IU Vitamin D3 Research Articles

Plasma parathyroid hormone response to vitamin D3 supplementation among women of reproductive age: A randomized double-blind placebo-control trial

While vitamin D inadequacy occurs worldwide, there is a lack of consensus internationally on the optimum plasma levels of 25(OH)D to maximally suppress the level of parathyroid hormone toward reducing bone loss. This study aimed to investigate the response of intact parathyroid hormone (iPTH) to vitamin D3 supplementation among Malaysian women of reproductive age in a randomised double-blind placebo-control trial [NMRR-15-479-25680]. A total of 106 women who fulfilled the study inclusion criteria were randomly assigned to receive daily one of these three supplement doses (i) 600 IU vitamin D3 + 500 mg calcium; (ii) 1200 IU vitamin D3 + 500 mg calcium; or (iii) 4000 IU vitamin D3 + 500 mg calcium. The placebo group received daily 500 mg calcium. The outcome examined was change in plasma iPTH concentration in response to daily vitamin D3 supplementation for 16 weeks. Fasting blood sample was obtained at baseline and post-supplementation. A total of 78 subjects (73.6%) completed the intervention. None of the supplementation groups brought about any detectable suppression of iPTH concentration post-supplementation. Vitamin D3 supplementation resulted in overall increase in plasma 25(OH)D levels, but only the 4000 IU/day group showed a significant dose effect post-supplementation (mean 49.7 ± 26.5 nmol/L) compared to placebo (29.3 ± 13.3 nmol/L). The lack of iPTH suppression is attributed to high prevalence of vitamin D insufficiency at baseline and the supplementation regimen was inadequate to raise the 25(OH)D level to cause PTH suppression. Inadequate calcium intake of the participants was also a likely contributing factor to the result. As prolonged vitamin D insufficiency and hypocalcaemia could lead to a compensatory rise in PTH resulting in accelerated bone loss, as well as posing increasing risks of non-skeletal morbidities, further clinical trials with an adequately powered sample size should be undertaken over an appropriate study duration to verify the results obtained in this study.

The effect of Ni gella sativa and vitamin D3 supplementation on the clinical outcome in COVID-19 patients: A randomized controlled clinical trial.

Background: The coronavirus disease 2019 (COVID-19) is a novel coronavirus that causes severe infection in the respiratory system. Since the immune status plays an essential role in combating COVID-19, herbal medicines, which have an immunomodulatory effect, may help prevent and even treat COVID-19. Nigella sativa is one of the herbal medicines with antiviral and immunomodulatory activities, and its therapeutic effectiveness makes it a promising add-on therapy for COVID-19. In addition, vitamin D3 has an immunomodulatory role, but the effect of therapeutic vitamin D3 supplementation in SARS-CoV-2 infection is still not well-known. Objective: This study aims to investigate the effects of Nigella sativa and vitamin D3 as single supplemental therapies and in combination on viral clearance indicated by a negative polymerase chain reaction and the alleviation of symptoms during the study follow-up duration of 14days. Patients and Methods: The study design was an open-label randomized controlled clinical trial conducted at the Respiratory Hospital at the Kobry El Qobba Armed Forces Medical Complex. In total, 120 COVID-19 patients with mild to moderate symptoms were randomly assigned to four groups, with thirty patients each, as follows: Group 1 received an oral dose of 900mg Nigella sativa through 450mg soft gelatin capsules twice daily for two weeks; Group 2 received 2,000 IU of vitamin D3 through 1000-IU tablets given as two tablets, once daily; Group 3 received 900mg of Nigella sativa and 2,000 IU of vitamin D3 in the same manner of dosing as in the previous groups; and Group 4 was the control group. All groups received standard therapy for COVID-19 infections and clinical management of COVID-19's clinical symptoms. Results: The Nigella sativa-vitamin D3 combination in addition to the standard therapy for COVID-19 infections significantly contributed to the alleviation of most COVID-19 symptoms: 50% of patients were free of cough after 7days, 70% showed an absence of fatigue after 4days, 80% had no headache after 5days, 90% were free of rhinorrhea after 7days, and 86.7% of the patients had no dyspnea after 7days. Moreover, patients in the four studied groups showed a reduced median temperature after 3days of treatment. Negative results of the polymerase chain reaction (PCR) test recorded on the 7th and 14thday of therapy were superior in the Nigella sativa and vitamin D3 combination arm compared to those of the other studied arms where the value of the odds ratio (OR) on the 7thday was 0.13 with 95% CI: 0.03-0.45 and that of the 14th day was 0.09 with 95% CI: 0.02-0.3. Conclusion: The results of this study showed a promising therapeutic benefit of the administration of Nigella sativa and vitamin D3 combination in COVID-19 patients with mild to moderate symptoms. Additionally, the remarkable viral clearance in a short time interval and reduction in the severity and progression of symptoms recommended the use of this combination as an add-on therapy for the management of COVID-19 patients. Clinical Trial Registration: ClinicalTrials.gov, Identifier: NCT04981743.

An open-label, randomized, crossover study to evaluate the bioavailability of nanoemulsion versus conventional fat-soluble formulation of cholecalciferol in healthy participants

BackgroundNanoemulsion preparations of cholecalciferol available in the market claim to have better bioavailability than the conventional fat-soluble cholecalciferol. However, limited data are available in humans for such preparations. We, therefore, compared the relative bioavailability of two formulations of 60,000 IU cholecalciferol (nanoemulsion oral solution, water-miscible vitamin D3 [test] vs soft gelatin capsules [reference]) in healthy adult participants. MethodsIn this randomized, open-label, two sequence, single-dose, two-way crossover study (CTRI/2018/05/013839), Indian participants aged 18–45 years received single dose of nanoemulsion and capsule formulations, under fasting conditions. Blood samples collected over 120 h were assessed to determine cholecalciferol concentrations. Pharmacokinetic parameters (area under the concentration-time curve up to 120 h [AUC0–120h], maximum observed drug concentration [Cmax], time to reach maximum drug concentration [Tmax], terminal half-life [T½el], and terminal elimination rate constant [Kel]) were estimated using baseline corrected data and analyzed using analysis of variance. ResultsAmong the 24 eligible participants, the relative bioavailability of nanoemulsion was significantly higher than the capsules by 36% (p = 0.0001) based on AUC0–120h. Similarly, Cmax of the nanoemulsion was significantly higher by 43% (p = 0.0001) than that of the capsules. The intra-participant variability for AUC0–120h and Cmax were 23.22% and 26.51%, respectively. The Tmax, T½el, and Kel were comparable for both the formulations. No adverse effects were noted with either of the two formulations. ConclusionsNanoemulsion oral solution of cholecalciferol showed a greater bioavailability compared with soft gelatin capsules, under fasting conditions, in healthy human participants.

Effect of vitamin D3 supplementation on cellular immunity and inflammatory markers in COVID-19 patients admitted to the ICU

Vitamin D as an immunomodulator has not been studied in patients with severe COVID-19. This study aimed to estimate the efficacy of vitamin D3 supplementation on cellular immunity and inflammatory markers in patients with COVID-19 admitted to the intensive care unit (ICU). A single-center, double-blind, randomized, placebo-controlled pilot trial was conducted (N = 110). Patients were randomly assigned to receive a weekly oral dose of 60,000 IU of vitamin D3 followed by daily maintenance doses of 5000 IU (n = 55) or placebo (n = 55). Primary outcomes were lymphocyte counts, natural killer (NK) and natural killer T (NKT) cell counts, neutrophil-to-lymphocyte ratio (NLR), and serum levels of inflammatory markers on 7th day of treatment. On day 7, patients in the vitamin D3 group displayed significantly higher NK and NKT cell counts and NLR than those in the placebo group did. The mortality rate (37% vs 50%, P = 0.16), need for mechanical ventilation (63% vs 69%, P = 0.58), incidence of nosocomial infection (60% vs 41%, P = 0.05) did not significantly differ between groups. Vitamin D3 supplementation, compared with placebo, significantly increased lymphocyte counts, but did not translate into reduced mortality in ICU.Trial Registration: ClinicalTrials.gov Identifier: NCT05092698.

ODP542 Challenging Management of Fasting Hypoglycemia in a Patient With Pancreatic Neuroendocrine Tumor and Lupus Nephritis

Abstract Background Derangements of calcium metabolism are common in patients with cancer.1 Unlike hypercalcemia which is well-recognized, little is known about hypocalcemia of malignancy.2 In fact, there were only 2 studies published to date that investigated its incidence among cancer patients. 2,3 Clinical Case: A 40-year-old male consulted an ENT specialist for a 2×2 cm left parotid mass of 3 years duration. There was no fever, cough, night sweats or significant weight loss. Histological analysis of the mass revealed parotid gland adenocarcinoma. Tumor metastases to lung and spine were seen on PET CT scan. Consequently, he received 18 cycles of chemotherapy and 10 sessions of radiotherapy without surgery because of the advanced stage. He initially exhibited good response with the treatment. A year after, he developed shortness of breath, numbness of hands with seizure episode. Chest x-ray showed pleural effusion and osteoblastic changes while cranial CT scan revealed brain metastasis. Bone scintigraphy was evident for multiple osseous metastases. He underwent stereotactic brain surgery, and thoracentesis with pleural fluid analysis consistent with malignancy. Biochemical tests were remarkable for hypocalcemia (0.99, n>1.12 mmol/L, normomagnesemia (0.89, n>0.74 mmol/L), low vitamin D (11.6, n>30 ng/mL), elevated phosphate (1.73; n: <1.49 mg/dL), and elevated intact PTH which eventually dropped (157.7 to 9, n>15 pg/mL). Ultrasound of the neck revealed diffuse thyroid calcifications. Despite oral calcium supplementation (14.4 grams elemental calcium), calcium infusion (1.35 mg/kg/hour elemental calcium) and vitamin D supplementation (6000 IU cholecalciferol and 0.5 mg calcitriol daily), he remained hypocalcemic. His condition eventually worsened, and he succumbed to death in due course despite aggressive measures provided. Conclusion To our knowledge, this is the first case illustrating the therapeutic challenge in addressing an intractable hypocalcemia in the setting of an advanced parotid carcinoma in our country.Reference: (1)Carl Blomqvist. A Hospital Survey of Hypocalcemia in Patients with Malignant Disease. Acta Med Scand. 1986;220. (2) Schattner et al. Hypocalcaemia of Malignancy. The Netherlands Journal of Medicine. July 2016, Vol. 74, No. 6. (3) Goncalves. Hypocalcemia in cancer patients: An exploratory Study. Porto Biomed. J. (2019) 4: 4 Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.

ODP652 Challenges in the Management of Hypocalcemia in a Patient with Advanced Stage of Parotid Gland Adenocarcinoma

Abstract Background Derangements of calcium metabolism are common in patients with cancer. 1 Unlike hypercalcemia which is well-recognized, little is known about hypocalcemia of malignancy. 2 In fact, there were only 2 studies published to date that investigated its incidence among cancer patients. 2,3 Clinical Case: A 40-year-old male consulted an ENT specialist for a 2×2 cm left parotid mass of 3 years duration. There was no fever, cough, night sweats or significant weight loss. Histological analysis of the mass revealed parotid gland adenocarcinoma. Tumor metastases to lung and spine were seen on PET CT scan. Consequently, he received 18 cycles of chemotherapy and 10 sessions of radiotherapy without surgery because of the advanced stage. He initially exhibited good response with the treatment. A year after,he developed shortness of breath, numbness of hands with seizure episode. Chest x-ray showed pleural effusion and osteoblastic changes while cranial CT scan revealed brain metastasis. Bone scintigraphywas evident for multiple osseous metastases. He underwent stereotactic brain surgery, and thoracentesis with pleural fluid analysis consistent with malignancy. Biochemical tests were remarkable for hypocalcemia (0.99, n>1.12 mmol/L, normomagnesemia (0.89, n>0.74 mmol/L), low vitamin D (11.6, n>30 ng/mL), elevated phosphate (1.73; n: <1.49 mg/dL), and elevated intact PTH which eventually dropped (157.7 to 9, n>15 pg/mL). Ultrasound of the neck revealed diffuse thyroid calcifications. Despite oral calcium supplementation (14.4 grams elemental calcium),calcium infusion (1.35 mg/kg/hour elemental calcium) and vitamin D supplementation (6000 IU cholecalciferol and 0.5 mg calcitriol daily), he remained hypocalcemic. His condition eventually worsened, and he succumbed to death in due course despite aggressive measures provided. Conclusion To our knowledge, this is the first case illustrating the therapeutic challenge in addressing an intractable hypocalcemia in the setting of an advanced parotid carcinoma inour country. Reference: (1)Carl Blomqvist. A Hospital Survey of Hypocalcemia in Patients with Malignant Disease. Acta Med Scand. 1986;220. (2) Schattner et al. Hypocalcaemia of Malignancy. The Netherlands Journal of Medicine. July 2016, Vol. 74, No. 6. (3) Goncalves. Hypocalcemia in cancer patients: An exploratory Study. Porto Biomed. J. (2019) 4: 4 Presentation: No date and time listed

A Single Oral Vitamin D3 Bolus Reduces Inflammatory Markers in Healthy Saudi Males.

Vitamin D deficiency has increased in the general population and is a public health issue. Vitamin D plays an important role in regulating the immune system, e.g., by modulating the production of inflammatory cytokines. In most countries, the recommended maximal daily dose of vitamin D3 is 4000 IU (100 µg) per day. In this study, we investigated whether a single vitamin D3 bolus can reduce the levels of the inflammatory markers interleukin (IL) 6, IL8 and tumor necrosis factor (TNF) within one month. Fifty healthy Saudi males were recruited from the local community in Jeddah city and were orally supplemented with a single dose of 80,000 IU vitamin D3. Serum samples were collected at time points 0, 1 and 30 days, and serum levels of IL6, IL8 and TNF, parathyroid hormone (PTH), 25-hydroxyvitamin D3 (25(OH)D3), triglycerides, cholesterol, calcium (Ca2+) and phosphate (PO4−) were determined. On average, the vitamin D3 bolus resulted in a significant increase in vitamin D status as well as in a significant decrease in the levels of inflammatory cytokines even one month after supplementation without changing serum Ca2+, PO4− or lipid levels. In conclusion, single high-dose vitamin D3 supplementation is safe for reducing inflammation markers and may lead to an update of current recommendations for vitamin D intake, in order to prevent critical health problems.

Dietary Supplementation of 25-Hydroxyvitamin D3 Improves Growth Performance, Antioxidant Capacity and Immune Function in Weaned Piglets.

This study was conducted to evaluate the effects of 25-hydroxyvitamin D3 (25(OH)VD3) and Vitamin D3 (VD3) supplemented in the diet of weaned piglets on their growth performance, bone quality, intestinal integrity, immune function and antioxidant capacity. A total of 192 weaned piglets were allocated into four groups and they were fed a control diet containing 2000 IU VD3 (negative control, NC), NC + 100 ppm colistin sulfate (positive control, PC), NC + 2000 IU VD3 (VD3) and NC + 2000 IU 25(OH)VD3 (25(OH)VD3). The results showed that 25(OH)VD3 improved the growth performance, bone quality and antioxidase activity of piglets compared with the other groups. Meanwhile, 25(OH)VD3 up-regulated ileal mRNA expressions of tight junction proteins and host defense peptides. The VD3 group had an increased intestinal sIgA content and mRNA expression of pBD-1 compared with the NC group. Both groups of VD3 and 25(OH)VD3 altered the microbial β-diversity compared with the NC group, and 25(OH)VD3 increased ileal concentrations of acetate and butyrate. In conclusion, our findings indicated that a regular dosage of 2000 IU VD3 in the weaned piglets’ diet did not achieve optimal antioxidant capacity and immune function. 25(OH)VD3 had better growth performance than VD3 at the same inclusion level, which is associated with the improved intestinal integrity and antioxidant capacity.

The use of vitamin D for patients with inflammatory bowel diseases.

As vitamin D (VD) plays an essential role in inflammatory bowel diseases (IBD), this systematic review aimed to update the participation of this vitamin in the prevention or remission of these diseases. This review has included studies in MEDLINE-PubMed, EMBASE, and Cochrane databases. The authors have followed PRISMA (Preferred Reporting Items for a Systematic Review and Meta-analysis) guidelines. According to the inclusion and exclusion criteria, twenty-two randomized clinical trials were selected. In total, 1,209 patients were included in this systematic review: 1034 received only VD and 175 received VD in combination with calcium. The average doses of VD supplementation were from oral 400IU daily to 10,000IU per kilogram of body weight. Single injection of 300,000IU of VD was also used. Several studies have shown the crucial role that VD plays in the therapeutic approach of IBD due to its effects on the immune system. It effectively decreased inflammatory cytokines such as TNF-α and IFN-γ (p<0.05) and provided a reduction in disease activity assessed through different scores such as Crohn's Disease Activity Index (CDAI) (p<0.05) and Ulcerative Colitis Disease Activity Index (UCDAI) (p<0.05). Unfortunately, the available clinical trials are not standardized for of doses and routes of administration. Existing meta-analyses are biased because they compare studies using different doses or treatments in combination with different drugs or supplements such as calcium. Even though VD has crucial effects on inflammatory processes, there is still a need for standardized studies to establish how the supplementation should be performed and the doses to be administered.

Vitamin D modulates systemic inflammation in patients with severe COVID-19

AimsThe ability of vitamin D (VitD) to modulate immune responses in the clinical setting of COVID-19 infection is not well investigated. This study aimed to evaluate the ability of VitD to attenuate inflammatory responses in patients with severe COVID-19. Materials and methodsBlood samples and nasopharyngeal swabs were obtained from patients with severe COVID-19 who had been treated (20 patients), or not (25 patients), with VitD, during their stay in the intensive care unit. Western blotting was used to evaluate the expressions of STAT3, JNK and AKT signaling pathways and ELISA was used to measure levels of IL-6, IL-17, and IL-1β in blood of these patients. Key findingsReduced levels of STAT3, JNK and AKT pathways and lower levels of proinflammatory cytokines such as IL-6, IL-17, and IL-1β were observed in VitD treated patients (50,000 IU of cholecalciferol weekly for 3 weeks), and in vitro following treatment of poly I:C stimulated PBMCs with VitD (50 nM of calcitriol). Moreover, lower circulatory levels of these proinflammatory cytokines following treatment with VitD were associated with lower serum levels of COVID-19-related severity markers such as D-dimer and C-reactive proteins (P < 0.001) which in overall resulted in shorter length of ICU stay for VitD treated compared to untreated patients (18 days for VitD treated vs. 28 days for VitD untreated; P = 0.01). SignificanceThis study reveals that VitD plays immunomodulatory role during COVID-19 infection, which further emphasizes the importance of maintaining a normal level of this vitamin for the prevention of hyperinflammatory conditions associated with COVID-19.

The Impact of Vitamin D Supplementation on the IFNγ-IP10 Axis in Women with Hashimoto's Thyroiditis Treated with Levothyroxine: A Double-blind Randomized Placebo-controlled Trial.

Hashimoto's thyroiditis (HT) results from chemoattraction of inflammatory cells toward the thyroid gland by inducing the production of interferon-gamma (IFNγ)-induced protein 10 (IP10) by T helper (Th) 1 cells. Vitamin D may suppress the IFNγ-IP10 axis, but this new function of vitamin D has not yet been investigated in HT patients. In an intervention and control group, patients received 50000 IU cholecalciferol or placebo every week for three months, respectively. The CD4+ T cells of 40 patients were isolated, and the mRNA expression levels of vitamin D receptor (VDR), peroxisome proliferator-activated receptors (PPAR)-α, and PPAR-γ genes were determined by real-time PCR. ELISA method was used to determine serum levels of vitamin D, tumor necrosis factor-alpha (TNF-α), IFN-γ, and IP10. Vitamin D levels in the intervention group were significantly higher than in the placebo group after supplementation. PPAR-α and PPAR-γ gene expression levels did not differ significantly between the two groups. The serumlevels of IP10, IFNγ, and TNF-α decreased significantly in the vitamin D group, as well as in the placebo group. During this study, vitamin D levels significantly increased in the intervention group and inflammatory factors decreased. Based on the similar results obtained in the placebo group, further studies with larger sample sizes and longer intervention times are recommended.

High Prevalence of Hypovitaminosis D in Cutaneous and Systemic Lupus Erythematosus Patients and Its Associated Factors: A Cross-Sectional Study in Thailand.

ObjectiveTo investigate the prevalence of low vitamin D levels in patients with cutaneous lupus erythematosus (CLE) and systemic lupus erythematosus (SLE) in Thailand and determine the influential factors associated with inadequate levels.MethodsThe medical records of patients diagnosed with SLE and/or CLE and evaluated for serum 25-OH vitamin D were retrospectively reviewed from January 2014 to January 2021. Vitamin D deficiency (<20 ng/mL) and insufficiency (21–29 ng/mL) were indicated, and predictors of hypovitaminosis D were identified by multiple linear regression analysis.ResultsIn total, 414 patients with SLE and/or CLE were included in the study. Vitamin D deficiency was predominant in the CLE-only group (33.3%), followed by SLE without CLE (15.6%) and SLE with CLE (8%), p < 0.001. Likewise, vitamin D insufficiency was more prevalent in the CLE-only group (44.4%) compared to SLE with (35.8%) and without CLE (40%). Multivariate analysis showed that a higher SLEDAI-2K score and female sex had a negative association with vitamin D levels, while an intake of every 10,000 IU of vitamin D2 per week increased serum vitamin D levels by up to 2.37 ng/mL. Furthermore, forty-five percent of patients continued to have vitamin D depletion despite commencing the recommended doses of vitamin D replacement.ConclusionApproximately half of Thai patients with SLE and 80% of CLE had vitamin D inadequacy. Vitamin D replacement is a good predictor of high serum vitamin D levels, while lower serum levels were associated with higher disease severity. Therefore, serum vitamin D monitoring and supplementation are suggested for all lupus erythematosus cases, especially those with CLE.

Cholecalciferol Supplementation Does Not Affect the Risk of HIV Progression, Viral Suppression, Comorbidities, Weight Loss, and Depression among Tanzanian Adults Initiating Antiretroviral Therapy: Secondary Outcomes of a Randomized Trial

BackgroundObservational studies suggest that blood concentrations of 25-hydroxyvitamin D [25(OH)D] are associated with morbidity, viral suppression, and mortality among adults living with HIV. ObjectivesWe evaluated the effect of cholecalciferol (vitamin D3) supplementation on the risk of HIV disease progression, HIV-1 viral suppression, comorbidities, weight change, and depression among HIV-infected individuals that were initiating antiretroviral therapy (ART) in Dar es Salaam, Tanzania. MethodsWe conducted a randomized, double-blind, placebo-controlled trial of vitamin D3 supplementation among 4000 HIV-infected adult men and nonpregnant women initiating ART with insufficient serum 25(OH)D concentrations (<30 ng/mL). Participants were randomly assigned to receive either weekly 50,000-IU doses for 4 wk followed by daily 2000 IU vitamin D3 until 1 y or a matching placebo regimen given in weekly followed by daily doses until 1 y. Participants were followed up at weekly visits for the first month followed by monthly visits thereafter. We conducted intent-to-treat analyses to assess the effect of vitamin D3 supplementation on the secondary trial outcomes of HIV progression or death, viral suppression, comorbidities, change in BMI, >10% weight loss, incident wasting, and depression. ResultsDuring follow-up, 345 participants (17.2%) in the vitamin D3 group and 371 participants (18.6%) in the placebo group experienced HIV disease progression or death and there was no difference in risk between groups (RR: 0.91; 95% CI: 0.79, 1.06). Vitamin D3 supplementation did not affect the risk of an unsuppressed HIV-1 viral load (>1000 copies/mL) after 6 mo (RR: 1.10; 95% CI: 0.87, 1.41) and there was also no effect on change in BMI, risk of >10% weight loss, wasting, comorbidities, and depression (P values >0.05). ConclusionsVitamin D supplementation did not affect the risk of HIV progression, viral suppression, common morbidities, weight-related indicators, or depression among adults initiating ART in Tanzania.This trial was registered at clinicaltrials.gov as NCT01798680.

Evaluation of the safety, tolerability and plasma vitamin D response to long-term use of patented transdermal vitamin D patches in healthy adults: a randomised parallel pilot study

BackgroundVitamin D delivered transdermally may suppress hyperactivity in nociceptor pain receptors and alter pain intensity, offering a useful addition to localised pain management in varying clinical settings. Currently, little is...

Rapidly Increasing Serum 25(OH)D Boosts the Immune System, against Infections-Sepsis and COVID-19.

Vitamin D deficiency is a global public health problem, a pandemic that commonly affects the elderly and those with comorbidities such as obesity, diabetes, hypertension, respiratory disorders, recurrent infections, immune deficiency, and malignancies, as well as ethnic minorities living in temperate countries. The same groups were worst affected by COVID-19. Since vitamin D deficiency weakens the immune system, it increases the risk of infections, complications, and deaths, such as from sepsis and COVID-19. Deficiency can be remedied cost-effectively through targeted food fortification, supplementation, and/or daily safe sun exposure. Its endocrine functions are limited to mineral metabolism, musculoskeletal systems, specific cell membrane interactions, and parathyroid gland functions. Except for the rapid, endocrine, and cell membrane-based non-genomic functions, all other biological and physiological activities of vitamin D depend on the adequate intracellular synthesis of 1,25(OH)2D (calcitriol) in peripheral target cells via the genome. Calcitriol mediates autocrine (intracrine) and paracrine signalling in immune cells, which provides broader, protective immune functions crucial to overcoming infections. The synthesis of 1,25(OH)2D (calcitriol) in peripheral target cells is dependent on diffusion and endocytosis of D3 and 25(OH)D from the circulation into them, which requires maintenance of serum 25(OH)D concentration above 50 ng/mL. Therefore, in acute infections such as sepsis and respiratory infections like COVID-19, it is necessary to rapidly provide its precursors, D3 and 25(OH)D, through the circulation to generate adequate intracellular calcitriol. Immune defence is one of the crucial non-hormonal functions of vitamin D. A single oral (bolus) dose or divided upfront loading doses between 100,000 and 500,000 IU, using 50,000 IU vitamin D3 increase the serum 25(OH)D concentrations to a therapeutic level of above 50 ng/mL that lasts between two to three months. This takes three to five days to raise serum 25(OH)D. In contrast, a single oral dose of calcifediol (0.014 mg/kg body weight) can generate the needed 25(OH)D concentration within four hours. Considering both D3 and 25(OH)D enter immune cells for generating calcitriol, using the combination of D3 (medium-term) and calcifediol (immediate) is cost-effective and leads to the best clinical outcome. To maximise protection against infections, particularly to reduce COVID-19-associated complications and deaths, healthcare workers should advise patients on safe sun exposure, adequate vitamin D supplementation and balanced diets containing zinc, magnesium, and other micronutrients to support the immune system. Meanwhile, governments, the World Health Organisation, the Centers for Disease Control, and governments should consider similar recommendations to physicians and the public, change the outdated vitamin D and other micronutrient recommendations directed to their population, and organise targetted food fortification programs for the vulnerable groups. This article discusses a rational approach to maintaining a sustained serum 25(OH)D concentration above 50 ng/mL, necessary to attain a robust immune system for overcoming infections. Such would cost-effectively improve the population’s health and reduce healthcare costs. It also describes three cost-effective, straightforward protocols for achieving and sustaining therapeutic serum 25(OH)D concentrations above 50 ng/mL (>125 nmol/L) to keep the population healthy, reduce absenteeism, improve productivity, and lower healthcare costs.

Effect of Cholecalciferol Supplementation on the Clinical Features and Inflammatory Markers in Hospitalized COVID-19 Patients: A Randomized, Open-Label, Single-Center Study.

Recent studies showed that a low 25-hydroxyvitamin D (25(OH)D) level was associated with a higher risk of morbidity and severe course of COVID-19. Our study aimed to evaluate the effects of cholecalciferol supplementation on the clinical features and inflammatory markers in patients with COVID-19. A serum 25(OH)D level was determined in 311 COVID-19 patients. Among them, 129 patients were then randomized into two groups with similar concomitant medication. Group I (n = 56) received a bolus of cholecalciferol at a dose of 50,000 IU on the first and the eighth days of hospitalization. Patients from Group II (n = 54) did not receive the supplementation. We found significant differences between groups with the preferential increase in serum 25(OH)D level and Δ 25(OH)D in Group I on the ninth day of hospitalization (p < 0.001). The serum 25(OH)D level on the ninth day was negatively associated with the number of bed days (r = −0.23, p = 0.006); we did not observe other clinical benefits in patients receiving an oral bolus of cholecalciferol. Moreover, in Group I, neutrophil and lymphocyte counts were significantly higher (p = 0.04; p = 0.02), while the C-reactive protein level was significantly lower on the ninth day of hospitalization (p = 0.02). Patients with supplementation of 100,000 IU of cholecalciferol, compared to those without supplementation, showed a decrease in the frequencies of CD38++CD27 transitional and CD27−CD38+ mature naive B cells (p = 0.006 and p = 0.02) and an increase in the level of CD27−CD38− DN B cells (p = 0.02). Thus, the rise in serum 25(OH)D level caused by vitamin D supplementation in vitamin D insufficient and deficient patients may positively affect immune status and hence the course of COVID-19.

Can the Combination of Rehabilitation and Vitamin D Supplementation Improve Fibromyalgia Symptoms at All Ages?

Several studies have indicated a correlation between vitamin D deficiency and widespread chronic pain syndromes, such as fibromyalgia. During this study, the effect of supplementation with vitamin D in association with physical exercise in patients with fibromyalgia was evaluated, in terms of improvement of pain, functional capacity and quality of life, also evaluating the presence of any differences in age. A single-center, observational, comparative study was conducted in 80 fibromyalgia patients. They are randomized into 2 groups: Group A, consisting of patients ≤50 years; and group B, consisting of patients >50 years. Both received weekly supplementation with 50,000 IU cholecalciferol for 3 months in association with a rehabilitation protocol. Patients were assessed at enrollment (T0), 3 months (T1), and 6 months (T2) from the initial assessment with blood vitamin D dosage and administration of rating scales (NRS, FIQ, and SF-12). From the comparison between the two groups, we have seen that in young people, supplementation with high-dose vitamin D improves short-term musculoskeletal pain and long-term functional capacity. Conversely, musculoskeletal pain and long-term quality of life improve in the elderly. Supplementing with high doses of vitamin D in fibromyalgia patients improves the quality of life and pain in the elderly and also the functional capacity in the young.

Plasma renin, aldosterone, and urinary prostaglandin E2 levels in children with hypocalcemia due to vitamin D deficiency rickets

We investigated the effect of hypocalcemia on plasma renin, aldosterone, and urine PGE2 levels in children with vitamin D deficiency rickets (VDDR). In the study group, 25 patients with VDDR-induced hypocalcemia were treated with a single dose of 150,000–300,000 IU cholecalciferol and 50 mg/kg/day elemental Ca for 10 days. On any day between 21th and 30th days after the treatment, the patients’ clinical, biochemical and radiologic findings were re-evaluated. The healthy children with the same sex and similar age as the study group comprised the control group. Plasma sodium (Na), potassium (K), calcium (Ca), phosphorus (P), alkaline phosphatase (ALP), parathyroid hormone (PTH), 25- hydroxy vitamin D (25OHD), renin, aldosterone; and urinary Ca, creatinine (Cr) and prostaglandin E2 (PGE2) levels were measured in both the study (pre-treatment and post-treatment) and the control group. Plasma Ca, P, 25OHD and renin levels and urinary PGE2/Cr ratio in the post-treatment group were significantly higher than those in the pre-treatment group while K, ALP, and PTH concentrations were significantly lower. Plasma ALP and PTH levels in pre-treatment group were significantly higher than in the control group while Ca, P, 25OHD, aldosterone and renin concentrations and urinary PGE2/Cr ratio were significantly lower. Post-treatment plasma Ca level was significantly decreased in normal limits compared to the control group while other biochemical parameters were not different from the control group. Plasma Ca concentration was positively correlated with renin level and urinary PGE2/Cr ratio. The findings suggest that hypocalcemia may inhibit the production of renin, aldosterone and PGE2 and a blunt aldosterone secretion may develop even after recovery from hypocalcemia.

Vitamin D Supplementation and Muscle Strength and Bone Health Outcomes: A Phase 3 Randomized Trial in 8,851 Schoolchildren

ObjectivesTo determine the effects of vitamin D supplementation on muscle strength and bone health in vitamin D-deficient schoolchildren. MethodsWe performed a phase 3 randomized placebo-controlled clinical trial in Ulaanbaatar, Mongolia, to determine whether weekly oral supplementation with 14,000 IU vitamin D3, administered for 3 years in 8,851 schoolchildren aged 6 to 13 years. We evaluated effects of the intervention on bone mineral density (BMD) (n = 1,465), physical fitness (n = 615), long jump (n = 8,850), grip strength (n = 8,850) and incidence of fracture (n = 8,850). Analyses were conducted for all efficacy outcomes to determine whether the effect of the intervention varied according to baseline 25-hydroxyvitamin D levels and calcium intake. ResultsOf the 8,851 randomized participants, 95.6% had vitamin D deficiency (25[OH]D < 20 ng/mL) at baseline, and 91.7% completed the study. Mean end-study 25(OH)D levels were 29.8 vs. 9.7 ng/mL in children randomized to intervention vs. placebo (p < 0.001). Vitamin D supplementation did not reduce the incident fracture (P = 0.65), mean radial BMD z-score (P = 0.14), mean maximal oxygen consumption during a 20 meter shuttle run (VO2max, P = 0.22), mean grip strength (p = 0.77) and mean long jump distance (p = 0.23). Effects of the intervention did not differ according to baseline 25-hydroxyvitamin D levels (<10 ng/mL vs. ≥10 ng/mL) for any efficacy outcome studied in subset population. ConclusionsA weekly oral dose of 14,000 IU (3.5 mg) vitamin D3, administered for 3 years, was safe and effective in elevating 25-hydroxyvitamin D levels into the high physiological range in vitamin D-deficient schoolchildren, but it did not affect any efficacy outcome in muscle strength and bone health. Funding SourcesNational Institutes of Health, 1R01HL122624-01.

158-LB: Effect of Vitamin D Replacement on Glycemic Status and Pregnancy Outcomes in Vitamin D–Deficient Subjects with Gestational Diabetes Mellitus

Aims: To study the effect of Vitamin D replacement on glycaemic control and pregnancy outcomes in Gestational Diabetes Mellitus patient with Vitamin D deficiency. Methods: In this prospective, open-label interventional study 60 GDM subjects with Vitamin D deficiency were divided into 2 groups of 30 each, and the intervention group received 60,000 IU of cholecalciferol weekly for 6 weeks and then monthly for the duration of pregnancy. while the control group did not. Vitamin D status was re-assessed at 32 weeks of gestation for both groups. The glycaemic status was assessed using fasting plasma glucose and 1-hour and 2-hour postprandial glucose at 30 weeks of gestation and at time of delivery. Feto-maternal outcomes: Time of delivery (weeks of gestation) , method of delivery, pre-eclampsia, still-birth, neonatal hypoglycaemia, neonatal jaundice, birth weight, head circumference of the baby, APGAR score at 5 minutes in both groups were also assessed. Results: In the intervention group 87% (26 out of 30) of subjects had become vitamin D sufficient. None of the subjects in the control group had become vitamin D sufficient. Fasting Plasma Glucose was significantly lower in the intervention group as compared to the control group) at 30 weeks of gestation (99.57±18.12 vs. 107.90±17.53 mg/dl; p=0.039) and at time of delivery (98.53±15.41 vs. 104.47±18.71mg/dl; p=0.044) . Both 1 hour and 2-hour postprandial plasma glucose (136.81±20.29 vs. 152.58±16.76; p=0.004 and 118±22.10 vs. 132.64±18.48 mg/dl; p=0.017 respectively) values were also significantly lower in the intervention group at the time of delivery. Birth weight was significantly lower in the control group as compared to the intervention group (2348.13±388.965 vs. 2778.67±270.288 gm; p=0.034) . All other neonatal parameters were similar in the two groups. Two subjects in the control group had still-births. Conclusion: Correction of Vitamin D deficiency in GDM subjects may result in better control of their plasma glucose levels. Low Vitamin D levels in GDM subjects may be associated with lower birth weight. Disclosure A. Baidya: None. P. Gaikwad: None. N. Das: None. Y. Pathak: None. N. Sengupta: None. P. Sahana: None. S. Goswami: None. S. Tarenia: None. A. Banerjee: None. M. Chattopadhayay: None. D. Hathi: None.