Skip to main content

Advertisement

SpringerLink
Log in

The Effects of Probiotic and Selenium Co-supplementation on Clinical and Metabolic Scales in Chronic Schizophrenia: a Randomized, Double-blind, Placebo-Controlled Trial

  • Published:
Biological Trace Element Research Aims and scope Submit manuscript

Abstract

This study evaluated the effects of probiotic and selenium co-supplementation on clinical and metabolic symptoms in patients with chronic schizophrenia. A randomized, double-blind, placebo-controlled trial was conducted among 60 people with chronic schizophrenia to receive either 8 × 109 CFU/day probiotic plus 200 μg/day selenium (n = 30) or placebo (n = 30) for 12 weeks. Probiotic and selenium co-supplementation resulted in a significant improvement in the general Positive and Negative Syndrome Scale (PANSS) score (β − 1.29; 95% CI, − 2.48, − 0.10; P = 0.03) compared with the placebo. Compared with the placebo, probiotic and selenium co-supplementation resulted in a significant elevation in total antioxidant capacity (β 91.09 mmol/L; 95% CI, 35.89, 146.30; P = 0.002) and total glutathione (β 96.50 μmol/L; 95% CI, 26.13, 166.87; P = 0.008) and a significant reduction in high-sensitivity C-reactive protein levels (β − 1.44 mg/L; 95% CI, − 2.22, − 0.66; P = 0.001). Additionally, co-supplementation significantly decreased fasting glucose (β − 7.40 mg/dL; 95% CI, − 10.15, − 4.64; P < 0.001), insulin levels (β − 1.46 μIU/mL; 95% CI, − 2.35, − 0.57; P = 0.002), and homeostasis model of assessment-insulin resistance (β − 0.51; 95% CI, − 0.72, − 0.29; P < 0.001) and a significant increase in quantitative insulin sensitivity check index (β 0.01; 95% CI, 0.006, 0.01; P < 0.001) compared with the placebo. Probiotic and selenium co-supplementation for 12 weeks to patients with chronic schizophrenia had beneficial effects on the general PANSS score and some metabolic profiles. http://www.irct.ir, identifier IRCT20170513033941N41

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

Access this article

Log in via an institution

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

Data availability

The primary data for this study is available from the authors on direct request.

Abbreviations

BPRS:

Brief Psychiatric Rating Scale

FPG:

Fasting plasma glucose

GSH:

Total glutathione

HOMA-IR:

Homeostasis model of assessment-estimated insulin resistance

hs-CRP:

High-sensitivity C-reactive protein

MDA:

Malondialdehyde

PANSS:

Positive and Negative Syndrome Scale

QUICKI:

Quantitative insulin sensitivity check index

TAC:

Total antioxidant capacity.

References

  1. Seeman MV (2007) Symptoms of schizophrenia: normal adaptations to inability. Med Hypotheses 69(2):253–257

    Article  PubMed  Google Scholar 

  2. Kaplan HI (2005) Kaplan & Sadock’s Comprehensive Textbook of Psychiatry, (2 Volume Set, 2005)

  3. Chowdari KV, Bamne MN, Nimgaonkar VL (2011) Genetic association studies of antioxidant pathway genes and schizophrenia. Antioxid Redox Signal 15(7):2037–2045

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Rabinowitz J et al (2012) Negative symptoms have greater impact on functioning than positive symptoms in schizophrenia: analysis of CATIE data. Schizophr Res 137(1–3):147–150

    Article  PubMed  Google Scholar 

  5. Yao JK, Keshavan MS (2011) Antioxidants, redox signaling, and pathophysiology in schizophrenia: an integrative view. Antioxid Redox Signal 15(7):2011–2035

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Bloch MH (2009) Trichotillomania across the life span. J Am Acad Child Adolesc Psychiatry 48(9):879–883

    Article  PubMed  Google Scholar 

  7. Marek GJ et al (2010) Glutamatergic (N-methyl-D-aspartate receptor) hypofrontality in schizophrenia: too little juice or a miswired brain? Mol Pharmacol 77(3):317–326

    Article  CAS  PubMed  Google Scholar 

  8. Kaneko K (2018) Negative symptoms and cognitive impairments in schizophrenia: two key symptoms negatively influencing social functioning. Yonago Acta Med 61(2):91–102

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. MacKenzie NE et al (2018) Antipsychotics, metabolic adverse effects, and cognitive function in schizophrenia. Front Psychiatry 9:622

    Article  PubMed  PubMed Central  Google Scholar 

  10. Hamer S, Haddad PM (2007) Adverse effects of antipsychotics as outcome measures. Br J Psychiatry Suppl 50:s64–s70

    Article  PubMed  Google Scholar 

  11. Lewis R (2004) Should cognitive deficit be a diagnostic criterion for schizophrenia? J Psychiatry Neurosci 29(2):102–113

    PubMed  PubMed Central  Google Scholar 

  12. Li Z et al (2018) Association of elements with schizophrenia and intervention of selenium supplements. Biol Trace Elem Res 183(1):16–21

    Article  CAS  PubMed  Google Scholar 

  13. Cai L et al (2015) Serum trace element differences between Schizophrenia patients and controls in the Han Chinese population. Sci Rep 5:15013

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Lovell MA et al (2009) Organoselenium (Sel-Plex diet) decreases amyloid burden and RNA and DNA oxidative damage in APP/PS1 mice. Free Radic Biol Med 46(11):1527–1533

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Amirani E et al (2020) The effects of probiotic supplementation on mental health, biomarkers of inflammation and oxidative stress in patients with psychiatric disorders: a systematic review and meta-analysis of randomized controlled trials. Complement Ther Med 49:102361

    Article  PubMed  Google Scholar 

  16. Sayyah M, Andishmand M, Ganji R (2018) Effect of selenium as an adjunctive therapy in patients with treatment-resistant obsessive-compulsive disorder: a pilot randomized double blind placebo-controlled clinical trial. Archives of Psychiatry & Psychotherapy 20(4)

  17. Kryscio RJ et al (2017) Association of antioxidant supplement use and dementia in the Prevention of Alzheimer’s Disease by Vitamin E and Selenium Trial (PREADViSE). JAMA Neurol 74(5):567–573

    Article  PubMed  PubMed Central  Google Scholar 

  18. Ng QX et al (2019) A systematic review of the effect of probiotic supplementation on schizophrenia symptoms. Neuropsychobiology 78(1):1–6

    Article  PubMed  Google Scholar 

  19. Kim YK, Shin C (2018) The microbiota-gut-brain axis in neuropsychiatric disorders: pathophysiological mechanisms and novel treatments. Curr Neuropharmacol 16(5):559–573

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Dickerson FB et al (2014) Effect of probiotic supplementation on schizophrenia symptoms and association with gastrointestinal functioning: a randomized, placebo-controlled trial. Prim Care Companion CNS Disord 16:1

    Google Scholar 

  21. Akkasheh G et al (2016) Clinical and metabolic response to probiotic administration in patients with major depressive disorder: a randomized, double-blind, placebo-controlled trial. Nutrition 32(3):315–320

    Article  CAS  PubMed  Google Scholar 

  22. Mattmiller SA, Carlson BA, Sordillo LM (2013) Regulation of inflammation by selenium and selenoproteins: impact on eicosanoid biosynthesis. J Nutr Sci 2:e28

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Ghoneim MA, Moselhy SS (2016) Antioxidant status and hormonal profile reflected by experimental feeding of probiotics. Toxicol Ind Health 32(4):741–750

    Article  CAS  PubMed  Google Scholar 

  24. Carvalho BM, Saad MJ (2013) Influence of gut microbiota on subclinical inflammation and insulin resistance. Mediators Inflamm 2013:986734

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  25. Nido SA et al (2016) Effects of selenium-enriched probiotics on lipid metabolism, antioxidative status, histopathological lesions, and related gene expression in mice fed a high-fat diet. Biol Trace Elem Res 171(2):399–409

    Article  CAS  PubMed  Google Scholar 

  26. Ibrahim HA et al (2012) Selenium-enriched probiotics improves murine male fertility compromised by high fat diet. Biol Trace Elem Res 147(1–3):251–260

    Article  CAS  PubMed  Google Scholar 

  27. Tamtaji OR et al (2019) Probiotic and selenium co-supplementation, and the effects on clinical, metabolic and genetic status in Alzheimer’s disease: a randomized, double-blind, controlled trial. Clin Nutr 38(6):2569–2575

    Article  CAS  PubMed  Google Scholar 

  28. Risch SC et al (2007) Double-blind donepezil-placebo crossover augmentation study of atypical antipsychotics in chronic, stable schizophrenia: a pilot study. Schizophr Res 93(1–3):131–135

    Article  PubMed  Google Scholar 

  29. Lachar D et al (1999) Use of BPRS-A percent change scores to identify significant clinical improvement: accuracy of treatment response classification in acute psychiatric inpatients. Psychiatry Res 89(3):259–268

    Article  CAS  PubMed  Google Scholar 

  30. Benzie IF, Strain JJ (1996) The ferric reducing ability of plasma (FRAP) as a measure of “antioxidant power”: the FRAP assay. Anal Biochem 239(1):70–76

    Article  CAS  PubMed  Google Scholar 

  31. Beutler E, Gelbart T (1985) Plasma glutathione in health and in patients with malignant disease. J Lab Clin Med 105(5):581–584

    CAS  PubMed  Google Scholar 

  32. Janero DR (1990) Malondialdehyde and thiobarbituric acid-reactivity as diagnostic indices of lipid peroxidation and peroxidative tissue injury. Free Radic Biol Med 9(6):515–540

    Article  CAS  PubMed  Google Scholar 

  33. Tatsch E et al (2011) A simple and inexpensive automated technique for measurement of serum nitrite/nitrate. Clin Biochem 44(4):348–350

    Article  CAS  PubMed  Google Scholar 

  34. Pisprasert V et al (2013) Limitations in the use of indices using glucose and insulin levels to predict insulin sensitivity: impact of race and gender and superiority of the indices derived from oral glucose tolerance test in African Americans. Diabetes Care 36(4):845–853

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Stefanska E et al (2017) Eating habits and nutritional status of patients with affective disorders and schizophrenia. Psychiatr Pol 51(6):1107–1120

    Article  PubMed  Google Scholar 

  36. Vaddadi KS, Soosai E, Vaddadi G (2003) Low blood selenium concentrations in schizophrenic patients on clozapine. Br J Clin Pharmacol 55(3):307–309

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Dickerson F et al (2010) Markers of gluten sensitivity and celiac disease in recent-onset psychosis and multi-episode schizophrenia. Biol Psychiatry 68(1):100–104

    Article  CAS  PubMed  Google Scholar 

  38. De Hert M et al (2011) Prevalence and severity of antipsychotic related constipation in patients with schizophrenia: a retrospective descriptive study. BMC Gastroenterol 11:17

    Article  PubMed  PubMed Central  Google Scholar 

  39. Tomasik J et al (2015) Immunomodulatory effects of probiotic supplementation in schizophrenia patients: a randomized, placebo-controlled trial. Biomark Insights 10:47–54

    Article  PubMed  PubMed Central  Google Scholar 

  40. Severance EG et al (2017) Probiotic normalization of Candida albicans in schizophrenia: a randomized, placebo-controlled, longitudinal pilot study. Brain Behav Immun 62:41–45

    Article  PubMed  Google Scholar 

  41. Ghaderi A et al (2019) Clinical and metabolic response to vitamin D plus probiotic in schizophrenia patients. BMC Psychiatry 19(1):77

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  42. Diaz Heijtz R et al (2011) Normal gut microbiota modulates brain development and behavior. Proc Natl Acad Sci U S A 108(7):3047–3052

    Article  PubMed  Google Scholar 

  43. O'Mahony SM et al (2009) Early life stress alters behavior, immunity, and microbiota in rats: implications for irritable bowel syndrome and psychiatric illnesses. Biol Psychiatry 65(3):263–267

    Article  PubMed  Google Scholar 

  44. Xie Y et al (2018) Se-methylselenocysteine ameliorates neuropathology and cognitive deficits by attenuating oxidative stress and metal dyshomeostasis in Alzheimer model mice. Mol Nutr Food Res 62(12):e1800107

    Article  PubMed  CAS  Google Scholar 

  45. Zhang ZH et al (2017) Long-term dietary supplementation with selenium-enriched yeast improves cognitive impairment, reverses synaptic deficits, and mitigates tau pathology in a triple transgenic mouse model of Alzheimer’s disease. J Agric Food Chem 65(24):4970–4979

    Article  CAS  PubMed  Google Scholar 

  46. Rayman M et al (2006) Impact of selenium on mood and quality of life: a randomized, controlled trial. Biol Psychiatry 59(2):147–154

    Article  CAS  PubMed  Google Scholar 

  47. Cryan JF, Dinan TG (2012) Mind-altering microorganisms: the impact of the gut microbiota on brain and behaviour. Nat Rev Neurosci 13(10):701–712

    Article  CAS  PubMed  Google Scholar 

  48. Bested AC, Logan AC, Selhub EM (2013) Intestinal microbiota, probiotics and mental health: from Metchnikoff to modern advances: Part I - autointoxication revisited. Gut Pathog 5(1):5

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  49. Suvisaari J, Mantere O (2013) Inflammation theories in psychotic disorders: a critical review. Infect Disord Drug Targets 13(1):59–70

    Article  CAS  PubMed  Google Scholar 

  50. Uttara B et al (2009) Oxidative stress and neurodegenerative diseases: a review of upstream and downstream antioxidant therapeutic options. Curr Neuropharmacol 7(1):65–74

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Flatow J, Buckley P, Miller BJ (2013) Meta-analysis of oxidative stress in schizophrenia. Biol Psychiatry 74(6):400–409

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Bolisetty S, Jaimes EA (2013) Mitochondria and reactive oxygen species: physiology and pathophysiology. Int J Mol Sci 14(3):6306–6344

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Bitanihirwe BK, Woo TU (2011) Oxidative stress in schizophrenia: an integrated approach. Neurosci Biobehav Rev 35(3):878–893

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Wang Z et al (2017) Association between C-reactive protein and risk of schizophrenia: An updated meta-analysis. Oncotarget 8(43):75445–75454

    Article  PubMed  PubMed Central  Google Scholar 

  55. Pedrini M et al (2012) Similarities in serum oxidative stress markers and inflammatory cytokines in patients with overt schizophrenia at early and late stages of chronicity. J Psychiatr Res 46(6):819–824

    Article  PubMed  Google Scholar 

  56. Vaghef-Mehrabany E et al (2014) Probiotic supplementation improves inflammatory status in patients with rheumatoid arthritis. Nutrition 30(4):430–435

    Article  CAS  PubMed  Google Scholar 

  57. Mohammadi AA et al (2016) The effects of probiotics on mental health and hypothalamic-pituitary-adrenal axis: A randomized, double-blind, placebo-controlled trial in petrochemical workers. Nutr Neurosci 19(9):387–395

    Article  CAS  PubMed  Google Scholar 

  58. Tamtaji OR et al (2018) Probiotic and selenium co-supplementation, and the effects on clinical, metabolic and genetic status in Alzheimer’s disease: a randomized, double-blind, controlled trial. Clin Nutr

  59. Liu Y et al (2015) Protective effects of Selenium-enriched probiotics on carbon tetrachloride-induced liver fibrosis in rats. J Agric Food Chem 63(1):242–249

    Article  CAS  PubMed  Google Scholar 

  60. Wang Y et al (2017) Antioxidant properties of probiotic bacteria. Nutrients 9(5)

  61. Duntas LH (2009) Selenium and inflammation: underlying anti-inflammatory mechanisms. Horm Metab Res 41(6):443–447

    Article  CAS  PubMed  Google Scholar 

  62. Cohen D et al (2006) Hyperglycemia and diabetes in patients with schizophrenia or schizoaffective disorders. Diabetes Care 29(4):786–791

    Article  PubMed  Google Scholar 

  63. Lund BC et al (2001) Clozapine use in patients with schizophrenia and the risk of diabetes, hyperlipidemia, and hypertension: a claims-based approach. Arch Gen Psychiatry 58(12):1172–1176

    Article  CAS  PubMed  Google Scholar 

  64. van Beveren NJ et al (2014) Evidence for disturbed insulin and growth hormone signaling as potential risk factors in the development of schizophrenia. Transl Psychiatry 4:e430

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  65. Protopopova D et al (2014) Peripheral endothelial dysfunction as a marker of cardiovascular risk in physically healthy patients with schizophrenia and related psychoses: a matched case control study. Neuro Endocrinol Lett 35(6):503–509

    PubMed  Google Scholar 

  66. Pillinger T et al (2017) Cholesterol and triglyceride levels in first-episode psychosis: systematic review and meta-analysis. Br J Psychiatry 211(6):339–349

    Article  PubMed  PubMed Central  Google Scholar 

  67. Taha AY et al (2013) Altered fatty acid concentrations in prefrontal cortex of schizophrenic patients. J Psychiatr Res 47(5):636–643

    Article  PubMed  PubMed Central  Google Scholar 

  68. Jayawardena R et al (2012) Effects of zinc supplementation on diabetes mellitus: a systematic review and meta-analysis. Diabetol Metab Syndr 4(1):13

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Faure P et al (1995) Lipid peroxidation in insulin-dependent diabetic patients with early retina degenerative lesions: effects of an oral zinc supplementation. Eur J Clin Nutr 49(4):282–288

    CAS  PubMed  Google Scholar 

  70. Li C et al (2016) Effect of probiotics on metabolic profiles in type 2 diabetes mellitus: a meta-analysis of randomized, controlled trials. Medicine (Baltimore) 95(26):e4088

    Article  Google Scholar 

  71. Bahmani F et al (2016) Effect of selenium supplementation on glycemic control and lipid profiles in patients with diabetic nephropathy. Biol Trace Elem Res 172(2):282–289

    Article  CAS  PubMed  Google Scholar 

  72. Shimizu M et al (2015) Meta-Analysis: Effects of probiotic supplementation on lipid profiles in normal to mildly hypercholesterolemic individuals. PLoS One 10(10):e0139795

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  73. Kim JE et al (2012) Selenium significantly inhibits adipocyte hypertrophy and abdominal fat accumulation in OLETF rats via induction of fatty acid beta-oxidation. Biol Trace Elem Res 150(1–3):360–370

    Article  PubMed  CAS  Google Scholar 

  74. Hsieh FC et al (2013) Oral administration of Lactobacillus reuteri GMNL-263 improves insulin resistance and ameliorates hepatic steatosis in high fructose-fed rats. Nutr Metab (Lond) 10(1):35

    Article  CAS  Google Scholar 

  75. Huang Z et al (2015) Effects of dietary probiotic supplementation on LXRalpha and CYP7alpha1 gene expression, liver enzyme activities and fat metabolism in ducks. Br Poult Sci 56(2):218–224

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

We are thankful to all patients who participated in this project.

Funding

Arak University of Medical Sciences (AUMS) funds this study with a role in the design of the trial and collection, analysis, and interpretation of data and in writing the manuscript.

Author information

Authors and Affiliations

  1. Department of Psychiatry, Arak University of Medical Sciences, Arak, Iran

    Hamidreza Jamilian

  2. Clinical Research Development Unit-Matini/Kargarnejad Hospital, Kashan University of Medical Sciences, Kashan, IR, Iran

    Amir Ghaderi

  3. Department of Addiction studies, School of Medical, Kashan University of Medical Sciences, Kashan, Iran

    Amir Ghaderi

Authors
  1. Hamidreza Jamilian
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Amir Ghaderi
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

HJ and AG contributed in conception, design, statistical analysis, and drafting of the manuscript. HJ contributed in conception and data collection. The authors have read and approved the manuscript.

Corresponding author

Correspondence to Amir Ghaderi.

Ethics declarations

Ethics Approval and Consent to Participate

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and national research committee and with the 1964 Helsinki declaration and its later amendments.

Consent for Publication

Not applicable.

Competing Interests

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.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Jamilian, H., Ghaderi, A. The Effects of Probiotic and Selenium Co-supplementation on Clinical and Metabolic Scales in Chronic Schizophrenia: a Randomized, Double-blind, Placebo-Controlled Trial. Biol Trace Elem Res 199, 4430–4438 (2021). https://doi.org/10.1007/s12011-020-02572-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12011-020-02572-3

Keywords

Search

Navigation