School for Mental Health and Neuroscience, Maastricht University Medical Center, Maastricht, The Netherlands.
PLoS One. 2010 Dec 13;5(12):e15235. doi: 10.1371/journal.pone.0015235.
A poor vitamin D status has been associated with a high disease activity of multiple sclerosis (MS). Recently, we described associations between vitamin D status and peripheral T cell characteristics in relapsing remitting MS (RRMS) patients. In the present study, we studied the effects of high dose vitamin D3 supplementation on safety and T cell related outcome measures.
METHODOLOGY/PRINCIPAL FINDINGS: Fifteen RRMS patients were supplemented with 20,000 IU/d vitamin D3 for 12 weeks. Vitamin D and calcium metabolism were carefully monitored, and T cell characteristics were studied by flowcytometry. All patients finished the protocol without side-effects, hypercalcaemia, or hypercalciuria. The median vitamin D status increased from 50 nmol/L (31-175) at week 0 to 380 nmol/L (151-535) at week 12 (P<0.001). During the study, 1 patient experienced an exacerbation of MS and was censored from the T cell analysis. The proportions of (naïve and memory) CD4+ Tregs remained unaffected. Although Treg suppressive function improved in several subjects, this effect was not significant in the total cohort (P=0.143). An increased proportion of IL-10+ CD4+ T cells was found after supplementation (P=0.021). Additionally, a decrease of the ratio between IFN-γ+ and IL-4+ CD4+ T cells was observed (P=0.035).
CONCLUSION/SIGNIFICANCE: Twelve week supplementation of high dose vitamin D3 in RRMS patients was well tolerated and did not induce decompensation of calcium metabolism. The skewing towards an anti-inflammatory cytokine profile supports the evidence on vitamin D as an immune-modulator, and may be used as outcome measure for upcoming randomized placebo-controlled trials.
Clinicaltrials.gov NCT00940719.
维生素 D 状态不佳与多发性硬化症（MS）的高疾病活动度有关。最近，我们描述了维生素 D 状态与复发缓解型多发性硬化症（RRMS）患者外周 T 细胞特征之间的关系。在本研究中，我们研究了高剂量维生素 D3 补充对安全性和 T 细胞相关结果测量的影响。
方法/主要发现：15 例 RRMS 患者每天补充 20,000 IU 维生素 D3，持续 12 周。仔细监测维生素 D 和钙代谢情况，并通过流式细胞术研究 T 细胞特征。所有患者均完成了该方案，没有出现副作用、高钙血症或高钙尿症。中位维生素 D 状态从 0 周时的 50 nmol/L（31-175）增加到 12 周时的 380 nmol/L（151-535）（P<0.001）。在研究期间，1 例患者出现 MS 恶化，从 T 细胞分析中被剔除。（幼稚和记忆）CD4+Tregs 的比例保持不变。尽管在几个受试者中观察到 Treg 抑制功能改善，但在总队列中无统计学意义（P=0.143）。补充后发现 IL-10+CD4+T 细胞的比例增加（P=0.021）。此外，IFN-γ+和 IL-4+CD4+T 细胞的比例下降（P=0.035）。
结论/意义：RRMS 患者补充 12 周高剂量维生素 D3 耐受性良好，不会导致钙代谢恶化。向抗炎细胞因子谱倾斜支持了维生素 D 作为免疫调节剂的证据，并可作为即将进行的随机安慰剂对照试验的结果测量指标。
Clinicaltrials.gov NCT00940719。
