Joost Smolders1,2, Max Mimpen3, Johanna Oechtering4, Jan Damoiseaux5, Jody van den Ouweland6, Raymond Hupperts3, Jens Kuhle4. 1. Department of Neurology, Canisius Wilhelmina Ziekenhuis, Nijmegen, The Netherlands. 2. Neuroimmunology Research group, Netherlands Institute for Neuroscience, Amsterdam, The Netherlands. 3. Department of Neurology, Zuyderland Medical Center, Sittard, The Netherlands. 4. Department of Neurology, University Hospital Basel, Basel, Switzerland. 5. Central Diagnostic Laboratory, Maastricht University Medical Center, Maastricht, The Netherlands. 6. Department of Clinical Chemistry, Canisius Wilhelmina Ziekenhuis, Nijmegen, The Netherlands.
Abstract
OBJECTIVES: Low circulating vitamin D levels are associated with an increased risk of active MRI lesions and relapses in several cohorts with relapsing remitting multiple sclerosis (RRMS). Randomized controlled supplementation trials are, however, negative on their primary endpoints, while secondary MRI endpoints suggest anti-inflammatory effects. Circulating levels of neurofilament light chain (NfL) are a biomarker of disease activity in RRMS. We explored whether 48-week high-dose vitamin D3 supplements were associated with lower circulating NfL levels. MATERIALS & METHODS: Of N = 40 Dutch interferon beta-treated participants with RRMS of the SOLAR trial, plasma samples at baseline and 48-week follow-up were available. Of these participants, N = 24 were supplemented with 14 000 IU/d vitamin D3 and N = 16 with placebo. Twenty-five hydroxyvitamin D3 (25(OH)D3 ) levels were measured with LC-MS/MS, and NfL levels were measured in duplicate with Simoa. RESULTS:Serum 25(OH)D3 levels at 48 weeks were increased in the vitamin D3 when compared to placebo group (median level 281 [IQR 205-330] vs 72 [39-88] nmol/L; P < .01). NfL levels at 48 weeks did not differ between the treatment groups (median level 25.4 [IQR 19.6-32.2] vs 25.3 [17.9-30.1] pg/mL; P = .74). Higher week 48 NfL level showed a trend toward association with a higher risk of combined unique active lesions on the week 48 MRI scan (OR 2.39 [95% CI 0.93-6.12] for each 10 pg/mL increase; P = .07). CONCLUSIONS: Supplementation of high-dose vitamin D3 for 48 weeks was not associated with lower NfL levels. This study does not support an effect of vitamin D3 on this biomarker of neuro-axonal injury.
RCT Entities:
OBJECTIVES: Low circulating vitamin D levels are associated with an increased risk of active MRI lesions and relapses in several cohorts with relapsing remitting multiple sclerosis (RRMS). Randomized controlled supplementation trials are, however, negative on their primary endpoints, while secondary MRI endpoints suggest anti-inflammatory effects. Circulating levels of neurofilament light chain (NfL) are a biomarker of disease activity in RRMS. We explored whether 48-week high-dose vitamin D3 supplements were associated with lower circulating NfL levels. MATERIALS & METHODS: Of N = 40 Dutch interferon beta-treated participants with RRMS of the SOLAR trial, plasma samples at baseline and 48-week follow-up were available. Of these participants, N = 24 were supplemented with 14 000 IU/d vitamin D3 and N = 16 with placebo. Twenty-five hydroxyvitamin D3 (25(OH)D3 ) levels were measured with LC-MS/MS, and NfL levels were measured in duplicate with Simoa. RESULTS: Serum 25(OH)D3 levels at 48 weeks were increased in the vitamin D3 when compared to placebo group (median level 281 [IQR 205-330] vs 72 [39-88] nmol/L; P < .01). NfL levels at 48 weeks did not differ between the treatment groups (median level 25.4 [IQR 19.6-32.2] vs 25.3 [17.9-30.1] pg/mL; P = .74). Higher week 48 NfL level showed a trend toward association with a higher risk of combined unique active lesions on the week 48 MRI scan (OR 2.39 [95% CI 0.93-6.12] for each 10 pg/mL increase; P = .07). CONCLUSIONS: Supplementation of high-dose vitamin D3 for 48 weeks was not associated with lower NfL levels. This study does not support an effect of vitamin D3 on this biomarker of neuro-axonal injury.
Authors: Patrick Ostkamp; Anke Salmen; Béatrice Pignolet; Dennis Görlich; Till F M Andlauer; Andreas Schulte-Mecklenbeck; Gabriel Gonzalez-Escamilla; Florence Bucciarelli; Isabelle Gennero; Johanna Breuer; Gisela Antony; Tilman Schneider-Hohendorf; Nadine Mykicki; Antonios Bayas; Florian Then Bergh; Stefan Bittner; Hans-Peter Hartung; Manuel A Friese; Ralf A Linker; Felix Luessi; Klaus Lehmann-Horn; Mark Mühlau; Friedemann Paul; Martin Stangel; Björn Tackenberg; Hayrettin Tumani; Clemens Warnke; Frank Weber; Brigitte Wildemann; Uwe K Zettl; Ulf Ziemann; Bertram Müller-Myhsok; Tania Kümpfel; Luisa Klotz; Sven G Meuth; Frauke Zipp; Bernhard Hemmer; Reinhard Hohlfeld; David Brassat; Ralf Gold; Catharina C Gross; Carsten Lukas; Sergiu Groppa; Karin Loser; Heinz Wiendl; Nicholas Schwab Journal: Proc Natl Acad Sci U S A Date: 2021-01-05 Impact factor: 11.205
Authors: Max Mimpen; Linda Rolf; Geert Poelmans; Jody van den Ouweland; Raymond Hupperts; Jan Damoiseaux; Joost Smolders Journal: PLoS One Date: 2021-12-02 Impact factor: 3.240
Authors: James Bernard Walsh; Daniel M McCartney; Éamon Laird; Kevin McCarroll; Declan G Byrne; Martin Healy; Paula M O'Shea; Rose Anne Kenny; John L Faul Journal: Front Pharmacol Date: 2022-03-04 Impact factor: 5.810
Authors: Tamás Biernacki; Zsófia Kokas; Dániel Sandi; Judit Füvesi; Zsanett Fricska-Nagy; Péter Faragó; Tamás Zsigmond Kincses; Péter Klivényi; Krisztina Bencsik; László Vécsei Journal: Int J Mol Sci Date: 2022-03-21 Impact factor: 5.923