Serum 25-Hydroxyvitamin D and Neurological Disability in Multiple Sclerosis: A Cross-Sectional Study from the Mediterranean Epidemiological Frontier

Serum 25-Hydroxyvitamin D and Neurological Disability in Multiple Sclerosis: A Cross-Sectional Study from the Mediterranean Epidemiological Frontier | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Serum 25-Hydroxyvitamin D and Neurological Disability in Multiple Sclerosis: A Cross-Sectional Study from the Mediterranean Epidemiological Frontier osamah alrouwab, Hayet Benhiziaa, Issa Amara This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8895776/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background Vitamin D is widely studied in multiple sclerosis (MS), yet its clinical relevance for disability and relapse activity remains uncertain, especially in underrepresented populations. Objective To examine whether serum 25-hydroxyvitamin D [25(OH)D] levels are associated with disability or relapse activity in a multicenter cohort of Libyan adults with MS. Methods : In a cohort of adults with MS (n = 369), the exposure was 25(OH)D scaled per 10 ng/mL (vitD10). Primary outcomes were the continuous Expanded Disability Status Scale (EDSS) and annualized relapse rate (ARR). We prespecified equivalence margins of ± 0.30 EDSS points and ± 0.25 ARR, fit covariate‑adjusted models with HC3 robust standard errors, and conducted two one‑sided tests (TOST). Results For continuous EDSS, estimates were small and the 90% confidence interval lay within the ± 0.30 margin, supporting equivalence; ARR results were similar within ± 0.25. There was little evidence of non‑linearity and measurement‑error sensitivity (SIMEX) had negligible impact. An exploratory threshold analysis at EDSS ≥ 4 suggested a small, cut‑point–dependent increase in odds (OR 1.47, 95% CI 1.01–2.15) that warrants prospective replication. Conclusions In these cross‑sectional data, differences in 25(OH)D were unlikely to correspond to clinically meaningful differences in disability on the continuous scale. Correct vitamin D deficiency for general health and consider potential links with inflammatory activity, but avoid inferring large differences in established disability from a single measurement. Prospective studies with season, supplementation, and treatment information are needed to test effect modification and trajectories. Multiple Sclerosis (MS) Vitamin D Deficiency Neurological Disability Expanded Disability Status Scale (EDSS) North African Epidemiology Full Text Additional Declarations No competing interests reported. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8895776","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":592751275,"identity":"4700d3cc-8714-4bf0-af3b-fbf7bcbf3d0a","order_by":0,"name":"osamah alrouwab","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAuElEQVRIiWNgGAWjYJACZoYKCEOCgcGCWC1n4FokiNTC2EaKFvP2M4afC+cdlpNvYD54m4dBIrGBkBaZMznG0jO3HTZmbGBLtiZKiwRD7gZp3m2HE5sZeMykidPC/3bzb945hxPbGPi/EalFInebNG/D4cQeBh42YrW8/2Y941i6sQQzm7HlHAMJYyIclpZ8u6DGWk6+vfnhjTcVNrIEtSAAM4gwYHAkQQsU2JOsYxSMglEwCoY9AADNMDF4SgVcyAAAAABJRU5ErkJggg==","orcid":"","institution":"University Of Zintan","correspondingAuthor":true,"prefix":"","firstName":"osamah","middleName":"","lastName":"alrouwab","suffix":""},{"id":592751276,"identity":"28693752-7417-42b1-baba-c567c3127363","order_by":1,"name":"Hayet Benhiziaa","email":"","orcid":"","institution":"Constantine 1 University","correspondingAuthor":false,"prefix":"","firstName":"Hayet","middleName":"","lastName":"Benhiziaa","suffix":""},{"id":592751277,"identity":"28beb7c9-fb53-4795-889d-f7bca0dac05c","order_by":2,"name":"Issa Amara","email":"","orcid":"","institution":"University Of Zintan","correspondingAuthor":false,"prefix":"","firstName":"Issa","middleName":"","lastName":"Amara","suffix":""}],"badges":[],"createdAt":"2026-02-16 19:38:27","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8895776/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8895776/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":102964592,"identity":"d25bcdc0-57aa-443e-a6bd-635e722f2c98","added_by":"auto","created_at":"2026-02-19 04:22:55","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":949097,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8895776/v1_covered_d7fcb394-c123-43aa-91ec-4229472fb476.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Serum 25-Hydroxyvitamin D and Neurological Disability in Multiple Sclerosis: A Cross-Sectional Study from the Mediterranean Epidemiological Frontier","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Multiple Sclerosis (MS), Vitamin D Deficiency, Neurological Disability, Expanded Disability Status Scale (EDSS), North African Epidemiology","lastPublishedDoi":"10.21203/rs.3.rs-8895776/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8895776/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eVitamin D is widely studied in multiple sclerosis (MS), yet its clinical relevance for disability and relapse activity remains uncertain, especially in underrepresented populations.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eObjective\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTo examine whether serum 25-hydroxyvitamin D [25(OH)D] levels are associated with disability or relapse activity in a multicenter cohort of Libyan adults with MS.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e: In a cohort of adults with MS (n = 369), the exposure was 25(OH)D scaled per 10 ng/mL (vitD10). Primary outcomes were the continuous Expanded Disability Status Scale (EDSS) and annualized relapse rate (ARR). We prespecified equivalence margins of ± 0.30 EDSS points and ± 0.25 ARR, fit covariate‑adjusted models with HC3 robust standard errors, and conducted two one‑sided tests (TOST).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eFor continuous EDSS, estimates were small and the 90% confidence interval lay within the ± 0.30 margin, supporting equivalence; ARR results were similar within ± 0.25. There was little evidence of non‑linearity and measurement‑error sensitivity (SIMEX) had negligible impact. An exploratory threshold analysis at EDSS ≥ 4 suggested a small, cut‑point–dependent increase in odds (OR 1.47, 95% CI 1.01–2.15) that warrants prospective replication.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIn these cross‑sectional data, differences in 25(OH)D were unlikely to correspond to clinically meaningful differences in disability on the continuous scale. Correct vitamin D deficiency for general health and consider potential links with inflammatory activity, but avoid inferring large differences in established disability from a single measurement. Prospective studies with season, supplementation, and treatment information are needed to test effect modification and trajectories.\u003c/p\u003e","manuscriptTitle":"Serum 25-Hydroxyvitamin D and Neurological Disability in Multiple Sclerosis: A Cross-Sectional Study from the Mediterranean Epidemiological Frontier","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-02-18 15:28:20","doi":"10.21203/rs.3.rs-8895776/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"597b7b36-e300-47cd-96c7-39ddba78b88e","owner":[],"postedDate":"February 18th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-05-11T10:53:15+00:00","versionOfRecord":[],"versionCreatedAt":"2026-02-18 15:28:20","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8895776","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8895776","identity":"rs-8895776","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}