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We thank Shukla et al. for their critical appraisal of our work. Regarding the first comment: we agree, as already mentioned in themanuscript, that our exploratory study has its limitations and did not reveal major new insights in the role vitamin D3 may have in the treatment of major depression in multiple sclerosis (MS). Regarding the ethical concerns of Shukla et al., we think there are some important nuanceswhich make our study different from the study discussed by Lo and Grady [1]. First, all participants were treated with a first-line MS disease modifying treatment, Interferon Beta 1a. Second, participants were aware that they could be randomized in a high-dose vitaminD3 arm for theduration of the trial. Risk-analyses provided confidence about safety, which was further supported by a recent study [2]. In the parental study, SOLAR, detailed safety analyses were performed and supervised by an independent data safety monitoring board, with individual dose-adjustments if toxicity was suspected (NCT01285401). Third, the risk of exposing participants to an adverse disease course of MS by not correcting low 25-hydroxyvitamin D (25(OH)D) levels is uncertain. The association between 25(OH)D levels and MS outcomes may be driven by a disease modulating effect of vitamin D3 metabolites [3]. However, a progressing disease severity ofMS induces sun-avoiding behavior [4]. Sunlight is not only the main source of vitamin D3, but has also been argued to have direct disease-modulating effects independent from vitamin D3 [5]. Additionally, an activated immune system may lower 25(OH)D levels [6]. Although high 25(OH)D levels are associated with favorable MS outcomes in observational studies, it is uncertain whether vitamin D3 supplements improve these outcomes. From this perspective, it could even be argued to be unethical to advise patients vitamin D3 supplements with the goal of improving disease outcome. Furthermore, most efficacious 25(OH)D levels to aim for may be above thephysiological range. To substantiate such advises, randomized controlled clinical studies with (high doses of) vitamin D3 should reveal benefit for patients on targeted disease outcomes. In the study discussed by Lo and Grady [1], a mild anemia was not disclosed to participants, which may hamper the diagnosis of underlying disease. In the case of vitamin D3, low 25(OH)D levels are frequently found in MS [7] as well as in the general population [4], and its etiology is unlikely to comprise alternative diseases. Patients have their physiological vitamin D3 exposure from diet and sunlight and were allowed to take 1.000 IU/d vitamin D3 supplements. As a result of participation in our study, they were actively informed about the possible implications of low 25(OH)D levels in MS. Although we agree with Shukla et al. that our dataset failed to provide a clear answer to our patients on vitamin D3 supplementation and the endpoint depressive symptoms inMS, we think our data should encourage investigators to further address this issue. Whether