D3 Levels Research Articles

Biochanin A Induces Apoptosis in MCF‐7 Breast Cancer Cells through Mitochondrial Pathway and Pi3K/AKT Inhibition

ABSTRACTThe study aimed to investigate the molecular mechanisms by which Biochanin A inhibits proliferation and induces apoptosis in breast cancer cells. Cultured MCF‐7 cells were divided into four groups: Group 1‐control, while Groups 2, 3, and 4 were treated with Biochanin A at different concentrations. After treatment, the cells were monitored, and morphological changes were examined after 24 h of incubation. The results showed that Biochanin A inhibited cell proliferation, increased reactive oxygen species formation, and induced apoptosis. Furthermore, western blot analysis revealed that Biochanin A‐treated cells exhibited lower expression of the Bcl‐2, p‐PI3K and p‐AKT and higher expression of proapoptotic genes, including Bax, Caspase‐3, Caspase‐9, and cytochrome c. Additionally, PCR array analysis indicated that the gene expression levels of cyclin D3, cyclin B1, CDK1, CDK2, and CDK4 were downregulated, while the expression levels of p21, p27, and p53 were significantly upregulated. These results suggest that Biochanin A can suppress the viability of breast cancer cells and induce apoptosis via the mitochondrial pathway, along with inhibition of the Pi3K/Akt signaling pathway and modulation of cell cycle markers.

Long-term effect of postoperative radioactive iodine therapy on parathyroid function in patients with differentiated thyroid cancer.

The study aimed to assess the impact of postoperative radioactive iodine (RAI) therapy on parathyroid function in patients who underwent total or subtotal thyroidectomy for differentiated thyroid cancer (DTC). Data from 150 patients treated with RAI for DTC and 76 patients with low-risk DTC not receiving RAI were retrospectively analyzed. Clinical characteristics, preoperative and 1-month postoperative biochemical parameters, and adjusted calcium, phosphorus, parathyroid hormone (PTH), and 25-hydroxyvitamin D3 (25-OH-D) levels at 3months, 1year, 3years, and 5years post-RAI (or in the low-risk group) were recorded. A total of 226 DTC patients were included in the study (80.5% female, mean age 42.7 ± 13.2years). Total thyroidectomy was performed in 97.3% (n = 220) of patients, with central lymph node dissection (CLND) in 41.6% (n = 94). No significant preoperative differences in PTH, aCa, P, Mg, or 25-hydroxyvitamin D3 levels were observed. However, patients receiving ≥ 3.7GBq (or 100mCi) RAI (n = 70) had lower calcium and PTH levels at the end of the first year following RAI treatment (p = 0.048, p = 0.032). The non-RAI group showed significantly higher calcium levels at one month postoperatively (p = 0.031) and lower rates of CLND and neck dissection. No significant differences in biochemical parameters were found at the five-year follow-up, except for one patient who developed normocalcemic hyperparathyroidism after RAI. High-dose RAI therapy may lead to transient decreases in calcium and PTH levels in the early post-treatment period. However, long-term parathyroid function appears to remain unaffected in DTC patients, regardless of the RAI dose administered. Nonetheless, close monitoring of calcium and PTH levels is recommended, particularly in the early post-treatment period, to promptly manage any potential transient hypoparathyroidism.

"The Association between Vitamin D Deficiency and Childhood Obesity and Its Impact on Children’s Serum Calcium, Alkaline Phosphatase, and Bone Age"

ObjectiveThe research aimed to investigate the Association between Vitamin D deficiency and childhood obesity and its Impact on children’s serum calcium, alkaline Phosphatase, and bone Age MethodsThe study analyzed clinical data from 159 school-aged children who underwent medical examinations. The children were divided into a 25-(OH)D3 deficiency group and a non-25-(OH)D3 deficiency group based on their serum 25-hydroxy Vitamin D3 levels. The two groups were compared regarding BMI, TC, TG, FBG, HbA1c, Ca, ALP, and bone age differences. ResultsIndividuals with a deficiency in 25-(OH)D3 exhibited higher levels of BMI, TC, TG, and ALP, and lower levels of Ca and bone age than those without the deficiency. These differences were statistically significant (P<0.05). Further analysis revealed a negative association between 25-(OH)D3 levelsa positive correlation between Ca and bone age, and a positive correlation with, BMI, TC, TG, and ALP. ConclusionThe deficiency of 25-(OH)D3 in school-aged children is linked to obesity and impacts bone growth. Monitoring vitamin D levels is crucial for clinical practitioners.

Day-to-Day Fluctuation in Micronutrient Content in Human Milk Relative to Maternal Diet

Background/Objectives: The impact of daily variations in habitual maternal intake on human milk (HM) composition has been poorly studied. We aimed to investigate the associations between day-to-day fluctuation in the micronutrient concentration in HM and daily maternal diet. Methods: To this end, an observational longitudinal study was carried out. A total of 143 lactating women each compiled a five-day weighed dietary record and concomitantly expressed milk for four successive days. Maternal daily intakes of micronutrients and food groups were analyzed. Free thiamine, free riboflavin, nicotinamide, pantothenic acid, pyridoxal, folic acid, cobalamin, ascorbic and dehydroascorbic acids, retinol, alpha- and gamma-tocopherol, cholecalciferol, and calcidiol in HM were determined for each of the four investigated days. A longitudinal data analysis with generalized estimating equation models was performed. Results: For each daily serving of meat, fish, and eggs, total vitamin D3 levels increased by 243.2 pg/mL (p = 0.027) and selenium levels increased by 0.16 ppb (p = 0.031) in HM. For every 1 mg/day of riboflavin supplementation, free riboflavin levels in HM increased by 28.6 mcg/L (p = 0.019). Pyridoxal levels in HM increased by 6.3 mcg/L per 1 mg/day of vitamin B6 supplementation (p = 0.001), and by 2 mcg/L per daily fruit ration (p = 0.016). Conclusions: In conclusion, we were able to quantify the impact of the usual day-to-day variations in the diet and in the intake of commonly used supplements on the fluctuation of vitamin D, free riboflavin, pyridoxal, and selenium concentration in the milk of lactating women.

The association of vitamin D insufficiency with the prevalence of obesity in children: implications for serum calcium levels, alkaline phosphatase activity, and bone maturation

BackgroundVitamin D deficiency has been identified as a potential risk factor for various adverse health outcomes. However, its specific role in metabolic regulation and skeletal development in school-aged children is not fully understood. This study aimed to explore the correlation between vitamin D deficiency and childhood obesity rates, and its impact on serum calcium, alkaline phosphatase, and bone age in children.MethodsThe study analyzed clinical data from 159 school-aged children who underwent medical examinations. Participants were divided into the 25-hydroxyvitamin D3 (25(OH)D3) deficiency group and the 25(OH)D3 normal group based on their serum levels. We compared body mass index (BMI), total cholesterol (TC), triglycerides (TG), Ca, ALP, bone age, fasting blood glucose (FBG), and hemoglobin A1c (HbA1c) between the two groups. Logistic regression and Spearman correlation analyses were performed to further investigate relationships between 25(OH)D3 levels and metabolic and bone-related markers.ResultsThis study showed that the 25(OH)D3 deficiency cohort exhibited significantly higher BMI, TC, TG, and ALP levels, with lower Ca levels and delayed bone age compared to the normal group. Logistic regression analysis identified Ca, ALP, and bone age as significant predictors of 25(OH)D3 deficiency. Subgroup analysis showed that in the 25(OH)D3 deficient group, children with higher BMI had elevated TC, ALP levels, and delayed bone age, while Ca levels were lower. Correlation analysis confirmed the predictive value of these markers for 25(OH)D3 deficiency.ConclusionOur findings demonstrate that 25(OH)D3 deficiency is strongly associated with obesity in school-aged children and may negatively affect normal skeletal development. Regular monitoring of 25(OH)D3 levels in school-aged children is essential for ensuring proper growth and development, especially in those at risk for obesity.

Filling the Gaps: Vitamin D Status in Diffuse Hair Fall Among Pakistanis

Introduction: Hair loss can happen for various reasons, including emotional stress, physical strain, certain medical issues, and nutritional gaps. When it comes to nutrition, a lack of vitamin D3 could be linked to diffuse hair loss. Objectives: The aim was to look for the frequency of vitamin D3 deficiency with diffuse hair fall especially in Pakistani population. Methods: A total of 120 patients of both genders and all ages presenting to the Dermatology Clinic with complaints of non-scarring alopecia and loss of over 100 strands of hair within a 24-hour period (counted by patient), of any duration and positive hair pull test were advised to take serum vitamin D3. Tests and results were then analyzed by SPSS statistical software package (version 19.0 for Windows). Results: The mean age of participants enrolled in the study was 28.56 ± 11.62 years. The majority of the patients, i.e., 77 (63.64%) were ≤30 years of age. Among the 120 patients, 17 were males and 103 were females. Mean serum vitamin D3 levels were 17.33 ± 5.43 ng/ml. Frequency of vitamin D3 deficiency in patients with diffuse hair fall was seen in 95 (79.17%) patients with 37 patients having female pattern hair loss, 7 patients with male pattern hair loss, 7 patients with diffuse alopecia areata, and 44 patients with telogen effluvium. Conclusions: This study concluded that there is considerable frequency of vitamin D3 deficiency in individuals with diffuse hair fall. So, we recommend that there should be early recognition and treatment of this condition in these particular patients in order to reduce hair fall.

The Association between Vitamin D3 Deficiency and Cataract Formation in Baghdad Al-Karkh

Background: Visual impairment is a global issue that is particularly problematic for poor nations. It is linked to diminished physical activity, social isolation, reliance on everyday tasks, and even death. The clouding of the lens inside the eye is called a cataract. It is one of the main causes of blindness and visual impairment in the world. Because of its anti-inflammatory and antioxidant properties, vitamin D, a prohormone in the blood, is crucial to the pathophysiology of many ocular illnesses. Given that oxidative stress and inflammation are significant contributors to the development of cataracts, a number of research have evaluated the relationship between vitamin D3 deficiency and cataract formation. Objective: Determine whether a vitamin D3 deficiency and cataracts are related. Patients and Methods: A cross-sectional study that was carried out included a total of 100 cataract patients who are 60 years of age or younger from September 2023 to March 2024 in the Ophthalmology Department of Imamein Kadhimein Medical City, Baghdad, Iraq. Questionnaire form was used which consist of sociodemographic information, socioeconomic status, dietary sources of vitamin D3, sun exposure, anthropometric measures and ophthalmic examination. Vitamin D3 level had been investigated in laboratory of the hospital. Results: Thirty percent of patients had cortical cataracts, 57% had nuclear cataracts, and 13% had posterior subcapsular cataracts. Sixty-nine percent of patients had a vitamin D3 level that is less than 20 ng/ml. Of the patients, 13% had a vitamin D3 level between 20 and 30 ng/ml, while 18% had a level greater than 30 ng/ml. There is a significant association between the level of vitamin D3 and the type of cataract (p-value = 0.013). Sixty-nine percent of patients with deficient vitamin D3 levels had 9% posterior subcapsular cataracts, 36% cortical cataracts, and 55% nuclear cataracts. Patients with insufficient vitamin D3 levels had 8% posterior subcapsular cataracts, 8% cortical cataracts, and 84% nuclear cataracts. While patients with sufficient vitamin D3 levels had 33% posterior subcapsular cataracts, 22% cortical cataracts, and 45% nuclear cataracts. The body mass index and vitamin D3 level were significantly associated (p-value = 0.003). Patients with a vitamin D3 level less than 20 ng/ml comprised 31% overweight patients, 26% class I obese patients, 26% class II obese patients, and 4% class III obese patients. Thirteen percent of these patients had normal weights. Patients with a vitamin D3 level 20-30 ng/ml comprised 46% overweight patients, 23% class II obese patients, and 31% with normal weight. While patients with a vitamin D3 level more than 30 ng/ml comprised 33% normal weight patients and 67% overweight. Conclusion: Vitamin D3 deficiency has a significant association with cataract formation, especially nuclear and cortical types, sun exposure, educational level, socioeconomic status, and obesity.

Ethnic Differences in Response to Oral Vitamin D Supplementation: A Systematic Review and Meta-analysis.

Individual variability in oral vitamin D supplement response hinders the understanding of its clinical impact, and while ethnicity has been implicated in this variability it has not been well described. The aim was to systematically assess the impact of ethnicity on response to oral vitamin D supplementation. The Web of Science and PubMed databases were searched for articles published from 1960 to the end of 2020. All trials in adults measuring 25(OH)D3 blood levels were included. Two reviewers independently extracted the data from the eligible studies. The change in 25(OH)D3 blood levels (95% CI) and P values were extracted, and grouped according to ethnicity, then subjected to random-effects meta-analysis. The primary outcome measurement was mean serum 25(OH)D3 levels and the secondary outcome was dose-adjusted mean serum 25(OH)D3 levels, both compared with baseline. A total of 18 studies were identified, and data from 1131 participants were extracted. Body mass index (BMI) and dose were significant covariates (Pearson correlation coefficient, P = .016 and .017) and were normalized in the meta-analysis to minimize heterogeneity, but latitude was not (P = .66). Meta-analysis showed an effect of ethnicity on dose and BMI-adjusted mean serum 25(OH)D3 levels compared with baseline (P < .00001, I2 = 98%). Asian and White study participants demonstrated a statistically higher increase in dose and BMI-adjusted 25(OH)D3 blood levels (183 nmol/L [95% CI, 163-203] and 173 nmol/L [95% CI, 152-194], respectively), compared with Arab and Black study participants (37 nmol/L [95% CI, 35-39] and 99 nmol/L [95% CI, 90-108]) using repeated t tests. Sensitivity analysis demonstrated that these findings were not impacted by potential study bias or the inclusion of immigrant populations. Ethnicity had an impact on oral vitamin D response. Further prospective studies should examine if ethnicity-based dose stratification in both clinical practice and clinical trials is warranted. PROSPERO registration no. CRD42023410076.

Effects of vitamin D supplementation on serum 25(OH)D3 levels and neurobehavioral development in premature infants after birth

This study explored the factors influencing serum 25(OH)D3 levels and the effects of Vitamin D deficiency (VDD) and VD supplementation on 25(OH)D3 levels and neuropsychobehavioral development in premature infants, to provide a theoretical basis for improving their prognosis. Physical examination, neuropsychobehavioral development and serum 25(OH)D3 levels were assessed regularly in 158 preterm infants supplemented with VD formulation. 25(OH)D3 levels were analyzed at 3, 6, 9, 12, and 18 months after birth. The Gesell neuropsychological development test was conducted at 6, 9, 12, and 18 months after birth to obtain the developmental quotient (DQ). Based on the serum 25(OH)D3 levels at 42 days of age, the infants were divided into VDD and non-VDD groups. Preterm infants in the VDD group were supplemented with more VD until their 25(OH)D3 levels were normal, and were divided into sustained VDD (SVDD) and corrected VDD (CVDD) groups according to serum 25(OH)D3 levels at 3 months of age. Appropriate statistical methods were chosen to compare differences in 25(OH)D3 and DQ between or among different groups, screen for the factors influencing 25(OH)D3 levels in preterm infants at 42 days of age, and analyze the relationship between 25(OH)D3 and DQ. The 25(OH)D3 levels of preterm infants at 42 days of age were positively correlated with VD supplementation during pregnancy, and before 42 days after birth (P < 0.05). The 25(OH)D3 levels in preterm infants at 42 days and 3 months of age were positively correlated with the DQ levels at 6, 9, 12, and 18 months of age (P < 0.05). The DQ level in the VDD group, especially SVDD group, was lower than that in CVDD and non-VDD groups at the same time point (P < 0.05). This research thus demonstrates that VD supplementations during pregnancy and after birth is a major factor affecting 25(OH)D3 levels in premature infants. Early VDD and SVDD can affect their neuropsychobehavioral development, and effective VD supplementation can gradually correct VDD and mitigate this influence.

Cardiometabolic factors and vitamin D deficiency in pediatric patients with chronic kidney disease.

Patients with chronic kidney disease (CKD) are at increased risk for cardiovascular disease. Up to 80% of patients with CKD may exhibit inadequate vitamin D (VD) levels, which have been linked to the presence of cardiometabolic factors (CFs) in the adult population. However, research on this association in the pediatric population is limited. To analyze the effects of 25-hydroxyvitamin D3 (25-[OH]D) levels and status on the presence of CFs in children receiving kidney replacement therapy (KRT). This cross-sectional study included pediatric patients receiving KRT, aged 8-17 years, who were receiving hemodialysis or peritoneal dialysis from January 2021 to March 2024. We conducted anthropometric measurements, blood pressure assessments, and glucose, 25-(OH)D, and lipid profiling for all participants. The daily dose of cholecalciferol supplementation, as well as other medications affecting bone and lipid metabolism and antihypertensive drugs, were documented. Statistical analyses were performed using Student's t-tests and chi-square tests to compare the CFs between groups with and without VD deficiency. The study involved 156 patients with an average age of 12.9 years and a mean serum VD level of 22.5 ng/dL. Patients with VD deficiency presented higher levels of total cholesterol and diastolic blood pressure (p < 0.05). No statistically significant differences were found in other biochemical profile variables or in the frequency of cardiometabolic factors. Vitamin D deficiency seems to increase the risk of dyslipidemia and uncontrolled hypertension in children and adolescents with end-stage CKD.

Effects of D3K2 With Periodontal Therapy in Diabetes Mellitus and Stage I-II Periodontitis Patients.

The aim of this study is to look into the clinical and biochemical outcomes of D3K2 supplementation in addition to nonsurgical periodontal treatment (NSPT) for patients suffering from diabetes mellitus (DM) and periodontitis. Thirty-eight participants with DM and periodontitis were randomized into two different groups. The test group provided NSPT with D3K2 whereas the control group received NSPT with placebo. Clinical periodontal parameters were recorded and serum and gingival crevicular fluid (GCF) were sampled at baseline and at the third and the sixth months after treatment. Glycated hemoglobin A1c (HbA1c), fasting blood glucose (FBG), 25(OH)D3, parathyroid hormone (PTH), calcium (Ca) and magnesium (Mg) values were determined in blood samples. GCF and serum interleukin (IL)-1β and IL-10 levels were analyzed using enzyme-linked immunosorbent assay. All clinical periodontal parameters were importantly decreased at the third and sixth months after treatment compared to baseline in both groups. At the sixth month, 25(OH)D3 levels in the test group were observed to be statistically significantly higher than in the control group (p = 0.02). Serum IL-1β showed a statistically significant decrease at the sixth month compared to baseline and the third month in control group. According to this study, there is limited additional benefit of D3K2 given with NSPT in individuals with DM and periodontitis.

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

6874 A Rare Case Of Hereditary 1,25 (OH)2D Resistant Rickets

Abstract Disclosure: G. Umarji: None. F. Thelmo: None. S.A. Jabbour: None. Vitamin D-dependent rickets type 2A (VDDR2A) also known as hereditary 1,25 (OH)2D resistant rickets is due to biallelic loss-of-function mutations in the gene encoding vitamin D receptor on chromosome 12q13.11, thus, it represents a true form of tissue resistance to vitamin D. It is a scarce form of rickets with approximately only 120 cases reported. A 37-year-old male was referred to endocrinology by neurosurgery for evaluation of metabolic bone disease. Seven years ago, he was in a car accident which resulted in a lumbar spine injury causing radiculopathy and severe low back pain leading to lumbar spine decompression/fusion. However, he suffered from nonunion of bones and had to undergo another surgery a year later with recurrent postoperative nonunion of bones. During the operation, the surgeon noticed that his spine seemed demineralized. He had a history of multiple minor fractures in childhood, decreased hearing in left ear for two years, fragile teeth for many years, and some hair loss since age 30. Physical exam showed a height of 1.82 m, weight 89.3 kg with body mass index of 26 kg/m2, broken teeth, no leg bowing and normal stance. Laboratory results showed normal renal function, thyroid function tests and testosterone level, corrected calcium 8.3 mg/dL (8.7-10.2), 25-OH-vitamin D 54 ng/mL (30-100), phosphorus 2.8 mg/dL (2.8-4.1), intact parathyroid hormone 65 pg/mL (15-65), bone-specific alkaline phosphatase 21 mcg/L (4-27), 24-hour urine calcium 156 mg/day (100-300), 24-hour urine phosphorus 1,752 mg/day (390-1,425), FGF-23: 93 RU/mL (44-215) and 1,25 (OH)2D 92 pg/mL (24-81.5). Dual absorptiometry of the lumbar spine and hip showed osteopenia with Z scores of -2.2 and -1.2 respectively. Genetic testing for metabolic bone disease panel showed heterozygous mutation in VDR gene at nucleotide position c.146+9dup associated with autosomal recessive VDDR2A. We present a very rare form of vitamin D resistant rickets. As many patients with VDDR2A are unable to respond to any form of vitamin D, it is suggested that VDDR2 be more appropriately described as hereditary 1,25 (OH)2D resistant rickets (HVDRR), hereditary resistance to 1,25 (OH)2D, or even pseudovitamin D-deficiency type IIA (PDDR IIA). Clinical features include severe rickets, bone pain, hypotonia, dental caries and alopecia. Biochemical features include hypocalcemia, hypophosphatemia, normal to elevated alkaline phosphatase, normal 25(OH)D and importantly, elevated 1,25-(OH)2D levels. Management is with high doses of calcium and vitamin D therapy. While rare, this disease highlights the need for a comprehensive evaluation of metabolic bone diseases and a thorough understanding of calcium and vitamin D metabolism. Presentation: 6/2/2024

8596 Brain Type 3 Deiodinase Is Induced in Two Disease Models That Lead to Cognitive Impairment: Liver Dysfunction and Alzheimer Disease

Abstract Disclosure: S. Wajner: None. T. Oliveira: None. M. Dreher: None. R. Ribeiro: None. C. Gonçalves: None. M.R. Alveres-da-Silva: None. Thyroid hormone is the leading regulator of cell energy production in most tissues, mainly the brain. While the activation process of T4 into T3 depends on D1 and D2 deiodinases, type 3 is the main enzyme that inactivates T3. Several mechanisms, among them oxidative stress, led by disease, imbalances and induces D3, diminishing T3 levels. The response of D3 in the brain in the context of different disease models has yet to be studied. Here we evaluated D3 induction in the brain in two animal disease models, one systemic and the other local. Methodology: To the metabolic dysfunction-associated steatosis liver disease model Male/adult Sprague Dawley rats (n=20) were assigned to control group (standard diet-2.93kcal/g) or high-fat-diet group (CDHF-4.3kcal/g). In the streptozotocin-induced (STZ) Alzheimer's model Adult Wistar rats (n=16) were allocated to the control group (5uL of citrate) or 5uL of streptozotocin. Sham animals were used as controls. D3 expression, oxidative stress parameters, endoplasmic stress and mitochondrial amount measured in the brain. Levels of D3 increased in the brain (∼30% in each group, P&amp;lt;0.0001) in both MASLD and STZ groups. Cerebral tissue from both groups had augmented carbonyl levels (P&amp;lt;0.001) and reduced sulfhydryl (P&amp;lt;0.001). Glutathione was diminished. Antioxidant defenses endoplasmic reticulum function and mitochondrial concentration were altered (P=0.001). The augmented T3 inactivation by D3 dysfunction in brain due to oxidative stress disrupts ER-mitochondrial contact interaction, changing the function of organelles in both brain disease models, shedding light to new mechanisms of action of thyroid hormone in severe brain disease. Presentation: 6/3/2024

Presentation and outcome in carriers of pathogenic variants in SLC34A1 and SLC34A3 encoding sodium-phosphate transporter NPT 2a and 2c

Pathogenic variants in SLC34A1 and SLC34A3 encoding sodium-phosphate transporter 2a and 2c are rare causes of phosphate wasting. Since data on presentation and outcomes are scarce, we collected clinical, biochemical and genetic data via an online questionnaire and the support of European professional organizations. One hundred thirteen patients (86% children) from 90 families and 17 countries with pathogenic or likely pathogenic variants in SLC34A1 or SLC34A3 and a median follow-up of three years were analyzed. Biallelic SLC34A1 variant carriers showed polyuria, failure to thrive, vomiting, constipation, hypercalcemia and nephrocalcinosis in infancy, while biallelic SLC34A3 carriers presented in childhood or even adulthood with rickets/osteomalacia and/or osteopenia/osteoporosis, hypophosphatemia and, less frequently, nephrocalcinosis, while the prevalences of kidney stones were comparable. Adult biallelic SLC34A3 carriers had a six-fold increase chronic kidney disease (CKD) prevalence compared to the general population. All biallelic variant carriers shared a common biochemical pattern including elevated 1,25(OH)2D and alkaline phosphatase levels, suppressed parathyroid hormone (PTH), and hypercalciuria. Heterozygous carriers showed similar but less pronounced phenotypes. In biallelic SLC34A1 carriers, an attenuation of clinical features was observed after infancy, independent of treatment. Phosphate treatment was given in 55% of patients, median duration two years, and resulted in significant reduction, although not normalization, of alkaline phosphatase and of hypercalciuria but an increase in PTH levels, while 1,25(OH)2D levels remained elevated. Thus, our study indicates that biallelic SLC34A1 and SLC34A3 carriers show distinct, albeit overlapping phenotypes, with the latter having an increased risk of CKD in adulthood. Phosphate treatment may promote kidney phosphate loss and enhance 1,25(OH)2D synthesis via increased PTH production.

Effect of 25-hydroxycholecalciferol and high phytase doses on performance, vitamin D status, bone mineralization, and mechanistic target of rapamycin kinase gene expression of broilers

The use of exogenous phytase and vitamin D3 metabolites such as 25-hydroxycholecalciferol (25-OH-D3) for poultry is well consolidated, but the potential for additive effects when supplementing both requires further investigation. This study investigated possible interactions between supplementation of 25-OH-D3 and high doses of phytase for broilers fed Ca− and P-deficient diets. A total of 1 200 one-d-old male broiler chicks were randomly allocated from one of four dietary treatments in a 2 × 2 factorial arrangement: 600 or 2 000 phytase units (FYT)/kg and with or without the inclusion of 25-OH-D3 at 69 µg/kg, with 12 replicates of 25 broilers each. Two feeding phases were stablished (1-to-21 and 22-to-42 d) and all diets contained commercial levels of vitamin D3 (100 µg/kg) with total Ca and available P respectively set to 0.6 and 0.3%. Supplementation with 25-OH-D3 increased body weight gain (BWG) and reduced feed conversion ratio (FCR) from 1 to 21 d (P < 0.05), as well as increased BWG from 1 to 42 d (P < 0.05). Serum 25-OH-D3 levels at 21 and 42 d were increased with 25-OH-D3 (P < 0.001). Phytase did not affect growth performance from 1 to 21 d, but a higher dose (2 000 FYT/kg) reduced feed intake and FCR from 22 to 42 d compared to 600 FYT/kg, also reducing FCR in the total period (P < 0.05). Expression of the mechanistic target of rapamycin mRNA in breast muscle assessed at 42 d was enhanced with 2 000 FYT/kg (P < 0.001). Bone weight, bone contents of ash, Ca, and P, and bone breaking strength of tibia bone measured at 42 d were not affected by any dietary treatment. Although both additives are known to improve dietary Ca and P utilization, there were no detected additive or synergic effects. The results suggested that the inclusion of 25-OH-D3 and phytase combined with regular vitamin D3 levels can help minimize losses of performance and bone mineralization of broilers fed Ca- and P-deficient diets. Furthermore, vitamin D status is refined with dietary 25-OH-D3 and potential improvements on breast meat yield can be obtained with a high phytase dose of 2 000 FYT/kg.

High ratio of epi-25-(OH)-vitamin D3 to 25-(OH)-vitamin D3 increases the risk of asthma attack in American asthma adults: a population study.

The relationship between vitamin D3 and asthma remains controversial. However, previous studies have largely overlooked the impact of epi-25-(OH)-vitamin D3. This study aims to investigate the effects of different forms of vitamin D3 on asthma attack in adults. In this cross-sectional study, a total of 3,873 eligible adult participants were extracted from the national health and nutrition examination survey (NHANES) database from 2007 to 2018. Based on quartiles method, different levels of vitamin D were divided into four groups (Quartile 1-4). Bivariate correlation analysis was performed for vitamin D and covariates to avoid multicollinearity. Multivariate logistic regression was used to investigate the association between serum levels of vitamin D3 (epi-25-(OH)-vitamin D3 and 25-(OH)-vitamin D3) and asthma attack, adjusting for covariates including age, gender, race, length of time in the U.S., house poverty income ratio (PIR), education level, smoking history, hypertension history, and diabetes history. The ratio of epi-25-(OH)-vitamin D3 to 25-(OH)-vitamin D3 was used for secondary analysis of its association with asthma attack. The outcomes were assessed by odds ratios (ORs) and 95% confidence intervals (CIs). Among the 3,873 eligible adults American with asthma, 1,508 (38.94%) had experienced at least one acute asthma attack in the past year. There was no significant correlation between vitamin D and covariates. After adjusting for covariates including age, gender, race, length of time in the U.S., house poverty income ratio (PIR), education level, smoking history, hypertension history and diabetes history, we found a positive correlation between the ratio of epi-25-(OH)-vitamin D3 to 25-(OH)-vitamin D3 and asthma attack. Additionally, a high ratio of epi-25-(OH)-vitamin D3 to 25-(OH)-vitamin D3 was more common among elder, male, of normal weight, non-Hispanic American, have a long time stay in the U.S., a high house PIR, and a history of hypertension individuals. Our findings suggest that attention should be given to asthma attack associated with a high ratio of epi-25-(OH)-vitamin D3 to 25-(OH)-vitamin D3 in American adults who are elderly, male, of normal weight, non-Hispanic Americans, have long-term residence in the U.S., a high house PIR, and a history of hypertension.

Evaluation of the Level of Alkaline Phosphatase, Calcium, and Vitamin D3 in Patients with Celiac Disease

Background: Celiac disease, sometimes called wheat allergy, is multiple names for one disease. It is a long-term acquired autoimmune disease that primarily affects the small intestine, as individuals develop intolerance to gluten, which is found in foods such as wheat, rye, and barley. Aim of the study: Our study aims to monitor biochemical parameters such as alkaline phosphatase, calcium, and vitamin D3 as an indicator to monitor the progress of bone health in the blood serum of patients with celiac disease in Wasit Governorate/Iraq. Materials and methods: In this research, studied 80 samples, including 50 samples from patients with celiac disease of both sexes, 19 men and 31 women With 30 control samples for both sexes equally. used an Enzyme-linked immunosorbent assay (ELISA) kit to measure the concentrations of vitamin D3 and alkaline phosphatase, while a Cobas c111 device was used for calcium. Results: The results showed that the level of alkaline phosphatase increased more in patients with celiac disease than in the control group at p≤(0.05), while the concentrations of calcium and vitamin D3 decreased more than in the control group at p≤(0.05). Conclusion: The studied criteria contribute as indicators of developing health risks to the body and bone health in patients with celiac disease.

VITAMIN D STATUS AMONG FEMALE STUDENTS IN FACULTY OF MEDICINE AND HEALTH SCIENCES UNIVERSITY OF ADEN- YEMEN

Vitamin D deficiency is not only associated with rickets and osteomalacia, but with several chronic diseases, such as cancer, ischemic heart disease and type 1 and 2 diabetes mellitus. Vitamin D deficiency is prevalent across all age groups in epidemic proportions. Worldwide, an estimated one billion people suffer from vitamin D deficiency. One of the major reasons for the worldwide spread of this disorder has been deficient awareness about the importance of vitamin D, its benefits on health, and prevention of deficiency state across different populations. This study aimed to investigate the prevalence of vitamin D deficiency among female medical students regarding the importance of vitamin D and to determine its correlates among female students in Aden, Yemen. A cross-sectional study was conducted with 70 adult female students aged 19-30 years enrolled in Faculty of Medicine and Health Sciences University of Aden in the period April to October 2019. A self-administered questionnaire was used to collect information for participants data such as age, place of residence (urban or rural), skin color (pigmentation) and applying of sun protection creams. Blood samples were taken to investigate serum 25-(OH)D3 level for all participants through laboratory examination using Roche Cobas e 411 Automatic Analyzer, after recruiting their sociodemographic, health and lifestyle. Serum 25-hydroxyvitamin D levels were classified as normal (&gt;30 ng/ml), insufficiency (10-30 ng/ml) and deficiency (&lt;10 ng/ml). The data statistically analyzed using SPSS version 24. The mean age (SD) of participants 22.4 ± 2.01years. The prevalence of vitamin D deficiency among all participants was 34.3% while 65.7% had vitamin D insufficiency. low concentrations of serum vitamin D is highly prevalent among female medical students. It is advisable to increase their consumption of foods rich in vitamin D. the incidence of VDD among growing girls is concerning and necessitates preventive intervention. Importantly, health strategy plan requires considerations of more promotion of safe sun exposure practice, sufficient vitamin D supplements and vitamin D fortification of foods.

Relationship between 25-OH-D3 levels and cognitive functions in children with obesity

Aims: The inconsistent results about neurocognitive functions in children with obesity may be suggestive of factors like vitamin deficiencies rather than the disorder itself. So we aimed to investigate the 25(OH)D3 levels and cognitive functions in obese children in the present study. Methods: Seventy-two children were included to this study. Forty-one of them were obese children and 31 children were with normal weight. The patients were diagnosed as obese according to body mass index &gt;95 percentile, considering the sex and age-specific growth curves for Turkish children. The participants completed the battery tests of the central nervous system vital signs (CNSVS), a neurocognitive test battery, via computer. The battery calculates seven domain scores (Memory, Psychomotor speed, Processing speed, Reaction time, Complex attention, Executive function, Cognitive flexibility) and a summary score (Neurocognition Index). 25(OH)D3 levels were measured in residual samples using a Shimadzu HPLC system with the aid of a 25(OH)D3 kit. The scores were compared by using commercial software (IBM SPSS Statistics 18). Results: The mean 25-OH-vitamin D levels were 13.41±7.91 µg/L in obese children and 20.31±5.92µg/L in controls. Vitamin D3 levels were significantly lower in obese children than in control group (p