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Salivary cortisol levels, repeatedly measured during the day, and serum 25(OH)D levels were assessed before (T0) and after (T1) this treatment period. Methods: Female patients with relapsing-remitting MS received vitamin D 3 supplements (4,000 IU/day n = 22) or placebo ( n = 19) during 16 weeks. Since nuclear receptor ligands may regulate each other, we explored the association of vitamin D 3 supplements with circadian cortisol levels in a double-blind and placebo-controlled supplementation study. Introduction: Multiple sclerosis (MS) has been associated with both a poor vitamin D status and hyperactivity of the hypothalamus–pituitary–adrenal (HPA) axis.

6Canisius Wilhelmina Hospital, Department of Neurology, Nijmegen, Netherlands.

5Canisius Wilhelmina Hospital, Department of Clinical Chemistry, Nijmegen, Netherlands.

4Netherlands Institute for Neuroscience, Neuroimmunology Research Group, Amsterdam, Netherlands.

3Maastricht University Medical Center, Central Diagnostic Laboratory, Maastricht, Netherlands.

2Zuyderland Medical Center, Academic MS Center Limburg, Sittard, Netherlands.

1School for Mental Health and Neuroscience, Maastricht University, Maastricht, Netherlands.

Raymond Hupperts 1,2 and Joost Smolders 1,4,6*