Vitamin D supplementation and non-alcoholic fatty liver disease: A critical and systematic review of clinical trials

Previous observational studies have found a relationship between vitamin D deficiency and non-alcoholic fatty liver disease (NAFLD). However, this type of study could not show the causal relationship between these two conditions. Therefore, we systematically and critically reviewed the available clinical trials to elucidate such relationship. We searched databases such as Medline, Scopus and Cochrane to identify the clinical trials that assessed the effects of vitamin D supplementation in adults with NAFLD. The outcome variables of interest were indicators of hepatic steatosis, liver enzymes, insulin resistance, inflammation and oxidative stress. A total of 6 studies were included in the qualitative analysis. Only in two studies the grade of hepatic steatosis decreased significantly after vitamin D supplementation. The changes in insulin resistance parameters were reported significant only in one. Of the 3 included studies that measured biomarkers of inflammation and oxidative stress, one revealed a significant decrease in these biomarkers after vitamin D supplementation. Findings from current review study provided new insight into the factors that could affect the therapeutic role of vitamin D in NAFLD. Factors such as gender differences, baseline serum status of vitamin D, co-supplementation with calcium and gene polymorphism should be considered when designing future clinical trials.

既往观察性研究已发现维生素D缺乏与非酒精性脂肪性肝病（non-alcoholic fatty liver disease, NAFLD）之间存在关联，但此类研究无法明确二者间的因果关系。据此，本研究系统且批判性地梳理现有临床试验，以阐明二者间的因果关联。我们检索了Medline、Scopus及Cochrane等数据库，以识别评估维生素D补充疗法对成人NAFLD患者干预效果的临床试验。本研究关注的结局变量包括肝脂肪变指标、肝酶水平、胰岛素抵抗、炎症反应及氧化应激相关标志物。最终共计纳入6项研究进行定性分析。其中仅2项研究显示，维生素D补充后受试者的肝脂肪变等级显著降低。胰岛素抵抗相关参数的变化仅在1项研究中被报道具有统计学意义。在纳入的3项检测炎症与氧化应激生物标志物的研究中，1项结果表明补充维生素D后此类生物标志物水平显著下降。本综述的研究结果为影响维生素D治疗NAFLD疗效的相关因素提供了新的视角。在设计未来临床试验时，应考虑性别差异、基线血清维生素D水平、联合钙剂补充以及基因多态性等因素。