{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T06:46:13Z","timestamp":1790837173478,"version":"4.1.0"},"reference-count":63,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2020,3,16]],"date-time":"2020-03-16T00:00:00Z","timestamp":1584316800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Multiple sclerosis (MS) is a chronic inflammatory demyelinating and neurodegenerative disease of the central nervous system (CNS). In recent years, vitamin D has gained attention, as low serum levels are suspected to increase the risk for MS. Cholecalciferol supplementation has been tested in several clinical trials, since hypovitaminosis D was linked to higher disease activity and may even play a role in long-term outcome. Here, we review the current understanding of the molecular effects of vitamin D beyond calcium homeostasis, the potential beneficial action in MS and hazards including complications of chronic and high-dose therapy. In clinical trials, doses of up to 40,000 IU\/day were tested and appeared safe as add-on therapy for short-term periods. A recent meta-analysis of a randomized, double-blind, placebo-controlled clinical trial investigating vitamin D as add-on therapy in MS, however, suggested that vitamin D had no therapeutic effect on disability or relapse rate. We recognize a knowledge gap for chronic and high-dose therapy, which can lead to life-threatening complications related to vitamin D toxicity including renal failure, cardiac arrythmia and status epilepticus. Moreover, vitamin D toxicity may manifest as fatigue, muscle weakness or urinary dysfunction, which may mimic the natural course of progressive MS. Given these limitations, vitamin D supplementation in MS is a sensitive task which needs to be supervised by physicians. While there is strong evidence for vitamin D deficiency and the development of MS, the risk-benefit profile of dosage and duration of add-on supplementation needs to be further clarified.<\/jats:p>","DOI":"10.3390\/nu12030783","type":"journal-article","created":{"date-parts":[[2020,3,17]],"date-time":"2020-03-17T09:27:41Z","timestamp":1584437261000},"page":"783","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":114,"title":["Vitamin D Supplementation in Multiple Sclerosis: A Critical Analysis of Potentials and Threats"],"prefix":"10.3390","volume":"12","author":[{"given":"Julia","family":"Feige","sequence":"first","affiliation":[{"name":"Department of Neurology, Christian Doppler Medical Center, Paracelsus Medical University, 5020 Salzburg, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5397-5595","authenticated-orcid":false,"given":"Tobias","family":"Moser","sequence":"additional","affiliation":[{"name":"Department of Neurology, Christian Doppler Medical Center, Paracelsus Medical University, 5020 Salzburg, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lara","family":"Bieler","sequence":"additional","affiliation":[{"name":"Department of Neurology, Christian Doppler Medical Center, Paracelsus Medical University, 5020 Salzburg, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kerstin","family":"Schwenker","sequence":"additional","affiliation":[{"name":"Department of Neurology, Christian Doppler Medical Center, Paracelsus Medical University, 5020 Salzburg, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Larissa","family":"Hauer","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Psychotherapy and Psychosomatic Medicine, Christian Doppler Medical Center, Paracelsus Medical University, Salzburg"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8749-5533","authenticated-orcid":false,"given":"Johann","family":"Sellner","sequence":"additional","affiliation":[{"name":"Department of Neurology, Christian Doppler Medical Center, Paracelsus Medical University, 5020 Salzburg, Austria"},{"name":"Department of Neurology, Klinikum rechts der Isar, Technische Universit\u00e4t M\u00fcnchen, 81675 M\u00fcnchen, Germany"},{"name":"Department of Neurology, Landesklinikum Mistelbach-G\u00e4nserndorf, 2130 Mistelbach, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,3,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1622","DOI":"10.1016\/S0140-6736(18)30481-1","article-title":"Multiple sclerosis","volume":"391","author":"Thompson","year":"2018","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1212\/WNL.0b013e31829a3388","article-title":"Mortality in patients with multiple sclerosis","volume":"81","author":"Scalfari","year":"2013","journal-title":"Neurology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1111\/ane.12724","article-title":"Causes of death in critically ill multiple sclerosis patients","volume":"136","author":"Karamyan","year":"2017","journal-title":"Acta Neurol. 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