Data_Sheet_2_Is There a Role for Vitamin D in Amyotrophic Lateral Sclerosis? A Systematic Review and Meta-Analysis.docx

Background: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative condition characterized by the progressive loss of motor neurons. Patients usually die 3–5 years after diagnosis from respiratory failure. Several studies investigated the role of vitamin D as a biomarker or a therapeutic option for ALS patients. To clarify the scientific evidence, we performed a systematic review and different meta-analyses regarding the potential role of vitamin D in ALS.
Methods: We performed a systematic review of clinical trials, cohorts, and case–control studies retrieved from PubMed, EMBASE, and Cochrane databases reporting vitamin D levels as a putative biomarker for ALS diagnosis or prognosis or the effect of vitamin D supplementation in ALS patients. Whenever possible, data were pooled using a random-effects model, with an assessment of heterogeneity.
Results: Out of 2,996 articles retrieved, we finally included 13 research articles, 12 observational studies (50% prospective), and 1 clinical trial. We found that ALS patients had slightly lower levels of vitamin D than controls (mean difference −6 ng/ml, 95% CI [−10.8; −1.3]), but important confounding factors were not considered in the studies analyzed. We found no relationship between vitamin D levels and ALS functional rate score—revised (ALSFRS-R), with highly heterogeneous results. Discordant results were reported in three studies regarding survival. Finally, five studies reported the effects of vitamin D supplementation with discordant results. Two of them showed a small improvement, whereas two others showed a deleterious effect on ALSFRS-R. One very small clinical trial with important methodological limitations showed some improvement in ALSFRS-R with high doses of vitamin D compared with normal doses.
Conclusions: Our review did not find evidence to support the role of vitamin D on ALS diagnosis, prognosis, or treatment. Most studies had important limitations, mostly regarding the risk of bias for not considering confounding factors. Vitamin D supplementation should be offered to ALS patients to avoid other health issues related to vitamin D deficiency, but there is not enough evidence to support the use of vitamin D as a therapy for ALS.

背景：肌萎缩侧索硬化（Amyotrophic Lateral Sclerosis, ALS）是一种以运动神经元进行性丧失为特征的神经退行性疾病。患者通常在确诊后3~5年内因呼吸衰竭死亡。已有多项研究探讨了维生素D作为ALS患者生物标志物或治疗选择的作用。为明确相关科学证据，我们开展了一项针对维生素D在ALS中潜在作用的系统综述及多项荟萃分析。方法：我们对检索自PubMed、EMBASE及Cochrane数据库的临床试验、队列研究及病例对照研究进行了系统综述，这些研究均报道了维生素D水平作为ALS诊断或预后的潜在生物标志物，或维生素D补充剂对ALS患者的疗效。在条件允许的情况下，采用随机效应模型合并数据，并评估异质性。结果：在检索到的2996篇文献中，最终纳入13篇研究论文，其中12项为观察性研究（50%为前瞻性研究），1项为临床试验。我们发现，ALS患者的维生素D水平略低于对照组（均数差为-6 ng/ml，95%置信区间[−10.8; −1.3]），但纳入分析的研究未考虑重要的混杂因素。我们未发现维生素D水平与修订版ALS功能评定量表（ALS Functional Rating Scale-Revised, ALSFRS-R）评分之间存在关联，且结果存在高度异质性。三项关于生存情况的研究结果存在分歧。最终，五项研究报道了维生素D补充剂的疗效，结果同样不一致：其中两项显示ALSFRS-R评分小幅改善，另外两项则显示对ALSFRS-R评分存在有害影响。一项样本量极小且存在重要方法学局限的临床试验表明，与常规剂量相比，高剂量维生素D可使ALSFRS-R评分出现一定改善。结论：本综述未发现证据支持维生素D可用于ALS的诊断、预后评估或治疗。大多数研究存在重要局限，主要为未考虑混杂因素导致的偏倚风险。虽然可向ALS患者提供维生素D补充剂以避免维生素D缺乏相关的其他健康问题，但尚无足够证据支持将维生素D作为ALS的治疗手段。