Received on July 13, 2006
Accepted on November 17, 2006

General Clinical Chemistry

Biomarkers of Folate and Vitamin B₁₂ Are Related in Blood and Cerebrospinal Fluid

¹ Department of Clinical Chemistry and Laboratory Medicine, University Hospital of Saarland, Homburg/Saar, Germany
² Department of Neurology, Faculty of Medicine, University Hospital of Saarland, Homburg/Saar, Germany

^* To whom correspondence should be addressed. E-mail: kchwher{at}uniklinikum-saarland.de.

Background: B-vitamins (folate, B₁₂) are important micronutrients for brain function and essential cofactors for homocysteine (HCY) metabolism. Increased HCY has been related to neurological and psychiatric disorders. We studied the role of the B-vitamins in HCY metabolism in the brain.

Methods: We studied blood and cerebrospinal fluid (CSF) samples from 72 patients who underwent lumbar puncture. We measured HCY, methylmalonic acid (MMA), and cystathionine by gas chromatography-mass spectrometry; S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH) by liquid chromatography-tandem mass spectrometry; and the B-vitamins by HPLC or immunoassays.

Results: Concentrations were lower in CSF than serum or plasma for HCY (0.09 vs 9.4 µmol/L), SAH (13.2 vs 16.8 nmol/L), cystathionine (54 vs 329 nmol/L), and holotranscobalamin (16 vs 63 pmol/L), whereas concentrations in CSF were higher for MMA (359 vs 186 nmol/L) and SAM (270 vs 113 nmol/L; all P <0.05). CSF concentrations of HCY correlated significantly with CSF folate (r = -0.46), CSF SAH (r = 0.48), CSF-albumin (r = 0.31), and age (r = 0.32). Aging was also associated with lower concentrations of CSF-folate and higher CSF-SAH. The relationship between serum and CSF folate depended on serum folate: the correlation (r) of serum and CSF-folate was 0.69 at serum folate <15.8 nmol/L. CSF concentrations of MMA and holotranscobalamin were not significantly correlated.

Conclusions: CSF and serum/plasma concentrations of vitamin biomarkers are significantly correlated. Older age is associated with higher CSF-HCY and CSF-SAH and lower CSF-folate. These metabolic alterations may be important indicators of low folate status, hyperhomocysteinemia, and neurodegenerative diseases.