中老年人血液维生素D适宜水平研究

Vitamin D (VD) is an essential nutrient for life. Its optimal blood level for the bone health maintenance is basic data used for the development of dietary reference intakes (DRIs) in China and other countries. At current stage, the studies of the optimal VD blood level were mainly cross-sectional or retrospective case-control studies, very limited numbers of prospective studies with large study size and long-term follow-up period (particular for bone density) are available in Chinese populations. It is difficult to determine causal dose-effect relationship between blood VD levels and bone health based on current data. On the other hand, VD supplementation studies suggested it was hard to increase the blood 25-OH-D level to the “sufficient level (> 75nmol/l)” defined by the US Endocrinology society, even if the supplemental doses increased from 400 IU/d to 2000 IU/d (UL for Chinese) and the blood level reached high plateau level at the dose of 1200 IU/d. Moreover, many factors (e.g., genetic, sexual hormone, body composition, dietary factors, etc.) might modify the VD effect on bone health, and these factors were quite different between Chinese and Western populations. These studies suggested that the optimal VD blood level in Chinese might differ from the Western people. Therefore, it is urgent to identify the optimal blood VD level in Chinese populations. To address this issue, this study will based on a 12-y prospective cohort study (visited very 3 years) in 4500 community-based Guangzhou residents (40-83 years) and 1510 cases and controls of hip fractures. In the cohort study, average serum VDs (25OHD2 and D3, 1,25(OH)2D2 and D3) and VD binding protein (DBP) were measured, changes in DXA-derived bone density and bone mineral content and PTH, incidences of total fractures and osteoporosis during the follow-up period and fractional calcium absorption and calcium balance were determined as the outcomes of bone health. And the VD and DBP indices were also measured in the case-control study. Our results will identify the optimal various types of serum VD (ie, total 25OHD, 1,25(OH)2D, non-DBP-binding 25OHD) based on the dose-dependent associations between VD indices and above-mentioned bone outcomes in the cohort and case-control studies. Potential effects’ modifiers, such as VD related SNPs, sexual hormones, body composition, diet, physical activity, etc., were also determined, and used to determine the optimal VD levels at the subgroups of the effect modifiers (if any). Our results will provide solid and basic evidence for the revisions of VD DRIs for the Chinese population.

维生素D（VD）是人生命所必需，维持骨健康所需适宜血液水平是确定其参考摄入量的基础。国内VD适宜水平研究多为横断面或回顾性研究，尚无大样本长时间的前瞻性研究，难以确定VD与骨健康的量效因果关系。而国人VD补充量由低增至UL，血浓度达最高平台时亦难达欧美确定的充裕水平，且中西方人的VD效应调节因素（遗传、激素和膳食等）差异大，提示国人适宜浓度有别于白人，亟需确定国人适宜VD血浓度。为此，本题基于4500名12年的前瞻性中老年队列和1510名髋骨骨折病例和对照，检测血液不同类型的VD及其结合蛋白，以随访期间骨密度、骨钙和PTH变化值，骨折和骨质疏松发病率，钙吸收和平衡为骨健康结局，阐明达到最佳骨健康效应时所需的各类VD（25OHD，1,25OH2D，结合与非结合型）的血浓度；检测并分析在不同（基因型、性激素、体成分、膳食等）条件下上述VD的适宜浓度。为确定我国人群VD的参考摄入量提供科学依据。

背景：维生素D（VD）是人体内重要脂溶性维生素。其体内适宜水平不仅是维持机体钙和磷的内稳态和骨骼健康所必须，亦对调节免疫，预防慢病及死亡起重要作用。解答“我国人群体内VD适宜水平是多少”，是制订我国居民VD膳食参考摄入量的基础。 .目的：（1）以骨健康及心血管代谢性指标为结局，探索我国中老年人体内血浆25(OH)VD(简称VD)的适宜水平；（2）探索肠道菌群及代谢组在VD与代谢性疾病关联的作用机制。.研究内容：基于2008年起建立的4048人40~80岁的“广州营养与健康研究”中老年队列，每3年随访1次，项目执行期间完成了4轮并进入第5轮调查。每次访问调查了一般情况、详细膳食及运动情况、检查体格指标等；检测了血浆VD，采用DXA检测了骨密度及体成分，采用超声检测了颈动脉内中膜厚度（IMT）、有无增厚及斑块。检测了2200人肠道菌群及1200人粪便及血清代谢组。本文利用前4轮调查和检测指标，研究VD与相关结局的横向及纵向关联，以及适宜水平和菌群相关组学机制。.结果：（1）血浆VD水平越高，骨密度及其改变值越高、骨质疏松、代谢综合征（MetS）、高血压和颈动脉粥样硬化（AS）患病及发病风险越低；（2）血浆VD在305ng/ml范围下列结局指标的保护性关联呈现平台效应或最佳效应：腰椎骨质疏松，代谢综合征（MetS）、高血压、高血糖、低HDL以及颈动脉斑块的发生及颈总动脉的增厚风险等。显示VD在达到30ng/ml或以上为体内适宜剂量；部分指标在观察的剂量范围内依然呈现直线线性关系，如股骨颈骨质疏松发病、骨密度变化、肥胖的发生风险及颈动脉分叉增厚风险等。（3）在作用机制上，发现血浆VD越高肠道菌群多样性、g19、g171和g197号菌和该CLR菌群评分（CLR）越高粪便甘氨鹅脱氧胆酸水平降低 抑制颈动脉CCA-IMT的增长；VD升高可以增加血液乙酰乙酸水平和酮体代谢通路活性，从而抑制IMT的增长。.意义：本研究通过横断面和前瞻性分析，支持VD与骨健康、代谢综合征及其各组分异常、颈动脉粥样硬化等代谢性疾病具有保护性关联。血浆VD在30ng/ml左右或以上对上述疾病的预防较为适宜，为制定VD的膳食推荐量提供了科学依据。此外，机制研究提供了确定作用的潜在靶点。