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Despite the currently used disease-modifying therapies, patients are exposed to persistent neuropathy, pinpointing the need for supportive therapy. Neurotropic vitamins B1, B6, and B12 have been used to offer relief from immunological and neurological MS manifestations. The present study aimed to provide some mechanistic insights into the relationship of B1\/B6\/B12 vitamin supplementation with the development of MS regarding lipid metabolism and epigenetics. In this cross-sectional observational study, blood samples were obtained from 53 MS patients, including 25 patients, who had received daily vitamin B1\/B6\/B12 supplementation for over six months and 28 patients without supplementation. Plasma sphingosine-1-phosphate (S1P) and S1P receptor-1 (S1PR1) levels, lipid profile, and gene expression of ApoA1, sphingosine kinases 1&amp;2 (SPHK1&amp;2), S1PR1, as well as the lncRNAs APOA1-AS and LISPR1 were evaluated. Gene ontology and KEGG pathway enrichment analyses were conducted. Vitamin B1\/B6\/B12 supplementation was associated with a more favorable lipid profile. Supplemented patients also exhibited higher ApoA1 and lower APOA1-AS expressions compared with non-supplemented patients. Additionally, vitamin B1\/B6\/B12 supplementation was associated with lower expression levels of SPHK1, SPHK2, LISPR1, and S1PR1 and reduced circulating S1P concentrations. These findings imply significant associations between long-term vitamin B1\/B6\/B12 supplementation and alterations in lipid-related markers and sphingosine-associated signaling in MS patients. However, the observational design, selection bias, and small sample size limit causal inference and may not fully capture the heterogeneity of MS population. Besides, supplement adherence was self-reported and not objectively verified, and circulating vitamin levels were not measured.<\/jats:p>","DOI":"10.1042\/bsr20260065","type":"journal-article","created":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T08:29:02Z","timestamp":1777624142000},"update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Association of vitamin B1\/B6\/B12 supplementation with sphingosine-1-phosphate signaling and its receptors in multiple sclerosis patients: relevance to LISPR1 and APOA1-AS"],"prefix":"10.1042","volume":"46","author":[{"given":"Noha\u00a0A.","family":"Mehana","sequence":"first","affiliation":[{"name":"1Biochemistry Department, Faculty of Pharmacy, Cairo University, Cairo, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4765-0353","authenticated-orcid":false,"given":"Heba\u00a0R.","family":"Ghaiad","sequence":"additional","affiliation":[{"name":"1Biochemistry Department, Faculty of Pharmacy, Cairo University, Cairo, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9794-4099","authenticated-orcid":false,"given":"Mohammed\u00a0M.","family":"Nooh","sequence":"additional","affiliation":[{"name":"1Biochemistry Department, Faculty of Pharmacy, Cairo University, Cairo, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mai\u00a0A.","family":"Amer","sequence":"additional","affiliation":[{"name":"2Microbiology and Immunology Department, Faculty of Pharmacy, October University for Modern Sciences and Arts (MSA), Giza, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lobna\u00a0Talaat","family":"El-Ghoneimy","sequence":"additional","affiliation":[{"name":"3Neurology Department, Faculty of Medicine, Cairo University, Cairo, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7177-915X","authenticated-orcid":false,"given":"Maheera\u00a0H.","family":"Safwat","sequence":"additional","affiliation":[{"name":"1Biochemistry Department, Faculty of Pharmacy, Cairo University, Cairo, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"288","published-online":{"date-parts":[[2026,5,21]]},"reference":[{"key":"2026052104562515400_B1","doi-asserted-by":"publisher","first-page":"942","DOI":"10.1056\/NEJMra052130","article-title":"Multiple sclerosis\u2014the plaque and its pathogenesis","volume":"354","author":"Frohman","year":"2006","journal-title":"N. 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