Plasma homocysteine levels in multiple sclerosis

BACKGROUND: There is evidence that homocysteine contributes to various neurodegenerative disorders, and elevated plasma homocysteine levels have been observed in patients with multiple sclerosis (MS). OBJECTIVE: To investigate if and why plasma homocysteine levels are increased in MS, and whether they play a role in the disease course. METHODS: We compared plasma levels of homocysteine in 88 patients with MS and 57 healthy controls. In the MS group, 28 had a benign course, 37 were secondary progressive, and 23 primary progressive. To explore the underlying mechanisms, we measured serum levels of vitamins B6 and B12, folate, interleukin (IL)-12, tumour necrosis factor (TNF)-alpha, leukocyte nitric oxide production, and plasma diene conjugate levels (measure of oxidative stress). RESULTS: Mean (SD) plasma homocysteine concentration was higher in patients (13.8 (4.9) micromol/l) than in controls (10.1 (2.5) micromol/l; p<0.0001). However, there were no significant differences in homocysteine levels between the three clinical subgroups of MS. Serum concentrations of vitamin B6, vitamin B12, and folate were not different between patients with MS and controls. In the MS group, there were no correlations between plasma homocysteine levels and the serum concentrations of IL-12 or TNF-alpha, leukocyte nitric oxide production, or plasma diene conjugate levels. CONCLUSIONS: Elevated plasma homocysteine occurs in both benign and progressive disease courses of MS, and seems unrelated to immune activation, oxidative stress, or a deficiency in vitamin B6, vitamin B12, or folate.