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Aspirin and omega-3 polyunsaturated fatty acid use and their interaction in cardiovascular diseases and colorectal adenomas

Published online by Cambridge University Press:  13 July 2021

Ivan E. Wang Open the ORCID record for Ivan E. Wang [Opens in a new window] ,
Shana Yi ,
Robert C. Block  and
Shaker A. Mousa Open the ORCID record for Shaker A. Mousa [Opens in a new window]
Ivan E. Wang
Affiliation:
The Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, 1 Discovery Drive, Rensselaer, NY122144, USA
Shana Yi
Affiliation:
Department of Public Health Sciences, and Cardiology Division, Department of Medicine, University of Rochester School of Medicine and Dentistry, 601 Elmwood Avenue, Rochester, NY14642, USA
Robert C. Block
Affiliation:
Department of Public Health Sciences, and Cardiology Division, Department of Medicine, University of Rochester School of Medicine and Dentistry, 601 Elmwood Avenue, Rochester, NY14642, USA
Shaker A. Mousa*
Affiliation:
The Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, 1 Discovery Drive, Rensselaer, NY122144, USA
*
*Corresponding Author: Shaker A. Mousa, email: [email protected]
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Abstract

Aspirin (acetylsalicylic acid, ASA) is inexpensive and is established in preventing cardiovascular disease (CVD) and colorectal adenomas. Omega-3 (n3) polyunsaturated fatty acids (PUFA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have also shown benefit in preventing CVD. The combination could be an effective preventative measure in patients with such diseases. ASA and n3 PUFA reduced the risk of CVD in ASA-resistant or diabetic patients. EPA- and DHA-deficient patients also benefited the most from n3 PUFA supplementation. Synergistic effects between ASA and EPA and DHA are ‘V-shaped’ such that optimal ASA efficacy is dependent on EPA and DHA concentrations in blood. In colorectal adenomas, ASA (300 mg/d) and EPA reduced adenoma burden in a location- and subtype-specific manner. Low doses of ASA (75–100 mg/d) were used in CVD prevention; however, ultra-low doses (30 mg/d) can also reduce thrombosis. EPA-to-DHA ratio is also important with regard to efficacy. DHA is more effective in reducing blood pressure and modulating systemic inflammation; however, high-dose EPA can lower CVD events in high-risk individuals. Although current literature has yet to examine ASA and DHA in preventing CVD, such combination warrants further investigation. To increase adherence to ASA and n3 PUFA supplementation, combination dosage form may be required to improve outcomes.

Keywords

Low-dose aspirinFish oilOmega-3 fatty acidsEPADHACardiovascular diseaseThrombosisColorectal adenomaColorectal cancer
Type
Review Article
Information
Nutrition Research Reviews , Volume 35 , Issue 2 , December 2022 , pp. 295 - 307
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Copyright
© The Author(s), 2021. Published by Cambridge University Press on behalf of The Nutrition Society

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References

Arnett, DK, Blumenthal, RS, Albert, MA et al. (2019) 2019 ACC/AHA guideline on the primary prevention of cardiovascular disease: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol 74, e177–e232.CrossRefGoogle Scholar
Benamouzig, R, Deyra, J, Martin, A et al. (2003) Daily soluble aspirin and prevention of colorectal adenoma recurrence: one-year results of the APACC trial. Gastroenterology 125, 328–336.CrossRefGoogle ScholarPubMed
Sezai, A, Unosawa, S, Taoka, M et al. (2019) Long-term comparison of ethyl icosapentate vs. omega-3-acid ethyl in patients with cardiovascular disease and hypertriglyceridemia (DEFAT Trial). Circ J 83, 1368–1376.CrossRefGoogle Scholar
Lev, EI, Solodky, A, Harel, N et al. (2010) Treatment of aspirin-resistant patients with omega-3 fatty acids versus aspirin dose escalation. J Am Coll Cardiol 55, 114–121.CrossRefGoogle ScholarPubMed
World Health Organization (2017) Cardiovascular diseases (CVDs). https://www.who.int/news-room/fact-sheets/detail/cardiovascular-diseases-(cvds) (accessed November 19 2020)Google Scholar
Centers for Disease Control and Prevention (2020) NHANES – National Health and Nutrition Examination Survey. https://www.cdc.gov/nchs/nhanes/ (accessed November 19 2020)Google Scholar
Roth, GA, Johnson, CO, Abate, KH et al. (2018) The burden of cardiovascular diseases among US states, 1990-2016. JAMA Cardiol 3, 375–389.Google ScholarPubMed
Danaei, G, Ding, EL, Mozaffarian, D et al. (2009) The preventable causes of death in the United States: comparative risk assessment of dietary, lifestyle, and metabolic risk factors. PLoS Med 6, e1000058.CrossRefGoogle ScholarPubMed
Blackwell, DL & Villarroel, MA (2018) Tables of Summary Health Statistics for U.S. Adults: 2017 National Health Interview Survey. http://www.cdc.gov/nchs/nhis/SHS/tables.htm Google Scholar
American Heart Association and American Stroke Association (2017) Cardiovascular disease: a costly burden for America, Projections through 2035. https://healthmetrics.heart.org/wp-content/uploads/2017/10/Cardiovascular-Disease-A-Costly-Burden.pdf (accessed November 20 2020)Google Scholar
Siegel, RL, Miller, KD, Goding Sauer, A et al. (2020) Colorectal cancer statistics, 2020. CA Cancer J Clin 70, 145–164.CrossRefGoogle ScholarPubMed
Levine, GN, Bates, ER, Bittl, JA et al. (2016) 2016 ACC/aha guideline focused update on duration of dual antiplatelet therapy in patients with coronary artery disease: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol 68, 1082–1115.CrossRefGoogle Scholar
Serhan, CN (2014) Pro-resolving lipid mediators are leads for resolution physiology. Nature 510, 92–101.CrossRefGoogle ScholarPubMed
Chiang, N, Bermudez, EA, Ridker, PM et al. (2004) Aspirin triggers antiinflammatory 15-epi-lipoxin A4 and inhibits thromboxane in a randomized human trial. Proc Natl Acad Sci U S A 101, 15178–15183.CrossRefGoogle Scholar
Sorokin, AV, Yang, ZH, & Remaley, AT (2016) Anti-inflammatory and atheroprotective properties of omega-3 polyunsaturated fatty acids. J Clin Exp Cardiolog 7, 478.CrossRefGoogle Scholar
Franzese, CJ, Bliden, KP, Gesheff, MG et al. (2015) Relation of fish oil supplementation to markers of atherothrombotic risk in patients with cardiovascular disease not receiving lipid-lowering therapy. Am J Cardiol 115, 1204–1211.CrossRefGoogle Scholar
Block, RC, Duff, R, Lawrence, P et al. (2010) The effects of EPA, DHA, and aspirin ingestion on plasma lysophospholipids and autotaxin. Prostaglandins Leukot Essent Fatty Acids 82, 87–95.CrossRefGoogle ScholarPubMed
Poreba, M, Mostowik, M, Siniarski, A et al. (2017) Treatment with high-dose n-3 PUFAs has no effect on platelet function, coagulation, metabolic status or inflammation in patients with atherosclerosis and type 2 diabetes. Cardiovasc Diabetol 16, 50.CrossRefGoogle ScholarPubMed
Ramirez, JL, Gasper, WJ, Khetani, SA et al. (2019) Fish oil increases specialized pro-resolving lipid mediators in PAD (The OMEGA-PAD II Trial). J Surg Res 238, 164–174.Google Scholar
Siniarski, A, Haberka, M, Mostowik, M et al. (2018) Treatment with omega-3 polyunsaturated fatty acids does not improve endothelial function in patients with type 2 diabetes and very high cardiovascular risk: a randomized, double-blind, placebo-controlled study (Omega-FMD). Atherosclerosis 271, 148–155.Google Scholar
Amarin Pharma, I (2017) Highlights of Prescribing Information VASCEPA ® (icosapent ethyl) Capsules. https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/202057s019lbl.pdf (accessed November 20 2020)Google Scholar
AstraZeneca Pharmaceuticals LP (2014) Highlights of Prescribing Information EPANOVA ® (omega-3-carboxylic acids) Capsules. https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/205060s000lbl.pdf (accessed November 20 2020)Google Scholar
GlaxoSmithKline (2014) Highlights of Prescribing Information LOVAZA (omega-3-acids ethyl esters) Capsules. https://www.gsksource.com/pharma/content/dam/GlaxoSmithKline/US/en/Prescribing_Information/Lovaza/pdf/LOVAZA-PI-PIL.PDF (accessed 20 November 2020)Google Scholar
Trygg Pharma, I (2014) Highlights of Prescribing Information OMTRYG™ (omega-3-acids ethyl esters A) Capsules. https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/204977s000lbl.pdf (accessed November 20 2020)Google Scholar
Kalish, BT, Le, HD, Fitzgerald, JM et al. (2013) Intravenous fish oil lipid emulsion promotes a shift toward anti-inflammatory proresolving lipid mediators. Am J Physiol Gastrointest Liver Physiol 305, G818–G818.CrossRefGoogle ScholarPubMed
Merched, AJ, Serhan, CN, & Chan, L (2011) Nutrigenetic disruption of inflammation-resolution homeostasis and atherogenesis. J Nutrigenet Nutrigenomics 4, 12–24.Google ScholarPubMed
Schaller, MS, Zahner, GJ, Gasper, WJ et al. (2017) Relationship between the omega-3 index and specialized pro-resolving lipid mediators in patients with peripheral arterial disease taking fish oil supplements. J Clin Lipidol 11, 1289–1295.CrossRefGoogle ScholarPubMed
Hishikawa, D, Shindou, H, Kobayashi, S et al. (2008) Discovery of a lysophospholipid acyltransferase family essential for membrane asymmetry and diversity. Proc Natl Acad Sci U S A 105, 2830–2835.CrossRefGoogle ScholarPubMed
Shimizu, T, Ohto, T, & Kita, Y (2006) Cytosolic phospholipase A2: biochemical properties and physiological roles. IUBMB Life 58, 328–333.CrossRefGoogle ScholarPubMed
Wang, D & Dubois, RN (2006) Prostaglandins and cancer. Gut 55, 115–122.CrossRefGoogle ScholarPubMed
West, NJ, Clark, SK, Phillips, RKS et al. (2010) Eicosapentaenoic acid reduces rectal polyp number and size in familial adenomatous polyposis. Gut 59, 918–925.CrossRefGoogle ScholarPubMed
Guillot, N, Caillet, E, Laville, M et al. (2009) Increasing intakes of the long-chain ω-3 docosahexaenoic acid: effects on platelet functions and redox status in healthy men. FASEB J 23, 2909–2916.CrossRefGoogle ScholarPubMed
Sorokin, AV, Yang, ZH, Vaisman, BL et al. (2016) Addition of aspirin to a fish oil-rich diet decreases inflammation and atherosclerosis in ApoE-null mice. J Nutri Biochem 35, 58–65.CrossRefGoogle ScholarPubMed
Block, RC, Abdolahi, A, Tu, X et al. (2015) The effects of aspirin on platelet function and lysophosphatidic acids depend on plasma concentrations of EPA and DHA. Prostaglandins Leukot Essent Fatty Acids 96, 17–24.CrossRefGoogle ScholarPubMed
Block, RC, Kakinami, L, Jonovich, M et al. (2012) The combination of EPA+DHA and low-dose aspirin ingestion reduces platelet function acutely whereas each alone may not in healthy humans. Prostaglandins Leukot Essent Fatty Acids 87, 143–151.CrossRefGoogle ScholarPubMed
Lagarde, M, Calzada, C, Guichardant, M et al. (2013) Dose-effect and metabolism of docosahexaenoic acid: pathophysiological relevance in blood platelets. Prostaglandins Leukot Essent Fatty Acids 88, 49–52.CrossRefGoogle ScholarPubMed
Block, RC, Abdolahi, A, Smith, B et al. (2013) Effects of low-dose aspirin and fish oil on platelet function and NF-kappaB in adults with diabetes mellitus. Prostaglandins Leukot Essent Fatty Acids 89, 9–18.CrossRefGoogle ScholarPubMed
Abdolahi, A, Georas, SN, Thomas Brenna, J et al. (2014) The effects of aspirin and fish oil consumption on lysophosphatidylcholines and lysophosphatidic acids and their correlates with platelet aggregation in adults with diabetes mellitus. Prostaglandins Leukot Essent Fatty Acids 90, 61–68.CrossRefGoogle ScholarPubMed
Gaire, BP, Sapkota, A, Song, MR et al. (2019) Lysophosphatidic acid receptor 1 (LPA1) plays critical roles in microglial activation and brain damage after transient focal cerebral ischemia. J Neuroinflammation 16, 170.CrossRefGoogle ScholarPubMed
Holub, A, Mousa, S, Abdolahi, A et al. (2020) The effects of aspirin and N-3 fatty acids on telomerase activity in adults with diabetes mellitus. Nutr Metab Cardiovasc Dis 30, 1795–1799.CrossRefGoogle ScholarPubMed
Mizia-Stec, K, Mizia, M, Haberka, M et al. (2013) N-3 polyunsaturated fatty acids do not influence the efficacy of dual antiplatelet therapy in stable angina pectoris patients after percutaneous coronary intervention. Cardiol J 20, 478–485.CrossRefGoogle Scholar
Gajos, G, Zalewski, J, Rostoff, P et al. (2011) Reduced thrombin formation and altered fibrin clot properties induced by polyunsaturated omega-3 fatty acids on top of dual antiplatelet therapy in patients undergoing percutaneous coronary intervention (OMEGA-PCI Clot). Arterioscler Thromb Vasc Biol 31, 1696–1702.Google Scholar
Elajami, TK, Colas, RA, Dalli, J et al. (2016) Specialized proresolving lipid mediators in patients with coronary artery disease and their potential for clot remodeling. FASEB J 30, 2792–2801.CrossRefGoogle ScholarPubMed
Bowman, L, Mafham, M, Stevens, W et al. (2018) ASCEND: A Study of Cardiovascular Events iN Diabetes: characteristics of a randomized trial of aspirin and of omega-3 fatty acid supplementation in 15,480 people with diabetes. Am Heart J 198, 135–144.CrossRefGoogle ScholarPubMed
Bowman, L, Mafham, M, Wallendszus, K et al. (2018) Effects of n-3 fatty acid supplements in diabetes mellitus. N Engl J Med 379, 1540–1550.Google ScholarPubMed
Hernáez, Á, Sanllorente, A, Castañer, O et al. (2019) Increased consumption of virgin olive oil, nuts, legumes, whole grains, and fish promotes HDL functions in humans. Mol Nutr Food Res 63, 1800847–1800847.CrossRefGoogle ScholarPubMed
Pintó, X, Fanlo-Maresma, M, Corbella, E et al. (2019) A Mediterranean diet rich in extra-virgin olive oil is associated with a reduced prevalence of nonalcoholic fatty liver disease in older individuals at high cardiovascular risk. J Nutr 149, 1920–1929.CrossRefGoogle Scholar
Sanchez-Rodriguez, E, Biel-Glesson, S, Fernandez-Navarro, JR et al. (2019) Effects of virgin olive oils differing in their bioactive compound contents on biomarkers of oxidative stress and inflammation in healthy adults: a randomized double-blind controlled trial. Nutrients 11, 561.CrossRefGoogle ScholarPubMed
Schwingshackl, L, Christoph, M, & Hoffmann, G (2015) Effects of olive oil on markers of inflammation and endothelial function – a systematic review and meta-analysis. Nutrients 7, 7651–7675.CrossRefGoogle Scholar
Irish, AB, Viecelli, AK, Hawley, CM et al. (2017) Effect of fish oil supplementation and aspirin use on arteriovenous fistula failure in patients requiring hemodialysis a randomized clinical trial. JAMA Int Med 177, 184–193.Google ScholarPubMed
Viecelli, AK, Polkinghorne, KR, Pascoe, EM et al. (2019) Fish oil and aspirin effects on arteriovenous fistula function: secondary outcomes of the randomised omega-3 fatty acids (Fish oils) and Aspirin in Vascular access OUtcomes in REnal Disease (FAVOURED) trial. PLoS One 14, e0213274.CrossRefGoogle ScholarPubMed
Patrignani, P, Sacco, A, Sostres, C et al. (2017) Low-dose aspirin acetylates cyclooxygenase-1 in human colorectal mucosa: implications for the chemoprevention of colorectal cancer. Clin Pharmacol Ther 102, 52–61.CrossRefGoogle ScholarPubMed
Fedirko, V, Bradshaw, PT, Figueiredo, JC et al. (2015) Urinary metabolites of prostanoids and risk of recurrent colorectal adenomas in the Aspirin/Folate Polyp Prevention Study (AFPPS). Cancer Prev Res (Phila) 8, 1061–1068.Google Scholar
Chubak, J, Whitlock, EP, Williams, SB et al. (2016) Aspirin for the prevention of cancer incidence and mortality: systematic evidence reviews for the U.S. Preventive Services Task Force. Ann Intern Med 164, 814–814.CrossRefGoogle ScholarPubMed
Whitlock, EP, Burda, BU, Williams, SB et al. (2016) Bleeding risks with aspirin use for primary prevention in adults: a systematic review for the U.S. Preventive Services Task Force. Ann Intern Med 164, 826–826.CrossRefGoogle ScholarPubMed
White, MN, Shrubsole, MJ, Cai, Q et al. (2019) Effects of fish oil supplementation on eicosanoid production in patients at higher risk for colorectal cancer. Eur J Cancer Prev 28, 188–195.CrossRefGoogle ScholarPubMed
Hull, MA, Sandell, AC, Montgomery, AA et al. (2013) A randomized controlled trial of eicosapentaenoic acid and/or aspirin for colorectal adenoma prevention during colonoscopic surveillance in the NHS Bowel Cancer Screening Programme (The seAFOod Polyp Prevention Trial): Study protocol for a randomized cont. Trials 14, 237–237.CrossRefGoogle Scholar
Hull, MA, Sprange, K, Hepburn, T et al. (2018) Eicosapentaenoic acid and aspirin, alone and in combination, for the prevention of colorectal adenomas (seAFOod Polyp Prevention trial): a multicentre, randomised, double-blind, placebo-controlled, 2 × 2 factorial trial. Lancet 392, 2583–2594.Google ScholarPubMed
van Gijn, J (1991) A comparison of two doses of aspirin (30 mg vs. 283 mg a day) in patients after a transient ischemic attack or minor ischemic stroke. N Engl J Med 325, 1261–1266.Google ScholarPubMed
Patrono, C, Coller, B, FitzGerald, GA et al. Platelet-active drugs: the relationships among dose, effectiveness, and side effects – The Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Comparative Study 126, 234S–264S.Google Scholar
Baron, JA, Cole, BF, Sandler, RS et al. (2003) A randomized trial of aspirin to prevent colorectal adenomas. N Engl J Med 348, 891–899.Google ScholarPubMed
Cole, BF, Logan, RF, Halabi, S et al. (2009) Aspirin for the chemoprevention of colorectal adenomas: meta-analysis of the randomized trials. J Natl Cancer Inst 101, 256–266.CrossRefGoogle ScholarPubMed
Logan, RFA, Grainge, MJ, Shepherd, VC et al. (2008) Aspirin and folic acid for the prevention of recurrent colorectal adenomas. Gastroenterology 134, 29–38.Google ScholarPubMed
Sandler, RS, Halabi, S, Baron, JA et al. (2003) A randomized trial of aspirin to prevent colorectal adenomas in patients with previous colorectal cancer. N Engl J Med 348, 883–890.CrossRefGoogle ScholarPubMed
Allaire, J, Couture, P, Leclerc, M et al. (2016) A randomized, crossover, head-to-head comparison of eicosapentaenoic acid and docosahexaenoic acid supplementation to reduce inflammation markers in men and women: The Comparing EPA to DHA (ComparED) Study. Am J Clin Nutr 104, 280–287.Google ScholarPubMed
Allaire, J, Vors, C, Tremblay, AJ et al. (2018) High-dose DHA has more profound effects on LDL-related features than high-dose EPA: The ComparED study. J Clin Endocrinol Metab 103, 2909–2917.CrossRefGoogle ScholarPubMed
Vors, C, Allaire, J, Marin, J et al. (2017) Inflammatory gene expression in whole blood cells after EPA vs. DHA supplementation: results from the ComparED study. Atherosclerosis 257, 116–122.CrossRefGoogle ScholarPubMed
Hirayama, S, Miida, T (2012) Small dense LDL: an emerging risk factor for cardiovascular disease. Clin Chim Acta 414, 215–224.CrossRefGoogle ScholarPubMed
Allaire, J, Harris, WS, Vors, C et al. (2017) Supplementation with high-dose docosahexaenoic acid increases the Omega-3 Index more than high-dose eicosapentaenoic acid. Prostaglandins Leukot Essent Fatty Acids 120, 8–14.CrossRefGoogle ScholarPubMed
Lee, JB, Notay, K, Klingel, SL et al. (2019) Docosahexaenoic acid reduces resting blood pressure but increases muscle sympathetic outflow compared with eicosapentaenoic acid in healthy men and women. Am J Physiol Heart Circ Physiol 316, H873–H881.Google ScholarPubMed
Mori, TA, Bao, DQ, Burke, V et al. (1999) Docosahexaenoic acid but not eicosapentaenoic acid lowers ambulatory blood pressure and heart rate in humans. Hypertension 34, 253–260.CrossRefGoogle Scholar
Rontoyanni, VG, Hall, WL, Pombo-Rodrigues, S et al. (2012) A comparison of the changes in cardiac output and systemic vascular resistance during exercise following high-fat meals containing DHA or EPA. Br J Nutr 108, 492–499.CrossRefGoogle ScholarPubMed
Block, RC, Holub, A, Abdolahi, A et al. (2017) Effects of aspirin in combination with EPA and DHA on HDL-C cholesterol and ApoA1 exchange in individuals with type 2 diabetes mellitus. Prostaglandins Leukot Essent Fatty Acids 126, 25–31.CrossRefGoogle ScholarPubMed
Anuar, N, Sabri, AH, Bustami Effendi, TJ et al. (2020) Development and characterisation of ibuprofen-loaded nanoemulsion with enhanced oral bioavailability. Heliyon 6, e04570.Google ScholarPubMed
Serini, S, Cassano, R, Corsetto, PA et al. (2018) Omega-3 PUFA loaded in resveratrol-based solid lipid nanoparticles: physicochemical properties and antineoplastic activities in human colorectal cancer cells in vitro. Int J Mol Sci 19, 586.CrossRefGoogle ScholarPubMed