在过去的100年中，与维生素D研究相关的许多重大突破和发现已经发生。这些进展包括1919年治愈佝偻病、维生素D化合物的发现、维生素D分子生物学的进步以及我们对维生素D代谢内分泌调控的理解的提高。此外，已经制定了维生素D的建议每日摄入量，并完成了旨在澄清维生素D对预防多种疾病的作用的大型临床试验。然而，令人失望的是，这些临床试验没有实现许多人10年前的期望。在几乎每个试验中，各种剂量和给药途径并没有显示维生素D在预防骨折、跌倒、癌症、心血管疾病、2型糖尿病、哮喘和呼吸道感染方面的疗效。虽然长期高剂量治疗的副作用问题，如高钙血症和肾结石，已经存在四十年之久，但过去5年的一些试验却出现了新的意外不良事件。这些不良事件包括老年人（年龄> 65岁）中骨折、跌倒和住院率的增加。其中几项临床试验的主要结局的功率恰当，但没有包括剂量反应研究，并且在二次分析方面功率不足。此外，需要更多关注高剂量维生素D补充的安全性，特别是对于老年人。此外，尽管骨质疏松学会普遍建议将钙补充剂与维生素D结合使用，但在最高风险群体中，其功效和对骨折风险的影响仍缺乏数据支持。需要进行更多针对严重维生素D缺乏症的人（即血清25-羟基维生素D<25nmol/L [10ng/mL]）的试验。在本篇个人观点中，我们总结和讨论了维生素D领域的一些主要发现和争议。 Copyright © 2023 Elsevier Ltd. All rights reserved.

Over the past 100 years, many major breakthroughs and discoveries have occurred in relation to vitamin D research. These developments include the cure of rickets in 1919, the discovery of vitamin D compounds, advances in vitamin D molecular biology, and improvements in our understanding of endocrine control of vitamin D metabolism. Furthermore, recommended daily allowances for vitamin D have been established and large clinical trials of vitamin D, aimed at clarifying the effect of Vitamin D in the prevention of multiple diseases, have been completed. However, disappointingly, these clinical trials have not fulfilled the expectations many had 10 years ago. In almost every trial, various doses and routes of administration did not show efficacy of vitamin D in preventing fractures, falls, cancer, cardiovascular diseases, type 2 diabetes, asthma, and respiratory infections. Although concerns about side-effects of long-term high-dose treatments, such as hypercalcaemia and nephrocalcinosis, have been around for four decades, some trials from the past 5 years have had new and unexpected adverse events. These adverse events include increased fractures, falls, and hospitalisations in older people (aged >65 years). Several of these clinical trials were powered appropriately for a primary outcome but did not include dose response studies and were underpowered for secondary analyses. Furthermore, more attention should be paid to the safety of high doses of vitamin D supplementation, particularly in older people. In addition, despite universal recommendations by osteoporosis societies for combining calcium supplements with vitamin D there remains insufficient data about their efficacy and effect on fracture risk in the highest risk groups. More trials are needed for people with severe vitamin D deficiency (ie, serum 25-hydroxyvitamin D <25nmol/L [10ng/mL]). In this Personal View, we summarise and discuss some of the major discoveries and controversies in the field of vitamin D.Copyright © 2023 Elsevier Ltd. All rights reserved.