A Novel Method for the Determination of Vitamin D Metabolites Assessed at the Blood-Cerebrospinal Fluid Barrier

Sieglinde Zelzer; Andreas Meinitzer; Markus Herrmann; Walter Goessler; Dietmar Enko

doi:10.3390/biom11091288

A Novel Method for the Determination of Vitamin D Metabolites Assessed at the Blood-Cerebrospinal Fluid Barrier

Biomolecules. 2021 Aug 29;11(9):1288. doi: 10.3390/biom11091288.

Authors

Sieglinde Zelzer¹, Andreas Meinitzer¹, Markus Herrmann¹, Walter Goessler², Dietmar Enko^{1

3}

Affiliations

¹ Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, 8036 Graz, Austria.
² Institute of Chemistry, University of Graz, 8010 Graz, Austria.
³ Institute of Clinical Chemistry and Laboratory Medicine, General Hospital Hochsteiermark, 8700 Leoben, Austria.

Abstract

The brain's supply with vitamin D is poorly understood. Therefore, the present study aimed to determine 25-hydroxy vitamin D3 (25(OH)D) and 24,25-dihydroxy vitamin D (24,25(OH)₂D₃) in serum and cerebrospinal fluid (CSF) from individuals with intact and disturbed brain-CSF-barrier (BCB) function. In 292 pairs of serum and CSF samples the vitamin D metabolites were measured with liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). CSF/serum ratios (Q_ALB, Q_25(OH)D, Q_24,25(OH)2D3) were calculated. Median (IQR) serum concentrations of 25(OH)D and 24,25(OH)₂D₃ were 63.8 (43.4-83.9) nmol/L and 4.2 (2.2-6.2) nmol/L. The CSF concentrations of both metabolites accounted for 3.7 and 3.3% of the respective serum concentrations. Serum 25(OH)D correlated inversely with Q_25(OH)D and Q_24,25(OH)2D3 implying a more efficient transport of both metabolites across the BCB when the serum concentration of 25(OH)D is low. In patients with BCB dysfunction, the CSF concentrations and the CSF/serum ratios of both vitamin D metabolites were higher than in individuals with intact BCB. The CSF concentrations of 25(OH)D and 24,25(OH)₂D₃ depend on BCB function and the respective serum concentrations of both metabolites. Higher vitamin D metabolite concentrations in CSF of patients with impaired BCB function may be due to passive diffusion across the BCB.

Keywords: biomarkers; blood-cerebrospinal fluid barrier; cerebrospinal fluid; liquid chromatography-tandem mass spectrometry; vitamin D metabolites.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Blood-Brain Barrier / metabolism*
Chromatography, Liquid
Female
Humans
Male
Metabolome*
Metabolomics / methods*
Middle Aged
Regression Analysis
Tandem Mass Spectrometry
Vitamin D / analogs & derivatives
Vitamin D / blood*
Vitamin D / cerebrospinal fluid*

Substances

Vitamin D
25-hydroxyvitamin D