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1.
Mortality in Hemodialysis Patients with COVID-19, the Effect of Paricalcitol or Calcimimetics.
Arenas Jimenez, MD, González-Parra, E, Riera, M, Rincón Bello, A, López-Herradón, A, Cao, H, Hurtado, S, Collado, S, Ribera, L, Barbosa, F, et al
Nutrients. 2021;(8)
Abstract
BACKGROUND In COVID-19 patients, low serum vitamin D (VD) levels have been associated with severe acute respiratory failure and poor prognosis. In regular hemodialysis (HD) patients, there is VD deficiency and markedly reduced calcitriol levels, which may predispose them to worse outcomes of COVID-19 infection. Some hemodialysis patients receive treatment with drugs for secondary hyperparathyroidism, which have well known pleiotropic effects beyond mineral metabolism. The aim of this study was to evaluate the impact of VD status and the administration of active vitamin D medications, used to treat secondary hyperparathyroidism, on survival in a cohort of COVID-19 positive HD patients. METHODS A cross-sectional retrospective observational study was conducted from 12 March to 21 May 2020 in 288 HD patients with positive PCR for SARS-CoV2. Patients were from 52 different centers in Spain. RESULTS The percent of HD patients with COVID-19 was 6.1% (288 out of 4743). Mortality rate was 28.4% (81/285). Three patients were lost to follow-up. Serum 25(OH)D (calcidiol) level was 17.1 [10.6-27.5] ng/mL and was not significantly associated to mortality (OR 0.99 (0.97-1.01), p = 0.4). Patients receiving active vitamin D medications (16/94 (17%) vs. 65/191(34%), p = 0.003), including calcimimetics (4/49 (8.2%) vs. 77/236 (32.6%), p = 0.001), paricalcitol or calcimimetics (19/117 (16.2%) vs. 62/168 (36.9%); p < 0.001), and also those on both paricalcitol and calcimimetics, to treat secondary hyperparathyroidism (SHPTH) (1/26 (3.8%) vs. 80/259 (30.9%), p < 0.001) showed a lower mortality rate than patients receiving no treatment with either drug. Multivariate Cox regression analysis confirmed this increased survival. CONCLUSIONS Our findings suggest that the use of paricalcitol, calcimimetics or the combination of both, seem to be associated with the improvement of survival in HD patients with COVID-19. No correlation was found between serum VD levels and prognosis or outcomes in HD patients with COVID-19. Prospective studies and clinical trials are needed to support these findings.
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2.
Relative Efficacy of Vitamin D2 and Vitamin D3 in Improving Vitamin D Status: Systematic Review and Meta-Analysis.
Balachandar, R, Pullakhandam, R, Kulkarni, B, Sachdev, HS
Nutrients. 2021;(10)
Abstract
BACKGROUND Widespread prevalence of vitamin D deficiency has been documented globally. Commonly used interventions to address this deficiency include supplementation and/or fortification with either ergocalciferol (vitamin D2) or cholecalciferol (vitamin D3), but the relative efficacy of these two vitamers is unclear. The current study aimed to evaluate the relative efficacy of ergocalciferol (vitamin D2) and cholecalciferol (vitamin D3) for raising the serum levels of vitamin D metabolites and functional indicators including serum parathyroid (PTH) levels, isometric muscle strength, hand grip strength and bone mineral density. METHODS Randomized and non-randomized controlled studies evaluating relative efficacy of ergocalciferol and cholecalciferol were systematically reviewed to synthesize quantitative and qualitative evidence as per the recommendations of according to "Preferred Reporting Items for Systematic reviews and Meta-analysis" guidelines. Search terms were constructed on the basis of the "participants", "intervention", "control", "outcome" and "study type" (PICOS) strategy to systematically search the popular electronic databases. Relevant data from studies meeting inclusion and exclusion criteria were extracted and analyzed. Meta-regression, subgroup and sensitivity analyses were performed to investigate the influence of study-level characteristics including intervention dosage, frequency of dosing, interval between the last dose and test for outcome assessment, participant characteristics and analytical methods. RESULTS Apparently healthy human participants (n = 1277) from 24 studies were included for meta-analysis. The quantitative analysis suggested higher efficacy of cholecalciferol than ergocalciferol in improving total 25(OH)D (mean difference: 15.69, 95%CI: 9.46 to 21.93 nmol/L) and reducing PTH levels, consistently across variable participant demographics, dosage and vehicle of supplementation. Meta-regression suggested smaller differences in the efficacy of cholecalciferol and ergocalciferol at lower doses. Average daily dose was the single significant predictor of effect size, as revealed by multivariate meta-regression analysis. CONCLUSIONS Compared to ergocalciferol, cholecalciferol intervention was more efficacious in improving vitamin D status (serum levels of total 25(OH)D and 25(OH)D3) and regulating PTH levels, irrespective of the participant demographics, dosage and vehicle of supplementation.
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3.
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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Exploring the potential effect of paricalcitol on markers of inflammation in de novo renal transplant recipients.
Pihlstrøm, HK, Ueland, T, Michelsen, AE, Aukrust, P, Gatti, F, Hammarström, C, Kasprzycka, M, Wang, J, Haraldsen, G, Mjøen, G, et al
PloS one. 2020;(12):e0243759
Abstract
Following a successful renal transplantation circulating markers of inflammation may remain elevated, and systemic inflammation is associated with worse clinical outcome in renal transplant recipients (RTRs). Vitamin D-receptor (VDR) activation is postulated to modulate inflammation and endothelial function. We aimed to explore if a synthetic vitamin D, paricalcitol, could influence systemic inflammation and immune activation in RTRs. Newly transplanted RTRs were included in an open-label randomized controlled trial on the effect of paricalcitol on top of standard care over the first post-transplant year. Fourteen pre-defined circulating biomarkers reflecting leukocyte activation, endothelial activation, fibrosis and general inflammatory burden were analyzed in 74 RTRs at 8 weeks (baseline) and 1 year post-engraftment. Mean changes in plasma biomarker concentrations were compared by t-test. The expression of genes coding for the same biomarkers were investigated in 1-year surveillance graft biopsies (n = 60). In patients treated with paricalcitol circulating osteoprotegerin levels increased by 0.19 ng/ml, compared with a 0.05 ng/ml increase in controls (p = 0.030). In graft tissue, a 21% higher median gene expression level of TNFRSF11B coding for osteoprotegerin was found in paricalcitol-treated patients compared with controls (p = 0.026). Paricalcitol treatment did not significantly affect the blood- or tissue levels of any other investigated inflammatory marker. In RTRs, paricalcitol treatment might increase both circulating and tissue levels of osteoprotegerin, a modulator of calcification, but potential anti-inflammatory treatment effects in RTRs are likely very modest. [NCT01694160 (2012/107D)]; [www.clinicaltrials.gov].
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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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Comparison of Paricalcitol and Calcitriol in Dialysis Patients With Secondary Hyperparathyroidism: A Meta-Analysis of Randomized Controlled Studies.
Zhang, T, Ju, H, Chen, H, Wen, W
Therapeutic apheresis and dialysis : official peer-reviewed journal of the International Society for Apheresis, the Japanese Society for Apheresis, the Japanese Society for Dialysis Therapy. 2019;(1):73-79
Abstract
Paricalcitol and calcitriol are widely used for the treatment of secondary hyperparathyroidism in dialysis patients. We conducted a systematic review and meta-analysis to compare the efficacy and safety of paricalcitol and calcitriol for secondary hyperparathyroidism in dialysis patients. PubMed, EMbase, Web of Science, EBSCO, and Cochrane library databases were systematically searched. Randomized controlled trials (RCT) assessing the efficacy of paricalcitol and calcitriol for secondary hyperparathyroidism in dialysis patients are included. Two investigators independently searched articles, extracted data, and assessed the quality of included studies. Meta-analysis was carried out using the random-effect model. Six randomized controlled trials are included in the meta-analysis. Overall, compared with calcitriol treatment for secondary hyperparathyroidism in dialysis patients, paricalcitol treatment has comparable ≥50% reduction of parathyroid hormone (risk ratio [RR] = 1.33; 95% CI = 0.93-1.91; P = 0.12), calcium concentration (standard mean difference [Std. MD] = -0.21; 95% CI = -0.94 to 0.52; P = 0.58), phosphate concentration (Std. MD = -0.17; 95% CI = -0.58 to 0.24; P = 0.42), calcium phosphate (Std. MD = -0.08; 95% CI = -0.49-0.34; P = 0.71), alkaline phosphatase (Std. MD = -0.21; 95% CI = -0.73-0.31; P = 0.43), hypercalcemia (RR = 1.43; 95% CI = 0.51 to 3.98; P = 0.49), adverse events (RR = 0.79; 95% CI = 0.42-1.49; P = 0.47), and serious adverse events (RR = 0.78; 95% CI = 0.47-1.30; P = 0.33). Paricalcitol and calcitriol result in similar ≥50% reduction of parathyroid hormone, calcium concentration, phosphate concentration, calcium phosphate, alkaline phosphatase, hypercalcemia, adverse events, and serious adverse events for secondary hyperparathyroidism in dialysis patients.
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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.