A systematic review of modifiable risk factors in the progression of multiple sclerosis

Background: The presenting symptoms and rate of progression of multiple sclerosis (MS) are very heterogeneous. The diverse clinical manifestations and the clinical course of the disease may vary with modifiable risk factors. Objective: To systematically review modifiable risk factors and exposures associated with MS progression. Methods: We searched six databases till March 2015, reference-mined reviews, and consulted with experts (PROSPERO 2015:CRD42015016461). Two reviewers screened and extracted data. We used random meta-analysis models and Grading of Recommendations Assessment, Development, and Evaluation (GRADE) to assess the quality of evidence. Results: In total, 59 studies met inclusion criteria. Lower vitamin D levels were associated with higher Expanded Disability Status Scale (EDSS) scores ( r = −0.22; confidence interval (CI) = −0.32, −0.12; 11 studies; I2 = 66%), smokers had an increased risk of MS progression (hazard ratio (HR) = 1.55; CI = 1.10, 2.19; I2 = 72%; seven studies), and there was no association of MS progression with the use of epidural analgesics during childbirth delivery (three studies). There was insufficient evidence to draw conclusions for 11 risk factors due to conflicting results or use of different predictor and outcome measures. Conclusion: MS progression was consistently associated with low vitamin D levels, and smoking was associated with a more rapid decline in MS disability. Studies used a variety of methods, predictors, and outcomes making it difficult to draw conclusions. Future studies should focus on prospective assessments.

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Prenatal vitamin D status and offspring’s growth, adiposity and metabolic health: a systematic review and meta-analysis

British Journal Of Nutrition ◽

10.1017/s0007114517003646 ◽

2018 ◽

Vol 119 (3) ◽

pp. 310-319 ◽

Cited By ~ 14

Author(s):

Christina Santamaria ◽

Wei Guang Bi ◽

Line Leduc ◽

Negar Tabatabaei ◽

Prévost Jantchou ◽

...

Keyword(s):

Systematic Review ◽

Vitamin D ◽

Observational Studies ◽

Growth Parameters ◽

Meta Analysis ◽

Metabolic Health ◽

Vitamin D Status ◽

Increased Risk ◽

Vitamin D Levels ◽

Offspring Growth

AbstractIn this systematic review and meta-analysis of observational studies, we aimed to estimate the associations between prenatal vitamin D status and offspring growth, adiposity and metabolic health. We searched the literature in human studies on prenatal vitamin D status and offspring growth in PubMed, up to July 2017. Studies were selected according to their methodological quality and outcomes of interest (anthropometry, fat mass and diabetes in offspring). The inverse variance method was used to calculate the pooled mean difference (MD) with 95 % CI for continuous outcomes, and the Mantel–Haenszel method was used to calculate the pooled OR with 95 % CI for dichotomous outcomes. In all, thirty observational studies involving 35 032 mother–offspring pairs were included. Vitamin D status was evaluated by circulating 25-hydroxyvitamin D (25(OH)D) level. Low vitamin D status was based on each study’s cut-off for low 25(OH)D levels. Low prenatal vitamin D levels were associated with lower birth weight (g) (MD −100·69; 95 % CI −162·25, −39·13), increased risk of small-for-gestational-age (OR 1·55; 95 % CI 1·16, 2·07) and an elevated weight (g) in infant at the age of 9 months (g) (MD 119·75; 95 % CI 32·97, 206·52). No associations were observed between prenatal vitamin D status and other growth parameters at birth, age 1 year, 4–6 years or 9 years, nor with diabetes type 1. Prenatal vitamin D may play a role in infant adiposity and accelerated postnatal growth. The effects of prenatal vitamin D on long-term metabolic health outcomes in children warrant future studies.

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Association of 25-hydroxyvitamin D with cardiometabolic risk factors and metabolic syndrome: a mendelian randomization study

Nutrition Journal ◽

10.1186/s12937-019-0494-7 ◽

2019 ◽

Vol 18 (1) ◽

Cited By ~ 3

Author(s):

Chi Chen ◽

Yi Chen ◽

Pan Weng ◽

Fangzhen Xia ◽

Qin Li ◽

...

Keyword(s):

Risk Factors ◽

Metabolic Syndrome ◽

Vitamin D ◽

Cardiometabolic Risk ◽

Mendelian Randomization ◽

Cardiometabolic Risk Factors ◽

Metabolic Traits ◽

Increased Risk ◽

Vitamin D Levels ◽

Genetically Determined

Abstract Background Low circulating vitamin D levels have been associated with increased risk of metabolic syndrome (MS) and cardiometabolic risk factors in multiple epidemiology studies. However, whether this association is causal is still unclear. We aimed to test whether genetically lowered vitamin D levels were associated with MS and its metabolic traits, using mendelian randomization (MR) methodology. Methods Ten thousand six hundred fifty-five participants were enrolled from the SPECT-China study, which was performed in 23 sites in East China during 2014 to 2016. Using four single-nucleotide polymorphisms (SNPs) in the DHCR7, CYP2R1, GC and CYP24A1 genes with known effects on 25(OH) D concentrations, we created a genetic risk score (GRS) as instrumental variable (IV) to estimate the effect of genetically lowered 25(OH) D on MS and cardiometabolic risk factors. MS was defined according to the International Diabetes Federation criteria. Results Lower measured 25(OH)D levels were associated with MS (OR 0.921, 95% CI 0.888, 0.954) after multivariable adjustment. However, the MR-derived odds ratio of genetically determined 25(OH) D for risk of MS was 0.977 (95% CI 0.966, 1.030). The MR-derived estimates for raised fasting plasma glucose was 0.578 (95% CI 0.321, 0.980) per 10 nmol/L GRSsynthesis determined increase of 25(OH) D levels. Conclusions We found no evidence that genetically determined reduction in 25(OH)D conferred an increased risk of MS and its metabolic traits. However, we created our GRS only on the basis of common variants, which represent limited amount of variance in 25(OH)D. MR studies using rare variants, and large-scale well-designed RCTs about the effect of vitamin D supplementation on MS are warranted to further validate the findings.

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Polymorphisms CYP2R1 rs10766197 and CYP27B1 rs10877012 in Multiple Sclerosis: A Case-Control Study

Journal of Immunology Research ◽

10.1155/2021/7523997 ◽

2021 ◽

Vol 2021 ◽

pp. 1-11

Author(s):

A. Martinez-Hernandez ◽

E. E. Perez-Guerrero ◽

M. A. Macias-Islas ◽

C. A. Nava-Valdivia ◽

A. Villagomez-Vega ◽

...

Keyword(s):

Multiple Sclerosis ◽

Vitamin D ◽

Disease Progression ◽

Case Control Study ◽

Case Control ◽

Nucleotide Polymorphisms ◽

Increased Risk ◽

Vitamin D Levels ◽

25 Oh Vitamin D ◽

Control Study

Background. Multiple sclerosis (MS) is a chronic autoimmune inflammatory disease. Low vitamin D levels have been reported to be a risk factor for MS, and genetic variances could be implicated. The aim of this study was to evaluate the association of MS with rs10766197 polymorphism of CYP2R1 gene and rs10877012 polymorphism of CYP27B1 gene. The second aim was to analyse whether these polymorphisms are associated with the severity of the progression of MS. Material and Methods. In a case-control study, we included 116 MS patients and 226 controls, all of whom were Mexican Mestizo. MS was diagnosed by McDonald criteria (2017). A complete neurological evaluation was performed to evaluate the severity of disease progression. Serum 25-hydroxyvitamin D [25(OH) vitamin D] levels were measured by ELISA. Single nucleotide polymorphisms rs10766197 of CYP2R1 gene and rs10877012 SNP of CYP27B1 gene were genotyped by real-time PCR. Results. Serum 25(OH) vitamin D levels were lower in MS patients than in controls ( p = 0.009 ). No differences were observed between serum 25(OH) vitamin D levels of MS patients with severe progression compared to low progression ( p = 0.88 ). A higher frequency of the A allele of CYP2R1 rs10766197 was observed between MS patients and controls ( p = 0.05 ). No differences were observed in the frequency of T allele of CYP27B1 rs10877012 ( p = 0.65 ). In subanalysis, patients with GA + AA genotypes of CYP2R1 rs10766197 had an increased risk of MS compared to controls ( p = 0.03 ). No increased risk was observed in GT + TT genotypes of CYP27B1 rs10877012 ( p = 0.63 ). No differences were observed in allele frequencies of either polymorphism between patients with severe vs. low disease progression. Conclusion. Lower serum 25(OH) vitamin D levels were observed in MS patients than in controls, although these levels were not associated with disease progression. Carriers of GA + AA genotypes of CYP2R1 rs10766197 had an increased risk of MS. None of these polymorphisms was associated with severe progression of MS.

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Season of birth is associated with multiple sclerosis and disease severity

Multiple Sclerosis Journal - Experimental Translational and Clinical ◽

10.1177/20552173211065730 ◽

2021 ◽

Vol 7 (4) ◽

pp. 205521732110657

Author(s):

P Stridh ◽

J Huang ◽

AK Hedström ◽

L Alfredsson ◽

T Olsson ◽

...

Keyword(s):

Multiple Sclerosis ◽

Vitamin D ◽

Severe Disease ◽

Winter Season ◽

Sun Exposure ◽

Month Of Birth ◽

Multiple Sclerosis Risk ◽

Increased Risk ◽

Vitamin D Levels ◽

Early Fall

Background The latitude gradient in multiple sclerosis incidence indicates that low sun exposure and therefore vitamin D deficiency is associated with multiple sclerosis risk. Objective Investigation of the effect of month of birth, which influences postnatal vitamin D levels, on multiple sclerosis risk and severity in Sweden. Methods Patients and population-based controls were included from three nationwide cohorts. Differences in month of birth between cases and controls were analyzed using logistic regression and examined for effect modification by calendar year and geographic region at birth. Results Males had a reduced risk of multiple sclerosis if born in the winter and increased risk if born in the early fall. Individuals born before 1960 had an increased risk if born in summer or fall. Being born in late summer and early fall was associated with more severe disease. Conclusions We identified a birth cohort effect on the association between the month of birth and multiple sclerosis, with a more significant effects for births before 1960. This coincides with a period of lower breastfeeding rates, recommended intake of vitamin D, and sun exposure, resulting in a lower vitamin D exposure during the fall/winter season for infants born in the summer.

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Vitamin D Status and SARS-CoV-2 Infection and COVID-19 Clinical Outcomes

Frontiers in Public Health ◽

10.3389/fpubh.2021.736665 ◽

2021 ◽

Vol 9 ◽

Author(s):

Iacopo Chiodini ◽

Davide Gatti ◽

Davide Soranna ◽

Daniela Merlotti ◽

Christian Mingiano ◽

...

Keyword(s):

Intensive Care Unit ◽

Vitamin D ◽

Intensive Care ◽

Meta Analysis ◽

Vitamin D Status ◽

Icu Admission ◽

Primary Endpoints ◽

Severe Deficiency ◽

Increased Risk ◽

Vitamin D Levels

Background: Several studies suggest an association between serum 25-hydroxyvitamin D (25OHD) and the outcomes of Severe Acute Respiratory Syndrome Corona-Virus-2 (SARS-CoV-2) infection, in particular Coronavirus Disease-2019 (COVID-19) related severity and mortality. The aim of the present meta-analysis was to investigate whether vitamin D status is associated with the COVID-19 severity, defined as ARDS requiring admission to intensive care unit (ICU) or mortality (primary endpoints) and with the susceptibility to SARS-CoV-2 and COVID-19-related hospitalization (secondary endpoints).Methods: A search in PubMed, ScienceDirect, Web of Science, Google Scholar, Scopus, and preprints repositories was performed until March 31th 2021 to identify all original observational studies reporting association measures, or enough data to calculate them, between Vitamin D status (insufficiency <75, deficiency <50, or severe deficiency <25 nmol/L) and risk of SARS-CoV-2 infection, COVID-19 hospitalization, ICU admission, or death during COVID-19 hospitalization.Findings: Fifty-four studies (49 as fully-printed and 5 as pre-print publications) were included for a total of 1,403,715 individuals. The association between vitamin D status and SARS-CoV2 infection, COVID-19 related hospitalization, COVID-19 related ICU admission, and COVID-19 related mortality was reported in 17, 9, 27, and 35 studies, respectively. Severe deficiency, deficiency and insufficiency of vitamin D were all associated with ICU admission (odds ratio [OR], 95% confidence intervals [95%CIs]: 2.63, 1.45–4.77; 2.16, 1.43–3.26; 2.83, 1.74–4.61, respectively), mortality (OR, 95%CIs: 2.60, 1.93–3.49; 1.84, 1.26–2.69; 4.15, 1.76–9.77, respectively), SARS-CoV-2 infection (OR, 95%CIs: 1.68, 1.32–2.13; 1.83, 1.43–2.33; 1.49, 1.16–1.91, respectively) and COVID-19 hospitalization (OR, 95%CIs 2.51, 1.63–3.85; 2.38, 1.56–3.63; 1.82, 1.43–2.33). Considering specific subgroups (i.e., Caucasian patients, high quality studies, and studies reporting adjusted association estimates) the results of primary endpoints did not change.Interpretations: Patients with low vitamin D levels present an increased risk of ARDS requiring admission to intensive care unit (ICU) or mortality due to SARS-CoV-2 infection and a higher susceptibility to SARS-CoV-2 infection and related hospitalization.

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The prevention of infection

The Bone & Joint Journal ◽

10.1302/0301-620x.101b1.bjj-2018-0233.r1 ◽

2019 ◽

Vol 101-B (1_Supple_A) ◽

pp. 3-9 ◽

Cited By ~ 24

Author(s):

V. K. Alamanda ◽

B. D. Springer

Keyword(s):

Risk Factors ◽

Staphylococcus Aureus ◽

Vitamin D ◽

Glycaemic Control ◽

Operating Room ◽

Joint Infection ◽

High Morbidity ◽

Modifiable Risk Factors ◽

Skin Preparation ◽

Vitamin D Levels

AimsProsthetic joint infection (PJI) remains a serious complication that is associated with high morbidity and costs. The aim of this study was to prepare a systematic review to examine patient-related and perioperative risk factors that can be modified in an attempt to reduce the rate of PJI.Materials and MethodsA search of PubMed and MEDLINE was conducted for articles published between January 1990 and February 2018 with a combination of search terms to identify studies that dealt with modifiable risk factors for reducing the rate of PJI. An evidence-based review was performed on 12 specific risk factors: glycaemic control, obesity, malnutrition, smoking, vitamin D levels, preoperative Staphylococcus aureus screening, the management of anti-rheumatic medication, perioperative antibiotic prophylaxis, presurgical skin preparation, the operating room environment, irrigant options, and anticoagulation.ResultsPoor glycaemic control, obesity, malnutrition, and smoking are all associated with increased rates of PJI. Vitamin D replacement has been shown in preliminary animal studies to decrease rates of PJI. Preoperative Staphylococcus aureus screening and appropriate treatment results in decreased rates of PJI. Perioperative variables, such as timely and appropriate dosage of prophylactic antibiotics, skin preparation with chlorohexidine-based solution, and irrigation with dilute betadine at the conclusion of the operation, have all been associated with reduced rates of PJI. Similarly, aggressive anticoagulation and increased operating room traffic should be avoided to help minimize risk of PJI.ConclusionPJI remains a serious complication of arthroplasty. Surgeons should be vigilant of the modifiable risk factors that can be addressed in an attempt to reduce the risk of PJI.

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Association between vitamin D receptor (VDR) polymorphisms and the risk of multiple sclerosis (MS): an updated meta-analysis

BMC Neurology ◽

10.1186/s12883-019-1577-y ◽

2019 ◽

Vol 19 (1) ◽

Cited By ~ 7

Author(s):

Danyal Imani ◽

Bahman Razi ◽

Morteza Motallebnezhad ◽

Ramazan Rezaei

Keyword(s):

Multiple Sclerosis ◽

Vitamin D ◽

Gene Polymorphisms ◽

Genetic Model ◽

Meta Analysis ◽

Case Control ◽

Case Control Studies ◽

Asian Populations ◽

Increased Risk ◽

Apai Polymorphism

Abstract Background The association between the Vitamin D Receptor (VDR) gene polymorphism and the risk of Multiple sclerosis (MS) has been evaluated in several researches. However, the findings were inconsistent and inconclusive. Therefore, we set out a meta-analysis of all eligible published case-control studies to obtain an exact evaluation of the association between VDR gene polymorphisms and MS. Method All relevant studies reporting the association between the VDR gene FokI (rs2228570), or/and TaqI (rs731236) or/and BsmI (rs1544410) or/and ApaI (rs7975232) polymorphisms and susceptibility to MS published up to May, 2019 were identified by comprehensive systematic search in the electronic database of web of science, Scopus, and PubMed. After that, the strength of association between VDR gene polymorphisms and susceptibility to MS was evaluated by odds ratio (OR) and 95% confidence interval (CI). Results A total of 30 case–control studies were included in the meta-analysis. The overall results suggested a significant association between TaqI polymorphism and MS risk under heterozygote genetic model (OR = 1.27, 95%CI = 1.01–1.59, random effect). Moreover, the pooled results of subgroup analysis declined presence of significant association under all defined genetic model. In subgroup analysis, BsmI polymorphisms was associated with increased risk of MS under recessive model in Asian populations. On the other hand, ApaI polymorphism was associated with decreased risk of MS under recessive and aa vs. AA model in Asian populations. Conclusion This meta-analysis suggested a significant association between TaqI polymorphism and MS susceptibility. Furthermore, BsmI polymorphism was associated with increased risk of MS in Asian populations. In contrast, ApaI polymorphism was associated with decreased risk of MS in Asian populations. Future large-scale studies on gene–environment and gene–gene interactions are required to estimate risk factors and assist early diagnosis of patients at high risk for MS.

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Modifiable factors influencing relapses and disability in multiple sclerosis

Multiple Sclerosis Journal ◽

10.1177/1352458510367721 ◽

2010 ◽

Vol 16 (7) ◽

pp. 773-785 ◽

Cited By ~ 46

Author(s):

MB D'hooghe ◽

G. Nagels ◽

V. Bissay ◽

J. De Keyser

Keyword(s):

Multiple Sclerosis ◽

Vitamin D ◽

Life Events ◽

Strong Evidence ◽

Stressful Life Events ◽

Stressful Life ◽

Fertility Treatment ◽

Increased Risk ◽

Vitamin D Levels ◽

Modifiable Factors

A growing body of literature indicates that the natural course of multiple sclerosis can be influenced by a number of factors. Strong evidence suggests that relapses can be triggered by infections, the postpartum period and stressful life events. Vaccinations against influenza, hepatitis B and tetanus appear to be safe. Surgery, general and epidural anaesthesia, and physical trauma are not associated with an increased risk of relapses. Factors that have been associated with a reduced relapse rate are pregnancy, exclusive breastfeeding, sunlight exposure and higher vitamin D levels. A number of medications, including hormonal fertility treatment, seem to be able to trigger relapses. Factors that may worsen progression of disability include stressful life events, radiotherapy to the head, low levels of physical activity and low vitamin D levels. Strong evidence suggests that smoking promotes disease progression, both clinically and on brain magnetic resonance imaging. There is no evidence for an increased progression of disability following childbirth in women with multiple sclerosis. Moderate alcohol intake and exercise might have a neuroprotective effect, but this needs to be confirmed.

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Toward Understanding of Environmental Risk Factors in Systemic Sclerosis

Journal of Cutaneous Medicine and Surgery ◽

10.1177/1203475420957950 ◽

2020 ◽

pp. 120347542095795

Author(s):

Lydia Ouchene ◽

Anastasiya Muntyanu ◽

Jérôme Lavoué ◽

Murray Baron ◽

Ivan V. Litvinov ◽

...

Keyword(s):

Risk Factors ◽

Vitamin D ◽

Systemic Sclerosis ◽

Organic Solvents ◽

Epoxy Resins ◽

Twin Studies ◽

Breast Implants ◽

Welding Fumes ◽

Increased Risk ◽

Vitamin D Levels

Importance Systemic sclerosis (SSc) is a severe, chronic, and incurable autoimmune fibrotic skin disease with significant extracutaneous involvement. Low concordance rate in twin studies and unequal geographic distribution of SSc argues for importance of environment in disease initiation and progression. Objective In this manuscript we provide a summary of all investigated potential external risk factors for SSc. Data sources A literature search in PubMed and EMBASE database was performed for studies published until January 1, 2020 by 2 reviewers (EN and LO) independently. Findings Occupational and/or environmental exposures to silica and organic solvents are associated with increased incidence and severity of SSc. Exposure to epoxy resins, asbestos, and particulate air pollution favors increased risk of SSc, but data are based on limited number of observational studies. There is insufficient evidence to conclude an association between SSc development and other occupational (eg, welding fumes) or personal exposures (eg, smoking, vitamin D deficiency). Association of SSc with silicone breast implants has been disproven. Infectious pathogens (eg, Helicobacter pylori and angiotropic viruses) and dysbiosis seem to play a role in SSc development and severity, but their role remains to be clarified. Conclusions and relevance It may be prudent to counsel our patients with SSc (or those at risk of SSc) to avoid occupations with exposure to silica, organic solvents, asbestos and epoxy resins; restraint from smoking, using cocaine or drugs with pro-fibrotic potential. While the association between low vitamin D and SSc remains to be confirmed, we believe that SSc patients should be encouraged to maintain healthy vitamin D levels as benefits outweigh the risks.

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Timing of use of cod liver oil, a vitamin D source, and multiple sclerosis risk: The EnvIMS study

Multiple Sclerosis Journal ◽

10.1177/1352458515578770 ◽

2015 ◽

Vol 21 (14) ◽

pp. 1856-1864 ◽

Cited By ~ 28

Author(s):

Marianna Cortese ◽

Trond Riise ◽

Kjetil Bjørnevik ◽

Trygve Holmøy ◽

Margitta T Kampman ◽

...

Keyword(s):

Multiple Sclerosis ◽

Vitamin D ◽

Inverse Association ◽

Cod Liver Oil ◽

Dose Response Relationship ◽

Supplement Use ◽

Multiple Sclerosis Risk ◽

Increased Risk ◽

Vitamin D Levels ◽

Control Study

Background: Low vitamin D levels have been associated with an increased risk of multiple sclerosis (MS), although it remains unknown whether this relationship varies by age. Objective: The objective of this paper is to investigate the association between vitamin D3 supplementation through cod liver oil at different postnatal ages and MS risk. Methods: In the Norwegian component of the multinational case-control study Environmental Factors In Multiple Sclerosis (EnvIMS), a total of 953 MS patients with maximum disease duration of 10 years and 1717 controls reported their cod liver oil use from childhood to adulthood. Results: Self-reported supplement use at ages 13–18 was associated with a reduced risk of MS (OR 0.67, 95% CI 0.52–0.86), whereas supplementation during childhood was not found to alter MS risk (OR 1.01, 95% CI 0.81–1.26), each compared to non-use during the respective period. An inverse association was found between MS risk and the dose of cod liver oil during adolescence, suggesting a dose-response relationship ( p trend = 0.001) with the strongest effect for an estimated vitamin D3 intake of 600–800 IU/d (OR 0.46, 95% CI 0.31–0.70). Conclusions: These findings not only support the hypothesis relating to low vitamin D as a risk factor for MS, but further point to adolescence as an important susceptibility period for adult-onset MS.

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