Al Nozha Omar M
Int J Health Sci (Qassim). 2016 Jul;10(3):443-52.
Vitamin D deficiency /insufficiency is widely recognized as a global health problem that is likely to be involved in pathogenesis or progression of many acute and chronic health disorders. Its relation to skeletal health has been clearly demonstrated and thoroughly examined. This review aims to highlight the continuous debate about the relation between vitamin D and extra-skeletal health and whether it is a causality or just an association. Overall, the available evidence does not meet the criteria for establishing cause-and-effect relationships because of the limitations of observational studies to corroborate the causality due to many potential confounders. Moreover, the causal relationship couldn't be established in randomized studies or in many meta-analyses. This may reflect the fact that vitamin D level reduction is just a biomarker of ill health. The inflammatory processes involved in the disease occurrence and the functional limitations of the diseases would have a role in reducing serum 25-hydroxy vitamin D "25 (OH) D" level, which would explain why low vitamin D is reported in a wide range of disorders. This may underscore the possibility of harm instead of benefit of vitamin D supplementation when its exact role is not fully established, thus many guidelines and interest groups are still hesitant toward recommending replacement in extra-skeletal disease. Future directions entails the need for a large well-designed randomized control trials (RCTs) to resolve the active debate on the benefits of vitamin D replacement for extra-skeletal disease, and not only that, future studies should establish specific, clinically relevant effects of vitamin D repletion, provide cut-values for optimal serum levels of 25 (OH) D, and appropriate doses for non-skeletal health benefits.
维生素D缺乏/不足被广泛认为是一个全球性健康问题，可能与许多急慢性健康疾病的发病机制或病情进展有关。其与骨骼健康的关系已得到明确证实并被深入研究。本综述旨在强调关于维生素D与骨骼外健康之间关系的持续争论，以及这是一种因果关系还是仅仅是一种关联。总体而言，由于观察性研究存在局限性，难以证实因果关系，因为存在许多潜在混杂因素，现有证据不符合建立因果关系的标准。此外，在随机研究或许多荟萃分析中也无法确立因果关系。这可能反映出维生素D水平降低只是健康不佳的一个生物标志物这一事实。疾病发生过程中涉及的炎症过程以及疾病的功能限制会导致血清25-羟基维生素D[25(OH)D]水平降低，这可以解释为什么在多种疾病中都报告有低维生素D情况。当维生素D的确切作用尚未完全确立时，这可能凸显了补充维生素D可能有害而非有益的可能性，因此许多指南制定者和利益集团在骨骼外疾病中推荐补充维生素D时仍犹豫不决。未来的方向需要进行大规模精心设计的随机对照试验（RCT）来解决关于维生素D补充对骨骼外疾病益处的激烈争论，不仅如此，未来的研究应确定维生素D补充的具体、临床相关效果，提供25(OH)D最佳血清水平的临界值，以及对非骨骼健康有益的适当剂量。
