Excess Vitamin Research Articles

Enrichment of trimethyl histone 3 lysine 4 in the Dlk1 and Grb10 genes affects pregnancy outcomes due to dietary manipulation of excess folic acid and low vitamin B12.

The aberrant expression of placental imprinted genes due to epigenetic alterations during pregnancy can impact fetal development. We investigated the impact of dietary modification of low vitamin B12 with varying doses of folic acid on the epigenetic control of imprinted genes and fetal development using a transgenerational model of C57BL/6J mice. The animals were kept on four distinct dietary combinations based on low vitamin B12 levels and modulated folic acid, mated in the F0 generation within each group. In the F1 generation, each group of mice is split into two subgroups; the sustained group was kept on the same diet, while the transient group was fed a regular control diet. After mating, maternal placenta (F1) and fetal tissues (F2) were isolated on day 20 of gestation. We observed a generation-wise opposite promoter CpG methylation and gene expression trend of the two developmental genes Dlk1 and Grb10, with enhanced gene expression in both the sustained and transient experimental groups in F1 placentae. When fetal development characteristics and gene expression were correlated, there was a substantial negative association between placental weight and Dlk1 expression (r = -0.49, p < 0.05) and between crown-rump length and Grb10 expression (r = -0.501, p < 0.05) in fetuses of the F2 generation. Consistent with these results, we also found that H3K4me3 at the promoter level of these genes is negatively associated with all fetal growth parameters. Overall, our findings suggest that balancing vitamin B12 and folic acid levels is important for maintaining the transcriptional status of imprinted genes and fetal development.

8586 A Case Of Vitamin D Toxicity: From Michigan To Hawaii, Vitamin D Is Very High

Abstract Disclosure: A. Abu Limon: None. S.A. Aldasouqi: None. K. Patel: None. F. Akanbi: None. S. Khan: None. P. Kachhadia: None. We report a patient case who is a 46-year-old male, managed for Type 2 diabetes and Vitamin D deficiency (Defined by 25-hydroxy vitamin D levels less than 20ng/ml) at Michigan State University Endocrinology specialty clinic.He started taking 5000 IU daily Vitamin D supplements and on subsequent follow up his levels corrected to 88 ng/ml. His supplements were held.On a routine repeat lab check, his 25-hydroxy vitamin D level is reported to be higher than 200 ng/ml. Which meets the biochemical diagnosis of Vitamin D toxicity. His Calcium level was 9.7 mg/dL (N 8.7-10.3 mg/dL) and PTH-intact level was 38.3 pg/mL (N 14.0-72.0 pg/mL).On questioning the patient, he assured us he is still not on any Vitamin D supplements and that he just got back from a two-weeks long trip from Hawaii and spent hours daily on the beach without using sunblock.He is sure he didn't get tanning, sunburns, or any burns during that period.He was feeling fine without any symptoms or complications.While in Michigan during the winter, with limited number of sunny days, His 25-hydroxy vitamin D levels trended down slowly over the following few months, while Vitamin D supplements kept on hold.The most common cause of Vitamin D toxicity is excessive supplemental Vitamin D use. Other reasons can be related to excessive tanning or burns, that our patient didn't have. Excessive sun exposure or dietary intake is not a known reason to raise Vitamin D levels to a toxic range.Our patient lives in Mid-Michigan, an area known for low number of sunny days (150-180 sunny/ partly sunny days per year ), Which is a reason for high prevalence of vitamin D deficiency in the population. This is Compared to mostly sunny days on the Hawaiian Islands.Coming Back home for the winter season did help his Vitamin D levels to continue trending down back to a safe, non-toxic range. Presentation: 6/2/2024

8706 Hypoparathyroidism and Hypercalcemia in Premature Secondary to Excessive Vitamin D: Everything in Excess is Opposed

Abstract Disclosure: D.M. Bastos: None. A. Bastos: None. Introduction: Vitamin D intoxication in children is rare but its incidence is increasing as vitamin D is supplemented more often and in higher doses. Coma, ventricular fibrillation, and acute renal insufficiency are possible life-threatening presentations of vitamin D-induced hypercalcemia. Nephrocalcinosis, renal lithiasis, vascular calcifications, and arterial hypertension are known late complications of severe or longstanding hypercalcemia. The most common causes of vitamin D intoxication in children are manufacturing errors, parental dosing errors, and erroneous medical prescriptions. Case Presentation: A premature girl admitted to the neonatal ICU 3 months ago due to poor weight gain and was taking vitamin D and infant formulas and developed tachycardic heart rhythm with irregular rhythm and kidney changes. The investigation of the condition was re-evaluated, and the patient was seen with hypercalcemia, an increase of more than 100x in the dosage of 25(OH)vitamin D, an increase in the dosage of 1.25(OH)vitamin D, suppressed PTH, an increase in creatinine and urea. In addition, an ultrasound was performed showing the presence of small kidney stones, none of which were obstructive. After discontinuing vitamin D supplementation, the patient progressed satisfactorily with a reduction in cardiac and renal changes. Discussion: Currently, vitamin D supplementation has been carried out more frequently, as, in addition to increasing the absorption of calcium in the body, it reduces the risk of diseases, such as rickets and osteopenia of prematurity. The body is only able to produce vitamin D after exposure to sunlight. In the absence of regular exposure, dietary sources alone are not sufficient to maintain adequate levels. Cases of hypervitamin D generally occur in situations of excessive supplementation. In the present report, the dose used was 40 times higher than recommended. Initial tests revealed elevated calcium and undetectable PTH levels. The diagnosis of vitamin D intoxication is not common in cases of hypercalcemia, as it is infrequent, especially before the advent of vitamin D supplementation. Vitamin D toxicity is usually iatrogenic, or due to accidental overdose. These factors, along with a lack of public education about safe dosing, have likely contributed to the increase in reported cases of vitamin D toxicity. Conclusion: Vitamin D supplementation, especially when using compounded medications, must be adequately monitored due to the potential risk of poisoning. Vitamin D toxicity remains a pressing issue and its incidence will likely continue to grow, primarily because of the widespread availability of over-the-counter formulations and public interest. Presentation: 6/3/2024

Dietary Adherence to Recommendations among a Cohort of Adults and Teens with Celiac Disease Maintaining a Gluten-Free Diet Compared to a Nationally Representative Sample: A Cross-Sectional Study.

Celiac disease (CeD) is a common autoimmune condition, with a prevalence of ~1%. Currently, a gluten-free diet (GFD) is the only treatment option. Due to fortification rules excluding gluten-free products in the United States of America (U.S.A.), understanding the nutritional adequacy of a GFD is important for promoting optimal health among those with CeD. Cross-sectional examination of multiple 24 h dietary recalls from a study sample of 50 adults and 30 teens with CeD was used to determine nutritional adequacy and excesses according to U.S.A. recommendations. The results were compared with those of 15,777 adults and 2296 teens from a nationally representative sample not reporting CeD, the National Health and Nutrition Examination Survey (NHANES) 2009-2014. Compared with NHANES, our study population was more at risk of low folate and carbohydrate (adults) consumption, and of excessive niacin and vitamin A (teens), as well as saturated and total fat consumption (adults). Overall, though, compared with NHANES, our study participants had similar nutrient concerns but fewer nutritional imbalances, with some notable exceptions. In addition to maintaining a GFD, individuals with CeD should be counseled to maintain a balanced diet and to pay attention to nutrient-dense foods. Special attention should be given to teens in providing dietary counseling to potentially mitigate the risk of future morbidity.

The Association of Vitamin B-12 Plasma Concentration with Stroke Incidence According to Sex

BackgroundPrevious studies reported that vitamin B-12 deficiency is associated with an increased risk of stroke. However, studies examining the association between excessive vitamin B-12 and stroke risk are limited. Our study aimed to investigate the relationship between excessive vitamin B-12 concentrations and risk of stroke and explore whether this association varies according to sex. MethodsUtilizing the Korean Genome Epidemiology Study (KoGES) prospective cohort data, our primary exposure variables were vitamin B-12 plasma concentration and sex. The occurrence of stroke served as the main outcome of interest. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox regression analysis. An interaction analysis was conducted to assess the interaction effect of vitamin B-12 and sex on stroke incidence. ResultsCox proportional logistic regression analysis, adjusting for confounders, showed that excessive vitamin B-12 did not significantly alter stroke risk (HR: 1.22, 95% CI: 0.82, 1.71) and revealed no significant sex-based differences in stroke risk (HR: 0.90, 95% CI: 0.75, 1.04). However, interaction analysis indicated that excessive vitamin B-12 was linked to a significant increase in stroke risk in males (HR: 1.81, 95% CI: 1.10, 2.99) but not in females (HR: 1.04, 95% CI: 0.66, 1.60), with statistically significant interaction effect (P < 0.01). ConclusionsOur study demonstrated that although excessive vitamin B-12 alone does not significantly increase stroke risk, it increases risk in males when considering the interaction with sex.

Vitamin D Maintains Growth and Bone Mineral Density against a Background of Severe Vitamin A Deficiency and Moderate Toxicity in a Swine Model.

Excessive vitamin A (VA) negatively impacts bone. Interactions between VA and vitamin D (VD) in bone health are not well-understood. This study used a traditional two-by-two factorial design. Pigs were weaned and randomized to four treatments (n = 13/group): -A-D, -A+D, +A-D, and +A+D for 3 and 5 wk. Serum, liver, kidney, adrenal glands, spleen, and lung were analyzed by ultra-performance LC. Growth was evaluated by weight measured weekly and BMD by DXA. Weights were higher in -A+D (18.1 ± 1.0 kg) and +A+D (18.2 ± 2.3 kg) at 5 wk than in -A-D (15.5 ± 2.1 kg) and +A-D (15.8 ± 1.5 kg). Serum retinol concentrations were 0.25 ± 0.023, 0.22 ± 0.10, 0.77 ± 0.12, and 0.84 ± 0.28 µmol/L; and liver VA concentrations were 0.016 ± 0.015, 0.0065 ± 0.0035, 2.97 ± 0.43, 3.05 ± 0.68 µmol/g in -A-D, -A+D, +A-D, and +A+D, respectively. Serum 25(OH)D3 concentrations were 1.5 ± 1.11, 1.8 ± 0.43, 27.7 ± 8.91, and 23.9 ± 6.67 ng/mL in -A-D, +A-D, -A+D, +A+D, respectively, indicating a deficiency in -D and adequacy in +D. BMD was highest in +D (p < 0.001). VA and the interaction had no effect on BMD. Dietary VD influenced weight gain, BMD, and health despite VA status.

Excess Folic Acid and Vitamin B12 Deficiency: Clinical Implications?

In the 1940s to 1950s, high-dose folic acid supplements (>5 mg/d) were used clinically to reverse the megaloblastic anemia of vitamin B12 deficiency caused by pernicious anemia. However, this treatment strategy masked the underlying B12 deficiency and possibly exacerbated its neuropathological progression. The issue of masking and exacerbating B12 deficiency has recently been rekindled with the institution of folic acid fortification and the wide-spread use of folic acid supplements. The objectives of this review are to describe clinical and epidemiological evidence that excess folic acid exacerbates B12 deficiency, to summarize a hypothesis to explain this phenomenon, and to provide guidance for clinicians. Cognitive function test scores are lower and blood homocysteine and methylmalonic acid concentrations are higher in people with low B12 and elevated folate than in those with low B12 and nonelevated folate. High-dose folic acid supplementation in patients with pernicious anemia or epilepsy cause significant reductions in serum B12. It is hypothesized that high-dose folic acid supplements cause depletion of serum holotranscobalamin and thus exacerbate B12 deficiency. The evidence for excess folic acid exacerbating B12 deficiency is primarily correlative or from uncontrolled clinical observations, and the hypothesis to explain the phenomenon has not yet been tested. Nonetheless, the evidence is sufficiently compelling to warrant increased vigilance for identifying B12 deficiency in at risk individuals, including older adults and others with low B12 intake or conditions that are associated with B12 malabsorption, who also ingest excessive folic acid or are prescribed folic acid in high doses.

Scientific opinion on the tolerable upper intake level for preformed vitamin A and β‐carotene

Abstract Following two requests from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver a scientific opinion on the revision of the tolerable upper intake level (UL) for preformed vitamin A and β‐carotene. Systematic reviews of the literature were conducted for priority adverse health effects of excess vitamin A intake, namely teratogenicity, hepatotoxicity and endpoints related to bone health. Available data did not allow to address whether β‐carotene could potentiate preformed vitamin A toxicity. Teratogenicity was selected as the critical effect on which to base the UL for preformed vitamin A. The Panel proposes to retain the UL for preformed vitamin A of 3000 μg RE/day for adults. This UL applies to men and women, including women of child‐bearing age, pregnant and lactating women and post‐menopausal women. This value was scaled down to other population groups using allometric scaling (body weight0.75), leading to ULs between 600 μg RE/day (infants 4–11 months) and 2600 μg RE/day (adolescents 15–17 years). Based on available intake data, European populations are unlikely to exceed the UL for preformed vitamin A if consumption of liver, offal and products thereof is limited to once per month or less. Women who are planning to become pregnant or who are pregnant are advised not to consume liver products. Lung cancer risk was selected as the critical effect of excess supplemental β‐carotene. The available data were not sufficient and suitable to characterise a dose–response relationship and identify a reference point; therefore, no UL could be established. There is no indication that β‐carotene intake from the background diet is associated with adverse health effects. Smokers should avoid consuming food supplements containing β‐carotene. The use of supplemental β‐carotene by the general population should be limited to the purpose of meeting vitamin A requirements.

A journey in the world of craniofacial development: From 1968 to the future.

This article is based on my talk at the meeting "3rd Advances in Craniosynostosis: Basic Science to Clinical Practice", held at University College, London, on 25 August 2023. It describes my contribution, together with that of my research team and external collaborators, to the field of craniofacial development. This began with my PhD research on the effects of excess vitamin A in rat embryos, which led to a study of normal as well as abnormal formation of the cranial neural tube. Many techniques for analysing morphogenetic change became available to me over the years: whole embryo culture, scanning and transmission electron microscopy, cell division analysis, immunohistochemistry and biochemical analysis of the extracellular matrix. The molecular revolution of the 1980s, and key collaborations with international research teams, enabled functional interpretation of some of the earlier morphological observations and required a change of experimental species to the mouse. Interactions between the molecular and experimental analysis of craniofacial morphogenesis in my laboratory with specialists in molecular genetics and clinicians brought my research journey near to my original aim: to contribute to a better understanding of the causes of human congenital anomalies.

Dietary Super-Doses of Cholecalciferol Fed to Aged Laying Hens Illustrates Limitation of 24,25-Dihydroxycholecalciferol Conversion

BackgroundOlder humans taking high concentrations of vitamin D3 supplementation for a prolonged time may be at risk of vitamin D toxicity. It is unclear how dietary super-doses (10,000 times greater than the requirement) can affect vitamin D3 status in aged animals. Aged laying hens could be a model to compare vitamin D3 supplementation effects with women in peri- or postmenopausal stages of life. ObjectivesWe investigated the dietary super-dose impacts of cholecalciferol (vitamin D3) on vitamin D3 status in aged laying hens in production. MethodsForty-eight 68-wk-old Hy-Line Brown laying hens were individually housed in cages with 8 hens per dietary treatment for 11 wk. Hens were randomly assigned to 1 of 6 treatment groups of dietary vitamin D3 supplementation and consumed ad libitum. Supplementation concentrations were 400, 800, 7400, 14,000, 20,000, and 36,000 IU D3/kg of feed. At the end of the study, all hens were sacrificed, and tissue samples and feces were collected. Plasma and egg yolk vitamin D3 metabolites, calcium and phosphorus composition of eggshells, ileal digesta, and feces were measured. Duodenal, ileal, liver, and kidney gene expression levels were also measured. ResultsWe observed that increasing dietary vitamin D3 increased plasma vitamin D3 and egg yolk vitamin D3 (P < 0.0001 for both sites). We also observed an increase in plasma 24,25-dihydroxycholecalciferol as dietary vitamin D3 concentrations increased (P < 0.0001). The plasma 25-hydroxycholecalciferol:24,25-dihydroxycholecalciferol ratio exhibited an asymptotic relationship starting at the 14,000 IU/kg D3 treatment. ConclusionsDietary super-doses of vitamin D3 led to greater plasma and egg yolk vitamin D3 concentrations, which shows that aged laying hens can deposit excess vitamin D3 in egg yolk. We suggest future research should explore how 24-hydroxylation mechanisms are affected by vitamin D3 supplementation. Further understanding of 24-hydroxylation can help ascertain ways to reduce the risk of vitamin D toxicity.

Determination of vitamin c in raw fruit and vegetable homogenates: dietary exposure and health effects of excess intake in adults and children.

The aim of the study was to determine Vitamin C content in some fruits and vegetables (FAV) including apple, banana, orange, pineapple, watermelon, carrot and cucumber, sold in the local markets in Awka, Anambra State, Nigeria as well as Vitamin C content in two-component and three-component homogenates FAV. The work was also designed to investigate the dietary exposure and health effects of excess vitamin C intake in adults and children. Vitamin C as total ascorbic acid (AA) after reduction of dehydroascorbic acid was analyzed using both titrimetric and spectrophotometric methods. The titrimetric method involved iodometric back-titration while the spectrophotometric method was done at an absorbance of 530 nm. The dietary exposure was evaluated as the total FAV intake multiplied by chemical concentration in the FAV whereas the health effect of excess vitamin C intake was conducted using the hazard quotient (HQ). The results revealed that Vitamin C for single fruits ranged from 11.76 - 41.17 mg/L for spectroscopic method and 16.9 - 31.84 mg/L for titrimetric method. Fruit homogenates showed Vitamin C concentrations of 14.70 - 220.58 mg/L and 17.23 - 209.09 mg/L for two-components homogenates: 29.41-132.35 mg/L and 31.05-113.10 mg/L for tri-components homogenates for spectrophotometric and titrimetric methods respectively. The results of dietary exposure and the health effects of excess vitamin C intake showed that children are more susceptible to health issues than adults in illnesses such as nausea, gastrointestinal pains, increased kidney stones and hyperactivity. There is therefore the need for a national recommended dietary allowance for total ascorbic acid (AA) in FAV homogenates from a stakeholder point of view in Nigeria.

The interaction between lipid and vitamin D3 impacts lipid metabolism and innate immunity in Chinese mitten crabs Eriocheir sinensis

As a fat-soluble vitamin, vitamin D3 relies on fat to perform its biological function, affecting lipid metabolism and innate immunity. This study used different percentages of lipid and vitamin D3 diets to evaluate the synergistic effects on the growth, lipid metabolism and immunity of juvenile Eriocheir sinensis (5.83 ± 0.01 g) for 56 days, including low lipid (LL, 1.5%) and normal lipid (NL, 7.5%) and three levels of vitamin D3: low (LVD, 0 IU/kg), medium (MVD, 9000 IU/kg) and high (HVD, 27,000, IU/kg). The synergistic effect of lipid and vitamin D3 was not significant on growth but significant on ash content, total protein, hepatopancreas lipid content, hemolymph 1α,25-hydroxy vitamin D3 [1α,25(OH)2D3] content, hepatopancreas lipolysis and synthesis genes. Crabs fed normal lipid (7.5%) and medium vitamin D3 (9000 IU/kg) had the highest hepatopancreas index, hemolymph 1α,25(OH)2D3 content, antibacterial ability, immune-related genes and hepatopancreatic lipid synthesis genes expression, but down-regulated the lipolysis genes expression. In contrast, crabs fed diets with low lipid percentage (1.5%) had low growth performance, hemolymph 1α,25(OH)2D3, mRNA levels of lipid synthesis genes, antibacterial ability and immune-related gene expression. At the 1.5% lipid level, excessive or insufficient vitamin D3 supplementation led to the obstruction of ash and protein deposition, reduced growth and molting, aggravated the reduction in antioxidant capacity, hindered antimicrobial peptide gene expression and reduced innate immunity, and resulted in abnormal lipid accumulation and the risk of oxidative stress. This study suggests that diets' lipid and vitamin D3 percentage can enhance antioxidant capacity, lipid metabolism and innate immunity in E. sinensis. A low lipid diet can cause growth retardation, reduce antioxidant capacity and innate immunity, and enhance lipid metabolism disorder.

Vitamin A-Mediated Birth Defects: A Narrative Review.

Vitamin A deficiency (VAD) or excess in expectant mothers can result in fetal abnormalities such as night blindness, bone anomalies, or epithelial cell problems. In contrast, excessive vitamin A in pregnancy can precipitate fetal central nervous system deformities.During pregnancy, a pregnant woman should monitor her vitamin A intake ensuring she gets the recommended dosage, but also ensuring she doesn't exceed the recommended dosage, because either one can result interatogenicity in the fetus. The widespread and unregulated use of multivitamins and supplements makes consuming doses greater than the recommended quantity more common in developed countries. While vitamin A excess is more common in developed countries, deficiency is most prevalent in developing countries. With proper maintenance, regulation, and education about VAD and excess, a pregnant mother can diminish potential harm to her fetus and potential teratogenic risks.

High Levels of Vitamin A in Plant-Based Diets for Gilthead Seabream (Sparus aurata) Juveniles, Effects on Growth, Skeletal Anomalies, Bone Molecular Markers, and Histological Morphology.

Substitution of fish-based ingredients may alter the nutritional profile of the feeds, including the vitamin contents, ultimately leading to unbalanced vitamin supply. Vitamin A plays an essential role in epithelium preservation, cell differentiation, reproduction, and vision. It also intervenes in skeletogenesis through chondrocytes development. Therefore, low levels of vitamin A may cause poor growth and abnormal bone development among other symptoms. Besides, in gilthead seabream excess vitamin A altered bone structure and homeostasis, indicating that an upper level for vitamin A in feeds for this species must be defined. For this purpose, a practical plant-based diet (FM 10% and FO 6%) containing five increasing levels of vitamin A (24,000, 26,000, 27,000, 31,000, and 37,000 IU/kg) supplemented as retinyl acetate was formulated to identify the effects of high levels of vitamin A for gilthead seabream juveniles. The trial was conducted with 450 total fish distributed into 15 tanks, where each diet was tested in triplicates for 70 days. At the end of the trial, samples were taken for analyses of vitamin A-relevant markers. At the end of the trial the high levels of vitamin A supplementation did not cause a reduction in growth, whereas no significant effect was observed for the feed efficiency, specific growth rate, and feed convertion ratio. Although not significant, retinol content in liver showed a tendency to increase with the elevation of dietary vitamin A levels. Although minor, the highest level of vitamin A dietary content (37,000 IU/kg) caused a significant increase in caudal vertebrae partial fusion as well as caudal vertebrae malformations. Increasing dietary vitamin A was related to a reduction in the occurrence of microhemorrhages in the liver and a reduction in the presence of eosinophils associated to the pancreas. Overall, the results of the present study suggested that gilthead seabream juveniles fed a plant-based diet are able to tolerate very high levels of vitamin A supplementation when supplemented as retinyl acetate. Nevertheless, further supplementation should be avoided in order to reduce the prevalence of anomalies affecting the caudal vertebrae.

Cystitis pada anjing skye di klinik hewan raja petshop surabaya

On May 18, 2023, Mrs. Florensi had brought her dog Skye for a routine check-up. Anamnesis had been conducted for Skye, and the results indicated that Skye's appetite and drinking habits were normal. However, according to Mrs. Florensi, Skye had been urinating frequently in small amounts and There had been drops of blood on the pee pad, Leading her to believe that Skye had been in heat for an extended period. Upon palpation, the urinary bladder had felt hard, Prompting further examinations such as X-rays, urinalysis, and a vaginal swab to be conducted. The cytology results of the vaginal swab had shown the presence of red blood cells and bacterial colonies. Additionally, a significant number of parabasal and intermediate cells had been observed (indicating anestrus) rather than being in heat. The urinalysis had revealed leukocytes (+3), nitrites (+) indicating infection and inflammation in the urinary tract, protein (+2), microalbumin (+3), and creatinine (+1) indicating kidney filtration damage, vitamin C (+1) due to excessive vitamin administration, specific gravity of urine 1.030 (indicating concentrated urine), ketones (-), blood (-) normal, urobilinogen and bilirubin (-) indicating no liver disorders, pH 6.5 normal, and calcium (-). The lateral X-ray results showed no formation of urinary crystals in the urinary bladder but revealed urine accumulation. Based on the anamnesis, clinical symptoms, physical examination, and supporting tests, Skye's condition had indicated Cystitis.

PSVIII-24 Dietary Vitamin D Was Associated with Increased Circulating Vitamin D in Dogs with No Observable Adverse Effect Up to 9,992 Iu/Kg Dry Matter

Abstract Adult dogs have been reported to benefit from circulating 25 (OH) vitamin D above 100 ng/mL to support optimal health. Although there is no consensus for optimum concentrations of circulating vitamin D it has been reported that circulating vitamin D is positively related to a reduced severity of disease, decreased disease risk, enhanced efficacy of treatment and overall positive disease outcome. This association does not prove causality. However, the positive effect of circulating vitamin D suggests that this relationship is not simply an association or a response to disease but reflects a causal supporting function of increased circulating vitamin D above that required for bone health. Understanding the relationship between dietary vitamin D and circulating vitamin D status is essential to progress in using dietary vitamin D to influence health and disease in the dog. Five groups of 8 adult dogs each were fed for 6 months according to AAFCO maintenance protocols to evaluate the influence of dietary vitamin D on circulating vitamin D concentrations and indices of health. Body weight was recorded, and blood samples taken before being fed treatment foods. After initiation of treatment foods, intake was measured daily, body weight was measured weekly, and blood samples were taken initially, after 85 days of feeding, and at the end of the study. The dry matter concentrations of vitamin D (IU/kg) were 796, 3,087, 5,511, 7,314, and 9,992 in approximately 4,000 kcal/kg foods. There were no clinical signs of either deficiency or excess vitamin D. Normal circulating concentrations of hemoglobin, packed cell volume, albumin, total calcium, phosphorus and alkaline phosphatase were maintained in all groups. Circulating vitamin D increased in all groups except those consuming 796 IU/kg. All dogs consuming increased dietary vitamin D had increased concentrations of 25 (OH) D compared with the control group consuming 796 IU/kg. Concentration of calcium increased in all groups with no difference in calcium increase associated with dietary vitamin D. There was no difference in the change in concentration of parathyroid hormone or ionized calcium in response to treatment. Vitamin D increased in a linear and quadratic fashion in response to dietary vitamin D concentration. This resulted in all the dogs fed 5,511 IU/kg and above exceeding 100 ng/mL circulating 25 (OH) D. Dietary vitamin D was positively associated with increased circulating concentrations with no observable adverse effects in dietary concentrations up to 9,992 IU/kg dry matter. This allowed all dogs consuming 5,511 IU/kg and above to exceed the circulating concentration previously recommended for optimal health in dogs.

Is 25OH Vitamin D Excess before 36 Weeks Corrected Age an Independent Risk Factor for Bronchopulmonary Dysplasia or Death?

Low 25-Hydroxyvitamin D (25(OH)D) in preterm infants is a risk factor for bronchopulmonary dysplasia (BPD), but increased supplementation failed to demonstrate a beneficial effect on BPD. In neonatal animal models, deficiency and excessive vitamin D exposure have been associated with increased mortality and histological alterations in the lung evocative of BPD. Our hypothesis is that 25(OH)D levels ≥ 120 nmol/L are also a risk factor for BPD or death. This retrospective single-center cohort study included only infants born at <31 weeks gestational age without major malformations with at least a determination of 25(OH)D at <36 weeks corrected age and no determination <50 nmol/L. Routine 25(OH)D determination was performed at 1 month and monthly thereafter. A total of 175 infants were included. Infants with BPD or who died had a significantly lower term and weight, but a similar frequency of 25(OH)D ≥120 nmol/L (50.5% vs. 43.9%, p = 0.53). The logistic regression identified weight (OR 0.997, 95% CI [0.995-0.998]) and term (OR 0.737, 95% CI [0.551-0.975]) as significantly associated with BPD or death; the occurrence of excessive 25(OH)D was not significantly associated (OR 1.029, 95% CI [0.503-2.093]). The present study did not demonstrate any significant association between excessive 25(OH)D after one month of age and BPD or death.

SAT254 Elevated Vitamin D 1,25-Dioh Leading To The Diagnosis Of Diffuse Large B-cell Lymphoma With Excessive Vitamin D Intake Confounding The Clinical Picture

Abstract Disclosure: R. Barai: None. C. Hurtado: None. We present a patient with acute-onset hypercalcemia in the setting of excessive vitamin D intake, found to have elevated vitamin D 1,25-DiOH and PTHrP, eventually resulting in a diagnosis of diffuse large B-cell lymphoma. 76-year-old man with PMH of idiopathic pulmonary fibrosis s/p left lung transplant, CKD secondary to calcineurin inhibitor toxicity, hypothyroidism, HTN, type 2 DM, and OSA presented with progressively worsening fatigue for four weeks, found to be hypercalcemic to 15.3 mg/dL on presentation with low-normal intact PTH, 14 pg/mL. Three weeks prior to admission, patient had normal calcium, 9.9 mg/dL, with sudden increase to 12.8 mg/dL one week prior to admission, which was not treated. Patient reported taking 5,000 IU of vitamin D PO daily for 5 years, which confounded the clinical picture as the etiology was initially thought to be secondary to excessive vitamin D intake in the setting of frankly elevated vitamin D 25(OH)D of 160 ng/mL. Further work-up revealed elevated 1,25-DiOH of 339 pg/mL with elevated PTHrP of 5 pmol/L and low ACE level of &amp;lt;10 U/L, which was inconsistent with vitamin D intoxication and was concerning for malignancy as the etiology of the hypercalcemia. Patient was treated with 4 doses of calcitonin, fluids and 2 low-doses of pamidronate in the setting of AKI on CKD with only modest improvement in hypercalcemia during the hospitalization. Patient was discharged with calcium 11.4 mg/dL. On CT chest, patient was found to have an enlarged R epicardiac lymph node, prompting PET/CT that demonstrated extensive intensely FDG avid nodular thickening of the right pleura and peritoneum with FDG avid thoracic and abdominopelvic lymphadenopathy and two FDG avid liver masses. US-guided biopsy of a peritoneal nodule was consistent with diffuse large B-cell lymphoma (DLBCL). Colonoscopy demonstrated 5 cm cecal mass with DLBCL, and transverse colonic mass with adenocarcinoma. Liver biopsy flow cytometry was consistent with DLBCL. Patient’s calcium has since normalized with further treatments of denosumab, calcitonin, zoledronic acid and treatment of DLBCL with rituximab, high-dose prednisone, and cyclophosphamide with plan for surgical resection of colon adenocarcinoma. It is important to highlight that elevated 1,25-DiOH would not be typical of hypervitaminosis D as the activity of 1-alpha-hydroxylase (the enzyme that converts the inactive form of vitamin D, 25(OH)D, to the bioactive form, 1,25-DiOH) would be low with hypercalcemia. With the elevated 1,25-DiOH and PTHrP, we were concerned for granulomatous disease or malignancy as the etiology, and we recommended investigation for causes of hypercalcemia other than excessive vitamin D intake. The diagnosis of lymphoma was made due to the incongruity of the history of excessive vitamin D intake and the elevated 1,25-DiOH. Hypercalcemia, in our patient’s case, was due to lymphoma-induced vitamin D activation. Presentation: Saturday, June 17, 2023

SAT260 Asymptomatic Vitamin A Toxicity Causing Hypercalcemia

Abstract Disclosure: N. Seshan: None. G. Goswami: None. Background: Vitamin A toxicity is an overlooked cause of hypercalcemia. Most cases of hypercalcemia are secondary to primary hyperparathyroidism or malignancy. High levels of Vitamin A are thought to have a direct effect on the bone by stimulating osteoclast resorption or inhibiting osteoblastic formation, therefore increasing the fracture risk. Clinical Case: 56 year old female with history of alcoholic cirrhosis complicated by hepatic encephalopathy, acute kidney injury and now status post liver transplant five months prior that was admitted for asymptomatic hypercalcemia. Initially, hypercalcemia was thought to be secondary to cyclosporine, so medication was discontinued. Hypercalcemia resolved after hydration however she was again readmitted for hypercalcemia found on routine labs. She did not show any other signs of excess vitamin A. Lab work showed calcium 12.5 mg/dL (8.6 - 10.2mg/dL), albumin 4g/dL (3.4 - 4.8g/dL), normal 24 hour urine calcium excretion, eGFR 33mL/min, parathyroid hormone 16.9 pg/mL (8.7-77pg/mL), normal 1,25-OH and 25-OH vitamin D, PTHrP 25pmol/L, AM Cortisol 9mcg/dL, TSH 1.7 mIU/L (0.35 - 4.7mIU/L), serum protein electrophoresis unremarkable. Her vitamin A level was elevated to 113 ug/dL (30-75mcg/dL) and was diagnosed with hypercalcemia due to elevated vitamin A levels. Treatment involved hydration and discontinuation of her multivitamin containing vitamin A. Current limited literature suggests discontinuing vitamin A supplements will normalize vitamin A levels over time. Her vitamin A levels improved over several months. Incidentally, due to complaints of back aches from prior injury, imaging showed acute compression fracture deformities of two thoracic vertebrae. Bone density scan showed normal bone density. Bone turnover markers were elevated indicative of increased bone resorption. Clinical Lesson/Conclusion: Hypervitaminosis A is a rare etiology of hypercalcemia. Vitamin A toxicity may be due to excess ingestion of preformed vitamin A through supplements and animal sources. Though not well understood, the proposed mechanism of vitamin A actions on the bone involves stimulation of bone resorption through increase in osteoclastic activity and inhibition of bone formation through osteoblastic suppression, leading to high serum calcium and increasing the risk of fractures. We present a unique case in a patient who developed hypercalcemia secondary to hypervitaminosis A. Presentation: Saturday, June 17, 2023

SAT261 Hypervitaminosis A With Hypercalcemia Without Overtly Excessive Vitamin A Intake

Abstract Disclosure: C. Chiou: None. B. Greck: None. Background: Hypervitaminosis A (hypervitA) is an uncommon cause of hypercalcemia and is due to excessive intake of preformed vitamin A (vitA), i.e., retinoids, especially in emulsified form, a common preparation in supplement. In contrast, provitamin (carotenoids) does not cause hypervitA due to limit in absorption and conversion to vitA. The tolerable upper intake level (UL) and recommended dietary allowance (RDA) of vitA for adult are 3000 and 700 (female) - 900 (male) mcg retinoid activity equivalent (RAE) respectively. While daily intake of vitA &amp;gt; UL carries risk of chronic toxicity, there are reports of hypervitA with chronic intake of vitA below UL. VitA is mainly stored in hepatic stellate cells (HSC). Liver injury can induce HSC to transform, releasing vitA, and losing capacity of vitA storage. Renal insufficiency is known with higher vitA levels in blood. Potentially, the threshold of vitA toxicity from supplement is much less in conditions with hepatic and/or renal disease. Here we report a case without history of excessive vitA intake developed hypervitA in relatively short period of time after hospitalization while in the acute and long-term care unit. Clinical Case: A 57-year male was hospitalized for alcohol related pancreatitis. It was complicated by sepsis, multi-organ failure requiring respirator, parenteral nutrition and/or tube feeding. Mild hypercalcemia was noted 4 weeks after admission, initially intermittently, then persistently and progressively higher, peak of 12.6 mg/dL at 4 months after admission. Prior calcium levels were low or normal up to 6 years before admission. Evaluation of hypercalcemia found low i-PTH, low 1,25-D, hypercalciuria, negative serum protein electrophoresis, and normal PTH-related protein. VitA was surprisingly elevated at 137 [38-98] mcg/dL. Nutritional intake was reviewed. No history of excessive vitA intake. Patient was on total parenteral nutrition (TPN) and/or tube feeding most of time, the range and average of daily preformed vitA supplement from admission to onset of hypercalcemia were 0-1309 and 1006 mcg RAE respectively; while from onset to peak of hypercalcemia, 0-3327 and 1891 mcg RAE respectively. The maximal daily preformed vitA via TPN is 1000 mcg RAE. All preformed vitA in tube feeding is from original formula without extra addition. After discovery of hypervitA, feeding formula was changed to one containing much less preformed vitA, and hypercalcemia slowly improved. Conclusion: HypervitA can develop relatively easily with tube feeding and/or parenteral nutrition with average daily preformed vitA above RDA but way below UL in a susceptible patient. In patients with liver disease and/or renal insufficiency, careful selection of feeding formula and/or nutritional supplement regarding content of preformed vitA, and alert to potential development of hypervitA are advisable. Presentation: Saturday, June 17, 2023