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Fatty acid and vitamin interventions in adults with schizophrenia: a systematic review of the current evidence

  • Psychiatry and Preclinical Psychiatric Studies - Review Article
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Abstract

Current psychopharmacological approaches to reduce psychotic phenomenology in schizophrenia are associated with adverse effects including extrapyramidal and metabolic side effects. In view of the emerging data on nutritional supplementation interventions in schizophrenia which are not entirely consistent, we aimed to review existent studies focusing on fatty acid and vitamin interventions and summarise current evidence on such nutritional supplementations in schizophrenia. We searched the digital databases (ScienceDirect, Scopus, SpringerLINK, PubMed/Medline) for relevant studies pertaining to fatty acid and vitamin supplementation interventions in the management of psychotic symptoms in schizophrenia up to February 2015. Overall, there were more studies conducted on fatty acid over vitamin supplementations in patients with schizophrenia. There were more positive findings in support of fatty acid supplementation compared with vitamin supplementation in the context of specific intervention features (dose of nutrient supplementation, single versus combination nutritional interventions, specific antipsychotic), subject features (older age, long duration of illness, baseline polyunsaturated fatty acid levels) and clinical outcomes (improvements of psychotic symptoms and/or extrapyramidal side effects from antipsychotics). However, investigations of both supplementation modalities were limited by relatively small study sample sizes, short study duration, which precluded further segmentation of impact on more diverse patient subtypes and symptom profiles. Future studies may consider examining larger samples over a longer time period, recruiting younger subjects with shorter duration of illness, examination of different clinical features including specific cognitive domains, and use of single versus combination nutritional interventions.

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References

  • Arvindakshan M, Ghate M, Ranjekarm PK, Evans DR, Mahadik SP (2003) Supplementation with a combination of ω-3 fatty acids and antioxidants (vitamins E and C) improves the outcome of schizophrenia. Schizophr Res 62:195–204

    Article  PubMed  Google Scholar 

  • Assies J, Lieverse R, Vreken P, Wanders RJA, Dingemans PMJA, Linszen DH (2001) Significantly reduced docosahexaenoic and docosapentaenoic acid concentrations in erythrocyte membranes from schizophrenia patients compared with a carefully matched control group. Biol Psychiatry 49:510–522

    Article  CAS  PubMed  Google Scholar 

  • Barch DM (2005) The relationships among cognition, motivation, and emotion in schizophrenia: how much and how little we know. Schizophr Bull 31(4):875–881

    Article  PubMed  Google Scholar 

  • Bentsen H, Osnes K, Refsum H, Solberg DK, Bøhmer T (2013) A randomized placebo-controlled trial of an omega-3 fatty acid and vitamins E + C in schizophrenia. Transl Psychiatry 3(12):e335

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Carbon M, Correll CU (2014) Thinking and acting beyond the positive: the role of the cognitive and negative symptoms in schizophrenia. CNS Spectr 19(Suppl 1):38–52

    PubMed  Google Scholar 

  • Chue P, Lalonde JK (2014) Addressing the unmet needs of patients with persistent negative symptoms of schizophrenia: emerging pharmacological treatment options. Neuropsychiatr Dis Treat 10:777–789

    Article  PubMed  PubMed Central  Google Scholar 

  • Dakhale GN, Khanzode SD, Khanzode SS, Saoji A (2005) Supplementation of vitamin C with atypical antipsychotics reduces oxidative stress and improves the outcome of schizophrenia. Psychopharmacology 182(4):494–498

    Article  CAS  PubMed  Google Scholar 

  • Davidson M, Galderisi S, Weiser M, Werbeloff N, Fleischhacker WW, Keefe RS et al (2009) Cognitive effects of antipsychotic drugs in first-episode schizophrenia and schizophreniform disorder: a randomized, open-label clinical trial (EUFEST). Am J Psychiatry 166(6):675–682

    Article  PubMed  Google Scholar 

  • Dipasquale S, Pariante CM, Dazzan P, Aguglia E, McGuire P, Mondelli V (2013) The dietary pattern of patients with schizophrenia: a systematic review. J Psychiatr Res 47(2):197–207

    Article  PubMed  Google Scholar 

  • Emsley R, Myburgh C, Oosthuizen P, van Rensburg SJ (2002) Randomised, placebo-controlled study of ethyl-eicosapentaenoic acid as supplemental treatment in schizophrenia. Am J Psychiatry 159(9):1596–1598

    Article  PubMed  Google Scholar 

  • Fenton WS, Dickerson F, Boronow J, Hibbeln JR, Knable M (2001) A placebo-controlled trial of omega-3 fatty acid (ethyl eicosapentaenoic acid) supplementation for residual symptoms and cognitive impairment in schizophrenia. Am J Psychiatry 158(12):2071–2074

    Article  CAS  PubMed  Google Scholar 

  • Fett AKJ, Viechtbauer W, Penn DL, van OsJ Krabbendam L (2011) The relationship between neurocognition and social cognition with functional outcomes in schizophrenia: a meta-analysis. Neurosci Biobehav Rev 35(3):573–588

    Article  PubMed  Google Scholar 

  • Godfrey PSA, Toone BK, Carney MWP et al (1990) Enhancement of recovery from psychiatric illness by methylfolate. Lancet 336(8712):392–395

    Article  CAS  PubMed  Google Scholar 

  • Goldberg TE, Goldman RS, Burdick KE, Malhotra AK, Lencz T, Patel RC, Woerner MG, Schooler NR, Kane JM, Robinson DG (2007) Cognitive improvement after treatment with second-generation antipsychotic medications in First-Episode schizophrenia: is it a practice effect? Arch Gen Psychiatry 64(10):1115–1122

    Article  CAS  PubMed  Google Scholar 

  • Hasan A, Falkai P, Wobrock T, Lieberman J, Glenthoj B, Gattaz WF, Thibaut F, Möller HJ, WFSBP Task force on Treatment Guidelines for Schizophrenia (2013) World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for biological treatment of schizophrenia, part 2: update 2012 on the long-term treatment of schizophrenia and management of antipsychotic-induced side effects. World J Biol Psychiatry 14:2–44

    Article  PubMed  Google Scholar 

  • Hill M, Shannahan K, Jasinski S, Macklin EA, Raeke L, Roffman JL, Goff DC (2011) Folate supplementation in schizophrenia: a possible role for MTHFR genotype. Schizophr Res 127:41–45

    Article  PubMed  Google Scholar 

  • Horrobin DF (1999) The effects of antipsychotic drugs on membrane phospholipids: a possible novel mechanism of action of clozapine. In: Peet M, Glen I, Horrobin DF (eds) Phospholipid Spectr Dis Psychiatry. Marius Press, UK, pp 113–117

  • Huskisson E, Maggini S, Ruf M (2007) The influence of micronutrients on cognitive function and performance. J Int Med Res 35(1):1–19

    Article  CAS  PubMed  Google Scholar 

  • Insel TR (2010) Rethinking schizophrenia. Nature 468(7321):187–193

    Article  CAS  PubMed  Google Scholar 

  • Jeding I, Evans PJ, Akanmu D, Dexter D, Spencer JD, Aruoma OI, Jenner P, Halliwell B (1995) Characterization of the potential antioxidant and pro-oxidant actions of some neuroleptic drugs. Biochem Pharmacol 49:359–365

    Article  CAS  PubMed  Google Scholar 

  • Kale A, Naphade N, Sapkale S, Kamaraju M, Pillai A, Joshi S, Mahadik S (2010) Reduced folic acid, vitamin B 12 and docosahexaenoic acid and increased homocysteine and cortisol in never-medicated schizophrenia patients: implications for altered one-carbon metabolism. Psychiatry Res 175(1):47–53

    Article  CAS  PubMed  Google Scholar 

  • 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):1–10

    Article  PubMed  Google Scholar 

  • Marsden CD, Jenner P (1980) The pathophysiology of extrapyramidal side-effects of antipsychotic drugs. Psychol Med 10(01):55–72

    Article  CAS  PubMed  Google Scholar 

  • McCreadie RG, Kelly C, Connolly M, Williams S, Baxter G, Lean M, Paterson JR (2005) Dietary improvement in people with schizophrenia Randomised controlled trial. Br J Psychiatry 187(4):346–351

    Article  PubMed  Google Scholar 

  • Mellor JE, Laugharne JDE, Peet M (1996) Omega-3 fatty acid supplementation in schizophrenic patients. Hum Psychopharmacol 11:39–46

    Article  CAS  Google Scholar 

  • Miller ER, Pastor-Barriuso R, Dalal D, Riemersma RA, Appel LJ, Guallar E (2005) Meta-analysis: high-dosage vitamin E supplementation may increase all-cause mortality. Ann Intern Med 142(1):37–46

    Article  CAS  PubMed  Google Scholar 

  • Muntjewerff JW, Blom HJ (2005) Aberrant folate status in schizophrenic patients: what is the evidence. Prog Neuropsychopharmacol Biol Psychiatry 29(7):1133–1139

    Article  CAS  PubMed  Google Scholar 

  • Parletta N, Milte CM, Meyer BJ (2013) Nutritional modulation of cognitive function and mental health. J Nutr Biochem 24(5):725–743

    Article  CAS  PubMed  Google Scholar 

  • Peet M (2008) Omega-3 polyunsaturated fatty acids in the treatment of schizophrenia. Isr J Psychiatry Relat Sci 45(1):19–25

    PubMed  Google Scholar 

  • Peet M, Horrobin DF (2002) A dose-ranging exploratory study of the effects of ethyl-eicosapentaenoate in patients with persistent schizophrenic symptoms. J Psychiatr Res 36(1):7–18

    Article  PubMed  Google Scholar 

  • 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(3):243–251

    Article  CAS  PubMed  Google Scholar 

  • Rietjens IM, Boersma MG, de Haan L, Spenkelink B, Awad HM, Cnubben NH, van Zanden JJ, van der Woude H, Alink GM, Koeman JH (2002) The pro-oxidant chemistry of the natural antioxidants vitamin C, vitamin E, carotenoids and flavonoids. Environ Toxicol Pharmacol 11(3):321–333

    Article  CAS  PubMed  Google Scholar 

  • Roffman JL, Lamberti S, Achtyes E, Macklin EA, Galendez GC, Raeke LH, Silverstein NJ, Smoller JW, Hill M, Goff DC (2013) Randomized multicenter investigation of folate plus vitamin B12 supplementation in schizophrenia. JAMA Psychiatry 70(5):481–489

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shah S, Vankar GK, Telang SD, Ramchand CN, Peet M (1998) Eicosapentaenoic acid (EPA) as an adjunct in the treatment of schizophrenia. Schizophr Res 29:158

    Article  Google Scholar 

  • Sicras-Mainar A, Blanca-Tamayo M, Rejas-Gutiérrez J, Navarro-Artieda R (2008) Metabolic syndrome in outpatients receiving antipsychotic therapy in routine clinical practice: a cross-sectional assessment of a primary health care database. Eur Psychiatry 23(2):100–108

    Article  PubMed  Google Scholar 

  • Sivrioglu EY, Kirli S, Sipahioglu D, Gursoy B, Sarandol E (2007) The impact of ω-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 31:1493–1499

    Article  CAS  PubMed  Google Scholar 

  • Strassnig M, Brar JS, Ganuli R (2005) Dietary fatty acid and antioxidant intake in community-dwelling patients suffering from schizophrenia. Schizophr Res 76:343–351

    Article  PubMed  Google Scholar 

  • 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 157:87–93

    Article  CAS  PubMed  Google Scholar 

  • van Rensburg SJ, Smuts CM, Hon D, Kidd M, van der Merwe S, Myburgh C, Oosthuizen P, Emsley R (2009) Changes in erythrocyte membrane fatty acids during a clinical trial of eicosapentaenoic acid (EPA) supplementation in schizophrenia. Metab Brain Dis 24(4):659–672

    Article  CAS  PubMed  Google Scholar 

  • Vaughan K, McConaghy N (1999) Megavitamin and dietary treatment in schizophrenia: a randomised, controlled trial. Aust N Z J Psychiatry 33(1):84–88

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Clinical Nutrition Research Centre, Singapore Institute for Clinical Sciences, 14 Medical Drive, #07-02, Singapore, 117599, Singapore

    Siok Ching Chia & Jeyakumar Henry

  2. Institute of Mental Health/Woodbridge Hospital, 10, Buangkok View, Singapore, 539747, Singapore

    Yee Ming Mok & Kang Sim

  3. Jack Bell Chair in Schizophrenia, Department of Psychiatry, Director, Institute of Mental Health, University of British Columbia, Detwiller Pavilion, 2255 Wesbrook Mall, Vancouver, BC, V6T 2A1, Canada

    William G. Honer

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  1. Siok Ching Chia
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  2. Jeyakumar Henry
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  3. Yee Ming Mok
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  5. Kang Sim
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Correspondence to Kang Sim.

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Chia, S.C., Henry, J., Mok, Y.M. et al. Fatty acid and vitamin interventions in adults with schizophrenia: a systematic review of the current evidence. J Neural Transm 122, 1721–1732 (2015). https://doi.org/10.1007/s00702-015-1451-z

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  • DOI: https://doi.org/10.1007/s00702-015-1451-z

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