Increased plasma homocysteine levels with signs of vitamin B12 deficiency in patients with multiple sclerosis

There is evidence that homocysteine contributes to various neurodegenerative disorders, and elevated plasma homocysteine levels have been observed in patients with multiple sclerosis (MS). To investigate if and why plasma homocysteine levels are increased in MS, and whether they play a role in the disease course. The literature review presents the studies that reported plasma homocysteine levels in multiple sclerosis between 1980 and 2016 and the search was conducted using the databases PubMed, Medline, EMBASE and Web of Science. We also searched ClinicalTrials.gov and requested relevant published or unpublished trials from manufacturers of increased plasma homocysteine levels with signs of vitamin B12 deficiency in patients with multiple sclerosis assessed by blood and cerebrospinal fluid homocysteine and methylmalonic acid. In recent years, there has been increasing interest in the role of plasma homocysteine (Hcy) as a possible risk factor for several diseases of the central nervous system. Deficiencies in vitamin B6, vitamin B12, or folate are associated with elevated plasma levels of homocysteine. In the search for a possible relationship between vitamin B12 deficiency and multiple sclerosis (MS), two studies found elevated plasma homocysteine levels in patients with MS. The frequency of biologically relevant vitamin B12 deficiency in MS is low, and it is uncertain, whether this provides a satisfactory explanation for the raised plasma homocysteine concentrations. There is evidence that homocysteine contributes to various neurodegenerative disorders, and elevated plasma homocysteine levels have been observed in patients with multiple sclerosis (MS). The nervous system may be particularly sensitive to extracellular homocysteine, as it promotes excitotoxicity via stimulation of N‐methyl‐D‐asparate receptors, and damages neuronal DNA, thereby triggering apoptosis. Increased levels of homocysteine may play a role in the pathogenesis of Alzheimer's disease, through both vascular and degenerative mechanisms, and hasten the onset and progression of Parkinson's disease. High homocysteine resulting from poor reconversion to methionine is related to low methionine availability. Elevated homocysteine (Hcy) levels exert several neurotoxic actions and vascular dysfunctions that may be involved in pathogenesis and progression of multiple sclerosis (MS). Also, 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.

Keywords:

Multiple sclerosis , Homocysteine , B vitamins , Oxidative stress , Benign MS