Biomarkers of folate and vitamin B12 are related in blood and cerebrospinal fluid.

BACKGROUND: B-vitamins (folate, B(12)) 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 micromol/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.

CSF-methionine is elevated in psychotic patients.

Cerebrospinal fluid levels of methionine (MET), homocysteine (HCY) and cystathionine were studied in patients with psychotic disorders (n=36) and in healthy controls (n=25). Patients had significantly higher MET than controls (p<0.00001), and ten of the patients had MET levels above anyone of the controls. Moreover, three young male patients had HCY levels highly above any of the controls. There were no significant gender differences in any of the parameters. Neither ageing nor neuroleptic treatment offered an explanation for the increase of MET, because also young and drug-naive patients had significantly higher MET than the controls. We conclude that patients with psychotic disorders, at least in a phase of acute exacerbation, are often in a state of disturbed one-carbon metabolism.

Increased concentrations of homocysteine in the cerebrospinal fluid in patients with fibromyalgia and chronic fatigue syndrome.

Twelve outpatients, all women, who fulfilled the criteria for both fibromyalgia and chronic fatigue syndrome were rated on 15 items of the Comprehensive Psychopathological Rating Scale (CPRS-15). These items were chosen to constitute a proper neurasthenic subscale. Blood laboratory levels were generally normal. The most obvious finding was that, in all the patients, the homocysteine (HCY) levels were increased in the cerebrospinal fluid (CSF). There was a significant positive correlation between CSF-HCY levels and fatiguability, and the levels of CSF-B12 correlated significantly with the item of fatiguability and with CPRS-15. The correlations between vitamin B12 and clinical variables of the CPRS-scale in this study indicate that low CSF-B12 values are of clinical importance. Vitamin B12 deficiency causes a deficient remethylation of HCY and is therefore probably contributing to the increased homocysteine levels found in our patient group. We conclude that increased homocysteine levels in the central nervous system characterize patients fulfilling the criteria for both fibromyalgia and chronic fatigue syndrome.