Supplemental Doses Research Articles

Dietary sanguinarine supplementation improves the growth performance and intestinal immunity of broilers

Dietary sanguinarine (SAN) can enhance the growth performance of poultry and livestock, but the regulatory mechanism of the SAN monomer on intestinal homeostasis and how it promotes growth performance has not yet been clarified. In this study, 200 chickens were divided into four groups and fed different doses of SAN (0, 0.225, 0.75, 2.25mg/kg) for transcriptome and microbiota analysis. The data showed that different doses of SAN supplementation increased the feed conversion rate (FCR) of 22 to 42 d old and 1 to 42 d old broilers (P < 0.01), and 0.225 mg/kg SAN reduced the contents of alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine (CREA) and blood urea nitrogen (BUN) in serum (P < 0.01). Dietary SAN increased the villus height and the villus height/crypt depth (V/C) ratio in the ileum (P < 0.01). The levels of tight junction proteins (zonula occludens-1, occludin and claudin-1) were up-regulated in the ileum and cecum (P < 0.01) and the levels of immunoglobulin (Ig) A, IgM, IgG, interleukin (IL)-4, IL-10 and interferon (IFN)-γ were up-regulated in the serum and ileum (P < 0.01). RNA-seq analysis revealed 385 differentially expressed genes (DEGs) (|log2 fold change| ≥ 1, FDR < 0.05) between the SAN group and CON group. Kyoto Encyclopedia of Genes and Genomes pathway analysis showed 15 pathways mostly associated with the immune system. Additionally, the reverse transcription-PCR results showed that the relative mRNA expression of β-defensin and mucin 2 were up-regulated (P < 0.01) and Toll-like receptor (TLR) 2 and TLR 4 mRNA were down-regulated by SAN (P < 0.01), which was consistent with the transcriptomic analysis. Western blot analysis also showed that SAN reduced the expression of inflammatory proteins such as TLR4, nuclear factor-kappa B and IL-1β in the ileum (P < 0.01). In addition, at the genus level, SAN significantly increased the relative abundance of bacteria (Bacteroides, unclassified_f__Lachnospiraceae, Lactobacillus and Romboutsia) involved in acetate and butyrate production in the cecum, which are associated with enhanced intestinal immune function and maintaining intestinal health. In conclusion, SAN ameliorates the growth performance of broilers, enhances intestinal immune function, regulates the structure of microbiota and maintains intestinal health.

Absorption, Anti-inflammatory, Antioxidant, and Cardioprotective Impacts of a Novel Fasting Mimetic Containing Spermidine, Nicotinamide, Palmitoylethanolamide, and Oleoylethanolamide: A Pilot Dose-Escalation Study in Healthy Young Adult Men

This pilot dose-escalation study evaluated the absorption and metabolism of a novel fasting mimetic formulation containing spermidine, nicotinamide, palmitoylethanolamide (PEA), and oleoylethanolamide (OEA) taken as oral supplements in young adults. Five healthy men consumed a standardized breakfast, followed by control (wheat flour) or low, medium, or high doses of supplements containing spermidine, nicotinamide, PEA, and OEA 2 h later. Blood was drawn at 0, 1, 2, and 4 h after the supplement (2, 3, 4, and 6 h postprandial). Plasma concentrations of spermidine, 1-methylnicotinamide (1-MNA), PEA and OEA were quantified by LC-MS. The secretion of tumor necrosis factor alpha (TNF-α) and production of reactive oxygen species (ROS) by stimulated macrophages incubated with plasma, and cholesterol efflux capacity (CEC) of plasma were analyzed. Plasma 1-MNA, PEA and OEA concentrations increased after supplement intake (P < 0.05). Spermidine concentrations decreased in the control arm (P < 0.05) but not the supplement arms. Net incremental area under the curve for TNF-α and ROS in stimulated macrophages decreased when incubated with plasma following supplement intake (P < 0.05). Intake of the combined supplements showed they were bioavailable and increased in plasma in a dose-dependent manner, and provide preliminary data showing enhanced plasma anti-inflammatory and antioxidant functions.This trial was registered at clinicaltrials.gov (NCT05017428).

Investigating the Relationship Between β-Carotene Intake from Diet and Supplements, Smoking, and Lung Cancer Risk

β-carotene is a naturally occurring and safe dietary source of vitamin A that is associated with cancer risk reductions when consumed in typical dietary amounts. However, two clinical trials reported increased incidence of lung cancer and total mortality among heavy smokers taking β-carotene supplements (20 or 30 mg/day). Based on these findings, the Joint FAO/WHO Expert Committee on Food Additives withdrew Acceptable Daily Intake values for β-carotene (0-5 mg/kg bw). We evaluated relevant epidemiological and toxicological literature to assess the biological plausibility of this relationship and identified three mechanisms involving cellular proliferation signaling, a mode of action for cancer promotion. The overall weight of evidence consistently demonstrated typical dietary doses of β-carotene decreased cellular proliferation signaling via these mechanisms, even in the presence of smoke, while co-exposure to smoke and higher, supplemental doses increased cellular proliferation signaling through these same pathways. The production of excessive oxidative β-carotene metabolites via reactions with smoke constituents may be a key event underlying this relationship. Consistent with previous findings, our evaluation indicated consumption of up to 50 mg/day β-carotene does not present safety concerns for the non-smoking general population. Heavy smokers consuming less than 15 mg β-carotene/day are not expected to be at an increased risk of lung cancer.

The effect of folate deficiency and different doses of folic acid supplementation on liver diseases.

Liver has multiple functions such as detoxification, metabolism, synthesis and storage. Folate is a water-soluble vitamin B9, which participates in one-carbon transfer reactions, maintains methylation capacity, and improves oxidative stress. Folic acid is a synthetic form commonly used as a dietary supplement. The liver is the main organ for storing and metabolizing folate/folic acid, and the role of folate/folic acid in liver diseases has been widely studied. Deficiency of folate results in methylation capacity dysfunction and can induce liver disorders. However, adverse effects of excessive use of folic acid on the liver have also been reported. This review aims to explore the mechanism of folate/folic acid in different liver diseases, promote further research on folate/folic acid, and contribute to its rational clinical application.

Synergistic Effects of Dietary Tryptophan and Dip Vaccination in the Immune Response of European Seabass Juveniles

Vaccination is an effective, cost-efficient method to preventing disease outbreaks. However, vaccine procedures can induce adverse reactions due to stress, increasing plasma cortisol in the short term. In this context, tryptophan may prove to be fundamental as it has been demonstrated to have various desirable neuroendocrine attributes in different fish species. Therefore, this study aimed to evaluate both short-term (3 days) and long-term (21 days) effects of dietary tryptophan supplementation on European seabass juveniles’ (26.23 ± 7.22 g) response to vaccination and disease resistance to Tenacibaculum maritimum. The short-term tryptophan-fed fish exhibited increased hepatic superoxide dismutase and plasma cortisol levels, along with the downregulation of immune-related genes. Despite these changes, disease resistance was unaffected. When fish were later dip vaccinated, tryptophan prevented the stress-induced plasma cortisol increase and upregulated the gene expression of igm, suggesting tryptophan’s role in enhancing vaccination efficiency by counteracting stress-associated effects. In the long term, the lowest supplementation dose counteracted vaccine-mediated reduced gene expression, and fish fed this diet showed a more modest molecular response. Overall, the findings suggest a complex interplay between tryptophan supplementation, immune responses, and vaccine efficiency in fish. Further research is necessary to clarify how tryptophan could consistently improve vaccine efficiency in aquaculture.

D-hypovitaminosis in menopausal disorders clinic: Correction possibilities

Introduction. The postmenopausal period being a significant part of a modern woman’s life. The persistence of menopausal disorders clinic can be combined with the hypovitaminosis D state, which, in turn, can further aggravate the existing symptoms. Vitamin D supplementation may be one of the pharmacological approaches to correct menopausal disorders.Aim. To evaluate the contribution of hypovitaminosis D to the clinic of menopausal disorders; to determine the clinical efficacy of using cholecalciferol in late postmenopausal residents of Yekaterinburg.Materials and methods. During the period from 2018 to 2021, 144 late postmenopausal patients from 56 to 79 years old living in Yekaterinburg and do not need outside help in everyday life took part. The following parameters of anthropometry, the severity of modified menopausal index (MMI), hospital anxiety and depression scales (HADS), Mini-Mental State Examination (MMSE), an assessment of serum 25(OH)D level (chemiluminescent immunoassay; Access 2, Beckman Coulter, USA) were studied. Clinical efficacy of cholecalciferol was evaluated in 68 patients in the prospective cohort study design. Micellated water-soluble form of cholecalciferol in standard doses recommended by the Russian Association of Endocrinologists (RAE) was used.Results. Vitamin D deficiency and insufficiency are associated with increased parameters of body weight (p = 0.048), waist circumference (p = 0.018) and hips (p = 0.016), increased cases of decreased performance (p = 0.046) and subclinical symptoms anxiety (p = 0.033). Supplementation of standard therapeutic and maintenance doses of cholecalciferol for 6 months contributed to a significant reduction in neurovegetative component of modified menopausal index in 54.4% of cases (p = 0.035) and improvement in cognitive function parameters in 50.0% of cases (p = 0.023) in late postmenopausal patients.Conclusions. The use of cholecalciferol in adequate doses can be considered as an important component of complex therapy for women in late postmenopausal period.

A comprehensive evaluation of bioremediation effects of oil-contaminated soils using various dosages of exogenous nitrogen supplementation: TPH removal, ecological toxicity, and microecological response

A comprehensive evaluation of bioremediation effects of oil-contaminated soils using various dosages of exogenous nitrogen supplementation: TPH removal, ecological toxicity, and microecological response

Supplementation practices among pregnant women and those trying to conceive: a population-representative survey in Vancouver, Canada.

Dietary supplements including vitamins, minerals, and natural health products are commonly consumed by those aiming to optimize fertility and pregnancy outcomes. The aim of this survey was to describe supplementation practices among individuals who were pregnant or trying to conceive in Vancouver, Canada. An online survey was conducted among 500 individuals who were pregnant (n=250) or trying to conceive (n=250). Participants met a substantial proportion of vitamin and mineral recommendations through supplements alone. Exceptions included calcium, magnesium, and choline, with median (interquartile range (IQR)) supplementation doses reported by those who were pregnant and trying to conceive, respectively, of: 250 (200 and 250mg) and 250 (200 and 250mg), 50 (50 and 75mg) and 50 (50 and 90mg), and 53 (10 and 150mg) and 55 (10 and 100mg), as compared to perinatal recommendations of 1000mg/day (calcium), 350mg/day (magnesium), and 450mg/day (choline). Conversely, median (IQR) doses of folate reported by those who were pregnant and trying to conceive, respectively, were: 1000 (780 and 1000µg) and 1000 (800 and 1000µg), with ∼70% overall (337/471) reporting doses ≥1000µg (the tolerable upper intake level). Most participants (451/500; 90%) reported supplementation with a prenatal multivitamin; of these, 83% reported that supplementation occurred daily. Overall, as diet was not considered, we cannot ascertain whether recommendations for calcium, magnesium, and choline were met through the combination of supplements and foods; however, we believe that additional supplementation with choline may be required to meet recommendations in pregnancy. Excessive folate supplementation has been previously identified as a concern throughout North America; here, we provide further evidence for excessively high doses consumed via supplements.

Response of One-Carbon Biomarkers in Maternal and Cord Blood to Folic Acid Dose During Pregnancy.

The folate Recommended Daily Allowance (RDA) for pregnant women is 600 μg/day dietary folate equivalents, which is equivalent to approximately 400 μg folic acid. Many prenatal supplements contain much higher doses of folic acid. The body's ability to reduce synthetic folic acid to the metabolically active form may be exceeded with high levels of supplementation. The objective of this double-blinded randomized controlled intervention trial was to determine changes in unmetabolized folic acid and other biomarkers of folate and one-carbon metabolism in maternal and cord blood in response to a folic acid dose commonly found in prenatal supplements (800 μg/day) compared to the dose equivalent of the RDA (400 μg/day). Healthy pregnant women were randomized and provided supplements from their first prenatal visit (<12 weeks gestation) through delivery. Maternal blood was collected at baseline and delivery. Umbilical cord blood from the mothers was collected at delivery. A repeated measures analysis of variance revealed that there was a significant group supplemental dose effect (p = 0.0225) on serum unmetabolized folic acid concentration in mothers but no difference in cord blood unmetabolized folic acid concentrations between groups. Mixed effects analysis found a significant overall effect of pre-pregnancy BMI (p = 0.0360) and length of previous folic acid supplementation (p = 0.0281) on serum folate concentrations. No treatment effect was seen in RBC folate concentrations. Choline concentrations were higher in cord blood from the 800 μg/day group compared to the 400 μg/day group, but there was no group effect in maternal choline concentrations. The results indicate that folic acid dose during pregnancy affects certain folate and one-carbon biomarkers, and these effects are not consistent between maternal and cord blood. Potential long-term effects of these results on both mothers and offspring are unknown and merit further investigation.

Supplementation of Chlorogenic Acid Alleviates the Effects of H2O2-Induced Oxidative Stress on Laying Performance, Egg Quality, Antioxidant Capacity, Hepatic Inflammation, Mitochondrial Dysfunction, and Lipid Accumulation in Laying Hens

This research examined the impact of chlorogenic acid (CGA) on laying performance, antioxidant capacity, egg quality, hepatic inflammation, mitochondrial function, and lipid metabolism in hens subjected to hydrogen peroxide (H2O2)-induced oxidative stress (OS). Three hundred sixty healthy 43-wk-old Hy-Line brown hens were randomly assigned to six treatments: a basal diet + 0 (control and H2O2), 600 (600 mg/kg CGA and 600 mg/kg CGA + H2O2), and 800 (800 mg/kg CGA and 800 mg/kg CGA + H2O2) mg/kg CGA for 84 d. On the 64th and 78th days of the trial, hens in groups H2O2, 600 mg/kg CGA + H2O2, and 800 mg/kg CGA + H2O2 were injected intraperitoneally with 10% H2O2. The results demonstrated that 600 and 800 mg/kg CGA significantly improved the egg production rate (EPR) and egg quality and reduced lipid peroxidation compared to the control group. The 800 mg/kg CGA showed greater improvements in the EPR and average egg weight (AEW) compared to the 600 mg/kg dose. Conversely, H2O2 exposure significantly decreased the EPR, AEW, and egg quality and increased feed conversion rate and average daily feed intake. H2O2 exposure significantly decreased serum T-AOC and increased serum MDA levels while reducing hepatic T-SOD, GSH-Px, and CAT activities. Meanwhile, H2O2 exposure significantly elevated liver reactive oxygen species levels, pathological damage, and NF-κB, TNFα, and IL-1β gene expression. Additionally, H2O2 treatment disrupted hepatocyte mitochondrial structure and significantly increased the expression of VDAC1 protein, and IP3R, GRP75, MCU, Fis1, and MFF genes, while downregulating the expression of MFN2 protein and PGC1α gene. Oil Red O staining demonstrated that H2O2 induced significant lipid accumulation in hepatocytes. Concurrently, H2O2 significantly increased serum triglycerides, total cholesterol, and liver triglycerides levels while decreasing serum hepatic lipase activity. This was primarily attributed to the significant upregulation of liver SREBP1, FASN, and ACC genes and the downregulation of the liver CPT1 gene induced by H2O2. Furthermore, CGA pretreatment effectively prevented the degeneration in laying performance and egg quality, as well as OS, liver inflammation, pathological damage, and mitochondrial dysfunction induced by H2O2. CGA inhibited H2O2-induced hepatic lipid accumulation by upregulating fatty acid oxidation-related gene expression and downregulating fatty acid synthesis-related gene expression. These findings indicate that the dietary addition of 800 mg/kg of CGA is the optimum supplementation dose. CGA can enhance laying performance and egg quality while alleviating OS, hepatic inflammation, mitochondrial dysfunction, and lipid accumulation in H2O2-challenged laying hens.

Sublingual β-Glucan/Vitamin C-loaded nanoparticle-embedded polyethylene oxide nanofibrous mats

Nutritional supplements available in various forms provide the consumer with essential molecules demanded for well-being retention. Despite the conveniences provided by oral administration, significant disadvantages such as hepatic first-pass effect, limited absorption, and age-related swallowing problems have been recognized which should be addressed appropriately. Nano-sized biomaterials, which have recently gained popularity in numerous medical fields, have the potential to resolve these problems. In this study, a drug delivery system was designed for sublingual administration and fabricated as β-glucan/vitamin C-loaded chitosan/tripolyphosphate/polyvinylpyrrolidone (CS/TPP/PVP) nanoparticles (DNPs) embedded in polyethylene oxide (PEO) nanofibrous mats (DNFs). The optimum PNP size and DNP size for sublingual administration were obtained as 236 ± 1 nm and 257 ± 1 nm, respectively. The homogenous appearance of DNFs was demonstrated and measured as 783 ± 290 nm using scanning electron microscopy. The synthesized biomaterials were analyzed chemically, 3D-wisely, and thermally. The in vitro drug release kinetics investigation concluded that the sustained drug release of DNP over 15 days proceeded based on the first-order model, and 99.30 % of vitamin C and 99.70 % of β-glucan were released. Neither pure nor drug-loaded samples showed notable cytotoxicity in the 24-h 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay in the L929 cell line. Herein, it has been comprehended that DNF nutritional supplement can be a promising novel supplement dosage form with ease of use, high efficiency, and bioavailability than the conventional methods.

Effects of phytosterol supplementation on lipid profiles and apolipoproteins: A meta-analysis of randomized controlled trials.

The use of phytosterols and phytostanols (PS) as food supplements to control plasma cholesterol concentrations has recently received attention as its efficacy has been endorsed by scientific authorities and leading guidelines. However, the effects of phytosterols on lipid profiles and atherosclerosis remain incomplete and controversial. This study aims to investigate the effects of PS supplementation on lipid profiles and apolipoproteins in adults based on a systematic review of the literature and a meta-analysis of randomized controlled trials (RCTs). A comprehensive search was conducted for RCTs published in PubMed, Embase, Cochrane Library, and Web of Science as of May 2024. Random effects model was utilized to determine the mean differences and 95% confidence interval for changes in circulating lipid profiles and apolipoproteins. Twenty-eight RCTs with a total of 1777 participants (895 cases and 882 controls) are included in the qualitative synthesis. PS supplementation significantly reduced total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c), and apolipoprotein B (Apo-B) levels, as well as Apo-B/apolipoprotein A1 ratios, but increased high-density lipoprotein cholesterol levels. PS supplementation dose is associated with TC, LDL-c, and Apo-B levels in a dose-response manner. Our findings suggest that dietary phytosterols can effectively promote the reduction of TC, LDL-c, and Apo-B, along with increased high-density lipoprotein cholesterol in adults.

No evidence of improvements in energy metabolism after 1week of nitrate and citrulline co-supplementation in elite rowers.

Citrulline (CIT) and beetroot extract (BR) supplements positively impacts exercise performance in elite rowers. However, its influence on metabolic outcomes such as whole-body volumes of oxygen consumption (VO2) and carbon dioxide production (VCO2), substrate oxidation, energy expenditure (EE), and gross efficiency remains unknown. We studied the effects of 1week of daily co-supplementation of 3.5g BR (500mg NO3-) plus 6g CIT on VO2 and VCO2 kinetics, substrate utilization, EE, and gross efficiency in elite male rowers compared to a placebo and to a BR supplementation. Twenty elite rowers participated in this randomized, double-blind, placebo-controlled crossover trial completing 1week of supplementation in each group of study: Placebo (PLAG); BRG; and BR-CITG. Efficiency (70% VO2max) and performance (incremental maximal) tests were performed, and gas-exchange data were collected via indirect calorimetry. Analysis of covariance (ANCOVA) showed no mean between-condition differences on respiratory exchange ratio (RER), EE, and gross efficiency in the efficiency test (all P > 0.06), and in the performance test (all P > 0.28). Moreover, in both tests no interaction Time × Supplement effects were observed for VO2, VCO2, RER, EE, substrate oxidation, and, gross efficiency (all P > 0.12). After 1week, no effects on energy metabolism and substrate utilization were observed after the daily co-ingestion of BR extract plus CIT supplement, therefore longer (> 7days) and higher doses of supplementation might be needed to influence metabolism.

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.

Acute Effects of Citrulline Malate Supplementation on Nocturnal Blood Pressure Dipping After Exercise in Hypertensive Patients: A Randomized, Placebo-Controlled Trial

Background Citrulline malate (CM), especially when used in conjunction with physical exercise, has demonstrated potential as a non-pharmacological adjunct in the management of hypertension. Nevertheless, its impact on nocturnal blood pressure dipping remains unexplored. Objective Evaluate the impact of a single dose of CM on nocturnal blood pressure dipping after exercise in hypertensive individuals. Methods In a double-blind, placebo-controlled, parallel-group clinical trial, twenty hypertensive adults (55 ± 16 years) were randomly assigned to either a CM (6 g) or placebo (6 g of corn starch) group (PLA). Resting blood pressure was measured after a 20-min period of comfortable seating in a calm environment. Both groups underwent 40 min of treadmill running/walking at an intensity of 60–70% of their reserve heart rate, 120 min after ingesting the substances. Ambulatory blood pressure monitoring was employed to measure blood pressure over 24 h. Results No significant differences in systolic blood pressure values were observed between the CM and PLA groups at rest, during wakefulness, sleep, or over a 24-h period. However, CM exhibited a significant reduction in diastolic blood pressure in several metrics: delta 24 h (-14 mmHg vs −6 mmHg, p = 0.047), delta wakefulness (-12 mmHg vs −4 mmHg, p = 0.024), percent delta 24 h (-16% vs −6%, p = 0.024), and percent delta wakefulness (-14% vs −4%, p = 0.013). No significant differences were found between CM and PLA in terms of systolic and diastolic nocturnal absolute reductions (-13 mmHg vs −12 mmHg, p = 0.808, and −13 mmHg vs −8 mmHg, p = 0.273, respectively) or nocturnal percentage decrease (-9.9% vs −9.4%, p = 0.844, and −15.3% vs −11.7%, p = 0.399, respectively). Conclusions The study found no significant changes in the post-exercise nocturnal blood pressure dip following a single dose of CM supplementation. However, a notable reduction in diastolic blood pressure was observed during the waking period and over the average 24-h monitoring period. Clinical trial registry number and website ClinicalTrials.gov platform (NCT03378596).

8533 Salt on the Kidneys A case of DDAVP induced arginine vasopressin resistance

Abstract Disclosure: M.M. Jordan: None. J.R. Islam: None. R. Hassan: None. A 63-year old female with a history of head trauma complicated by polyuria and excessive fatigue diagnosed with central DI and started on treatment with oral Desmopressin. She had no other known pertinent medical history. Patient was lost to follow-up with an eventual visit to the emergency department with complaints of bilateral leg cramps, nausea and persistent headaches. She was noted to have been initiated intranasal desmopressin in addition to oral DDAVP. On initial lab work, Sodium was 114 along with acute kidney injury. She was admitted to ICU and treated with hypertonic saline. DDAVP was withheld until sodium normalized and stabilization of renal functions. GFR still remained impaired on discharge at 40 mL/min/1.73m*2. She was then discharged on DDAVP with reestablished follow up in the endocrinology clinic with complaints of persistent polyuria. Once more, she was sent to the emergency room and was admitted for acute renal injury secondary to dehydration in the setting of polyuria and altered mentation. Upon review of her medications, the patient continued both oral and inhaled DDAVP. No other medications or supplements were reported. During this subsequent hospitalization, sodium remained between 131-135 with urine output 4.5L/ day despite increasing doses of oral DDAVP and oral sodium supplementation. At which point, suspicion for mixed DI was hypothesized (central DI and arginine vasopressin resistance). Other causes of polyuria were ruled out. Labs for persistent AKI revealed gross proteinuria. Renal biopsy was performed during hospitalization which showed acute to chronic vascular thrombotic microangiopathy and focal segmental glomerulosclerosis with collapsing features. Extensive workup for chronic infections, autoimmune conditions and hematological malignancies were negative. This showed concerns for possible DDAVP induced renal injury. Presentation: 6/2/2024

8104 Rare Case Of Ectopic Cushing’s Syndrome Secondary To Metastatic Parotid Pleomorphic Adenocarcinoma

Abstract Disclosure: B.S. Neutel: None. P. Manroa: None. Background: Pleomorphic adenocarcinoma of the parotid gland is a rare malignancy and ectopic ACTH secretion from these tumors is very rarely described. We report a case of ectopic Cushing’s syndrome (CS) in such a patient and describe the clinical course. Clinical Case: A 69-year-old female with left parotid pleomorphic adenocarcinoma status post surgery and adjuvant radiotherapy presented to her local hospital approximately 7 months after initial treatment with proximal muscle weakness and near-syncope. Workup revealed profound hypokalemia at 1.6 mmol/L (n 3.5-5.3 mmol/L) along with new-onset hypertension (BP 175/110 mm Hg) and hyperglycemia with a HbA1c 6.5 % (n &amp;lt;5.7%), as well as metabolic alkalosis with a bicarbonate level of &amp;gt;40 mmol/L (n 22-32 mmol/L). A CT scan showed multiple liver metastases and a biopsy confirmed metastatic parotid pleomorphic adenocarcinoma. She was then transferred to our comprehensive cancer center for further management. She reported muscle weakness, easy bruising, and facial edema. She denied acne, hirsutism, or abdominal striae. Endocrine workup revealed a random cortisol of 56 mcg/dL (n 3-18 mcg/dL) and ACTH of 378 pg/mL (n 7.2-63.3 pg/mL). Her AM cortisol level remained unsuppressed at 79.2 and 59.4 mcg/dL (n&amp;lt; 1.8 mcg/dL) after 1 mg and 8 mg overnight dexamethasone suppression tests respectively. Late-night salivary cortisol was 7.9 mcg/dL (n &amp;lt;0.112 mcg/dL). An MRI of the sella was negative for any pituitary lesions. After stabilizing her clinical condition and correcting electrolyte abnormalities, she was started on chemotherapy with paclitaxel and carboplatin by the oncologist. Based on clinical suspicion of ectopic CS, ketoconazole was started and titrated upwards with rapid improvement of blood pressure, hypokalemia, and hyperglycemia. She was discharged home and antihypertensives were tapered off. ACTH staining on the liver biopsy was unable to be performed due to paucity of the specimen. A Ga-68-DOTATATE PET CT revealed increased radiotracer uptake in the liver lesion suggestive of SSTR 2 receptor positivity. Despite initial clinical improvement, her disease progressed with widespread liver, lymph node, and osseous metastases within 3 months necessitating escalating doses of ketoconazole, spironolactone, and potassium supplementation. The patient elected to pursue hospice care due to intolerance to chemotherapy and passed away shortly afterward. Conclusion: Although ectopic CS caused by parotid pleomorphic adenocarcinoma is rare, prompt recognition and treatment is necessary because ectopic ACTH production is associated with poor prognosis in these patients. Presentation: 6/3/2024

Iron status, anemia, and birth outcomes among pregnant women in urban Bloemfontein, South Africa: the NuEMI study

BackgroundDespite routine iron supplementation for pregnant women in South Africa, anaemia and iron deficiency (ID) in pregnancy remain a public health concern.ObjectiveTo determine the associations between iron status and birth outcomes of pregnant women attending antenatal clinic at a regional hospital in Bloemfontein.MethodsIn this cross-sectional study of 427 pregnant women, blood was taken to analyze biomarkers of anaemia (haemoglobin), iron status (ferritin and soluble transferrin receptor) and inflammation (C-reactive protein and α-1-acid glycoprotein). A questionnaire was used to collect information about birth outcomes (birth weight and gestational age at birth), HIV exposure, sociodemographics, iron supplement intake, and maternal dietary iron intake using a validated quantified food frequency questionnaire.ResultsThe median (Q1, Q3) weeks of gestation of participants was 32 (26, 36) at enrolment. Anaemia, iron deficiency (ID), ID anaemia (IDA) and ID erythropoiesis (IDE) were present in 42%, 31%, 19% and 9.8% of participants, respectively. Median (Q1, Q3) dietary and supplemental iron intake during pregnancy was 16.8 (12.7, 20.5) mg/d and 65 (65, 65) mg/d, respectively. The median (max-min) total iron intake (diet and supplements) was 81 (8.8-101.8) mg/d, with 88% of participants having a daily intake above the tolerable upper intake level of 45 mg/d. No significant associations of anaemia and iron status with low birth weight and prematurity were observed. However, infants born to participants in the third hemoglobin (Hb) quartile (Hb > 11.3–12.2 g/dL) had a shorter gestation by 1 week than those in the fourth Hb quartile (Hb > 12.2 g/dL) (p = 0.009). Compared to pregnant women without HIV, women with HIV had increased odds of being anaemic (OR:2.14, 95%CI: 1.41, 3.247), having ID (OR:2.19, 95%CI: 1.42, 3.37), IDA (OR:2.23, 95%CI: 1.36, 3.67), IDE (OR:2.22, 95%CI: 1.16, 4.22) and delivering prematurely (OR:2.39, 95%CI: 1.01, 5.64).ConclusionIn conclusion, anaemia, ID, and IDA were prevalent in this sample of pregnant women, despite the reported intake of prescribed iron supplements, with HIV-infected participants more likely to be iron deficient and anaemic. Research focusing on the best formulation and dosage of iron supplementation to enhance iron absorption and status, and compliance to supplementation is recommended, especially for those living with HIV infection.Graphical

A systematic review on clinical practice guidelines for managing pregnancy following metabolic-bariatric surgery.

The ongoing pandemic of obesity is associated with an increase of weight loss surgeries in women of reproductive age. This study was conducted to review clinical practice guidelines (CPGs) for managing pregnancy following metabolic-bariatric surgery. We conducted a comprehensive literature search of all CPGs that covered the management of pregnancy following metabolic-bariatric surgery, 2010 through 2022, and that were published in English. Two authors independently scored the quality and usefulness of CPGs using the Appraisal of Guidelines for Research and Evaluation II tool (AGREE II). From a total of 20 CPGs, consistent recommendations included the following: 1) contraception with long-acting reversible contraceptives before surgery until the optimal time of pregnancy; 2) nutritional care by a dietitian; 3) considering gastrointestinal discomforts during pregnancy as a potential surgical complication; and 4) modified screening for gestational diabetes instead of glucose tolerance tests preventing post-bariatric hypoglycemia. There was a lack of uniformity concerning surgery-to-conception interval and dose of supplements, as well as research gaps regarding the surgical type, mental health, delivery type, breastfeeding, neonatal care, and weight retention. All recommendations for managing pregnancy after metabolic-bariatric surgery were deemed clinically useful. Although consistent recommendations should be implemented, inconsistencies should be the focus of research.

Effects of zinc supplementation on sleep quality in humans: A systematic review of randomized controlled trials.

Alternative therapies, such as zinc supplementation, have been explored as potential interventions for sleep disorders. However, the efficacy of zinc supplementation inimproving sleep quality remains uncertain. This systematic review aims to examine the impacts ofzinc supplementation on sleep qualityin humans. The Web of Science, Medline, Scopus, and Google Scholar databases were comprehensively searched to find studies investigating the effect of zinc supplementation on sleep quality. After identifying relevant studies byscreening, relevant data were extracted from them. The quality assessment was conducted using the Cochrane quality assessment tool. This systematic review included eight studies. The interventions ranged from 4 to 48 weeks, with a daily dose of zinc supplementation varying between 10 and 73.3 mg. The majority of the evidence examined in this review pointed to the significant improvement effect of zinc supplementation on sleep quality in adults compared to the control groups. Furthermore, zinc supplementation did not have a significant effect on sleep disorders. However, there was no consensus about these findings. Also, the effect of supplementation on sleep duration in nonadults was contradictory. This systematic review suggests that zinc supplementation may lead to improvements in sleep quality. However, more research, primarily clinical trials, is needed to clarify the beneficial effects of zinc supplementation on sleep quality with consideration of dietary zinc intake and the Recommended Dietary Allowancesof zinc (RDA) in the different populations. It is also recommended to investigate the effect of zinc supplementation on sleep quality in people with zinc deficiency in future studies.