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Effectiveness of vitamin D2 supplementation on high-sensitivity C-reactive protein and other metabolic indices in menopausal Thai women: a randomized-controlled trial.
Indhavivadhana, S, Boonyachan, W, Rattanachaiyanont, M, Wongwananuruk, T, Techatraisak, K, Sa-Nga-Areekul, N
Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology. 2022;(1):83-89
Abstract
OBJECTIVE To investigate the effectiveness of vitamin D2 supplementation with ergocalciferol on high-sensitivity C-reactive protein (hsCRP) level and other cardio-metabolic indices in menopausal Thai women. MATERIALS AND METHODS A double-blind, randomized, placebo-controlled trial was conducted at the menopause clinic of a university hospital in Thailand from May 2017 to 2018. Participants were 80 postmenopausal women randomly assigned to treatment (N = 40, receiving vitamin D2 40,000 IU/week) or control (N = 40, receiving placebo) for 12 weeks. The primary outcome was hsCRP level, and secondary outcomes were cardio-metabolic profiles and 10-year risk of developing cardiovascular disease using the Framingham risk score. The changes from baseline to week-12 (Δ) of all outcomes were analyzed using a modified intention-to-treat (ITT) population. RESULTS The vitamin D2 (N = 39) and placebo (N = 37) groups were comparable in all baseline characteristics. The hsCRP level was significantly reduced in the vitamin D2 group (Δ of -0.39 ± 1.30 mg/L, p = .024) but not in the placebo group (Δ of -0.15 ± 1.15 mg/L, p = .521). However, the Δ of hsCRP had no statistical difference between groups; neither did the Δ of other cardio-metabolic parameters. CONCLUSION In menopausal Thai women, vitamin D2 supplementation with ergocalciferol 40,000 IU/week for 12 weeks can reduce hsCRP level; and the treatment might be superior to placebo. However, the hsCRP levels after 12 weeks between both groups were not statistically different. Clinical Trial Registration: Thai Clinical Trials Registry (TCTR20161216001).
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The Effects of Vitamin D-Enriched Mushrooms and Vitamin D3 on Cognitive Performance and Mood in Healthy Elderly Adults: A Randomised, Double-Blinded, Placebo-Controlled Trial.
Zajac, IT, Barnes, M, Cavuoto, P, Wittert, G, Noakes, M
Nutrients. 2020;(12)
Abstract
Despite abundant cross-sectional evidence that low vitamin D status is associated with risk of cognitive decline in ageing, interventional evidence for benefits of vitamin D supplementation is lacking. This study was a 6 month randomised, double-blinded placebo-controlled clinical trial of the effects of vitamin D3 (D3), enhanced vitamin D2 in a mushroom matrix (D2M), standard mushroom (SM) and placebo (PL) on cognition and mood in n = 436 healthy older male (49%) and female volunteers aged ≥ 60 years. Primary end points were change in serum vitamin D metabolites (25-OH-D, 25-OH-D2 and 25-OH-D3), cognitive performance, and mood over 24 weeks. Levels of total 25-OH-D and 25-OH-D3 were maintained in the D3 arm but decreased significantly (p < 0.05) in the remaining arms (D2M, SM and PL). Analysis also revealed differential changes in these metabolites depending on total vitamin D status at baseline. There were no significant effects of treatment on any of the measures of cognitive function or mood. Overall, the results show that daily supplementation of ~600 IU of vitamin D3 was sufficient to maintain 25-OH-D throughout winter months, but in contrast to existing cross-sectional studies there was no support for benefit of vitamin D supplementation for mood or cognition in healthy elderly people.
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A randomized double-blinded placebo controlled trial of ergocalciferol 40,000 versus 100,000 IU per week for vitamin D inadequacy in institutionalized postmenopausal women.
Mueangpaisarn, P, Chaiamnuay, S
Aging clinical and experimental research. 2020;(1):41-48
Abstract
BACKGROUND Vitamin D inadequacy is common in institutionalized post-menopausal women who are at the highest risk for osteoporotic fracture. AIM: To evaluate efficacy and safety of ergocalciferol 40,000 versus 100,000 IU per week for 12 weeks for vitamin D inadequacy in institutionalized postmenopausal women. METHOD A randomized double-blinded placebo-controlled trial was conducted in 94 institutionalized subjects with baseline 25(OH)D levels < 30 ng/mL. Subjects were randomized to receive ergocalciferol 40,000 (standard dose) or ergocalciferol 100,000 IU (high dose) per week. Serum 25(OH)D levels, calcium, phosphate, handgrip strength, time up and go (TUG) test and quality of life by EQ-5D-5L were measured at baseline and 12 weeks after randomization. RESULTS Of the 94 subjects enrolled, 85 subjects completed the study. Subjects in the high dose group had higher mean 25(OH)D levels than subjects in the standard group (51.73 ± 19.35 and 34.5 ± 9.12, p < 0.001). More subjects in the high dose group (90.9%) achieved optimal 25(OH)D levels (> 30 ng/mL) than those in the standard group (65.9%), p = 0.007. In a subgroup analysis of subjects with vitamin D deficiency (< 20 ng/mL, n = 44) and severe vitamin D deficiency (< 10 ng/mL, n = 9), more subjects in the high dose group achieved optimal 25(OH)D levels than those in the standard group (88% and 100% versus 47.4% and 16.7% with p of 0.007 and 0.018, respectively). There were no differences in handgrip strength, TUG, EQ-5D-5L and adverse events between groups. DISCUSSION/CONCLUSIONS Subjects who received high dose ergocalciferol achieved more optimal 25(OH)D levels than those who received standard dose. High dose ergocalciferol is preferred to optimize 25(OH)D levels in subjects with severe vitamin D deficiency.
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FGF23 and the PTH response to paricalcitol in chronic kidney disease.
D'Arrigo, G, Pizzini, P, Cutrupi, S, Tripepi, R, Tripepi, G, Mallamaci, F, Zoccali, C
European journal of clinical investigation. 2020;(2):e13196
Abstract
BACKGROUND The parathyroid glands are endowed both with receptors responsive to FGF23 and to 1,25 vitamin D. Vitamin D receptor (VDR) activation, besides lowering PTH, also raises serum FGF23. FGF23 has been implicated in parathyroid resistance to VDR activation but the issue has never been investigated in predialysis CKD patients. METHODS In the Paricalcitol and Endothelial Functio in Chronic Kidney Disease (PENNY) study (NCT01680198), a 12-week randomized trial in stage G3-4 CKD patients (placebo n = 44 and paricalcitol n = 44), we measured PTH and the active form of FGF23 with no missing value across the trial. RESULTS At baseline, serum FGF23 and PTH were inter-related (r = .54, P < .01). Paricalcitol reduced serum PTH (-75.1 pg/mL, 95% CI: -90.4 to -59.8; P < .001) and increased FGF23 (+107 pg/mL, 95% CI: 44-170 pg/mL, P = .001). Changes in the Ca × P product in response to paricalcitol were closely related to simultaneous FGF23 changes in an analysis adjusted for changes in serum calcium and phosphate (P < .001). Of note, baseline FGF23, appropriately adjusted for baseline PTH, was unrelated with the PTH response to paricalcitol (r = -.06, P = .72). Placebo did not change neither PTH nor FGF23. CONCLUSION Serum FGF23 and PTH are inter-related and changes in the Ca × P product induced by paricalcitol per se correlate with the FGF23 response to this drug. Independently of serum FGF23, the parathyroid glands of patients with moderate to severe CKD maintain an intact ability to respond to VDR activation.
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Vitamin D: does it help Tregs in active rheumatoid arthritis patients.
El-Banna, HS, Gado, SE
Expert review of clinical immunology. 2020;(8):847-853
Abstract
Background Regulatory T cells (Tregs) play an important role in the maintenance of immunological tolerance. Tregs deficiency or suppressor functions reduction may be associated with autoimmune diseases development. Objectives To estimate the effect of vitamin D supplementation on Tregs level in the peripheral blood of active rheumatoid arthritis (RA) patients. Methods 40 active RA patients were randomly assigned into two groups. Group I received methotrexate (MTX) plus hydroxychloroquine, group II received MTX, hydroxychloroquine plus vitamin D supplementation for 3 months, and 30 healthy volunteers as control group. Peripheral blood Tregs were measured at baseline and after 3 months by Flow Cytometry. Results At baseline, Tregs percentage was significantly decreased (p<0.001) in both RA patient groups (13.52±1.95%, 13.65±2.98% respectively), compared to controls (28.44±7.37%) with no significant difference between the two patient groups (p=0.866). After 3 months, there was a significant elevation in Tregs percentage in group II compared to group I (p<0.001). Tregs elevation was associated with significant DAS-28 score reduction (p<0.001). Conclusion Vitamin D appears to have important immunomodulatory functions. Vitamin D supplementation can be combined safely with traditional DMARDs to regulate the immune system. Clinical trial registration Tanta University Protocol Record 33846, Vitamin D Effect in Rheumatoid Arthritis, http://www.clinicaltrials.gov, NCT04472481.
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Effect of Vitamin D Supplement on Vulvovaginal Atrophy of the Menopause.
Kamronrithisorn, T, Manonai, J, Vallibhakara, SA, Sophonsritsuk, A, Vallibhakara, O
Nutrients. 2020;(9)
Abstract
The effects of oral vitamin D supplements on vaginal health in postmenopausal women with vulvovaginal atrophy (VVA) was evaluated. A double-blinded, randomized placebo-controlled trial was conducted for 12 weeks to investigate changes on vaginal maturation index (VMI), vaginal pH, and the visual analog scale (VAS) of VVA symptoms. The vitamin D group received oral ergocalciferol, at 40,000 IU per week, while the placebo group received an identical placebo capsule. Eighty postmenopausal women were enrolled. There were no significant differences in baseline characteristics between both groups. In an intention-to-treat analysis, VMI, vaginal pH, and VAS of VVA symptoms showed no significant differences between both groups at the six and 12 weeks. However, the mean difference of VMI in the vitamin D group between baseline and at six weeks showed significant improvement (5.5 + 16.27, p <0.05). Moreover, the mean vaginal pH and VAS of VVA patients in the vitamin D group were significantly improved at both six and 12 weeks compared to baseline. The oral vitamin D supplementation for 12 weeks potentially improves vaginal health outcomes in postmenopausal women with VVA symptoms, demonstrated by the improved mean VMI, vaginal pH, and VAS at six and 12 weeks between baseline, however, no significant differences were observed from the placebo treatment.
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Differential Effects of Oral Boluses of Vitamin D2 vs Vitamin D3 on Vitamin D Metabolism: A Randomized Controlled Trial.
Martineau, AR, Thummel, KE, Wang, Z, Jolliffe, DA, Boucher, BJ, Griffin, SJ, Forouhi, NG, Hitman, GA
The Journal of clinical endocrinology and metabolism. 2019;(12):5831-5839
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Abstract
CONTEXT Vitamin D2 and vitamin D3 have been hypothesized to exert differential effects on vitamin D metabolism. OBJECTIVE To compare the influence of administering vitamin D2 vs vitamin D3 on metabolism of vitamin D3. METHODS We measured baseline and 4-month serum concentrations of vitamin D3, 25-hydroxyvitamin D3 [25(OH)D3], 25-hydroxyvitamin D2, 24R,25-dihydroxyvitamin D3 [24R,25(OH)2D3], 1α,25-dihydroxyvitamin D3 [1α,25(OH)2D3], and 4β,25-dihydroxyvitamin D3 [4β,25(OH)2D3] in 52 adults randomized to receive a total of four oral bolus doses of 2.5 mg vitamin D2 (n = 28) or vitamin D3 (n = 24) over four months. Metabolite-to-parent compound ratios were calculated to estimate hydroxylase activity. Pairwise before vs after comparisons were made to evaluate effects of vitamin D2 and vitamin D3 on metabolism of vitamin D. Mean postsupplementation metabolite-to-parent ratios were then compared between groups. RESULTS Vitamin D2 was less effective than vitamin D3 in elevating total serum 25(OH)D concentration. Vitamin D2 suppressed mean four-month serum concentrations of 25(OH)D3, 24R,25(OH)2D3, 1α,25(OH)2D3, and 4β,25(OH)2D3 and mean ratios of 25(OH)D3 to D3 and 1α,25(OH)2D3 to 25(OH)D3, while increasing the mean ratio of 24R,25(OH)2D3 to 25(OH)D3. Vitamin D3 increased mean four-month serum concentrations of 25(OH)D3, 24R,25(OH)2D3, 1α,25(OH)2D3, and 4β,25(OH)2D3 and the mean ratio of 24R,25(OH)2D3 to 25(OH)D3. Participants receiving vitamin D2 had lower mean postsupplementation ratios of 25(OH)D3 to vitamin D3 and 1α,25(OH)2D3 to 25(OH)D3 than those receiving vitamin D3. Mean postsupplementation ratios of 24R,25(OH)2D3 to 25(OH)D3 and 4β,25(OH)2D3 to 25(OH)D3 did not differ between groups. CONCLUSIONS Bolus-dose vitamin D2 is less effective than bolus-dose vitamin D3 in elevating total serum 25(OH)D concentration. Administration of vitamin D2 reduces 25-hydroxylation of vitamin D3 and 1-α hydroxylation of 25(OH)D3, while increasing 24R-hydroxylation of 25(OH)D3.
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Effect of Treating Vitamin D Deficiency in Uncontrolled Type 2 Diabetes: A Randomized, Placebo-Controlled Study.
Lo, MC, Abushamat, L, Mramba, LK
American journal of therapeutics. 2019;(4):e441-e451
Abstract
BACKGROUND Literature increasingly supports the inverse relationship of vitamin D (VitD) level and type 2 diabetes (T2DM). Proposed protective mechanisms of VitD include its anti-inflammatory effects, increased insulin secretion via pancreatic β-cell stimulation, and downregulation of parathyroid hormone levels. Interventional studies show mixed results of VitD therapy in prediabetic patients with VitD deficiency or diabetic patients with normal VitD levels. STUDY QUESTION Does high-dose VitD replacement improve glycemic control and microalbuminuria (MAU) in uncontrolled T2DM and concurrent VitD deficiency? STUDY DESIGN This placebo-controlled, double-blinded study randomized 30 subjects aged 30-65 years with an elevated HbA1c level of 7.5%-10% and a low total 25-hydroxyvitamin-D value of <20 ng/mL to either placebo (n = 16) or ergocalciferol 50,000 IU (n = 14) once weekly for 8 weeks then once monthly for 4 months. MEASURES AND OUTCOMES Primary outcome was difference in HbA1c from baseline to month 6 between the VitD-intervention group and the placebo-controlled group. Secondary end points were differences in total 25-hydroxyvitamin-D and MAU. Paired t tests and linear mixed-effects models were used for statistical analysis. RESULTS No significant differences were seen in HbA1c or MAU between baseline versus postintervention visits within the placebo group (HbA1c: 8.4% ± 0.2 vs. 8.1% ± 0.3, P = 0.088; MAU: 94.1 mg/g ± 43.9 vs. 45.9 mg/g ± 20.2, P = 0.152) and the intervention group (HbA1c: 8.8% ± 0.3 vs. 8.7% ± 0.4, P = 0.692; MAU: 167.8 mg/g ± 70.1 vs. 108.5 mg/g ± 39.9, P = 0.356). The difference between placebo-slope and intervention-slope was nonsignificant for MAU (β = -0.1 mg/g ± 0.4, P = 0.835) but was significant for total 25-hydroxyvitamin-D (β = 11.7 ng/mL ± 2.5, P ≤ 0.001). Greater HbA1c reduction occurred unexpectedly in the placebo group ((Equation is included in full-text article.)= -0.4% ± 0.2) than in the intervention group ((Equation is included in full-text article.)= -0.2% ± 0.4), although the difference in slopes was not significant (β = 0.2% ± 0.4, P = 0.640). CONCLUSIONS Our proof-of-concept study found no benefit of high-dose VitD therapy in glycemic control and MAU in uncontrolled T2DM and VitD deficiency. Post hoc analyses raise concerns for high-dose VitD therapy to delay glycemic improvement. Large-scale interventional trials are much needed in this patient population to substantiate our findings and elucidate VitD's mechanisms on glucose metabolism.
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Changes in microparticle profiles by vitamin D receptor activation in chronic kidney disease - a randomized trial.
Lundwall, K, Mörtberg, J, Mobarrez, F, Jacobson, SH, Jörneskog, G, Spaak, J
BMC nephrology. 2019;(1):290
Abstract
BACKGROUND Microparticles (MPs) are biomarkers and mediators of disease through their expression of surface receptors, reflecting activation or stress in their parent cells. Endothelial markers, ICAM-1 and VCAM-1, are implicated in atherosclerosis and associated with cardiovascular risk. Chronic kidney disease (CKD) patients have endothelial dysfunction and high levels of endothelial derived MPs. Vitamin D treatment has been reported to ameliorate endothelial function in CKD patients. We aimed to examine cell specific MP profiles and concentrations of MPs expressing the atherosclerotic markers ICAM-1 and VCAM-1 after treatment with paricalcitol in patients with CKD stage 3-4. METHODS Sub-study of the previously reported SOLID trial where 36 patients were randomly assigned to placebo, 1 or 2 μg paricalcitol, for 12 weeks. MPs were measured by flow cytometry after labelling with antibodies against endothelial (CD62E), platelet (CD62P, CD41, CD154) leukocyte (CD45) and vascular (CD54, CD106) markers. RESULTS Patients had a mean age of 65 years with a mean eGFR of 40 mL/min/1.73m2. Concentrations of ICAM-1 positive MPs were significantly reduced by treatment (repeated measures ANOVA p = 0.04). Repeated measures MANOVA of concentrations of endothelial, platelet and leukocyte MPs showed sustained levels in the 2 μg treatment group (p = 0.85) but a decline in the 1 μg (p = 0.04) and placebo groups (p = 0.005). CONCLUSIONS Treatment with paricalcitol reduces concentrations of ICAM-1 positive MPs. This is accompanied by sustained concentrations of all cell specific MPs in the 2 μg group, and decreasing concentrations in the other groups, possibly due to a more healthy and reactive endothelium with paricalcitol treatment.
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Vitamin D receptor activation raises soluble thrombomodulin levels in chronic kidney disease patients: a double blind, randomized trial.
D'arrigo, G, Pizzini, P, Cutrupi, S, Tripepi, R, Tripepi, G, Mallamaci, F, Zoccali, C
Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. 2019;(5):819-824
Abstract
BACKGROUND Thrombomodulin (TM) is a proteoglycan highly represented in the endothelial glycocalix that regulates the haemostasis and the endothelial response to inflammation. High soluble TM levels underlie a lower risk for coronary heart disease in population studies. Activation of vitamin D receptor (VDR) upregulates TM, but the effect of this intervention on soluble TM has never been tested in chronic kidney disease (CKD) patients. METHODS We performed a post hoc analysis of a 12 weeks double blind, randomized, placebo-controlled trial testing the effect of VDR activation by paricalcitol (PCT) on endothelium-dependent flow-mediated vasodilatation (FMD) in the forearm (ClinicalTrials.gov identifier: NCT01680198). Circulating TM was measured in the whole CKD population [88 patients: PCT n = 44; placebo n = 44] that took part into this trial. RESULTS Soluble TM at baseline was inversely related to the glomerular filtration rate (r = -0.65, P < 0.001) and to FMD (Spearman's ρ = -0.29, P = 0.01). Alongside the expected effects on bone mineral biomarkers, PCT produced a consistent rise (P = 0.005) in TM levels, from a median value of 8446.0 pg/mL [interquartile range (IQR): 6227.8-10 910.8 pg/mL] to 9127.5 pg/mL (6393.0-11 287.3 pg/mL) while placebo had no effect (between-groups difference P = 0.008). TM levels re-approached baseline values 2 weeks after stopping PCT. TM changes across the trial paralleled simultaneous changes in FMD. CONCLUSIONS VDR activation by PCT raises TM levels and FMD and such effects are rapidly reversible after stopping the treatment. The TM rise induced by PCT is a possible mechanism whereby improvement in endothelial function by VDR activation may favourably impact upon vascular health in CKD patients.