VitD Deficient Research Articles

6652 Precision Diagnostic Approaches for Assessing Clinical Vitamin D Status

Abstract Disclosure: Z. Shahidzadeh Yazdi: None. E.A. Streeten: None. H.B. Whitlatch: Grant Recipient; Self; Regeneron Pharmaceuticals. M.E. Montasser: Grant Recipient; Self; Regeneron Pharmaceuticals. A.L. Beitelshees: None. S.I. Taylor: Consulting Fee; Self; Ionis Pharmaceuticals Inc.. Background . The body has evolved effective homeostatic mechanisms to maintain free 1,25-dihydroxyvitamin D [1,25(OH)2D] within narrow physiological ranges. Using a mathematical model to quantitate 24-hydroxylase activity, we concluded that mild-moderate vitamin D [VitD] deficiency suppresses 24-hydroxylase activity (the first line of defense), thereby suppressing clearance of 1,25(OH)2D. Severe VitD deficiency triggers secondary hyperparathyroidism (the second line of defense) to sustain physiological levels of 1,25(OH)2D. Objective. To compare performance of various indices of VitD status in predicting whether homeostatic mechanisms have been triggered. Methods. We studied 11 otherwise healthy VitD deficient (25-hydroxyvitamin D [25(OH)D] ≤20 ng/mL) participants before and after VitD3 supplementation (50,000 IU once or twice a week depending on BMI for 4-6 weeks). We measured 25(OH)D, 1,25(OH)2D, 24,25-dihydroxyvitamin D [24,25(OH)2D], PTH, and FGF23 before and after VitD3 supplementation. We calculated three VitD metabolite ratios and also a PTH index (i.e., PTH level before divided by PTH level after VitD3 supplementation) to normalize PTH levels relative to each individual’s setpoint. We then compared the correlation between the PTH index and various indices of VitD status. Results. VitD3 supplements induced a 2.7-fold increase (p=0.0006) in mean 25(OH)D and a 4.3-fold increase (p=0.0002) in 24,25(OH)2D, but did not change 1,25(OH)2D, PTH, or FGF23. While relative 24-hydroxylase activity (h) was highly correlated with the 1,25(OH)2D/24,25(OH)2D ratio (ρ2=0.94; p=3E-13), it was less well correlated with the 24,25(OH)2D/25(OH) ratio (ρ2=0.67; p=3E-06) and baseline total 25(OH)D (ρ2=0.72; p=7E-07). Furthermore, we investigated the correlation between the PTH index and baseline 25(OH)D and three VitD metabolite ratios. The correlation coefficient was higher when we plotted the PTH index as a function of baseline 25(OH)D before VitD3 supplementation (R2=0.23; p=2E-06) compared to the correlation of baseline PTH with baseline 25(OH)D (R2=0.08; p=5E-05). While the correlation coefficient for the correlation of PTH index with 1,25(OH)2D/24,25(OH)2D was 0.60 (R2=0.36; p=0.0002), it was 0.44 for 25(OH)D/1,25(OH)2D ratio (R2=0.20; p=0.0001) and 0.35 for the 24,25(OH)2D/25(OH)D ratio (R2=0.12; p=2E-06). Conclusions. Measuring total 25(OH)D level did not provide optimal assessment of clinical VitD status – probably because it does not account for the threefold inter-individual variation in VitD binding protein level. Of all the indices, the 1,25(OH)2D/24,25(OH)2D ratio best predicted triggering of two homeostatic mechanisms: suppression of 24-hydroxylase and induction of secondary hyperparathyroidism due to VitD deficiency. Presentation: 6/2/2024

Recovery of optimal vitamin D improves responsiveness to phosphodiesterase-5 inhibitors therapy in pulmonary arterial hypertension

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – EU funding. Main funding source(s): R.A. has received funding from the European Union’s Horizon 2020 research and innovation programme under Marie-Curie grant agreement Nº 847635. Introduction Vitamin D (vitD) deficiency is highly prevalent in patients with pulmonary arterial hypertension (PAH). Moreover, PAH-patients with lower levels of vitD have worse prognosis. We demonstrated that in animals with PAH and severe deficit of vitD, restoring vitD levels to an optimal range partially improves some pathophysiological features of PAH. Also, recent evidence suggests that vitD deficiency may cause insufficient response to phosphodiesterase-5 inhibitors (PDE5i), such as sildenafil, in some patients with PAH. Thus, in this study, we hypothesize that the recovery of optimal vitD levels in experimental PAH might help to improve responsiveness to PDE5i therapy. Methods Male Wistar rats were fed a vitD-free diet for five weeks and then received a single dose of Su5416 (20 mg/Kg) and were exposed to vitD-free diet and chronic hypoxia (10% O2) for three weeks to induce PAH. Following this, vitD deficient rats with PAH were housed in room air and divided into two groups: (a) daily tadalafil therapy (oral;10mg/kg) + continued vitD-free diet (n=9) or (b) daily tadalafil therapy (oral;10mg/kg) + single oral dose of 50,000 IU/Kg of vitD plus standard diet (n=9) for four weeks. Animals were then used for exercise capacity evaluation, invasive haemodynamic, pulmonary vascular analysis, and sample collection. Evolution of cardiac (dys)function was assessed by echocardiography. Results Recovering optimal vitD levels improved pulmonary endothelial function, measured by an increase in the endothelium-dependent vasodilator response to acetylcholine. It also increased the vasodilator response to sildenafil. Moreover, pulmonary small artery (<55 µm) remodeling was decreased in vitD-restored group, as measured by a decline in mean lumen/total ratio and mean medial thickness. In a morphometric analysis, vitD treatment attenuated increases in both right ventricle (RV) and right atrial hypertrophy, as well as the fulton index. VitD supplementation also improved the exercise capacity with increases seen in distance run, evaluated by endurance tests in a treadmill set. RV catheterization showed that vitD did not decreased the RV dysfunction, evaluated by end-systolic and end-diastolic pressure. Similar to the RV, no alterations were observed in pulmonary artery pressures. However, echocardiographic analysis revealed an improved pulmonary flow in the vitD-restored group, where pulmonary artery acceleration time normalized to ejection time ratio and pulmonary artery velocity-time integral were increased. It also improved tricuspid annular plane systolic excursion (TAPSE). Conclusion Altogether, these data suggest that in animals with PAH treated with tadalafil, restoring vitD levels to an optimal range improves some pathophysiological features of PAH. Therefore, in addition to recovery of optimal vitD status being indicated to restore calcium homeostasis in those PAH patients with severe deficiency, it might help to improve responsiveness to PDE5i.

The Role of 24-hydroxylase in Homeostatic Regulation of 1,25-dihydroxyvitamin D

Background. Because of the importance of vitamin D (VitD) in calcium balance and bone health, the body has evolved effective homeostatic mechanisms to maintain 1,25-dihydroxyvitamin D [1,25(OH)2D] — the biologically active form — in a narrow physiological range. Objective and hypothesis. We developed a mathematical model to investigate homeostatic mechanisms regulating VitD metabolism with the objective of elucidating regulatory mechanisms maintaining levels of 1,25(OH)2D within a narrow physiological range despite wide variation in availability of VitD. Methods. We studied 11 otherwise healthy VitD deficient [25(OH)D<20 ng/mL] participants before and after VitD3 supplementation (50,000 IU once or twice a week depending on BMI for 4-6 weeks). We measured 25(OH)D, 1,25(OH)2D, 24,25(OH)2D, PTH, and FGF23. We used a 2-tailed paired Student’s t-test to analyze our data; p=0.05 was selected as the criterion for statistical significance. This represents a secondary analysis of a previously published clinical trial [Shahidzadeh Yazdi et al. (2023) J Clin Endocrinol Metab, doi: 10.1210/clinem/dgad554]. Results. VitD3 supplements induced a significant 2.7-fold increase (p=0.0006) in mean 25(OH)D and a 4.3-fold increase (p=0.0002) in 24,25(OH)2D, but did not change 1,25(OH)2D, PTH, or FGF23. Our model showed that 24-hydroxylase activity was regulated over a 10-fold range — with maximal induction for 25(OH)D>50 ng/mL and maximal suppression for 25(OH)D<10-20 ng/mL). Because 24-hydroxylase catalyzes metabolic clearance of 1,25(OH)2D, high levels protect against VitD toxicity and low levels preserve 1,25(OH)2D when VitD is scarce. Thus, suppression of 24-hydroxylase activity is a homeostatic mechanism reflecting the body’s perception of VitD deficiency. Accordingly, measurements of 24,25(OH)2D levels can contribute to assessment of VitD status. However, measurements of total levels of all VitD metabolites [including 24,25(OH)2D] are confounded by the ~3-fold inter-individual variation in VitD binding protein (VDBP) levels. Fortunately, the ratio of 1,25(OH)2D /24,25(OH)2D is independent of VDBP levels. Our analysis suggests that this ratio provides a superior assessment of VitD status compared to the current recommendation to measure total 25(OH)D. For example, 24-hydroxylase activity is highly correlated with 1,25(OH)2D /24,25(OH)2D (ρ2=0.91) but less well correlated with 25(OH)D (ρ2=0.91). Conclusions. The body has two defense mechanisms to protect against VitD deficiency. The first line of defense is suppression of 24-hydroxylase, which is triggered by mild-moderate VitD deficiency and preserves VitD from degradation. However, at times of severe VitD deficiency, the first line of defense may be insuffcient to maintain 1,25(OH)2D in a physiological range. Therefore, the body triggers a second line of defense — secondary hyperparathyroidism, which in turn upregulates 1-hydroxylation and increases production of 1,25(OH)2D. By better understanding the physiology of homeostatic regulation of VitD metabolism, physicians can advance the state-of-the-art in diagnosing and treating VitD deficiency. Funding: R01DK118942; T32DK098107. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

An Adapted Questionnaire Tailored for Assessing the Risk of Vitamin D Deficiency in Children That Is Proving Useful in Guiding Clinical Interventions.

The identification of vitamin D (VitD) deficiency in pediatric populations is essential for preventive healthcare. We refined and tested the Evaluation of Deficiency Questionnaire (EVIDENCe-Q) for its utility in detecting VitD insufficiency among children. We enrolled 201 pediatric patients (aged between 3 and 18 years). Clinical evaluation and serum vitamin D levels were assessed in all subjects. The EVIDENCe-Q was updated to incorporate factors influencing VitD biosynthesis, intake, assimilation, and metabolism, with scores spanning from 0 (optimal) to 36 (poor). We established scores for severe deficiency (<10 mg/dL) at 20, deficiency (<20 mg/dL) at 22, and insufficiency (<30 mg/dL) at 28. A score of 20 or greater was determined as the optimal cut-off for distinguishing VitD deficient from sufficient statuses, as evidenced by ROC curve analysis AUC = 0.7066; SE = 0.0841; sensitivity 100%, 95% CI 0.561-1. The most accurate alignment was seen with VitD insufficiency, defined as 25-OH-D3 < 20 ng/mL. This study confirms that the EVIDENCe-Q is a valid instrument for assessing the risk of vitamin D deficiency and insufficiency in children. It offers a practical approach for determining the need for clinical intervention and dietary supplementation of VitD in the pediatric population.

Magnetic resonance spectroscopy in the hippocampus of adult APP/PS1 mice following chronic vitamin D deficiency

Vitamin D (VitD) deficiency can exacerbate AD progression and may cause changes in brain metabolite levels that can be detected by magnetic resonance spectroscopy (MRS). The purpose of this study was to determine whether chronic VitD deficiency in an AD mouse model caused persistent metabolite levels changes in the hippocampus associated with memory performance. Six-month-old APPSwe/PS1ΔE9 (APP/PS1) mice (N = 14 mice/group) were fed either a VitD deficient (VitD-) diet or a control diet. Metabolite level changes in the hippocampus were evaluated by 1H MRS using a 9.4 T MRI. Ventricle volume was assessed by imaging and spatial memory was evaluated using the Barnes maze. All measurements were made at 6, 9, 12, and 15 months of age. At 15 months of age, amyloid plaque load and astrocyte number were evaluated histologically (N = 4 mice/group). Levels of N-acetyl aspartate and creatine were lower in VitD- mice compared to control diet mice at 12 months of age. VitD deficiency did not change ventricle volume. Lactate levels increased over time in VitD- mice and increases from 12 to 15 months were negatively correlated with changes in primary latency to the target hole in the Barns Maze. VitD- mice showed improved spatial memory performance compared to control diet mice. VitD- mice also had more astrocytes in the cortex and hippocampus at 15 months than control diet mice. This study suggests that severe VitD deficiency in APP/PS1 mice may lead to compensatory changes in metabolite and astrocyte levels that contribute to improved performance on spatial memory tasks.

An investigation into the correlation of vitamin D status and management outcomes in patients with severe COVID-19 at a South African tertiary hospital

BackgroundSevere coronavirus disease 2019 (COVID-19) has a poor prognosis, and biomarkers may predict disease severity. The aim of this study was to assess the effect of baseline vitamin D (VitD) inadequacy on the outcomes of patients with severe COVID-19 admitted to the intensive care unit (ICU) of a tertiary hospital in South Africa. MethodsPatients with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were recruited during wave II of the pandemic in Cape Town. Eighty-six patients were included in the study. They were categorized into three groups: VitD deficient, VitD insufficient, and VitD sufficient. The VitD deficient and VitD insufficient groups were combined to form a ‘VitD inadequate’ group. Cox regression analysis was done to assess the association between VitD status and mortality. Factors with P < 0.05 in the adjusted multivariable Cox regression analysis were considered statistically significant. ResultsThe proportion of VitD inadequacy was 64% (55/86); this group had a significantly higher proportion with hypertension (66%; P = 0.012). The Kaplan–Meier curve showed no significant difference in the probability of survival among the COVID-19 patients admitted to the ICU with or without VitD inadequacy. However, patients with elevated serum creatinine were significantly more at risk of dying (adjusted hazard ratio 1.008, 95% confidence interval 1.002–1.030; P = 0.017). ConclusionsThis study found a high prevalence of VitD inadequacy (combined deficiency and insufficiency) in COVID-19 patients admitted to the ICU. This may indicate a possible risk of severe disease. Whilst there was no statistically significant relationship between VitD status and mortality in this cohort, baseline VitD may be an important prognostic biomarker in COVID-19 patients admitted to the ICU, particularly in those with comorbidities that predispose to VitD deficiency.

Association between Vitamin D Status and Health Status of Adults in Western Libya

Vitamin D (VitD) is essential for health and preventing diseases. This study aimed to investigate the possible association between VitD status and health status in 306 Libyan male and female young adults (18–25 Y) and adults (26–65 Y). There were 89.54% of subjects that had VitD levels below normal (&lt;30 ng/mL), of which 45.42% were VitD deficient (&lt;10 ng/mL) and 44.12% were VitD insufficient (10–29.9 ng/mL). VitD deficiency was associated with higher fasting blood sugar (FBS), low-density lipoprotein (LDL), and triacylglycerol (TAG) levels. Young adults had lower VitD levels than adults, which was associated with some health conditions. VitD insufficiency was associated with higher body mass index (BMI) values in adults, especially females, with higher FBS levels in adult males and higher hemoglobin A1c (HbA1c) levels in adult females. VitD deficiency in young adults was associated with higher TAG levels (more likely in adults) and lower high-density lipoprotein (HDL) values. Furthermore, VitD deficient adult females appeared to have a higher risk of sleeping problems, psychological disorders, headache, and osteoporosis, whereas their male counterparts appeared to be at a higher risk of developing obesity and diabetes mellitus (DM). Findings showed a serious prevalence of VitD inadequacy in the Libyan population, which appears to negatively affect health status and be associated with some disease conditions.

Trends in vitamin D level and risk of vitamin D deficiency after gastrectomy for gastric cancer: A retrospective study of a single high-volume center experience

Post-gastrectomy vitamin D deficiency can result in osteoporosis and fractures, which can decrease patient quality of life and increase their socioeconomic burden. However, because there is no consensus around preoperative measurement and regular postoperative monitoring of serum vitamin D [25(OH)vitD] level for gastric cancer patients, we performed a retrospective study with a single high-volume center experience. We reviewed a database of 614 gastric cancer patients who underwent curative gastrectomy between December 2015 and December 2019. Multivariate analyses were performed to identify risk factors for 25(OH)vitD deficiency after one year postoperative (n=546). A linear mixed model was used to evaluate changes between preoperative (n=585) and postoperative (6 [n=504] and 12 months [n=572]) 25(OH)vitD values. Preoperative 25(OH)vitD deficiency occurred in 67.7% of patients with gastric cancer. Patients who underwent postoperative chemotherapy for advanced pathologic disease were more likely to be 25(OH)vitD deficient at postoperative year one than those who did not receive chemotherapy (P=0.005). Postoperative chemotherapy was an independent risk factor along with preoperative 25(OH)vitD level for one year postoperative 25(OH)vitD deficiency (P=0.002). Meanwhile, there was significant change in 25(OH)vitD level after surgery according to reconstruction (increased in Billroth I group compared to gastrojejunostomy group, P=0.016), pathologic stage (increased in stage I group, decreased in stage II and III group, P=0.005), postoperative chemotherapy (increased in non-chemotherapy group, decreased in chemotherapy group, P=0.001), and season of surgery (increased when the blood tests were performed at summer, decreased when tested in non-summer season, P=0.009). More than half of gastric cancer patients had preoperative 25(OH)vitD deficiency, and those who had postoperative chemotherapy were at risk for 25(OH)vitD deficiency one year after surgery. There was a significant change in 25(OH)vitD level after surgery according to reconstruction method and postoperative chemotherapy. Preoperative measurement and regular postoperative monitoring should be considered for high-risk patients.

A randomized, double-blind, placebo-controlled, 12-week trial of vitamin D augmentation in major depressive disorder associated with vitamin D deficiency

BackgroundRandomized controlled trials (RCTs) of vitamin D (VitD) supplementation for depression have yielded inconsistent results. We conducted the first RCT of VitD supplementation with multipoint serum 25(OH)D assessments in major depressive disorder (MDD) patients with concurrent severe VitD deficiency. MethodsWe randomized antidepressant-free depressed adults with mean baseline 25(OH)D of 11.5 ng/ml to VitD (60,000 IU every 5 days; n = 31) or placebo (n = 28) for 12 weeks. All patients also received escitalopram (10–20 mg/day). Patients were rated at baseline and at the end of weeks 4, 8, and 12. Serum 25(OH)D was estimated at baseline, week 8, and week 12. ResultsIn an intent-to-treat analysis, mean Hamilton Depression Scale scores dropped from 25.7 to 5.7 and from 25.8 to 5.0 in VitD and placebo groups, respectively (primary outcome; P = 0.92). VitD and placebo groups did not differ on other objective and subjective ratings of depression, or on global ratings. Similar findings characterized completer analyses. No significant correlations were observed between 25(OH)D levels and depression ratings across the course of the study. Importantly, endpoint escitalopram doses were 4 mg/day higher in placebo than in VitD patients, and 4 mg/day higher in VitD deficient than in VitD sufficient patients. LimitationsA ceiling effect with escitalopram may have prevented the discovery of benefits with VitD supplementation. ConclusionsVitD supplementation does not improve antidepressant outcomes with flexibly dosed escitalopram. VitD deficient depressed patients may require higher antidepressant doses to experience benefits similar to those whose deficiency is corrected by VitD supplementation.

Effect of Replacement of Vit-D in Diabetic Painful Neuropathy among Chronic Type 2 Diabetic Patients

Background: Painful symptoms of diabetic neuropathy are more common in patients having type 2 diabetes. The objective in this trial was assessment of mean change in pain score upon giving Vit-D supplementation in patients with diabetic painful neuropathy.&#x0D; Methodology: This study was conducted from December 2019 to June 2020 in OPD of Fauji Foundation Hospital, Rawalpindi after the ethical approval. A total of 251 diagnosed cases of diabetes (both male and female patients), with high HbA1c and low Vit-D levels were included in the study. Patients having Vit-D deficiency and chronic diabetic neuropathy were given Vitamin supplementation and results were assessed after 1 month through change in pain score according to Douleur Neuropathique 4. A document of consent form was filled by patients who were recruited for this study. Data analysis was done on SPSS version 16.Paired sample t- test, was used to compare pain score where p value less than 0.05 was considered statistically significant.&#x0D; Results: Among the participants mean age was 48.22+17.06. There were 106 (42.2%) males and 145 (57.8%) female patients. A statistically significant (p&lt;0.05)mean reduction in pain score of 2.20±1.19 was observed, upon giving Vit-D supplementation in Vit-D deficient patients having painful diabetic neuropathy.&#x0D; Conclusion: Vit-D supplementation significantly reduced pain in patients having diabetic painful neuropathy.&#x0D; Keywords: Diabetes Mellitus, Diabetic Neuropathy, Vitamin D3

Correlation of vitamin D with clinical, biochemical and anthropometrical parameters of PCOS patients

Objective: To find correlation of 25-hydroxy vitamin D (25OHD) levels with various clinical biochemicals, anthropometric parameters in patients of PCOS. Study design: Cross-sectional observational study. Materials and Methods: The study was conducted at Obstetrics and Gynaecological dept. of Jawaharlal Lal Nehru medical college, AMU, Aligarh, for a period of 2 years, 2018-2020. A total number of 100 PCOS patients satisfying inclusion criteria were enrolled for the study. Frequency of Vit-D deficiency in study group was estimated. Correlation of Vit-D levels with various clinical, anthropometrical, biochemical parameters was evaluated. Based on Vit –D levels the study population was divided in to Vit-D deficient and non-deficient individuals and Paired sample t-test was used to assess changes in quantitative variables. Pearson product moment co-relation analysis was used to see correlation among different variables. Qualitative variables were interpreted using Chi square test. Statistical analysis was performed using computer program SPSS version 25.0. Observations and Results: The results of 100 PCOS patients were analysed. Vit-D deficiency was found in 74% of PCOS population. Vitamin D correlated inversely with LH, FSH Prolactin and Testosteron levels (r=-0.213, p&lt;0.05,r=-0.176;p&gt;0.05,r=-0.101;p&gt;0.05; r = 0.246, p&lt;0.01).)Though significant correlation was found with LH and testosteron only.

The relationship between vitamin D deficiency, body composition, and physical/cognitive functions.

SummaryVitamin D deficiency is still an important subject due to its significant effects on various tissues and functions. We found a relationship between vitamin D deficiency and increase in adipose tissue thicknesses. This situation reveals the importance of vitamin D supplementation, the harms of weight gain and obesity, and the importance of a balanced diet. PurposeAlthough the relationship between vitamin D (VitD) levels with body composition and physical/cognitive functions have been investigated in various studies, however, there is no study evaluating all these parameters together. In accordance with, we aimed to evaluate the relationship between VitD deficiency with body composition (i.e., skin, subcutaneous fat, and muscle thicknesses) and physical/cognitive functions. MethodsA total of 203 adults (78 M, 125 F, aged 19–91 years) who had recent 25-OH-vitamin D measurements were included. Ultrasonographic (US) measurements (skin, subcutaneous fat, and muscle thicknesses) were made from the dorsum of the hand, and anterior sides of forearm, arm, and thigh. Handgrip strength, gait speed, Timed Up and Go Test, and Chair Stand Test were evaluated. Additionally, cognitive status was also evaluated with Mini-Mental State Exam.ResultsSubjects were classified as VitD deficient group (< 20 ng/ml, N = 125) and control group (≥ 20 ng/ml, N = 78). The groups were not significantly different as regards age, gender, and anthropometric measurements (all p > 0.05). Subcutaneous fat tissues were thicker in the VitD deficient group (all p < 0.05). All the other US measurements and functional/cognitive tests were not significantly different between the groups (all p > 0.05). According to linear regression analyses, body mass index (BMI) was independently related with all subcutaneous fat thicknesses in both genders, and VitD deficiency was related with all subcutaneous fat thicknesses in females and anterior forearm subcutaneous fat thickness in males (all p < 0.05).ConclusionWe imply that together with BMI, VitD deficiency is independently related with increased regional subcutaneous fat tissue. We also underscore the role of US measurements for evaluation of body composition in related clinical scenarios.

Effect of memantine and combination with vitamin D enrichment on body composition in APP/PS1 Alzheimer’s mice following vitamin D deprivation

AbstractBackgroundVitamin D (vitD) deficiency and changes in body composition are frequently observed in Alzheimer’s disease (AD). The combination of memantine and vitD has been shown to protect cortical axons from glutamate toxicity and beta‐amyloid in AD. Further to these central effects, vitD and memantine may act peripherally to alter metabolism. The purpose of this study was to assess changes in body composition (lean, adipose, and skeletal tissue) in an AD mouse model due to vitD deprivation and subsequent treatment with memantine and memantine combined with high dose vitD supplementation.MethodMale APP/PS1 mice were randomized into four groups. Controls (n=14) received a standard diet throughout. The other three groups started a vitD deficient diet at month 6. At month 9, the VitD‐ group (n=14) remained on this diet, while the Mem&amp;VitD‐ group (n=14) had memantine added, and the Mem&amp;VitD+ group (n=14) had both memantine and 10 IU/g vitD added to their diet. Serum 25(OH)D3 levels were measured at months 6, 9, 12 and 15. Micro‐computed tomography scans were acquired at month 15 and segmented based on signal‐intensity to measure lean, adipose, and skeletal tissue mass and volume.ResultSerum 25(OH)D3 measurements confirmed that mice on vitD‐deficient diets had lower levels (89% decrease), and mice on the vitD‐enriched diet (Mem&amp;VitD+) had higher levels (129% increase), of 25(OH)D3 relative to mice on the standard diet. No differences were observed in adipose or lean tissue mass and volume between the four groups, however, there was a significant increase in skeletal tissue mass (9.3% increase, p&lt;0.05) and volume (9.2% increase, p&lt;0.05), and bone mineral content (8.7% increase, p&lt;0.01) in the Mem&amp;VitD‐ group relative to controls.ConclusionWhile vitD deprivation did not affect body composition in APP/PS1 mice at 15 months, memantine increased absolute skeletal tissue in mice that were vitD‐deficient. However, memantine did not have this effect in mice that were vitD‐enriched. We conclude that combination treatment of memantine and vitD enrichment had no negative effects on body composition in the APP/PS1 mouse model. Future work should clarify whether vitD status impacts the effects of memantine on bone physiology in people with AD.

The Effects of Vitamin D Supplementation and 25-Hydroxyvitamin D Levels on the Risk of Myocardial Infarction and Mortality

ObjectiveThe aim of the study was to examine the effects of the vitamin D (Vit-D) treatment and nontreatment on Vit-D–deficient patients without a prior history of myocardial infarction (MI).Materials and MethodsThis was a retrospective, observational, nested case–control study of patients (N = 20 025) with low 25-hydroxyvitamin D ([25-OH]D) levels (<20 ng/mL) who received care at the Veterans Health Administration from 1999 to 2018. Patients were divided into 3 groups: Group A (untreated, levels ≤20 ng/mL), Group B (treated, levels 21-29 ng/mL), and Group C (treated, levels ≥30 ng/mL). The risk of MI and all-cause mortality were compared utilizing propensity score–weighted Cox proportional hazard models.ResultsAmong the cohort of 20 025 patients, the risk of MI was significantly lower in Group C than in Group B (hazard ratio [HR] 0.65, 95% CI 0.49-0.85, P = .002) and Group A (HR 0.73, 95% CI 0.55-0.96), P = .02). There was no difference in the risk of MI between Group B and Group A (HR 1.14, 95% CI 0.91-1.42, P = 0.24). Compared with Group A, both Group B (HR 0.59, 95% CI 0.54-0.63, P < .001) and Group C (HR 0.61, 95% CI 0.56-0.67, P < .001) had significantly lower all-cause mortality. There was no difference in all-cause mortality between Group B and Group C (HR 0.99, 95% CI 0.89-1.09, P = .78).ConclusionsIn patients with Vit-D deficiency and no prior history of MI, treatment to the (25-OH)D level of >20 ng/mL and >30 ng/mL was associated with a significantly lower risk of all-cause mortality. The lower risk of MI was observed only in individuals maintaining (25-OH)D levels ≥30 ng/mL.

Restoration of Vitamin D Levels Improves Endothelial Function and Increases TASK-Like K+ Currents in Pulmonary Arterial Hypertension Associated with Vitamin D Deficiency.

Background: Vitamin D (vitD) deficiency is highly prevalent in patients with pulmonary arterial hypertension (PAH). Moreover, PAH-patients with lower levels of vitD have worse prognosis. We hypothesize that recovering optimal levels of vitD in an animal model of PAH previously depleted of vitD improves the hemodynamics, the endothelial dysfunction and the ionic remodeling. Methods: Male Wistar rats were fed a vitD-free diet for five weeks and then received a single dose of Su5416 (20 mg/Kg) and were exposed to vitD-free diet and chronic hypoxia (10% O2) for three weeks to induce PAH. Following this, vitD deficient rats with PAH were housed in room air and randomly divided into two groups: (a) continued on vitD-free diet or (b) received an oral dose of 100,000 IU/Kg of vitD plus standard diet for three weeks. Hemodynamics, pulmonary vascular remodeling, pulmonary arterial contractility, and K+ currents were analyzed. Results: Recovering optimal levels of vitD improved endothelial function, measured by an increase in the endothelium-dependent vasodilator response to acetylcholine. It also increased the activity of TASK-1 potassium channels. However, vitD supplementation did not reduce pulmonary pressure and did not ameliorate pulmonary vascular remodeling and right ventricle hypertrophy. Conclusions: Altogether, these data suggest that in animals with PAH and severe deficit of vitD, restoring vitD levels to an optimal range partially improves some pathophysiological features of PAH.

Vitamin D Deficiency and Outcome of COVID-19 Patients.

Infection with the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) poses an enormous challenge to health care systems throughout the world. Without causal treatment, identification of modifiable prognostic factors may help to improve outcomes. To explore possible associations of vitamin D (VitD) status with disease severity and survival, we studied 185 patients diagnosed with coronavirus disease 2019 (COVID-19) and treated at our center. VitD status at first presentation was assessed retrospectively using accredited laboratory methods. VitD deficiency was defined as serum total 25-hydroxyvitamin D level < 12 ng/mL (<30 nM). Primary endpoint was severe course of disease (i.e., need for invasive mechanical ventilation and/or death, IMV/D). Within a median observation period of 66 days (range 2–92), 23 patients required IMV. A total of 28 patients had IMV/D, including 16 deaths. Ninety-three (50%) patients required hospitalization (inpatient subgroup). A total of 41 (22%) patients were VitD deficient. When adjusted for age, gender, and comorbidities, VitD deficiency was associated with higher risk of IMV/D and death (HR 6.12, 95% CI 2.79–13.42, p < 0.001 and HR 14.73, 95% CI 4.16–52.19, p < 0.001, respectively). Similar correlations were observed in the inpatient subgroup. Our study demonstrates an association between VitD deficiency and severity/mortality of COVID-19, highlighting the need for interventional studies on VitD supplementation in SARS-CoV-2 infected individuals.

Evidence for possible association of vitamin D status with cytokine storm and unregulated inflammation in COVID-19 patients

ObjectivesWe present evidence for a possible role of Vitamin D (VitD) deficiency in unregulated cytokine production and inflammation leading to complications in COVID-19 patients.DesignThe time-adjusted case mortality ratio (T-CMR) was estimated as the ratio of deceased patients on day N to the confirmed cases on day N-8. The adaptive average of T-CMR (A-CMR) was calculated as a metric of COVID-19 associated mortality. A model based on positivity change (PC) and an estimated prevalence of COVID-19 was used to determine countries with similar screening strategies. A possible association of A-CMR with the mean concentration of 25-hydroxyvitamin D (25(OH)D) in elderly individuals in countries with similar screening strategy was investigated. We considered high C-reactive protein (CRP) in severe COVID-19 patients (CRP ≥ 1 mg/dL) as a surrogate of a cytokine storm. We considered high-sensitivity CRP (hs-CRP) in healthy subjects as hs-CRP ≥ 0.2 mg/dL.ResultsA link between 25(OH)D and A-CMR in countries with similar screening strategy is evidence for VitD’s possible role in reducing unregulated cytokine production and inflammation among patients with severe COVID-19. We observed an odds ratio (OR) of 1.8 with 95% confidence interval (95% CI) (1.2 to 2.6) and an OR of 1.9 with 95% CI (1.4 to 2.7) for hs-CRP in VitD deficient elderly from low-income families and high-income families, respectively. COVID-19 patient-level data show an OR of 3.4 with 95% CI (2.15 to 5.4) for high CRP in severe COVID-19 patients.ConclusionWe conclude that future studies on VitD’s role in reducing cytokine storm and COVID-19 mortality are warranted.

Vitamin D Status in Postmenopausal Females in Saudi Arabia

AbstractVitamin D (vitD) deficiency is highly prevalent in the Middle East (including Saudi Arabia) despite the abundance of sunlight. Older individuals in particular are at high risk of being vitD deficient. VitD binding protein (DBP), which acts as a carrier of vitD and its metabolites, has been reported to influence vitD status. In our study we aimed to investigate vitD status among postmenopausal women and its relation to DBP. A cross-sectional study was conducted at the King Fahad Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia. Seventy six postmenopausal females (age ≥ 50 years) who were not taking vitD supplementation and who were resident in Jeddah city, were randomly recruited from internal medicine clinics at King Abdulaziz University Hospital. Anthropometric measures, blood pressure, lifestyle history, dietary vitD intake and fasting blood samples were obtained from all study participants. Serum total 25 hydroxy-vitamin D (25(OH)D), DBP, albumin, parathyroid hormone, calcium, phosphate, magnesium and metabolic bone parameters were analysed. VitD deficiency was defined as serum total 25(OH)D level below 30 nmol/L. The mean (± SD) serum level of total 25(OH)D was 46.9 ± 28.9 nmol/L with 36 % of the study population being vitD deficient. Although non-significant, the vitD deficient group had lower DBP and higher dietary vitD intake levels when compared with those with serum vitD &gt; 30nmol/L. In addition, DBP was inversely correlated with vitD dietary intake (r = -0.233, P = 0.046). In conclusion, vitD deficiency is highly prevalent among postmenopausal women living in Jeddah, Saudi Arabia. Intake of a vitD rich food seems to be associated with low DBP levels. Genetic polymorphisms in DBP will be studied in the future to find out a possible explanation for the differences in vitD status and DBP between individuals as well as the concomitant relationship between dietary vitD intake, DBP and serum 25(OH)D levels.

Association of Vitamin D with Type 2 Diabetes in Postmenopausal Females in Saudi Arabia

AbstractVitamin D (vitD) deficiency has been suspected as a risk factor for type 2 diabetes mellitus (T2DM). It has been reported that an inverse relationship exists between vitD status and risk of T2DM. The aim of this study was to investigate whether there is an association between vitD status and glycemic profile and other metabolic parameters among postmenopausal women with T2DM (living in Saudi Arabia). A cross-sectional study was conducted at King Fahad Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia. One thirty six (n = 136) postmenopausal females (age ≥ 50 years) living in Jeddah city, Saudi Arabia, with T2DM were randomly recruited in this study. Anthropometric measures, blood pressure readings and fasting blood samples were obtained fro all study participants. Several biochemical parameters were estimated in fasting serum samples including total 25(OH)D, HbA1c, insulin, glucose, c-peptide and lipid profile. Surrogate markers for insulin resistance were calculated using Homeostasis Model Assessment for insulin resistance and beta cell activity (HOMA-IR, HOMA-β), Quantitative insulin sensitivity check index (QUICK-I) and McAuley's index. VitD deficiency was defined as serum total 25(OH)D level below 20 ng/ml.The Mean (± SD) serum levels of total 25(OH)D were 13.8 ± 8.6 ng/ml with 79% of the study cohort being vitD deficient. Furthermore, serum total 25(OH)D levels were found to be inversely correlated with fasting insulin (r = -0.24, p = 0.029), HOMA-IR (r = -0.24, p = 0.03), and positively correlated with McAuley's index (r = 0.22, p = 0.048) and QUICK-I (r = 0.25, p = 0.024). In conclusion, vitD deficiency is highly prevalent among postmenopausal women with T2DM living in Jeddah, Saudi Arabia. VitD was found to be associated with insulin resistance. Whether vitD supplements are able to improve insulin sensitivity and other parameters in T2DM postmenopausal women should be further investigated.

Effect of serum vitamin D level on IL-17, LL-37 in peritoneal dialysis patients

Objective To analyze the relationship between 25 hydroxyl vitamin D (25(OH)D) and IL-17 and LL-37 in serum of patients with maintenance peritoneal dialysis(PD), and to explore the relationship between vitamin D deficiency and immune dysfunction in patients with PD. Methods PD patients dialysis-age between 6 months and 2 years in our hospital from September 2015 to September 2016 were selected, exclusion criteria: Autoimmune diseases and malignant tumors, in patients recently treated with antibiotics, combined with active infectious diseases (new infections within two months), kidney transplant, pregnancy, received treatment with immunosuppressive agents within the last 6 months, stress states. Patients were divided into two groups: VitD normal group [25(OH)D>30 ng/mL], 26 cases, VitD deficiency group [25(OH)D<20 ng/mL], 44 cases. Venous blood was collected and IL-17, LL-37, 25(OH) D were detected by ELISA. The measurement data in line with normal distribution were expressed as mean plus or minus standard deviation(Mean±SD). Correlation analysis between variables was performed by Pearson or Spearman rank correlation analysis and multiple linear regression analysis. Results PD patients with VitD deficiency were 62.9%. The total number of peripheral blood lymphocytes in the VitD deficient group was significantly lower than that in the VitD normal group. The serum IL-17 in VitD deficient group was higher than that in VitD normal group[ (217.02±33.33 )pg/mL vs.(244.58±30.01) pg/mL, P<0.05]. The serum LL-37 content of the VitD deficient group was lower than that of the VitD normal group [(2692.84±559.53) pg/mL vs.(1957.6±312.74) pg/mL, P<0.01]. There was a linear regression relationship between IL-17 and 25(OH)D. There was a linear regression relationship between LL-37 and 25(OH)D and corrected calcium, but the effect of 25(OH)D was more significant. Conclusions Vitamin D deficiency may be associated with IL-17/LL-37, abnormal immune function in PD patients. Key words: Peritoneal Dialysis; Vitamin D; Cytokines; Peptides