The exact cause of multiple sclerosis (MS) is unknown; however, it is considered to be an inflammatory disease of the central nervous system (CNS) triggered by a combination of both environmental and genetic factors. Vitamin D deficiency is also discussed as a possible disease-promoting factor in MS, as low vitamin D status is associated with increased formation of CNS lesions, elevated number of relapses and accelerated disease progression. However, it remains unclear whether this association is causal and related and most importantly, whether vitamin D supplementation in MS is of direct therapeutic benefit. Recently, we could show that in a murine model of MS, administration of a moderate vitamin D dose was of clinical benefit, while excessive vitamin D supplementation had a negative effect on disease severity. Of note, disease exacerbation was associated with high-dose vitamin D caused secondary hypercalcemia. Mechanistically dissecting this outcome, we found that hypercalcemia independent of vitamin D similarly triggered activation of disease-perpetuating T cells. These findings caution that vitamin D should be supplemented in a controlled and moderate manner in patients with MS and concomitantly highlight calcium as a novel potential MS risk factor by itself. In this review, we will summarize the current evidence from animal and clinical studies aiming to assess whether vitamin D may be of benefit in patients with MS. Furthermore, we will discuss any possible secondary effects of vitamin D with a particular focus on the role of calcium on immune cells and in the pathogenesis of CNS demyelinating disease.

多发性硬化症（MS）的确切原因尚不清楚；然而，它被认为是由环境和遗传因素共同引发的中枢神经系统（CNS）炎症性疾病。维生素D缺乏症也被认为是MS中可能的疾病促进因素，因为低维生素D状态与中枢神经系统病变的形成增加，复发次数增加和疾病进展加快有关。但是，尚不清楚这种关联是否是因果关系和相关性，最重要的是，在MS中补充维生素D是否具有直接的治疗益处。最近，我们可以证明，在MS的鼠模型中，适量的维生素D给药具有临床益处，而过量补充维生素D对疾病的严重程度却具有负面影响。值得注意的是 疾病恶化与大剂量维生素D引起继发性高钙血症有关。从机械角度剖析这一结果，我们发现独立于维生素D的高钙血症类似地触发了永生性T细胞的激活。这些发现提示，MS患者应以可控和适度的方式补充维生素D，并同时强调钙本身就是一种新的潜在MS危险因素。在这篇综述中，我们将总结来自动物和临床研究的最新证据，旨在评估维生素D是否对MS患者有益。此外，我们将讨论维生素D的任何可能的继发作用，尤其是钙对免疫细胞的作用以及中枢神经系统脱髓鞘疾病的发病机理。