|
 
 |
| ORIGINAL ARTICLE |
|
| Year : 2016 | Volume
: 53
| Issue : 2 | Page : 107-110 |
|
Vitamin D levels in a sample of Egyptian patients with multiple sclerosis
Dina A Zamzam1, Mohamed M Fouad1, Doaa A Elaidy1, Doaa M Abd-Elaziz2, Azza A Abd-Elaziz1
1 Department of Neurology, Faculty of Medicine, Ain Shams University, Cairo, Egypt
2 Department of Clinical Pathology, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| Date of Submission | 21-Jan-2016 |
| Date of Acceptance | 21-Feb-2016 |
| Date of Web Publication | 2-Jun-2016 |
Correspondence Address:
Mohamed M Fouad
MD, Department of Neurology and Psychiatry, Ain Shams University, Cairo
Egypt
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/1110-1083.183437
Background
Environmental factors such as vitamin D deficiency have been linked to the etiology of multiple sclerosis (MS) through interaction with genetic factors. Researches must be carried out to answer the question whether the relationship between vitamin D and MS is consistent and reproducible.
Objective
The aim of the present study was to assess the level of vitamin D in Egyptian MS patients.
Subjects and methods
In total, 111 patients with MS and 33 normal subjects were included in this study. Vitamin D level was estimated for each participant using the enzyme linked immunosorbent assay technique.
Results
Vitamin D levels were significantly lower among MS patients (ranging from 5 to 75 ng/ml with a mean ± SD of 26.4 ± 18.5) when compared with controls [ranging from 25 to 80 ng/ml with a mean of 51.2 ± 19.6 (P < 0.001)]. High expanded disability status scale scores were found to be related to low vitamin D levels.
Conclusion
Patients with MS tended to have lower vitamin D levels, and those with higher (expanded disability status scale) scores were more likely to have lower levels of vitamin D. Keywords: Egyptian, multiple sclerosis, vitamin D
How to cite this article:
Zamzam DA, Fouad MM, Elaidy DA, Abd-Elaziz DM, Abd-Elaziz AA. Vitamin D levels in a sample of Egyptian patients with multiple sclerosis. Egypt J Neurol Psychiatry Neurosurg 2016;53:107-10 |
How to cite this URL:
Zamzam DA, Fouad MM, Elaidy DA, Abd-Elaziz DM, Abd-Elaziz AA. Vitamin D levels in a sample of Egyptian patients with multiple sclerosis. Egypt J Neurol Psychiatry Neurosurg [serial online] 2016 [cited 2023 Nov 29];53:107-10. Available from: http://www.ejnpn.eg.net/text.asp?2016/53/2/107/183437 |
| Introduction | |  |
The racial and ethnic factors that influence the occurrence of multiple sclerosis (MS) have been a major concern in many studies, yet these factors are not exclusive for the prevalence of MS. The geographical or socioeconomic environmental factors, which can modify genetic susceptibility, play an important causal role in the pathogenesis of MS [1-3]. For example, an increased risk for MS was found in areas with low ultraviolet index such as high latitudes, which corresponds with the reduced ultraviolet B sun exposure and subsequently lower serum levels of vitamin D [4],[5]. Exposure to sunlight is essential for the transformation of 7-dehydrocholesterol in the skin into vitamin D3. The liver converts vitamin D3 into 25-hydroxyvitamin D3 [25(OH)D3], which circulates in the blood as a biologically inactive hormone precursor. Kidney, the immune system, the central nervous system (CNS), the intestinal tract, skin, and probably other tissues convert 25(OH)D3 into calcitriol. Calcitriol is a biologically active hormone that works by affecting the expression of particular genes, which in turn coordinates biological processes such as growth, metabolism, reproduction, and immunity [6].
There is a consistent and reproducible correlation and a logical timeline linking low vitamin D status [serum 25(OH)D] and high MS risk, frequent relapses, and rapid disease progression [7]. Children who took supplementary vitamin D3 had a lower risk of MS as adults. In addition, among MS patients living where serum vitamin D levels fluctuate seasonally, a winter drop in vitamin D usually precedes a spring surge in relapses [6].
| Aim of work | | |
This study aimed to detect the serum levels of vitamin D in an Egyptian sample of patients with MS.
| Subjects and methods | | |
This study was conducted in the MS unit of the Neurology Department, Ain Shams University Hospital. It included 111 patients with the diagnosis of MS and 33 age and sex matched healthy controls. Patients were recruited consecutively after their agreement to participate in the study. Neither patients nor controls were receiving vitamin D supplementation at the time of their enrolment. Patients had no past history of hepatic or renal troubles. At the time of blood withdrawal, patients had not been receiving any corticosteroid therapy during the last 3 months and did not show any evidence of relapse. All subjects gave their written informed consent before participation.
Vitamin D level was measured by using the sandwich enzyme linked immunosorbent assay technique (lot n. VDS4203; Calbiotech Inc., Austin Drive, Spring Vall, California, USA). The procedure was carried out according to the manufacturer's instruction, as supplied with kit. All biochemical measures were performed in a single batch and a comparable number of patient and control samples were always assayed simultaneously in the same enzyme linked immunosorbent assay plate. The kit recorded the result as deficient if vitamin D level was less than 10 ng/ml, insufficient if it ranged from 10 to 30 ng/ml, sufficient if it ranged from 30 to 100 ng/ml, and toxic if it was more than 100 ng/ml.
Statistical analysis
The collected data were coded, tabulated, and statistically analyzed using IBM SPSS statistics software, version 22.0 (2013; IBM Corp., Chicago, Illinois, USA). Descriptive statistics were carried out for quantitative data, which were presented as minimum and maximum of the range and mean ± SD, whereas qualitative data were presented as number and percentage. Inferential analyses were carried out using the independent t-test for the two independent groups with quantitative parametric data; the c2 -test was used for differences between independent proportions, whereas correlations were assessed using the partial correlation (controlling for skin type and sun exposure hours). Linear regression model was used to find out independent factors affecting vitamin D level. The level of significance was set at a P value of less than 0.05.
| Results | | |
Analysis of the demographic data showed that the MS patients included 26 males (23.4%) and 85 females (76.6%), and their age ranged from 16 to 53 years with mean age of 30.2 ± 8.2 years. On the other hand, the controls included 10 males (30.3%) and 23 females (69.7%), and their ages ranged from 24 to 55 years, with a mean age of 31.2 ± 7.3 years. Among the MS patients, 90 patients were relapsing remittent MS (RRMS), 18 patients were secondary progressive MS (SPMS), and three patients were primary progressive MS. The mean age at the onset of disease was 25.3 ± 7.4 years and the duration of illness ranged from 1 month to 24 years with a mean of 62.8 ± 55 months. Their expanded disability status scale (EDSS) scores ranged from 0 to 7.5, with a mean score of 3.1 ± 1.7.
Analysis of the laboratory data showed that vitamin D levels among MS patients ranged from 5 to 75 ng/ml with a mean value of 26.4 ± 18.5, whereas vitamin D levels among controls ranged from 25 to 80 ng/ml with a mean value of 51.2 ± 19.6, as shown in [Figure 1]. | Figure 1: Comparison between cases and control groups regarding serum vitamin D level.
Click here to view |
Vitamin D levels were significantly lower among MS patients when compared with healthy controls (P < 0.001). Vitamin D was deficient in 37 MS patients (33.3% of total MS patients), whereas none of the controls had deficient vitamin D levels. In total, 36 MS patients (32.4%) had insufficient vitamin D levels, whereas only seven controls (21.2%) had insufficient vitamin D levels. Sufficient vitamin D levels were detected for 38 patients (34.2%) and 26 controls (78.8%), as shown in [Table 1]. | Table 1: Comparison between cases and control groups regarding serum vitamin D level
Click here to view |
The comparison of vitamin D levels among RRMS and SPMS patients showed that vitamin D levels ranged from 5 to 75 ng/ml with a mean value of 29.6 ± 19 among RRMS patients, whereas it ranged from 6 to 25 ng/ml with a mean value of 12.8 ± 6.5 among SPMS patients. Vitamin D levels were significantly lower among RRMS patients when compared with SPMS patients (P < 0.001).
Data showed a significant negative correlation between vitamin D levels and EDSS scores (P < 0.001). There was no significant relationship between the vitamin D levels and any of the age at onset of disease, the number of relapses or the duration of disease.
| Discussion | | |
The results of the present study showed significant lower levels of vitamin D among MS patients compared with the controls; moreover, vitamin D levels were significantly lower among RRMS patients compared with SPMS patients, and vitamin D levels were inversely correlated to EDSS scores, which is in agreement with many studies. In a 5-year study, low vitamin D levels predicted higher MS activity, lesion load, brain atrophy, and clinical progression [8]. In adults and pediatrics, higher serum vitamin D levels correlated with fewer lesions and relapses. MS patients who began taking vitamin D supplementation had 33% fewer new MRI lesions for each 10 ng/ml increase in the serum vitamin D level [9],[10]. A case-controlled study demonstrated that the odds of having MS were lower in the group with the highest vitamin D levels [6]. The results of this study and the above-mentioned studies strengthen the role of vitamin D in the pathogenesis of MS and indicate that vitamin D3 might be a major conduit for environmentally directed protective mechanisms in MS.
Although Egypt is known for receiving ample sunshine for the most part of the year, the results showed vitamin D levels to be either deficient or insufficient in 65.7% of the patients and 21.2% of the controls. Low vitamin D levels are expected among the patients, but its incidence among controls should be investigated. The Middle East population show low levels of serum vitamin D, especially among females, low socioeconomic status, and urban living. This is in large part explained by limited sun exposure due to cultural practices or hot weather, and prolonged breast-feeding without a vitamin D supplementation [11]. In one international study conducted on women with osteoporosis, the highest proportion of hypovitaminosis D was reported in the Middle East [12].
It is important to note that in one study conducted in Norway, the Middle East immigrants had a higher prevalence of MS despite a shorter duration of residence than did other non-western patients. This can suggest that people from the Middle East have a high genetic disposition for MS and may point to the importance of an environmental factor such as ultraviolet exposure, and hence low vitamin D levels in the pathogenesis of MS [13].
There are some biological explanations for the link between vitamin D and MS. There is a possible role of vitamin D as a neuroprotective agent, and supports memory, cognition, neurotransmission, and neuroplasticity [14]. Vitamin D also opposes autoimmunity and inflammation in the CNS by reducing autoimmune T-cell access to the CNS, increasing autoimmune T-cell elimination from the CNS, and promoting the induction of T-regulatory cells, which maintain immunological self-tolerance [15],[16]. Vitamin D3 may also influence the HLA DRB1*1501 gene, the strongest genetic risk factor for MS [17].
Some researchers suggest that estrogen is important to enable the protective functions of vitamin D in females, especially in the CNS [18],[19]. The transition from RRMS to SPMS in females occurs around menopause [20]. If estrogen is essential to support vitamin D functions, then as estrogen declines, the protective benefits of both estrogen and vitamin D3 may be lost simultaneously. This can explain lower levels of vitamin D in patients with SPMS compared with those with RRMS in the present study. However, more research is needed to investigate this biological relationship and how it may influence the progression of MS in women.
It is clear that the design of this study was observational, which can only demonstrate associations and is susceptible to giving confounding results. Therefore, there is a need for larger scale multicenter randomized control trials to confirm the association between vitamin D deficiency and MS in the Egyptian population, trials that can balance the unmeasured confounding variables such as the duration of sun exposure, skin type, and adiposity. This recommended study can support a cause-effect relationship, and can assess whether altering vitamin D status affects MS severity.
A blood test for serum vitamin D level is appropriately recommended for every MS patients or even for those with clinically isolated syndrome. It may be beneficial for the MS patients with low vitamin D levels or limited sunlight exposure to have a daily vitamin D3 supplement. MS disease activity was found to be lowest among patients whose vitamin D levels were greater than 40 ng/ml, and thus this might be assumed as the target level [21]. Vitamin D level is influenced by seasonal variations, latitude, sun exposure, skin pigmentation, and genetics [22],[23]. Consequently, individuals differ in the vitamin D3 supplement needed to achieve the target level. Serum level of vitamin D shall be checked after 2-3 months from the initiation of the supplement therapy, and if the level is found to be below the target, a gradual vitamin D3 dose escalation with intermittent rechecking will identify the daily vitamin D3 supplement needed [23]. MS patients safely can take 14 000 IU/day [21].
Two randomized, controlled studies have reported a beneficial effects of vitamin D supplementation in MS patients. MS patients in a Canadian study, who took an average of 14 000 IU/day of vitamin D3, had fewer relapses and less disability progression over the course of 1 year [21]. A Finnish study found that patients who received vitamin D3, in a dose 20 000 IU weekly, had 85% fewer new MRI lesions, lower total lesion burden, and reduced EDSS, in addition to improved timed 10-foot tandem walk scores over the course of 1 year [24].
Another important and applicable advice is for MS patients to have a daily sun exposure; a single exposure to the summer sun in a bathing suit for 20 min produces the equivalent of 15 000-20 000 IU of vitamin D3 [25].
| Conclusion | | |
Patients with MS tended to have lower vitamin D levels; in addition, those with higher EDSS scores were more likely to have lower levels of vitamin D. Despite ample sunshine in Egypt, it appears that many Egyptian MS patients have vitamin D deficiency or insufficiency, which points to the role of vitamin D in the pathogenesis of MS and the activity of the disease. This study may lead a neurologist to consider vitamin D assessment in every MS or even clinically isolated syndrome patient, and to consider vitamin D supplementation and recommend adequate sun exposure if needed.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
| References | | |
| 1. | Rosati G. The prevalence of multiple sclerosis in the world: an update. Neurol Sci 2001; 22 :117-139.  |
| 2. | Bohlega S, Inshasi J, Al Tahan AR, Madani AB, Qahtani H, Rieckmann P. Multiple sclerosis in the Arabian Gulf countries: a consensus statement. J Neurol 2013; 260 :2959-2963. |
| 3. | Ebers G. Interactions of environment and genes in multiple sclerosis. J Neurol Sci 2013; 334 :161-163. |
| 4. | Sloka JS, Pryse-Phillips WE, Stefanelli M. The relation of ultraviolet radiation and multiple sclerosis in Newfoundland. Can J Neurol Sci 2008; 35 :69-74. |
| 5. | Beretich BD, Beretich TM. Explaining multiple sclerosis prevalence by ultraviolet exposure: a geospatial analysis. Mult Scler 2009; 15 :891-898. |
| 6. | Munger KL, Levin LI, Hollis BW, Howard NS, Ascherio A. Serum 25-hydroxyvitamin D levels and risk of multiple sclerosis. JAMA 2006; 296 :2832-2838. |
| 7. | Hayes CE, Nashold FE, Mayne CG, Spanier JA, Nelson CD. Vitamin D. and multiple sclerosis. In: Feldman D, Pike JW, Adams JS, editors. Vitamin D. 3rd ed. San Diego, California: Elsevier; 2011. 1843-1877. |
| 8. | Ascherio A, Munger KL, White R, Köchert K, Simon KC, Polman CH, et al. Vitamin D as an early predictor of multiple sclerosis activity and progression. JAMA Neurol 2014; 71 :306-314. |
| 9. | Simpson S Jr, Taylor B, Blizzard L, Ponsonby AL, Pittas F, Tremlett H, et al. Higher 25-hydroxyvitamin D is associated with lower relapse risk in multiple sclerosis. Ann Neurol 2010; 68 :193-203. |
| 10. | Mowry EM, Waubant E, McCulloch CE, Okuda DT, Evangelista AA, Lincoln RR, et al. Vitamin D status predicts new brain magnetic resonance imaging activity in multiple sclerosis. Ann Neurol 2012; 72 :234-240. |
| 11. | Al-Mohaimeed A, Khan NZ, Naeem Z, Al-Mogbe E, Vitamin D. status among women in Middle East. J Health Sci 2012; 2 :49-56. |
| 12. | Lips P. Vitamin D physiology. Prog Biophys Mol Biol 2006; 92 :4-8. |
| 13. | Smestad C, Sandvik L, Holmoy T, Harbo HF, Celius EG. Marked differences in prevalence of multiple sclerosis between ethnic groups in Oslo, Norway. J Neurol 2008; 255 :49-55. |
| 14. | DeLuca GC, Kimball SM, Kolasinski J, Ramagopalan SV, Ebers GC. Review: the role of vitamin D in nervous system health and disease. Neuropathol Appl Neurobiol 2013; 39 :458-484. |
| 15. | Kang SW, Kim SH, Lee N, Lee WW, Hwang KA, Shin MS, et al. 1,25-Dihyroxyvitamin D3 promotes FOXP3 expression via binding to vitamin D response elements in its conserved non coding sequence region. J Immunol 2012; 188 : 5276-5282. |
| 16. | Nashold FE, Nelson CD, Brown LM, Hayes CE. One calcitriol dose transiently increases Helios+ FoxP3+ T cells and ameliorates autoimmune demyelinating disease. J Neuroimmunol 2013; 263 :64-74. |
| 17. | Ramagopalan SV, Maugeri NJ, Handunnetthi L, Lincoln MR, Orton SM, Dyment DA, et al. Expression of the multiple sclerosis-associated MHC class II Allele HLA-DRB1FNx011501 is regulated by vitamin D. PLoS Genet 2009; 5 :e1000369. |
| 18. | Kragt J, van Amerongen B, Killestein J, Dijkstra C, Uitdehaag B, Polman CH, Lips P. Higher levels of 25-hydroxyvitamin D are associated with a lower incidence of multiple sclerosis only in women. Mult Scler 2009; 15 :9-15. |
| 19. | Correale J, Ysrraelit MC, Gaitán MI. Gender differences in 1,25 dihydroxyvitamin D3 immunomodulatory effects in multiple sclerosis patients and healthy subjects. J Immunol 2010; 185 : 4948-58. |
| 20. | Tutuncu M, Tang J, Zeid NA, Kale N, Crusan DJ, Atkinson EJ, et al. Onset of progressive phase is an age-dependent clinical milestone in multiple sclerosis. Mult Scler 2013; 19 :188-98. |
| 21. | Burton JM, Kimball S, Vieth R, Bar-Or A, Dosch HM, Cheung R, et al. A phase I/II dose-escalation trial of vitamin D3 and calcium in multiple sclerosis. Neurology 2010; 74 :1852-1859. |
| 22. | Ahn J, Yu K, Stolzenberg-Solomon R, Simon KC, McCullough ML, Gallicchio L, et al. Genome-wide association study of circulating vitamin D levels. Hum Mol Genet 2010; 19 :2739-45. |
| 23. | Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon CM, Hanley DA, Heaney RP, et al. Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2011; 96 :1911-1930. |
| 24. | Soilu-Hänninen M, Aivo J, Lindström BM, Elovaara I, Sumelahti ML, Färkkilä M, et al. A randomised, double blind, placebo controlled trial with vitamin D3 as an add on treatment to interferon β-1b in patients with multiple sclerosis. J Neurol Neurosurg Psychiatry 2012; 83 :565-71. |
| 25. | Thacher TD, Clarke BL. Vitamin D insufficiency. Mayo Clin Proc 2011; 8:50-60. |
[Figure 1]
[Table 1]
|
Search Pubmed for