Vitamin D and its main active metabolite 1,25-dihydroxyvitamin D serve a crucial role in maintenance of a healthy calcium metabolism, yet have additional roles in immune and central nervous system cell homeostasis. Serum levels of 25-hydroxyvitamin D are a biomarker of future disease activity in patients with early relapsing-remitting multiple sclerosis (RRMS), and vitamin D supplementation in patients with low circulating 25-dihydroxyvitamin D levels has been anticipated as a potential efficacious treatment strategy. The results of the first large randomized clinical trials (RCTs), the SOLAR and CHOLINE studies, have now been published. The SOLAR study compared 14,000 IU of vitamin D3 (cholecalciferol) per day with placebo for 48 weeks in 232 randomized patients, whereas CHOLINE compared vitamin D3 100,000 IU every other week with placebo for 96 weeks in 129 randomized patients. All patients in both studies also used interferon-β-1a. None of the studies met their primary endpoints, which were no evidence of disease activity (NEDA-3) at 48 weeks in SOLAR and annualized relapse rate at 96 weeks in CHOLINE. Both studies did, however, suggest modest effects on secondary endpoints. Thus, vitamin D reduced the number of new or enlarging lesions and new T2 lesions in SOLAR, and the annualized relapse rate and number of new T1 lesions, volume of hypointense T1 lesions, and disability progression in the 90 patients who completed 96 weeks' follow-up in CHOLINE. We conclude that none of the RCTs on vitamin supplementation in MS have met their primary clinical endpoint in the intention to treat cohorts. This contrasts the observation studies, where each 25 nmol/l increase in 25-hydroxyvitamin D levels were associated with 14-34% reduced relapse risk and 15-50% reduced risk of new lesions on magnetic resonnance imaging. This discrepancy may have several explanations, including confounding and reverse causality in the observational studies. The power calculations of the RCTs have been based on the observational studies, and the RCTs may have been underpowered to detect less prominent yet important effects of vitamin D supplementation. Although the effect of vitamin D supplementation is uncertain and less pronounced than suggested by observational studies, current evidence still support that people with MS should avoid vitamin D insufficiency, and preferentially aim for vitamin D levels around 100 nmol/L or somewhat higher.

中文翻译：

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多发性硬化症中维生素D和疾病活性的更新。

维生素D及其主要活性代谢物1,25-二羟基维生素D在维持健康的钙代谢中起着至关重要的作用，但在免疫和中枢神经系统细胞稳态方面也具有其他作用。血清25-羟基维生素D是早期复发-缓解型多发性硬化症（RRMS）患者未来疾病活动的生物标志物，低循环25-二羟基维生素D水平的患者补充维生素D已被视为一种有效的治疗策略。第一个大型随机临床试验（RCT）的结果，即SOLAR和CHOLINE研究，现已发表。SOLAR研究在232位随机分组的患者中比较了每天14,000 IU维生素D3（胆钙化醇）和安慰剂治疗48周的情况，而CHOLINE比较了维生素D3 100 在129名随机分组的患者中，每隔2000 IU用安慰剂治疗96周。两项研究中的所有患者均使用了干扰素-β-1a。没有一项研究达到其主要终点，这没有证据表明SOLAR在48周时有疾病活动（NEDA-3），在CHOLINE中则没有在96周时的年复发率。但是，两项研究均提示对次要终点的影响中等。因此，在完成96周随访的90例患者中，维生素D减少了SOLAR中新的或扩大的病灶和新的T2病灶的数量，以及年复发率和新T1病灶的数量，Hypointense T1病灶的数量以及残疾进展。胆碱。我们得出的结论是，关于MS中补充维生素的RCT均未达到治疗队列的主要临床终点。这与观察研究形成对比，其中每25 nmol / l的25-羟基维生素D水平增加与磁共振成像上14-34％的复发风险降低和15-50％的新病变风险降低相关。这种差异可能有几种解释，包括观察研究中的混淆和反向因果关系。RCT的功效计算是基于观察性研究，RCT可能不足以检测补充维生素D的次要但重要的作用。尽管补充维生素D的效果尚不确定，并且不如观察性研究建议的那么明显，但目前的证据仍支持MS患者应避免维生素D不足，并优先将维生素D的水平定为100 nmol / L或更高。