Dose-dependent anti-inflammatory effects of vitamin D in a human gingivitis model

描述（由申请人提供）：在美国，非西班牙裔黑人与非西班牙裔白人相比，慢性牙龈炎和牙周炎的负担不成比例地高。慢性牙龈炎是一种非常普遍的慢性炎症性疾病，可能会发展成牙周炎，这是牙齿脱落的主要原因。来自体外和动物研究的数据表明维生素D具有抗炎作用；然而，维生素D是否以及在多大剂量范围内对人体具有抗炎作用尚不确定。最近的临床研究表明,维生素D的有利影响的几个重要的结果可能会出现在一个广泛的血清浓度(25-OHD)浓度,浓度可能到这需要维生素D摄入量范围从2到10倍高于当前RDA维生素D,因为黑皮肤色素沉着是维生素D光合作用的有效抑制剂,非西班牙裔黑人比非拉美裔白人25-OHD血清水平较低。维生素D水平的这些差异可能部分解释了在美国观察到的慢性牙龈炎和牙周炎患病率的种族差异。

DESCRIPTION (provided by applicant): The burden of chronic gingivitis and periodontitis in the US is disproportionately high among Non-Hispanic Blacks compared to Non-Hispanic Whites. Chronic gingivitis is a highly prevalent chronic inflammatory disease that may progress into periodontitis, a major cause of tooth loss. Data from in-vitro and animal studies suggest anti-inflammatory effects of vitamin D; however, if and over what dose-range vitamin D may have anti- inflammatory effects in humans is uncertain. Recent clinical studies indicate that beneficial effects of vitamin D for several important outcomes may occur over a wide range of serum 25-hydroxyvitamin D (25-OHD) concentrations, possibly up to concentrations that would require vitamin D intakes ranging from 2 to more than ten times higher than the current RDA for vitamin D. Because dark skin pigmentation is a potent inhibitor of vitamin D photosynthesis, Non-Hispanic Blacks have much lower 25-OHD serum levels than Non-Hispanic Whites. These differences in vitamin D status may partially explain the racial disparities in prevalence of chronic gingivitis and periodontitis observed in the US. We hypothesize that oral cholecalciferol supplementation can reduce susceptibility to gingivitis over a wide range of serum 25-OHD concentrations in Non-Hispanic Whites and Non-Hispanic Blacks. We propose to conduct a simple, single-center, randomized, double-blind, placebo-controlled parallel-group dose-ranging study. We will compare placebo to doses of 500 IU, 2,500 IU and 5,000 IU vitamin D3 per day. We will compare the severity of gingival inflammation that develops in response to a 28-day period of unlimited plaque growth (experimental gingivitis) between dosage groups. Furthermore, we will evaluate the association between achieved 25-OHD levels and gingival inflammation. The results of this study will have several important implications, as dietary vitamin D supplementation may be a simple, safe and inexpensive means by which to reduce racial/ethnic disparities in gingivitis, as well as to reduce the overall burden of oral disease in the population as a whole. The study will elucidate the dose- response relationship of the anti-inflammatory effects of vitamin D, which in turn may lead to a revision of the current recommendations regarding nutritional supplementation of vitamin D in order to optimize the prevention of important medical conditions and diseases and reduce racial health disparities.