Increased plasma homocysteine levels without signs of vitamin B-12 deficiency in patients with multiple sclerosis assessed by blood and cerebrospinal fluid homocysteine and methylmalonic acid

Objective: The aim of this study was to evaluate if multiple sclerosis (MS) is associated with vitamin B-12 (cobalamin) deficiency. Methods: We measured serum vitamin B12, plasma folate, serum methylmalonic acid (MMA), plasma homocysteine (tHcy) and also cerebro spinal fluid (CSF) MMA and tHcy in 72 patients with MS and 23 controls. Results: The mean plasma tHcy level was significantly increased in MS patients (11.6 mumol/L) compared with controls (7.4 mumol/L) (P=0.002). Seven patients showed low serum vitamin B-12 levels but only one of them had concomitant high plasma tHcy. None of them showed high serum MMA. Plasma or blood folate levels did not differ between MS patients and controls. We found no significant differences in mean values or frequency of pathological tests of serum B-12, serum MMA, mean corpuscular volume (MCV), haemoglobin concentration, CSF tHcy or CSF MMA between patients and healthy subjects. There were no correlations between C SF and serum/plasma levels of MMA or tHcy. Serum vitamin B-12, serum MMA, plasma tHcy, CSF Hcy or CSF MMA were not correlated to disability status, activity of disease, duration of disease or age. Conclusions: The relevance of the increased mean value of plasma tHcy thus seems uncertain and does not indicate functional vitamin B-12 deficiency. We can not, however, exclude the possibility of a genetically induced dysfunction of the homocysteine metabolism relevant for the development of neuro inflammation/degeneration. Our findings indicate that, regardless of a significant increase in plasma tHcy in MS patients, the MS disease is not generally associated with vitamin B-12 deficiency since we did not find any other factors indicating vitamin B-12 deficiency. Analysis of CSF MMA and CSF tHcy, which probably reflects the brain vitamin B-12 status better than serum, are not warranted in MS. We conclude that B-12 deficiency, in general, is not associated with MS.