Parenteral Omega-3 Fatty Acids (Omegaven) and Intestinal Recovery

Living reference work entry

Abstract

Growing evidence from several clinical and experimental studies indicates that omega-3 polyunsaturated fatty acids (n-3 PUFAs) can reduce not only the activity of inflammatory processes but may also improve the immune system and protect the organism against the negative effect of the systemic inflammatory response syndrome. The positive anti-inflammatory effect of n-3 PUFAs has been described in several inflammatory conditions such as inflammatory bowel disease, rheumatoid arthritis, and hepatitis. In this report, we discuss the use of a fish oil-based lipid emulsion in the treatment of different gastrointestinal disorders including intestinal ischemia-reperfusion, short bowel syndrome, chemotherapy-induced mucositis, microvillous inclusion disease, etc. The mechanisms of action of n-3 PUFAs on intestinal cell turnover (proliferation and apoptosis) as well as the effects of this agent on intestinal regrowth after bowel resection and intestinal recovery following intestinal ischemia or chemotherapy-induced damage in rodent models are discussed. Such knowledge may allow us to exploit omega-3 polyunsaturated fatty acids that act as gut-trophic agent for the bowel mucosa and suggests new therapeutic strategies to maintain gut integrity after massive bowel resection or intestinal injury, eliminating the dependence on total parenteral nutrition.

Keywords

Fatigue Hepatitis Ischemia Methotrexate Luminal 

List of Abbreviations

DHA

Docosahexaenoic acid

EPA

Eicosapentaenoic acid

IR

Ischemia-reperfusion

MOF

Multiple-organ failure

MTX

Methotrexate

n-3 PUFAs

Omega-3 polyunsaturated fatty acids

SBS

Short bowel syndrome

References

  1. Arisue A, Shimojima N, Tomiya M, Shimizu T, Harada D, Nakayama M, Tomita H, Shinoda M, Tanabe M, Maruyama I, Mizuno M, Kuroda T, Wakabayashi G, Morikawa Y. Effect of an omega-3 lipid emulsion in reducing oxidative stress in a rat model of intestinal ischemia-reperfusion injury. Pediatr Surg Int. 2012;28:913–8.PubMedCentralPubMedCrossRefGoogle Scholar
  2. Bjerknes M, Cheng H. The stem-cell zone of the small intestinal epithelium. I. Evidence from Paneth cells in the adult mouse. Am J Anat. 1981;160:51–63.PubMedCrossRefGoogle Scholar
  3. Booth IW, Lander AD. Short bowel syndrome. Baillieres Clin Gastroenterol. 1998;12:739–72.PubMedCrossRefGoogle Scholar
  4. Burlamaqui IM, Dornelas CA, Valença Júnior JT, Mota DM, Mesquita FJ, Veras LB, Vasconcelos PR, Rodrigues LV. Effect of a hyperlipidic diet rich in omegas 3, 6 and 9 on aberrant crypt formation in rat colonic mucosa. Acta Cir Bras. 2012;27:30–6.PubMedCrossRefGoogle Scholar
  5. Calder PC. Fatty acids and immune function: relevance to inflammatory bowel diseases. Int Rev Immunol. 2009;28:506–34.PubMedCrossRefGoogle Scholar
  6. Calderaro V, Parrillo C, Balestrieri ML, Giovane A, Filippelli A, Rossi F. Docosahexaenoic acid and signaling pathways in rabbit colon. Mol Pharmacol. 1994;45:737–46.PubMedGoogle Scholar
  7. Coran AG, Spivak D, Teitelbaum DH. An analysis of the morbidity and mortality of short bowel syndrome in the pediatric age group. Eur J Pediatr Surg. 1999;9:228–30.PubMedCrossRefGoogle Scholar
  8. Davidson LA, Nguyen DV, Hokanson RM, Callaway ES, Isett RB, Turner ND, Dougherty ER, Lupton JR, Carroll RJ, Chapkin RS. Chemo-preventive n-3 polyunsaturated fatty acids reprogram genetic signatures during colon cancer initiation and progression in the rat. Cancer Res. 2004;64:6797–804.PubMedCrossRefGoogle Scholar
  9. Diamond IR, Sterescu A, Pencharz PB, Wales PW. The rationale for the use of parenteral omega-3 lipids in children with short bowel syndrome and liver disease. Pediatr Surg Int. 2008;24:773–8.PubMedCrossRefGoogle Scholar
  10. Dyerberg J, Bang HO, Hjorne N. Fatty acid composition of the plasma lipids in Greenland Eskimos. Am J Clin Nutr. 1975;28:958–63.PubMedGoogle Scholar
  11. Empey LR, Walker K, Fedorak RN. Fish oil-enriched diet is mucosal protective against acetic acid-induced colitis in rats. Can J Physiol Pharmacol. 1992;70:660–8.PubMedCrossRefGoogle Scholar
  12. Geusens P, Wouters C, Nijs J. Long term effect of omega-3 fatty acid supplementation in active rheumatoid arthritis: a 12 month, double blind, controlled study. Arthritis Rheum. 1994;37:824–31.PubMedCrossRefGoogle Scholar
  13. Granger DN, Hollwarth ME, Park DA. Ischemia reperfusion injury: role of oxygen-derived free radicals. Acta Physiol Scand Suppl. 1986;548:47–56.PubMedGoogle Scholar
  14. Haglund U, Bergqvist D. Intestinal ischemia-the basics. Langenbecks Arch Surg. 1999;384:233–8.PubMedCrossRefGoogle Scholar
  15. Harris WS, Pottala JV, Lacey SM, Vasan RS, Larson MG, Robins SJ. Clinical correlates and heritability of erythrocyte eicosapentaenoic and docosahexaenoic acid content in the Framingham Heart Study. Atherosclerosis. 2012;225:425–31.PubMedCentralPubMedCrossRefGoogle Scholar
  16. Hart MH, Grandjean CJ, Park JHY, Erdman SH, Vanderhoof JA. Essential fatty acid deficiency and postresection mucosal adaptation in the rats. Gastroenterology. 1988;94:682–7.PubMedGoogle Scholar
  17. Hassan IR, Gronert K. Acute changes in dietary omega-3 and omega-6 polyunsaturated fatty acids have a pronounced impact on survival following ischemic renal injury and formation of renoprotective docosahexaenoic acid-derived protectin D1. J Immunol. 2009;182:3223–32.PubMedCrossRefGoogle Scholar
  18. Hawthorne AB, Daneshmend TK, Hawkey CJ. Treatment of ulcerative colitis with fish oil supplementation: a prospective 12 month randomised controlled trial. Gut. 1992;33:922–8.PubMedCentralPubMedCrossRefGoogle Scholar
  19. Helland IB, Smith L, Saarem K, Saugstad OD, Drevon CA. Maternal supplementation with very-long-chain n-3 fatty acids during pregnancy and lactation augments children’s IQ at 4 years of age. Pediatrics. 2003;111(1):e39–44.PubMedCrossRefGoogle Scholar
  20. Hillier K, Jewell R, Dorrell L, Smith CL. Incorporation of fatty acids from fish oil and olive oil into colonic mucosal lipids and effects upon eicosanoid synthesis in inflammatory bowel disease. Gut. 1991;32:1151–5.PubMedCentralPubMedCrossRefGoogle Scholar
  21. Khanna A, Rossman J, Caty MG, Fung HL. Beneficial effects of intraluminal nitroglycerin in intestinal ischemia-reperfusion injury in rats. J Surg Res. 2003;114:15–24.PubMedCrossRefGoogle Scholar
  22. Kidd PM. Omega-3 DHA and EPA for cognition, behavior, and mood: clinical findings and structural-functional synergies with cell membrane phospholipids. Altern Med Rev. 2007;12:207–27.PubMedGoogle Scholar
  23. Koppelmann T, Pollak Y, Mogilner J, Bejar J, Coran AG, Sukhotnik I. Reversal of severe MTX- induced intestinal damage using enteral Omega-3 fatty acids. Br J Nutr. 2012;28:1–10.Google Scholar
  24. Kremer JM, Lawrence DA, Petrillo GF, et al. Effects of high-dose fish oil on rheumatoid arthritis after stopping nonsteroidal antiinflammatory drugs: clinical and immune correlates. Arthritis Rheum. 1995;38:1107–12.PubMedCrossRefGoogle Scholar
  25. Larque E, Demmelmair H, Koletzko B. Perinatal supply and metabolism of long-chain polyunsaturated fatty acids: importance for the early development of the nervous system. Ann N Y Acad Sci. 2002;967:299–310.PubMedCrossRefGoogle Scholar
  26. Levy AE, Alexander JW. Nutritional immunomodulation enhances cardiac allograft survival in rats treated with donor-specific transfusion and CsA. Transplantation. 1995;60:812–8.PubMedCrossRefGoogle Scholar
  27. Lewis RA, Lee TH, Austen KF. Effects of omega-3 fatty acids on the generation of products of the 5-lipoxygenase pathway. In: Simopoulos AP, Kifer RR, Martin RE, editors. Health effects of polyunsaturated fatty acids in seafoods. Orlando: Academic; 1986. p. 227–38.CrossRefGoogle Scholar
  28. Liosis S, Bauer T, Schiele R, Gohlke H, Gottwik M, Katus H, Sabin G, Zahn R, Schneider S, Rauch B, Senges J, Zeymer U. Predictors of 1-year mortality in patients with contemporary guideline-adherent therapy after acute myocardial infarction: results from the OMEGA study. Clin Res Cardiol. 2013;102(9):671–7.PubMedCrossRefGoogle Scholar
  29. Marchioli R, Levantesi G, Silletta MG. Effect of n-3 polyunsaturated fatty acids and rosuvastatin in patients with heart failure: results of the GISSI-HF trial. Expert Rev Cardiovasc Ther. 2009;7:735–48.PubMedCrossRefGoogle Scholar
  30. Menge H, Grafe M, Lorenz-Meyer H, Riecken EO. The influence of food intake on the development of structural and functional adaptation following ileal resection in the rat. Gut. 1975;16:468–72.PubMedCentralPubMedCrossRefGoogle Scholar
  31. Naidu MUR, Ramana GV, Rani PU, et al. Chemotherapy-induced and/or radiation therapy-induced oral mucositis? Complicating the treatment of cancer. Neoplasia. 2004;6:423–31.PubMedCentralPubMedCrossRefGoogle Scholar
  32. Niemoller TD, Bazan NG. Docosahexaenoic acid neurolipidomics. Prostaglandins Other Lipid Mediat. 2010;91:85–9.PubMedCentralPubMedCrossRefGoogle Scholar
  33. O’Brien DP, Nelson LA, Huang FS. Intestinal adaptation: structure, function, and regulation. Semin Pediatr Surg. 2001;10:55–64.Google Scholar
  34. Park JHY, Grandjean CJ, Hart MH, Vanderhoof JA. Effects of dietary linoleic acid on mucosal adaptation after small bowel resection. Digestion. 1989;44:57–65.PubMedCrossRefGoogle Scholar
  35. Potten CS, Nellet M, Roberts SA, Revi RA, Wilson GD. Measurement of in vivo proliferation in human colorectal mucosa using bromodeoxyuridine. Gut. 1992;33:71–8.PubMedCentralPubMedCrossRefGoogle Scholar
  36. Sauder KA, Skulas-Ray AC, Campbell TS, Johnson JA, Kris-Etherton PM, West SG. Effects of omega-3 fatty acid supplementation on heart rate variability at rest and during acute stress in adults with moderate hypertriglyceridemia. Psychosom Med. 2013;75:382–9.PubMedCentralPubMedCrossRefGoogle Scholar
  37. Schmöcker C, Weylandt KH, Kahlke L, et al. Omega-3 fatty acids alleviate chemically induced acute hepatitis by suppression of cytokines. Hepatology. 2007;45:864–9.PubMedCrossRefGoogle Scholar
  38. Shoda R, Matsueda K, Yamato S, Umeda N. Therapeutic efficacy of n-3 polyunsaturated fatty acid in experimental Crohn’s disease. J Gastroenterol. 1995;30 Suppl 80:98–101.PubMedGoogle Scholar
  39. Simopoulos AP. Essential fatty acids in health and chronic disease. Am J Clin Nutr. 1999;70(Suppl):560S–9.PubMedGoogle Scholar
  40. Simopoulos AP, Kifer RR, Martin RE, Barlow SM. Health effects of v3 polyunsaturated fatty acids in seafoods. World Rev Nutr Diet. 1991;66:591–2.Google Scholar
  41. Sonis ST. Complications of cancer and their treatment: oral complications. In: Holland JF, Frei E, Bast RC, editors. Cancer medicine. 3rd ed. Philadelphia: Lea and Febiger; 1993. p. 2381–8.Google Scholar
  42. Sonis ST, Elting LS, Keefe DMK, Peterson DE, Schubert M, Hauer-Jensen M, Bekele BN, Raber-Durlacher J, Donnelly JP, Rubenstein EB. Perspectives on cancer therapy-induced mucosal injury: pathogenesis, measurement, epidemiology, and consequences for patients. Cancer. 2004;100:1995–2025.PubMedCrossRefGoogle Scholar
  43. Sukhotnik I, Hayari L, Bashenko Y, Chemodanov E, Mogilner J, Shamir R, Shaoul R, Coran AG. Dietary palmitic acid modulates intestinal re-growth after massive small bowel resection in a rat. Pediatr Surg Int. 2008;24:1313–21.PubMedCrossRefGoogle Scholar
  44. Sukhotnik I, Shany A, Bashenko Y, Hayari L, Chemodanov E, Mogilner J, Coran AG, Shaoul R. Parenteral but not enteral omega-3 fatty acids (omegaven) modulate intestinal re-growth after massive small bowel resection in a rat. J Parenter Enteral Nutr. 2010;34:503–12.CrossRefGoogle Scholar
  45. Sukhotnik I, Slijper N, Chemodanov E, Bashenko Y, Shaoul R, Coran AG, Mogilner JG. Parenteral omega-3 fatty acids (Omegaven) modulate intestinal recovery following intestinal ischemia-reperfusion in a rat. J Pediatr Surg. 2011;46:1353–60.PubMedCrossRefGoogle Scholar
  46. Thomson AB, Keelan M, Garg M, Clandinin MT. Dietary effects of omega 3-fatty acids on intestinal transport function. Can J Physiol Pharmacol. 1988;66:985–92.PubMedCrossRefGoogle Scholar
  47. Vanderhoof JA. Short bowel syndrome. Neonat Gastroenterol. 1996;23:377–86.Google Scholar
  48. Vanderhoof JA, Kollman KA, Lien EL. The role of eicosanoid synthesis in intestinal adaptation. J Pediatr Gastroenterol Nutr. 1999;28:596–603.CrossRefGoogle Scholar
  49. Weber TR, Keller MS. Adverse effects of liver dysfunction and portal hypertension on intestinal adaptation in short bowel syndrome in children. Am J Surg. 2002;184:582–6.PubMedCrossRefGoogle Scholar
  50. Weber PC, Fischer S, von Schacky C, Lorenz R, Strasser T. Dietary omega-3 polyunsaturated fatty acids and eicosanoid formation in man. In: Simopoulos AP, Kifer RR, Martin RE, editors. Health effects of polyunsaturated fatty acids in seafoods. Orlando: Academic; 1986. p. 49–60.CrossRefGoogle Scholar
  51. Wright N, Alison M. The biology of epithelial cell populations. Oxford: Clarendon; 1984.Google Scholar
  52. Wu XT, Li JS, Zhao XF, Li N, Ma YK, Zhuang W, Zhou Y, Yang G. Effects of n-3 fatty acid, fructose-1,6-diphosphate and glutamine on mucosal cell proliferation and apoptosis of small bowel graft after transplantation in rats. World J Gastroenterol. 2003;9:1323–6.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  1. 1.Department of Pediatric Surgery and Pathology, The Ruth and Bruce Rappaport Faculty of MedicineTechnion-Israel Institute of Technology, Bnai Zion Medical CenterHaifaIsrael

Personalised recommendations