2 diabetes: a review. J Am Diet Assoc 2005; 105(3): 428–40PubMedCrossRefGoogle Scholar
  44. 44.
    Hooper L, Thompson RL, Harrison RA, et al. Risks and benefits of omega 3 fats for mortality, cardiovascular disease, and cancer: systematic review. BMJ 2006; 332: 752–60PubMedCrossRefGoogle Scholar
  45. 45.
    Guallar E, Sanz-Gallardo MI, van’t Veer P, et al. Mercury, fish oils, and the risk of myocardial infarction. Heavy Metals and Myocardial Infarction Study Group. N Engl J Med 2002; 347: 1747–54PubMedCrossRefGoogle Scholar
  46. 46.
    Cohen JT, Bellinger DC, Connor WE, et al. A quantitative risk-benefit analysis of changes in population fish consumption. Am J Prev Med 2005; 29(4): 325–34PubMedCrossRefGoogle Scholar
  47. 47.
    Gaziano TA. Cardiovascular disease in the developing world and its cost-effective management. Circulation 2005; 112(23): 3547–53PubMedCrossRefGoogle Scholar
  48. 48.
    McInnes GT. Lowering blood pressure for cardiovascular risk reduction. J Hypertens Suppl 2005; 23(1): S3–8PubMedCrossRefGoogle Scholar
  49. 49.
    Cicero AFG, Gaddi AV, Borghi C. Complementary medicine for hypertension: what evidence for herbalist suggestions? Evaluation of risks and potential applications. Evid Based Integr Med 2005; 2(1): 47–55CrossRefGoogle Scholar
  50. 50.
    Wang C, Harris WS, Chung M, et al. n-3 Fatty acids from fish or fish-oil supplements, but not alpha-linolenic acid, benefit cardiovascular disease outcomes in primary- and secondary-prevention studies: a systematic review. Am J Clin Nutr 2006; 84(1): 5–17PubMedGoogle Scholar
  51. 51.
    Tavazzi L, Tognoni G, Franzosi MG, et al. GISSI-HF Investigators. Rationale and design of the GISSI heart failure trial: a large trial to assess the effects of n-3 polyunsaturated fatty acids and rosuvastatin in symptomatic congestive heart failure. Eur J Heart Fail 2004; 6(5): 635–41PubMedGoogle Scholar
  52. 52.
    Mori TA. Omega-3 fatty acids and hypertension in humans. Clin Exp Pharmacol Physiol 2006; 33(9): 842–6PubMedCrossRefGoogle Scholar

Copyright information

© Adis Data Information BV 2007

Authors and Affiliations

  1. 1.Hypertension Research Unit, “D. Campanacci” Clinical Medicine and Applied Biotechnology Department, Sant’Orsola-Malpighi HospitalUniversity of Bologna “Alma Mater Studiorum”BolognaItaly
  2. 2.Atherosclerosis Research Unit, “D. Campanacci” Clinical Medicine and Applied Biotechnology DepartmentUniversity of Bologna “Alma Mater Studiorum”BolognaItaly

Personalised recommendations