Oral Vitamin D3 Research Articles

A Comparison between Severity-dependent Protocol and Fixed Dose Regimen of Oral Vitamin D Supplementation on Correction of Hypovitaminosis D among Dialysis Patients.

Low vitamin D status is associated with either low muscle mass or impaired muscle function in dialysis patients. However, there is no consensus on how best to correct hypovitaminosis D, defined as serum 25-hydroxyvitamin D [25(OH)D] level <30 ng/mL, in patients with end-stage kidney disease (ESKD). This study investigated the effect of different vitamin D supplementation regimens on sarcopenia outcomes in dialysis patients. This was a prospective randomized controlled trial. ESKD patients treated with maintenance hemodialysis (HD) or peritoneal dialysis (PD) with low vitamin D status on a ratio of 1:1, randomized to either receive oral ergocalciferol utilizing a severity-dependent treatment protocol for low vitamin D status suggested by the K/DOQI as a control group, or a fixed-dose regimen of 20,000 international units (IU)/week. The changes in muscle mass were measured by bioimpedance spectroscopy (BIS), muscle strength was assessed by a hand grip dynamometer, physical performance was determined by gait speed, and muscle-related biomarkers were examined. A total of 76 dialysis patients were randomized (HD=43.4%). Baseline characteristics, including age, dialysis vintage, and muscle parameters were similar. After supplementation, the average serum 25(OH)D levels in the severity-dependent and fixed-dose groups were significantly elevated from 14.5±7.3 to 27.2±13.2 ng/mL, p<0.001 and from 15.1±6.4 to 28.8±11.5 ng/mL, p<0.001, respectively, and did not differ between groups at six months (p=0.60). Despite comparable energy and protein intake, the mean BIS-derived total-body muscle mass normalized to height squared was significantly increased at six months in the fixed-dose group (14.5±3.3 to 15.3±3.0 kg/m2, p=0.03) compared with the severity-dependent protocol (13.5±2.7 to 13.7±2.9 kg/m2, p=0.58). In the subgroup analysis, muscle mass improvement was statistically elevated in PD patients (p=0.01) while unaltered among HD patients (p=0.88) in the fixed-dose group. Muscle strength, gait speed, and serum insulin-like growth factor-1 level, as the mediators of muscle cell growth, were not different between the two groups at six months (p>0.05). Neither hypercalcemia nor hyperphosphatemia was found throughout the study. A fixed-dose ergocalciferol supplementation demonstrates similar performance in the correction of low vitamin D status but better muscle mass improvement than a severity-dependent protocol among ESKD patients. Regular dosing intervals of weekly vitamin D supplementation appear to be a promising treatment for sarcopenia among patients undergoing dialysis.

Blood Pressure Decreases in Overweight Elderly Individuals on Vitamin D: A Randomized Trial.

Evidence for a beneficial role of vitamin D on blood pressure (BP) outcomes is inconclusive. This work aimed to investigate the effect of 2 doses of cholecalciferol (vitamin D3) supplementation coadministered with calcium on systolic blood pressure (SBP) and diastolic blood pressure (DBP). Exploratory analyses were conducted from a 1-year, multicenter, double-blind, randomized controlled trial (RCT). Total of 221 ambulatory older overweight individuals received calcium dose and oral vitamin D3, at the equivalent of 600 IU/day or 3750 IU/day. SBP and DBP decreased significantly in the overall group, and in the high-dose group at 6 and 12 months. Similar trends were observed in the low-dose group, but did not achieve statistical significance. In participants with a body mass index (BMI) greater than 30, SBP decreased significantly in both treatment groups whereas DBP significantly decreased in the high-dose group only. In the subgroups of hypertensive participants (N = 143), there was a decrease in SBP and DBP at 6 and 12 months, with both vitamin D doses and independently of BMI levels. Using multivariate linear mixed models with random effects in the overall group of participants, SBP at 6 and 12 months was significantly predicted by BMI (β = .29; P = .05) and by baseline SBP (β = .16; P < .001), but not by vitamin D treatment dose. Vitamin D and calcium decrease SBP and DBP in overweight older individuals, but more is not necessarily better. This effect is seen in individuals with BMI greater than 30, in hypertensive patients, and seems to be largely independent of dose.

7793 Bone Mineral Density, Turnover And Bone Microarchitecture Alterations With Dapagliflozin In Post-menopausal Women With Type 2 Diabetes Mellitus: An Open-Label, Parallel-Arm, Randomized, Controlled Study

Abstract Disclosure: S.K. Bhadada: None. L. Das: None. M. Baruah: None. V. Singla: None. V. Dhiman: None. S. Ram: None. S. Sharma: None. N. Sachdeva: None. P. Dutta: None. Introduction: Evidence is limited and there is no consensus about the effects of SGLT2i on bone metabolism. The objective of the current study was to assess changes in bone mineral density (BMD), turnover markers (BTMs), and microarchitecture with the use of dapagliflozin in type 2 diabetes mellitus (T2DM). Methods: Post-menopausal women (&amp;lt;65 years) with T2DM (both menopause and T2DM duration &amp;gt; 5 years and HbA1c 7-11%) were randomly allocated (1:1) to receive either add-on dapagliflozin with standard-of-care or standard-of-care alone for T2DM management. Those with osteoporosis, on anti—osteoporotic medication, chronic glucocorticoids (&amp;gt;3 months), thiazolidinediones, phenytoin, tamoxifen, estrogen, eGFR&amp;lt;30ml/min/1.73m2, contraindication/past usage of SGLT2i, or with known endocrinopathy were excluded. Patients were made Vitamin D sufficient [25(OH)D &amp;gt; 30ng/ml] with oral cholecalciferol (60K daily for 1 week), if deficient. BMD (DXA, Hologic), BTMs (P1NP, CTX) and microarchitecture were assessed at baseline, 6 and 12 months. Results: A total of 131 patients were screened, of which 101 were randomized (50 dapagliflozin, 51 non-dapagliflozin). The mean age (± SD) in the dapagliflozin group was 58.1 ± 5.8 years, diabetes duration was 9.4 ± 5.2 years and HbA1c was 8.5 ± 1.7%. Baseline clinico-biochemical, areal BMD, volumetric BMD, trabecular structural (number, thickness, separation) and cortical structural (thickness and porosity) parameters were comparable between both groups. Only cortical pore diameter (Ct.Po.Dm) (±SD) at radius (0.199 ± 0.04 vs 0.180 ± 0.03, p =0.01) and tibia (0.256 ± 0.04 vs 0.226 ± 0.03, p =0.001) were higher in the dapagliflozin than the non-dapagliflozin group. At 6 months, BMD at lumbar spine (LS), hip, femoral neck (FN), and distal radius and BTMs were comparable between the dapagliflozin (n=38) and the non-dapagliflozin (n=39) groups. However, there was significantly higher trabecular thickness (Tb.Th) (0.230 ± 0.02 vs 0.218 ± 0.01, p=0.003), cortical thickness (Co.Th) (1.104 ± 0.2 vs 0.998 ± 0.2, p=0.04), intra-cortical porosity (Ct.Po) (0.008 ± 0.005 vs 0.005 ± 0.003, p= 0.020) and Ct.Po.Dm (0.192 ± 0.03 vs 0.169 ± 0.02, p=0.003), all at radius in the dapagliflozin group. At 12 months follow-up, BMD (g/cm2) at all 4 sites were again comparable between the dapagliflozin (n=36) and non-dapagliflozin (n=36) groups. Serum CTX (pg/ml) (388.8 ± 191.5 vs 327.4 ± 140.8, p = 0.06), and P1NP (ng/ml) (38.8 ± 16.3 vs 32.5 ± 16.3, p = 0.12) were non-significantly higher with dapagliflozin use. Among microarchitecture parameters, only Ct.Po.Dm at the radius (0.189 ± 0.03 vs 0.169 ± 0.03, p= 0.025) and tibia (0.251 ± 0.05 vs 0.228 ± 0.03, p= 0.030) remained significantly higher in the dapagliflozin group. Conclusion: Dapagliflozin has no long-term detrimental effects on BMD, BTMs or bone microarchitecture after 1 year of treatment in postmenopausal women with T2DM. Presentation: 6/1/2024

8126 PTH-Independent, Calcitriol-Mediated Hypercalcemia In Renal Cell Carcinoma

Abstract Disclosure: G.K. Rai: None. A. De Rosairo: None. K. Madani: None. D. Sacoto: None. A.A. Franco-Akel, MD: None. R. Belokovskaya: None. Hypercalcemia of malignancy is a known complication of advanced cancer. It occurs through various mechanisms, one of which is via 1,25-dihydroxyvitamin D (calcitriol). Calcitriol-mediated hypercalcemia accounts for approximately 1% of cases of hypercalcemia in the setting of malignancy and is usually seen in lymphomatous solid tumors. We present a gentleman with clear cell renal cell carcinoma associated with hypercalcemia with normal levels of intact parathyroid hormone (PTH), PTH-related protein (PTHrP), and 25-hydroxyvitamin D but elevated calcitriol levels. A 48 year-old-male with no significant past medical history with complaints of fatigue, hematuria, and weight loss of 38 pounds in 3 months was following urology for an elective right-sided nephrectomy. MRI of the abdomen and pelvis found a 16.1 cm renal mass with necrotic areas, causing mass effects on the liver, pancreas, and IVC. Preoperative laboratory showed hypercalcemia of 13.7 mg/dL (corrected 13.9 mg/dL) with microcytic anemia (hemoglobin 8.8 g/dL, MCV 72 fl). Workup showed low iPTH (3 pg/dL), 25-hydroxyvitamin D (16.9 ng/dL), and phosphorus level (1.7mg/dL) with elevated calcitriol (94.3 pg/dL) and a normal PTHrP. CT chest showed multiple pulmonary nodules on bilateral lobes, with the largest nodule ∼ 4.5 mm. Hypercalcemia was managed with IV fluids, calcitonin 300 units Q12 for two days, Denosumab IV infusion, prednisone 60 mg for three days, and oral ergocalciferol 50,000 units weekly. Calcium levels normalized, after which the patient underwent nephrectomy. Pathology revealed renal cell carcinoma grade G4 with mixed features of clear cell carcinoma with sarcomatoid and rhabdoid features. We report an incidental finding of hypercalcemia in a patient with renal mass. The elevated calcitriol levels can be attributed to ectopic calcitriol production through the renal mass. Post nephrectomy calcium levels remained within normal range for consecutive weeks. With this, we concur that hypercalcemia most likely originated from the renal mass that had ectopic production of calcitriol. Dysregulated calcitriol production is a well-known complication of lymphomas and granulomatous disease but is seldom reported with solid tumors. Usually, the etiology for hypercalcemia in patients with renal cell carcinoma is the overproduction of PTHrP, which was not the case with our patient. The ultimate resolution of hypercalcemia of malignancy was attained by treating the underlying malignancy. Presentation: 6/1/2024

8126 PTH-independent, Calcitriol-mediated Hypercalcemia in Renal Cell Carcinoma

Abstract Disclosure: G.K. Rai: None. A. De Rosairo: None. K. Madani: None. D. Sacoto: None. A.A. Franco-Akel, MD: None. R. Belokovskaya: None. Hypercalcemia of malignancy is a known complication of advanced cancer. It occurs through various mechanisms, one of which is via 1,25-dihydroxyvitamin D (calcitriol). Calcitriol-mediated hypercalcemia accounts for approximately 1% of cases of hypercalcemia in the setting of malignancy and is usually seen in lymphomatous solid tumors. We present a gentleman with clear cell renal cell carcinoma associated with hypercalcemia with normal levels of intact parathyroid hormone (PTH), PTH-related protein (PTHrP), and 25-hydroxyvitamin D but elevated calcitriol levels. A 48 year-old-male with no significant past medical history with complaints of fatigue, hematuria, and weight loss of 38 pounds in 3 months was following urology for an elective right-sided nephrectomy. MRI of the abdomen and pelvis found a 16.1 cm renal mass with necrotic areas, causing mass effects on the liver, pancreas, and IVC. Preoperative laboratory showed hypercalcemia of 13.7 mg/dL (corrected 13.9 mg/dL) with microcytic anemia (hemoglobin 8.8 g/dL, MCV 72 fl). Workup showed low iPTH (3 pg/dL), 25-hydroxyvitamin D (16.9 ng/dL), and phosphorus level (1.7mg/dL) with elevated calcitriol (94.3 pg/dL) and a normal PTHrP. CT chest showed multiple pulmonary nodules on bilateral lobes, with the largest nodule ∼ 4.5 mm. Hypercalcemia was managed with IV fluids, calcitonin 300 units Q12 for two days, Denosumab IV infusion, prednisone 60 mg for three days, and oral ergocalciferol 50,000 units weekly. Calcium levels normalized, after which the patient underwent nephrectomy. Pathology revealed renal cell carcinoma grade G4 with mixed features of clear cell carcinoma with sarcomatoid and rhabdoid features. We report an incidental finding of hypercalcemia in a patient with renal mass. The elevated calcitriol levels can be attributed to ectopic calcitriol production through the renal mass. Post nephrectomy calcium levels remained within normal range for consecutive weeks. With this, we concur that hypercalcemia most likely originated from the renal mass that had ectopic production of calcitriol. Dysregulated calcitriol production is a well-known complication of lymphomas and granulomatous disease but is seldom reported with solid tumors. Usually, the etiology for hypercalcemia in patients with renal cell carcinoma is the overproduction of PTHrP, which was not the case with our patient. The ultimate resolution of hypercalcemia of malignancy was attained by treating the underlying malignancy. Presentation: 6/1/2024

6970 Severe Symptomatic Hypophosphatemia After Intravenous Iron Therapy: An Under-recognized Adverse Reaction

Abstract Disclosure: A. Morvant: None. O. Olajide: None. Introduction: Iron deficiency is a common condition that is often treated with intravenous preparations of iron supplementation. It has been documented in the literature that ferric carboxymaltose is the form of intravenous iron supplementation that is associated with the highest incidence of hypophosphatemia, when compared to other formulations of intravenous iron therapy. This case highlights a severe case of hypophosphatemia after ferric carboxymaltose therapy that led to multiple hospitalizations and required several months of oral and intravenous phosphorus repletion. Clinical Case A 36-year-old woman presented to the ED with severe diffuse arthralgias, generalized muscle weakness, and fatigue. Laboratory analysis revealed the following: phosphorus 1.2 mg/dL (2.3-4.7 mg/dL), 25-hydroxyvitamin D 13 ng/mL (25-80 ng/mL), parathyroid hormone 220 pg/mL (16-77 pg/mL), and calcium 8.5 mg/dL (8.4-10.5 mg/dL). She was admitted and started on intravenous and oral phosphorus repletion as well as oral ergocalciferol. She was subsequently discharged home on oral phosphorus and ergocalciferol supplementation, with a phosphorus level of 1.8 mg/dL. She was readmitted one day later with persistent arthralgias, myalgias, and severe fatigue, and found to have a phosphorus level of 1.1 mg/dL. Additional laboratory studies revealed the following: FGF23 41 pg/mL (&amp;lt;59 pg/mL) and 24-hour urine phosphorus 2191 mg/24hr (400-1300 mg/24hr). The patient notably had a history of chronic severe iron deficiency anemia due to menorrhagia and had been treated with intravenous iron sucrose infusions 7 months prior to her presentation. Due to adverse reactions to iron sucrose, this was switched to ferric carboxymaltose, and she had received two doses; one month and two weeks prior to her initial presentation. She was treated again with intravenous and oral phosphorus repletion and ergocalciferol and discharged after two weeks on oral phosphorus and ergocalciferol as well as thrice-weekly intravenous phosphorus infusions in the outpatient setting. She continued intravenous phosphorus infusions for about three months, and this was subsequently discontinued without recurrent hypophosphatemia. She is currently on low doses of oral phosphorus with normophosphatemia. Conclusion: Intravenous ferric carboxymaltose therapy can lead to severe and long-lasting, treatment-resistant hypophosphatemia due to increased urinary phosphate excretion. An increased awareness about this is needed by clinicians in treating patients who receive ferric carboxymaltose and monitoring phosphorous levels is crucial.

7387 A Rare Case Of Concomitant Intrathyroidal Parathyroid Carcinoma With Osteitis Fibrosa Cystica, Masquerading As Oncocytic Thyroid Carcinoma - A Post-operative Diagnosis

Abstract Disclosure: Y. Koh: None. D.E. Chew: None. T.P. Quek: None. Introduction: Parathyroid carcinoma is a rare form of malignancy. An intrathyroidal location of parathyroid carcinoma further complicates the diagnosis as it may be mistakenly presumed to be of thyroid origin instead. We present a case report of an intrathyroidal parathyroid carcinoma which was diagnosed post-total thyroidectomy. Clinical case: A 72-year-old lady was found to have an intrathyroidal mass after presenting with unintentional weight loss and chronic constipation. Ultrasound of the neck showed a 4.0 x 2.9cm markedly hypoechoic solid mass in the mid-lower right thyroid lobe. Fine needle aspiration of the mass was suspicious for an oncocytic neoplasm. She underwent total thyroidectomy with central neck dissection for concerns of oncocytic thyroid carcinoma. Intraoperatively, a 4cm right hard intrathyroidal nodule invading into the right recurrent laryngeal nerve was observed. All 4 parathyroids were identified and preserved. Post-operatively, routine biochemistry to monitor for hypocalcemia showed hypercalcemia instead. This quickly transitioned into hypocalcemia on post-operative day 4, with biochemistry supportive of hungry bone syndrome [adjusted calcium 2.05mmol/L [normal range (NR) 2.15-2.5], phosphate 0.6mmol/L (NR 0.8-1.4), PTH 8.2pmol/L (NR 0.8-6.8), 25-OH vitamin D 18ug/L (NR 30-100)]. She was started on oral calcium carbonate, calcitriol and cholecalciferol aiming for normocalcemia. Evidence for underlying primary hyperparathyroidism were sought for, which showed osteitis fibrosa cystica, severe osteoporosis and an ossifying fibroma of the mandible, suggesting underlying hyperparathyroidism-jaw tumour-syndrome. The intra-operative histology was reported as oncocytic carcinoma with angio- and perineural invasion, presumed to be thyroid in origin. Given our suspicion of underlying primary hyperparathyroidism, we requested our pathology colleagues to perform additional immunochemical stains, which stained diffusely positive for parathyroid hormone, GATA3 but were negative for thyroglobulin, thyroid transcriptor factor-1, confirming its parathyroid origin. Her hungry bone syndrome resolved 22 weeks post-operatively. Till present (14 months post-operatively), her calcium and PTH levels remain normal and ultrasound of the neck did not reveal any evidence of recurrence. She declined genetic screening. Clinical Lesson: A high index of suspicion is required for the diagnosis of parathyroid carcinoma. In a patient who presents with constitutional symptoms and a neck mass, it is imperative to consider parathyroid disease as a differential diagnosis. A lesion with oncocytic morphology may be of parathyroid or thyroid origin, and the use of immunochemical stains can help differentiate them. Effective communication between clinicians and pathologists is essential in clinching the correct cytopathological diagnosis. Presentation: 6/3/2024

6990 Vitamin D Supplementation in Primary Hyperparathyroidism: Effects on 1,25(OH)Vitamin D and FGF23 Levels

Abstract Disclosure: S.G. Pallone: None. M. Ohe: None. L.D. Santos: None. I.O. Nakaguma: None. I.S. Kunii: None. R.E. Silva: None. S.S. Maeda: None. C.M. Brandao: None. J.G. Vieira: None. M. Lazaretti-Castro: None. Background: Primary hyperparathyroidism (PHPT) is a condition characterized by high levels of PTH in the presence of hypercalcemia. Vitamin D deficiency has been associated with more severe presentations. Our aim was to evaluate the effects of Vitamin D supplementation on mineral homeostasis and related hormones in individuals with PHPT compared to controls without PHPT. Materials and methods: Individuals with and without PHPT 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)2 vitamin D (1,25(OH)2D), intact Fibroblast Growth Factor 23 (FGF23), 25-hydroxyvitamin D (25OHD), Parathormon (PTH), total calcium (tCa), phosphorus and other biochemical markers. The intact FGF23 was measured using an automated Diasorin LIAISON kit. The 1,25(OH)2D measurement was performed using liquid chromatography and mass spectrometry (LC-MS/MS). Results: 70 PHPT patients and 75 healthy individuals (CTRL) were included, and 55 PHPT and 64 CTRL completed the 12-week protocol. At baseline, tCa, PTH, 1,25(OH)2D, and intact FGF23 concentrations were significantly higher in PHTP, with no difference in 25OHD levels. After the intervention, the 25OHD levels increased significantly in both groups (PHPT: 22.6.9±6.1 to 31.5±6.8; CTRL: 20.3±5.7 to 32.5±6.4 ng/mL, p&amp;lt;0.001). There was significative increase in intact FGF23 levels in both groups (PHPT: 47.9±27.1 to 76.3±33.3; CTRL: 40.5±13.9 to 59.8±19.8 pg/mL, p&amp;lt;0.001). After the vitamin D replacement, the tubular reabsorption of phosphate (TRP) was significantly reduced in both groups (PHPT: 85.0±7.4% to 83.6±7.75% CTRL: 89.5±4.5% to 88.7±4.8%, p=0.031), without changes in serum phosphorus levels, possibly indicating phosphaturic response to the intervention. Moreover, this decrease of TRP was positively correlated to the increment of FGF23 in the PHPT group. A paradoxical decrease in 1,25(OH)2D levels after vitamin D supplementation was observed in both groups (PHPT: 94.8±34.6 to 68.9±25.3; CTRL: 68.7±23.5 to 56.4±20.7 pg/mL, p&amp;lt;0.001). The reduction of 1,25(OH) 2 D was inversely correlated with the elevation of FGF23 in both groups (r=-0.302, p=0.028). In both groups, no changes in tCa were observed (PHPT: from 11.02±0.9 to 11.1±0.8; CTRL: 9.6±0.3 to 9.6±0.3 pg/mL, p=0.153), as the same for urinary calcium (p=0.534) and PTH measurements (p=0.516). Conclusion: The weekly administration of 14,000 IU of Vitamin D3 was safe and the increase in 25OHD after supplementation did not change the serum or urinary calcium levels in adults with and without PHPT. In both groups, it was observed a paradoxical decrease in 1,25(OH)2D levels after supplementation, which was associated with significant increase in intact FGF23 levels. This effect can maybe explain the safety response on calcium levels in face of vitamin D supplementation among PHPT patients. Presentation: 6/2/2024

Effect of cholecalciferol supplementation on PTH and increasing the glomerular filtration rate in kidney transplant patients at King Faisal Specialist Hospital and Research Center

The association between oral cholecalciferol and GFR has been identified in various renal transplant populations around the globe. This study aimed to evaluate the effect of oral cholecalciferol supplementation on the GFR and serum PTH levels, with other parameters in the Saudi kidney transplant population. A retrospective observational study was conducted on a cohort of 174 kidney recipients who underwent transplantation and had serum 25-Hydroxy VD level tests performed (2018-2022) at King Faisal Specialist Hospital and Research Center in Jeddah, KSA. Generalized and linear mixed effects regression models were conducted. The percentage of GFR &gt;60 (25.86% vs 78.16%, P&lt;.0001) and VD insufficiency (&lt; 30 ng/mL) (36.21% vs 6.90%, P&lt;.0001) were significantly different between pre-&amp; post-transplant periods, respectively. After adjustment, significant changes were found in post-transplant GFR, hemoglobin levels, serum creatinine levels, blood urea nitrogen levels, hematocrit levels, PTH levels, and VD 25-Hydroxy from the baseline. Calciferol 1000/2000 IU and 50,000 IU (P&lt;.0001) were significantly more effective in increasing the odds of having GFR &gt;60 as compared to other supplements (P=0.75). VD supplementations may be particularly beneficial in improving kidney function in kidney transplant patients, as this contributes to normalizing GFR levels and creatinine levels and reducing PTH levels.

Cholecalciferol effect on oxidative stress and novel predictors of inflammation in hemodialysis patients: a prospective randomized trial

BackgroundEmerging evidence links vitamin D deficiency to oxidative stress (OS) and inflammation, posing ongoing risks to cardiovascular outcomes in hemodialysis (HD) patients. Despite this, current data are lacking regarding the optimal approach or schedule for administering vitamin D in this population. This study investigated the effectiveness of oral weekly versus oral monthly cholecalciferol supplementation on 25-hydroxy vitamin D (25(OH)D) levels, oxidative stress, inflammatory indicators, and secondary hyperparathyroidism in HD population. HD patients (N = 50) were randomly allocated to Group A (oral weekly 50,000 IU cholecalciferol) or Group B (oral monthly 200,000 IU cholecalciferol) for a 3 months duration. Serum levels of 25(OH)D, malondialdehyde (MDA), superoxide dismutase (SOD), high sensitivity C-reactive protein (HsCRP), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and intact parathyroid hormone (iPTH) were assessed at baseline and upon completion of the study.ResultsA notable increase in serum 25(OH)D levels observed in both groups, with Group A showing a notably greater increase (p = 0.003). Group A demonstrated significant reductions in serum MDA and increases in SOD, along with declines in hsCRP and NLR levels, which were not observed in Group B. Moreover, Group A exhibited a greater drop in iPTH (ΔiPTH = − 30 pg/mL vs. − 3 pg/mL) compared to Group B. Clinicaltrial.gov: NCT05460338, registered 13/07/2022.ConclusionsWeekly oral 50,000 IU cholecalciferol supplementation emerges as a tolerable, safe and effective approach for restoring vitamin D levels in HD patients, while concurrently mitigating inflammation, OS, and secondary hyperparathyroidism. This finding suggests that the more frequent the administration of oral cholecalciferol, the higher the efficiency observed.

Efficacy of oral calcium carbonate and vitamin D3 granules for the management of pains in growing limbs in children

Efficacy of oral calcium carbonate and vitamin D3 granules for the management of pains in growing limbs in children

Effect of Vitamin D Supplementation on Glycemic Control in Newly Diagnosed Patients With Type 2 Diabetes Mellitus: A Randomized Controlled Trial.

Vitamin D deficiency is commonly associated with type 2 diabetes and it has been linked to impaired glycemic control in these patients. This study was done to determine if vitamin D supplementation improves glycemic parameters in type 2 diabetes. This randomized controlled trial was done in 140 newly diagnosed adult patients with type 2 diabetes. The participants were randomly divided into two groups where one group received vitamin D (60,000 International Units (IU) of oral vitamin D3 weekly for a duration of three months, followed by 1000 IU twice daily for another three months in vitamin D deficient patients; 1000 IU (25 mcg) twice daily for six months for subjects with sufficient vitamin D level) along with standard anti-diabetic drugs while the other group received standard anti-diabetic drugs only. The effect of vitamin D supplementation was assessed by measuring glycated haemoglobin (HbA1c), fasting blood sugar (FBS), postprandial blood sugar (PPBS), fasting insulin, and insulin resistance as Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) at the baseline and after six months. Vitamin D deficiency was observed in 60% (n=84) of the subjects with the rest 40% (n=56) having sufficient serum vitamin D levels. The baseline mean HbA1c was 8.48 ± 1.46% and 8.21 ± 1.24% in the control and vitamin D group, respectively. After supplementing vitamin D for six months, no significant difference was observed between the two groups in terms of HbA1c (p= 0.263). Similarly, there was no significant change in other parameters like FBS, PPBS, fasting insulin, and insulin resistance (HOMA-IR). A subgroup analysis within the vitamin D group between the vitamin D sufficient and deficient patients also revealed no significant changes in the above parameters. Vitamin D supplementation, within the parameters of this study, did not yield a distinctive advantage in improving glycemic outcomes in individuals with type 2 diabetes.

UV light exposure versus vitamin D supplementation: A comparison of health benefits and vitamin D metabolism in a pig model

There is limited data on the effect of UV light exposure versus orally ingested vitamin D3 on vitamin D metabolism and health. A 4-week study with 16 pigs (as a model for human physiology) was conducted. The pigs were either supplemented with 20 µg/d vitamin D3 or exposed to UV light for 19 min/d to standardize plasma 25-hydroxyvitamin D3 levels. Important differences were higher levels of stored vitamin D3 in skin and subcutaneous fat, higher plasma concentrations of 3-epi-25-hydroxyvitamin D3 and increases of cutaneous lumisterol3 in UV-exposed pigs compared to supplemented pigs. UV light exposure compared to vitamin D3 supplementation resulted in lower hepatic cholesterol, higher circulating plasma nitrite, a marker of the blood pressure-lowering nitric oxide, and a reduction in the release of pro- and anti-inflammatory cytokines from stimulated peripheral blood mononuclear cells. However, plasma metabolome and stool microbiome analyses did not reveal any differences between the two groups. To conclude, the current data show important health relevant differences between oral vitamin D3 supplementation and UV light exposure. The findings may also partly explain the different vitamin D effects on health parameters obtained from association and intervention studies.

Daily versus fortnightly oral vitamin D3 in treatment of symptomatic vitamin D deficiency in children aged 1-10 years: An open labelled randomized controlled trial.

Compare the efficacy and safety of daily versus fortnightly oral vitamin D3 in treating symptomatic vitamin D deficiency in children aged 1-10 years. Open labelled randomized controlled trial. Eighty children with symptomatic vitamin D deficiency were randomized into group daily (D) and group bolus (B) [40 in each group] to receive oral vitamin D3, 4000 IU daily or 60,000 IU fortnightly for 12 weeks respectively. Both groups received daily oral calcium of 500 mg/day. Serum calcium (Ca), phosphate (P), alkaline phosphatase (ALP), 25-hydroxy cholecalciferol (25(OH)D), parathyroid hormone (PTH) levels, urine calcium: creatinine ratio and radiological score were assessed at baseline, 4 weeks and 12 weeks. At the end of 12 weeks, 74 children were available for evaluation of the efficacy and safety of both regimens. Both regimens led to a significant increase in Ca and P levels and a fall in ALP and PTH levels from baseline to 4 and 12 weeks of therapy, with no intergroup difference. At 4- and 12-week assessments, all children in both treatment arms achieved 25(OH)D level in sufficiency range,with no significant difference in their geometric mean. Both regimens were associated with asymptomatic transient hypercalcemia [group D-51.4% vs. group B-34.3%; p-0.14] and hypercalciuria (5.7%) in group D that resolved spontaneously on follow-up. Daily and fortnightly oral vitamin D3 in similar cumulative doses are efficacious for treating symptomatic vitamin D deficiency in children (1-10 years). Treated children should be monitored for serum 25(OH)D, Ca and urinary calcium creatinine ratio.

Impact of high-dose cholecalciferol (vitamin D3) and inulin prebiotic on intestinal and airway microbiota in adults with cystic fibrosis: A 2 × 2 randomized, placebo-controlled, double-blind pilot study

BackgroundCystic fibrosis (CF) is a multi-organ disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR). Individuals with CF often have gastrointestinal (GI) dysbiosis due to chronic inflammation and antibiotic use. Previous studies suggested a role for vitamin D in reversing the GI dysbiosis found in CF. ObjectiveTo explore the potential role of a combination of high-dose oral cholecalciferol (vitamin D3) and fermentable dietary fiber, inulin, to impact bacterial composition, richness, and diversity of intestinal and airway microbiota in adults with CF. MethodsThis was a 2 × 2 factorial, double-blinded, placebo-controlled, randomized, pilot clinical trial in which adults with CF received oral cholecalciferol (vitamin D3) (50,000 IU/week) and/or inulin (12 g/day) for 12 weeks. Thus, there were 4 study groups (n = 10 subjects per group); 1) placebo 2) vitamin D3 3) inulin 4) vitamin D3 plus inulin. Stool and sputum samples were collected at baseline (just before) and after the intervention and were analysed using 16S ribosomal RNA gene sequencing for gut and airway microbiota composition. Statistical analyses assessed alpha and beta diversity to evaluate microbial community changes. ResultsOf a total of 254 screened participants, 40 eligible participants were randomized to one of the 4 treatment arms. Participants receiving vitamin D3 plus inulin exhibited greater changes in microbiome indexes in both intestinal and airway relative to those in the other study groups. Specific taxonomic changes supported the potential beneficial influence of this combination to mitigate both intestinal and airway dysbiosis in adults with CF. ConclusionThis pilot study established that the combination of oral vitamin D3 and the prebiotic inulin was well tolerated over 12 weeks in adults with CF and altered gut and airway bacterial communities. Future research appear warranted to define clinical outcomes and the role of microbiota changes therein with this approach.

Comparison of Oral Vitamin D2 and Vitamin D3 Supplementation in Raising Serum 25-Hydroxy Vitamin D Status in Pediatric Patients

Abstract Background there is a controversy regarding the effect of vitamin D2 and D3 in elevating and sustaining 25-hydroxyvitamin D (25(OH)D) levels in pediatric patients. It has been suggested that vitamin D3 may be superior to vitamin D2 in raising and sustaining adequate 25(OH)D values. Aim: To study the difference between the effect of enteral vitamin D2 and vitamin D3 administration in raising and maintaining serum 25(OH)D in pediatric patients. Methods Randomized controlled clinical trial, conducted in Pediatric Endocrinology Unit, Ain Shams University, Cairo, Egypt, where 60 participants who had vitamin D deficiency were recruited. Subjects were divided into two groups, 30 patients per group (group A received 2400 IU of oral vitamin D2 daily and group B received 2400 IU of oral vitamin D3 daily). History of sun exposure and dietary intake of calcium, assessment of anthropometric measures and Tanner staging, laboratory investigations were documented. Follow up of serum level of 25(OH)D was done every month for three consecutive months. Results Oral vitamin D3 supplementation in group B patients resulted in significantly higher increments in 25(OH)D levels than that achieved by oral vitamin D2 supplementation in group A after 2nd, and 3rd months of the supplementation (P=0.000). Vitamin D3 supplementation resulted in a significantly greater increment in serum 25(OH)D levels from 1st to 2nd month and from 1st to 3rd month than Vitamin D2 supplementation (P=0.000). All participants in group B (100%) who received vitamin D3 reached sufficient levels (≥ 30 ng/ml) after 2 months while 76.7% of participants in group A who received vitamin D2 reached sufficient levels after 2 months and 23.3% of participants after 3 months (P= 0.017). Conclusion Oral vitamin D3 supplementation was more effective in raising serum 25(OH)D status in pediatric patients than oral vitamin D2 supplementation.

Role of vitamin D supplement adjunct to topical benzoyl peroxide in acne: a randomized double-blinded controlled study

Background: Acne is an inflammatory condition of the pilosebaceous unit. Previous studies have established a link between acne and vitamin D deficiency and the potential effectiveness of vitamin D supplementation in treatment. However, the efficacy of vitamin D as an adjuvant treatment for acne remains unknown. Objective: To evaluate the efficacy of weekly vitamin D2 oral administration as an adjunctive treatment to standard topical care for acne. Methods: This study was a randomized, double-blind, placebo-controlled trial including subjects with mild-to-moderate acne. Topical 2.5% benzoyl peroxide was applied twice daily for 12 weeks to all subjects. Subjects were randomly allocated to receive either oral vitamin D2 40,000 IU weekly or placebo weekly during the treatment period. No additional treatment was administered during the 4-week follow-up period. Results: A total of 44 subjects were included in this study. All of them had inadequate 25(OH)D levels. Both regimens showed significant improvement in acne during the treatment period. Weekly vitamin D2 supplementation significantly prevented the relapse of inflammatory acne lesions (P = .048) at the follow-up visit. No adverse effects or biochemical changes were observed. Limitations: There were no subjects of severe acne vulgaris. Conclusion: Adjunctive weekly vitamin D2 supplementation to standard topical benzoyl peroxide could reduce relapses of inflammatory lesions in mild-to-moderate acne.

Vitamin D attenuates monosodium glutamate-induced behavioural anomalies, metabolic dysregulation, cholinergic impairment, oxidative stress, and astrogliosis in rats

BackgroundMonosodium glutamate (MSG) is a commonly used flavor enhancer that has raised concerns due to its potential adverse effects on various organs. This study explored the neuroprotective potential of Vitamin D, a beneficial micronutrient, in mitigating MSG-induced neurotoxicity. Materials and methodsAdult male Wistar rats were categorized into five groups: control (2 ml/kg PBS orally for 30 days), MSG (40 mg/kg orally for 30 days), VIT-D (oral cholecalciferol; 500 IU/kg for 30 days), MSG+VIT-D (MSG for 30 days followed by VIT-D for another 30 days), and VIT-D/MSG (concurrent VIT-D and MSG for 30 days). The rats underwent neurobehavioral, histochemical, and biochemical analyses following the treatments. ResultsMSG treatment caused a decline in both long and short-term memory, along with reduced exploratory and anxiogenic behavior, mitigated by vitamin D treatment. MSG exposure also induced impaired behavior, dyslipidemia, oxidative stress, lipid peroxidation, altered cholinergic transmission, and increased chromatolysis and neuroinflammation in the frontal cortex, hippocampus, and cerebellum. ConclusionsVIT-D demonstrated a mitigating effect on MSG-induced adverse outcomes, highlighting its potential to attenuate neurodegenerative cascades. This investigation contributes to understanding MSG-associated neurotoxicity and suggests vitamin D as a valuable and potential intervention for neuroprotection.

Bone Disease among Children with Sickle Cell Disease: A Scoping Review of Incidence and Interventions.

Children with sickle cell disease (SCD) are more likely to have deficient serum levels of vitamin D for bone metabolism. However, appropriate interventions are essential to prevent its progression and alleviate symptoms. The aim of this study is to determine interventions for managing bone disease in children with SCD. This study uses a scoping review. A literature review was conducted using PubMed, CINAHL, ScienceDirect, Scopus, and Google Scholar search engines. The study was eligible for inclusion if it included articles published from 2013 to 2023, full-text, and original study design. Study quality was assessed using the Joanna Briggs Institute (JBI) appraisal tool. This review identified six studies and 114 children with SCD, including 57 boys (50%) and 57 girls (50%). The majority of SCD types experienced were HbSS (86.84%), HbS-B0 Thal (7.01%), HbSC (5.27%), and the HbSS Arab-Indian haplotype (0.88%). Bone disease problems that often arise in children with SCD include Avascular Necrosis (AVN) (78.08%), Osteonecrosis of the Femoral Head (ONFH) (18.42%), and other bone problems (3.50%). Meanwhile, four types of intervention findings were used in managing bone disease among children with SCD: 1). Surgical procedures 53 (41.09%) included total hip arthroplasty (THA), Osteotomy, and Multiple epiphyseal drilling with Autologous Bone Marrow Implantation (AMBI); 2). Invasive procedures 67 (51.93%) included intravenous bisphosphonates, hydroxyurea (HU), and core decompression (CD) with bone marrow aspirate concentrate injection: 3). Oral pharmacological or Vitamin D3 (cholecalciferol) 4 (3.10%); 4). Non-pharmacology or physical therapy 5 (3.88%). Our findings highlight that surgical, invasive, pharmacological, and physical therapy interventions positively impact increasing bone mineral density (BMD) and functional improvement of bone disease among children with SCD. The interventions provided excellent functional outcomes with minimal complications and no life-threatening side effects.

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

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. Individuals with and without PHPT (CTRL) received 14,000IU/week of oral vitamin D3 for 12weeks. 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). 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 ± 19.8pg/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 ± 20.7pg/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. The weekly administration of 14,000IU 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.