An Evidence Based Review of Vitamin D in COVID-19 Severity and Mortality - Juniper Publishers

 Complementary Medicine & Alternative Healthcare - Juniper Publishers

Abstract

Introduction: This evidence-based review aims to explore the association between vitamin D status and the severity and mortality of COVID-19, providing insights for healthcare professionals and policymakers in managing the disease.

Methods: A systematic review process was conducted to identify relevant studies on vitamin D and COVID-19 using electronic databases and specific search terms. Thirteen studies were selected and analyzed, including quantitative research at levels III, IV, and V.

Results: The analysis revealed a significant association between vitamin D deficiency and increased severity and mortality of COVID-19. Vitamin D levels were found to be inversely related to the severity of the disease, with deficiency acting as an independent predictor of COVID-19-related mortality. Studies demonstrated a higher prevalence of vitamin D deficiency among hospitalized COVID-19 patients. Bolus doses of vitamin D supplementation were associated with improved clinical outcomes and lower mortality rates in COVID-19 patients.

Conclusion: The evidence suggests that maintaining adequate vitamin D levels may have a protective effect against the severity and mortality of COVID-19. Vitamin D supplementation, in combination with safe sun exposure education, could be a cost-effective and safe measure to mitigate the impact of the SARS-CoV-2 pandemic. However, further interventional studies are needed to evaluate the efficacy and optimal dosing regimens of vitamin D supplementation in COVID-19 patients.

Keywords: COVID-19; SARS-CoV-2; vitamin D; Severity; Mortality; Supplementation; Evidence-based practice

Introduction

Coronavirus disease 2019 (COVID-19), declared a global pandemic by the World Health Organization (WHO), presents a significant challenge to healthcare systems worldwide (WHO, 2020) [1]. In January 2022, COVID-19 ranked among the top four leading causes of death for all age groups, with older adults being particularly vulnerable [2]. Hospitalizations and mortality rates are significantly higher in adults over 65 years of age compared to those under 65 [3,4].

Between January 2020 and July 2022, there were over 562 million confirmed cases of COVID-19, resulting in approximately 6.3 million deaths worldwide (WHO, 2022). The economic impact of COVID-19 is staggering, estimated at over $16 trillion, which accounts for approximately 90% of the annual gross domestic product (GDP) of the United States [5].

Vitamin D, a hormone produced by both the kidneys and the skin, plays a crucial role in regulating blood calcium concentration and impacting the immune system. It is known by various names, including calcitriol, ergocalciferol, calcidiol, and cholecalciferol.

The two widely available pharmacologic preparations are cholecalciferol (D3) and ergocalciferol (D2). More recently, vitamin D has shown antiviral effects and plays a crucial role in the immune system [6-8]. It is being investigated for its potential in mitigating infections, enhancing immune responses, and suppressing the cytokine storm [9-11] Comparatively, vitamin D deficiency has been linked to increased susceptibility to viral infections. Research has not demonstrated a strong association between vitamin D levels and the prevention of COVID-19 infection [12-15]. However, there is a growing interest in exploring the potential role of vitamin D in relation to the severity of COVID-19 disease.

At the time of submission, COVID-19 has tragically resulted in the loss of over 6 million lives globally (WHO, 2022). Despite this significant impact, there remains limited knowledge about potential protective factors against the disease. Notably, advanced age and underlying chronic medical conditions, especially chronic pulmonary and cardiac diseases, have emerged as prominent predisposing factors for severe COVID-19 development and subsequent mortality [16,17]. This comprehensive literature appraisal aims to investigate potential associations between vitamin D status and disease severity and survival in COVID-19 patients. By analyzing the available evidence, this analysis provides a recommendation while considering the balance of benefit, harm, and cost.

Methods

This systematic review, conducted in collaboration with a faculty advisor and university librarian, examines the relationship between vitamin D and COVID-19, focusing on severity and mortality outcomes. The review process involved comprehensive searches of electronic databases, including PubMed, using key terms such as Vitamin D, Vitamin D Level, Vitamin D Deficiency, Covid, Covid-19, and Coronavirus. Inclusion criteria were limited to English-language articles published between 2020 and 2022, and excluded research proposals and protocols. A total of 20 articles were retrieved, and after reviewing the title and abstracts, 13 relevant studies were selected for appraisal using the Johns Hopkins Appraisal Tool. The levels of evidence were graded using Johns Hopkins Level of Evidence table. This review is comprised of 11 non experimental level III research articles, the highest level of evidence available to date.

Literature Review

Vitamin D levels have been found to be notably depleted among the aging population, a group that exhibits heightened vulnerability to COVID-19 [15]. Further evidence highlights the prevalence of vitamin D deficiency among hospitalized COVID-19 patients, with 59% of admitted individuals presenting vitamin D insufficiency. Vitamin Ds deficiency upon admission has demonstrated a significant association with COVID-19 severity and mortality, even after adjusting for factors such as age, gender, and comorbidity.

There is possibly a blood level dependent association between vitamin D level and COVID-19 severity. A retrospective multicentric study of 212 patients [7] found that critical COVID-19 cases had the lowest levels of vitamin D, whereas mild cases had the highest levels. Similarly, found similar results when stratifying COVID-19 patients by vitamin D level. There were two additional studies conducted by that reported weaker correlations between vitamin D levels and COVID-19 cases and mortality. Finally, there is a small body of evidence supporting the use of bolus doses of vitamin D3 supplementation administered during or shortly before the onset of COVID-19 (2020) [9] and Karahan and Katkat (2021) [5] both demonstrated a lower incidence of COVID-19 infection and improvement in COVID-19 severity with bolus dosed vitamin D.

There were a few studies that failed to demonstrate a positive effect of vitamin D on COVID-19. These studies were small, completed on a younger and healthier population, and primarily studied the relationship between vitamin D level and COVID-19 infection rates, but did not study the correlation between the vitamin D level and COVID-19 severity or mortality (Table 1).

Discussion

In response to the profound burden imposed by the COVID-19 pandemic and the potential for mitigating severe disease outcomes through the exploration of protective factors, numerous researchers have established a compelling association between vitamin D deficiency and the severity of COVID-19 [18-21]. While research has failed to demonstrate that Vitamin D prevents Covid-19 infection, there is a moderate amount of research establishing that optimal vitamin D levels are associated with less severe cases of COVID-19 and conversely, low vitamin D levels have been associated with more severe cases. Furthermore, bolus dosing Vitamin D3 may provide some protection in the severity of the infection, particularly in populations at risk [22,23].

Implications for Practice

Nurse practitioners manage patients in primary care who are at risk of COVID-19. Staying up to date with the current evidence is crucial in supporting clinical practice. The evidence appraised in this review are all non-experimental research. Observational and cohort studies provide valuable insights into potential associations, and the majority of the reviewed studies indicate a positive correlation between vitamin D levels and COVID-19 outcomes. Moreover, vitamin D supplementation is generally considered safe when administered within the recommended dosage range. Although further experimental research is needed to establish a causal relationship, considering the low risk profile of vitamin D supplementation, it is the recommendation of the authors that nurse practitioners consider prescribing Vitamin D supplementation to improve the severity of COVID-19 infections and that blood levels should be monitored to achieve optimal circulating levels ranging from 75 to 100 nmol/L. As healthcare leaders, nurse practitioners have the responsibility to actively seek opportunities to educate both patients and colleagues. By doing so, we can drive practice change and promote the adoption of evidence-based approaches. Disseminating evidence-based practices is vital in improving patient outcomes and ultimately enhancing the overall quality of care.

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Probiotics Use in Horse Feeding - Juniper Publishers

 JOJ Sciences - Juniper Publishers

Abstract

Probiotics are live microorganisms, offered in animal feed at adjusted doses, providing improvements in host health. Several studies have confirmed the yeasts effect on the health, digestibility coefficient, and performance of horses, that way, the Saccharomyces cerevisiae yeast can become an important probiotic additive for equines besides reducing the incidence of colic in these animals.

Keywords: Equine; Saccharomyces cerevisiae; Yeasts; Intestinal microorganisms; Supplementation; Additives normal; Microbiota; Intestinal environment; Digestive tract; Horse feeding; Microorganism; Food digestibility; Gastric environment; Antimicrobial properties; pH; Temperature; Probiotics

Introduction

In equidae, probiotics are used trying to establish a desirable balance among intestinal microorganisms, especially that beneficial. For these benefits, supplementation of these additives in the diet creates an expectation, after use, to provide viable and suitable microscopic organisms for adaptation in the intestinal environment, acting in a beneficial way in the balance of the normal microbiota of the digestive tract, increasing zootechnical performance and/or preventing pathologies of the digestive tract [1]. Therefore, it is essential to evaluate in a more specific way the use of yeasts in the horse feeding as potential probiotics for the specie, considering there are indications of these acting positively on the food digestibility and health of the horses.

Probiotics Characterization

For a microorganism to be considered a good probiotic must have some attributes such as being able to survive the gastric environment, antimicrobial properties, higher growth rate than its elimination by intestinal peristalsis, able to adhere to mucus and epithelial cells, and it is essential to be produced and remains viable for long periods. The first three mechanisms are usually attributed to lactic acid producing bacteria, while the latter two are more yeast specific [1].

The characteristics attributed to probiotic microorganisms are related to the production of substances that suppress pathogens or prevent their growth, competition with them for adhesion sites and nutrients, preventing they to produce toxins as well as inhibiting their action; to be innocuous to the host to not cause any disease, and it must be natural to the digestive system, being able to resist to this environment, mainly to changes in pH and temperature [2].

Several microorganisms are currently used as probiotics, the most common of which are Lactobacillus, Bifidobacterium, Streptococcus, and live yeasts such as Saccharomyces cerevisiae [3]. Saccharomyces cerevisiae yeast has good results, promoting intestinal microbiota balance, which can be observed in an experiment where it was used a dose of 2g/day of yeast for 4-year-old mini-horses, showing balance in the intestinal microflora, and with changes in the bacterial population [4].

Effect of the Saccharomyces cerevisiae Use on the Diet of Horses

Probiotics are widely used for equines in the recovery of animals undergoing some type of stress, such as deficiency in colostrum consumption, stress generated by the weaning process, during transportation with significant water and food restrictions, abrupt climatic changes, chronic morbidities due to mismanagement such as laminitis or gastrointestinal diseases, supplements for animals with low body score, and long-term therapy in order to circumvent the use of antibiotics [5]. In addition, it is used to try to establish a desirable balance between intestinal microorganisms, especially those beneficial. These additives have become a differentiated option due to their attributes, as their ability to reduce infectious pathologies and, consequently, reduce the use of antibiotics [6], as well as to reduce cases of intestinal obstruction. They may be offered to animals in a variety of ways, such as powders, pastes, gels and most often orally, mixed with food during the meal or supplied with water [7].

Among these probiotics, Saccharomyces cerevisiae has potential to be used as a probiotic in equines, since research in other species of animals has shown positive effects [8,9]. In weanling foals, the use of Saccharomyces cerevisiae yeast at 5 g/day showed positive results in hemicellulose digestibility [1]. In diets with low-quality bulky food supplemented with this yeast, the use was approximately 9% better, with an increase in the digestibility coefficient values when compared to the yeast-free diet FURTADO [10]. Similar results were observed when supplementing 20 g of the probiotic Saccharomyces cerevisiae per day for horses under training, with an increase in hemicellulose digestibility of 4.1% [11]. Thus, in order to improve the digestibility of the fibrous portion and increase the energy available to the animals, the diet can be increased with these probiotic additives

Conclusion

The information presented demonstrates that the use of the probiotic Saccharomyces cerevisiae improves the actions of the intestinal microbiota, allowing the greater degradation of the fibrous components of the diet, which predisposes better health conditions to the supplemented animals.

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