Vitamin D3 (Calcitriol) Monotherapy Decreases Tumor Growth, Increases Survival, and Correlates with Low Neutrophil-to-Lymphocyte Ratio in a Murine HPV-16-Related Cancer Model.

Vitamin D3 or calcitriol (VitD3) has been shown to have anticancer and anti-inflammatory activity in in vitro models and clinical studies. However, its effect on HPV-16-related cancer has been sparsely explored. In this study, we aimed to determine whether monotherapy or combination therapy with cisplatin (CP) reduces tumor growth and affects survival and systemic inflammation. Treatments were administered to C57BL/6 mice with HPV-16-related tumors (TC-1 cells) as follows: (1) placebo (100 µL vehicle, olive oil, orally administered daily); (2) VitD3 (3.75 µg/kg calcitriol orally administered daily); (3) CP (5 mg/kg intraperitoneally, every 7 days); and (4) VitD3+CP. Tumor growth was monitored for 25 days, survival for 60 days, and the neutrophil-to-lymphocyte ratio (NLR) was evaluated on days 1 (baseline), 7, and 14. VitD3+CP showed greater success in reducing tumor volume compared to CP monotherapy (p = 0.041), while no differences were observed between CP and VitD3 monotherapy (p = 0.671). Furthermore, VitD3+CP prolonged survival compared to CP (p = 0.036) and VitD3 (p = 0.007). Additionally, at day 14 the VitD3 and VitD3+CP groups showed significantly lower NLR values than the CP group (p < 0.05, for both comparisons). Vitamin D3 could be a promising adjuvant in the treatment of cervical cancer or solid tumors and deserves further investigation.

Temporal patterns of food consumption and their association with cardiovascular risk in rotating shift workers.

OBJECTIVE: We aimed to evaluate the association of temporal patterns of food consumption with cardiovascular disease (CVD) risk. METHODS: This cross-sectional study included male rotating shift workers in an iron ore extraction company. Data on food consumption was collected using a 24 h recall, applied by trained interviewers. The variables for temporal patterns of food consumption were: eating window, eating at night, number of meals and omission of breakfast. CVD-risk was measured by calculating the Framingham coronary heart disease risk score (FCRS), and classified as low risk or intermediate to high risk. Descriptive, univariate and multivariate logistic regression analyses examined the association between variables related to temporal patterns of food consumption and CVD-risk. RESULTS: The study assessed 208 workers, the majority with 20-34 years (45.1%), non-white (77.2%), and 5 years or more in shift work (76.0%). Most participants had a feeding window exceeding 12 h (63.9%), consumed meals until 10 p.m. (68.1%), had five or more meals per day (54.8%), and did not skip breakfast (86.5%). Regarding CVD-risk, 43.8% of the participants were classified with intermediate to high risk for CVD. In the multivariate model, a feeding window (OR: 2.32; 95%CI: 1.01-5.35), eating after 10 p.m. (OR: 3.31; 95%CI: 1.01-11.0), and skipping breakfast (OR: 2.58; 95%CI: 1.07-6.19) increased the likelihood of intermediate to high CVD-risk. Conversely, having five or more meals per day decreased the odds (OR: 0.27; 95%CI: 0.08-0.92). CONCLUSION: Eating window longer than 12 h, eating after 10 p.m., less than four meals a day and omission of breakfast, are associated with cardiovascular risk in shift workers.

Vitamin D supplementation in primary hyperparathyroidism: effects on 1,25(OH)2 vitamin D and FGF23 levels.

PURPOSE: In patients with Primary Hyperparathyroidism (PHPT) vitamin D deficiency has been associated with more severe presentations. Our aim was to investigate the effects of Vitamin D supplementation on mineral homeostasis and related hormones in individuals with and without PHPT. METHODS: Individuals with and without PHPT (CTRL) received 14,000 IU/week of oral vitamin D3 for 12 weeks. At baseline and endpoint, blood samples were collected to measure 1,25(OH)2vitamin D (1,25(OH)2D), intact Fibroblast Growth Factor 23 (FGF23), 25OHD, Parathormone, and other biochemical markers. The 1,25(OH)2D measurement was performed using liquid chromatography and mass spectrometry (LC-MS/MS). RESULTS: 70 PHPT patients and 75 CTRL were included, and 55 PHPT and 64 CTRL completed the 12-week protocol. After the intervention, there were significant increases in the FGF23 levels (PHPT: 47.9 ± 27.1 to 76.3 ± 33.3; CTRL: 40.5 ± 13.9 to 59.8 ± 19.8 pg/mL, p < 0.001), and significant decreases in 1,25(OH)2D levels (PHPT: 94.8 ± 34.6 to 68.9 ± 25.3; CTRL: 68.7 ± 23.5 to 56.4 ± 20.7 pg/mL, p < 0.001). The reduction of 1,25(OH)2D was inversely associated with the increase of FGF23 in both the PHPT (r = -0.302, p = 0.028) and CTRL (r = -0.278, p = 0.027). No changes in plasmatic or uninary calcium concentrations were observed in both groups. CONCLUSION: The weekly administration of 14,000 IU of Vitamin D3 was safe and efficient to increase in 25OHD levels in both groups. However, a paradoxical decrease in 1,25(OH)2D levels measured by LC-MS/MS was associated with a significant increase in FGF23 levels in both groups. This phenomenon might represent a defense against hypercalcemia after vitamin D supplementation and paves the way for new studies in this regard.

Efficacy and safety of burosumab compared with conventional therapy in patients with X-linked hypophosphatemia: A systematic review.

Burosumab, a monoclonal antibody directed against the fibroblast growth factor 23 (FGF23), has been approved for the treatment of X-linked hypophosphatemia (XLH). We conducted a systematic review to compare the efficacy and safety of burosumab versus conventional therapy (phosphorus and calcitriol) on XLH treatment. After a comprehensive literature search on MEDLINE/PubMed and Embase, we found nine studies for inclusion in the analysis. Risk of bias was assessed, and a random-effects model was used to determine the effect size. Clinical, biochemical, and radiological parameters of disease severity before and after treatment were analyzed and expressed in standardized mean difference (SMD). Burosumab resulted in normalization of phosphate homeostasis with an increase in renal tubular phosphate reabsorption and significant resolution of skeletal lesions (change in Thacher's total rickets severity score SMD: -1.46, 95% confidence interval [CI]: -1.76 to -1.17, p < 0.001, improvement in deformities, and decline in serum alkaline phosphatase levels [SMD: 130.68, 95% CI: 125.26-136.1, p < 0.001)]. Conventional therapy led to similar improvements in all these parameters but to a lower degree. In adults, burosumab normalized phosphorus levels (SMD: 1.23, 95% CI: 0.98-1.47, p < 0.001) with resultant clinical improvement. Burosumab treatment was well tolerated, with only mild treatment-related adverse effects. The present review indicates a potential role for burosumab in improving rickets, deformities, and growth in children with XLH. Given its superior efficacy and safety profile, burosumab could be an effective therapeutic option in children. We suggest further studies comparing burosumab versus conventional therapy in children and adults with XLH.

Calcitriol Treatment Decreases Cell Migration, Viability and ß-Catenin Signaling in Oral Dysplasia.

Nearly 90% of oral cancers are characterized as oral squamous cell carcinoma (OSCC), representing the sixth most common type of cancer. OSCC usually evolves from oral potentially malignant disorders that, in some cases, are histologically consistent with a oral dysplasia. The levels of 1α,25 dihydroxyvitamin D3 (1,25-(OH)2D3; calcitriol), the active form of vitamin D3, have been shown to be decreased in patients with oral dysplasia and OSCC. Moreover, treatment with 1,25-(OH)2D3 has been proven beneficial in OSCC by inhibiting the Wnt/ß-catenin pathway, a signaling route that promotes cell migration, proliferation, and viability. However, whether this inhibition mechanism occurs in oral dysplasia is unknown. To approach this question, we used dysplastic oral keratinocyte cultures and oral explants (ex vivo model of oral dysplasia) treated with 1,25-(OH)2D3 for 48 h. Following treatment with 1,25-(OH)2D3, both in vitro and ex vivo models of oral dysplasia showed decreased levels of nuclear ß-catenin by immunofluorescence (IF) and immunohistochemistry (IHC). Consistently, reduced protein and mRNA levels of the Wnt/ß-catenin target gene survivin were observed after treatment with 1,25-(OH)2D3. Moreover, 1,25-(OH)2D3 promoted membranous localization of E-cadherin and nuclear localization of vitamin D receptor (VDR). Functionally, DOK cells treated with 1,25-(OH)2D3 displayed diminished cell migration and viability in vitro.

Analysis of Potential Vitamin D Molecule Biomarkers: Association of Calcitriol and Its Hydroxylation Efficiency Ratio with Cardiovascular Disease Risk in Rheumatoid Arthritis Patients.

Rheumatoid arthritis (RA) is a multifactorial autoimmune disease in which hypovitaminosis D by calcidiol quantification has been associated with disease severity. However, other vitamin D molecules could be implicated in RA pathophysiology and its comorbidities such as cardiovascular disease (CVD), which impacts the severity and mortality of RA patients. This study aimed to assess the relationship between calcidiol, calcitriol, its hydroxylation efficiency ratio, and the soluble vitamin D receptor (sVDR) and clinical and CVD risk variables to propose potential vitamin D molecule biomarkers for RA. A cross-sectional study of females was conducted on 154 RA patients and 201 healthy subjects (HS). Calcidiol, calcitriol, and the sVDR were measured in blood serum, and vitamin D hydroxylation efficiency was estimated using the calcitriol/calcidiol ratio score. CVD risk was calculated by the high-sensitivity C-reactive protein (hs-CRP) cutoff values. Disease activity was evaluated with the Disease Activity Score for 28 standard joints (DAS28-CRP). Results: The hydroxylation efficiency ratio and calcitriol serum levels were higher in RA patients with hypovitaminosis D (p < 0.001). Moreover, RA patients had a higher probability of a high hydroxylation efficiency ratio (OR = 2.02; p = 0.02), calcitriol serum levels (OR = 2.95; p < 0.001), and sVDR serum levels (OR = 5.57; p < 0.001) than HS. This same pattern was also observed in RA patients with high CVD risk using CRP serum levels; they showed a higher hydroxylation efficiency ratio (OR = 4.51; p = 0.04) and higher calcitriol levels (OR = 5.6; p < 0.01). Calcitriol correlates positively with the sVDR (r = 0.21, p = 0.03), CRP (r = 0.28, p < 0.001), and cardiometabolic indexes (p < 0.001) also showed discrimination capacity for CVD risk in RA patients with CRP ≥ 3 mg/L (AUC = 0.72, p < 0.01). In conclusion, hypovitaminosis D in RA patients was characterized by a pattern of a higher hydroxylation efficiency ratio and higher calcitriol and sVDR serum levels. Notably, higher calcitriol serum levels and a higher vitamin D hydroxylation efficiency ratio were associated with higher CVD risk in RA patients.

Efficacy and safety of burosumab compared with conventional therapy in patients with X-linked hypophosphatemia: A systematic review

ABSTRACT Burosumab, a monoclonal antibody directed against the fibroblast growth factor 23 (FGF23), has been approved for the treatment of X-linked hypophosphatemia (XLH). We conducted a systematic review to compare the efficacy and safety of burosumab versus conventional therapy (phosphorus and calcitriol) on XLH treatment. After a comprehensive literature search on MEDLINE/PubMed and Embase, we found nine studies for inclusion in the analysis. Risk of bias was assessed, and a random-effects model was used to determine the effect size. Clinical, biochemical, and radiological parameters of disease severity before and after treatment were analyzed and expressed in standardized mean difference (SMD). Burosumab resulted in normalization of phosphate homeostasis with an increase in renal tubular phosphate reabsorption and significant resolution of skeletal lesions (change in Thacher's total rickets severity score SMD: −1.46, 95% confidence interval [CI]: −1.76 to −1.17, p < 0.001, improvement in deformities, and decline in serum alkaline phosphatase levels [SMD: 130.68, 95% CI: 125.26-136.1, p < 0.001)]. Conventional therapy led to similar improvements in all these parameters but to a lower degree. In adults, burosumab normalized phosphorus levels (SMD: 1.23, 95% CI: 0.98-1.47, p < 0.001) with resultant clinical improvement. Burosumab treatment was well tolerated, with only mild treatment-related adverse effects. The present review indicates a potential role for burosumab in improving rickets, deformities, and growth in children with XLH. Given its superior efficacy and safety profile, burosumab could be an effective therapeutic option in children. We suggest further studies comparing burosumab versus conventional therapy in children and adults with XLH.

Effects of calcitriol upon TGF-ßs and their receptors in trophoblast cells.

Calcitriol levels increase during pregnancy, contributing to the hormonal and immunological balance, but its deficiency has been associated with problems during this period. Meanwhile, transforming growth factors-ß (TGF-ßs) play an important role in the maintenance of fetal-maternal immune tolerance; however, exacerbated concentrations of this growth factor are associated with complicated pregnancies. Therefore, we studied the effects of calcitriol on TGF-ßs and their receptors in trophoblast cells. Term placentas from uncomplicated pregnancies after cesarean sections were used for cell cultures. Basal gene expression and the effect of calcitriol upon TGF-ß1, TGF-ß2, TGF-ß3, and their receptors TGF-ßR1 and TGF-ßR2 were assessed using real-time PCR from trophoblast cells. The presence of TGF-ß1, 2, 3, and TGF-ßR1 were evaluated by immunofluorescence, and the protein abundance and secretion of TGF-ß1 were assessed by Western blot and ELISA, respectively. Basal gene expression of TGF-ß1 in trophoblast from term placentas was higher than TGF-ß2 and TGF-ß3, while TGF-ßR2 was higher than TGF-ßR1. The presence and cellular localization of TGF-ß1, 2, 3, and TGF-ßR1 were detected in the cytoplasm of syncytiotrophoblast, with TGF-ß1 showing the highest intensity. Calcitriol significantly inhibited gene expression of TGF-ß1, TGF-ß2, and TGF-ßR1. Likewise, calcitriol decreased the secretion and abundance of TGF-ß1. In conclusion, results indicate that calcitriol is a regulator of TGF-ßs in cultured trophoblast cells from term placentas and therefore may be an important player in the development of healthy pregnancies.

Sulforaphane Combined with Vitamin D Induces Cytotoxicity Mediated by Oxidative Stress, DNA Damage, Autophagy, and JNK/MAPK Pathway Modulation in Human Prostate Tumor Cells.

Prostate cancer ranks second in incidence worldwide. To date, there are no available therapies to effectively treat advanced and metastatic prostate cancer. Sulforaphane and vitamin D alone are promising anticancer agents in vitro and in vivo, but their low bioavailability has limited their effects in clinical trials. The present study examined whether sulforaphane combined with vitamin D at clinically relevant concentrations improved the cytotoxicity of the compounds alone towards DU145 and PC-3 human prostate tumor cells. To assess the anticancer activity of this combination, we analyzed cell viability (MTT assay), oxidative stress (CM-H2DCFDA), autophagy (fluorescence), DNA damage (comet assay), and protein expression (Western blot). The sulforaphane-vitamin D combination (i) decreased cell viability, induced oxidative stress, DNA damage, and autophagy, upregulated BAX, CASP8, CASP3, JNK, and NRF2 expression, and downregulated BCL2 expression in DU145 cells; and (ii) decreased cell viability, increased autophagy and oxidative stress, upregulated BAX and NRF2 expression, and downregulated JNK, CASP8, and BCL2 expression in PC-3 cells. Therefore, sulforaphane and vitamin D in combination have a potential application in prostate cancer therapy, and act to modulate the JNK/MAPK signaling pathway.

Effects of Vitamin D Supplementation in Diabetic Kidney Disease: An Systematic Review.

Diabetes Mellitus is a highly prevalent condition in which Diabetes Mellitus type 2 is the most common. Diabetic Kidney Disease is one of the most relevant complications and affects approximately one-third of patients with Diabetes Mellitus. It is characterized by increased urinary protein excretion and a decrease in glomerular filtration rate, assessed by serum creatinine levels. Recent studies have shown that vitamin D levels are low in these patients. This study aimed to conduct a systematic review of the effects of vitamin D supplementation on proteinuria and creatinine, which are important markers for assessing the severity of kidney disease in patients with Diabetic Kidney Disease. PUBMED, EMBASE, and COCHRANE databases were consulted, Preferred Reporting Items for a Systematic Review and Meta-Analysis guidelines were followed, and the COCHRANE toll for bias assessment was applied. Six papers were quantitative studies and fulfilled the inclusion criteria for this review. The results showed that vitamin D supplementation of 50,000 I.U./week for 8 weeks effectively reduced proteinuria and creatinine in patients with Diabetic Kidney Disease, particularly in patients with Diabetes Mellitus type 2. Vitamin D supplementation is beneficial for patients with Diabetic Kidney Disease by having essential effects on disease-related inflammatory markers, such as the reduction of proteinuria and creatinine. However, more clinical trials must be conducted to evaluate the intervention among more significant numbers of patients.

The Preventive Role of the Vitamin D Endocrine System in Cervical Cancer.

Vitamin D along with its active metabolite calcitriol and its metabolic and signaling system, known as the vitamin D endocrine system, have been widely recognized as a pivotal regulator of calcium homeostasis in addition to non-calcemic antitumoral effects in a variety of human cancers, including cervical cancer. Several studies have found an inverse relationship between the incidence of cervical neoplasia and vitamin D levels. This narrative review updates the current evidence supporting the notion that the vitamin D endocrine system has a preventive role on cervical cancer, mainly in the early phases of the disease, acting at the level of suppressing cell proliferation, promoting apoptosis, modulating inflammatory responses, and probably favoring the clearance of human papillomavirus-dependent cervical lesions. Although an optimal vitamin D status helps in the prevention and regression of low-grade squamous intraepithelial lesions of the cervix, it appears that vitamin D alone or combined with chemotherapeutic agents has little effectivity once advanced cervical cancer is established. These observations suggest that an optimal vitamin D status might exert beneficial actions in the early phases of cervical cancer by preventing its onset and progression.

Vitamin D in Depression: A Potential Bioactive Agent to Reduce Suicide and Suicide Attempt Risk.

Suicide is one of the leading causes of death worldwide. According to the World Health Organization (WHO), every year, more than 700 thousand people die from this cause. Therefore, suicide is a public health issue. The complex interaction between different factors causes suicide; however, depression is one of the most frequent factors in people who have attempted suicide. Several studies have reported that vitamin D deficiency may be a relevant risk factor for depression, and vitamin D supplementation has shown promising effects in the adjunctive treatment of this mood disorder. Among the beneficial mechanisms of vitamin D, it has been proposed that it may enhance serotonin synthesis and modulate proinflammatory cytokines since low serotonin levels and systemic inflammation have been associated with depression and suicide. The present narrative review shows the potential pathogenic role of vitamin D deficiency in depression and suicide and the potential benefits of vitamin D supplementation to reduce their risk.

Corrigendum: Impact of vitamin D on cognitive functions in healthy individuals: A systematic review in randomized controlled clinical trials.

[This corrects the article DOI: 10.3389/fpsyg.2022.987203.].

Cost-effectiveness analysis of intravenous paricalcitol vs. oral calcitriol in the treatment of hyperparathyroidism secondary to chronic kidney disease / Análise de custo-efetividade do paricalcitol intravenoso vs. calcitriol oral no tratamento do hiperparatireoidismo secundário à doença renal crônica

Abstract Introduction: Hyperparathyroidism (SHPT) secondary to chronic kidney disease (CKD) is characterized by high levels of parathyroid hormone (PTH), hyperplasia of the parathyroid glands and cardiovascular disease. Selective and non-selective and selective vitamin D-receptor activators, calcimimetics, are available in the Brazilian market to reduce PTH levels. Objectives: To develop a cost-effectiveness (C/E) and budgetary impact (BI) analysis of intravenous paricalcitol vs. oral calcitriol for patients on dialysis with SHPT, from the perspective of the Brazilian Public Health Care System (SUS). Methodology: We built a decision-tree model to analyze C/E, which considered the outcome of avoided death and a time horizon of 1 year. As for the BI analysis, two scenarios were considered, one of demand and one of epidemiological approach, based on data from the Brazilian Society of Nephrology. Results: The analysis showed that the C/E ratio was R$ 1,213.68 per year, and an incremental effectiveness of 0.032, referring to avoided death. The incremental C/E ratio was R$37,927.50 per death averted by paricalcitol. It was estimated that the incremental BI with the expansion of paricalcitol use will be between R$1,600,202.28 and R$4,128,565.65 in the first year, considering the main and epidemiological scenarios. At the end of 5 years after the expansion of its use, an incremental BI was estimated between R$ 48,596,855.50 and R$ 62,90,555.73. Conclusion: Intravenous paricalcitol has superior efficacy and similar safety to oral calcitriol, reducing the overall mortality of dialysis patients, although it implies a higher cost.

Resumo Introdução: O hiperparatireoidismo secundário (HPTS) à doença crônica renal (DRC) é caracterizado por elevados níveis de paratormônio (PTH), hiperplasia das glândulas paratireoides e doença cardiovascular. Para a redução dos níveis do PTH, estão disponíveis no mercado brasileiro os ativadores não seletivos e seletivos do receptor da vitamina D e os calcimiméticos. Objetivos: Desenvolver análise de custo-efetividade (C/E) e de impacto orçamentário (IO) do paricalcitol intravenoso vs. calcitriol oral para pacientes em diálise com HPTS, na perspectiva do Sistema Único de Saúde. Metodologia: Foi construído um modelo de árvore de decisão para a análise de C/E, que considerou o desfecho morte evitada e um horizonte temporal de 1 ano. Quanto à análise de IO, foram considerados dois cenários, sendo um de demanda aferida e um de abordagem epidemiológica, baseado nos dados da Sociedade Brasileira de Nefrologia. Resultados: A análise mostrou que a relação de C/E foi de R$ 1.213,68 ao ano, e uma efetividade incremental de 0,032, referente à morte evitada. A razão de C/E incremental foi de R$ 37.927,50 por morte evitada para o paricalcitol. Estimou-se que o IO incremental com a ampliação do uso do paricalcitol estará entre R$ 1.600.202,28 e R$ 4.128.565,65 no primeiro ano, considerando os cenários principal e o epidemiológico. Já no fim de 5 anos após a ampliação do uso, estimou-se IO incremental entre R$ 48.596.855,50 e R$ 62.90.555,73. Conclusão: O paricalcitol intravenoso tem eficácia superior e segurança semelhante ao comparador calcitriol oral, diminuindo a mortalidade geral dos pacientes em diálise, embora implique maior custo.

Effects of Vitamin D on Cardiovascular Risk and Oxidative Stress.

INTRODUCTION: Vitamin D has been primarily studied as an important factor influencing bone and calcium metabolism. Metabolites of vitamin D are essential for whole-body calcium homeostasis, maintaining serum calcium levels within a narrow range by regulating this process in the bones and gut. Nevertheless, its deficiency is also related to increased risk of type 2 diabetes mellitus (T2DM), metabolic syndrome (MS), and cardiovascular disease (CVD)-with increased visceral adipose tissue and body mass index (BMI), as well as the frequently associated hypercholesterolemia. It has been reported that vitamin D levels are inversely related to cardiovascular (CV) risk in men and women. However, the effects of vitamin D on distinct outcomes in women and the dose of supplementation needed to improve clinical endpoints have not been established. 25-Hydroxyvitamin D [25(OH)D] reduces systemic inflammatory mediators in CVD and favors the release of anti-inflammatory cytokines from the immune system. In addition, 25(OH)D can be primarily converted into calcitriol (1,25-dihydroxycholecalciferol [1,25(OH)2D]) in the kidneys through the action of the 1-α-hydroxylase enzyme. Calcitriol, through the downregulation mechanism of renin expression, renin-angiotensin-aldosterone system (RAAS) activity, and its interaction with the vitamin D receptor, can bring CV benefits. The calcitriol form also lowers parathyroid hormone (PTH) levels by indirectly causing a reduction in aldosterone and mineralocorticoid synthesis. Elevated plasma aldosterone is related to endothelial dysfunction and CVD in hypovitaminosis D status. CONCLUSION: Vitamin D supplementation may benefit certain risk groups, as it improves metabolic variables, reducing oxidative stress and CV outcomes. More studies are needed to define interventions with vitamin D in men and women.

Association between genetic variants in key vitamin-D-pathway genes and external apical root resorption linked to orthodontic treatment.

This study evaluated the association between single-nucleotide polymorphisms (SNPs) in vitamin-D-related genes and the amount of external apical root resorption linked to orthodontic treatment. One hundred and forty-three individuals were assessed. The amount of external apical root resorption of upper central incisors (EARRinc ) and lower first molars (EARRmol ) were evaluated in radiographs. Seven SNPs were genotyped across four genes including the vitamin D receptor [VDR], group-specific component [GC], cytochrome P450 family 27 subfamily B member 1 [CYP27B1], and cytochrome P450 family 24 subfamily A member 1 [CYP24A1]. Linear regressions were implemented to determine allele-effects on external apical root resorption. Individuals carrying the AA genotype in VDR rs2228570 had a 21% higher EARRmol than those having AG and GG genotypes (95% CI: 1.03,1.40). EARRmol in heterozygous rs2228570, was 12% lower than for homozygotes (95%CI: 0.78,0.99). Participants with the CCG haplotype (rs1544410-rs7975232-rs731236) in VDR had an EARRmol 16% lower than those who did not carry this haplotype. Regarding CYP27B1 rs4646536, EARRinc in participants who had at least one G allele was 42% lower than for homozygotes AA (95%CI: 0.37,0.93). Although these results did not remain significant after multiple testing adjustment, potential associations may still be suggested. Further replication studies are needed to confirm or refute these findings.

Impact of vitamin D on cognitive functions in healthy individuals: A systematic review in randomized controlled clinical trials.

Various functions in the central nervous system, such as growth, development, and cognition can be influenced by vitamins and minerals, which are capable of helping to maintain brain health and function throughout life. Cognition is understood as the aspects related to knowledge, learning, and understanding, as well as the ability to develop these functions. A possible association between low levels of vit D and deficit in the performance of cognitive functions in healthy humans or with some pathological condition is discussed. Because of this, the present systematic review analyzed only randomized clinical trials carried out in healthy non-athlete adults about intellectual and/or mental processes involving cognitive functions to identify whether these individuals with different levels of vit D are capable of interfering with the performance of the cognitive function. To do so, we adopted the PRISMA method criteria and registered it in the PROSPERO database. The search was performed in PubMed (MEDLINE), PsycINFO, Science Direct, Scopus, and Web of Science databases, 2,167 records were identified. The 5 most frequent cognitive domains in the selected studies were: processing speed, attention, verbal learning/memory, executive function, and general cognitive functions. We found that there are positive changes in the following domains: verbal memory and verbal working memory, learning memory, attention, executive function, and also cognitive function in general. We highlight the following suggestions for improvements that vitamin D supplementation may promote in the cognitive domains of healthy adults: a) low doses between 400 and 600 IU/d seem to be more effective when compared to doses between 2,400 and 5,000 IU/d and b) food fortification and enrichment with vit D, need further studies, as they seem to be more or as effective as synthetic supplementation. We evident that there is a need for trials that evaluate the control of vit D levels for healthy adult individuals is important, as they have the potential to minimize health problems, especially those involved in the reduction of cognitive abilities. Thus, the development of more clinical trials to obtain satisfactory answers on this topic needs to be encouraged. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, identifier: CRD42021262413.

Calcitriol Reduces the Inflammation, Endothelial Damage and Oxidative Stress in AKI Caused by Cisplatin.

Cisplatin treatment is one of the most commonly used treatments for patients with cancer. However, thirty percent of patients treated with cisplatin develop acute kidney injury (AKI). Several studies have demonstrated the effect of bioactive vitamin D or calcitriol on the inflammatory process and endothelial injury, essential events that contribute to changes in renal function and structure caused by cisplatin (CP). This study explored the effects of calcitriol administration on proximal tubular injury, oxidative stress, inflammation and vascular injury observed in CP-induced AKI. Male Wistar Hannover rats were pretreated with calcitriol (6 ng/day) or vehicle (0.9% NaCl). The treatment started two weeks before i.p. administration of CP or saline and was maintained for another five days after the injections. On the fifth day after the injections, urine, plasma and renal tissue samples were collected to evaluate renal function and structure. The animals of the CP group had increased plasma levels of creatinine and of fractional sodium excretion and decreased glomerular filtration rates. These changes were associated with intense tubular injury, endothelial damage, reductions in antioxidant enzymes and an inflammatory process observed in the renal outer medulla of the animals from this group. These changes were attenuated by treatment with calcitriol, which reduced the inflammation and increased the expression of vascular regeneration markers and antioxidant enzymes.

Vitamin D Receptor (VDR) Genetic Variants: Relationship of FokI Genotypes with VDR Expression and Clinical Disease Activity in Systemic Lupus Erythematosus Patients.

Vitamin D (VD) deficiency is more frequent in systemic lupus erythematosus (SLE) patients than in control subjects (CS); genetic variants in the VD receptor (VDR) could contribute to the clinical disease activity. This study was aimed to determine the association of the VDR variants FokI (rs2228570), BsmI (rs1544410), ApaI (rs7975232), and TaqI (rs731236) with susceptibility to the disease, VD status, VDR mRNA expression, and clinical disease activity in SLE patients. A cross-sectional study was conducted in 194 SLE and 196 CS Mexican women. Immunoassays quantified serum calcidiol and calcitriol. Genotyping was performed by allelic discrimination assays and mRNA VDR expression by qPCR. The FokI variant was not in linkage disequilibrium with BsmI, ApaI, and TaqI VDR variants. SLE patient carriers of the TT FokI genotype showed higher clinical disease activity scores. Notably, the mRNA VDR expression was higher in SLE patients vs. CS, in active vs. inactive SLE patients, and in participants of both study groups with vitamin D deficiency, higher calcitriol levels, and TT FokI genotype carriers. In conclusion, the TT FokI VDR genotype was related to high VDR expression and clinical disease activity in systemic lupus erythematosus patients.

Efetividade de vitamina D para rinite alérgica: sinopse baseada em evidências / Vitamin D effectiveness for allergic rhinitis: evidence-based synopsis

Contexto: A suplementação de vitamina é considerada na prevenção de muitas doenças, incluindo a rinite alérgica, cuja prevalência tem aumentado nos últimos anos, impactando a saúde pública. Objetivo: Avaliar a efetividade da suplementação de vitamina D para a prevenção e o tratamento da rinite alérgica. Material e Métodos: Trata-se de sinopse baseada em evidências. Procedeu-se à busca por estudos que associavam a vitamina D à rinite alérgica em três bases eletrônicas de dados: Cochrane - Central de Registros de Ensaios Clínicos - CENTRAL (2022), PubMed (1966-2022) e Portal BVS (1982-2022) e no megabuscador de evidências TRIPDATABASE (2022). Dois pesquisadores independentemente extraíram os dados e avaliaram a qualidade dos estudos para a síntese. O desfecho primário de análise envolveu a redução de crises de rinite. Resultados: Foram encontrados 125 estudos. Cinco estudos (três ensaios clínicos randomizados e dois coortes) foram incluídos. Discussão: A literatura apresenta poucos estudos relacionando vitamina D e rinite alérgica. Os estudos em humanos são ensaios clínicos de baixa amostragem e elevada heterogeneidade, que avaliaram efetividade da suplementação de vitamina D para redução de sintomas da rinite. Os dois estudos coorte encontrados não estabeleceram relação entre a exposição à vitamina D e menor manifestação de doença alérgica. O nível de evidência é muito baixo e não permite, nesse momento, aferir a efetividade da vitamina D para essa finalidade. Conclusões: Não há evidência de efetividade da suplementação de vitamina D para tratamento e prevenção da rinite alérgica, sendo recomendada a realização de novos estudos de boa qualidade metodológica.