Rolf Linda, Damoiseaux Jan, Huitinga Inge, Kimenai Dorien, van den Ouweland Jody, Hupperts Raymond, Smolders Joost
School for Mental Health and Neuroscience, Maastricht University, Maastricht, Netherlands.
Zuyderland Medical Center, Academic MS Center Limburg, Sittard, Netherlands.
Front Neurol. 2018 Apr 26;9:263. doi: 10.3389/fneur.2018.00263. eCollection 2018.
Multiple sclerosis (MS) has been associated with both a poor vitamin D status and hyperactivity of the hypothalamus-pituitary-adrenal (HPA) axis. Since nuclear receptor ligands may regulate each other, we explored the association of vitamin D supplements with circadian cortisol levels in a double-blind and placebo-controlled supplementation study.
Female patients with relapsing-remitting MS received vitamin D supplements (4,000 IU/day; = 22) or placebo ( = 19) during 16 weeks. Salivary cortisol levels, repeatedly measured during the day, and serum 25(OH)D levels were assessed before (T0) and after (T1) this treatment period.
Median 25(OH)D levels at T1 were 139.9 (interquartile range 123.5-161.2) and 74.5 nmol/L (58.6-88.1) in the vitamin D and placebo group, respectively ( < 0.001). Comparisons within and between groups showed no differences in area under the curve (AUC) and slope of the cortisol day curve. Although the AUC of the cortisol awakening response (CAR, sampling each 15 min the first hour after awakening) showed a reduction over time in the vitamin D group [39.16 nmol/L (27.41-42.07) at T0 to 33.37 nmol/L (26.75-38.08) at T1] compared to the placebo group [33.90 nmol/L (25.92-44.61) at T0 to 35.00 nmol/L (25.46-49.23) at T1; = 0.044], there was no significant difference in AUC of CAR at T1 corrected for baseline AUC of CAR ( = 0.066).
Suppression of HPA-axis activity by vitamin D supplements in non-depressed MS patients may be best reflected by CAR as primary outcome measure. Further studies should address this interaction and its potential implications for the disease course of MS.
This study was registered on ClinicalTrials.gov (NCT02096133) and EudraCT (2014-000728-97).
多发性硬化症（MS）与维生素D水平低下以及下丘脑 - 垂体 - 肾上腺（HPA）轴功能亢进均有关联。由于核受体配体可能相互调节，我们在一项双盲、安慰剂对照的补充研究中探讨了维生素D补充剂与昼夜皮质醇水平之间的关联。
复发缓解型MS女性患者在16周内接受维生素D补充剂（4000国际单位/天；n = 22）或安慰剂（n = 19）。在该治疗期之前（T0）和之后（T1）评估白天反复测量的唾液皮质醇水平以及血清25（OH）D水平。
维生素D组和安慰剂组在T1时的25（OH）D水平中位数分别为139.9（四分位间距123.5 - 161.2）和74.5 nmol/L（58.6 - 88.1）（P < 0.001）。组内和组间比较显示，皮质醇日曲线的曲线下面积（AUC）和斜率无差异。尽管与安慰剂组相比，维生素D组的皮质醇觉醒反应（CAR，觉醒后第一小时每15分钟采样一次）的AUC随时间有所降低[从T0时的39.16 nmol/L（27.41 - 42.07）降至T1时的33.37 nmol/L（26.75 - 38.08）]，而安慰剂组从T0时的33.90 nmol/L（25.92 - 44.61）降至T1时的35.00 nmol/L（25.46 - 49.23）；P = 0.044，但校正CAR基线AUC后，T1时CAR的AUC无显著差异（P = 0.066）。
对于非抑郁型MS患者，维生素D补充剂对HPA轴活性的抑制作用可能最好以CAR作为主要结局指标来体现。进一步的研究应探讨这种相互作用及其对MS病程的潜在影响。
本研究已在ClinicalTrials.gov（NCT02096133）和EudraCT（2014 - 000728 - 97）上注册。
