Metabolic Brain Disease

, 24:659 | Cite as

Changes in erythrocyte membrane fatty acids during a clinical trial of eicosapentaenoic acid (EPA) supplementation in schizophrenia

  • Susan J. van Rensburg
  • Cornelius M. Smuts
  • Dinie Hon
  • Martin Kidd
  • Sulene van der Merwe
  • Christo Myburgh
  • Piet Oosthuizen
  • Robin Emsley
Original Paper


In a previously reported double-blind, placebo-controlled trial of eicosapentaenoic acid (EPA) as supplemental treatment in 40 patients with schizophrenia, we found significant improvement in symptoms as measured by the Positive and Negative Syndrome Scale (PANSS) compared to placebo (Emsley et al. 2002). Here we report changes in fatty acid composition of erythrocyte membranes in the same sample (n = 16 in each group). After 12 weeks of receiving EPA, levels of several saturated and mono-unsaturated fatty acids decreased significantly while levels of n-3 fatty acids increased significantly compared to the placebo group. Increases of n-3 and n-6 fatty acids in the erythrocyte membranes were greater in subjects who improved more than 20% on overall symptoms. Changes in fatty acids correlated significantly with improvement in PANSS sub-scale scores, more so in females than in males. Docosahexaenoic acid (DHA) (22:6n-3) levels increased less than expected, suggesting a possible defect in synthesis or incorporation of DHA into membranes in schizophrenia. Improvement in dyskinesia correlated significantly with an increase in alpha-linolenic acid (18:3n-3; p = 0.03), and a decrease in 20:1n-9 (p = 0.005).


Schizophrenia Fatty acids Eicosapentaenoic acid Dyskinesia 



The authors gratefully acknowledge financial support by the Medical Research Council of South Africa, and technical assistance rendered by the staff of Stikland Hospital (especially Deanna Grobler and Sheena Price) and the Divisions of Chemical Pathology and Haematology, Tygerberg Hospital. The authors also wish to acknowledge the support and advice of the late Dr David Horrobin, and to thank Laxdale Ltd. for providing the EPA and placebo capsules for the trial. Thank you to Anne MacKenzie, Fiona Duffy and Lorraine McMullan for their participation.


  1. Christensen O, Christensen E (1988) Fat consumption and schizophrenia. Acta Psychiatr. Scand. 78:587–591CrossRefPubMedGoogle Scholar
  2. Condray R, Yao JK, Steinhauer SR, van Kammen DP, Reddy RD, Morrow LA (2008) Semantic memory in schizophrenia: association with cell membrane essential fatty acids. Schizophr Res. 106:13–28CrossRefPubMedGoogle Scholar
  3. De Hert M, Schreurs V, Vancampfort D, Van Winkel R (2009) Metabolic syndrome in people with schizophrenia: a review. World Psychiatry 8:15–22Google Scholar
  4. Emsley R, Myburgh C, Oosthuizen P, Van Rensburg SJ (2002) Randomized placebo-controlled study of ethyl-eicosapentaenoic acid as supplemental treatment in schizophrenia. Am. J. Psychiatry 159:1596–1598CrossRefPubMedGoogle Scholar
  5. Emsley R, Oosthuizen P, Van Rensburg SJ (2003) Clinical Potential of Omega-3-Fatty Acids in the treatment of schizophrenia. CNS Drugs 17:1081–1091CrossRefPubMedGoogle Scholar
  6. Emsley R, Niehaus DJ, Koen L, Oosthuizen PP, Turner HJ, Carey P, Van Rensburg SJ, Maritz JS, Murck H (2006) The effects of eicosapentaenoic acid in tardive dyskinesia: a randomized, placebo-controlled trial. Schizophr Res. 84:112–20CrossRefPubMedGoogle Scholar
  7. Evans DR, Parikh VV, Khan MM, Coussons C, Buckley PF, Mahadik SP (2003) Red blood cell membrane essential fatty acid metabolism in early psychotic patients following antipsychotic drug treatment. Prostaglandins Leukot Essent Fatty Acids. 69:393–399CrossRefPubMedGoogle Scholar
  8. Farooqui AA, Ong WY, Horrocks LA (2006) Inhibitors of brain phospholipase A2 activity: their neuropharmacological effects and therapeutic importance for the treatment of neurologic disorders. Pharmacol Rev. 58:591–620CrossRefPubMedGoogle Scholar
  9. Fenton WS, Dickerson F, Boronow J, Hibbeln JR, Knable MA (2001) Placebo-controlled trial of omega-3 fatty acid (ethyl eicosapentaenoic acid) supplementation for residual symptoms and cognitive impairment in schizophrenia. Am. J. Psychiatry 158:2071–2074CrossRefPubMedGoogle Scholar
  10. Finnen MJ, Lovell CR (1991) Purification and characterisation of phospholipase A2 from human epidermis. Biochem. Soc. Trans. 19:91SPubMedGoogle Scholar
  11. Folch J, Lees M, Sloane-Stanley GH (1957) A simple method for the isolation and purification of total lipids from animal tissues. J. Biol. Chem. 226:497–509PubMedGoogle Scholar
  12. Gattaz WF, Hubner CK, Nevalainen TJ, Thuren T, Kinnunen PJK (1990) Increased serum phospholipase-A2 activity in schizophrenia: a replication study. Biol Psychiatry 28:495–501PubMedGoogle Scholar
  13. Gebauer SK, Psota TL, Harris WS, Kris-Etherton PM (2006) n-3 fatty acid dietary recommendations and food sources to achieve essentiality and cardiovascular benefits. Am. J. Clin. Nutr. 83(6 Suppl):1526S–1535SGoogle Scholar
  14. Horrobin DF (1999) The phospholipid concept of psychiatric disorders and its relationship to the neurodevelopmental concept of schizophrenia. In: Peet M, Glen I, Horrobin DF (eds) Phospholipid spectrum disorder in psychiatry. Marius, Lancashire, pp 3–20Google Scholar
  15. Horrobin DF, Jenkins K, Bennett CN, Christie WW (2002) Eicosapentaenoic acid and arachidonic acid: collaboration and not antagonism is the key to biological understanding. Prostagland Leurkotr Essent Fatty Acids 66:83–90CrossRefGoogle Scholar
  16. Khan MM, Evans DR, Gunna V, Scheffer RE, Parikh VV, Mahadik SP (2002) Reduced erythrocyte membrane essential fatty acids and increased lipid peroxides in schizophrenia at the never-medicated first-episode of psychosis and after years of treatment with antipsychotics. Schizophr. Res. 58:1–10CrossRefPubMedGoogle Scholar
  17. Kemperman RF, Veurink M, van der Wal T, Knegtering H, Bruggeman R, Fokkema MR, Kema IP, Korf J, Muskiet FA (2006) Low essential fatty acid and B-vitamin status in a subgroup of patients with schizophrenia and its response to dietary supplementation. Prostaglandins Leukot Essent Fatty Acids. 74:75–85CrossRefPubMedGoogle Scholar
  18. Kruger M, Langenhoven M, Faber M (1991) Fatty acid and amino acid composition tables. Supplement to MRC Food Composition Tables. MRC, ParowGoogle Scholar
  19. Levine J, Stahl Z, Sela BA, Ruderman V, Shumaico O, Babushkin I, Osher Y, Bersudsky Y, Belmaker RH (2006) Homocysteine-reducing strategies improve symptoms in chronic schizophrenic patients with hyperhomocysteinemia. Biol Psychiatry. 60:265–9CrossRefPubMedGoogle Scholar
  20. McNamara RK, Able JA, Jandacek R, Rider T, Tso P (2009) Chronic risperidone treatment preferentially increases rat erythrocyte and prefrontal cortex omega-3 fatty acid composition: evidence for augmented biosynthesis. Schizophr Res. 107:150–157CrossRefPubMedGoogle Scholar
  21. Mellor JE, Laugharne JDE, Peet M (1995) Schizophrenic symptoms and dietary intake of n-3 fatty acids. Schizophr. Res. 18:85–86CrossRefPubMedGoogle Scholar
  22. Ohara K (2007) The n-3 polyunsaturated fatty acid/dopamine hypothesis of schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry. 31:469–74CrossRefPubMedGoogle Scholar
  23. Peet M, Brind J, Ramchand CN, Shah S, Vankar GK (2001) Two double-blind placebo-controlled pilot studies of eicosapentaenoic acid in the treatment of schizophrenia. Schizophr. Res. 49:243–251CrossRefPubMedGoogle Scholar
  24. Peet M, Shah S, Selvam K, Ramchand CN (2004) Polyunsaturated fatty acid levels in red cell membranes of unmedicated schizophrenic patients. World J Biol Psychiatry. 5:92–99CrossRefPubMedGoogle Scholar
  25. Peet M (2008) Omega-3 polyunsaturated fatty acids in the treatment of schizophrenia. Isr J Psychiatry Relat Sci. 45:19–25PubMedGoogle Scholar
  26. Puri BK, Ross BM, Treasaden IH (2008) Increased levels of ethane, a non-invasive, quantitative, direct marker of n-3 lipid peroxidation, in the breath of patients with schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry. 32:858–862CrossRefPubMedGoogle Scholar
  27. Ranjekar PK, Hinge A, Hegde MV, Ghate M, Kale A, Sitasawad S, Wagh UV, Debsikdar VB, Mahadik SP (2003) Decreased antioxidant enzymes and membrane essential polyunsaturated fatty acids in schizophrenic and bipolar mood disorder patients. Psychiatry Res. 121:109–122CrossRefPubMedGoogle Scholar
  28. Reddy RD, Keshavan MS, Yao JK (2004) Reduced red blood cell membrane essential polyunsaturated fatty acids in first episode schizophrenia at neuroleptic-naive baseline. Schizophr Bull. 30:901–11PubMedGoogle Scholar
  29. Sivrioglu EY, Kirli S, Sipahioglu D, Gursoy B, Sarandöl E (2007) The impact of omega-3 fatty acids, vitamins E and C supplementation on treatment outcome and side effects in schizophrenia patients treated with haloperidol: an open-label pilot study. Prog Neuropsychopharmacol Biol Psychiatry. 31:1493–1499CrossRefPubMedGoogle Scholar
  30. Sumiyoshi T, Matsui M, Itoh H, Higuchi Y, Arai H, Takamiya C, Kurachi M (2008) Essential polyunsaturated fatty acids and social cognition in schizophrenia. Psychiatry Res. 157:87–93CrossRefPubMedGoogle Scholar
  31. Vaddadi KS, Gilleard CJ, Soosai E, Polonowita AK, Gibson RA, Burrows GD (1996) Schizophrenia, tardive dyskinesia and essential fatty acids. Schizophr. Res. 20:287–294CrossRefPubMedGoogle Scholar
  32. Van Jaarsveld PJ, Smuts CM, Tichelaar HY, Kruger M, Benadé AJS (2000) Effect of palm oil on plasma lipoprotein concentrations and plasma low-density lipoprotein composition in non-human primates. Int. J. Food Sci. Nutr. 51:S21–S30CrossRefPubMedGoogle Scholar
  33. Von Hausswolff-Juhlin Y, Bjartveit M, Lindström E, Jones P (2009) Schizophrenia and physical health problems. Acta Psychiatr Scand Suppl 438:15–21CrossRefGoogle Scholar
  34. Yao JK, Leonard S, Reddy RD (2000) Membrane phospholipid abnormalities in postmortem brains from schizophrenic patients. Schizophr. Res. 42:7–17CrossRefPubMedGoogle Scholar
  35. Yao JK, Stanley JA, Reddy RD, Keshavan MS, Pettegrew JW (2002) Correlations between peripheral polyunsaturated fatty acid content and in vivo membrane phospholipid metabolites. Biol. Psychiatry 52:823–830CrossRefPubMedGoogle Scholar
  36. Yao JK, Magan S, Sonel AF, Gurklis JA, Sanders R, Reddy RD (2004) Effects of omega-3 fatty acid on platelet serotonin responsivity in patients with schizophrenia. Prostaglandins Leukot Essent Fatty Acids. 71:171–6CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Susan J. van Rensburg
    • 1
    • 7
  • Cornelius M. Smuts
    • 2
  • Dinie Hon
    • 3
  • Martin Kidd
    • 4
  • Sulene van der Merwe
    • 5
  • Christo Myburgh
    • 6
  • Piet Oosthuizen
    • 6
  • Robin Emsley
    • 6
  1. 1.Division of Chemical Pathology, National Health Laboratory ServiceUniversity of StellenboschStellenboschSouth Africa
  2. 2.Nutritional Intervention Research Unit, Medical Research Council, Parow, Centre of Excellence in NutritionNorth-West UniversityPotchefstroomSouth Africa
  3. 3.Cape Peninsula University of TechnologyCape TownSouth Africa
  4. 4.Centre for Statistical ConsultationUniversity of StellenboschStellenboschSouth Africa
  5. 5.Division of Human NutritionUniversity of StellenboschStellenboschSouth Africa
  6. 6.Department of PsychiatryUniversity of StellenboschStellenboschSouth Africa
  7. 7.Division of Chemical Pathology, Tygerberg HospitalNHLS and University of StellenboschTygerbergSouth Africa

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