Effect of Vitamin D Supplementation on Doxorubicin-Induced Cardiotoxicity in Rats

Abstract Background Doxorubicin-induced cardiotoxicity is a worldwide problem. Vitamin D is a well-known beneficial vitamin for bone growth and calcium homeostasis but recently it is also known for its cardioprotective effects. The aim of this study is to investigate the potential protective role of vitamin D on the cardiac dysfunction induced by chronic doxorubicin exposure, and to throw more light on the possible underlying mechanism (s) for such effect. Materials and Methods: 70 female Albino-rats were divided into 4 groups; control group (C), Doxorubicin-treated group (Dox): given i.p. injection of Dox in a dose of 2.5 mg/kg body weight (cumulative dose: 15 mg/kg) over 3 weeks, vitamin Dsupplemented group (Vit D): given vitamin D by oral gavage in a dose of 500 IU/kg daily, 5 days a week, also for 3 weeks and the combined Doxorubicintreated+vitamin D-supplemented group (Dox+Vit D). At the end of the experiment, ECG was recorded and in vitro isolated heart study was performed on Langendoroff preparation to measure peak tension (PT), time to peak tension (TPT), half relaxation time (HRT) and myocardial flow rate (MFR). Body and cardiac weights, plasma levels of brain naturetic peptide (BNP), cardiac troponin I (cTnI), vitamin D and total calcium and cardiac tissue heat shock protein 20, total antioxidant capacity (TAC) and malondialdehyde (MDA) were measured. Also, cardiac tissues were histopathologically assessed. Results: Dox-treated rats showed significant decrease in the final body weight (fBW), significant prolongation of the P-R interval, QRS duration, observed Q-T (Q-TO) and corrected Q-T (Q-Tc) with significant depression of the R voltage. In addition, there was a significant decrease in the in vitro heart rate, significant depression in PT, PT/LV and MFR together with significant prolongation in TPT& 3 HRT. These changes were accompanied by significant elevation of plasma BNP, cTnI and in cardiac tissue MDA and a significant decrease in plasma vit D, total calcium and cardiac tissue TAC and HSP20. Histopathological examination revealed markedly distorted muscle fibers with indistinct cell borders, bright eosinophilic cytoplasm, intra-cytoplasmic vacuoles and small pyknotic nuclei or absent nuclei, together with interstitial edema & aggregates of inflammatory cells and thick irregular collagen fibers in between the muscle fibers. Concomitant supplementation of vitamin D to the doxorubicin treated rats resulted in significant decrease in PR interval, QRS duration, MDA and significant increase PT, PT/LV, MFR, MFR/LV, plasma vitamin D, total calcium and TAC compared to the Dox treated rats to be insignificantly different from the control group. Plasma BNP and cTnI were significantly decreased while cardiac HSP20 was significantly increased compared to the Dox-treated rats, yet these parameters were still significant from the control group. Meanwhile, fBW, Q-TO and Q-Tc intervals, and TPT remained insignificantly changed from the DOX group. These findings were associated by regaining the normal collagen fiber distribution between cardiac muscle fibers with resolution of interstitial edema. Conclusion: Vitamin D supplementation can partially mitigate cardiac dysfunction induced by chronic doxorubicin by improving the cardiac antioxidant state and heat shock protein 20 level. Key words: Doxorubicin, cardiac dysfunction, vitamin D, isolated heart studies, BNP, HSP20.

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Synergistic Effects of Exercise Training and Vitamin D Supplementation on Mitochondrial Function of Cardiac Tissue, Antioxidant Capacity, and Tumor Growth in Breast Cancer in Bearing-4T1 Mice

Frontiers in Physiology ◽

10.3389/fphys.2021.640237 ◽

2021 ◽

Vol 12 ◽

Author(s):

Ali Jafari ◽

Dariush Sheikholeslami-Vatani ◽

Farnoosh Khosrobakhsh ◽

Neda Khaledi

Keyword(s):

Breast Cancer ◽

Gene Expression ◽

Vitamin D ◽

Exercise Training ◽

Cardiac Tissue ◽

Synergistic Effects ◽

Cancer Control ◽

Heart Tissue ◽

Vitamin D Supplementation ◽

Control Group

Both regular exercise training and vitamin D consumption are beneficial for patients with cancer. The study investigated the effects of interval exercise training (IET) or/and vitamin D supplementation on the gene expression involved in mitochondrial function of heart tissue, tumor size, and total antioxidant capacity (TAC) in breast cancer (BC) model mice. We assigned random 40 female NMRI mice to five equal groups (n = 8); the healthy control group (H.C), cancer control group (Ca.C), cancer with the vitamin D group (Ca.VD), cancer exercise group (Ca.Ex), and cancer exercise along with the vitamin D group (Ca.Ex.VD). Forty-eight hours after treatment, we anesthetized the animals and performed the isolation of heart tissue and blood serum for further studies. The results showed that the lowest mean body weight at the end of the treatments was related to Ca.C (p = 0.001). Vitamin D treatment alone has increased tumor volume growth by approximately 23%; in contrast, co-treatment with exercise and vitamin D inhibited tumor growth in mice (P = 0.001), compared with the cancer control (12%). TAC levels were higher in the group that received both vitamin D and exercise training (Ca.Ex.VD) than in the other treatment groups (Ca.VD and Ca.Ex) (p = 0.001). In cardiac tissue, vitamin D treatment induces an elevation significantly of the mRNA expression of Pgc1−α, Mfn-1, and Drp-1 genes (p = 0.001). The study has shown the overexpression of vitamin D in female mice, and synergistic effects of IET with vitamin D on weight loss controlling, antitumorigenesis, improvement of antioxidant defense, and the modulation of gene expression. The synergistic responses were likely by increasing mitochondrial fusion and TAC to control oxidative stress. We recommended being conducted further studies on mitochondrial dynamics and biogenesis focusing on risk factors of cardiovascular disease (CVD) in patients with BC.

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Single High-Dose Vitamin D Supplementation as an Approach for Reducing Ultramarathon-Induced Inflammation: A Double-Blind Randomized Controlled Trial

Nutrients ◽

10.3390/nu13041280 ◽

2021 ◽

Vol 13 (4) ◽

pp. 1280

Author(s):

Jan Mieszkowski ◽

Andżelika Borkowska ◽

Błażej Stankiewicz ◽

Andrzej Kochanowicz ◽

Bartłomiej Niespodziński ◽

...

Keyword(s):

Vitamin D ◽

Inflammatory Marker ◽

Controlled Trial ◽

Vitamin D Supplementation ◽

Oncostatin M ◽

Control Group ◽

High Dose ◽

Double Blind ◽

Single High Dose ◽

High Dose Vitamin

Purpose: A growing number of studies indicate the importance of vitamin D supplementation for sports performance. However, the effects of a single high-dose vitamin D supplementation on ultramarathon-induced inflammation have not been investigated. We here analyzed the effect of a single high-dose vitamin D supplementation on the inflammatory marker levels in ultramarathon runners after an ultramarathon run (maximal run 240 km). Methods: In the study, 35 runners (amateurs) were assigned into two groups: single high-dose vitamin D supplementation group, administered vitamin D (150,000 IU) in vegetable oil 24 h before the start of the run (n = 16); and placebo group (n = 19). Blood was collected for analysis 24 h before, immediately after, and 24 h after the run. Results: Serum 25(OH)D levels were significantly increased after the ultramarathon in both groups. The increase was greater in the vitamin D group than in the control group. Based on post-hoc and other analyses, the increase in interleukin 6 and 10, and resistin levels immediately after the run was significantly higher in runners in the control group than that in those in the supplementation group. Leptin, oncostatin M, and metalloproteinase tissue inhibitor levels were significantly decreased in both groups after the run, regardless of the supplementation. Conclusions: Ultramarathon significantly increases the serum 25(OH)D levels. Attenuation of changes in interleukin levels upon vitamin D supplementation confirmed that vitamin D has anti-inflammatory effect on exercise-induced inflammation.

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Abstract 14201: The Application of Hipsc-derived Cardiomyocytes Paced by Re-entrant Waves for Drug Assessment

Circulation ◽

10.1161/circ.142.suppl_3.14201 ◽

2020 ◽

Vol 142 (Suppl_3) ◽

Author(s):

Junjun Li ◽

Itsunari Minami ◽

Shigeru Miyagawa ◽

Xiang Qu ◽

YING HUA ◽

...

Keyword(s):

Cardiac Tissue ◽

Troponin T ◽

Field Potential ◽

Electrical Signal ◽

Assessment System ◽

K Channel ◽

Control Group ◽

Culture Dish ◽

Robust Response

Introduction: How to precisely evaluate response in newly developed medications in vitro may be a great concern in drug screening. We modified normal low-attachment culture dish and created closed-loop tissue ring from single hiPSC-CMs. We hypothesized that the re-entrant wave (ReW) could originate and pace the cardiac tissue ring, and the CMs under pacing could be matured and used for drug assessment. Methods: PDMS wells and pillars were mounted in low-attachment petri dishes (Figure 1A). 4 х 10 5 hiPSC-CMs were plated into the wells to form tissue ring where the ReW could spontaneously originate. After cultivation for 14 days, the hiPSC-CMs were evaluated by immunostaining and gene expression. Micro electrode array (MEA) were used to evaluating the CM response to different drugs. Results: The electrical signal recorded by MEA indicated that the ReWs could make the CMs beat at a much higher rate than the Control group (Figure 1B, 123.26 ± 10.36 bpm vs. 14.08 ± 4.53 bpm, p<0.0001). After 14 day culture, the ReW group demonstrated significantly higher expression of Troponin T (TnT2), myosin heavy chain 7 (β-MHC), and α-actinin. Interestingly, the α-actinin staining indicated alignment of CMs within the ReW group (Figure 1C). The CMs under ReW pacing showed robust response to several cardiac compounds including E4031, (hERG K+ channel blocker, Figure 1D and E), isoproterenol (β adrenoceptor agonist) and propranolol (beta-blocker). Both the field potential as well as the Ca 2+ transients showed correlated dose-dependent change and the recovering after washout of the drugs. Conclusions: The ReWs could spontaneously originate in the cultured cardiac tissue ring with enhancement of the maturation in the hiPSC-CMs and robust response to various drugs, indicating the system as a robust drug assessment system with multiple read-out methods.

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Vitamin D Supplementation Modestly Reduces Serum Iron Indices of Healthy Arab Adolescents

Nutrients ◽

10.3390/nu10121870 ◽

2018 ◽

Vol 10 (12) ◽

pp. 1870 ◽

Cited By ~ 5

Author(s):

Mohammad Masoud ◽

Majed Alokail ◽

Sobhy Yakout ◽

Malak Khattak ◽

Marwan AlRehaili ◽

...

Keyword(s):

Vitamin D ◽

Vitamin D Deficiency ◽

Serum Iron ◽

Iron Status ◽

Group Analysis ◽

Vitamin D Supplementation ◽

Control Group ◽

Post Intervention ◽

King Saud University ◽

Deficiency Type

Vitamin D deficiency has been shown to affect iron status via decreased calcitriol production, translating to decreased erythropoiesis. The present study aimed to determine for the first time whether vitamin D supplementation can affect iron levels among Arab adolescents. A total of 125 out of the initial 200 Saudi adolescents with vitamin D deficiency (serum 25(OH)D < 50 nmol/L) were selected from the Vitamin D-School Project of King Saud University in Riyadh, Saudi Arabia. Cluster randomization was done in schools, and students received either vitamin D tablets (1000 IU/day) (N = 53, mean age 14.1 ± 1.0 years) or vitamin D-fortified milk (40IU/200mL) (N = 72, mean age 14.8 ± 1.4 years). Both groups received nutritional counseling. Anthropometrics, glucose, lipids, iron indices, and 25(OH)D were measured at baseline and after six months. Within group analysis showed that post-intervention, serum 25(OH)D significantly increased by as much as 50%, and a parallel decrease of −42% (p-values <0.001 and 0.002, respectively) was observed in serum iron in the tablet group. These changes were not observed in the control group. Between-group analysis showed a clinically significant increase in serum 25(OH)D (p = 0.001) and decrease in iron (p < 0.001) in the tablet group. The present findings suggest a possible inhibitory role of vitamin D supplementation in the iron indices of healthy adolescents whose 25(OH)D levels are sub-optimal but not severely deficient, implying that the causal relationship between both micronutrients may be dependent on the severity of deficiency, type of iron disorder, and other vascular conditions that are known to affect hematologic indices. Well-designed, randomized trials are needed to confirm the present findings.

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Effects of Stratified Vitamin D Supplementation in Middle-Aged and Elderly Individuals with Vitamin D Insufficiency

Hormone and Metabolic Research ◽

10.1055/a-0746-5031 ◽

2018 ◽

Vol 50 (10) ◽

pp. 747-753

Author(s):

Yanhui Lu ◽

Xiaomin Fu ◽

Lili Zhang ◽

Minyan Liu ◽

Xiaoling Cheng ◽

...

Keyword(s):

Vitamin D ◽

Vitamin D Deficiency ◽

Vitamin D3 ◽

Intervention Group ◽

Vitamin D Insufficiency ◽

Vitamin D Supplementation ◽

Control Group ◽

Middle Aged ◽

Oral Vitamin ◽

Severe Vitamin

AbstractThe incidence of vitamin D deficiency is high globally, and vitamin D supplementation draws particular attention. The objective of this study was to investigate the effects of stratified vitamin D supplementation in middle-aged and elderly individuals with vitamin D insufficiency in Beijing. A total of 448 subjects aged over 40 years old were selected from a community in Beijing. Among them, 100 middle-aged and elderly people with vitamin D insufficiency were randomly selected on a voluntary basis. They were further divided into control group and intervention group. The control group received health education and lifestyle guidance, and the intervention group received lifestyle guidance and vitamin D supplementation for nine months. The doses were stratified as follows: for vitamin D insufficiency, oral vitamin D3 supplement was given at 5000 IU/w; for mild vitamin D deficiency, oral vitamin D3 supplement was given at 10 000 IU/w; for severe vitamin D deficiency, oral vitamin D3 supplement was given at 15 000 IU/w. Safety evaluation was conducted after three-month treatment. The intervention group consisted of 8%, 62%, and 30% of cases who had vitamin D insufficiency, mild vitamin D deficiency, and severe vitamin D deficiency, respectively, which were similar with the control group. It showed that the blood 25(OH)D level increased significantly in the intervention group, from 14.30±4.30 ng/ml to 33.62±6.99 ng/ml (p<0.001), in contrast to insignificant change in the control group. Stratified vitamin D supplementation effectively increased the blood 25(OH)D level, as well as the number of cases with corrected vitamin D insufficiency or deficiency.

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Effect of vitamin D supplementation on disease activity (SLEDAI) and fatigue in Systemic Lupus Erythematosus patients with hipovitamin D: An Open Clinical Trial

Indonesian Journal of Rheumatology ◽

10.37275/ijr.v8i2.59 ◽

2018 ◽

Vol 8 (2) ◽

Author(s):

Achmad Rifa’i ◽

Handono Kalim ◽

Kusworini Kusworini ◽

Cesarius Singgih Wahono

Keyword(s):

Systemic Lupus Erythematosus ◽

Clinical Trial ◽

Vitamin D ◽

Placebo Group ◽

Disease Activity ◽

Lupus Erythematosus ◽

Vitamin D Supplementation ◽

Control Group ◽

Systemic Lupus ◽

Significant Difference

Background : Low level of vitamin D impact the disease activity and the degree of fatigue in SLE patients. This study aims to determine the effect of vitamin D supplementation on disease activity and fatigue condition in Systemic Lupus Erythematosus (SLE) patients with hipovitamin D.Methods: We performed an open clinical trial. Subjects were randomized into two different groups (supplementation or placebo) using simple random sampling. The treatment group got vitamin D3 softgel/ cholecalciferol 1200 IU/day or 30 mg/day, while the control group gotplacebo for 3 months. SLEDAI scores and FSS scores were calculated at pre and posttreatment.Results: There were 20 subjectsfor supplementation group and 19 subjects in the placebo group. From this study, before and after treatment, we found a significant difference of mean level of vitamin D in supplementation group (p=0.000), and no significant difference inpatients with placebo (p=0.427). Moreover, from the SLEDAI score analysis, observed a significant difference bothin the supplemented group (p=0.000) and the placebo group (p=0.006). FSS scores significantly different in the supplemented group (p=0.000). Incorrelation test,there was a negative correlation (r=-0763) between vitamin D level and disease activity (SLEDAI), and both showing stastistical significance between thepre supplementation (p=0.000) and post supplementation (r=-0846; p=0.000). Similarly to theFSS scores, there was a meaningfulnegative correlation (r=-0.931, p=0.000) between the level of vitamin D with FSS scores pre and post supplementation (r=-0.911; p= 0.000). Furthermore, there was a significant correlation between disease activity (SLEDAI) pre supplementation with fatigue condition pre supplementation (r=0.846; p = 0.000) and postsupplementation (r=0.913; p= 0.000).Conclusion: The supplementation of vitamin D 1200 IU per day in patients with SLE improve disease activity and degree of fatigue. Keywords: vitamin D, disease activity, fatigue, SLE

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The combination of miacalcic, calcium lactate, and vitamin C as postextracted alveolar bone resorption inhibitor

Dental Journal (Majalah Kedokteran Gigi) ◽

10.20473/j.djmkg.v43.i3.p141-145 ◽

2010 ◽

Vol 43 (3) ◽

pp. 141

Author(s):

Sri Kentjananingsih

Keyword(s):

Vitamin D ◽

Bone Density ◽

Bone Resorption ◽

Vitamin C ◽

Group Treatment ◽

Alveolar Bone ◽

Vitamin D Supplementation ◽

Calcium Lactate ◽

Control Group ◽

Significant Difference

Background: Tooth extraction can cause alveolar resorption, and will reduce the denture retention. The process of bone resorption looks like the process of osteoporosis. Calcium and vitamin D supplementation is the rational therapy for minimizing bone loss. Miacalcic is the drug of choice for osteporotic patient. Purpose: This study is aimed to know whether the combination of miacalcic, calcium lactate, and vitamin C are effective in inhibiting post extracted alveolar resorption. Methods: Thirty three healthy postmenopausal women were chosen as samples and they were classified randomly into control group (without treatment), 1st experiment group (treatment was started 3 months post extraction), and 2nd experiment group (treatment was started at the 2nd day post extraction). The treatment was done by giving miacalcic nasal spray, calcium lactate 500 mg and vitamin C 100 mg tablets every morning in 10 days every month for 3 months. X-ray photo of the post extracted area were taken an hour, 3 months, and 6 months post-extraction. Results: After 6 month, there was significant difference in buccolingual thickness decreasing among three groups (p<0.05). The maximum mean difference of buccolingual thickness decreasing was 0.72 mm, between control and 2nd experiment groups. There was no significant difference about decreasing bone density among them (p>0.10). The maximum difference of the mean of density decreasing was 1,906 g/cm2/mm between control and 2nd experiment groups. The increasing density mostly occurred in the 2nd experiment group. Conclusion: The combination of miacalcic, calcium lactate, and vitamin C are effective for inhibiting alveolar resorption, although statistically there was no significant difference about bone density decreasing. The sooner this treatment is given the better result will be achieved.Latar belakang: Pencabutan gigi menyebabkan resorpsi tulang alveolaris, dan akan mengurangi retensi geligi tiruan. Proses resorpsi tulang alveol pada osteoporosis mirip dengan proses resorpsi tulang pada penyembuhan luka bekas pencabutan. Miacalcic adalah obat utama untuk penderita osteoporosis. Kalsium dan vitamin D merupakan terapi yang rasional untuk meminimalkan resorpsi tulang. tujuan: Membuktikan apakah kombinasi miacalcic, kalsium laktat, and vitamin C juga efektif menghambat resorpsi tulang alveol pasca pencabutan. Metode: Sampel 33 wanita postmenopause yang sehat, terbagi secara acak ke dalam kelompok kontrol (tanpa perlakuan), kelompok eksperimen 1 (perlakuan mulai 3 bulan pasca pencabutan) dan kelompok eksperimen 2 (perlakuan mulai hari kedua pasca pencabutan). Perlakuannya yaitu: pemberian miacalcic semprot hidung, tablet kalsium laktat 500 mg dan vitamin C 100 mg setiap pagi, 10 hari dalam sebulan, selama tiga bulan. Foto sinar-X dari regio pasca pencabutan dibuat satu jam, 3 bulan, dan 6 bulan pasca pencabutan. Hasil: 6 bulan pasca-cabut, ada beda bermakna perihal selisih tebal bukolingual tulang alveol antar ketiga kelompok (p<0,05). Rerata penurunan ketebalan ini maksimal sebanyak 0.72 mm, antara kelompok kontrol dan kelompok eksperimen 2. Penurunan kepadatan tulang antar ketiga kelompok tidak bermakna (p>0,10). Beda maksimum rerata kepadatan tulang antara kelompok kontrol dan kelompok eksperimen 2 sebesar 1,906 g/cm2/mm. Peningkatan kepadatan terbanyak dialami anggota kelompok eksperimen 2. Kesimpulan: Kombinasi miacalcic, kalsium laktat, vitamin C efektif menghambat resorpsi tulang alveolaris, walaupun secara statistik beda penurunan kepadatan tidak bermakna. Makin awal pemberian perlakuan, hasilnya akan lebih baik.

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Paeoniflorin and Hydroxysafflor Yellow A in Xuebijing Injection Attenuate Sepsis-Induced Cardiac Dysfunction and Inhibit Proinflammatory Cytokine Production

Frontiers in Pharmacology ◽

10.3389/fphar.2020.614024 ◽

2021 ◽

Vol 11 ◽

Author(s):

Xin-Tong Wang ◽

Zhen Peng ◽

Ying-Ying An ◽

Ting Shang ◽

Guangxu Xiao ◽

...

Keyword(s):

Cardiac Function ◽

Cardiac Dysfunction ◽

Cardiac Tissue ◽

Myocardial Dysfunction ◽

Cecal Ligation ◽

Hydroxysafflor Yellow A ◽

Sepsis Management ◽

Xuebijing Injection

Sepsis-induced myocardial dysfunction is a major contributor to the poor outcomes of septic shock. As an add-on with conventional sepsis management for over 15 years, the effect of Xuebijing injection (XBJ) on the sepsis-induced myocardial dysfunction was not well understood. The material basis of Xuebijing injection (XBJ) in managing infections and infection-related complications remains to be defined. A murine cecal ligation and puncture (CLP) model and cardiomyocytes in vitro culture were adopted to study the influence of XBJ on infection-induced cardiac dysfunction. XBJ significantly improved the survival of septic-mice and rescued cardiac dysfunction in vivo. RNA-seq revealed XBJ attenuated the expression of proinflammatory cytokines and related signalings in the heart which was further confirmed on the mRNA and protein levels. Xuebijing also protected cardiomyocytes from LPS-induced mitochondrial calcium ion overload and reduced the LPS-induced ROS production in cardiomyocytes. The therapeutic effect of XBJ was mediated by the combination of paeoniflorin and hydroxysafflor yellow A (HSYA) (C0127-2). C0127-2 improved the survival of septic mice, protected their cardiac function and cardiomyocytes while balancing gene expression in cytokine-storm-related signalings, such as TNF-α and NF-κB. In summary, Paeoniflorin and HSYA are key active compounds in XBJ for managing sepsis, protecting cardiac function, and controlling inflammation in the cardiac tissue partially by limiting the production of IL-6, IL-1β, and CXCL2.

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Vitamin D/CD46 Crosstalk in Human T Cells in Multiple Sclerosis

Frontiers in Immunology ◽

10.3389/fimmu.2020.598727 ◽

2020 ◽

Vol 11 ◽

Author(s):

Justin Killick ◽

Joanne Hay ◽

Elena Morandi ◽

Sonja Vermeren ◽

Saniya Kari ◽

...

Keyword(s):

Multiple Sclerosis ◽

Vitamin D ◽

T Cells ◽

T Cell ◽

Chronic Inflammatory Disease ◽

Vitamin D Supplementation ◽

Type I ◽

T Cell Migration ◽

The Impact

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS), in which T-cell migration into the CNS is key for pathogenesis. Patients with MS exhibit impaired regulatory T cell populations, and both Foxp3+ Tregs and type I regulatory T cells (Tr1) are dysfunctional. MS is a multifactorial disease and vitamin D deficiency is associated with disease. Herein, we examined the impact of 1,25(OH)2D3 on CD4+ T cells coactivated by either CD28 to induce polyclonal activation or by the complement regulator CD46 to promote Tr1 differentiation. Addition of 1,25(OH)2D3 led to a differential expression of adhesion molecules on CD28- and CD46-costimulated T cells isolated from both healthy donors or from patients with MS. 1,25(OH)2D3 favored Tr1 motility though a Vitamin D-CD46 crosstalk highlighted by increased VDR expression as well as increased CYP24A1 and miR-9 in CD46-costimulated T cells. Furthermore, analysis of CD46 expression on T cells from a cohort of patients with MS supplemented by vitamin D showed a negative correlation with the levels of circulating vitamin D. Moreover, t-Distributed Stochastic Neighbor Embedding (t-SNE) analysis allowed the visualization and identification of clusters increased by vitamin D supplementation, but not by placebo, that exhibited similar adhesion phenotype to what was observed in vitro. Overall, our data show a crosstalk between vitamin D and CD46 that allows a preferential effect of Vitamin D on Tr1 cells, providing novel key insights into the role of an important modifiable environmental factor in MS.

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Effect of Maternal Postpartum and Infant Intermittent Vitamin D Supplementation on Infant Vitamin D Status: A Systematic Review and Meta-Analysis of Trials (P11-089-19)

Current Developments in Nutrition ◽

10.1093/cdn/nzz048.p11-089-19 ◽

2019 ◽

Vol 3 (Supplement_1) ◽

Author(s):

Karen O'Callaghan ◽

Mahgol Taghivand ◽

Anna Zuchniak ◽

Akpevwe Onoyovwi ◽

Jill Korsiak ◽

...

Keyword(s):

Vitamin D ◽

Meta Analysis ◽

Vitamin D Supplementation ◽

Small Sample ◽

Risk Of Bias ◽

World Health ◽

Control Group ◽

Cochrane Central Register ◽

Vitamin D Status ◽

Statistical Heterogeneity

Abstract Objectives To determine the response of infant (≤ 1 year) circulating 25-hydroxyvitamin D (25(OH)D) to maternal postpartum or infant intermittent vitamin D supplementation in comparison to current recommendations of direct daily oral infant supplementation (400 IU/d). Methods MEDLINE, MEDLINE In-Process, Embase, the Cochrane Database of Systematic Reviews, and the Cochrane Central Register of Controlled Trials were searched up to December 4th 2018. A systematic search of online trial registries for unpublished, ongoing, or planned trials was also completed. Risk of bias was assessed using the Cochrane Risk Assessment Tool. Meta-analysis was limited to trials with a control group of infants receiving 400 IU vitamin D/d. A weighted mean difference (WMD) and 95% confidence interval (CI) was generated using infant 25(OH)D as a continuous outcome. Random-effects models accounted for within- and between-study variability. Statistical heterogeneity was quantified with the I2 statistic. Results A total of 28 trials were included, representing data from all 6 World Health Organization world regions. Of the 25 trials that specified a calciferol form, the majority (88%) employed vitamin D3. Six trials (21%) had an overall low risk of bias. Six trials qualified for meta-analysis, stratified by maternal (n = 4) and infant (n = 2) administration. Maternal supplementation resulted in a modestly lower infant vitamin D status than daily infant supplementation (WMD =-7.3 nmol/L; 95% CI: -14.0 to -0.6; I2 = 37%, P = 0.17). Comparison of infant intermittent bolus dosing to daily supplementation was limited by a small sample size and substantial heterogeneity, resulting in a wide CI (WMD = 10.2 nmol/L; 95% CI: -42.9 to 63.3; I2 = 96%, P < 0.001). Safety outcomes, including effects on calcium homeostasis, were inconsistently reported. Four ongoing trials were identified as potential contributors to future reviews. Conclusions Evidence to support the use of specific alternative maternal or infant regimens to substitute for current daily infant vitamin D supplementation is weak and inconsistent. Dose-ranging, adequately powered trials are required to establish the efficacy and safety of feasible alternative strategies to prevent infant vitamin D deficiency Funding Sources SickKids C-GCH Growth and Development Fellowship.

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