Skip to main content
SpringerLink
Log in

Effects of omega-3 fatty acids on metabolic syndrome in patients with schizophrenia: a 12-week randomized placebo-controlled trial

  • Original Investigation
  • Published:
Psychopharmacology Aims and scope Submit manuscript

Abstract

Rationale

Individuals with schizophrenia are at increased risk of developing metabolic syndrome (MetS) due to their lifestyle and antipsychotic treatment. Our previous study showed that patients with both schizophrenia and MetS present an increased expression and production of tumor necrosis factor-alpha (TNF-alpha). Omega-3 fatty acids have a documented role in suppressing TNF-alpha; therefore, we hypothesized that they may be of value in relieving inflammation and improving metabolic disturbance in patients with both schizophrenia and MetS.

Objectives

This study employed a randomized placebo-controlled trial to investigate the effects of omega-3 fatty acids on MetS in patients with schizophrenia.

Methods

We recruited 80 patients with both schizophrenia and MetS who received long-term olanzapine monotherapy. The patients were randomly assigned to the OMG-3 group (n = 40) or the placebo group (n = 40).

Results

Patients with both schizophrenia and MetS had significantly higher levels of TNF-alpha than the control subjects (Z = − 4.37, P < 0.01). There was a significant correlation between omega-3 fatty acid treatment and reduced triglyceride (TG) levels (Fgroup × time = 13.42; df = 1, 66; P < 0.01) when the patients completed this study. Along with metabolic improvement, omega-3 fatty acids decreased TNF-alpha levels after 12 weeks of treatment (Fgroup × time = 6.71; df = 1, 66; P = 0.012). We also found that the extent of TNF-alpha decrease was significantly correlated with that of TG decrease (r = 0.38, P = 0.001).

Conclusions

Our findings provide suggestive evidence that omega-3 fatty acids have beneficial effects on TG metabolism in patients with both schizophrenia and MetS that parallel decreased inflammation levels.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  • Albracht-Schulte K, Kalupahana NS, Ramalingam L, Wang S, Rahman SM, Robert-McComb J, Moustaid-Moussa N (2018) Omega-3 fatty acids in obesity and metabolic syndrome: a mechanistic update. J Nutr Biochem 58:1–16

    Article  CAS  PubMed  Google Scholar 

  • Annamalai A, Kosir U, Tek C (2017) Prevalence of obesity and diabetes in patients with schizophrenia. World J Diabetes 8:390–396

    Article  PubMed  PubMed Central  Google Scholar 

  • Bao YQ, Lu JX, Wang C, Yang M, Li HT, Zhang XY, Zhu JH, Lu HJ, Jia WP, Xiang KS (2008) Optimal waist circumference cutoffs for abdominal obesity in Chinese. Atherosclerosis 201:378–384

    Article  CAS  PubMed  Google Scholar 

  • Behdani F, Roudbaraki SN, Saberi-Karimian M, Tayefi M, Hebrani P, Akhavanrezayat A, Amlashi SV, Ferns GA, Ghayour-Mobarhan M (2018) Assessment of the efficacy of omega-3 fatty acids on metabolic and inflammatory parameters in patients with schizophrenia taking clozapine and sodium valproate. Psychiatry Res 261:243–247

    Article  CAS  PubMed  Google Scholar 

  • Beumer W, Drexhage RC, De Wit H, Versnel MA, Drexhage HA, Cohen D (2012) Increased level of serum cytokines, chemokines and adipokines in patients with schizophrenia is associated with disease and metabolic syndrome. Psychoneuroendocrinology 37:1901–1911

    Article  CAS  PubMed  Google Scholar 

  • Birkenaes AB, Birkeland KI, Engh JA, Faerden A, Jonsdottir H, Ringen PA, Friis S, Opjordsmoen S, Andreassen OA (2008) Dyslipidemia independent of body mass in antipsychotic-treated patients under real-life conditions. J Clin Psychopharmacol 28:132–137

    Article  CAS  PubMed  Google Scholar 

  • Buckley PF (2001) Broad therapeutic uses of atypical antipsychotic medications. Biol Psychiatry 50:912–924

    Article  CAS  PubMed  Google Scholar 

  • Calder PC (2017) Omega-3 fatty acids and inflammatory processes: from molecules to man. Biochem Soc Trans 45:1105–1115

    Article  CAS  PubMed  Google Scholar 

  • Chesney E, Goodwin GM, Fazel S (2014) Risks of all-cause and suicide mortality in mental disorders: a meta-review. World Psychiatry 13:153–160

  • Cicero AF, Derosa G, Di Gregori V, Bove M, Gaddi AV, Borghi C (2010) Omega 3 polyunsaturated fatty acids supplementation and blood pressure levels in hypertriglyceridemic patients with untreated normal-high blood pressure and with or without metabolic syndrome: a retrospective study. Clin Exp Hypertens 32:137–144

    Article  CAS  PubMed  Google Scholar 

  • de Witte L, Tomasik J, Schwarz E, Guest PC, Rahmoune H, Kahn RS, Bahn S (2014) Cytokine alterations in first-episode schizophrenia patients before and after antipsychotic treatment. Schizophr Res 154:23–29

  • Devaraj S, Valleggi S, Siegel D, Jialal I (2010) Role of C-reactive protein in contributing to increased cardiovascular risk in metabolic syndrome. Curr Atheroscler Rep 12:110–118

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Elagizi A, Lavie CJ, Marshall K, DiNicolantonio JJ, O’Keefe JH, Milani RV (2018) Omega-3 polyunsaturated fatty acids and cardiovascular health: a comprehensive review. Prog Cardiovasc Dis 61:76–85

    Article  PubMed  Google Scholar 

  • Endres S, Ghorbani R, Kelley VE, Georgilis K, Lonnemann G, van der Meer JW, Cannon JG, Rogers TS, Klempner MS, Weber PC et al (1989) The effect of dietary supplementation with n-3 polyunsaturated fatty acids on the synthesis of interleukin-1 and tumor necrosis factor by mononuclear cells. N Engl J Med 320:265–271

    Article  CAS  PubMed  Google Scholar 

  • Gabay C, Kushner I (1999) Acute-phase proteins and other systemic responses to inflammation. N Engl J Med 340:448–454

    Article  CAS  PubMed  Google Scholar 

  • Grundy SM, Cleeman JI, Daniels SR, Donato KA, Eckel RH, Franklin BA, Gordon DJ, Krauss RM, Savage PJ, Smith SC, Spertus JA, Costa F (2005) Diagnosis and management of the metabolic syndrome—an American Heart Association/National Heart, Lung, and Blood Institute scientific statement. Circulation 112:2735–2752

    Article  PubMed  Google Scholar 

  • Gurusamy J, Gandhi S, Damodharan D, Ganesan V, Palaniappan M (2018) Exercise, diet and educational interventions for metabolic syndrome in persons with schizophrenia: A systematic review. Asian J Psychiatr 36:73–85

  • Huang M, Yu L, Pan F, Lu S, Hu S, Hu J, Chen J, Jin P, Qi H, Xu Y (2018) A randomized, 13-week study assessing the efficacy and metabolic effects of paliperidone palmitate injection and olanzapine in first episode schizophrenia patients. Prog Neuropsychopharmacol Biol Psychiatry 81:122–130

  • Kao AC, Spitzer S, Anthony DC, Lennox B, Burnet PWJ (2018) Prebiotic attenuation of olanzapine-induced weight gain in rats: analysis of central and peripheral biomarkers and gut microbiota. Transl Psychiatry 8:66

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kay SR, Fiszbein A, Opler LA (1987) The positive and negative syndrome scale (PANSS) for schizophrenia. Schizophr Bull 13:261–276

    Article  CAS  PubMed  Google Scholar 

  • Kim YS, Xun P, He K (2015) Fish consumption, long-chain omega-3 polyunsaturated fatty acid intake and risk of metabolic syndrome: a meta-analysis. Nutrients 7:2085–2100

  • Kvetny J, Heldgaard PE, Bladbjerg EM, Gram J (2004) Subclinical hypothyroidism is associated with a low-grade inflammation, increased triglyceride levels and predicts cardiovascular disease in males below 50 years. Clin Endocrinol 61:232–238

    Article  CAS  Google Scholar 

  • Labrousse VF, Leyrolle Q, Amadieu C, Aubert A, Sere A, Coutureau E, Gregoire S, Bretillon L, Pallet V, Gressens P, Joffre C, Nadjar A, Laye S (2018) Dietary omega-3 deficiency exacerbates inflammation and reveals spatial memory deficits in mice exposed to lipopolysaccharide during gestation. Brain Behav Immun 73:427–440

    Article  CAS  PubMed  Google Scholar 

  • Li Z, Qi D, Chen J, Zhang C, Yi Z, Yuan C, Wang Z, Hong W, Yu S, Cui D, Fang Y (2013) Venlafaxine inhibits the upregulation of plasma tumor necrosis factor-alpha (TNF-alpha) in the Chinese patients with major depressive disorder: a prospective longitudinal study. Psychoneuroendocrinology 38:107–114

    Article  CAS  PubMed  Google Scholar 

  • Lorente-Cebrián S, Costa AG, Navas-Carretero S, Zabala M, Martínez JA, Moreno-Aliaga MJ (2013) Role of omega-3 fatty acids in obesity, metabolic syndrome, and cardiovascular diseases: a review of the evidence. J Physiol Biochem 69:633–651

  • Memon RA, Grunfeld C, Moser AH, Feingold KR (1993) Tumor necrosis factor mediates the effects of endotoxin on cholesterol and triglyceride metabolism in mice. Endocrinology 132:2246–2253

    Article  CAS  PubMed  Google Scholar 

  • Meyer JM (2002) A retrospective comparison of weight, lipid, and glucose changes between risperidone- and olanzapine-treated inpatients: metabolic outcomes after 1 year. J Clin Psychiatry 63:425–433

    Article  CAS  PubMed  Google Scholar 

  • Mozurkewich EL, Berman DR, Vahratian A, Clinton CM, Romero VC, Chilimigras JL, Vazquez D, Qualls C, Djuric Z (2018) Effect of prenatal EPA and DHA on maternal and umbilical cord blood cytokines. BMC Pregnancy Childbirth 18:261

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • O’Mahoney LL, Matu J, Price OJ, Birch KM, Ajjan RA, Farrar D, Tapp R, West DJ, Deighton K, Campbell MD (2018) Omega-3 polyunsaturated fatty acids favourably modulate cardiometabolic biomarkers in type 2 diabetes: a meta-analysis and meta-regression of randomized controlled trials. Cardiovasc Diabetol 17:98

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Oh DY, Talukdar S, Bae EJ, Imamura T, Morinaga H, Fan WQ, Li PP, Lu WJ, Watkins SM, Olefsky JM (2010) GPR120 is an omega-3 fatty acid receptor mediating potent anti-inflammatory and insulin-sensitizing effects. Cell 142:687–698

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Penninx BWJH, Lange SMM (2018) Metabolic syndrome in psychiatric patients: overview, mechanisms, and implications. Dialogues Clin Neurosci 20:63–73

  • Popa C, Netea MG, van Riel PL, van der Meer JW, Stalenhoef AF (2007) The role of TNF-alpha in chronic inflammatory conditions, intermediary metabolism, and cardiovascular risk. J Lipid Res 48:751–762

    Article  CAS  PubMed  Google Scholar 

  • Pramyothin P, Khaodhiar L (2010) Metabolic syndrome with the atypical antipsychotics. Curr Opin Endocrinol Diabetes Obes 17:460–466

    Article  CAS  PubMed  Google Scholar 

  • Rahmani E, Jamilian M, Dadpour B, Nezami Z, Vahedpoor Z, Mahmoodi S, Aghadavod E, Taghizadeh M, Beiki Hassan A, Asemi Z (2018) The effects of fish oil on gene expression in patients with polycystic ovary syndrome. Eur J Clin Investig 48:e12893

  • Shearer GC, Borkowski K, Puumala SL, Harris WS, Pedersen TL, Newman JW (2018) Abnormal lipoprotein oxylipins in metabolic syndrome and partial correction by omega-3 fatty acids. Prostaglandins Leukot Essent Fat Acids 128:1–10

    Article  CAS  Google Scholar 

  • Sherman ML, Spriggs DR, Arthur KA, Imamura K, Frei E 3rd, Kufe DW (1988) Recombinant human tumor necrosis factor administered as a five-day continuous infusion in cancer patients: phase I toxicity and effects on lipid metabolism. J Clin Oncol 6:344–350

    Article  CAS  PubMed  Google Scholar 

  • Stapel B, Sieve I, Falk CS, Bleich S, Hilfiker-Kleiner D, Kahl KG (2018) Second generation atypical antipsychotics olanzapine and aripiprazole reduce expression and secretion of inflammatory cytokines in human immune cells. J Psychiatr Res 105:95–102

  • Stroup TS, McEvoy JP, Swartz MS, Byerly MJ, Glick ID, Canive JM, McGee MF, Simpson GM, Stevens MC, Lieberman JA (2003) The National Institute of Mental Health Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) project: schizophrenia trial design and protocol development. Schizophr Bull 29:15–31

    Article  PubMed  Google Scholar 

  • Vancampfort D, Stubbs B, Mitchell AJ, De Hert M, Wampers M, Ward PB, Rosenbaum S, Correll CU (2015) Risk of metabolic syndrome and its components in people with schizophrenia and related psychotic disorders, bipolar disorder and major depressive disorder: a systematic review and meta-analysis. World Psychiatry 14:339–347

    Article  PubMed  PubMed Central  Google Scholar 

  • von Schacky C (2006) A review of omega-3 ethyl esters for cardiovascular prevention and treatment of increased blood triglyceride levels. Vasc Health Risk Manag 2:251–262

    Article  Google Scholar 

  • Wang P, Cai J, Ni J, Zhang J, Tang W, Zhang C (2016) The NCAN gene: schizophrenia susceptibility and cognitive dysfunction. Neuropsychiatr Dis Treat 12:2875–2883

  • Zhang Y, Chen M, Wu Z, Chen J, Yu S, Fang Y, Zhang C (2013) Association study of Val66Met polymorphism in brain-derived neurotrophic factor gene with clozapine-induced metabolic syndrome: preliminary results. PLoS One 8:e72652

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang Y, Chen M, Chen J, Wu Z, Yu S, Fang Y, Zhang C (2014) Metabolic syndrome in patients taking clozapine: prevalence and influence of catechol-O-methyltransferase genotype. Psychopharmacology 231:2211–2218

    Article  CAS  PubMed  Google Scholar 

  • Zhang C, Chen MJ, Wu GJ, Wang ZW, Rao SZ, Zhang Y, Yi ZH, Yang WM, Gao KM, Song LS (2016) Effectiveness of antipsychotic drugs for 24-month maintenance treatment in first-episode schizophrenia: evidence from a community-based “real-world” study. J Clin Psychiatry 77:e1460–e1466

    Article  PubMed  Google Scholar 

  • Zhang C, Fang X, Yao P, Mao Y, Cai J, Zhang Y, Chen M, Fan W, Tang W, Song L (2017a) Metabolic adverse effects of olanzapine on cognitive dysfunction: a possible relationship between BDNF and TNF-alpha. Psychoneuroendocrinology 81:138–143

    Article  CAS  PubMed  Google Scholar 

  • Zhang C, Zhang Y, Cai J, Chen M, Song L (2017b) Complement 3 and metabolic syndrome induced by clozapine: a cross-sectional study and retrospective cohort analysis. Pharmacogenomics J 17:92–97

    Article  CAS  PubMed  Google Scholar 

  • Zhang C, Lv Q, Fan W, Tang W, Yi Z (2017c) Influence of CFH gene on symptom severity of schizophrenia. Neuropsychiatr Dis Treat 13:697–706

  • Zhang Y, Fang XY, Fan WX, Tang W, Cai J, Song LS, Zhang C (2018) Brain-derived neurotrophic factor as a biomarker for cognitive recovery in acute schizophrenia: 12-week results from a prospective longitudinal study. Psychopharmacology 235:1191–1198

    Article  CAS  PubMed  Google Scholar 

  • Zhou H, Guo ZR, Yu LG, Hu XS, Xu BH, Liu HB, Wu M, Zhou ZY (2010) Evidence on the applicability of the ATPIII, IDF and CDS metabolic syndrome diagnostic criteria to identify CVD and T2DM in the Chinese population from a 6.3-year cohort study in mid-eastern China. Diabetes Res Clin Pract 90:319–325

    Article  PubMed  Google Scholar 

  • Zhu Y, Wang Z, Ni J, Zhang Y, Chen M, Cai J, Li X, Zhang W, Zhang C (2014) Genetic variant in NDUFS1 gene is associated with schizophrenia and negative symptoms in Han Chinese. J Hum Genet 60:11–16

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We are deeply grateful to all participants.

Funding

This work was supported by the National Natural Science Foundation of China (81471358 and 81771450), the Shanghai Science and Technology Commission Foundation (14411969000), the Shanghai Municipal Education Commission—Gaofeng Clinical Medicine Grant Support (20152530), the Shanghai Municipal Commission of Health and Family Planning Foundation (201540029), and the Shanghai Municipal Commission of Health and Family Planning, Key Developing Disciplines (2015ZB0405).

Author information

Author notes

  1. Feikang Xu and Weixing Fan contributed equally to this work.

Authors and Affiliations

  1. Schizophrenia Program, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China

    Feikang Xu, Yi Zhang, Jun Cai, Lisheng Song & Chen Zhang

  2. Department of Psychiatry, Jinhua Second Hospital, Jinhua, Zhejiang, China

    Weixing Fan & Weiping Wang

  3. Department of Psychiatry, Wenzhou Kangning Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China

    Wei Tang, Fuyin Yang & Chen Zhang

  4. Shanghai Key Laboratory of Brain Functional Genomics (Ministry of Education), School of Psychology and Cognitive Science, East China Normal University, Shanghai, China

    Fuyin Yang

Authors
  1. Feikang Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Weixing Fan
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Weiping Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Wei Tang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Fuyin Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yi Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Jun Cai
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Lisheng Song
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Chen Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Chen Zhang.

Ethics declarations

All procedures for this study were reviewed and approved by the Institutional Review Boards of the Shanghai Mental Health Center and other participating institutions. This study was performed in strict accordance with the Declaration of Helsinki and other relevant national and international regulations.

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

ESM 1

(DOC 418 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Xu, F., Fan, W., Wang, W. et al. Effects of omega-3 fatty acids on metabolic syndrome in patients with schizophrenia: a 12-week randomized placebo-controlled trial. Psychopharmacology 236, 1273–1279 (2019). https://doi.org/10.1007/s00213-018-5136-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00213-018-5136-9

Keywords

Search

Navigation