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Neurotherapeutics

, Volume 16, Issue 1, pp 192–202 | Cite as

Supranutritional Sodium Selenate Supplementation Delivers Selenium to the Central Nervous System: Results from a Randomized Controlled Pilot Trial in Alzheimer’s Disease

  • Barbara R. CardosoEmail author
  • Blaine R. Roberts
  • Charles B. Malpas
  • Lucy Vivash
  • Sila Genc
  • Michael M. Saling
  • Patricia Desmond
  • Christopher Steward
  • Rodney J. Hicks
  • Jason Callahan
  • Amy Brodtmann
  • Steven Collins
  • Stephen Macfarlane
  • Niall M Corcoran
  • Christopher M. Hovens
  • Dennis Velakoulis
  • Terence J. O’Brien
  • Dominic J. HareEmail author
  • Ashley I. Bush
Original Article

Abstract

Insufficient supply of selenium to antioxidant enzymes in the brain may contribute to Alzheimer’s disease (AD) pathophysiology; therefore, oral supplementation may potentially slow neurodegeneration. We examined selenium and selenoproteins in serum and cerebrospinal fluid (CSF) from a dual-dose 24-week randomized controlled trial of sodium selenate in AD patients, to assess tolerability, and efficacy of selenate in modulating selenium concentration in the central nervous system (CNS). A pilot study of 40 AD cases was randomized to placebo, nutritional (0.32 mg sodium selenate, 3 times daily), or supranutritional (10 mg, 3 times daily) groups. We measured total selenium, selenoproteins, and inorganic selenium levels, in serum and CSF, and compared against cognitive outcomes. Supranutritional selenium supplementation was well tolerated and yielded a significant (p < 0.001) but variable (95% CI = 13.4–24.8 μg/L) increase in CSF selenium, distributed across selenoproteins and inorganic species. Reclassifying subjects as either responsive or non-responsive based on elevation in CSF selenium concentrations revealed that responsive group did not deteriorate in Mini-Mental Status Examination (MMSE) as non-responsive group (p = 0.03). Pooled analysis of all samples revealed that CSF selenium could predict change in MMSE performance (Spearman’s rho = 0.403; p = 0.023). High-dose sodium selenate supplementation is well tolerated and can modulate CNS selenium concentration, although individual variation in selenium metabolism must be considered to optimize potential benefits in AD. The Vel002 study is listed on the Australian and New Zealand Clinical Trials Registry (http://www.anzctr.org.au/), ID: ACTRN12611001200976.

Key words

Sodium selenate selenium Alzheimer’s disease supranutritional selenium supplementation randomized controlled trial 

Abbreviations

AD

Alzheimer’s disease

ApoE

Apolipoprotein E

CNS

Central nervous system

CSF

Cerebrospinal fluid

GPx

Glutathione peroxidase

ICP-MS

Inductively coupled plasma-mass spectrometry

MMSE

Mini-Mental Status Examination

MRI

Magnetic resonance imaging

Se

Selenium

SeMet

Selenomethionine

SeO42−

Selenate

SeO32−

Selenite

SAE

Serious adverse event

SEC

Size exclusion chromatography

TEAE

Treatment emergent adverse event

Notes

Acknowledgments

The Florey Institute of Neuroscience and Mental Health wishes to acknowledge the Victorian Government’s Operational Infrastructure Support Program, as well as the assistance of the Cooperative Research Centre for Mental Health and the Neuroproteomics Facility.

Funding Information

Funded by Fellowships from the Brazilian Government Science Without Borders program (Ciência sem Fronteiras; BRC), Deakin University (BRC), and the Australian National Health and Medical Research Council (GNT1138673, BRR; GNT1105784, SC; GNT1122981, DJH; GNT1103703, AIB); a Program Grant from the Australian National Health and Medical Research Council (GNT1132604, AIB); and by Velacor Therapeutics. Agilent Technologies provided material and research support (BRR, DJH).

Supplementary material

13311_2018_662_MOESM1_ESM.pdf (1.2 mb)
ESM 1 (PDF 1224 kb)
13311_2018_662_MOESM2_ESM.pdf (1.2 mb)
ESM 2 (PDF 1224 kb)
13311_2018_662_MOESM3_ESM.docx (21 kb)
Supplementary Table 1 (DOCX 20 kb)

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Copyright information

© The American Society for Experimental NeuroTherapeutics, Inc. 2018

Authors and Affiliations

  • Barbara R. Cardoso
    • 1
    Email author
  • Blaine R. Roberts
    • 2
  • Charles B. Malpas
    • 3
    • 4
    • 5
    • 6
  • Lucy Vivash
    • 3
    • 6
  • Sila Genc
    • 5
    • 7
  • Michael M. Saling
    • 4
  • Patricia Desmond
    • 8
  • Christopher Steward
    • 8
  • Rodney J. Hicks
    • 8
    • 9
  • Jason Callahan
    • 9
  • Amy Brodtmann
    • 2
    • 10
  • Steven Collins
    • 3
    • 11
  • Stephen Macfarlane
    • 12
  • Niall M Corcoran
    • 13
  • Christopher M. Hovens
    • 13
  • Dennis Velakoulis
    • 14
  • Terence J. O’Brien
    • 3
    • 6
  • Dominic J. Hare
    • 2
    Email author
  • Ashley I. Bush
    • 2
  1. 1.Institute for Physical Activity and Nutrition (IPAN), School of Exercise and Nutrition SciencesDeakin UniversityGeelongAustralia
  2. 2.Melbourne Dementia Research Centre, The Florey Institute of Neuroscience and Mental HealthThe University of MelbourneParkvilleAustralia
  3. 3.Department of MedicineRoyal Melbourne HospitalMelbourneAustralia
  4. 4.Melbourne School of Psychological SciencesThe University of MelbourneParkvilleAustralia
  5. 5.Developmental ImagingMurdoch Children’s Research InstituteMelbourneAustralia
  6. 6.Departments of Neuroscience and Neurology, The Central Clinical School and The Alfred HospitalMonash UniversityMelbourneAustralia
  7. 7.Department of PaediatricsThe University of MelbourneParkvilleAustralia
  8. 8.Department of Radiology, Royal Melbourne HospitalUniversity of MelbourneMelbourneAustralia
  9. 9.Centre for Molecular Imaging, Peter MacCallum Cancer CentreMelbourneAustralia
  10. 10.Eastern Cognitive Disorders Clinic, Department of Neurology, Eastern HealthMonash UniversityMelbourneAustralia
  11. 11.Department of Clinical Neurosciences and Neurological ResearchSt Vincent’s HospitalFitzroyAustralia
  12. 12.Caulfield HospitalAlfred HealthCaulfieldAustralia
  13. 13.Department of SurgeryRoyal Melbourne HospitalMelbourneAustralia
  14. 14.Department of PsychiatryThe University of MelbourneParkvilleAustralia

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