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

Abstract

Abstract 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 <15.7 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.