Homocysteine, vitamin B12 and folate levels in Iranian patients with Multiple Sclerosis: A case control study

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Abstract

Background

Recently, homocysteine (Hcy), folate, and vitamin B12 have been proposed to have several roles on MS pathogenesis.

Objective

We performed this study to determine the role of serum levels of Hcy, vitamin B12, and folate in patients with relapsing remitting MS (RRMS) and compared them with healthy controls.

Methods

We recruited 75 RRMS patients and 75 subjects as controls with the same age and sex. Homocysteine was measured using fluorimetric high-performance liquid chromatography. Plasma folate and vitamin B12 levels were measured through ion-capture method.

Results

Mean plasma levels of vitamin B12, folate, and Hcy in cases were 342.64 ± 210.66 pg/ml, 9.74 ± 4.77 ng/ml, and 22.73 ± 11.63 μM/L, respectively, which showed significant difference in comparison with the controls. In addition, there were significant correlations between mean serum Hcy levels and duration of disease (r = 0.2, p = 0.05) and treatment with interferon (r = 0.21, p = 0.01). In cases, Hcy level was higher among those on β interferon (24.56 ± 11.87 vs. 19.71 ± 10.75, p = 0.01).

Conclusions

We concluded that serum levels of vitamin B12 and folate decreased in RRMS patients, but Hcy levels increased significantly. It seems necessary to conduct prospective trials to determine whether the treatment with supplements and correct biomarker levels in the early stage of the disease can change the course of the disease. We recommend regular checking of the serum level of Hcy in patients who use disease-modifying drugs.

Introduction

Multiple sclerosis (MS) is one of the most common neurological disorders, which is more prevalent in women and causes major morbidity in young adults [1]. It imposes an enormous economic burden on individual and society. Its prevalence differs based on geographic latitude of countries and increased in recent years [2]. The definite mechanism of MS is still unknown, but overt reaction of the immune system to environmental factors is a well-known causing factor [2], [3], [4]. Among these factors, recent studies are focused on the role of vitamin B12, folate, and homocysteine (Hcy).

Folate and vitamin B12 have fundamental roles in CNS function especially methionine synthase-mediated conversion of homocysteine to methionine, which is essential for synthesis of DNA and RNA (Fig. 1) [5], [6]. Therefore, B12 and folate deficiency can lead to an increased level of Hcy [6].

On the other hand, Hcy may have a neurotoxin effect that activates aspartate receptor, which leads to cell death [7], [8]. Some studies showed the relation between high level of serum Hcy and low levels of serum B12 and folate in the MS groups [9], [10], [11], [12]. By contrast, some reports found no significant difference in Hcy level between MS patients and controls [12], [13]. Therefore, there are some controversies on the role of Hcy, folate, and vitamin B12 on MS pathogenesis. It seems necessary to elucidate the potential mechanisms of evolving MS and correct them for preventing more disability. It may lead to decrease the burden of disease on the society and young patients. We carried this study to determine the role of serum levels of Hcy, vitamin B12, and folate in Iranian patients with relapsing-remitting MS and compared them with healthy controls.

Section snippets

Study population

This case control study was conducted at Rasool Akram Hospital affiliated to Tehran University of Medical Sciences, Tehran, Iran. The institutional medical ethics committee approved the study, and all patients and controls enrolled after signing their written informed consent. Seventy-five patients with diagnosis of relapsing-remitting MS (RRMS) were enrolled as cases (n = 75). All of them were in remission. The diagnosis of RRMS was based on revised McDonald Criteria diagnostic scheme [14]. Age-

Results

A total of 75 RRMS patients with a mean age of 31.97 ± 9.05 years entered the study; 57 of whom were female subjects (76%). We included 75 healthy controls with the same age and sex (p = NS). Baseline characteristics of the subjects are listed in Table 1. The mean EDSS in the MS group was 2.54 (range, 2.00–8.00). There was a significant association between the type of first symptom of disease and EDSS (p < 0.001). EDSS was lower in patients with optic neuritis and pyramidal symptoms than in patients

Discussion

The purpose of this case–control study was to elucidate the role of serum Hcy, folate, and vitamin B12 levels in RRMS. We concluded that serum levels of vitamin B12 and folate decreased in RRMS patients; however, Hcy level increased.

Our findings are consistent with the most previous studies, in which low folate and vitamin B12 levels were seen in MS patients. On the other hand, there are some controversies about the role of Hcy metabolism in MS [11], [15], [16], [17]. This study is in line with

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