中国育龄女性维生素D适宜水平判定指标和界值探讨

The relationship between vitamin D (VD) and health，especially its nonskeletal effects, has been a hot topic in recent ten years, and it is very important to evaluate its nutritional status accurately. Yet so far there is no relevant standard in our country. Serum 25-hydrroxyvitmin D (25-OH-D) is considered to be the best indicator of overall VD status of an individual. Clinical thresholds to define vitamin D deficiency usually have been based on levels at which 25(OH)D maximally suppresses parathyroid hormone. Yet there was no consistency in the threshold level of serum 25(OH)D. And previous studies have been limited to predominantly White populations despite the optimal serum 25(OH)D concentrations for bone health may differ by race and ethnicity. This study plan to clarify whether or to what extent the PTH-based 25(OH)D threshold could reflect bone health in Chinese childbearing women. Using the nationally representative samples from Chinese Health and Nutrition Examination Survey (CHANES) conducted in 2015, we will examine the relationship between serum PTH and 25(OH)D for evidence of a threshold or plateaus and also examine the relationship between bone markers and serum 25(OH)D. Relying on accurate LC-MS/MS technology and multiphase statistical models, the error interference of methodology will be avoided. On the other hand, volunteers will be recruited in a randomized-controlled trial for three months to validate the preliminary threshold of our cross-sectional analysis. This study can provide a direct and reliable scientific basis for the formulation of VD nutritional status evaluation criteria and the revision of dietary VD recommended intake in Chinese population.

维生素D（VD）与健康的关系，尤其是其“骨外健康效应”近十年来一直是研究热点，准确评价机体VD营养状况也变得益发重要，而我国迄今没有相关标准。血清25(OH)D是公认的评估维生素D营养状况的客观指标，目前普遍采用使血清甲状旁腺激素（PTH）达到最大抑制时的25(OH)D水平定义维生素D缺乏。但以此方法得到的25(OH)D界值并未统一，且不同种族间差异较大。本研究将首次利用最新的“2015年成人慢性病与营养监测”全国代表性样本库，依托准确的VD质谱检测技术和多相统计分析模型，避免方法学的误差干扰，全面分析育龄女性血清PTH-25(OH)D分布、影响因素及对骨标志物的影响，从而提出以PTH为基础判定我国育龄女性VD缺乏的适宜指标及界值。上述结果还将在为期3个月的人群口服VD3随机对照试验中进一步验证。本研究可为制定我国人群维生素D营养状况评价标准及修订其膳食推荐摄入量提供直接可靠的科学依据。

背景：维生素D（VD）在维持钙磷平衡和骨骼健康中发挥关键作用，但目前缺乏针对中国特定人群的VD营养状况评价标准。.研究内容：1）利用具有全国代表性的“2015年中国成人慢性病与营养监测”样本库，分析我国育龄女性血清25(OH)D与甲状旁腺激素（PTH）、骨转换标志物（BTM）的分布和相互关系，探讨遗传和非遗传因素的影响；2）应用多种统计模型预测PTH和BTM平台期对应的25(OH)D浓度，初步提出育龄女性VD适宜水平的判定界值，并将该界值应用于代谢综合征（MetS）及其组分风险的评估；3）开展预期6个月的VD3补充干预研究，追踪观察受试者血清25(OH)D、PTH的变化趋势。估计血清PTH达到最大抑制或平台期时的25(OH)D浓度，并基于横断面研究得到的初步结果，比较不同基线25(OH)D水平亚组间PTH等指标对VD补充的响应差异，验证横断面研究的界值。最终提出适于我国育龄女性的维生素D缺乏或适宜判定界值。.结果：1）本实验室建立了血清25(OH)D检测的LC-MS/MS法，具有较好的灵敏度和精密度；2）育龄女性VD缺乏或不足率较高，纬度、采样季节、年龄、基因多态性等因素与血清25(OH)D水平和VD缺乏有关；3）局部加权回归散点平滑法、阈值回归、迭代搜索和分段线性回归拟合25(OH)D和PTH之间的非线性关系，趋势相似；4）充分控制混杂因素，以PTH预测的25(OH)D界值为13.15ng/mL-20.76ng/mL，以OC、β-CTX和P1NP预测的25(OH)D界值分别为：15.14ng/mL、14.79ng/mL和15.08ng/mL；5）25(OH)D浓度<13.15ng/mL可增加TG升高和HDL-C降低的风险；6）干预研究中，通过多项式回归获得的25(OH)D界值范围为17.21-23.95ng/mL，与高斯过程回归得到的界值（20.2-21.65ng/mL）有较好的一致性；对不同基线25(OH)D水平进行亚组分析，观察到VD补充对基线13.15ng/mL组的血清25(OH)D和PTH的改善效果显著优于>13.15ng/mL组。.科学意义：本项目通过国家代表性的横断面和多时间节点的干预研究，初步提出我国育龄女性VD缺乏和适宜的界值，为后续完善中国人群营养素评估标准体系提供科学数据，并为VD缺乏相关疾病的精准防控提供决策依据。