Dose-dependent Anti-inflammatory Effects of Vitamin D in a Human Gingivitis Model

• Status: Completed
• Trial end date: 2011-09-01
• Target enrollment: 0
• Participant gender: All

Summary

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 10 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.

• Phase: Early Phase 1
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Boston University
• Collaborator: National Center for Complementary and Integrative Health (NCCIH)
• Treatments: Anti-Inflammatory Agents; Cholecalciferol; Ergocalciferols; Vitamin D; Vitamins

Criteria

Inclusion Criteria:

• informed written consent

• healthy subjects age 18-64 years old

• serum 25-hydroxyvitamin D concentration <62.5 nmol/L (<25 ng/mL)

Exclusion Criteria:

• increased risk for infectious endocarditis that require antibiotic prophylaxis prior to periodontal probing

• women who are postmenopausal

• pregnancy or planned pregnancy within the period of the trial

• Periodontitis (attachment loss ≥4 mm and probing depths≥5 mm on at least one interproximal site)

• Any need for immediate dental treatment (can be eligible after completion of treatment)

• history of hypercalcemia, malabsorption syndrome, abnormal sensitivity to vitamin D or hypervitaminosis D

• < 3 teeth with bleeding on probing

• < 20 teeth present or <8 interproximal spaces (i.e., papillae) in upper jaw

• mean plaque index > 3

• Current smoking or former smoking with cessation <5 years ago

• regular use of any medication for prevention or treatment of disease (including Aspirin, NSAIDs, corticosteroids, but NOT including contraceptives)

• Diabetes mellitus

• hypercalcemia (serum calcium > ULN),

• hypocalcemia (serum calcium < ULN),

• hyperparathyroidism (serum PTH concentration > ULN),

• hypoparathyroidism (serum PTH concentration < LLN)

• any cardiac rhythm abnormalities on baseline ECG

• use of tanning beds/unwillingness to abstain from use of tanning beds during study

• planned travel during study period / unwillingness to abstain from travel to the South or High Altitudes

• unwillingness to abstain from use of any supplements (including vitamin/mineral and herbal supplements) during study period