VitD Supplementation Research Articles

Adjuvant Vitamin D Injection in Elderly Patients Before Intertrochanteric Fracture Surgery: A Randomised Controlled Trial.

There are multiple recommended protocols for Vitamin D (VitD) supplementation in elderly; however, only a few studies achieved to examine the role of VitD supplements before intertrochanteric fracture surgery on mortality and complications after surgery. This single-center block-randomized double-blinded trial was conducted on 80 patients with intertrochanteric fractures and a sufficient level of 25 (OH) VitD. The intervention group received an intramuscular 300,000IU VitD ampule before surgery. The primary outcome was a 6-month mortality rate, and the secondary outcomes were 1- and 2-year mortality rates and Harris Hip Score (HHS) in 6, 12, and 24months after surgery. Chi-square, t-test, repeated measure ANOVA, and Cox regression survival model was used for statistical analysis. 40 patients were allocated to each group. Demographic, clinical characteristics, and preoperative evaluations were not significantly different between the groups. Mortality rate 6-month after the surgery was 7.5% and 10% for the intervention and placebo groups respectively (P value = .71), 15% and 12.5% at 1-year (P value = .83), and 25% and 27.5% at 2-year (P value = .98). Based on the Cox regression model, only age was significantly associated with mortality (HR = 1.229, P value <.001). Significant HHS changes from baseline through 24 months after surgery were observed within both groups; however, mean differences were not significantly different between groups. A single preoperative 300,000IU VitD did not significantly impact 2-year survival and HHS in patients with intertrochanteric fractures and sufficient serum VitD level.

Improving the quality of life through vitamin D supplementation in people with multiple sclerosis: Pathobiological, immunologically based, A narrative review of the literature

An inadequate vitamin D nutritional status is associated with autoimmune diseases, heart disease, deadly types of cancer, neurological disorders and undesirable consequences in pregnancy, amongother things. In a nationally representative sample of adults in Australia on vitamin D (VitD) congestion in the general population, 20% of participants were verified to be Vit D deficient and 43% to have insufficient VitD levels [1]. It is therefore to be welcomed that in 2020 a guideline on VitD supplementation for medical use was created, taking into consideration the opinions of various global institutions [2]. For more than 15 years there have been reports that vitamin D (VitD) has an immunomodulatory function in multiple sclerosis (MS) [3] and that there is an association between low circulating serum levels of 25-hydroxyvitamin D [s25(OH)D] and an increase in inflammatory activity and impact on quality of life in persons with multiple sclerosis (PwMS) [4] [5]. Nevertheless, up to the present the "neurological community" has not been able to agree to start a daily add-on therapy using an easy to carry out, inexpensive and low-side effect vitamin D supplementation (VitD suppl. from the beginning of the diagnosed MS disease or the chronically isolated syndrome (CIS). In the last decade, there has been an accumulation of evidence of immunological and pathophysiological mechanisms that VitD positively influences the course of the disease and should become an eminent factor in therapy ([6]. For 13 years, neurologists in Sweden have been informing PwMS about the benefits of VitD-suppl. and given a recommendation for add-on therapy [7].

The effects of 12 weeks resistance training and vitamin D administration on neuromuscular joint, muscle strength and power in postmenopausal women

BackgroundThis study aimed to examine the effects of 12 weeks of resistance training (RT) and vitamin D (VitD) supplementation on muscle strength and C-terminal agrin fragment (CAF) and Neurotrophin-3 (NT-3) concentrations as potential biomarkers in postmenopausal women. MethodsThis was a randomized double-blind placebo-controlled study. Forty-four healthy postmenopausal women (55.84 ± 4.70 years and 29.61 ± 4.26 kg/m2) were randomly assigned into four groups: (1) Resistance training + placebo (RT + PLA), (2) Vitamin D supplementation (VitD), (3) Resistance training + vitamin D (RT + VitD), and (4) Placebo (PLA). VitD was supplemented as an oral capsule containing 50000 IU of cholecalciferol every two weeks. RT involved leg press, chest press, leg extension, leg curl, and shoulder press exercises, performed with 3–4 sets at 70–85 % of 1RM, three times a week. ResultsCirculating levels of CAF and NT-3 did not significantly change following the intervention period in the study groups (p > 0.05). There were significant increases in upper and lower body muscle strength and power for RT + VitD and RT + PLA ( < 0.05), but not for VitD or PLA (p > 0.05). The muscle function gains for RT + VitD and RT + PLA were higher than those for VitD and PLA but did not differ between them. Conclusion12-week of RT interventions resulted in significant increases in muscle strength and power in postmenopausal women. However, VitD supplementation did not result in any additional benefits. The positive changes in muscle function promoted by RT do not seem to be associated with changes in the neuromuscular joint via the CAF or NT-3 as potential biomarkers.

The relationship between serum 25-hydroxyvitamin D and iron status and anaemia in undernourished and non-undernourished children under five years in South Africa

BackgroundVitamin D (vitD) plays a role in iron metabolism by the suppression of hepcidin, while iron deficiency also impairs vitD metabolism. In undernourished children, iron and vitamin D deficiency are common. There is little knowledge of the inter-relationship between these two nutrients in undernourished and non-undernourished children. AimTo assess the association between 25-hydroxyvitamin D (25(OH)D) and iron status, and the effect of 3 doses of 50,000 IU of vitD on iron status in undernourished and non-undernourished children. MethodsWe measured serum 25(OH)D, haemoglobin (Hb), ferritin and soluble transferrin receptor in 121 undernourished and 51 non-undernourished children in clinics in the North-West Province of South Africa. Three doses of 50,000 IU/week of vitD was supplemented to children with suboptimal vitD levels. ResultsThe overall prevalence of suboptimal vitD concentration (25(OH)D < 30 ng/mL) was 20.3 %. Anaemia and iron deficiency anaemia (IDA) prevalence were 62 % and 49.2 % in the undernourished and 56.9 % and 42.9 % in the non-undernourished group. In the overall group, 25(OH)D < 30 ng/mL was associated with significantly higher IDA prevalence compared to those with 25(OH)D ≥ 30 ng/mL (64.7 % vs 43.0 %, p = 0.023), and was associated with an increased risk of IDA in the crude analysis (OR: 2.434 1.114, 5.318, p = 0.026). Serum 25(OH)D < 30 ng/mL was associated with 4 times (OR: 4.046, 95%CI: 1.022, 16.009, p = 0.046) and greater than 5 times (OR: 5.386, 95%CI: 1.528, 18.985, p = 0.009) increased odds of anaemia and IDA in the undernourished children, respectively. VitD supplementation resulted in a significant reduction of 55.9 % in TNF-α concentration (p = 0.008) in the overall group. ConclusionSuboptimal vitD concentration is associated with increased odds of anaemia and IDA. VitD status should be considered in anaemia prevention strategies, especially in populations where both vitD and iron deficiencies co-exist.

Abstract 13308: Characteristics of Participants Enrolled in a Randomized Controlled Trial Evaluating Vitamin D Normalization on Major Adverse Cardiovascular-Related Events: The Target-D Trial

Background: Many observational studies have reported associations between low 25-hydroxyvitamin D (25[OH] vit D) levels and adverse cardiovascular (CV) outcomes. Recent randomized clinical trials have not found vitamin (vit) D 3 supplementation to reduce CV risk. However, these trials gave “blanket” doses regardless of 25[OH] vit D level, with none having "treated to target". We are performing the first study where subjects are prescribed vit D 3 supplementation based on individual 25[OH] vit D levels. Methods: The purpose of Target-D (NCT: 02996721) is to determine if achieving 25[OH] vit D levels &gt;40 ng/mL among myocardial infarction (MI) patients will result in a reduction of adverse CV events. Subjects meeting study criteria from April 2017 to May 2023 were randomized to receive standard of care or clinical management of 25[OH] vit D levels. The treatment arm received targeted vit D 3 supplementation based on a dosing algorithm. Target-D is an event-driven trial that will conclude when 104 primary outcome events (composite of death, MI, heart failure hospitalization, and stroke) have occurred. Results: The study consort diagram is shown in Figure. Patient characteristics are shown in Table. Baseline 25[OH] vit D levels were 26.8±12.7 (median: 25) and were similar between arms (Table). Among those randomized to the treatment arm with a 25[OH] vit D levels &lt; 40, 58.5% of patients began vit D 3 dosing at 5000 IU. Conclusions: Average baseline 25[OH] vit D levels were deficient in Target-D participants. The discrepancy in findings between observational and randomized trials of vit D may be due to the inability of vit D 3 supplementation doses to achieve therapeutic 25[OH] vit D thresholds. Target-D will evaluate if it is the level of serum 25[OH] vit D achieved that provides CV benefit and not necessarily the vit D 3 supplementation dose that is received. It is anticipated that the number of events needed for this event-driven trial will be achieved by May 2024.

Abstract 14841: Higher Than Daily RDA Recommended Vitamin D 3 Dosing and Multiple Titrations Are Required to Achieve &gt;40 ng/mL 25-hydroxy Vitamin D Levels in Acute Coronary Syndrome (ACS) Participants Enrolled and Randomized to Targeted Vitamin D Treatment: The Target D Trial

Background: Low vitamin (vit) D serum levels in observational data are associated with increased cardiovascular (CV) events. Prevalence of vit D deficiency (≤20 ng/mL) in the USA is estimated at 40%. Meanwhile, doses for USA recommended dietary allowance (RDA) are 600-800 IU. Several randomized trials of vit D therapy did not use serum levels to target dosing, rather utilized doses from 2000 to 4000 IU daily. The Target-D trial utilizes an achieved vit D serum (&gt;40 ng/mL) strategy. We provide an initial overview of dosing and titration to achieve vit D serum levels &gt;40 ng/mL. Methods: Target-D (NCT: 02996721), a randomized event-driven trial, enrolled (April 2017-May 2023) a total of 632 (316/arm) acute coronary syndrome (ACS) patients to targeted vit D 3 treatment or standard of care. Vit D 3 supplementation was based on a dosing algorithm (Table 1). For baseline serum vit D &gt;40, no supplementation is given, and participants return at 12-months for reassessment. Those with a baseline serum vit D ≤40, the algorithm is applied, and participants return in 3-month intervals for assessment and dosing adjustment, until levels are &gt;40 ng/mL. Results: Of the 316 (62.8±11.3 yrs, 23.1% female, 90% white) treatment participants, 89.4% (n=279) required vit D 3 dosing. Mean serum vit D was 25.9±11.5 ng/mL (median: 24, range: 5-84). Table 2 shows the percent of participants achieving &gt;40 ng/mL at each interval by dose. Only 13.5% of participants were able to achieve &gt;40 ng/mL using &lt; 2000 IU, 20.8% needed 3000-4000 IU, 51% needed 5000-8000 IU, and 14.6% required &gt; 10,000 IU. Conclusions: At our center, ACS patients have low serum vit D levels. Participants randomized to vit D 3 required doses well above US daily RDA, with 86.5% requiring &gt;2,000 daily and 14.6% requiring &gt; 10,000 IU. Less than 65% achieved &gt;40 at 3 months, another 25% required 6 months. Contemporary vit D studies may have underdosed study participants, potentially achieving treatment serum levels less than “therapeutic”.

Effect of 25 hydroxyvitamin D on attention deficit and hyperactivity in school-age children with ADHD.

To observe the serum levels of 25 hydroxyvitamin D [25 (OH) D] in healthy school-age children and children with attention deficit hyperactivity disorder (ADHD) and to analyze the effects of serum 25 (OH) D on the symptoms of attention deficit and hyperactivity in school-age children with ADHD. According to the Diagnostic and Statistical Manual of Mental Disorders DSM-IV diagnostic criteria for ADHD in children, 80 healthy children aged 6 years or less than 10 years old and children diagnosed with ADHD in the Department of Rehabilitation Medicine, Department of Pediatrics and Department of Physical Examination of our hospital were randomly selected as research subjects. The serum 25 (OH) D level, attention deficit hyperactivity (Swanson, Nolan, and Pelham, version IV [SNAP-IV] parental version) score and Conners child behavior (PSQ) index were observed and compared between the 2 groups. In addition, the children with ADHD whose serum 25 (OH) D was lower than normal were treated with supplemental VitD3, and the changes in serum 25 (OH) D, SNAP-IV parental score and PSQ index of ADHD children were observed and compared. Serum 25(OH)D was insufficient or deficient in 26 healthy children, but the SNAP-IV score and PSQ index were normal. Serum 25(OH)D was lower than normal in 69 patients in the ADHD group, which was negatively correlated with SNAP-IV score (r = -0.3479, P = .0034) and negatively correlated with PSQ index (r = -0.3566, P = .0026). After vitamin D3 (VitD3) supplementation in 69 children with serum 25(OH)D levels lower than the normal ADHD group, it was found that the SNAP-IV score (r = -0.4654, P = .0037) and PSQ index (r = -0.5680, P = .0002) of 34 children with ADHD were negatively correlated with the increase in serum 25(OH)D. The SNAP-IV score and PSQ index of the other 35 children with ADHD showed no correlation with the increase in serum 25 (OH) D (P > .05). Serum 25(OH)D levels lower than normal are more common in school-age children, and levels lower than normal are not the key pathogenic factor of ADHD in school-age children, but serum 25(OH)D levels lower than normal may be the upregulation factor of attention deficit and hyperactivity disorder expression in some school-age children with ADHD. The lower level of serum 25(OH)D may be closely related to the severity of ADHD symptoms in some children.

Exposure to sunlight and allergic morbidity in children (Pollution and Asthma Risk: an Infant Study)

Abstract Background Sunlight relationship with allergies is poorly studied in children. Thus, we examined how early exposure to solar radiation is associated with allergic morbidity in the PARIS birth cohort. Methods This study dealt with children who attended at least one of the two health check-ups: 18 months (n = 2012) and 8/9 years (n = 1080). Early exposure (prenatal and during the first year of life) to solar radiation was assessed using meteorological data (solar radiation, temperature, relative humidity). Children with similar exposure trajectories were grouped by longitudinal and multidimensional cluster analysis. Association of solar radiation exposure with allergic morbidity (i.e. allergic sensitisation at 18 months and 8/9 y., current asthma, rhinitis, and eczema at 8/9 y.) was quantified by multivariable logistic regression models adjusted for potential confounders. The effect modification of maternal vitamin D (VitD) supplementation during pregnancy was also tested. Results Four exposure trajectories were found. The trajectory with the highest exposure to early solar radiation had a reduced risk of sensitisation at 8/9 y. compared to the trajectory with the lowest exposure (p = 0.06). This association was statistically significant in the VitD supplemented subgroup. Solar radiation during pre- and post-natal period was significantly associated with a lower risk of sensitisation at 8/9 y. (for ↗IQR, aOR: 0.47; 95%CI: 0.25-0.87 and 0.84;0.70-1.00, respectively). Increased prenatal exposure to solar radiation was significantly associated with a lower asthma risk at 8/9 y. (for ↗IQR, 0.32; 0.10-0.96). Conclusions Early sunlight exposure may reduce the risk of sensitisation and asthma in school-aged children, especially in those prenatally exposed to VitD intake. These findings highlight the importance of VitD in preventing allergic diseases in children, either through supplementation or sunlight exposure. Key messages • Pre-natal and early postnatal exposure to sunlight could reduce the risk of sensitisation and asthma among school-aged children. • The association may be explained by vitamin D immunomodulatory effect, highlighting its importance in preventing allergic diseases in children through supplementation or sunlight exposure.

THU397 Homeostatic Regulation Of 1,25-dihydroxyvitamin D: Critical Role Of 24-hydroxylation (CYP24A1)

Abstract Disclosure: Z. Shahidzadeh Yazdi: None. E.A. Streeten: Grant Recipient; Self; Regeneron Pharmaceuticals. 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. The VITAL study raised substantial questions whether current Endocrine Society guidelines provide optimal criteria to identify patients whose bone health would benefit from vitamin D (VitD) supplements. We investigated the impact of VitD supplements on levels of VitD metabolites and other biomarkers in the context of studying interactions between VitD and canagliflozin. 11 healthy Amish participants with 25-hydroxyvitamin-D (25(OH)D) levels ≤20 ng/mL were recruited in the context of our ongoing pharmacogenomic study of canagliflozin. RESULTS: VitD supplements increased mean levels of 25(OH)D from 16.5±1.6 ng/mL to 44.3±5.5 ng/mL (p=0.0006) and 24,25(OH)2D from 1.0±0.1 ng/mL to 4.3±0.6 ng/mL (p=0.0002). Mean levels of 1,25(OH)2D and PTH were unchanged: 43.8±3.6 vs. 44.9±4.1 pg/mL for 1,25(OH)2D and 47.5±4.8 vs. 48.4±5.1 pg/mL for PTH. We applied mathematical modeling, which suggested that regulation of 24-hydroxylation was the principal mechanism responsible for maintaining 1,25(OH)2D levels within a narrow range in our mildly VitD deficient research participants [25(OH)D levels: 10-20 ng/mL]. When 25(OH)D levels were low (&amp;lt;20 ng/mL), 24-hydroxylation was maximally suppressed. Low levels of 24-hydroxylase activity tend to sustain levels of 1,25(OH)2D by decreasing its rate of metabolic clearance. VitD supplementation induced 24-hydroxylase activity by ∼5-fold – reaching a plateau when 25(OH)D levels &amp;gt;60 ng/mL. As suggested in the literature (JCY Tang et al, Sci Rep, 9:6974, 2019), we calculated ratios of 1,25(OH)2D/24,25(OH)2D as an index for the homeostatic response to VitD status. When we plotted the 1,25(OH)2D/24,25(OH)2D ratio as a function of 25(OH)D/1,25(OH)2D, we observed an extremely high degree of correlation (Spearman correlation coefficient of -0.94; p=10-10). DISCUSSION: Clinical assessment of thyroid status provides a highly relevant historical precedent. 50 years ago, thyroid status was assessed by measurement of total serum thyroxine (T4) levels. Diagnostic accuracy was greatly improved when total T4 was replaced by laboratory measurement of either free T4 or TSH (an index of the homeostatic response to thyroid status). Current clinical guidelines recommend assessment of VitD status by measuring total levels of 25(OH)D, which unfortunately are confounded by inter-individual variation in levels of VitD binding proteins (VDBP). We anticipate that diagnostic accuracy would be greatly enhanced if clinicians replaced measurement of total 25(OH)D by laboratory measurements that are not affected by variation in levels of VDBP. By analogy to the approach to clinical assessment of thyroid status, we recommend consideration of VDBP-independent indices of VitD status including 25(OH)D/1,25(OH)2D as an index of VitD stores and 1,25(OH)2D/24,25(OH)2D as an index for the body’s homeostatic response to VitD status. Presentation: Thursday, June 15, 2023

SAT237 AZP-3601, A Novel PTH 1 Receptor Agonist, Induces Rapid Reduction And Normalization Of Urinary Calcium In Chronic Hypoparathyroid Patients

Abstract Disclosure: L. Figueres: None. I. Takacs: None. E. Mezosi: None. A. Soto: None. P. Kamenicky: None. S. Lemoine: None. F. Borson-Chazot: None. I. Capel: None. M.A. Galvez moreno: None. M. Ovize: Employee; Self; employee. T. OuldRouis: Employee; Self; employee. S. allas: Employee; Self; employee. M. Sumeray: Employee; Self; employee. M. Mannstadt: Consulting Fee; Self; consultant. Background: Conventional therapy with oral calcium (Ca) and active vitamin D (vitD) supplementation for chronic hypoparathyroidism (cHP) can induce or aggravate hypercalciuria and may lead to detrimental long-term renal complications. AZP-3601 is a novel 36-amino-acid peptide designed to activate the R0 conformation of the PTH 1 receptor which produces a prolonged calcemic response despite a short half-life. This phase 2 study examined the effects of AZP-3601 on urinary Ca (uCa) excretion in two consecutive cohorts (C1 and C2) of cHP patients. Methods: Following an optimization period, during which Ca and active vitD doses were adjusted to achieve baseline albumin-adjusted serum calcium within the target range of 7.8 to 9.0 mg/dL, patients received a daily sc. injection of AZP-3601 at initial doses of 20 µg/day (C1) or 10 µg/day (d) (C2), while simultaneously reducing their Ca and active vitD . Subsequent up-titration to a maximum daily dose of 60 µg (C1) or 80 µg(C2) was allowed. Twenty-four-hour urinary Ca excretion (24h-uCa), fractional excretion of Ca (FECa), 24h-urinary phosphate (24h-uP), serum phosphate (sP) were assessed at baseline and at D84. Pooled data from 24 patients who completed the study are presented here. Results: Twenty-four patients (18 women) aged (SD) 56(11) years were taking 0.61(0.26) µg/d active vitD and 1733(1442) mg oral Ca at baseline. At D84 , active vitD and oral Ca were each discontinued in 88% of patients, while mean albumin-adjusted serum calcium remained within the target range. Mean 24h-uCa decreased from 325(172) mg/24h to 207(107) mg/24h and 130(91) mg/24h at D14 and D84, respectively. In 13 patients with hypercalciuria at baseline, we observed a 67% reduction of 24h-uCa at D84 and a normalization of 24h-uCa in 92% of them. From baseline to D84, mean FECa decreased in the entire population and in patients with hypercalciuria. Between baseline to D84, 24h-uP excretion increased from 721(331) mg/24h to 794(238) mg/24h while mean sP decreased from 4.3(0.8) mg/dL to 3.7(0.6) mg/dL. Conclusion: These data demonstrate that AZP-3601 treatment maintained sCa within the target range after withdrawal of conventional therapy likely acting via a potent effect on the tubular reabsorption of calcium. The observed significant improvement in both uCa and sP is expected to translate to a clinically meaningful benefit for cHP patients in the long-term. Presentation: Saturday, June 17, 2023

Vitamin D Deficiency Increases Vulnerability to Canagliflozin-induced Adverse Effects on 1,25-Dihydroxyvitamin D and PTH.

Canagliflozin has been reported to increase the risk of bone fracture-possibly mediated by decreasing 1,25-dihydroxyvitamin D (1,25(OH)2D) and increasing parathyroid hormone (PTH). This work investigated whether baseline vitamin D (VitD) deficiency renders individuals vulnerable to this adverse effect and whether VitD3 supplementation is protective. This community-based, outpatient study had a paired design comparing individual participants before and after VitD3 supplementation. Eleven VitD-deficient (25-hydroxyvitamin D [25(OH)D] ≤ 20 ng/mL) individuals were recruited from the Amish population in Lancaster, Pennsylvania. Participants underwent 2 canagliflozin challenge protocols (300 mg daily for 5 days): the first before and the second after VitD3 supplementation. In the VitD3 supplementation protocol, participants received VitD3 supplementation (50 000 IU once or twice a week depending on body mass index for 4-6 weeks) to achieve 25(OH)D of 30 ng/mL or greater. Two coprimary end points were identified: effects of VitD3 supplementation on canagliflozin-induced changes in 1,25(OH)2D and PTH. Secondary end points included effects of VitD3 supplementation on baseline levels of VitD metabolites and PTH. VitD3 supplementation increased mean 25(OH)D from 16.5 ± 1.6 to 44.3 ± 5.5 ng/mL (P = .0006) and 24,25-dihydroxyvitamin D (24,25(OH)2D) from 1.0 ± 0.1 to 4.3 ± 0.6 ng/mL (P = .0002). Mean 1,25(OH)2D and PTH were unchanged. VitD3 supplementation decreased the magnitude of canagliflozin-induced changes in 1,25(OH)2D (from -31.3%±4.7% to -9.3%±8.3%; P = .04) and PTH (from +36.2%±6.2% to +9.7%±3.7%; P = .005). VitD deficiency rendered individuals more vulnerable to adverse effects of canagliflozin on biomarkers associated with bone health. VitD3 supplementation was protective against canagliflozin's short-term adverse effects on 1,25(OH)2D and PTH.

Multiple sclerosis with comorbidity depression and its association with vitamin D deficiency in a narrative review of the current literature

Over the past decade, knowledge of the pathophysiology and immunology of multiple sclerosis (MS) and depression, and the complex links to vitamin D (VitD) balance, has increased rapidly. Both diseases are characterized by an imbalance of proinflammatory and antiinflammatory cytokines, increased serum neurofilament light chains (sNfLs), disruption of the blood-brain barrier (BBB), abolition of the physiological function of the various types of microglia (MG), decreased calcidiol-serum levels, and disorders of the gut microbiome in combination with hyperactivity of the hypothalamic-pituitary-adrenal (HPA)-axis/microbiome-gut-brain-axis characterized. In depression, stress initiates cellular and molecular changes in the brain via increased cortisol release in the HPA-axis. Microglial activation and neuronal damage as well as dysregulation of neuroplastic and neurotrophic factors complete the spectrum of pathological damage. It is shown that gut dysbiosis leads to increased gut permeability, which favors endotoxemia and ultimately paves the way to systemic inflammation. A VitD supplementation could restore the balance of microorganisms in the intestine and reduce the inflammatory processes at various levels. VitD promotes regulatory T cell (Treg) proliferation, inhibits the expression of T helper 1 (Th1) cells and Th17 immune cells, and inhibits proinflammatory interleukin-17 (IL-17). 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] reduces also the secretion of interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α). Increased calcitriol levels lead to a reduction in MG activation, oxidative stress, and lower BBB permeability. An early, permanent, daily sufficient VitD supplementation as an add-on therapy under control of the serum 25-hydroxyvitamin D [s25(OH)D] levels is an essential therapeutic tool to slow down the disability caused by MS and thereby primarily prevent or reduce the stress and subsequently the manifestation of depression. Through the future continuous measurement of the biomarkers serum neurofilament ligth chains and glial fibrillary acidic proteins as well as the s25(OH)D level in MS and comorbidity depression, future therapy successes or failures can be avoided.

Vitamin D3 resolved human and experimental asthma via B lymphocyte-induced maturation protein 1 in T cells and innate lymphoid cells.

Vitamin D3 (VitD3) is known to have immunomodulatory functions, and VitD3 deficiency is associated with more severe asthma. We aimed to assess the immunoregulatory effects of VitD3 food supplementation on asthma manifestation, with particular focus on T cells and type 2 innate lymphoid cells. Preschool children and adult asthmatic cohorts were analyzed in the context of VitD3 supplementation and serum levels. In a murine model of ovalbumin-induced asthma, effects of diet VitD3 sufficiency and deficiency on T cells and type 2 innate lymphoid cells immune mechanisms were investigated. We found less severe and better-controlled asthma phenotypes along with reduced need for steroid medication in preschool children and asthmatic adults with VitD3 supplementation. VitD3 serum levels correlated with B lymphocyte-induced maturation protein 1 (Blimp-1) expression in blood peripheral mononuclear cells. VitD3-supplement-fed mice showed decreased asthmatic traits, with a decrease in IgE serum levels, reduced airway mucus, and increased IL-10 production by lung cells. Furthermore, we discovered an upregulation of effector T cells and Blimp-1+ lung tissue-resident memory T cells as well as induction of anti-inflammatory Blimp-1+ lung innate lymphoid cells producing IL-10. Supplementing VitD3 resulted in amelioration of clinical asthma manifestations in human studies as well as in experimental allergic asthma, indicating that VitD3 shifts proinflammatory immune responses to anti-inflammatory immune responses via upregulating Blimp-1 in lung innate lymphoid cells and tissue-resident memory cells.

High prevalence of hypovitaminosis D3 among pregnant women in central Iran: correlation with newborn vitamin D3 levels and negative association with gestational age.

Hypovitaminosis D3 is a significant concern among pregnant women and their newborns because vitamin D3 (Vit-D3) plays a crucial role in embryonic growth, development, and health. This study aimed to evaluate the Vit-D3 status of a group of pregnant Iranian women and its association with newborn Vit-D3 levels, medical and clinical indices after delivery. A total of 206 pregnant women and their newborns were assessed for Vit-D3 levels and their correlation with gestational age. Mean±standard deviation (SD) or the orders (non-parametric tests) of variables were compared, and correlation estimations were performed to elucidate any differences or associations between groups, with a confidence interval of at least 0.95. The mean±SD of mothers' age and gestational age were 29.65±6.18 years and 35.59±1.6 weeks, respectively. Neonatal Vit-D3 levels were associated with maternal age. Using a 30 ng/mL cutoff point for serum Vit-D3 levels, 83.5% of pregnant women and 84.7% of newborns had hypovitaminosis D3. The average Vit-D3 levels of mothers and newborns at delivery time were 23.5±8.07 ng/mL and 20.76±9.14 ng/mL, respectively. Newborn Vit-D3 levels were positively correlated with maternal Vit-D3 serum levels (R=0.744; P<0.001) and gestational age (R=0.161; P=0.022). In newborns, head circumference was inversely correlated with bilirubin level (R=-0.302; P<0.001) but directly associated with weight (R=0.640; P<0.001). Hypovitaminosis D3 remains a significant challenge for pregnant Iranian women. Maternal Vit-D3 levels provide for the newborn's needs, particularly in the late stages of pregnancy. Therefore, Vit-D3 supplementation and regular monitoring are essential for pregnant women and their newborns.

Six years' experience and trends of serum 25-hydroxy vitamin D concentration and the effect of vitamin D3 consumption on these trends.

Introduction: Vitamin D (vitD) deficiency may have importance in some diseases, but there is a lack of data in our country to clarify the current situation. Our aim was to examine the basic characteristics of patients' vitD status, and the ratio of vitD deficiency and its relation to certain diseases, assess seasonality and trends, and reveal the indirect impact of the COVID-19 pandemic on vitD3 supplementation at the patient population level. Methods: Anonymized data on 25(OH)D test results were obtained from the clinical data registry of a tertiary teaching hospital covering the period between 1 January 2015 and 30 June 2021. VitD consumption (pharmacy sale) data were retrieved from the database of the National Health Insurance Fund of Hungary in order to calculate the defined daily dose (DDD)/1,000 inhabitants/day. Descriptive statistics and odds ratios with their 95% confidence intervals were calculated. The two-sample t-test and F-test were used to analyze our patients' data. Significant differences were considered if p <0.05. Results: Altogether, 45,567 samples were investigated; the mean age was 49 ± 19.1years and 68.4% of them were female subjects. Overall, 20% of all patients had hypovitaminosis D, and just over 7% of patients had vitD deficiency. Male subjects had higher odds for hypovitaminosis or vitD deficiency (65.4 ± 28.2nmol/L vs. 68.4 ± 28.4nmol/L; p <0.0001). The mean 25(OH)D concentration has changed during the year, reaching a peak in September and a minimum in February. Patients with diseases of the circulatory system, genitourinary system, certain conditions originating in the perinatal period, and "sine morbo" (i.e., without a disease; such as those aged over 45years and female teenagers) had statistically higher odds for lower 25(OH)D concentrations (p <0.00001). VitD consumption showed seasonality, being higher in autumn and winter. A slight increase started in the season of 2017/18, and two huge peaks were detected at the beginning of 2020 and 2021 in association with the COVID-19 waves. Conclusion: Our data are the first to describe data concerning vitD in our region. It reinforces the notion of vitD3 supplementation for some risk groups and also in healthy individuals. To prevent the winter decline, vitD3 supplementation should be started in September. This and the results during the COVID-19 pandemic highlight the importance of health education encouraging vitamin D3 supplementation.

Does maternal vitamin D status influence placental weight or vascular and inflammatory pathology? Secondary analysis from the Kellogg Pregnancy Study

IntroductionPositive effects of vitamin D (vitD) supplementation on comorbidities of pregnancy (COP) have been explored; however, few studies have elucidated the pathophysiology behind the development of these COP and the potential relationship with derangements in placental development and morphology. Additionally, it is known that placentas weighing 10th-90th % for gestational age are associated with better outcomes. Therefore, the objective of this study was to assess the impact of resulting circulating serum 25(OH)D concentrations associated with intake of high or low doses of supplementary vitD on placental development and morphology in women who participated in a randomized double blind, placebo-controlled trial of vitD supplementation. We hypothesized that if maternal serum 25(OH)D concentration (vitD status marker) is insufficient/deficient, then placental weight and % for gestational age (GA) will be smaller and will correlate with increased vascular and inflammatory placental pathologic findings. MethodsThe findings of the present study are a secondary analysis of data generated from a previously reported randomized controlled trial (RCT), the Kellogg Vitamin D Pregnancy Study. Pregnant women (n = 297) in this RCT (January 2013 - April 2018) were randomly assigned to 400 IU vs. 4400 IU vitD/day (10–14 weeks’ gestational age) and followed to delivery. 132 placentas were analyzed by pathologists blinded to treatment, and the 2016 Amsterdam Consensus Criteria were used to categorize grouping/grading of placental pathology and weight. Total [25(OH)D] was measured using radioimmunoassay (ng/mL). Chi-square and Student’s t-test were used to show the difference in maternal characteristics by treatment group and by placental weight. Chi-square analysis was used to determine differences between the percent pathology findings by treatment group. Students t-test was used to determine the differences in vitD status and the frequency of placental lesions. Association between [25(OH)D] area under the curve (AUC) and placental morphology were determined in a regression model that included maternal BMI ≥ 30 kg/m2, race/ethnicity, and vitD treatment group allocation. Data were analyzed using SAS v9.4 (Cary, NC) and statistical significance was indicated by p < 0.05. ResultsThe percent pathology findings by treatment group were not significantly different for each of the placental pathology categories as defined by the 2016 Amsterdam Consensus Criteria including placental weight. However, when using 25(OH)D as a biomarker for vitD status, linear regression model showed maternal serum [25(OH)D] AUC was significantly associated with greater placental weight (p = 0.023). Logistic regression models showed mothers with BMI ≥ 30 kg/m2 had larger placental weight (p = 0.046), and Hispanic and white/Caucasian mothers had greater placental weights than Black American mothers (p = 0.025). When placentas ≥ 90th % for GA, n = 7, were removed from the placental pool, Pearson correlation still showed a positive association between maternal serum 25(OH)D AUC and placental weight (p = 0.011). In a second linear regression model of placentas ≥ 90th % for GA (n = 7) vs. placentas < 90th % (n = 108), maternal serum 25(OH)D AUC was significantly greater in those placentas ≥ 90th % (p = 0.03); however, this was not associated with increased perinatal mortality. Conclusion findingssuggest increasing maternal serum [25(OH)D] via vitamin D supplementation during pregnancy did not adversely affect placental morphology; trends showed those in the treatment group had fewer placental lesions. Placental weight was found to be significantly associated with [25(OH)D] AUC, which represents maternal vitamin D status over the course of pregnancy; 7 placentas ≥ 90th % for GA were not associated with perinatal mortality.

Post Hoc Analysis of National Institute of Child Health and Human Development Vitamin-D Pregnancy Cohort and The Role of Functional Vitamin-D Deficiency in Pregnancy.

Our objective was to conduct a secondary, post hoc analysis of the National Institute of Child Health and Human Development (NICHD) vitamin D (vitD) pregnancy study by Hollis et al, which reported on the effect of vitD supplementation in pregnant women and determine the potential interaction between intact parathyroid hormone (iPTH) concentrations, vitD status, and various comorbidities associated with pregnancy. Women with low 25-hydroxy vitamin D (25(OH)D) concentrations and high iPTH concentrations during pregnancy, known as functional vitamin-D deficiency (FVDD), were more likely to acquire complications also affecting their neonates. This post hoc analysis of data collected from a diverse group of pregnant women participating in the NICHD vitD pregnancy study was applied to investigate the applicability of the concept of FVDD in pregnancy (Hemmingway, 2018) in identifying potential risks for certain comorbidities of pregnancy. This analysis defines FVDD as maternal serum 25(OH)D concentrations below 20 ng/mL and iPTH concentrations above 65 pg/mL creating a definitive ratio number, 0.308, to classify mothers as having FVDD prior to delivery (PTD). Statistical analyses were performed using SAS 9.4 (Cary, NC). In total, 281 women (85 African American, 115 Hispanic, and 81 Caucasian) with 25(OH)D and iPTH concentrations measured at monthly visits were included in this analysis. No statistically significant association was found between mothers classified as having FVDD at baseline or 1-month PTD and hypertensive disorders of pregnancy, infection, or admittance to the neonatal intensive care unit. When combining all comorbidities of pregnancy in this cohort, results showed those with FVDD at baseline, 24 weeks' gestation, and 1-month PTD were more likely to experience a comorbidity (p = 0.001; p = 0.001; p = 0.004, respectively). Those with FVDD 1-month PTD were 7.1 times (confidence interval [CI]: 1.71-29.81) more likely to have preterm birth (<37 weeks) than women without FVDD. Participants were more likely to have experienced preterm birth if they met the criteria for FVDD. This study supports the importance of FVDD during pregnancy. · Functional vitamin D deficiency (FVDD) is defined as the ratio of 25(OH)D divided by iPTH concentration ≤0.308.. · At a minimum, it is recommended that vitamin D status be kept in the healthy range based on current recommendations for pregnant individuals.. · FVDD is a more sensitive predictor of pregnancy risk than 25(OH)D alone.. · FVDD identified those with greater risk of preterm birth in this cohort..

P-332 Standard-dose Vitamin D supplementation as an effective and safe non-hormonal treatment for the prevention of uterine fibroid growth in reproductive-age women: A pilot study

Abstract Study question Could low-dose vitamin D supplementation prevent uterine fibroid growth in reproductive-age women with hypovitaminosis D? Summary answer Six-month low-dose Vitamin D supplementation (≈ 1500 IU/day) in patients with hypovitaminosis D significantly decrease uterine fibroid growth compared to patients not receiving supplementation. What is known already Uterine fibroids (UF) are the most common tumor of the reproductive tract, affecting up to 77% of reproductive-age women. Due to the association between hypovitaminosis D and UF, several studies have evaluated the effect of a high Vitamin D (VitD) dose (3500-8500 IU/day) on UF size, proposing VitD supplementation as a therapeutic option. However, the standard dose recommended for VitD deficiency (800-2000 IU/day) has not been assessed. We aimed to evaluate if the restoration of normal serum levels of 25(OH)D by standard VitD dose in patients with UF and hypovitaminosis D can avoid the growth of UF in reproductive-age women. Study design, size, duration Ambispective observational study carried out at La Fe University Hospital. In the study group, patients (n = 6) were prospectively recruited from 2019 to 2022. Clinical data from the control group (n = 14) was collected retrospectively from 2016 to 2018. The study was approved by the autonomous government ethics committee (CAEPO; Spain) (ISS-COL-2028-01). Participants/materials, setting, methods Twenty women under 45 years old with uterine fibroids and hypovitaminosis D [25(OH)D levels &amp;lt; 30 ng/mL] were included. The study group received VitD for 6 months (25000 IU/2 weeks). Study outcomes: UF size determined by ultrasound, serum levels of 25(OH)D, Calcium, AST, ALT, Bilirubin and Creatinine were determined at 0, 3 and 6 months. Data from control group was obtained retrospectively from patients diagnosed with UF and hypovitaminosis D without VitD supplementation. Main results and the role of chance At the beginning of the treatment, no significant differences were found between patients included in the control and VitD group regarding age (40.57 ± 2.76 vs. 38.73 ± 4.92), BMI (23.6 5 ± 2.96 vs. 25.36 ± 4.25), VitD levels (18.57 ± 7.47 vs. 23.37 ± 37.29) and UF size (67.07 ± 20.68 vs. 56.17 ± 12.56). After treatment, VitD levels significantly increased in the study group (23.37 ± 37.29 vs. 37.02 ± 6.35, p = 0.001). Regarding size, the control group showed a significant UF growth of 17.3 ± 14.31% (p = 0.0005) after 6 months, while in patients treated with VitD UF size slightly decreased (-5.84 ± 2.14 %, p = 0.15). In addition, when comparing % of UF growth in both groups at the end of the treatment, UF growth was significantly lower in patients treated with VitD compared to control (-5.84% vs. 17.3%, p = 0.0002). There were no significant changes in serum parameters analyzed in the study group after 6 months of VitD supplementation: Calcium (9.15 vs. 9.20 mg/dL), AST (15.83 vs. 13 U/L), ALT (17.83 vs. 16 U/L), Bilirubin (0.42 vs. 0.48 mg/dL) and Creatinine (0.69 vs. 0.67 mg/dL). Limitations, reasons for caution This is an observational study and thus possible confounders cannot be completely excluded. More data are needed to draw firm conclusions and it will be critical to increase the sample size to check if the results observed in this work remain in the general population. Wider implications of the findings To our knowledge, this is the first study evaluating the effect of standard VitD dose on UF growth in reproductive-age women with hypovitaminosis D. Our results suggest that low-dose VitD could be a safe non-hormonal therapeutic option in the management of UF in patients willing to preserve their fertility. Trial registration number NCT03991078

Vitamin D Status, Cdx2 Genotype, and Colorectal Cancer Survival: Population-Based Patient Cohort.

According to recent evidence, the prognostic value of Vitamin D (VitD) status for colorectal cancer (CRC) patients might be confined to patients with the GG genotype of Cdx2, a functional polymorphism of the VitD receptor gene. We aimed to validate these findings in a cohort of CRC patients. Post-operative serum 25-hydroxyvitamin D concentration was determined by mass spectrometry and Cdx2 genotyping was performed from blood or buccal swabs using standard methods. Joint associations of VitD status and Cdx2 with overall survival (OS), CRC-specific survival (CSS), recurrence-free survival (RFS), and disease-free survival (DFS) were assessed using Cox regression. For patients with GG genotype, adjusted hazard ratios (95% confidence interval) for the associations of sufficient compared with deficient VitD were 0.63 (0.50-0.78), 0.68 (0.50-0.90), 0.66 (0.51-0.86), and 0.62 (0.50-0.77) for OS, CSS, RFS, and DFS, respectively. These associations were weaker and not statistically significant for the AA/AG genotype. Interaction between VitD status and genotype did not reach statistical significance. VitD deficiency is an independent predictor of poorer survival, particularly for the GG Cdx2 carriers, suggesting a potential role of VitD supplementation according to VitD status and genotype, which should be evaluated in randomised trials.

The Possible Influence of Vitamin D Levels on the Development of Atrial Fibrillation-An Update.

Atrial fibrillation (AF) is a severe and most common supraventricular arrhythmia in humans, which, if left untreated or treated ineffectively, can lead to ischemic stroke or heart failure. It has been suggested that serum vitamin D (VitD) deficiency may be one of the critical factors influencing the onset of AF, especially in the period after cardiac surgery, such as coronary artery bypass grafting. Several papers have indicated that VitD supplementation reduces the risk of AF, significantly reducing the proportion of patients between the control and study groups in both the pre- and postoperative periods. Factors that increase the risk of AF from VitD deficiency are also further indicated, and these are age, gender, weight, season or comorbidities. In addition, the cardiodepressive mechanism of VitD is not fully understood; however, it is suggested that it acts through at least two pathways. The first indicates a direct effect of VitD on atrial muscle degradation, while the second is related to the modulation of cardiovascular depression factors. Despite many reports showing correlations between no VitD concentrations on the development of AF, this topic is still widely debated and the results from these papers are still subject to doubt. Therefore, this review aims at describing in detail the problem of correlation between VitD deficiency and the development of AF associated mainly with the postoperative period, i.e., after cardiac surgery, especially pathogenesis, and results of this correlation, taking into account recent studies, limitations and future perspectives. Due to the fact that this is still a topical problem, we believe that the collection of the latest reports and a detailed description of the problem is most appropriate in this case.