Rhmannioside D

Rehmannioside D is a carotenoid glycoside.

Vitamin D reduces the inflammatory response by Porphyromonas gingivalis infection by modulating human beta-defensin-3 in human gingival epithelium and periodontal ligament cells.[Pubmed:28384529]

Int Immunopharmacol. 2017 Jun;47:106-117.

Periodontitis is a multifactorial polymicrobial infection characterized by a destructive inflammatory process. Porphyromonas gingivalis, a Gram-negative black-pigmented anaerobe, is a major pathogen in the initiation and progression of periodontitis; it produces several virulence factors that stimulate human gingival epithelium (HGE) cells and human periodontal ligament (HPL) cells to produce various inflammatory mediators. A variety of substances, such as vitamin D, have growth-inhibitory effects on some bacterial pathogens and have shown chemo-preventive and anti-inflammatory activity. We used a model with HGE and HPL cells infected with P. gingivalis to determine the influence of vitamin D on P. gingivalis growth and adhesion and the immunomodulatory effect on TNF-alpha, IL-8, IL-12 and human-beta-defensin 3 production. Our results demonstrated, firstly, the lack of any cytotoxic effect on the HGE and HPL cells when treated with vitamin D; in addition, vitamin D inhibited P. gingivalis adhesion and infectivity in HGE and HPL cells. Our study then showed that vitamin D reduced TNF-alpha, IL-8, IL-12 production in P. gingivalis-infected HGE and HPL cells. In contrast, a significant upregulation of the human-beta-defensin 3 expression in HGE and HPL cells induced by P. gingivalis was demonstrated. Our results indicate that vitamin D specifically enhances the production of the human-beta-defensin 3 antimicrobial peptide and exerts an inhibitory effect on the pro-inflammatory cytokines, thus suggesting that vitamin D may offer possible therapeutic applications for periodontitis.

Effect of Monthly High-Dose Vitamin D Supplementation on Cardiovascular Disease in the Vitamin D Assessment Study : A Randomized Clinical Trial.[Pubmed:28384800]

JAMA Cardiol. 2017 Jun 1;2(6):608-616.

Importance: Cohort studies have reported increased incidence of cardiovascular disease (CVD) among individuals with low vitamin D status. To date, randomized clinical trials of vitamin D supplementation have not found an effect, possibly because of using too low a dose of vitamin D. Objective: To examine whether monthly high-dose vitamin D supplementation prevents CVD in the general population. Design, Setting, and Participants: The Vitamin D Assessment Study is a randomized, double-blind, placebo-controlled trial that recruited participants mostly from family practices in Auckland, New Zealand, from April 5, 2011, through November 6, 2012, with follow-up until July 2015. Participants were community-resident adults aged 50 to 84 years. Of 47905 adults invited from family practices and 163 from community groups, 5110 participants were randomized to receive vitamin D3 (n = 2558) or placebo (n = 2552). Two participants retracted consent, and all others (n = 5108) were included in the primary analysis. Interventions: Oral vitamin D3 in an initial dose of 200000 IU, followed a month later by monthly doses of 100000 IU, or placebo for a median of 3.3 years (range, 2.5-4.2 years). Main Outcomes and Measures: The primary outcome was the number of participants with incident CVD and death, including a prespecified subgroup analysis in participants with vitamin D deficiency (baseline deseasonalized 25-hydroxyvitamin D [25(OH)D] levels <20 ng/mL). Secondary outcomes were myocardial infarction, angina, heart failure, hypertension, arrhythmias, arteriosclerosis, stroke, and venous thrombosis. Results: Of the 5108 participants included in the analysis, the mean (SD) age was 65.9 (8.3) years, 2969 (58.1%) were male, and 4253 (83.3%) were of European or other ethnicity, with the remainder being Polynesian or South Asian. Mean (SD) baseline deseasonalized 25(OH)D concentration was 26.5 (9.0) ng/mL, with 1270 participants (24.9%) being vitamin D deficient. In a random sample of 438 participants, the mean follow-up 25(OH)D level was greater than 20 ng/mL higher in the vitamin D group than in the placebo group. The primary outcome of CVD occurred in 303 participants (11.8%) in the vitamin D group and 293 participants (11.5%) in the placebo group, yielding an adjusted hazard ratio of 1.02 (95% CI, 0.87-1.20). Similar results were seen for participants with baseline vitamin D deficiency and for secondary outcomes. Conclusions and Relevance: Monthly high-dose vitamin D supplementation does not prevent CVD. This result does not support the use of monthly vitamin D supplementation for this purpose. The effects of daily or weekly dosing require further study. Trial Registration: clinicaltrials.gov Identifier: ACTRN12611000402943.