Effectiveness of In-Hospital Cholecalciferol Use on Clinical Outcomes in Comorbid COVID-19 Patients: A Hypothesis-Generating Study

Little information is available on the beneficial effects of cholecalciferol treatment in comorbid patients hospitalized for COVID-19. The aim of this study was to retrospectively examine the clinical outcome of patients receiving in-hospital high-dose bolus cholecalciferol. Patients with a positive diagnosis of SARS-CoV-2 and overt COVID-19, hospitalized from 15 March to 20 April 2020, were considered. Based on clinical characteristics, they were supplemented (or not) with 400,000 IU bolus oral cholecalciferol (200,000 IU administered in two consecutive days) and the composite outcome (transfer to intensive care unit; ICU and/or death) was recorded. Ninety-one patients (aged 74 ± 13 years) with COVID-19 were included in this retrospective study. Fifty (54.9%) patients presented with two or more comorbid diseases. Based on the decision of the referring physician, 36 (39.6%) patients were treated with vitamin D. Receiver operating characteristic curve analysis revealed a significant predictive power of the four variables: (a) low (<50 nmol/L) 25(OH) vitamin D levels, (b) current cigarette smoking, (c) elevated D-dimer levels (d) and the presence of comorbid diseases, to explain the decision to administer vitamin D (area under the curve = 0.77, 95% CI: 0.67–0.87, p < 0.0001). Over the follow-up period (14 ± 10 days), 27 (29.7%) patients were transferred to the ICU and 22 (24.2%) died (16 prior to ICU and six in ICU). Overall, 43 (47.3%) patients experienced the combined endpoint of transfer to ICU and/or death. Logistic regression analyses revealed that the comorbidity burden significantly modified the effect of vitamin D treatment on the study outcome, both in crude (p = 0.033) and propensity score-adjusted analyses (p = 0.039), so the positive effect of high-dose cholecalciferol on the combined endpoint was significantly amplified with increasing comorbidity burden. This hypothesis-generating study warrants the formal evaluation (i.e., clinical trial) of the potential benefit that cholecalciferol can offer in these comorbid COVID-19 patients.

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How Much Vitamin D is Too Much? A Case Report and Review of the Literature

Endocrine Metabolic & Immune Disorders - Drug Targets ◽

10.2174/1871530320666201007152230 ◽

2020 ◽

Vol 20 ◽

Author(s):

Sara De Vincentis ◽

Antonino Russo ◽

Marta Milazzo ◽

Amedeo Lonardo ◽

Maria Cristina De Santis ◽

...

Keyword(s):

Vitamin D ◽

Kidney Injury ◽

Serum Levels ◽

Repeated Measurements ◽

High Dose ◽

Integrative Therapy ◽

Beneficial Effects ◽

Vitamin D Intoxication ◽

Vitamin D Levels ◽

D Values

Background: The beneficial effects of vitamin D, together with the high prevalence of vitamin D deficiency, have led to an expanding use of vitamin D analogues. While inappropriate consumption is a recognized cause of harm, definition of doses at which vitamin D becomes toxic remain elusive. Case presentation: A 56-year woman was admitted to our Hospital following a 3-week history of nausea, vomiting and muscle weakness. The patient had been assuming very high dose of cholecalciferol since 20 months (cumulative 78,000,000UI, mean daily 130,000UI), as indicated by a non-conventional protocol for multiple sclerosis. Before starting vitamin D integration, serum calcium and phosphorus levels were normal, while 25OH-vitamin D levels were very low (12.25 nmol/L). On admission, hypercalcemia (3.23 mmol/L) and acute kidney injury (eGFR 20 mL/min) were detected, associated with high concentrations of 25OH-vitamin D (920 nmol/L), confirming the suspicion of vitamin D intoxication. Vitamin D integration was stopped and, in a week, hypercalcemia normalized. It took about 6 months for renal function and 18 months for vitamin D values to go back to normal. Conclusions: This case confirms that vitamin D intoxication is possible albeit with a really high dose. The doses used in clinical practice are far lower than these and, therefore, intoxication rarely occurs even in those individuals whose baseline vitamin D serum levels have never been assessed. Repeated measurements of vitamin D are not necessary in patients under standard integrative therapy. However, patients and clinicians should be aware of the potential dangers of vitamin D overdose.

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Association of Vitamin D Status With Liver and Kidney Disease: A Systematic Review of Clinical Trials, and Cross-Sectional and Cohort Studies

International Journal for Vitamin and Nutrition Research ◽

10.1024/0300-9831/a000540 ◽

2019 ◽

pp. 1-13 ◽

Cited By ~ 2

Author(s):

Seyed Mostafa Parizadeh ◽

Majid Rezayi ◽

Reza Jafarzadeh-Esfehani ◽

Amir Avan ◽

Hamideh Ghazizadeh ◽

...

Keyword(s):

Vitamin D ◽

Kidney Disease ◽

Renal Disease ◽

Cohort Studies ◽

Cochrane Library ◽

Major Public Health Problem ◽

Vitamin D Status ◽

Cross Sectional ◽

Beneficial Effects ◽

Vitamin D Levels

Abstract. Background: Vitamin D deficiency (VDD) is a major public health problem. There are few comprehensive systematic reviews about the relationship between Vitamin D status and liver and renal disease in Iran. Methods: We systemically searched the following databases: Web of Science; PubMed; Cochrane Library; Scopus; Science Direct; Google Scholar and two Iranian databases (Scientific Information Database (SID) and IranMedex) up until November 2017 to identify all randomized control trials (RCTs), case control, cross-sectional and cohort studies investigating the association between vitamin D and any form of liver or kidney disease. Results: Vitamin D insufficiency, or deficiency (VDD), is highly prevalent in Iran, reports varying between 44.4% in Isfahan to 98% in Gorgan. There is also a high prevalence of VDD among patients with liver or kidney disease, and the administration of vitamin D supplements may have beneficial effects on lipid profile, blood glucose, liver function and fatty liver disease, and bone health. Low serum vitamin D levels are related with abnormalities in these laboratory and clinical parameters. Conclusion: VDD is prevalent in patients with chronic liver or renal disease in Iran. There appear to be several beneficial effects of vitamin D supplementation in vitamin D deficient patients with liver or kidney disease.

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A variant in CYP2R1 predicts circulating vitamin D levels after supplementation with high‐dose of vitamin D in healthy adolescent girls

Journal of Cellular Physiology ◽

10.1002/jcp.28083 ◽

2019 ◽

Vol 234 (8) ◽

pp. 13977-13983 ◽

Cited By ~ 1

Author(s):

Sayyed Saeid Khayyatzadeh ◽

Mehrane Mehramiz ◽

Habibollah Esmaeily ◽

Seyed Jamal Mirmousavi ◽

Leila Khajavi ◽

...

Keyword(s):

Vitamin D ◽

Adolescent Girls ◽

High Dose ◽

Healthy Adolescent ◽

Vitamin D Levels

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Vitamin D Status Impacts Genital Mucosal Immunity and Markers of HIV-1 Susceptibility in Women

Nutrients ◽

10.3390/nu12103176 ◽

2020 ◽

Vol 12 (10) ◽

pp. 3176

Author(s):

Sharon M. Anderson ◽

Andrea R. Thurman ◽

Neelima Chandra ◽

Suzanne S. Jackson ◽

Susana Asin ◽

...

Keyword(s):

Vitamin D ◽

Reproductive Tract ◽

Serum Vitamin ◽

Female Reproductive Tract ◽

High Dose ◽

Vitamin D Status ◽

Serum Vitamin D ◽

Vitamin D Levels ◽

Hiv 1

While vitamin D insufficiency is known to impact a multitude of health outcomes, including HIV-1, little is known about the role of vitamin D-mediated immune regulation in the female reproductive tract (FRT). We performed a pilot clinical study of 20 women with circulating 25(OH)D levels <62.5 nmol/L. Participants were randomized into either weekly or daily high-dose oral vitamin D supplementation groups. In addition to serum vitamin D levels, genital mucosal endpoints, including soluble mediators, immune cell populations, gene expression, and ex vivo HIV-1 infection, were assessed. While systemic vitamin D levels showed a significant increase following supplementation, these changes translated into modest effects on the cervicovaginal factors studied. Paradoxically, post-supplementation vitamin D levels were decreased in cervicovaginal fluids. Given the strong correlation between vitamin D status and HIV-1 infection and the widespread nature of vitamin D deficiency, further understanding of the role of vitamin D immunoregulation in the female reproductive tract is important.

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Vitamin D and Atherosclerotic Cardiovascular Disease

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2019-00194 ◽

2019 ◽

Vol 104 (9) ◽

pp. 4033-4050 ◽

Cited By ~ 6

Author(s):

Thomas F Hiemstra ◽

Kenneth Lim ◽

Ravi Thadhani ◽

JoAnn E Manson

Keyword(s):

Cardiovascular Disease ◽

Vitamin D ◽

General Population ◽

Vitamin D Deficiency ◽

Randomized Trials ◽

Cardiovascular Health ◽

Vitamin D Supplementation ◽

High Dose ◽

Atherosclerotic Cardiovascular Disease ◽

Vitamin D Levels

Abstract Context A large body of experimental and observational data has implicated vitamin D deficiency in the development of cardiovascular disease. However, evidence to support routine vitamin D supplementation to prevent or treat cardiovascular disease is lacking. Design and Results A comprehensive literature review was performed using PubMed and other literature search engines. Mounting epidemiological evidence and data from Mendelian randomization studies support a link between vitamin D deficiency and adverse cardiovascular health outcomes, but randomized trial evidence to support vitamin D supplementation is sparse. Current public health guidelines restrict vitamin D intake recommendations to the maintenance of bone health and prevention of fractures. Two recently published large trials (VITAL and ViDA) that assessed the role of moderate- to high-dose vitamin D supplementation as primary prevention for cardiovascular outcomes in the general population had null results, and previous randomized trials have also been generally negative. These findings from general population cohorts that are largely replete in vitamin D may not be applicable to chronic kidney disease (CKD) populations, in which the use of active (1α-hydroxylated) vitamin D compounds is prevalent, or to other high-risk populations. Additionally, recent trials in the CKD population, as well as trials using vitamin D analogs, have been limited. Conclusions Current randomized trials of vitamin D supplementation do not support benefits for cardiovascular health, but the evidence remains inconclusive. Additional randomized trials assessing larger numbers of participants with low baseline vitamin D levels, having longer follow-up periods, and testing higher vitamin D dosages are needed to guide clinical practice.

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Potential Beneficial Effects of Vitamin D in Coronary Artery Disease

Nutrients ◽

10.3390/nu12010099 ◽

2019 ◽

Vol 12 (1) ◽

pp. 99 ◽

Cited By ~ 2

Author(s):

Christian Legarth ◽

Daniela Grimm ◽

Marcus Krüger ◽

Manfred Infanger ◽

Markus Wehland

Keyword(s):

Coronary Artery Disease ◽

Vitamin D ◽

Coronary Artery ◽

Vitamin D Supplementation ◽

Diabetic Patients ◽

Inverse Association ◽

Bone Homeostasis ◽

Beneficial Effects ◽

Vitamin D Levels ◽

Artery Disease

Vitamin D plays a pivotal role in bone homeostasis and calcium metabolism. However, recent research has indicated additional beneficial effects of vitamin D on the cardiovascular system. This review aims to elucidate if vitamin D can be used as an add-on treatment in coronary artery disease (CAD). Large-scale epidemiological studies have found a significant inverse association between serum 25(OH)-vitamin D levels and the prevalence of essential hypertension. Likewise, epidemiological data have suggested plasma levels of vitamin D to be inversely correlated to cardiac injury after acute myocardial infarction (MI). Remarkably, in vitro trials have showed that vitamin D can actively suppress the intracellular NF-κB pathway to decrease CAD progression. This is suggested as a mechanistic link to explain how vitamin D may decrease vascular inflammation and atherosclerosis. A review of randomized controlled trials with vitamin D supplementation showed ambiguous results. This may partly be explained by heterogeneous study groups. It is suggested that subgroups of diabetic patients may benefit more from vitamin D supplementation. Moreover, some studies have indicated that calcitriol rather than cholecalciferol exerts more potent beneficial effects on atherosclerosis and CAD. Therefore, further studies are required to clarify these assumptions.

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Impact of high-dose statins on vitamin D levels and platelet function in patients with coronary artery disease

Thrombosis Research ◽

10.1016/j.thromres.2016.12.019 ◽

2017 ◽

Vol 150 ◽

pp. 90-95 ◽

Cited By ~ 11

Author(s):

Monica Verdoia ◽

Patrizia Pergolini ◽

Roberta Rolla ◽

Matteo Nardin ◽

Alon Schaffer ◽

...

Keyword(s):

Coronary Artery Disease ◽

Vitamin D ◽

Coronary Artery ◽

Platelet Function ◽

High Dose ◽

Vitamin D Levels ◽

Artery Disease

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Vitamin-D status and bone mineral density in asthmatic children on long-term inhaled corticosteroids

Karnataka Pediatric Journal ◽

10.25259/kpj_7_2020 ◽

2020 ◽

Vol 35 ◽

pp. 39-47

Author(s):

B. Thanuja ◽

M. R. Savitha

Keyword(s):

Bone Mineral Density ◽

Vitamin D ◽

Bone Mineral ◽

Inhaled Corticosteroids ◽

High Dose ◽

Mineral Density ◽

Chronic Therapy ◽

Vitamin D Levels ◽

The Impact

Asthma is the most common chronic respiratory illness affecting children. Inhaled corticosteroids (ICS) form the main treatment modality in asthma. Reduction in bone mineral density (BMD) is an important adverse effect of steroid usage. This side effect is an established entity with oral corticosteroids but minimal with ICS therapy. However, there are reports regarding the detrimental effect of chronic therapy with ICS. Long-term high-dose budesonide more than 800 μg/day has been shown to reduce the BMD. However, this effect was not consistently seen with moderate doses of 400–800 μg/day. Anticipating the impact of steroids on bone metabolism and monitoring for it is essential. Annual monitoring of Vitamin-D levels and BMD in children on chronic therapy is beneficial for the early detection and management of steroid-induced osteopenia. Judicious ICS use at the lowest effective dose should be tailor-made for every individual.

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The effects of single high dose vs daily low dose oral cholecalciferol treatment on vitamin D levels and muscle strenght in posmenapousal women

Endocrine Abstracts ◽

10.1530/endoabs.37.ep313 ◽

2015 ◽

Author(s):

Mahmut Apaydin ◽

Asli Gencay Can ◽

Seyfullah Kan ◽

Selvihan Beysel ◽

Taner Demirci ◽

...

Keyword(s):

Vitamin D ◽

Low Dose ◽

High Dose ◽

Single High Dose ◽

Vitamin D Levels ◽

Dose Oral

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Vitamin D and COVID-19: evidence and recommendations for supplementation

Royal Society Open Science ◽

10.1098/rsos.201912 ◽

2020 ◽

Vol 7 (12) ◽

pp. 201912

Author(s):

George Griffin ◽

Martin Hewison ◽

Julian Hopkin ◽

Rose Kenny ◽

Richard Quinton ◽

...

Keyword(s):

Vitamin D ◽

Vitamin D Deficiency ◽

Experimental Models ◽

Vitamin D Supplementation ◽

Hospitalized Patients ◽

Lung Damage ◽

High Dose ◽

Vitamin D Levels ◽

Immune Health ◽

The Uk

Vitamin D is a hormone that acts on many genes expressed by immune cells. Evidence linking vitamin D deficiency with COVID-19 severity is circumstantial but considerable—links with ethnicity, obesity, institutionalization; latitude and ultraviolet exposure; increased lung damage in experimental models; associations with COVID-19 severity in hospitalized patients. Vitamin D deficiency is common but readily preventable by supplementation that is very safe and cheap. A target blood level of at least 50 nmol l −1 , as indicated by the US National Academy of Medicine and by the European Food Safety Authority, is supported by evidence. This would require supplementation with 800 IU/day (not 400 IU/day as currently recommended in UK) to bring most people up to target. Randomized placebo-controlled trials of vitamin D in the community are unlikely to complete until spring 2021—although we note the positive results from Spain of a randomized trial of 25-hydroxyvitamin D3 (25(OH)D3 or calcifediol) in hospitalized patients. We urge UK and other governments to recommend vitamin D supplementation at 800–1000 IU/day for all, making it clear that this is to help optimize immune health and not solely for bone and muscle health. This should be mandated for prescription in care homes, prisons and other institutions where people are likely to have been indoors for much of the summer. Adults likely to be deficient should consider taking a higher dose, e.g. 4000 IU/day for the first four weeks before reducing to 800 IU–1000 IU/day. People admitted to the hospital with COVID-19 should have their vitamin D status checked and/or supplemented and consideration should be given to testing high-dose calcifediol in the RECOVERY trial. We feel this should be pursued with great urgency. Vitamin D levels in the UK will be falling from October onwards as we head into winter. There seems nothing to lose and potentially much to gain.

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