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

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 (0.32mg sodium selenate, 3 times daily), or supranutritional (10mg, 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=13.4-24.8g/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.