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

描述（由申请人提供）：在美国，与非西班牙裔白人相比，非西班牙裔黑人的慢性牙龈炎和牙周炎负担不成比例地高。慢性牙龈炎是一种高度流行的慢性炎症性疾病，可进展为牙周炎，牙周炎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可能在人体中具有抗炎作用尚不确定。最近的临床研究表明，维生素D对几个重要结果的有益作用可能发生在广泛的血清25-羟基维生素D（25-OHD）浓度范围内，可能高达需要维生素D摄入量的浓度，范围为目前维生素D RDA的2至10倍以上。由于深色皮肤色素沉着是维生素D光合作用的有效抑制剂，非西班牙裔黑人的血清25-OHD水平比非西班牙裔白人低得多。这些维生素D状况的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。 我们假设口服胆钙化醇补充剂可以降低非西班牙裔白人和非西班牙裔黑人在广泛的血清25-OHD浓度范围内对牙龈炎的易感性。 我们拟进行一项简单、单中心、随机、双盲、安慰剂对照、平行组剂量范围研究。我们将比较安慰剂与每天500 IU、2,500 IU和5,000 IU维生素D3的剂量。我们将比较剂量组之间因28天无限制菌斑生长（实验性牙龈炎）而发生的牙龈炎症的严重程度。此外，我们将评估25-OHD水平与牙龈炎症之间的关系。 这项研究的结果将产生几个重要的影响，因为膳食维生素D补充剂可能是一种简单、安全且廉价的方法，可以减少牙龈炎的种族/民族差异，并减少口腔疾病的总体负担。整个人群。该研究将阐明维生素D抗炎作用的剂量-反应关系，这反过来可能导致修订目前关于维生素D营养补充的建议，以优化重要医疗状况和疾病的预防，减少种族健康差异。

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.