Dissecting high from low responders in a vitamin D3 intervention study

Saksa, Noora; Neme, Antonio; Ryynänen, Jussi; Uusitupa, Matti; Mello, Vanessa D. de; Voutilainen, Sari; Nurmi, Tarja; Virtanen, Jyrki K.; Tuomainen, Tomi‐Pekka; Carlberg, Carsten

doi:10.1016/j.jsbmb.2014.11.012

Cited by 48 publications

(62 citation statements)

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“…The VD 3 deficiency‐induced inflammatory status may create an environment conducive for the progression of T2DCP. Changes in serum 25(OH)D 3 could be reflected by alterations in the expression of genes involved in the VD 3 pathway . The elevated levels of VDR and PTPN2 expression after VD 3 treatment could result in the downregulation of downstream proinflammatory proteins such as NF‐κB .…”

Section: Discussionmentioning

confidence: 99%

Relationship between serum 25‐hydroxyvitamin D₃levels and severity of chronic periodontitis in type 2 diabetic patients: A cross‐sectional study

Wang

Xinyi

Jiang

et al. 2019

J of Periodontal Research

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Background and Objectives Serum 25‐hydroxyvitamin D3 (25(OH)D3), a newly emerged immune regulator, is considered to be involved in type 2 diabetic periodontitis (T2DCP). However, the risk factors and genes with altered expression that influence the progression and severity of T2DCP remain unknown. Accordingly, the aim of the present study was to elucidate the relationship between 25(OH)D3 deficiency and severity of T2DCP as well as the potential mechanisms. Material and Methods A total of 182 subjects were divided into two groups: chronic periodontitis without diabetes (P group, n = 88) and type 2 diabetes mellitus with periodontitis (DM+P group, n = 94). Patients in both groups were further classified according to age as young (Y) and elderly (E) for a total of four groups: P/Y, P/E, DM+P/Y, and DM+P/E. Periodontal status was evaluated based on the probing depth (PD) and clinical attachment loss (CAL). The serum levels of human 25(OH)D3, interleukin (IL)‐1β, and tumor necrosis factor (TNF)‐α were measured by enzyme‐linked immunosorbent assays. Immunohistochemistry was used to measure the expression of protein tyrosine phosphatase non‐receptor type 2 (PTPN2), vitamin D receptor (VDR), and JAK/STAT proteins in the gingival tissue. Results Serum 25(OH)D3 levels were lower in the DM+P group than those in the P group (P < 0.001). When the patients were subgrouped according to age, 25(OH)D3 deficiency was more commonly found in DM+P/E than in DM+P/Y (67% vs 51%), with a significant difference detected in the 25(OH)D3 quartile of 15‐20 ng/mL (P = 0.007). The 25(OH)D3 level showed a significant negative correlation with fasting blood glucose (FBG) (r = −0.623), serum IL‐1β (r = −0.392), serum TNF‐α (r = −0.218), PD (r = −0.269), and CAL (r = −0.305) in the DM+P group (all P < 0.05), but not with hemoglobin A1c (P = 0.123). Additionally, reduced VDR and PTPN2 expression levels were observed in DM+P patients, whereas JAK1 and p‐STAT5 protein levels were increased in this group. Conclusions Vitamin D3 deficiency is strongly associated with T2DCP, and age mediates this relationship. Abnormal FBG and IL‐1β levels should be considered as important potential risk factors for the progression and severity of T2DCP. Moreover, 25(OH)D3 deficiency may be related to the immune function of T2DCP by weakening PTPN2 signaling.

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Section: Discussionmentioning

confidence: 99%

Relationship between serum 25‐hydroxyvitamin D₃levels and severity of chronic periodontitis in type 2 diabetic patients: A cross‐sectional study

Wang

Xinyi

Jiang

et al. 2019

J of Periodontal Research

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“…Moreover, the large variation in biological response to vitamin D 3 supplementation observed in isolated human peripheral blood monocytes also supports the plausibility of our findings. 39,40 …”

Section: Discussionmentioning

confidence: 99%

Vitamin D Receptor Genotype, Vitamin D₃ Supplementation, and Risk of Colorectal Adenomas

et al. 2017

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IMPORTANCE Despite epidemiological and preclinical evidence suggesting that vitamin D and calcium inhibit colorectal carcinogenesis, daily supplementation with these nutrients for 3 to 5 years was not found to significantly reduce the risk of recurrent colorectal adenomas in a recent randomized clinical trial. OBJECTIVE To investigate whether common variants in 7 vitamin D and calcium pathway genes (VDR, GC, DHCR7, CYP2R1, CYP27B1, CYP24A1, and CASR) modify the effects of vitamin D3 or calcium supplementation on colorectal adenoma recurrence. DESIGN, SETTING, AND PARTICIPANTS We examined 41 candidate single-nucleotide polymorphisms (SNPs) in 2259 participants in a randomized, double-blind, placebo-controlled trial conducted at 11 clinical centers in the United States. Eligibility criteria included a recently diagnosed adenoma and no remaining colorectal polyps after complete colonoscopy. The study’s treatment phase ended on August 31, 2013, and the analysis for the present study took place from July 28, 2014, to October 19, 2016. INTERVENTIONS Daily oral supplementation with vitamin D3 (1000 IU) or calcium carbonate (1200 mg elemental calcium) or both or neither. MAIN OUTCOMES AND MEASURES The outcomes assessed were the occurrence of 1 or more adenomas or advanced adenomas (estimated diameter, ≥ 1 cm; or with villous histologic findings, high-grade dysplasia, or cancer) during follow-up. Treatment effects and genotype associations and interactions were estimated as adjusted risk ratios (RRs) and 95% confidence intervals (CIs). The effective number of independent SNPs was calculated to correct for multiple testing. RESULTS Among the 2259 participants randomized, 1702 were non-Hispanic whites who completed the trial and had genotype data for analysis (1101 men; mean [SD] age 58.1 [6.8] years). The effect of vitamin D3 supplementation on advanced adenomas, but not on adenoma risk overall, significantly varied according to genotype at 2 VDR SNPs (rs7968585 and rs731236) in linkage disequilibrium (D′ = 0.98; r2 = 0.6). For rs7968585, among individuals with the AA genotype (26%), vitamin D3 supplementation reduced risk by 64% (RR, 0.36; 95% CI, 0.19–0.69; P = .002; absolute risk decreased from 14.4% to 5.1%). Among individuals with 1 or 2 G alleles (74%), vitamin D3 supplementation increased risk by 41% (RR, 1.41; 95%CI, 0.99–2.00; P = .05; absolute risk increased from 7.7% to 11.1%; P < .001 for interaction). There were no significant interactions of genotypes with calcium supplementation. CONCLUSIONS AND RELEVANCE Our findings suggest that benefits from vitamin D3 supplementation for the prevention of advanced colorectal adenomas may vary according to vitamin D receptor genotype. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00153816

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“…When we investigated samples from the VitDmet study (Clinicaltrials.gov: NCT01479933), in which elderly, pre-diabetic persons were during Finnish winter daily supplemented with vitamin D 3 (0, 40 and 80 µg), we found that changes in serum 25(OH)D 3 concentrations do not completely correlate with alterations in the expression of vitamin D target genes in PBMCs and adipose tissue [20][21][22][23][24]. We used these vitamin D status-triggered gene expression changes to classify the pre-diabetic individuals into high and low vitamin D responders.…”

Section: Introductionmentioning

confidence: 99%

Molecular evaluation of vitamin D responsiveness of healthy young adults

Seuter

Virtanen

Nurmi

et al. 2017

The Journal of Steroid Biochemistry and Molecular Biology

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Dissecting high from low responders in a vitamin D3 intervention study

Cited by 48 publications

References 36 publications

Relationship between serum 25‐hydroxyvitamin D₃levels and severity of chronic periodontitis in type 2 diabetic patients: A cross‐sectional study

Relationship between serum 25‐hydroxyvitamin D₃levels and severity of chronic periodontitis in type 2 diabetic patients: A cross‐sectional study

Vitamin D Receptor Genotype, Vitamin D₃ Supplementation, and Risk of Colorectal Adenomas

Molecular evaluation of vitamin D responsiveness of healthy young adults

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Dissecting high from low responders in a vitamin D3 intervention study

Cited by 48 publications

References 36 publications

Relationship between serum 25‐hydroxyvitamin D3levels and severity of chronic periodontitis in type 2 diabetic patients: A cross‐sectional study

Relationship between serum 25‐hydroxyvitamin D3levels and severity of chronic periodontitis in type 2 diabetic patients: A cross‐sectional study

Vitamin D Receptor Genotype, Vitamin D3 Supplementation, and Risk of Colorectal Adenomas

Molecular evaluation of vitamin D responsiveness of healthy young adults

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Relationship between serum 25‐hydroxyvitamin D₃levels and severity of chronic periodontitis in type 2 diabetic patients: A cross‐sectional study

Relationship between serum 25‐hydroxyvitamin D₃levels and severity of chronic periodontitis in type 2 diabetic patients: A cross‐sectional study

Vitamin D Receptor Genotype, Vitamin D₃ Supplementation, and Risk of Colorectal Adenomas