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Abstract

The epidemic that emerged in recent months and related to severe acute respiratory syndrome coronavirus-2 (SARSCoV-2) caused a global threat. When ineffective treatment methods and the lack of vaccines were considered, these issues caused a serious international concern (1). 80% of people who have had COVID-19 disease as a result of SARS-CoV-2 infection have mild illness or no symptoms (asymptomatic). In the rest of population, serious illness can occur. In addition to the clinical picture difference in COVID-19 disease, another striking feature is the variability in mortality rates between regions / countries. This difference in clinical table can be attributed to changes in age, comorbidity, race, diet, climate (air temperature / sun exposure), access to healthcare, reporting and surveillance of the population. SARS-CoV-2, which initially shows its effect as immune suppression, continues its effect with excessive increase in immune system response and results in cytokine storm. Afterwards, with the development of acute respiratory distress syndrome (ARDS) and systemic inflammatory response syndrome (SIRS), the COVID-19 has far more severe consequences. On the other hand, the antiviral efficacy of vitamin D, which can also be thought as an immunomodulator and anti-inflammatory, has been shown in many studies of recent years (2, 3). Here, we will briefly examine the effects of vitamin D on the immune system as well as in the course and prognosis of COVID-19 disease under the light of recent literature data. As mentioned in a recent published review (4), where many large studies have been addressed, vitamin D enhances cellular immunity by inducing some antimicrobial peptides, such as some antimicrobial peptides, defensins, e.g. cathelicidine (5-7). Catelicidines have a direct antimicrobial effect against Gram-positive, Gram-negative bacteria, enveloped and nonenveloped viruses and fungi (8). These peptides kill pathogens by breaking their cell membranes. They can counteract the biological activities of their endotoxins and have many other significant functions like this (9). Vitamin D was shown to reduce influenza A virus replication in a mouse model (10). In another study, 1,25 (OH)2 D3 has been shown to reduce both in vitro and in vivo replication of rotavirus (11). In a clinical study, supplementation of 4000 IU / day vitamin D has also Received May 16, 2020 been reported to reduce Dengue virus infection severity (12). In addition, vitamin D increases cellular immunity by partially decreasing the cytokine storm caused by the innate immune system. The innate immune system produces both pro-inflammatory and anti-inflammatory cytokines in return to viral and bacterial infections, as seen in COVID-19 patients. Vitamin D can diminish the production of T helper 1 (Th1) cells such as IL-2, TNF-α, and interferons. Not only vitamin D supplementation decreases the expression of pro-inflammatory cytokines mentioned earlier but also enhances the expression of anti-inflammatory cytokines by monocytes / macrophages (13). Vitamin D deficiency is thought to be a risk element for ARDS itself as well. In experiments on animals with ARDS, it has also been shown that virus transmission to the lungs could be reduced by modulating the activity of renin-angiotensin system and ACE-2 expression with vitamin D treatment (14). Vitamin D deficiency poses an important health problem in all age groups (15). Quite a few foods contain vitamin D. Its main source is the non-enzymatic synthesis of ultraviolet-B (UVB) rays emitted from the sun. With increasing age, the production of vitamin D in the skin and serum 25 (OH) D3 concentrations decrease considerably (16). This may be one of the key factors for COVID-19 disease because case death rates rise with age. The reason may be due to less time exposure to the sun and decreased vitamin D production as a result of low 7-dehydrocholesterol levels in the skin. Additionally, medication use also characteristically increases with age. Some pharmaceutical medications activate the pregnan-X receptor, reducing serum 25 (OH) D concentrations. These drugs consist of antiepileptics, antineoplastics, antibiotics, anti-inflammatory agents, antihypertensives, antiretrovirals, endocrine drugs, and some herbal medicines. On the other hand, when we look at past pandemics in the world, a strong correlation was found between the case death rates and UVB exposure rates in the influenza epidemic of 1918-1919 (17). When the mortality rates in the United States (USA) were analyzed, the case mortality rate was approximately 6% in the northern states, whereas in the southern states it decreased to 3.5% (18). At this point, it comes to our mind that the change in mortality rates may be due to the difference of UVB exposure and vitamin D levels depending on the geographical locations in these regions. In accordance with our opinion, we see that the frequency of vitamin D deficiency is known to be very high in European countries such as Italy, Spain and France (19), where the mortality rates due to COVID-19 disease are the highest. When another study of 212 patients with proven SARSCoV-2 infection was examined, serum 25 (OH) D level was the lowest in clinically severe cases, whereas it was highest in mild cases. Relation with serum 25 (OH) D levels was demonstrated to be statistically meaningful among clinical results. When all the results in the study are evaluated, the rise in serum 25 (OH) D levels in the COVID-19 patients suggests that it may improve clinical course or alleviate clinical outcomes even in severe cases. On the other hand, it may mean that the decline in serum 25 (OH) D levels in the body may worsen the clinical outcomes in patients (20). In another study involving twenty European countries, a negative correlation was found between serum 25 (OH) D levels and the total number of cases with COVID-19 disease and mortality rates due to this disease (21). In the light of the literature knowledge above, we know that the antiviral and anti-inflammatory effectiveness of vitamin D is quite high. It comes to mind that vitamin D supplementation in the treatment may have a preventive effect on some negative consequences. Among the causes of this clinical diversity in the course and mortality rates of the COVID-19 cases, it is an important to remind that vitamin D deficiency can also be underlying comorbidity in the patients. As a conclusion, in this period when we fought against the COVID-19 pandemic, which affected many countries around the world and caused thousands of people to die, no clear agent has been found in its treatment. In fact, an easily accessible agent such as vitamin D may be an important weapon in our hands. However, there is no clear evidence for high-dose or dose of vitamin D supplementation in patients with SARSCoV-2 infection. Although there is a need for more research related to this subject, we think that supplementing vitamin D as a part of standard nutrition may be somewhat effective in providing clinical benefit.
1
Received May 16, 2020
Accepted for publication May 20, 2020
LETTER TO THE EDITOR
Dear Editor,
The epidemic that emerged in recent months and related
to severe acute respiratory syndrome coronavirus-2 (SARS-
CoV-2) caused a global threat. When ineffective treatment
methods and the lack of vaccines were considered, these issues
caused a serious international concern (1). 80% of people
who have had COVID-19 disease as a result of SARS-CoV-2
infection have mild illness or no symptoms (asymptomatic). In
the rest of population, serious illness can occur. In addition to
the clinical picture difference in COVID-19 disease, another
striking feature is the variability in mortality rates between
regions / countries. This difference in clinical table can be
attributed to changes in age, comorbidity, race, diet, climate (air
temperature / sun exposure), access to healthcare, reporting and
surveillance of the population.
SARS-CoV-2, which initially shows its effect as immune
suppression, continues its effect with excessive increase
in immune system response and results in cytokine storm.
Afterwards, with the development of acute respiratory distress
syndrome (ARDS) and systemic inflammatory response
syndrome (SIRS), the COVID-19 has far more severe
consequences. On the other hand, the antiviral efficacy of
vitamin D, which can also be thought as an immunomodulator
and anti-inflammatory, has been shown in many studies of
recent years (2, 3). Here, we will briefly examine the effects
of vitamin D on the immune system as well as in the course
and prognosis of COVID-19 disease under the light of recent
literature data.
As mentioned in a recent published review (4), where many
large studies have been addressed, vitamin D enhances cellular
immunity by inducing some antimicrobial peptides, such as
some antimicrobial peptides, defensins, e.g. cathelicidine
(5-7). Catelicidines have a direct antimicrobial effect against
Gram-positive, Gram-negative bacteria, enveloped and non-
enveloped viruses and fungi (8). These peptides kill pathogens
by breaking their cell membranes. They can counteract the
biological activities of their endotoxins and have many other
significant functions like this (9). Vitamin D was shown to
reduce influenza A virus replication in a mouse model (10). In
another study, 1,25 (OH)2 D3 has been shown to reduce both
in vitro and in vivo replication of rotavirus (11). In a clinical
study, supplementation of 4000 IU / day vitamin D has also
been reported to reduce Dengue virus infection severity (12).
In addition, vitamin D increases cellular immunity by
partially decreasing the cytokine storm caused by the innate
immune system. The innate immune system produces both
pro-inflammatory and anti-inflammatory cytokines in return to
viral and bacterial infections, as seen in COVID-19 patients.
Vitamin D can diminish the production of T helper 1 (Th1)
cells such as IL-2, TNF-α, and interferons. Not only vitamin D
supplementation decreases the expression of pro-inflammatory
cytokines mentioned earlier but also enhances the expression of
anti-inflammatory cytokines by monocytes / macrophages (13).
Vitamin D deficiency is thought to be a risk element for
ARDS itself as well. In experiments on animals with ARDS, it
has also been shown that virus transmission to the lungs could
be reduced by modulating the activity of renin-angiotensin
system and ACE-2 expression with vitamin D treatment (14).
Vitamin D deficiency poses an important health problem in
all age groups (15). Quite a few foods contain vitamin D. Its
main source is the non-enzymatic synthesis of ultraviolet-B
(UVB) rays emitted from the sun. With increasing age, the
production of vitamin D in the skin and serum 25 (OH) D3
concentrations decrease considerably (16). This may be one of
the key factors for COVID-19 disease because case death rates
rise with age. The reason may be due to less time exposure
to the sun and decreased vitamin D production as a result of
low 7-dehydrocholesterol levels in the skin. Additionally,
medication use also characteristically increases with age. Some
pharmaceutical medications activate the pregnan-X receptor,
reducing serum 25 (OH) D concentrations. These drugs consist
of antiepileptics, antineoplastics, antibiotics, anti-inflammatory
agents, antihypertensives, antiretrovirals, endocrine drugs, and
some herbal medicines.
On the other hand, when we look at past pandemics in
the world, a strong correlation was found between the
case death rates and UVB exposure rates in the influenza
epidemic of 1918-1919 (17). When the mortality rates in the
United States (USA) were analyzed, the case mortality rate
was approximately 6% in the northern states, whereas in the
southern states it decreased to 3.5% (18). At this point, it comes
to our mind that the change in mortality rates may be due to the
difference of UVB exposure and vitamin D levels depending
on the geographical locations in these regions. In accordance
LETTER TO THE EDITOR
M.T. Aslan1, İ.Ö. Aslan2, Ö. Özdemir3, 1. Istanbul University Istanbul Faculty of Medicine, Department of Pediatrics, Division
of Neonatology, Istanbul, Turkey; 2. University of Health Sciences, Bakirkoy Dr. Sadi Konuk Training and Research Hospital,
Department of Obstetrics and Gynecology, Istanbul, Turkey; 3. Sakarya University, Training and Research Hospital, Department
of Pediatrics, Division of Allergy and Immunology, Sakarya, Turkey. Corresponding author: Öner Özdemir, Sakarya University,
Training and Research Hospital, Department of Pediatrics, Division of Allergy and Immunology, Sakarya / Turkey, ozdemir_
oner@hotmail.com
IS VITAMIN D ONE OF THE KEY ELEMENTS IN COVID-19 DAYS?
© Serdi and Springer-Verlag International SAS, part of Springer Nature
J Nutr Health Aging. 2020;
IS VITAMIN D ONE OF THE KEY ELEMENTS IN COVID-19 DAYS?
J Nutr Health Aging
2
with our opinion, we see that the frequency of vitamin D
deficiency is known to be very high in European countries such
as Italy, Spain and France (19), where the mortality rates due to
COVID-19 disease are the highest.
When another study of 212 patients with proven SARS-
CoV-2 infection was examined, serum 25 (OH) D level was the
lowest in clinically severe cases, whereas it was highest in mild
cases. Relation with serum 25 (OH) D levels was demonstrated
to be statistically meaningful among clinical results. When all
the results in the study are evaluated, the rise in serum 25 (OH)
D levels in the COVID-19 patients suggests that it may improve
clinical course or alleviate clinical outcomes even in severe
cases. On the other hand, it may mean that the decline in serum
25 (OH) D levels in the body may worsen the clinical outcomes
in patients (20). In another study involving twenty European
countries, a negative correlation was found between serum 25
(OH) D levels and the total number of cases with COVID-19
disease and mortality rates due to this disease (21).
In the light of the literature knowledge above, we know that
the antiviral and anti-inflammatory effectiveness of vitamin D
is quite high. It comes to mind that vitamin D supplementation
in the treatment may have a preventive effect on some negative
consequences. Among the causes of this clinical diversity in
the course and mortality rates of the COVID-19 cases, it is
an important to remind that vitamin D deficiency can also be
underlying comorbidity in the patients.
As a conclusion, in this period when we fought against the
COVID-19 pandemic, which affected many countries around
the world and caused thousands of people to die, no clear agent
has been found in its treatment. In fact, an easily accessible
agent such as vitamin D may be an important weapon in our
hands. However, there is no clear evidence for high-dose or
dose of vitamin D supplementation in patients with SARS-
CoV-2 infection. Although there is a need for more research
related to this subject, we think that supplementing vitamin D
as a part of standard nutrition may be somewhat effective in
providing clinical benefit.
Acknowledgment: We would like to thank all our heroes actively working on this
subject, both in the field and on the scientific platform, during these challenging days in the
world, where the COVID-19 pandemic has been experienced.
References
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diseases. Expert Opin. Biol. Ther. 2007, 7, 1449–1461.
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cathelicidin LL-37. PLoS ONE 2011, 6, e25333.
11. Zhao Y, Ran Z, Jiang Q, Hu N, Yu B, Zhu L, Shen L, Zhang S, Chen L, Chen H, et al. Vitamin
D Alleviates Rotavirus Infection through a Microrna-155-5p Mediated Regulation of the TBK1/
IRF3 Signaling Pathway In Vivo and In Vitro. Int. J. Mol. Sci. 2019, 20.
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supplementation on dengue virus replication, Toll-like receptor expression, and cytokine profiles
on dendritic cells. Mol. Cell. Biochem. 2020, 464, 169–180
13. Cantorna MT, Snyder L, Lin YD, Yang L. Vitamin D and 1,25(OH)2D regulation of T cells.
Nutrients 2015, 7, 3011–3021.
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15. Palacios C, Gonzalez L. Is vitamin D deficiency a major global health problem.J Steroid
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18. Marik PE, Kory P, Varon J. Does vitamin D status impact mortality from SARS-CoV-2
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19. Lips P, Cashman K, Lamberg-Allardt C et al (2019) Current vitamin D status in European and
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European Calcified Tissue Society. Eur J Endocrinol 180:23–54
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doi:10.1007/s40520-020-01570-8
... За останні десятиліття були зареєстровані численні захворювання, асоційовані з дефіцитом VD, але не пов'язані зі скелетом, зокрема ІР, метаболічний синдром, ЦД 2-го типу (ЦД2), ССЗ, когнітивні порушення та ретинопатія. Крім того, останні дослідження показали, що VD може впливати на інфікування вірусом COVID-19 SARS-CoV-2 та перебіг хвороби [1][2][3]. ...
... Вважається, що дефіцит VD також є елементом ризику для самого ARDS (acute respiratory distress syndrome). В експериментах на тваринах з ARDS також було показано, що інфікування вірусом легень може бути зменшене шляхом модуляції активності РААС та експресії ACE2 при лікуванні вітаміном D [1]. ...
... Показано, що VD гальмує реплікацію вірусу грипу А, а також ротавірусу in vitro та in vivo. У клінічному дослідженні також повідомлялося, що добавки 4000 МО на добу VD зменшують ступінь тяжкості при захворюванні вірусом денге [1]. ...
Article
Full-text available
Вітамін D (vitamin D, VD), це універсальний стероїдний гормон, який регулює активність кількох тисяч генів. За останні десятиліття були зареєстровані численні захворювання, асоційовані з дефіцитом VD, зокрема інсулінорезистентність (ІР), метаболічний синдром, цукровий діабет (ЦД), серцево-судинні захворювання (ССЗ), рак та когнітивні порушення. Крім того, дослідження 2020 року показали, що VD може впливати на інфікування вірусом COVID‑19 SARS-CoV‑2 та перебіг хвороби. Важливим фактом є те, що епідеміологічні дослідження продемонстрували високий рівень поширення дефіциту або недостатності VD у всьому світі. Недостатність VD є сильним дієтичним пусковим механізмом, наслідком якого є важкі хронічні захворювання. Потенціал VD терапії для хворих на ЦД очевидний. Його імуномодулювальні ефекти сприяють індукції імунної толерантності та анергії Т-клітин, пригнічують активність В-клітин та вироблення антитіл, зменшують запальну реакцію, корисні для профілактики та лікування ЦД 1-го типу. VD здійснює прямий та побічний вплив на гомеостаз глюкози — секрецію інсуліну, чутливість до інсуліну та системне запалення, яке спостерігається при ЦД 2-го типу та ожирінні. Сигналінг VD необхідний для серцево-судинної функції, особливо для регуляції судинного тонусу, а також як антифібротичний та антигіпертрофічний фактор. Оскільки VD регулює нейромедіатори та нейротрофіни, багато досліджень свідчать про важливість VD для запобігання когнітивних порушень та ретинопатії. VD посилює протизапальну та противірусну реакцію епітеліальних клітин у дихальній системі при респіраторних вірусних інфекціях. Показано, що введення VD пацієнтам з його дефіцитом допомагає при інфікуванні вірусами, такими як COVID‑19. Приймання VD в осінньо-зимовий період для пацієнтів із високим ризиком розвитку захворювань дихальних шляхів надає їм додатковий захист. Під час пандемії бажано приймати 1000-2000 МО на день у формі полівітамінів або добавок VD. Щоденне вживання VD рекомендуєтьсячерез короткий період його напіврозпаду в циркуляції. VD може бути основною допоміжною терапією при лікуванні пацієнтів, які постраждали від COVID‑19, а також для осіб з його дефіцитом.
... За останні десятиліття були зареєстровані численні захворювання, асоційовані з дефіцитом VD, але не пов'язані зі скелетом, зокрема ІР, метаболічний синдром, ЦД 2-го типу (ЦД2), ССЗ, когнітивні порушення та ретинопатія. Крім того, останні дослідження показали, що VD може впливати на інфікування вірусом COVID-19 SARS-CoV-2 та перебіг хвороби [1][2][3]. ...
... Вважається, що дефіцит VD також є елементом ризику для самого ARDS (acute respiratory distress syndrome). В експериментах на тваринах з ARDS також було показано, що інфікування вірусом легень може бути зменшене шляхом модуляції активності РААС та експресії ACE2 при лікуванні вітаміном D [1]. ...
... Показано, що VD гальмує реплікацію вірусу грипу А, а також ротавірусу in vitro та in vivo. У клінічному дослідженні також повідомлялося, що добавки 4000 МО на добу VD зменшують ступінь тяжкості при захворюванні вірусом денге [1]. ...
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Full-text available
Effects of vitamin D in various pathologies L.K. Sokolova, V.M. Pushkarev, M.D. Tronko SI «VP Komisarenko Institute of Endocrinology and Metabolism of the National Academy of Medical Sciences of Ukraine» Abstract. Vitamin D (VD) is a universal steroid hormone that regulates the activity of several thousand genes. Numerous diseases associated with VD deficiency have been reported in recent decades, including insulin resistance (IR), metabolic syndrome, diabetes mellitus (DM), cardiovascular disease (CVD), cancer, and cognitive impairment. In addition, studies in 2020 have shown that VD can affect COVID‑19 SARS-CoV‑2 infection and disease. An important fact is that epidemiological studies have shown a high prevalence of VD deficiency or insufficiency worldwide. VD deficiency is a strong dietary trigger, resulting in severe, chronic disease. The potential of VD therapy for DM patients is obvious. Its immunomodulatory effects promote the induction of immune tolerance and T-cell anergy, inhibit B-cell activity and antibody production, reduce the inflammatory response, and are useful for the prevention and treatment of DM type 1. VD has direct and indirect effects on glucose homeostasis — insulin secretion, insulin sensitivity and systemic inflammation, which is observed in DM type 2 and obesity. VD signaling is required for cardiovascular function, especially for the regulation of vascular tone, as well as antifibrotic and antihypertrophic factors. Because VD regulates neurotransmitters and neurotrophins, many studies have shown the importance of VD in preventing cognitive impairment and retinopathy. VD enhances the anti-inflammatory and antiviral response of epithelial cells in the respiratory system at viral infections. Administration of VD to patients with VD deficiency has been shown to help with infections such as COVID‑19. Taking VD in the autumn-winter period for patients at high risk of development of respiratory diseases provides them additional protection. During a pandemic, it is desirable to take 1000-2000 IU per day in the form of multivitamins or VD supplements. Daily use of VD is recommended because of a short half-life in the circulation. VD may be the main adjunctive therapy in the treatment of patients with COVID‑19 for people with VD deficiency. Keywords: vitamin D, diabetes mellitus, cardiovascular diseases, COVID‑19, cognitive impairment, obesity, retinopathy, immune system.
... (151) Oral vitamin D supplements of 4000IU for 10 days were significantly more effective than 1000IU in reducing dengue virus replication and controlling the damaging cytokine hyper-reaction. (151)(152)(153)(154) Vitamin D supplementation also reduced rotavirus replication in pigs. (154) A recent review article by Sharma, et al., summarized biological plausibility arguments and found that vitamin D deficiency is associated with a wide range of viral illnesses, and that vitamin D supplementation was both preventative and decreased severity, limiting hyper-inflammatory complications. ...
... (151)(152)(153)(154) Vitamin D supplementation also reduced rotavirus replication in pigs. (154) A recent review article by Sharma, et al., summarized biological plausibility arguments and found that vitamin D deficiency is associated with a wide range of viral illnesses, and that vitamin D supplementation was both preventative and decreased severity, limiting hyper-inflammatory complications. (107) In the lungs, formation of the peptide LL37, an innate immune system component that, among other things, attacks enveloped viruses such as SARS-CoV-2 and modulates the immune system, requires sufficient vitamin D levels. ...
Article
Full-text available
As the world’s attention has been riveted upon the growing COVID-19 pandemic, many researchers have written brief reports supporting the hypothesis that vitamin D deficiency is related to the incidence and severity of COVID-19. The clear common thread among the top risk groups - vitamin D deficiency – may be being overlooked because of previous overstated claims of vitamin D benefits. However, the need to decrease COVID-19 fatalities among high-risk populations is urgent. Early researchers reported three striking patterns. Firstly, the innate immune system is impaired by vitamin D deficiency, which would predispose sufferers to viral infections such as COVID-19. Vitamin D deficiency also increases the activity of the X-chromosome-linked ‘Renin-Angiotensin’ System, making vitamin D deficient individuals (especially men) more susceptible to COVID-19’s deadly “cytokine storm” (dramatic immune system overreaction). Secondly, the groups who are at highest risk for severe COVID-19 match those who are at highest risk for severe vitamin D deficiency. This includes the elderly, men, ethnic groups whose skin is naturally rich in melanin (if living outside the tropics), those who avoid sun exposure for cultural and health reasons, those who live in institutions, the obese, and/or those who suffer with hypertension, cardiovascular disease, or diabetes. And thirdly, the pattern of geographical spread of COVID-19 reflects higher population vitamin D deficiency. Not only within the USA but throughout the world, COVID-19 fatality rates parallel vitamin D deficiency rates. A literature search was performed on PubMed, Google Scholar, and RSMLDS, with targeted Google searches providing additional sources. Although randomized controlled trial results may be available eventually, the correlational and causal study evidence supporting a link between vitamin D deficiency and COVID-19 risks is already so strong that it supports action. The 141 authorial groups writing primarily about biological plausibility detailed how vitamin D deficiency can explain every risk factor and every complication of COVID-19, but agreed that other factors are undoubtedly at work. COVID-19 was compared with dengue fever, for which oral vitamin D supplements of 4000IU for 10 days were significantly more effective than 1000IU in reducing virus replication and controlling the “cytokine storm” (dramatic immune system over-reaction) responsible for fatalities. Among the 47 original research studies summarized here, chart reviews found that serum vitamin D levels predicted COVID-19 mortality rates (16 studies) and linearly predicted COVID-19 illness severity (8 studies). Two causal modeling studies and several analyses of variance strongly supported the hypothesis that vitamin D deficiency is a causal, rather than a bystander, factor in COVID-19 outcomes. Three of the four studies whose findings opposed the hypothesis relied upon disproven assumptions. The literature review also found that prophylactically correcting possible vitamin D deficiency during the COVID-19 pandemic is extremely safe. Widely recommending 2000IU of vitamin D daily for all populations with limited ability to manufacture vitamin D from the sun has virtually no potential for harm and is reasonably likely to save many lives.
... (151) Oral vitamin D supplements of 4000IU for 10 days were significantly more effective than 1000IU in reducing dengue virus replication and controlling the damaging cytokine hyper-reaction. (151)(152)(153)(154) Vitamin D supplementation also reduced rotavirus replication in pigs. (154) A recent review article by Sharma, et al., summarized biological plausibility arguments and found that vitamin D deficiency is associated with a wide range of viral illnesses, and that vitamin D supplementation was both preventative and decreased severity, limiting hyper-inflammatory complications. ...
... (151)(152)(153)(154) Vitamin D supplementation also reduced rotavirus replication in pigs. (154) A recent review article by Sharma, et al., summarized biological plausibility arguments and found that vitamin D deficiency is associated with a wide range of viral illnesses, and that vitamin D supplementation was both preventative and decreased severity, limiting hyper-inflammatory complications. (107) In the lungs, formation of the peptide LL37, an innate immune system component that, among other things, attacks enveloped viruses such as SARS-CoV-2 and modulates the immune system, requires sufficient vitamin D levels. ...
Article
Full-text available
As the world’s attention has been riveted upon the growing COVID-19 pandemic, many researchers have written brief reports supporting the hypothesis that vitamin D deficiency is related to the incidence and severity of COVID-19. The clear common thread among the top risk groups - vitamin D deficiency – may be being overlooked because of previous overstated claims of vitamin D benefits. However, the need to decrease COVID-19 fatalities among high-risk populations is urgent. Early researchers reported three striking patterns. Firstly, the innate immune system is impaired by vitamin D deficiency, which would predispose sufferers to viral infections such as COVID-19. Vitamin D deficiency also increases the activity of the X-chromosome-linked ‘Renin-Angiotensin’ System, making vitamin D deficient individuals (especially men) more susceptible to COVID-19’s deadly “cytokine storm” (dramatic immune system overreaction). Secondly, the groups who are at highest risk for severe COVID-19 match those who are at highest risk for severe vitamin D deficiency. This includes the elderly, men, ethnic groups whose skin is naturally rich in melanin (if living outside the tropics), those who avoid sun exposure for cultural and health reasons, those who live in institutions, the obese, and/or those who suffer with hypertension, cardiovascular disease, or diabetes. And thirdly, the pattern of geographical spread of COVID-19 reflects higher population vitamin D deficiency. Not only within the USA but throughout the world, COVID-19 fatality rates parallel vitamin D deficiency rates. A literature search was performed on PubMed, Google Scholar, and RSMLDS, with targeted Google searches providing additional sources. Although randomized controlled trial results may be available eventually, the correlational and causal study evidence supporting a link between vitamin D deficiency and COVID-19 risks is already so strong that it supports action. The 141 authorial groups writing primarily about biological plausibility detailed how vitamin D deficiency can explain every risk factor and every complication of COVID-19, but agreed that other factors are undoubtedly at work. COVID-19 was compared with dengue fever, for which oral vitamin D supplements of 4000IU for 10 days were significantly more effective than 1000IU in reducing virus replication and controlling the “cytokine storm” (dramatic immune system over-reaction) responsible for fatalities. Among the 47 original research studies summarized here, chart reviews found that serum vitamin D levels predicted COVID-19 mortality rates (16 studies) and linearly predicted COVID-19 illness severity (8 studies). Two causal modeling studies and several analyses of variance strongly supported the hypothesis that vitamin D deficiency is a causal, rather than a bystander, factor in COVID-19 outcomes. Three of the four studies whose findings opposed the hypothesis relied upon disproven assumptions. The literature review also found that prophylactically correcting possible vitamin D deficiency during the COVID-19 pandemic is extremely safe. Widely recommending 2000IU of vitamin D daily for all populations with limited ability to manufacture vitamin D from the sun has virtually no potential for harm and is reasonably likely to save many lives.
... (151) Oral vitamin D supplements of 4000IU for 10 days were significantly more effective than 1000IU in reducing dengue virus replication and controlling the damaging cytokine hyper-reaction. (151)(152)(153)(154) Vitamin D supplementation also reduced rotavirus replication in pigs. (154) A recent review article by Sharma, et al., summarized biological plausibility arguments and found that vitamin D deficiency is associated with a wide range of viral illnesses, and that vitamin D supplementation was both preventative and decreased severity, limiting hyper-inflammatory complications. ...
... (151)(152)(153)(154) Vitamin D supplementation also reduced rotavirus replication in pigs. (154) A recent review article by Sharma, et al., summarized biological plausibility arguments and found that vitamin D deficiency is associated with a wide range of viral illnesses, and that vitamin D supplementation was both preventative and decreased severity, limiting hyper-inflammatory complications. (107) In the lungs, formation of the peptide LL37, an innate immune system component that, among other things, attacks enveloped viruses such as SARS-CoV-2 and modulates the immune system, requires sufficient vitamin D levels. ...
Article
Full-text available
As the world’s attention has been riveted upon the growing COVID-19 pandemic, many researchers have written brief reports supporting the hypothesis that vitamin D deficiency is related to the incidence and severity of COVID-19. The clear common thread among the top risk groups - vitamin D deficiency – may be being overlooked because of previous overstated claims of vitamin D benefits. However, the need to decrease COVID-19 fatalities among high-risk populations is urgent. Early researchers reported three striking patterns. Firstly, the innate immune system is impaired by vitamin D deficiency, which would predispose sufferers to viral infections such as COVID-19. Vitamin D deficiency also increases the activity of the X-chromosome-linked ‘Renin-Angiotensin’ System, making vitamin D deficient individuals (especially men) more susceptible to COVID-19’s deadly “cytokine storm” (dramatic immune system overreaction). Secondly, the groups who are at highest risk for severe COVID-19 match those who are at highest risk for severe vitamin D deficiency. This includes the elderly, men, ethnic groups whose skin is naturally rich in melanin (if living outside the tropics), those who avoid sun exposure for cultural and health reasons, those who live in institutions, the obese, and/or those who suffer with hypertension, cardiovascular disease, or diabetes. And thirdly, the pattern of geographical spread of COVID-19 reflects higher population vitamin D deficiency. Not only within the USA but throughout the world, COVID-19 fatality rates parallel vitamin D deficiency rates. A literature search was performed on PubMed, Google Scholar, and RSMLDS, with targeted Google searches providing additional sources. Although randomized controlled trial results may be available eventually, the correlational and causal study evidence supporting a link between vitamin D deficiency and COVID-19 risks is already so strong that it supports action. The 141 authorial groups writing primarily about biological plausibility detailed how vitamin D deficiency can explain every risk factor and every complication of COVID-19, but agreed that other factors are undoubtedly at work. COVID-19 was compared with dengue fever, for which oral vitamin D supplements of 4000IU for 10 days were significantly more effective than 1000IU in reducing virus replication and controlling the “cytokine storm” (dramatic immune system over-reaction) responsible for fatalities. Among the 47 original research studies summarized here, chart reviews found that serum vitamin D levels predicted COVID-19 mortality rates (16 studies) and linearly predicted COVID-19 illness severity (8 studies). Two causal modeling studies and several analyses of variance strongly supported the hypothesis that vitamin D deficiency is a causal, rather than a bystander, factor in COVID-19 outcomes. Three of the four studies whose findings opposed the hypothesis relied upon disproven assumptions. The literature review also found that prophylactically correcting possible vitamin D deficiency during the COVID-19 pandemic is extremely safe. Widely recommending 2000IU of vitamin D daily for all populations with limited ability to manufacture vitamin D from the sun has virtually no potential for harm and is reasonably likely to save many lives.
... Вітамін D (VD) -це стероїдний гормон, що відіграє вирішальну роль у підтриманні кісткового й кальцієвого гомеостазу. Хоча він був відкритий ще в 1922-1923 рр., актуальною темою ендокринологічних досліджень цей вітамін став лише в останні десятиріччя, а нещодавно він привернув особливу увагу у зв'язку з пандемією COVID-19 через кореляцію між гіповітамінозом D і високим ризиком хронічних легеневих захворювань і смерті [1,2]. Зараз стало ясно, що VD характеризується складним, багатоступеневим метаболізмом і діє як гормон на багато мішеней. ...
Article
Full-text available
Effects of vitamin D in thyroid autoimmune pathologies: literature review and own data. Abstract. Background. Vitamin D (VD) is a versatile steroid hormone that regulates the activity of several thousand genes. Over the past decades, numerous diseases associated with VD deficiency have been reported, including cancer and autoimmune thyroid disorders. Researches revealed that VD can influence the development and course of these diseases. The VD participation in modulation of the hypothalamus-pituitary-thyroid gland axis, both at the level of the pituitary gland and at that of the thyroid, has been shown. The effect of VD on autoimmune diseases, including thyroid autoimmune diseases, is widely studied. Most of the existing data support the relationship between VD deficiency and a greater tendency to develop and higher antibody titers associated with Hashimoto’s thyroiditis, Graves’ disease (GD) and postpartum thyroiditis. An important fact is that epidemiological studies have demonstrated a high prevalence of VD deficiency or insufficiency throughout the world. VD insufficiency is a potent dietary trigger that results in severe, chronic diseases. The question arises how reliable is the relationship between VD and autoimmune thyroid diseases (AITD). Although the results of the studies performed are somewhat contradictory, the vast majority of data indicates a link between VD deficiency and an increased risk of developing the disease, high antibody titers, and difficulties in treatment. Genetic polymorphisms associated with VD function and metabolism also have some influence on the risk of ATD. With regard to the precise nature of the relationship between VD and AITD, it is believed that VD plays a small but significant role in the AITD pathogenesis. After the AITD development, its consequence may be an increase in VD deficiency. It is the need to determine the effect of VD supplementation in the prevention and treatment of AITD and its optimal level directly for clinical practice. It is necessary for clinical practice to determine the effect of VD supplements in the prevention and treatment of AITD and its optimal level. A study, the purpose of which was to study the content of VD, namely 25(OH)D in 176 patients with GD complicated by autoimmune ophthalmopathy (AO) and to identify a correlation relationship with antithyroid antibodies (TPO, TSHR-Ab) was carried out at the State Institution “V.P. Komissarenko Institute of Endocrinology and Metabolism of the National Academy of Medical Sciences of Ukraine”. Materials and methods. The levels of 25(OH)D, TSH, TSHR-Ab, TPO were determined by enzyme immunoassay using standard kits from Siemens firm. During the study, 176 patients were divided into two groups, depending on the presence of AO: the first group consisted of patients with GD without AO (62 people), the second group included patients with GD and AO (114 people). Results. In GD, 91.78 % of patients (161 people) have an insufficient level of 25(OH)D content: a suboptimal level was recorded in 42 patients (23.86 %), and a deficit — in 119 patients (67.61 %). A significant negative correlation relationship was revealed between TSHR-Ab and 25(OH)D in the group of patients with GD and AO — with a lower level of 25(OH)D, the higher values of TSHR-Ab correlate. Compensation of the 25(OH)D deficiency leads to a significant (P < 0.05) decrease in the levels of TSHR-Ab and TPO in patients with GD. Besides, there is a large body of literature available linking vitamin D to thyroid autoimmunity as a result of cross-sectional studies and observations. Conclusions. Thus, there is still an urgent need for large multicenter studies to evaluate the effect of vitamin D supplementation on meaningful long-term clinical endpoints in AITD. Keywords: vitamin D; thyroid gland; autoimmune diseases; immune system
... Вітамін D (VD) -це стероїдний гормон, що відіграє вирішальну роль у підтриманні кісткового й кальцієвого гомеостазу. Хоча він був відкритий ще в 1922-1923 рр., актуальною темою ендокринологічних досліджень цей вітамін став лише в останні десятиріччя, а нещодавно він привернув особливу увагу у зв'язку з пандемією COVID-19 через кореляцію між гіповітамінозом D і високим ризиком хронічних легеневих захворювань і смерті [1,2]. Зараз стало ясно, що VD характеризується складним, багатоступеневим метаболізмом і діє як гормон на багато мішеней. ...
Article
Full-text available
Background. Vitamin D (VD) is a versatile steroid hormone that regulates the activity of several thousand genes. Over the past decades, numerous diseases associated with VD deficiency have been reported, including cancer and autoimmune thyroid disorders. Researches revealed that VD can influence the development and course of these diseases. The VD participation in modulation of the hypothalamus-pituitary-thyroid gland axis, both at the level of the pituitary gland and at that of the thyroid, has been shown. The effect of VD on autoimmune diseases, including thyroid autoimmune diseases, is widely studied. Most of the existing data support the relationship between VD deficiency and a greater tendency to develop and higher antibody titers associated with Hashimoto’s thyroiditis, Graves’ disease (GD) and postpartum thyroiditis. An important fact is that epidemiological studies have demonstrated a high prevalence of VD deficiency or insufficiency throughout the world. VD insufficiency is a potent dietary trigger that results in severe, chronic diseases. The question arises how reliable is the relationship between VD and autoimmune thyroid diseases (AITD). Although the results of the studies performed are somewhat contradictory, the vast majority of data indicates a link between VD deficiency and an increased risk of developing the disease, high antibody titers, and difficulties in treatment. Genetic polymorphisms associated with VD function and metabolism also have some influence on the risk of ATD. With regard to the precise nature of the relationship between VD and AITD, it is believed that VD plays a small but significant role in the AITD pathogenesis. After the AITD development, its consequence may be an increase in VD deficiency. It is the need to determine the effect of VD supplementation in the prevention and treatment of AITD and its optimal level directly for clinical practice. It is necessary for clinical practice to determine the effect of VD supplements in the prevention and treatment of AITD and its optimal level. A study, the purpose of which was to study the content of VD, namely 25(OH)D in 176 patients with GD complicated by autoimmune ophthalmopathy (AO) and to identify a correlation relationship with antithyroid antibodies (TPO, TSHR-Ab) was carried out at the State Institution “V.P. Komissarenko Institute of Endocrinology and Metabolism of the National Academy of Medical Sciences of Ukraine”. Materials and methods. The levels of 25(OH)D, TSH, TSHR-Ab, TPO were determined by enzyme immunoassay using standard kits from Siemens firm. During the study, 176 patients were divided into two groups, depending on the presence of AO: the first group consisted of patients with GD without AO (62 people), the second group included patients with GD and AO (114 people). Results. In GD, 91.78 % of patients (161 people) have an insufficient level of 25(OH)D content: a suboptimal level was recorded in 42 patients (23.86 %), and a deficit — in 119 patients (67.61 %). A significant negative correlation relationship was revealed between TSHR-Ab and 25(OH)D in the group of patients with GD and AO — with a lower level of 25(OH)D, the higher values of TSHR-Ab correlate. Compensation of the 25(OH)D deficiency leads to a significant (P < 0.05) decrease in the levels of TSHR-Ab and TPO in patients with GD. Besides, there is a large body of literature available lin-king vitamin D to thyroid autoimmunity as a result of cross-sectional studies and observations. Conclusions. Thus, there is still an urgent need for large multicenter studies to evaluate the effect of vitamin D supplementation on meaningful long-term clinical endpoints in AITD.
... Also, a European study analysis of SARS-CoV-2 severity based on vitamin D status suggested that countries with the highest rate of vitamin D deficiency are associated with the highest rates of COVID-19 infection and mortality [150]. Therefore, vitamin D supplements as a part of standard nutrition in COVID-19 may provide certain clinical benefits though more research related to this subject is solicited [151]. ...
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Vitamin D known for its vital role in diverse biological function such as calcium and phosphorus homeostasis, also exert an anticoagulant effect emphasizing its essential role in the thrombosis pathogenesis. Thrombosis is the formation and propagation of a blood clot or thrombus either in the arterial or the venous system resulting in several severe complications. Various studies have also reported the association of vitamin D deficiency with the increased incidences of thromboembolism. This may be in part due to its anticoagulant effects through upregulation of thrombomodulin, an anticoagulant glycoprotein, and downregulation of Tissue Factor, a critical coagulation factor. The protective effects of vitamin D and its receptor in endothelial cells may further explain some of the reported beneficial effects of vitamin D in the prevention or treatment of cardiovascular diseases. Additionally, the immunomodulatory role of vitamin D has been observed through its ability to alter the secretion of inflammatory cytokines that can induce a procoagulant milieu by multiple pathways. Therefore, it becomes pertinent to discuss the close link between vitamin D and human health and to improve our knowledge of the molecular pathways regulated or influenced by vitamin D and its associated metabolites.
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Vitamin D deficiency (serum 25-hydroxyvitamin D (25(OH)D) < 50 nmol/l or 20 ng/ml), is common in Europe and the Middle East. It occurs in < 20 % of the population in Northern Europe, in 30-60% in Western, Southern and Eastern Europe and up to 80 % in Middle East countries. Severe deficiency (serum 25(OH)D < 30 nmol/l or 12 ng/ml) is found in > 10 % of Europeans. The ECTS advises that the measurement of serum 25(OH)D be standardized e.g. by the Vitamin D Standardization Program. Risk groups include young children, adolescents, pregnant women, older people, especially the institutionalized, and non-western immigrants. Consequences of vitamin D deficiency include mineralization defects and lower bone mineral density causing fractures. Extra-skeletal consequences may be muscle weakness, falls and acute respiratory infection, and are the subject of large ongoing clinical trials. The ECTS advises to improve vitamin D status by food fortification and the use of vitamin D supplements in risk groups. Fortification of foods by adding vitamin D to dairy products, bread and cereals can improve the vitamin D status of the whole population, but quality assurance monitoring is needed to prevent intoxication. Specific risk groups such as infants and children up to 3 years, pregnant women, older persons and non-western immigrants should routinely receive vitamin D supplements. Future research should include genetic studies to better define individual vulnerability for vitamin D deficiency, and Mendelian randomization studies to address the effect of vitamin D deficiency on long term non-skeletal outcomes such as cancer.
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The pleiotropic role of vitamin D has been explored over the past decades and there is compelling evidence for an epidemiological association between poor vitamin D status and a variety of diseases. While the potential anti‐viral effect of vitamin D has recently been described, the underlying mechanisms by which vitamin D deficiency could contribute to viral disease development remain poorly understood. The possible interactions between viral infections and vitamin D appear to be more complex than previously thought. Recent findings indicate a complex interplay between viral infections and vitamin D, including the induction of anti‐viral state, functional immunoregulatory features, interaction with cellular and viral factors, induction of autophagy and apoptosis, and genetic and epigenetic alterations. While crosstalk between vitamin D and intracellular signalling pathways may provide an essential modulatory effect on viral gene transcription, the immunomodulatory effect of vitamin D on viral infections appears to be transient. The interplay between viral infections and vitamin D remains an intriguing concept, and the global imprint that vitamin D can have on the immune signature in the context of viral infections is an area of growing interest.