Intensive Care Medicine

, Volume 36, Issue 2, pp 289–295 | Cite as

Blunting the response to endotoxin in healthy subjects: effects of various doses of intravenous fish oil

  • Yann K. Pittet
  • Mette M. BergerEmail author
  • Thomas-Thi Pluess
  • Pierre Voirol
  • Jean-Pierre Revelly
  • Luc Tappy
  • René L. Chioléro



To test the dose response effect of infused fish oil (FO) rich in n-3 PUFAs on the inflammatory response to endotoxin (LPS) and on membrane incorporation of fatty acids in healthy subjects.


Prospective, sequential investigation comparing three different FO doses.


Three groups of male subjects aged 26.8 ± 3.2 years (BMI 22.5 ± 2.1).


One of three FO doses (Omegaven®10%) as a slow infusion before LPS: 0.5 g/kg 1 day before LPS, 0.2 g/kg 1 day before, or 0.2 g/kg 2 h before.

Measurements and results

Temperature, hemodynamic variables, indirect calorimetry and blood samples (TNF-α, stress hormones) were collected. After LPS temperature, ACTH and TNF-α concentrations increased in the three groups: the responses were significantly blunted (p < 0.0001) compared with the control group of the Pluess et al. trial. Cortisol was unchanged. Lowest plasma ACTH, TNF-α and temperature AUC values were observed after a single 0.2 g/kg dose of FO. EPA incorporation into platelet membranes was dose-dependent.


Having previously shown that the response to LPS was reproducible, this study shows that three FO doses blunted it to various degrees. The 0.2 g/kg perfusion immediately before LPS was the most efficient in blunting the responses, suggesting LPS capture in addition to the systemic and membrane effects.


Inflammation Sepsis PUFA Downregulation 



We are grateful to Prof. Yvon Carpentier and his team (NUTRISUB Laboratory ULB, Brussels, Belgium) for the determinations of the fatty acid membrane incorporation and to Dr. Christiane Ruffieux and Pierre Bady (Institute of Social and Preventive Medicine, University of Lausanne) for statistical advice. The study was primarily supported by a grant from the Swiss National Science Foundation (no. 32-61582.00) and completed by a partial grant from Fresenius Kabi AG (Bad Homburg, Germany) for laboratory determinations.

Conflict of interest statement

None of the authors has any conflict of interest, such as bonds, or any economic implications in the industry. R.L. Chiolero and M.M. Berger deliver invited lectures for Fresenius Kabi AG, B. Braun and Nestlé. The groups research is partially supported by grants from Fresenius Kabi AG and B. Braun.


  1. 1.
    Calder PC (2004) N-3 fatty acids, inflammation, and immunity–relevance to postsurgical and critically ill patients. Lipids 39:1147–1161CrossRefPubMedGoogle Scholar
  2. 2.
    Calder PC (2008) The relationship between the fatty acid composition of immune cells and their function. Prostaglandins Leukot Essent Fatty Acids 79:101–108 Epub 2008 Oct 2023CrossRefPubMedGoogle Scholar
  3. 3.
    Yaqoob P, Pala HS, Cortina-Borja M, Newsholme EA, Calder PC (2000) Encapsulated fish oil enriched in alpha-tocopherol alters plasma phospholipid and mononuclear cell fatty acid compositions but not mononuclear cell functions. Eur J Clin Invest 30:260–274CrossRefPubMedGoogle Scholar
  4. 4.
    Pluess TT, Hayoz D, Berger MM, Tappy L, Revelly JP, Michaeli B, Carpentier YA, Chiolero RL (2007) Intravenous fish oil blunts the physiological response to endotoxin in healthy subjects. Intensive Care Med 33:789–797CrossRefPubMedGoogle Scholar
  5. 5.
    Simoens C, Richelle M, Rossle C, Derluyn M, Deckelbaum RJ, Carpentier YA (1995) Manipulation of tissue fatty acid profile by intravenous lipids in dogs. Clin Nutr 14:177–185CrossRefPubMedGoogle Scholar
  6. 6.
    Livesey G, Elia M (1988) Estimation of energy expenditure, net carbohydrate utilization, and net fat oxidation and synthesis by indirect calorimetry: evaluation of errors with special reference to detailed composition of fuels. Am J Clin Nutr 47:608–628PubMedGoogle Scholar
  7. 7.
    Katan MB, Deslypere JP, van Birgelen AP, Penders M, Zegwaard M (1997) Kinetics of the incorporation of dietary fatty acids into serum cholesteryl esters, erythrocyte membranes, and adipose tissue: an 18-month controlled study. J Lipid Res 38:2012–2022PubMedGoogle Scholar
  8. 8.
    Calder PC, Bond JA, Harvey DJ, Gordon S, Newsholme EA (1990) Uptake and incorporation of saturated and unsaturated fatty acids into macrophage lipids and their effect upon macrophage adhesion and phagocytosis. Biochem J 269:807–814PubMedGoogle Scholar
  9. 9.
    Wanten GJ, Calder PC (2007) Immune modulation by parenteral lipid emulsions. Am J Clin Nutr 85:1171–1184PubMedGoogle Scholar
  10. 10.
    Finnegan YE, Minihane AM, Leigh-Firbank EC, Kew S, Meijer GW, Muggli R, Calder PC, Williams CM (2003) Plant- and marine-derived n-3 polyunsaturated fatty acids have differential effects on fasting and postprandial blood lipid concentrations and on the susceptibility of LDL to oxidative modification in moderately hyperlipidemic subjects. Am J Clin Nutr 77:783–795PubMedGoogle Scholar
  11. 11.
    Simoens CM, Deckelbaum RJ, Massaut JJ, Carpentier YA (2008) Inclusion of 10% fish oil in mixed medium-chain triacylglycerol-long-chain triacylglycerol emulsions increases plasma triacylglycerol clearance and induces rapid eicosapentaenoic acid (20:5n-3) incorporation into blood cell phospholipids. Am J Clin Nutr 88:282–288PubMedGoogle Scholar
  12. 12.
    Carpentier YA, Peltier S, Portois L, Sener A, Malaisse WJ (2008) Rapid lipid enrichment in omega3 fatty acids: plasma data. Int J Mol Med 21:355–365PubMedGoogle Scholar
  13. 13.
    Singer P, Shapiro H, Theilla M, Anbar R, Singer J, Cohen J (2008) Anti-inflammatory properties of omega-3 fatty acids in critical illness: novel mechanisms and an integrative perspective. Intensive Care Med 34:1580–1592CrossRefPubMedGoogle Scholar
  14. 14.
    Mascioli EA, Babayan VG, Bistrian BR, Blackburn GL (1988) Novel triglycerides for special medical purposes. J Parenter Enteral Nutr 12:127S–132SCrossRefGoogle Scholar
  15. 15.
    Pscheidl E, Schywalsky M, Tschaikowsky K, Böke-Pröls T (2000) Fish oil-supplemented parenteral diets normalize splanchnic blood flow and improve killing of translocated bacteria in a low-dose endotoxin rat model. Crit Care Med 28:1489–1496CrossRefPubMedGoogle Scholar
  16. 16.
    Michaeli B, Berger MM, Revelly JP, Tappy L, Chioléro R (2007) Effects of fish oil on the neuro-endocrine responses to an endotoxin challenge in healthy volunteers. Clin Nutr 26:70–77CrossRefPubMedGoogle Scholar
  17. 17.
    Feingold KR, Funk JL, Moser AH, Shigenaga JK, Rapp JH, Grunfeld C (1995) Role for circulating lipoproteins in protection from endotoxin toxicity. Infect Immun 63:2041–2046PubMedGoogle Scholar

Copyright information

© Copyright jointly hold by Springer and ESICM 2009

Authors and Affiliations

  • Yann K. Pittet
    • 1
  • Mette M. Berger
    • 1
    Email author
  • Thomas-Thi Pluess
    • 1
  • Pierre Voirol
    • 2
  • Jean-Pierre Revelly
    • 1
  • Luc Tappy
    • 3
  • René L. Chioléro
    • 1
  1. 1.Service of Adult Intensive Care Medicine and Burns CentreCHUVLausanneSwitzerland
  2. 2.PharmacyCHUVLausanneSwitzerland
  3. 3.Institute of PhysiologyUNILLausanneSwitzerland

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