ABSTRACT
The importance of the prevention and control of non-communicable diseases, including obesity, metabolic syndrome, type 2 diabetes, cardiovascular diseases, and cancer, is increasing as a requirement of the aging population in developed countries and the sustainability of healthcare. Similarly, the 2013-2030 action plan of the WHO for the prevention and control of non-communicable diseases seeks these achievements. Adequate lifestyle changes, alone or with the necessary treatments, could reduce the risk of mortality or the deterioration of quality of life. In our recent work, we summarized the role of two central factors, i.e., appropriate levels of vitamin D and SIRT1, which are connected to adequate lifestyles with beneficial effects on the prevention and control of non-communicable diseases. Both of these factors have received increased attention in relation to the COVID-19 pandemic as they both take part in regulation of the main metabolic processes, i.e., lipid/glucose/energy homeostasis, oxidative stress, redox balance, and cell fate, as well as in the healthy regulation of the immune system. Vitamin D and SIRT1 have direct and indirect influence of the regulation of transcription and epigenetic changes and are related to cytoplasmic signaling pathways such as PLC/DAG/IP3/PKC/MAPK, MEK/Erk, insulin/mTOR/cell growth, proliferation; leptin/PI3K-Akt-mTORC1, Akt/NFĸB/COX-2, NFĸB/TNFα, IL-6, IL-8, IL-1ß, and AMPK/PGC-1α/GLUT4, among others. Through their proper regulation, they maintain normal body weight, lipid profile, insulin secretion and sensitivity, balance between the pro- and anti-inflammatory processes under normal conditions and infections, maintain endothelial health; balance cell differentiation, proliferation, and fate; and balance the circadian rhythm of the cellular metabolism. The role of these two molecules is interconnected in the molecular network, and they regulate each other in several layers of the homeostasis of energy and the cellular metabolism. Both have a central role in the maintenance of healthy and balanced immune regulation and redox reactions; therefore, they could constitute promising targets either for prevention or as complementary therapies to achieve a better quality of life, at any age, for healthy people and patients under chronic conditions.
Subject(s)
COVID-19 , Diabetes Mellitus, Type 2 , Neoplasms , Noncommunicable Diseases , Humans , Aged , Vitamin D/therapeutic use , Sirtuin 1/metabolism , Diabetes Mellitus, Type 2/metabolism , Quality of Life , Pandemics , Phosphatidylinositol 3-Kinases , Proto-Oncogene Proteins c-akt , Vitamins , Neoplasms/prevention & control , LipidsABSTRACT
Vitamin D is a group of lipophilic hormones with pleiotropic actions. It has been traditionally related to bone metabolism, although several studies in the last decade have suggested its role in sarcopenia, cardiovascular and neurological diseases, insulin-resistance and diabetes, malignancies, and autoimmune diseases and infections. In the pandemic era, by considering the response of the different branches of the immune system to SARS-CoV-2 infection, our aims are both to analyse, among the pleiotropic effects of vitamin D, how its strong multimodal modulatory effect on the immune system is able to affect the pathophysiology of COVID-19 disease and to emphasise a possible relationship between the well-known circannual fluctuations in blood levels of this hormone and the epidemiological trend of this infection, particularly in the elderly population. The biologically active form of vitamin D, or calcitriol, can influence both the innate and the adaptive arm of the immune response. Calcifediol levels have been found to be inversely correlated with upper respiratory tract infections in several studies, and this activity seems to be related to its role in the innate immunity. Cathelicidin is one of the main underlying mechanisms since this peptide increases the phagocytic and germicidal activity acting as chemoattractant for neutrophils and monocytes, and representing the first barrier in the respiratory epithelium to pathogenic invasion. Furthermore, vitamin D exerts a predominantly inhibitory action on the adaptive immune response, and it influences either cell-mediated or humoral immunity through suppression of B cells proliferation, immunoglobulins production or plasma cells differentiation. This role is played by promoting the shift from a type 1 to a type 2 immune response. In particular, the suppression of Th1 response is due to the inhibition of T cells proliferation, pro-inflammatory cytokines production (e.g., INF-γ, TNF-α, IL-2, IL-17) and macrophage activation. Finally, T cells also play a fundamental role in viral infectious diseases. CD4 T cells provide support to B cells antibodies production and coordinate the activity of the other immunological cells; moreover, CD8 T lymphocytes remove infected cells and reduce viral load. For all these reasons, calcifediol could have a protective role in the lung damage produced by COVID-19 by both modulating the sensitivity of tissue to angiotensin II and promoting overexpression of ACE-2. Promising results for the potential effectiveness of vitamin D supplementation in reducing the severity of COVID-19 disease was demonstrated in a pilot clinical trial of 76 hospitalised patients with SARS-CoV-2 infection where oral calcifediol administration reduced the need for ICU treatment. These interesting results need to be confirmed in larger studies with available information on vitamin D serum levels.
Subject(s)
COVID-19 , Vitamin D , Aged , Humans , Vitamin D/therapeutic use , Vitamin D/pharmacology , COVID-19/epidemiology , Calcifediol , SARS-CoV-2 , Vitamins/therapeutic use , Vitamins/pharmacologyABSTRACT
Over the past 100 years, many major breakthroughs and discoveries have occurred in relation to vitamin D research. These developments include the cure of rickets in 1919, the discovery of vitamin D compounds, advances in vitamin D molecular biology, and improvements in our understanding of endocrine control of vitamin D metabolism. Furthermore, recommended daily allowances for vitamin D have been established and large clinical trials of vitamin D, aimed at clarifying the effect of Vitamin D in the prevention of multiple diseases, have been completed. However, disappointingly, these clinical trials have not fulfilled the expectations many had 10 years ago. In almost every trial, various doses and routes of administration did not show efficacy of vitamin D in preventing fractures, falls, cancer, cardiovascular diseases, type 2 diabetes, asthma, and respiratory infections. Although concerns about side-effects of long-term high-dose treatments, such as hypercalcaemia and nephrocalcinosis, have been around for four decades, some trials from the past 5 years have had new and unexpected adverse events. These adverse events include increased fractures, falls, and hospitalisations in older people (aged >65 years). Several of these clinical trials were powered appropriately for a primary outcome but did not include dose response studies and were underpowered for secondary analyses. Furthermore, more attention should be paid to the safety of high doses of vitamin D supplementation, particularly in older people. In addition, despite universal recommendations by osteoporosis societies for combining calcium supplements with vitamin D there remains insufficient data about their efficacy and effect on fracture risk in the highest risk groups. More trials are needed for people with severe vitamin D deficiency (ie, serum 25-hydroxyvitamin D <25nmol/L [10ng/mL]). In this Personal View, we summarise and discuss some of the major discoveries and controversies in the field of vitamin D.
Subject(s)
Diabetes Mellitus, Type 2 , Fractures, Bone , Osteoporosis , Vitamin D Deficiency , Humans , Aged , Diabetes Mellitus, Type 2/drug therapy , Vitamin D/therapeutic use , Vitamins/therapeutic use , Fractures, Bone/epidemiology , Fractures, Bone/prevention & control , Osteoporosis/complications , Vitamin D Deficiency/drug therapy , Dietary SupplementsABSTRACT
OBJECTIVE: This work aims to review and discuss controversial topics in the field of vitamin D, SARS-CoV-2 infection, and COVID-19. METHODS: The International Conferences "Controversies in Vitamin D" are a series of workshops that started in 2017 featuring international experts and leaders in vitamin D research and clinical practice. The fifth annual conference was held in Stresa, Italy, September 15 to 18, 2021. EVIDENCE: Before the event, participants reviewed available studies on their assigned topic, drafted a related abstract, and presented their findings at the time of the conference. Relevant literature that became available since was also discussed within the panel and updated accordingly. CONSENSUS: Before the event, the drafted abstracts had been merged to prepare a preliminary document. After the conference presentations, in-depth discussions in open sessions led to consensus. The document was subsequently modified according to discussions and up-to-date literature inclusion. CONCLUSIONS: There is quite consistent evidence for an association between low 25 OH vitamin D (25(OH)D) levels and poor COVID-19 outcomes, despite heterogeneous publications of variable quality. However, the low vitamin D status in COVID-19 patients might also reflect reverse causality. Vitamin D supplementation might have a positive role in COVID-19 prevention. The evidence supporting a beneficial effect of vitamin D treatment in decreasing the risk of COVID-19 complications is conflicting. Conclusive statements regarding the beneficial effect of vitamin D in this context await high-quality, randomized controlled trials.
Subject(s)
COVID-19 , Vitamin D Deficiency , Humans , Consensus , COVID-19/epidemiology , SARS-CoV-2 , Vitamin D/therapeutic use , Vitamin D Deficiency/drug therapy , Vitamins/therapeutic useABSTRACT
Vitamin D is indicated to be beneficial for the prevention and treatment of both respiratory health and mental health problems, while mental health issues are a common consequence of diseases of the respiratory system. The aim of the presented systematic review was to gather available evidence regarding the influence of the supplementation of vitamin D on mental health in adults with respiratory system diseases obtained within randomized controlled trials (RCTs). The systematic review was conducted on the basis of the PubMed and Web of Science databases in agreement with the guidelines of Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), while being registered within the database of the International Prospective Register of Systematic Reviews (PROSPERO) (CRD42020155779). A total of 8514 studies published before September 2021 were screened and 5 RCTs were included, which were assessed using the revised Cochrane risk-of-bias tool for randomized trials. Screening, inclusion, reporting, and assessment were conducted by two researchers independently. The studies focused on the assessment of patients with chronic obstructive pulmonary disease, but also increased susceptibility to respiratory tract infections, pulmonary tuberculosis, and bronchial asthma. The studies were conducted for various periods of time-from 2 months to a year-while the dose of vitamin D applied was also diverse-from 4000 IU applied daily, to 100,000 IU applied weekly, or monthly. The psychological measures applied within the studies allowed the assessment, mainly, of quality of life, but also well-being, and depression. For the majority of studies, some concerns regarding risk of bias were defined, resulting from the randomization process and selection of reported results; however, for one study, the risk was even defined as high. Within the included studies, three studies confirmed a beneficial effect of vitamin D (including those with a high risk of bias), but two studies did not confirm it. Taking into account the evidence gathered, in spite of a positive influence of vitamin D on mental health in individuals with increased susceptibility to respiratory tract infections and bronchial asthma, the conducted systematic review is not a strong confirmation of the beneficial effect of the supplementation of vitamin D on mental health in adults with respiratory system diseases.
Subject(s)
Asthma , Respiratory Tract Infections , Adult , Humans , Vitamin D/therapeutic use , Mental Health , Randomized Controlled Trials as Topic , Vitamins , Respiratory Tract Infections/prevention & control , Asthma/drug therapy , Dietary SupplementsABSTRACT
Coronavirus disease 2019 (COVID-19) has a wide-ranging spectrum of clinical symptoms, from asymptomatic/mild to severe. Recent research indicates that, among several factors, a low vitamin D level is a modifiable risk factor for COVID-19 patients. This study aims to evaluate the effect of vitamin D on hospital and laboratory outcomes of patients with COVID-19.Five databases (PubMed, Embase, Scopus, Web of Science, and Cochrane Library) and clinicaltrials.gov were searched until July 2022, using relevant keywords/Mesh terms. Only randomized clinical trials (RCTs) that addressed the topic were included. The Cochrane tool was used to assess the studies' risk of bias, and the data were analyzed using the review manager (RevMan 5.4).We included nine RCTs with 1586 confirmed COVID-19 patients. Vitamin D group showed a significant reduction of intensive care unit (ICU) admission (risk ratio = 0.59, 95% confidence interval (CI) [0.41, 0.84], P = 0.003), and higher change in vitamin D level (standardized mean difference = 2.27, 95% CI [2.08, 2.47], P < 0.00001) compared to the control group. Other studied hospital and laboratory outcomes showed non-significant difference between vitamin D and the control group (P ≥ 0.05).In conclusion, vitamin D reduced the risk of ICU admission and showed superiority in changing vitamin D level compared to the control group. However, other outcomes showed no difference between the two groups. More RCTs are needed to confirm these results.
Subject(s)
COVID-19 , Humans , Randomized Controlled Trials as Topic , Vitamin D/therapeutic use , Vitamins , Dietary Supplements , HospitalsABSTRACT
BACKGROUND: Disease and treatment-associated immune system abnormalities may confer higher risk of Coronavirus disease 2019 (COVID-19) to people with multiple sclerosis (PwMS). We assessed modifiable risk factors associated with COVID-19 in PwMS. METHODS: Among patients referring to our MS Center, we retrospectively collected epidemiological, clinical and laboratory data of PwMS with confirmed COVID-19 between March 2020 and March 2021 (MS-COVID, n = 149). We pursued a 1:2 matching of a control group by collecting data of PwMS without history of previous COVID-19 (MS-NCOVID, n = 292). MS-COVID and MS-NCOVID were matched for age, expanded disability status scale (EDSS) and line of treatment. We compared neurological examination, premorbid vitamin D levels, anthropometric variables, life-style habits, working activity, and living environment between the two groups. Logistic regression and Bayesian network analyses were used to evaluate the association with COVID-19. RESULTS: MS-COVID and MS-NCOVID were similar in terms of age, sex, disease duration, EDSS, clinical phenotype and treatment. At multiple logistic regression, higher levels of vitamin D (OR 0.93, p < 0.0001) and active smoking status (OR 0.27, p < 0.0001) emerged as protective factors against COVID-19. In contrast, higher number of cohabitants (OR 1.26, p = 0.02) and works requiring direct external contact (OR 2.61, p = 0.0002) or in the healthcare sector (OR 3.73, p = 0.0019) resulted risk factors for COVID-19. Bayesian network analysis showed that patients working in the healthcare sector, and therefore exposed to increased risk of COVID-19, were usually non-smokers, possibly explaining the protective association between active smoking and COVID-19. CONCLUSIONS: Higher Vitamin D levels and teleworking may prevent unnecessary risk of infection in PwMS.
Subject(s)
COVID-19 , Multiple Sclerosis , Humans , Multiple Sclerosis/complications , Multiple Sclerosis/epidemiology , Multiple Sclerosis/drug therapy , Case-Control Studies , Retrospective Studies , Bayes Theorem , Vitamin D/therapeutic use , Risk FactorsABSTRACT
Thromboembolic complications including cerebrovascular accidents, pulmonary embolism, myocardial infarction, deep vein thrombosis and disseminating intravascular coagulopathy are serious encounters in sever coronavirus disease 2019 (COVID-19) infected patients. This worsens the prognosis and may lead to death or life long morbidities. The laboratory finding of the disturbed haemostasias and the hyperinflammatory response are almost invariably present in COVID-19 patients. Multiple treatment modalities are utilized by the healthcare professionals to overcome the cytokine storm, oxidative stress, endothelial dysfunction, and coagulopathy in these patients. The combined actions of vitamin D (VitD) as a steroid hormone with anti-inflammatory, immunomodulatory, and antithrombotic properties increase the potential of the possible involvement of hypovitaminosis D in the thromboembolic complications of COVID-19 infection, and stimulated researchers and physicians to administer VitD therapy to prevent the infection and/or overcome the disease complications. The current review highlighted the immunomodulatory, anti-inflammatory, antioxidative and hemostatic functions of VitD and its interrelation with the renin-angiotensin-aldosterone system (RAAS) pathway and the complement system. Additionally, the association of VitD deficiency with the incidence and progression of COVID-19 infection and the associated cytokine storm, oxidative stress, hypercoagulability, and endothelial dysfunction were emphasized. Normalizing VitD levels by daily low dose therapy in patients with hypovitaminosis D below (25ânmol/l) is essential for a balanced immune response and maintaining the health of the pulmonary epithelium. It protects against upper respiratory tract infections and decreases the complications of COVID-19 infections. Understanding the role of VitD and its associated molecules in the protection against the coagulopathy, vasculopathy, inflammation, oxidative stress and endothelial dysfunction in COVID-19 infection could lead to new therapeutic strategies to prevent, treat, and limit the complications of this deadly virus infection.
Subject(s)
Blood Coagulation Disorders , COVID-19 , Thromboembolism , Thrombosis , Vitamin D Deficiency , Humans , COVID-19/complications , Cytokine Release Syndrome/complications , SARS-CoV-2 , Thrombosis/etiology , Vitamin D Deficiency/complications , Vitamin D Deficiency/epidemiology , Blood Coagulation Disorders/complications , Vitamin D/therapeutic use , Anti-Inflammatory AgentsABSTRACT
Vitamin D has a well-known role in the calcium homeostasis associated with the maintenance of healthy bones. It increases the efficiency of the intestinal absorption of dietary calcium, reduces calcium losses in urine, and mobilizes calcium stored in the skeleton. However, vitamin D receptors are present ubiquitously in the human body and indeed, vitamin D has a plethora of non-calcemic functions. In contrast to most vitamins, sufficient vitamin D can be synthesized in human skin. However, its production can be markedly decreased due to factors such as clothing, sunscreens, intentional avoidance of the direct sunlight, or the high latitude of the residence. Indeed, more than one billion people worldwide are vitamin D deficient, and the deficiency is frequently undiagnosed. The chronic deficiency is not only associated with rickets/osteomalacia/osteoporosis but it is also linked to a higher risk of hypertension, type 1 diabetes, multiple sclerosis, or cancer. Supplementation of vitamin D may be hence beneficial, but the intake of vitamin D should be under the supervision of health professionals because overdosing leads to intoxication with severe health consequences. For monitoring vitamin D, several analytical methods are employed, and their advantages and disadvantages are discussed in detail in this review.
Subject(s)
Rickets , Vitamin D Deficiency , Humans , Vitamin D/metabolism , Vitamin D/therapeutic use , Calcium , Vitamin D Deficiency/complications , Vitamin D Deficiency/drug therapy , Vitamins , Rickets/complications , Rickets/drug therapy , Calcium, DietaryABSTRACT
Medicines have been re-purposed as therapeutics for COVID-19 and it is with great interest that we read the publication entitled, "Effects of Vitamin D Supplementation on COVID-19 Related Outcomes: A Systematic Review and Meta-Analysis" [...].
Subject(s)
COVID-19 , Humans , Vitamin D/therapeutic use , Dietary Supplements , NutrientsABSTRACT
The specialized literature emphasizes the fact that vitamin D has a potentially beneficial effect in the context of the current COVID-19 pandemic. The purpose of this article is to highlight the role of vitamin D, both prophylactic and curative, in the treatment of patients diagnosed with COVID-19. Even though its relevance is still unknown and causes various controversies, there is currently no specific treatment for patients diagnosed with COVID-19. There are various prevention strategies with new vaccination schedules, but additional randomized and clinical trials are still needed to combat this pandemic. In addition to the systemic manifestations of SARS-CoV-2 infection, oral manifestations of this disease have also been described in the literature. The etiology of oral manifestations associated with COVID-19 infection and vitamin D deficiency remains controversial. In the present studies, oral manifestations such as salivary gland infections, aphthae, erythema, gingivitis, ulcers, etc. have been reported. This is a new topic, and the prevalence of manifestations is described in only a few studies, which is inconsistent with the number of COVID-19 cases reported since the beginning of the pandemic. The clinical symptomatology in patients with current COVID-19 infection is polymorphic. Whether the oral manifestation is directly caused by SARS-CoV-2 or a secondary manifestation remains an important topic to analyze and discuss.
Subject(s)
COVID-19 , Vitamin D Deficiency , Humans , COVID-19/complications , COVID-19/epidemiology , SARS-CoV-2 , Pandemics/prevention & control , Vitamin D Deficiency/drug therapy , Vitamin D/therapeutic use , VitaminsABSTRACT
The coronavirus disease (COVID-19) pandemic represents a global health challenge, particularly considering concomitant diseases. Patients with inflammatory bowel diseases (IBD) can be considered a population at risk. On the other hand, the risk of developing IBD and COVID-19 have both been described as modulated by vitamin D (VD) levels. In this work, a cohort of 106 adult patients affected by IBD was prospectively enrolled, during the second wave of the pandemic in Italy. In these patients, VD plasma levels, demographic, and clinical characteristics were tested for a correlation/an association with the risk of infection with SARS-CoV-2 in the study period (anti-spike IgG positivity) and the severity of COVID-19 symptoms. By multivariate logistic regression analysis, VD supplementation (Odds Ratio; OR 0.116, p = 0.002), therapy with monoclonal antibodies (OR 0.227, p = 0.007), and the use of mesalazine (OR 2.968, p = 0.046) were found to be independent predictors of SARS-CoV-2 positivity. Moreover, hypertension was associated with severe disease (p = 0.019), while a VD level higher than 30 ng/mL (p = 0.031, OR 0.078) was associated with asymptomatic infection. No interplay between IBD activity and COVID-19 risk of infection or symptoms was observed. These results confirm the importance of VD levels in defining the risk of COVID-19 and give encouraging data about the safety of maintaining immunomodulatory treatments for IBD during the COVID-19 pandemic.
Subject(s)
COVID-19 , Inflammatory Bowel Diseases , Adult , Humans , COVID-19/epidemiology , Vitamin D/therapeutic use , SARS-CoV-2 , Pandemics , Inflammatory Bowel Diseases/complications , Inflammatory Bowel Diseases/drug therapy , Inflammatory Bowel Diseases/epidemiology , Vitamins/therapeutic use , Dietary SupplementsABSTRACT
Vitamin D is an important immune-modulator with anti-inflammatory properties. While this prohormone has been studied extensively in the prevention and treatment of COVID-19, findings have been inconsistent regarding its overall benefit in patients hospitalized with COVID-19. Most studies to date have been observational in nature, not accounting for the use of corticosteroids. Furthermore, the few randomized clinical trials designed to examine the effect of vitamin D supplementation on COVID-19 outcomes have been relatively small and thus insufficiently powered to assure a balance of corticosteroid use between study arms. The current perspective addresses the interaction of vitamin D and corticosteroids as a potential explanation for the divergent results reported in the literature. Future research on vitamin D and COVID-19 will benefit by considering this interaction, especially among hospitalized patients requiring oxygen and mechanical ventilation.
Subject(s)
COVID-19 Drug Treatment , Adrenal Cortex Hormones/therapeutic use , Humans , SARS-CoV-2 , Vitamin D/therapeutic use , VitaminsABSTRACT
BACKGROUND: Elderly long-term care residents (ELTCRs) face considerable burden of infection, especially evident during the COVID-19 pandemic. The nutritional status of the host can influence susceptibility to infection by altering immune system integrity, therefore, nutrition-based interventions may be a viable complement to existing infection prevention measures. OBJECTIVE: This scoping review sought to identify nutritional interventions and factors that have the strongest evidence to benefit ELTCRs, and thus best poised for rigorous clinical trial evaluation and subsequent implementation. METHODS: A database search of OVID-Medline, OVID-Embase, and Web of Science was performed from 2011 to 2021 to identify nutritional intervention studies which attribute to changes in infection in contemporary ELTCR settings. Articles were screened in duplicate and data extraction completed by a single reviewer, while a second reviewer verified the data which was fitted to identify evidence for nutritional interventions related to reducing rates of infection among ELTCRs. RESULTS: The search identified 1018 studies, of which 11 (nine clinical trials and two observational cohort studies) satisfied screening criteria. Interventions that significantly reduced risk of infection included whey protein (any infection), Black Chokeberry (urinary tract infection), and vitamin D (acute respiratory tract infection, skin and soft tissue infection). Both zinc and a dedicated meal-plan significantly improved lymphocyte parameters. Vitamin D deficiency was associated with the development of respiratory tract infections. Probiotic and soy-based protein interventions did not significantly affect risk of infection or lymphocyte parameters, respectively. CONCLUSION: The current scoping review was effective in identifying the use of nutrition-based interventions for infection prevention among ELTCRs. In this study, some nutrition-based interventions were observed to significantly influence the risk of infection among ELTCRs. Nutritional interventions such as vitamin D (preventing deficiency/insufficiency), Black Chokeberry juice, zinc gluconate, whey protein, and varied and nutrient dense meal plans may be suitable for future rigorous clinical trial evaluation.
Subject(s)
COVID-19 , Respiratory Tract Infections , Aged , COVID-19/prevention & control , Humans , Long-Term Care , Pandemics/prevention & control , Vitamin D/therapeutic use , Vitamins , Whey ProteinsABSTRACT
Patients with pre-existing cardiovascular disease (CVD) are at high risk for adverse outcomes with coronavirus disease 2019 (COVID-19). Further, COVID-19 infection is associated with numerous cardiovascular (CV) complications including arrhythmia, myocardial injury, cardiomyopathy, and thrombotic events. Increased susceptibility to COVID-19 and CV complications related to COVID-19 may be in part related to immune dysregulation and inflammation associated with CV disease which is exacerbated with viral infection. Vitamin D plays a major role in immune function and exerts anti-inflammatory effects, which may prove important in the context of CVD and COVID-19. To date, studies have shown minimal benefit for vitamin D supplementation in patients with COVID-19, though there are no studies specific to patients with CVD and related complications. Further, given that vitamin D has important protective effects on the CV system, including augmentation of myocardial contractility and anti-thrombotic effects, it is unknown if supplementation with vitamin D can mitigate CVD complications associated with COVID-19.
Subject(s)
COVID-19 Drug Treatment , COVID-19 , Cardiovascular Diseases , Vitamin D Deficiency , COVID-19/complications , Cardiovascular Diseases/etiology , Cardiovascular Diseases/prevention & control , Humans , Vitamin D/physiology , Vitamin D/therapeutic use , Vitamin D Deficiency/complications , Vitamin D Deficiency/drug therapy , Vitamins/therapeutic useABSTRACT
Vitamin C, (ascorbic acid), vitamin D (cholecalciferol) and zinc (zinc sulfate monohydrate) supplements are important in immunity against coronavirus disease-2019 (COVID-19). However, a limited number of studies have been conducted on the association of vitamins and supplements with the reduced risks of COVID-19 infection. This study aims to evaluate the association of vitamins and supplements as treatment options to reduce the severity of COVID-19. Data were collected from 962 participants from 13 December 2020 to 4 February 2021. The presence of COVID-19 was confirmed by qRT-PCR. The Chi-square test and multivariate regression analyses were conducted. The ratio of uptake of vitamin C:vitamin D:zinc was 1:1:0.95. Uptake of vitamin C, vitamin D and zinc were significantly associated with the reduced risk of infection and severity of COVID-19 (OR: 0.006 (95% CI: 0.03-0.11) (p = 0.004)) and (OR: 0.03 (95% CI: 0.01-0.22) (p = 0.005)). The tendency of taking supplements was associated with the presence of infection of COVID-19 (p = 0.001), age (p = 0.02), sex (p = 0.05) and residence (p = 0.04). The duration of supplementation and medication was significantly associated with reduced hospitalization (p = 0.0001). Vitamins C, D and zinc were not significantly (p = 0.9) associated with a reduced risk of severity when taken through the diet. Hospitalization (p = 0.000001) and access to health facilities (p = 0.0097) were significantly associated with the survival period of the participants. Participants with better access to health facilities recovered early (OR: 6.21, 95% CI 1.56-24.7). This study will add knowledge in the field of treatment of COVID-19 by using vitamins and zinc supplements.
Subject(s)
Ascorbic Acid , COVID-19 , Humans , Ascorbic Acid/therapeutic use , Zinc/therapeutic use , Cross-Sectional Studies , Vitamins/therapeutic use , Vitamin A , Dietary Supplements , Vitamin D/therapeutic useABSTRACT
Vitamin D supplementation and its impact on immunoregulation are widely investigated. We aimed to assess the prevention and treatment efficiency of vitamin D supplementation in the context of coronavirus disease 2019 (COVID-19) and any disease-related complications. For this systematic review and meta-analysis, we searched databases (PubMed, Embase, Scopus, Web of Science, The Cochrane Library, medRxiv, Cochrane COVID-19 Study Register, and ClinicalTrial.gov) for studies published between 1 November 2019 and 17 September 2021. We considered randomized trials (RCTs) as potentially eligible when patients were tested for SARS-CoV-2 infection and received vitamin D supplementation versus a placebo or standard-of-care control. A random-effects model was implemented to obtain pooled odds ratios for the effect of vitamin D supplementation on the main outcome of mortality as well as clinical outcomes. We identified a total of 5,733 articles, of which eight RCTs (657 patients) met the eligibility criteria. Although no statistically significant effects were reached, the use of vitamin D supplementation showed a trend for reduced mortality [odds ratio (OR) 0.74, 95% confidence interval (CI) 0.32-1.71, p = 0.48] compared with the control group, with even stronger effects, when vitamin D was administered repeatedly (OR 0.33, 95% CI 0.1-1.14). The mean difference for the length of hospitalization was -0.28 (95% CI -0.60 to 0.04), and the ORs were 0.41 (95% CI 0.15-1.12) and 0.52 (95% CI 0.27-1.02) for ICU admission and mechanical ventilation, respectively. In conclusion, vitamin D supplementation did not improve the clinical outcomes in COVID-19 patients, but trends of beneficial effects were observed. Further investigations are required, especially studies focusing on the daily administration of vitamin D.
Subject(s)
COVID-19 Drug Treatment , Humans , Dietary Supplements , SARS-CoV-2 , Randomized Controlled Trials as Topic , Vitamin D/therapeutic use , Vitamins/therapeutic useABSTRACT
Active vitamin D [1,25(OH)2D3-calcitriol] is a secosteroid hormone whose receptor is expressed on all cells of the immune system. Vitamin D has a global anti-inflammatory effect and its role in the management of a SARS-CoV-2 infection has been investigated since the beginning of the COVID-19 pandemic. In this narrative review, the laboratory and clinical results of a vitamin D supplementation have been collected from both open-label and blinded randomized clinical trials. The results are generally in favor of the utility of maintaining the serum concentrations of calcifediol [25(OH)D3] at around 40 ng/mL and of the absolute usefulness of its supplementation in subjects with deficient serum levels. However, two very recent large-scale studies (one open-label, one placebo-controlled) have called into question the contribution of vitamin D to clinical practice in the era of COVID-19 vaccinations. The precise role of a vitamin D supplementation in the anti-COVID-19 armamentarium requires further investigations in light of the breakthrough which has been achieved with mass vaccinations.
Subject(s)
COVID-19 , Vitamin D , Humans , Vitamin D/therapeutic use , Pandemics , Dietary Supplements , SARS-CoV-2 , Vitamins/therapeutic useABSTRACT
Vitamin D deficiency is associated with a higher risk of SARS-CoV-2 infection and poor outcomes of the COVID-19 disease. However, a satisfactory mechanism explaining the vitamin D protective effects is missing. Based on the anti-inflammatory and anti-oxidative properties of classical and novel (CYP11A1-derived) vitamin D and lumisterol hydroxymetabolites, we have proposed that they would attenuate the self-amplifying damage in lungs and other organs through mechanisms initiated by interactions with corresponding nuclear receptors. These include the VDR mediated inhibition of NFκß, inverse agonism on RORγ and the inhibition of ROS through activation of NRF2-dependent pathways. In addition, the non-receptor mediated actions of vitamin D and related lumisterol hydroxymetabolites would include interactions with the active sites of SARS-CoV-2 transcription machinery enzymes (Mpro;main protease and RdRp;RNA dependent RNA polymerase). Furthermore, these metabolites could interfere with the binding of SARS-CoV-2 RBD with ACE2 by interacting with ACE2 and TMPRSS2. These interactions can cause the conformational and dynamical motion changes in TMPRSS2, which would affect TMPRSS2 to prime SARS-CoV-2 spike proteins. Therefore, novel, CYP11A1-derived, active forms of vitamin D and lumisterol can restrain COVID-19 through both nuclear receptor-dependent and independent mechanisms, which identify them as excellent candidates for antiviral drug research and for the educated use of their precursors as nutrients or supplements in the prevention and attenuation of the COVID-19 disease.
Subject(s)
COVID-19 Drug Treatment , Vitamin D , Humans , Vitamin D/pharmacology , Vitamin D/therapeutic use , Ergosterol , Cholesterol Side-Chain Cleavage Enzyme , Angiotensin-Converting Enzyme 2 , SARS-CoV-2 , VitaminsABSTRACT
Vitamin D deficiency has long been associated with reduced immune function that can lead to viral infection. Several studies have shown that Vitamin D deficiency is associated with increases the risk of infection with COVID-19. However, it is unknown if treatment with Vitamin D can reduce the associated risk of COVID-19 infection, which is the focus of this study. In the population of US veterans, we show that Vitamin D2 and D3 fills were associated with reductions in COVID-19 infection of 28% and 20%, respectively [(D3 Hazard Ratio (HR) = 0.80, [95% CI 0.77, 0.83]), D2 HR = 0.72, [95% CI 0.65, 0.79]]. Mortality within 30-days of COVID-19 infection was similarly 33% lower with Vitamin D3 and 25% lower with D2 (D3 HR = 0.67, [95% CI 0.59, 0.75]; D2 HR = 0.75, [95% CI 0.55, 1.04]). We also find that after controlling for vitamin D blood levels, veterans receiving higher dosages of Vitamin D obtained greater benefits from supplementation than veterans receiving lower dosages. Veterans with Vitamin D blood levels between 0 and 19 ng/ml exhibited the largest decrease in COVID-19 infection following supplementation. Black veterans received greater associated COVID-19 risk reductions with supplementation than White veterans. As a safe, widely available, and affordable treatment, Vitamin D may help to reduce the severity of the COVID-19 pandemic.