Search Results (39)

Background: Cervical dysplasia is a pre-malignant condition of the uterine cervix and is highly prevalent in Sub-Saharan Africa; especially affecting HIV-infected Black women. The anti-dysplastic effect of vitamin D hormones in cervical dysplasia is poorly understood. Therefore, we conducted a cross-sectional case–control observational study to assess the relationship between serum 25-hydroxycholecalciferol (25(OH)D) and cervical dysplasia, amongst Black women with and without HIV infection. Methods: The study participants attended a gynaecologic oncology clinic at an academic hospital in Pretoria, South Africa (n = 109). Patient clinical data were obtained during consultation. Cervical dysplasia was identified by cytology (PAP smear) which classified the case group as high-grade squamous epithelial lesions (HSILs), and the control group as <HSIL. Serum biochemistry measured 25(OH)D and its covariate biochemical variables. The data were statistically modelled to adjust for clinical and biochemical covariates, identify a significant relationship (p ≤ 0.05) between 25(OH)D and cervical dysplasia, and analyse subgroup interaction between HIV status and cervical dysplasia. Results: The data showed high levels of vitamin D insufficiency and deficiency in Black women with and without HIV infection. After covariate adjustment, 25(OH)D demonstrated an inverse relationship with HSIL in HIV-uninfected Black women. Furthermore, an interaction effect between women with and without HIV infection was observed. Conclusions: The role of 25(OH)D in the primary prevention of cervical dysplasia in Black women without HIV infection is promising, and dosing strategies require investigation. Also, future studies exploring the immunomodulatory role of 25(OH)D in cervical dysplasia in HIV-infected women is warranted. Full article

Vitamin D and its metabolites exert anti-cancer properties in various cancers; however, their effects on cervical cancer remain largely unexplored. To investigate this gap, we exposed HeLa adenocarcinoma cervical cells to physiological and the growth inhibition 20% (GI20) concentration of 25-hydroxycholecalciferol, the precursor hormone of active 1,25-dihydroxycholecalciferol. We then assessed its impact on cell health, and the expression of the genes and proteins involved in the activation and catabolism of vitamin D at the cellular level by autocrine vitamin D metabolism via the vitamin D metabolizing system (VDMS). Cell health was evaluated by crystal violet and alamarBlue assays, while cell cycle progression and apoptotic cell death markers were assessed by flow cytometry. Gross morphology and ultrastructure were observed using brightfield microscopy and transmission electron microscopy. Gene and protein analyses of the autocrine VDMS were assessed using reverse transcription polymerase chain reaction and Western blot, respectively. Our findings reveal that 25(OH)D₃ inhibits cell growth and induces apoptosis in HeLa cervical cells in a dose-dependent manner through the autocrine upregulation of CYP27B1 and VDR. These autocrine effects most likely promote the bioactivation of 25(OH)D₃ and intracellular signaling of pro-apoptotic genomic pathways by liganded VDR. Furthermore, the upregulation of CYP24A1 at GI20 treatment likely increases the catabolism of 25(OH)D₃ and 1,25(OH)₂D_3, and therefore may mitigate the anti-cancer action of the high-treatment dose. In summary, 25(OH)D₃ holds immense potential as a complementary therapeutic treatment for cervical cancer. Full article

In this study, the aim was to evaluate the effects of dietary 25-hydroxycholecalciferol supplementation from day 85 of gestation on performance, antioxidant capacity, and immunoglobulin level of sows and newborn piglets. On day 85 of gestation, forty Landrace × Yorkshire gestating sows (average body weight of 241 ± 6.8 kg; average parity of 3.47 ± 0.6) were allotted into two treatments (20 replicates per treatment) based on parity, body weight, and back fat thickness. From day 85 of gestation to farrowing, sows were fed a normal vitamin D₃ diet as control (containing 50 μg/kg vitamin D₃; CON), or a 25-hydroxycholecalciferol-supplemented diet (containing 50 μg/kg 25-hydroxycholecalciferol). Compared with CON, dietary 25-hydroxycholecalciferol supplementation increased (p < 0.05) protein and fat content in colostrum and the average birth body weight of newborn piglets. Sows fed 25-hydroxycholecalciferol showed increased (p < 0.05) apparent total tract digestibility of crude protein compared with CON. Diets supplemented with 25-hydroxycholecalciferol also increased (p < 0.05) the content of superoxide dismutase (SOD), and tended to increase (p = 0.06) the total antioxidant capacity content and reduce (p = 0.09) the malondialdehyde (MDA) level in colostrum. An increase (p < 0.05) in the content of SOD and a reduction (p < 0.05) in the content of MDA in the serum of newborn piglets was also observed in the 25-hydroxycholecalciferol treatment compared with CON. Dietary 25-hydroxycholecalciferol supplementation also enhanced (p < 0.05) the immunoglobulin G content and reduced (p < 0.05) the concentration of tumor nuclear factor-α in the serum of sows, as well as reducing (p < 0.05) the content of immunoglobulin G and immunoglobulin A in the serum of newborn piglets compared with CON. Supplementation of 25-hydroxycholecalciferol in sow diets increased (p < 0.05) the content of alkaline phosphatase in the serum and colostrum of sows, the concentration of insulin and crosslap in serum of sows, and the serum calcium content of newborn piglets compared with CON. In conclusion, dietary 25-hydroxycholecalciferol supplementation from day 85 of gestation could enhance performance, antioxidant capacity, and immunoglobulin in sows and newborn piglets. Full article

Broiler breeder hens allowed ad libitum (Ad) feed intake developed obesity and cardiac pathogenesis and thereby were susceptible to sudden death. A supplement of 69 µg 25-hydroxycholecalciferol (25-OH-D3)/kg feed rescued the livability of feed-restricted (R) and Ad-hens (mortality; 6.7% vs. 8.9% and 31.1% vs. 48.9%). Necropsy with the surviving counterparts along the time course confirmed alleviation of myocardial remodeling and functional failure by 25-OH-D3, as shown by BNP and MHC-β expressions, pathological hypertrophy, and cardiorespiratory responses (p < 0.05). 25-OH-D3 mitigated cardiac deficient bioenergetics in Ad-hens by rescuing PGC-1α activation, mitochondrial biogenesis, dynamics, and electron transport chain complex activities, and metabolic adaptions in glucose oxidation, pyruvate/lactate interconversion, TCA cycle, and β-oxidation, as well as in TG and ceramide accumulation to limit lipotoxic development (p < 0.05). Supplemental 25-OH-D3 also sustained Nrf2 activation and relieved MDA accumulation, protein carbonylation, and GSH depletion to potentiate cell survival in the failing heart (p < 0.05). Parts of the redox amendments were mediated via lessened blood hematocrit and heme metabolism, and improved iron status and related gene regulations (p < 0.05). In conclusion, 25-OH-D3 ameliorates cardiac pathological remodeling and functional compromise to rescue the livability of obese hens through metabolic flexibility and mitochondrial bioenergetics, and by operating at antioxidant defense, and heme and iron metabolism, to maintain redox homeostasis and sustain cell viability. Full article

(1) Background and Objectives: Vitamin D is implicated in the pathogenesis of Chronic Kidney Disease—Mineral and Bone Disorder (CKD-MBD) in hemodialysis (HD) patients, including the development of secondary hyperparathyroidism (SHP). While cholecalciferol supplementation is recommended for vitamin D deficiency correction, its impact on CKD-MBD remains inconsistent. The aim of this observational prospective study was to assess the effect of cholecalciferol in achieving high–normal serum 25-hydroxycholecalciferol (25(OH)D > 75 ng/mL) levels and its impact on CKD-MBD biochemical markers, including 1,25-dihydroxycholecalciferol (1,25(OH)₂D) and parathormone (PTH) in HD patients. The study also evaluated the maintenance dosage required to sustain 25(OH)D levels within the 50–75 ng/mL range. (2) Materials and Methods: A total of 22 HD patients with baseline 25(OH)D levels 30–50 ng/mL received cholecalciferol (70,000 IU/week) to achieve the target serum 25(OH)D > 75 ng/mL. Baseline data on calcium, phosphate, 1–84 PTH, 25(OH)D, and 1,25(OH)₂D serum levels were compared with the data when 25(OH)D > 75 ng/mL was targeted or when the highest 25(OH)D levels were noted. (3) Results: Cholecalciferol significantly improved vitamin D status in HD patients, with 73% reaching the target 25(OH)D level >75 ng/mL in a median time of 7.5 weeks, with a median total dose of 525,000 IU. This was associated with a significant rise in 1,25(OH)₂D, decrease in 1–84 PTH, and no significant effect on calcium and phosphate levels. The median maintenance dose of cholecalciferol was established at 30,000 IU/week. (4) Conclusions: The findings support the use of cholecalciferol targeting high normal 25(OH)D levels to improve biochemical markers of CKD-MBD in HD patients. Full article

A cross-sectional study was performed in healthy adults (mean age 28 y, 67% women) whose habitual diet was an omnivore, lacto-ovo vegetarian, or vegan diet. The total sample (n = 297) was divided into two groups according to the parathormone (PTH) cut-off value of 65 pg/mL of either normal-PTH (n = 228) or high-PTH (n = 69). Vitamin D status (25-hydroxycholecalciferol, 25-OHD), PTH, and bone formation (bone alkaline phosphatase, BAP) and bone resorption (N-telopeptides of type I collagen, NTx) markers were determined. Hematocrit, erythrocytes, hemoglobin, platelets, serum iron, serum transferrin, transferrin saturation, and serum ferritin were also measured. In the total sample, 25-OHD and PTH were negatively correlated, and all subjects with high PTH presented vitamin D insufficiency (25-OHD < 75 nmol/L). High bone remodeling was observed in the high-PTH group, with significantly higher NTx and marginally higher BAP compared to the normal-PTH group. Hematocrit and ferritin were significantly lower in the high-PTH compared to the normal-PTH group. However, serum iron was higher in the high-PTH group, which was only observed for the lacto-ovo vegetarian and vegan subjects. It is concluded that both low vitamin D and low iron status are associated with elevated PTH and bone resorption, more in vegetarians than omnivores, which is in line with the hypothesis that chronic iron deficiency in adulthood mainly predisposes to osteoporosis in postmenopausal women and the elderly. Full article

The effects of the Marek’s disease vaccine (MDV) on the live performance, breast meat yield, and incidence of woody breast myopathy (WBM) of Ross 708 broilers were investigated when administered alone or in conjunction with in ovo and dietary supplemental 25-hydroxycholecalciferol (25OHD₃). At 18 d of incubation (doi), four in ovo injection treatments were randomly assigned to live embryonated Ross 708 broiler hatching eggs: (1) non-injected; (2) commercial MDV alone; or MDV containing either (3) 1.2 or (4) 2.4 μg of 25OHD₃. An Inovoject multi-egg injector was used to inject a 50 μL solution volume into each egg. The birds were provided a commercial diet that contained 250 IU of cholecalciferol/kg of feed (control) or a commercial diet that was supplemented with an additional 2760 IU of 25OHD₃/kg of feed (HyD-diet). In the growout period, 14 male broilers were placed in each of 48 floor pens resulting 6 replicated pens per in ovo x dietary treatment combination. Live performance variable were measured at each dietary phases from 0 to 14, 15 to 28, and 29 to 40 d of age (doa). At 14 and 40 doa, pectoralis major (P. major) and pectoralis minor (P. minor) muscles were determined for one bird within each of the six replicate pens. At 41 doa, WBM incidence was determined. No significant main or interaction effects occurred for WBM among the dietary or in ovo injection treatments. However, in response to in ovo 25OHD₃ supplementation, BW and BWG in the 29 to 40 doa period and BWG and FCR in the 0 to 40 doa period improved. In addition, at 40 and 41 doa, breast meat yield increased in response to in ovo and dietary 25OHD₃ supplementation. Future research is needed to determine the possible reasons that may have been involved in the aforementioned improvements. Full article

This study aimed to investigate whether a dietary 25-OHD₃ addition improved the performance, egg quality, blood indexes, antioxidant status, jejunal morphology, and tibia quality of aged laying hens compared to a dietary VD₃ addition. A total of 270 Hy-Line Brown laying hens at 55 wk of age were randomly assigned to three dietary treatments with six replicates (15 birds per replicate with 3 birds per cage). Chickens were fed a corn–soybean meal diet supplementation of 4000 IU/kg VD₃ (control group), 50 μg/kg 25-OHD₃ and 2000 IU/kg VD₃ (experimental group 1), or 50 μg/kg 25-OHD₃ and 4000 IU/kg VD₃ (experimental group 2) for 12 weeks. The results demonstrated that 25-OHD₃ caused a significant increase in the laying rate, especially in the 50 μg/kg 25-OHD₃ + 2000 IU/kg VD₃ group; the laying rate reached the maximum compared with other groups after 12 weeks (p < 0.05). However, there were no significant effects on the average egg weight, average daily feed intake, or feed-to-egg ratio (p > 0.05). A dietary supplementation of 50 μg/kg 25-OHD₃ and 2000 IU/kg VD₃ provided an improved eggshell strength, thick albumen height, and Haugh unit after 12 weeks (p < 0.05). Further analysis of the blood indexes showed that alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, calcium, and phosphorus were enhanced significantly in the 50 μg/kg 25-OHD₃ + 2000 IU/kg VD₃ group, while the content of total bilirubin decreased significantly (p < 0.05). In addition, the 25-OHD₃ addition in diets improved the calcium and phosphorus contents in the serum (p < 0.05). The concentrations of 25-OHD₃, parathyroid hormones, follicle-stimulating hormone, and progesterone were increased in the 50 μg/kg 25-OHD₃ + 2000 IU/kg VD₃ group, and the levels of cortisol, calcitonin, bone gla protein, and endotoxin in the serum reached a minimum in the 50 μg/kg 25-OHD₃ + 4000 IU/kg VD₃ group (p < 0.05), which constitutes an advantage for the aged laying hens. The antioxidant enzyme activities and free radical scavenging abilities in the 50 μg/kg 25-OHD₃ + 2000 IU/kg VD₃ group increased markedly, and the MDA level decreased significantly in the 50 μg/kg 25-OHD₃ + 4000 IU/kg VD₃ group (p < 0.05). Improvements in jejunal morphology and intestinal integrity resulted in an increased villi-length-to-crypt-depth ratio in the 50 μg/kg 25-OHD₃ + 2000 IU/kg VD₃ group (p < 0.05). Dietary 50 μg/kg 25-OHD₃ and 2000 IU/kg VD₃ additions improved the tibia quality, including fresh tibia weight, strength, mineral content (Ca), and trabeculae area (p < 0.05). Taken together, compared with the dietary VD₃ addition, dietary supplementation of 25-OHD₃ supported a stable physiological status for sustained egg production, egg quality, and bone quality in late-phase laying hens, and the addition levels of 50 μg/kg 25-OHD₃ and 2000 IU/kg VD₃ had the best effect. Therefore, this could provide a theoretical basis for the use of 25-OHD₃ as a substitute forVD₃. Full article

Vitamin D deficiency and insufficiency are highly prevalent in CKD, affecting over 80% of hemodialysis (HD) patients and requiring therapeutic intervention. Nephrological societies suggest the administration of cholecalciferol according to the guidelines for the general population. The aim of the observational study was to evaluate the efficacy and safety of the therapy with a high dose of cholecalciferol in HD patients with 25(OH)D deficiency and insufficiency to reach the target serum 25(OH)D level > 30 ng/mL. A total of 22 patients (16 M), with an average age of 72.5 ± 13.03 years and 25(OH)D concentration of 13.05 (9.00–17.90) ng/mL, were administered cholecalciferol at a therapeutic dose of 70,000 IU/week (20,000 IU + 20,000 IU + 30,000 IU, immediately after each dialysis session). All patients achieved the target value > 30 ng/mL, with a mean time of 2.86 ± 1.87 weeks. In the first week, the target level of 25(OH)D (100%) was reached by 2 patients (9.09%), in the second week by 15 patients (68.18%), in the fourth week by 18 patients (81.18%), and in the ninth week by all 22 patients (100%). A significant increase in 1,25(OH)₂D levels was observed during the study. However, only 2 patients (9.09%) achieved a concentration of 1,25(OH)₂D above 25 ng/mL—the lower limit of the reference range. The intact PTH concentrations remained unchanged during the observation period. No episodes of hypercalcemia were detected, and one new episode of hyperphosphatemia was observed. In conclusion, our study showed that the administration of a high-therapeutic dose of cholecalciferol allowed for a quick, effective, and safe leveling of 25(OH)D concentration in HD patients. Full article

Sustainable healthy diets are promoted, and consequently vegetarian diets are currently increasing. However, scientific information on their effects on bone health is scarce. A cross-sectional study was performed in adults (66% women) classified into three groups: omnivores (n = 93), lacto-ovo vegetarians (n = 96), and vegans (n = 112). Nutrient intake, body composition, physical activity, vitamin D status (25-hydroxycholecalciferol, 25-OHD), parathormone (PTH), and bone formation (bone alkaline phosphatase, BAP) and resorption (N-telopeptides of type I collagen, NTx) markers were determined. Lacto-ovo vegetarians and especially vegans showed lower protein, fat, calcium, phosphorous, vitamin D, retinol, iodine, and zinc intakes, and higher carbohydrate, fibre, carotenes, magnesium, and vitamin K intakes compared to omnivores. Body composition was similar in the three groups that performed vigorous physical activity regularly. Body bone mass and muscle mass were positively correlated with BAP, and time performing physical activity with 25-OHD. The prevalence of vitamin D deficiency or insufficiency (25-OHD < 75 nmol/L) was 93.7% in the studied population, and vitamin D deficiency (25-OHD < 25 nmol/L) was significantly higher in vegans. Vegetarians of both groups had increased PTH and NTx with vegans showing significantly higher PTH and NTx than omnivores. Conclusion: Adult vegetarians, especially vegans, should reduce the risk of bone loss by appropriate diet planning and vitamin D supplementation. Full article

In ovo injection of the Marek’s disease (MD) vaccine (MDV) has been widely practiced in commercial US hatcheries. However, the MDV is very sensitive and may not be compatible with some nutrients when administered together by in ovo injection. When individually administered by in ovo injection, L-Ascorbic acid (L-AA) and 25-hydroxyvitamin D₃ (25OHD₃) have previously exhibited very promising results on the post-hatch physiological and immunological characteristics of broilers subjected to stressful commercial conditions. However, the compatibility of the MDV with these vitamins has not been previously explored. Their compatibility must first be established before their combined administration by in ovo injection can be considered. Therefore, the objective in this study was to determine the compatibility of the MDV with various levels of 25OHD₃ or L-AA. The treatments employed were MDV-alone, MDV in combination with 0.6 (low) or 2.4 (high) μg doses of 25OHD₃, or MDV in combination with 1.2 (low) or 12 (high) mg doses of L-AA. The live and dead ratio of primary chick embryo fibroblast cells infected by the MD virus (CEF-MDV) in each treatment was determined every 30 min for 2 h. The L-AA at both the low and high doses resulted in a 70% death of CEF-MDV within 1 h, but either dose of the 25OHD₃ exhibited only an approximate 5% lower CEF-MDV survival as compared to those in the MDV-alone treatment. Therefore, it is suggested that the two designated doses of 25OHD₃ have the potential to be effectively combined with the MDV for subsequent administration by in ovo injection. Full article

Preclinical studies show that the anticancer actions of vitamin D metabolites are mediated by apoptosis, inhibition of cell proliferation and induction of cell cycle arrest. Cervical cancer cells express an autocrine vitamin D metabolising system (VDMS) comprised of a vitamin D receptor, vitamin D catabolic enzyme (CYP24A1), and the activating enzyme of 25-hydroxycholecalciferol (25(OH)D3), CYP27B1. We assessed the anticancer effects of 25(OH)D3 at clinically relevant concentrations on a cervical squamous cell cancer cell line, SiHa. We evaluated cell health parameters (cell count, viability, and cell cycle), cell death modes (apoptosis, autophagic-dependent death, and necrosis by flow cytometry and transmission electron microscopy), and autocrine VDMS gene and protein expression by qPCR and Western blot, respectively. Our study demonstrates that physiological and supraphysiological doses of 25(OH)D3 inhibit cell growth and viability and induce biochemical and morphological apoptosis in SiHa cells. These growth effects are mediated by alteration in the VDMS gene and protein expression, with prominent negative feedback at supraphysiological treatment dose. These data identify promising therapeutic potential of 25(OH)D3 in cervical cancer, which warrants further clinical translational investigations. Full article

Background: Tinnitus is a highly prevalent and frequently disabling condition, such that the identification of possible causal mechanisms would yield significant clinical and social benefits. Since vitamin D (Vit D) is involved in the pathogenesis of several ear disturbances, we review here the current scientific literature addressing the relationship between Vit D status and tinnitus. Methods: An electronic search was conducted in PubMed, Scopus and Web of Science with the keywords “tinnitus” and “Vitamin D” or “Vit D” or “25OH-D” or “cholecalciferol” or “ergocalciferol” or “hydroxycholecalciferol”, without date (i.e., up to 8 February 2023) or language restrictions, in accordance with a protocol based on the transparent reporting of systematic reviews and meta-analysis (PRISMA) 2020 checklist, for identifying studies which assayed serum Vit D concentration in patients with or without tinnitus. Results: Three observational, case-control studies encompassing four cohorts and totaling 468 patients with (n = 268) or without tinnitus (n = 200) were included in this meta-analysis. Pooled analysis with quality effects models evidenced significantly reduced serum Vit D levels in patients with tinnitus compared to those without (weighted mean difference [WMD], −6.2 ng/mL; 95% CI, −10.3 to −2.1 ng/mL; I², 56%). Serum Vit D was found to be 22% lower in patients with tinnitus compared to those without. Conclusions: Lower serum Vit D levels may be associated with tinnitus, thus paving the way to plan future trials aimed at exploring whether Vit D supplementation may aid in preventing and/or improving tinnitus. Full article

Thyroid neoplasms (tumors) are the most common pathology of the endocrine system that requires surgery, and in most cases changes are benign. The surgical treatment of thyroid neoplasms consists in total, subtotal, or one lobe excision. Our study aimed to assess the concentration of vitamin D and its metabolites in patients before thyroidectomy. The study included 167 patients with thyroid pathology. Before the thyroidectomy procedure calcidiol (25-OHD), calcitriol (1,25-(OH)₂D), and vitamin D binding protein (VDBP), as well as basic biochemical parameters, were measured using an enzyme-linked immunosorbent assay kit. Data analysis showed that the cohort of patients has a significant 25-OHD deficiency and proper concentration of 1,25-(OH)₂D. Before the surgery, more than 80% of patients have extreme vitamin D deficiency (<10 ng/mL), and only 4% of the study group has proper 25-OHD concentration. Patients undergoing thyroidectomy are exposed to many complications, including calcium reduction. Our research has shown that patients prior to surgery have a marked vitamin D deficiency, an indicator that may affect their subsequent convalescence and prognosis. The results suggest that determination of vitamin D levels prior to thyroidectomy may be useful for potential consideration of supplementation when vitamin D deficiency is marked and needs to be incorporated into the good clinical management of these patients. Full article

Background: The aim of the present review was to summarize the current evidence about the impact of vitamin D deficiency on pathology and clinical manifestations of Sjögren’s disease (SD). Methods: Databases PubMed, Web of Science, Scopus, and Cochrane library were searched for studies assessing the levels of vitamin D in SD patients using the following keywords: (vitamin D OR calciferol OR cholecalciferol OR 25-hydroxyvitamin D OR 25-hydroxycholecalciferol OR calcidiol OR calcitriol OR 1,25-dihydroxycholecalciferol) AND (Sjögren’s Syndrome OR Sjögren’s disease) accessed on 20 September 2022. Out of 248 retrieved studies, following the systematic review methodology and defined inclusion and exclusion criteria, 9 clinical studies were eligible to be included in the present review: 4 of them case-control, 4 cross-sectional, and 1 cohort study. Results: Nine studies totaling 670 SD patients and 857 healthy controls were eligible for meta-analysis with moderate to high methodological quality as determined by the Newcastle–Ottawa Quality Scale (NOS). According to the obtained results, a high prevalence of hypovitaminosis D was observed in SD patients when compared to healthy controls (95% CI −10.43, −2.39; p < 0.01). Conclusion: Available evidence points to lower levels of vitamin D in patients with SD in comparison to healthy controls. However, further studies are necessary to understand the underlying mechanisms associated with the role of vitamin D in the development and disease severity of SD. Full article