Table 1.

Data of the main studies of homocysteine level in relapsing-remitting multiple sclerosis (RRMS), secondary-progressive multiple sclerosis (SPMS), primary-progressive multiple sclerosis (PPMS), and clinically isolated syndrome (CIS) patients.

Disease	Results of the Study	Authors
MS	No significant differences in the homocysteine serum levels between the MS group and healthy subjects.	Rio et al., 1994 [52]
MS	The increases in homocysteine in both the serum and CSF levels compared with healthy subjects.	Baig et al., 1995 [53]
RRMS SPMS PPMS	The increases in the homocysteine plasma levels in RRMS, SPMS, and PPMS patients (overall) compared with healthy subjects. No significant differences in the CSF homocysteine levels between the MS patients (overall) and the control group.	Vrethem et al., 2003 [54]
SPMS	The increases in the homocysteine plasma level in SPMS patients compared with healthy subjects.	Besler et al., 2003 [55]
RRMS SPMS	The increases in the homocysteine serum levels in RRMS and MS patients (overall) compared with healthy subjects.	Ashtari et al., 2005 [56]
RRMS SPMS PPMS	The increases in the homocysteine plasma levels in RRMS, SPMS, and PPMS patients compared with healthy subjects. No significant differences in the homocysteine plasma levels in MS patients, depending on the type of MS course.	Ramsaransing et al., 2006 [37]
RRMS	The increases in the homocysteine plasma levels in RRMS patients compared with healthy subjects.	Sahin et al., 2007 [57]
RRMS SPMS PPMS	The increases in the homocysteine plasma levels in RRMS, SPMS, and PPMS patients (overall) compared with healthy subjects. Association of a high homocysteine plasma level with cognitive impairment in MS patients (overall).	Russo et al., 2008 [47]
RRMS	The increases in the homocysteine plasma level in RRMS patients compared with healthy subjects.	Aksungar et al., 2008 [58]
RRMS	The increases in the homocysteine serum level in RRMS patients compared with healthy subjects. Association of a high homocysteine serum level with depression in RRMS patients.	Triantafyllou et al., 2008 [59]
RRMS SPMS PPMS	No significant differences in the homocysteine serum levels between the RRMS, SPMS, and PPMS groups (overall) and healthy subjects. No significant differences in the homocysteine plasma levels in MS patients, depending on the type of MS course. The increases in the homocysteine serum levels in male RRMS and SPMS patients compared with female RRMS and SPMS patients.	Teunissen et al., 2008 [49]
RRMS SPMS PPMS	No significant differences in the homocysteine serum levels between the RRMS, SPMS and PPMS groups (overall) and healthy subjects.	Kocer et al., 2009 [60]
RRMS SPMS	The increases in the homocysteine plasma levels in RRMS and SPMS patients (overall) compared with healthy subjects.	Salemi et al., 2010 [38]
RRMS SPMS PPMS	The increases in the homocysteine serum levels in RRMS, SPMS, and PPMS patients (overall) compared with the control group.	Zhu et al., 2011 [61]
RRMS SPMS PPMS CIS	The increases in the homocysteine plasma levels in RRMS, SPMS, PPMS, CIS patients (overall) compared with the control group. The increases in the homocysteine plasma level in male patients (overall) compared with female patients (overall). The decreases in the homocysteine plasma level in CIS patients compared with RRMS, SPMS, and PPMS patients. Association of a high homocysteine plasma level with the duration of disease.	Zoccolella et al., 2012 [51]
RRMS	The increases in the homocysteine plasma level in RRMS patients compared with healthy subjects. Association of a high homocysteine plasma level with the duration of disease and treatment with interferon in RRMS patients.	Moghaddasi et al., 2013 [39]
RRMS SPMS PPMS CIS	No significant differences in the homocysteine serum levels between the RRMS, SPMS, PPMS, and CIS patients (overall) and healthy subjects. No significant differences in the homocysteine serum levels between the RRMS and SPMS groups. No significant differences in the homocysteine serum levels between the treatment (with DMT) and non-treatment patients. The increases in the homocysteine serum level in male patients (overall) compared with female patients (overall).	Kararizou et al., 2013 [62]
RRMS	The increases in the homocysteine plasma level in males compared with females in both RRMS patients and healthy subjects.	Davis et al., 2014 [63]
RRMS RRMS (relapse) SPMS PPMS	The increases in the homocysteine plasma levels in RRMS patients during relapse compared with RRMS patients during remission and SPMS and PPMS patients. No significant differences in the homocysteine serum levels between the RRMS, SPMS, PPMS, and CIS patients (overall) and healthy subjects.	Adamczyk-Sowa et al., 2016 [64]
MS	No significant differences in the homocysteine serum levels between MS patients and healthy subjects. Association of a high homocysteine serum level with the cognitive impairments in MS patients.	Fahmy et al., 2018 [48]
RRMS SPMS PPMS	The increases in the homocysteine plasma levels in RRMS, SPMS, and PPMS patients (overall) compared with healthy subjects. The increases in the homocysteine plasma level in RRMS patients compared with SPMS and PPMS patients (overall). The increases in the ICAM-1 plasma levels in MS patients (overall) with higher homocysteine levels compared to the MS patients (overall) with lower homocysteine plasma levels.	Oliveira et al., 2018 [40]
MS	The increases in the homocysteine serum levels in RRMS patients during relapse compared with healthy subjects.	Pan et al., 2019 [65]
RRMS	The improvement with vitamin B12 and folic acid decreases in the homocysteine serum levels in RRMS patients.	Nozari et al., 2019 [66]
RRMS SPMS	The increases in the homocysteine serum levels in RRMS and SPMS patients compared with healthy subjects. Cladribine treatment decreases in homocysteine serum levels in SPMS patients.	Jamroz-Wiśniewska et al., 2020 [67]
RRMS SPMS PPMS	The increases in the homocysteine plasma levels in RRMS, SPMS, and PPMS patients (overall) with an EDSS score ≥3.	Flauzino et al., 2019 [68]
RRMS SPMS PPMS	The increases in the homocysteine serum levels in RRMS patients compared with healthy controls. No significant differences in the homocysteine serum levels between the SPMS and PPMS groups and healthy controls.	Li et al., 2020 [69]