Increased plasma homocysteine levels without signs of vitamin B12 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 B₁₂ (cobalamin) deficiency. Methods: We measured serum vitamin B₁₂, plasma folate, serum methylmalonic acid (MMA), plasma homocysteine (tHcy) and also cerebrospinal fluid (C SF) 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 mmol/L) compared with controls (7.4 mmol/L) (P =4-0.002). Seven patients showed low serum vitamin B₁₂levels 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 B₁₂, serum MMA, mean corpuscular volume (MC V), haemoglobin concentration, C SF tHcy or C SF MMA between patients and healthy subjects. There were no correlations between C SF and serum/plasma levels of MMA or tHcy. Serum vitamin B₁₂, serum MMA, plasma tHcy, C SF Hcy or C SF 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 B₁₂ deficiency. We can not, however, exclude the possibility of a genetically induced dysfunction of the homocysteine metabolism relevant for the development of neuroinflammation/degeneration. O ur findings indicate that, regardless of a significant increase in plasma tHcy in MS patients, the MS disease is not generally associated with vitamin B₁₂ deficiency since we did not find any other factors indicating vitamin B₁₂ deficiency. A nalysis of C SF MMA and C SF tHcy, which probably reflects the brain vitamin B₁₂ status better than serum, are not warranted in MS. We conclude that B₁₂ deficiency, in general, is not associated with MS.