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Abstract

The study discusses the possible role of adequate vitamin D status in plasma or serum for preventing acute respiratory infections during the Covid-19 pandemic. Our arguments respond to an article, published in Italy, that describes the high prevalence of hypovitaminosis D in older Italian women and raises the possible preventive and therapeutic role of optimal vitamin D levels. Based on literature review, we highlight the findings regarding the protective role of vitamin D for infectious diseases of the respiratory system. However, randomized controlled trials are currently lacking. Adequate vitamin D status is obtained from sun exposure and foods rich in vitamin D. Studies in Brazil have shown that hypovitaminosis D is quite common in spite of high insolation. Authors recommend ecological, epidemiological and randomized controlled trials studies to verify this hypothesis.
1
https://doi.org/10.11606/s1518-8787.2020054002545
CommentRev Saude Publica. 2020;54:53
Does Vitamin D play a role in the
management of Covid-19 in Brazil?
Helena RibeiroI, Keila Valente de Souza de SantanaII , Soa Lizarralde OliverII ,
Patricia Helen de Carvalho RondóIII , Marcela Moraes MendesIV , Karen CharltonV ,
Susan Lanham-NewIV
I Universidade de São Paulo. Faculdade de Saúde Pública. Departamento de Saúde Ambiental. São Paulo, SP,
Brasil
II Universidade de São Paulo. Faculdade de Saúde Pública. Programa de Pós-Graduação em Saúde Global e
Sustentabilidade. São Paulo, SP, Brasil
III Universidade de São Paulo. Faculdade de Saúde Pública. Departamento de Nutrição. São Paulo, SP, Brasil
IV University of Surrey. School of Biosciences and Medicine. Faculty of Health and Medical Sciences. Department
of Nutritional Sciences. Guildford, Surrey, United Kingdom
V University of Wollongong. School of Medicine. Faculty of Science. Medicine and Health. Nutrition and
Dietetics. Wollongong, Australia
ABSTRACT
e study discusses the possible role of adequate vitamin D status in plasma or serum for
preventing acute respiratory infections during the Covid-19 pandemic. Our arguments respond
to an article, published in Italy, that describes the high prevalence of hypovitaminosis D in older
Italian women and raises the possible preventive and therapeutic role of optimal vitamin D levels.
Based on literature review, we highlight the ndings regarding the protective role of vitamin
D for infectious diseases of the respiratory system. However, randomized controlled trials are
currently lacking. Adequate vitamin D status is obtained from sun exposure and foods rich in
vitamin D. Studies in Brazil have shown that hypovitaminosis D is quite common in spite of
high insolation. Authors recommend ecological, epidemiological and randomized controlled
trials studies to verify this hypothesis.
DESCRIPTORS: Coronavirus Infections, prevention & control. Vitamin D. Review.
Correspondência:
Helena Ribeiro
Universidade de São Paulo
Faculdade de Saúde Pública
Departamento de Saúde Ambiental
Av. Dr. Arnaldo, 715
01246-904 São Paulo, SP, Brasil
E-mail: lena@usp.br
Received: Apr 13, 2020
Approved: Apr 22, 2020
How to cite: Ribeiro H, Santana
KVS, Oliver SL, Rondó PHC,
Mendes MM, Charlton K, Lanham-
New S. Does Vitamin D play a role
in the management of Covid-19
in Brazil? Rev Saude Publica.
2020;54:53.
Copyright: This is an open-access
article distributed under the
terms of the Creative Commons
Attribution License, which permits
unrestricted use, distribution, and
reproduction in any medium,
provided that the original author
and source are credited.
http://www.rsp.fsp.usp.br/
2
Vitamin D in the management of Covid-19 in Brazil Ribeiro H et al.
https://doi.org/10.11606/s1518-8787.2020054002545
INTRODUCTION
On March 25, 2020, doctors Isaia and Medicoa, from Università degli Studi of Turin, Italy,
released study, still in pre-print form, based on literature review, titled Possible preventive
and therapeutic role of vitamin D in the management of the Covid-19 pandemic. In the
manuscript1, the authors relate hypovitaminosis D to the prevention and treatment of
Covid-19, in association with other essential preventive measures. According to the authors:
Sulla base di numerose evidenze scientiche e di considerazioni epidemiologiche, sembra che il
raggiungimento di adeguati livelli plasmatici di Vitamina D sia necessario anzitutto per prevenire
le numerose patologie croniche che possono ridurre l’aspettativa di vita nelle persone anziane,
ma anche per determinare una maggiore resistenza all’infezione COVID-19 che, sebbene con
minore evidenza scientica, può essere considerata verosimile. (Isaia and Medico, 2020, p.1)a
Reference studies show the role of optimal vitamin D levels in the prevention and control
of severe respiratory infections.
Since the authors collaborate in an international research aimed to investigate vitamin D
status in older women from four continentsb, contributions to this topic are being made
within the context of the Covid-19 pandemic. e rationale is based on evidence of the
potential protective role of vitamin D in several diseases.
VITAMIN D AND THE HEALTH OF THE OLDER POPULATION
Adequate vitamin D status can be obtained from adequate sun exposure and foods rich
in vitamin D. Recently, vitamin D deciency has been considered a global and widespread
health concern at all ages2. Older people are the most prone to hypovitaminosis D due to
(a) low sun exposure when homebound or institutionalized, (b) reduced skin capacity to
convert dehydrocholesterol into cholecalciferol, (c) changes in appetite and diet predisposing
suboptimal vitamin D intake accompanied by reduced gastrointestinal absorption, (d)
polypharmacy including medications that interfere in vitamin absorption or metabolism
and (e) impairment of renal function3.
Changes or deciencies in the activation and control of vitamin D absorption result in
organic disorders that may evolve to important pathologies such as rickets in children
and osteomalacia or osteoporosis in adults3–6. A body of analyses from epidemiological
evidence shows an association between vitamin D deciency and increased risk of diabetes,
cardiovascular diseases, osteoporosis, osteoarthritis, Alzheimer’s/dementia, myopia,
macular degeneration, multiple sclerosis and some types of cancer7, 8. However, the impact
of vitamin D supplementation on these outcomes in randomized controlled trials (RCT)
has not been reported.
VITAMIN D AND COVID-19
Researchers have been studying the protective potential of vitamin D against diseases and
health-related problems for many years, but here we highlight the protective role of vitamin
D for infectious diseases of the respiratory system. In their review, Isaia and Medico1 cite the
study of Bischo-Ferrari9, in which reduced concentrations of 25 (OH)D increase the risk of
osteoporosis in older adults, being also associated with tumors, cardiovascular diseases,
chronic autoimmune respiratory diseases, diabetes mellitus, neurological diseases and
hypertension. As highlighted by Isaia and Medico1, “these pathologies potentially cause
higher mortality, especially if these patients are aected by Covid-19” (p.2), but this has
not yet been proven.
Experimental studies using cell lines and mice have been conducted to elucidate the
pulmonary activation of vitamin D3 and its preventive eect against interstitial pneumonia10.
a Based on numerous scientic
evidences and epidemiological
considerations, it seems that
the achievement of adequate
plasma levels of Vitamin D
is necessary rst of all to
prevent the numerous chronic
pathologies that can reduce life
expectancy in elderly, but also to
determine a greater resistance to
covidCovid-19 infection which,
although with less scientic
evidence, can be considered
similar.(our translation)
b University Global Partnership
Network. Healthy living for
healthy ageing. Surrey, UK
UGPN; 2017 Award. Available
from: https://ugpn.org
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Vitamin D in the management of Covid-19 in Brazil Ribeiro H et al.
https://doi.org/10.11606/s1518-8787.2020054002545
Findings suggest that vitamin D is activated in the lungs and that its dietary intake can
prevent interstitial pneumonia by suppressing pulmonary brosis. Another study11 found
that vitamin D injected into veins of rats, in pharmacological doses, relieved acute lung
injur y induced by lipopolysaccharide (LPS). Sabetta et al.12 hypothesize that supplementation
with vitamin D, to increase concentrations in the general population, above 38 ng/ml,
would result in signicant health benet, by reducing the burden of viral infections of the
respiratory tract in healthy adults living in temperate climates. However, this is based solely
on speculation over the results of animal testing.
Isaia and Medico1, based on these and other studies, address hypovitaminosis D and the
epidemiology of Covid-19 that has been aecting Italy. ey argue that Italy is a country
with a high proportion of older people, and that 76% of older Italian women show vitamin
D deciency, without signicant regional dierences13. Nevertheless, Dr. Isaia informed: “I
have to underline that it is not a scientic paper, but only a literature review and an invitation
to reach normal levels of vitamin D in ageing population, and in particular in Coronavirus
patients” (Isaia, March 28, 2020, personal communication to these authors).
Recently, Sociedade Brasileira de Endocrinologia e Metabologia (SBEM – Brazilian Society of
Endocrinology and Metabolism) and Associação Brasileira de Avaliação Óssea e Osteometabolismo
(ABR ASSO – Brazilian Association of Bone Assessment and Osteometabolism) published a notec
highlighting that no indication for vitamin D supplementation was approved for eects
other than bone health. In this note, they mention an article of the Italian newspaper La
Reppublica, regarding a study conducted at Turin University, which suggested that vitamin
D could act in the prevention and treatment of Covid-19. Without mentioning the author’s
name, the note informs that this study has not been published in a scientic journal and
that relevant data were not cited, including the number and age of participants and their
25 (OH) D levels.
We believe this debate is based mainly on news of a non-scientic periodical and gained
importance in social media, erroneously motivating self-administration of high doses of
vitamin D. Meanwhile, the Brazilian president announced that vitamin D would be exempt
of import tax as a measure to combat coronavirus.
OTHER STUDIES THAT POTENTIALLY SUPPORT THE ROLE OF VITAMIN D
Ergocalciferol (D2) and cholecalciferol (D3) are among the most important compounds
that make up vitamin D. Ergocalciferol or vitamin D2 results from ultraviolet irradiation of
sunlight on ergosterol5. Pre-vitamin D3 or cholecalciferol originates from a photochemical
cleavage suered by the cutaneous precursor of vitamin D, 7-dehydrocholesterol, when
exposed to ultraviolet radiation5,14 . Current ly, there is no universal consensus on the optimal
concentrations for plasma/serum 25-hydroxyvitamin D [25 (OH) D]. In the USA, vitamin
D deciency is dened as a plasma/serum 25 (OH) D status below 12 ng/ml (30 nmol/L)
and insuciency of 25 (OH) D status below 20 ng/ml (50nmol/l)15. In the UK, vitamin D
deciency is dened as a plasma/serum 25 (OH) D status below 10 ng/ml (25 nmol/L)16.
Cannel et al.17 suggest 50 ng/ml is protective against viral respiratory infections, particularly
in obese, older population, and those with dark skin. is nding, however, is not based on
the results of a vitamin D RCT in humans. Dancer et al.18 referred that patients with, and
at risk of, acute respiratory distress syndrome, are highly likely to be decient in vitamin
D, based on evidence from human, murine and vitro experimental studies.
Ultraviolet B (UVB) radiation is the main source of the vitamin, providing around 80%. Foods
such as salmon and other oily sh, cod liver oil, egg yolk, milk and sun-dried mushrooms
are natural sources of vitamin D. Vitamin D supplementation and fortied foods such as
butter and milk are widely used in countries at high latitude with long winters such as
the USA. is is not the case in Brazil. e time of year, latitude, skin color, age and use
of sunscreen inuence skin production19,4. e widespread prevalence of hypovitaminosis
c Sociedade Brasileira de
Endocrinologia e Metabologia.
Nota de esclarecimento:
Vitamina D e COVID-19. Rio de
Janeiro: SBEM; 2020 [cited 2020
Apr 1]. Available from: https://
www.endocrino.org.br/nota-de-
esclarecimento-vitamina-d-e-
covid-19/
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Vitamin D in the management of Covid-19 in Brazil Ribeiro H et al.
https://doi.org/10.11606/s1518-8787.2020054002545
D can also be attributed to environmental factors, such as air pollution, which reduces
sunlight exposure2,20.
Exposure to chemical products and microparticles, dispersed in the urban atmosphere,
and tobacco smoke can disturb biochemical pathways and cause harmful consequences,
such as vitamin D deciency21. ese factors are directly or indirectly implicated in the
interruption of the endocrine system of vitamin D and in the decrease in serum levels of
two main metabolites: Calcifediol and Calcitriol21. While the shade of trees allows sucient
transmission of UVB for vitamin synthesis, that of buildings and glass windows attenuates
biologically signicant wavelengths22 . e time spent in outdoor activities by the population
is directly and indirectly related to the existence of green areas, levels of air pollution, safety,
and urban mobility.
Behavioral and cultural factors that inuence the way of life can also reduce the ability to
synthetize vitamin D by sunlight exposure. People with long working hours indoors and
ethnic minority groups with formal requirement for heavy and covered clothing style have
reduced capacity to synthesize vitamin D from UVB radiation23, 24. Darker skinned ethnic
groups are the most aected by the lack of UVB availability for the production of vitamin
D by the skin24.
With the exception of countries located at high latitudes, most individuals would obtain
sucient levels of vitamin D through sunlight exposure. However, the prevalence of vitamin
D deciency has also been reported in low latitude regions. In Brazil, a study conducted
in the city of São Paulo found that 72% of institutionalized older adults and 43.8% of older
people attending outpatient clinics showed lower levels of vitamin D3 than recommended,
contradicting the inference that in Brazil the population is vitamin D-replete due to the
high degree of insolation3.
Results of our study on vitamin D levels, in Araraquara, SP, called Morada do Sol (House of
the Sun), with 101 community-dwelling healthy women aged 35 years or older, show that
15.8% and 1% had vitamin D insuciency and deciency, respectively. However, 25% of Brow n
women had insuciency, according to IOM guidel ines15 , which is relevant to many Brazilia ns.
Higher prevalence of vitam in D insucienc y was also fou nd in women who worked in hea lth
and aesthetics services. is shows that even in tropical climates, a person’s occupation
may inuence sun exposure and vitamin D concentrations. In our study, vitamin D levels
were also inversely correlated with body mass index and waist circumference. Obesity is
linked to vitamin D insuciency because it hinders the bioavailability of vitamin D25 and
can lead to health complications, such as the development of some types of diabetes.
Many factors worsen vulnerability of populations to viral diseases, such as comorbidities
that might be associated with vitamin D deciency. Comorbidities have also been associated
with higher risk of hospitalization and deaths among those infected by Covid-19, increasing
the demand for beds and intensive care units, at a time of shortage.
FINAL CONSIDERATIONS
Hypovitaminosis D constitutes an additional risk to respiratory tract infections and to the
response of the immune system among the Brazilian population, despite high insolation,
even in winter. Further studies are urgently needed to investigate whether vitamin D status
or supplementation might decrease severity of Covid-19, particularly vitamin D randomized
controlled trials. Regular sunlight exposure is a preventive measure against vitamin D
deciency and can prevent diseases related to it. e urban population, especially the
older one, tends to be less exposed to sunlight, due to many factors24. us, people must
achieve and maintain adequate serum 25 (0H) D levels in a period of social distancing and
self-isolation. is might be obtained through lifestyle strategies, and a healthy balanced
diet. Considering the pandemic risk, the WHO and health authorities’ recommendations
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Vitamin D in the management of Covid-19 in Brazil Ribeiro H et al.
https://doi.org/10.11606/s1518-8787.2020054002545
for staying at home must be followed. For those who do not live in houses with gardens,
sunlight exposure can be obtained from open windows or balconies. Only if that is not
possible, should an oral vitamin D supplement be considered at SACN/IOM recommended
doses to maintain adequate vitamin D levels for general good health. We strongly advise
against hig h vitami n D supplements (e.g. 10,000IU per day) being cu rrently recommended26.
Adequate vitamin D status may play a role in prevention and management of respiratory
tract infections, which might include the Covid-19 pandemic, especially among the
older population and health professionals worldwide. We highly recommend ecological,
epidemiological and RCT studies to verify this hypothesis.
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19. Webb AR, Kline L, Holick MF. Inuence of season and latitude on the cutaneous
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promote vitamin D3 synthesis in human skin. J Clin Endocrinol Metab 1988;67(2):373-8.
https://doi.org/10.1210/jcem-67-2-373
20. Lee DH, Park KS, Cho MC. Laboratory conrmation of the effect of occupational sun exposure
on serum 25-hydroxyvitamin D concentration. Medicine (Baltimore).2018;97(27):e11419.
https://doi.org/10.1097/MD.0000000000011419
21. Mousavi SE, Amini H, Heydarpour P, Amini Chermahini F, Godderis L. Air pollution,
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mechanisms. Environ Int. 2019;122:67-90. https://doiorg/10.1016/j.envint.2018.11.052
22. Turnbull DJ, Parisi AV, Kimlin MG. Vitamin D effective ultraviolet wavelengths due to scattering in
shade. J Steroid Biochem Mol Biol. 2005;96(5):431-6. https://doi.org/10.1016/j.jsbmb.2005.04.039
23. Buckley AJ, Hammoun Z, Lessan N, Barakat MT. Environmental determinants of previtamin
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https://doi.org/10.1080/19381980.2016.1267079
24. Mendes MM, Darling AL, Hart KH, Morse S, Murphy RJ, Lanham-New SA. Impact of high latitude,
urban living and ethnicity on 25-hydroxyvitamin D status: a need for multidisciplinary action? J
Steroid Biochem Mol Biol. 2019;188:95-102. https://doi.org/10.1016/j.jsbmb.2018.12.012
25. Wortsman J, Matsuoka LY, Chen TC, Lu Z, Holick MF. Decreased bioavailability of vitamin D in
obesity. Am J Clin Nutr. 2000;72(3):690-3. htpps://doi.org/10.1093/ajcn/72.3.690
26. Grant WB, Lahore H, McDonnell S, Baggerly CA, French CB, Aliano JL, et al. Evidence that
vitamin d supplementation could reduce risk of inuenza and COVID-19 infections and deaths.
Nutrients. 2020;12(4):E988. https://doi.org/10.3390/nu12040988
Funding: UGPN - University Global Partnership Network, Research Collaboration Fund (RCF 2017) Healthy
Living for Healthy Ageing: a Global Focus. Award received in 2018. Capes PhD scholarship for KVSS. Capes PNPD
scholarship for SLO. CNPq productivity grant 1A for HR.
Authors’ Contribution: Work’s design, analysis, interpretation, and writing: HR. Manuscript draft writing:
KVSS, SLO. Writing of the nal manuscript: HR, KVSS, SLO, PHCR, MMM, KC, SLN. Final Approval: HR, KVSS,
SLO, PHCR, MMM, KC, SLN.
Conict of Interest: e authors declare no conict of interest.
... (29,55) Alarmed by the media response to a literature review suggesting a link between COVID-19 and vitamin D, two Brazilian medical associations jointly published a note stating that vitamin D supplements are only approved for bone health. (56)(57)(58) The high mortality rates among minorities are providing momentum for various public health program expansions, which could diminish if vitamin D deficiency, rather than access to care and economic disparities, were found to be even a partial explanation. (59)(60)(61)(62) In addition, previous studies of dubious quality suggesting that vitamin D can "cure" various chronic illnesses and may be influencing the reluctance to recommend supplements for COVID-19. ...
... (189) In part because vitamin D is fat-soluble, obese individuals have increased daily vitamin D intake requirements and are often deficient. (22,46,57,91,175,190,191) In addition, vitamin D deficiency causes the body to store more fat by increasing parathyroid hormone levels. (192) Obesity is a major risk factor for fatal COVID-19 complications, particularly in younger adults. ...
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.
... Riberio et al. [31] Adequate vitamin D status may play a role in prevention and management of respiratory tract infections such as COVID-19 ...
... One of these might be air pollution. As based on current data, the present working hypothesis, while limited by the lack of adequate research, would in our view thus tend to support, rather than refute the idea of a possible clinically relevant linkage between air pollution, and vitamin D deficiency and COVID-19 among the elderly that warrants attention [12,31,48,49]. In addition, efforts to maximize vitamin D serum levels, while ensuring air pollution is kept to a minimum, and does not impact adversely on COVID-19 prevalence and fatality rates as a result of its ability to increase susceptibility to bacteria and viruses in the respiratory system appear especially relevant among adults with pre existing health conditions [43,29,50,51]. ...
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Most current Corona virus or COVID-19 pandemic deaths have been found to occur among older adults. This article examines the possible independent and interactive factors of vitamin D and air pollution on the risk of COVID-19 disease among the older population.
... (29,55) Alarmed by the media response to a literature review suggesting a link between COVID-19 and vitamin D, two Brazilian medical associations jointly published a note stating that vitamin D supplements are only approved for bone health. (56)(57)(58) The high mortality rates among minorities are providing momentum for various public health program expansions, which could diminish if vitamin D deficiency, rather than access to care and economic disparities, were found to be even a partial explanation. (59)(60)(61)(62) In addition, previous studies of dubious quality suggesting that vitamin D can "cure" various chronic illnesses and may be influencing the reluctance to recommend supplements for COVID-19. ...
... (189) In part because vitamin D is fat-soluble, obese individuals have increased daily vitamin D intake requirements and are often deficient. (22,46,57,91,175,190,191) In addition, vitamin D deficiency causes the body to store more fat by increasing parathyroid hormone levels. (192) Obesity is a major risk factor for fatal COVID-19 complications, particularly in younger adults. ...
Article
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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.
... Desse modo, a prevalência de deficiência deve ser interpretada de acordo com os contextos e os fatores associados (ROTH et al., 2018). Há alguns fatores que são mais relacionados a tal deficiência, como mostram as seguintes pesquisas a serem relatadas, dentre os quais, podem-se destacar: idade, sexo, renda, escolaridade, cor da pele, atividade física, latitude, estação do ano, exposição solar, ocupação, vestimenta utilizada, além de ingestão de alimentos fonte (RIBEIRO et al., 2020). ...
... Additional therapies targeted at the exaggerated immune response, which commonly accompanies SARS-CoV-2 in severely ill patients include dexamethasone and targeted immune inhibitors, like sarilumab, an anti-interleukin 6 (IL-6) receptor antibody. Type 1 interferons (especially interferon-alpha), which have broad antiviral activity have been successful treatments in in-vitro studies against of SARS-CoV-2 [156] and have since then been evaluated in clinical trials to treat SARS-CoV-2 [14,157]. ...
Article
Background and aims The novel SARS-CoV-2 has been rattling the world since its outbreak in December 2019, leading to the COVID-19 pandemic. The learning curve of this new virus has been steep, with a global scientific community desperate to learn how the virus is transmitted, how it replicates, what cause such a wide spectrum of disease manifestations, causing none or few symptoms in some. Others are burdened by an intense immune response that resembles the cytokine storm syndrome (CSS), which leads to severe disease manifestations, often complicated by fatal acute respiratory distress syndrome and death. Research efforts have been focusing on finding effective cures and vaccinations for this virus. The presence of SARS-CoV-2 in the gastrointestinal (GI) tract, represented by several GI manifestations, has led to its investigation as a target for the virus and as an indicator of disease severity. The response of the microbiome (which is heavily linked to immunity) to the novel SARS-CoV-2 virus, and its role in igniting the exaggerated immune response has therefore become a focus of interest. The objective of our study was to gather the data connecting between the microbiome, the GI tract and COVID-19 and to investigate whether these reported alterations in the gut microbiome bear any resemblance to those seen in lupus, the prototypical autoimmune disease. Confirming such changes may become the steppingstone to potential therapies that may prevent transmission, progression and immune related manifestations of COVID-19, via manipulation of the gut microbiota. Methods We performed an extensive literature review, utilizing the Pubmed search engine and Google Scholar for studies evaluating the microbiome in COVID-19 patients and compared results with studies evaluating the microbiome in lupus. We searched for the terms: microbiome, dysbiosis, COVID-19, SARS-CoV-2, gastrointestinal as well as lupus and autoimmune. While there were hundreds of articles which referred to gastrointestinal manifestations in COVID-19, to date only 4 studies investigated the gastrointestinal microbiome in this setting. We compared the similarities between microbiome of COVID-19 patients and lupus patients. Results We found that there are several similar processes of immune dysregulation in patients with COVID-19 and in those with lupus, with several other alterations seen in other pathological states. Some of these similarities include loss of microbiota biodiversity, increased representation of pathobionts, which are microbes associated with inflammation and disease (i.e Proteobacteria) and a relative decrease of symbionts, which are protective microbes, associated with anti-inflammatory properties (i.e Lactobacillus). Compromise to the intestinal barrier has also been reported in both. Conclusions We conclude that the gastrointestinal tract contributes to the disease manifestations in COVID-19. Whether gastrointestinal dysbiosis is the cause or effect of gastrointestinal manifestations and several severe systemic manifestations, which may be the response to an increased pro-inflammatory environment, is still debatable and warrants further investigation. Given the resemblance of the microbiome in COVID-19 patients to that seen in lupus patients, it becomes clearer why several therapies used in autoimmune conditions are currently under investigation for the treatment of COVID-19 patients. Moreover, these findings should promote further investigating the utility of manipulation of the microbiome, via nutritional supplementation or even fecal transplantations, interventions that may alter the course of the disease, and potentially prevent disease transmission at low cost and low risk.
... [38][39] Some studies showed that the suggested protective roles of vitamin D are possible to inhibit the risk of coronavirus infection, or might be decreased the immunological risk related to its respiratory effects. [40][41][42][43][44][45][46][47][48][49] Vitamin D has immunomodulatory functions that include low regulation of proinflammatory cytokines. 50 63 Vitamin D with melatonin could prevent and treat of pulmonary infection by coronavirus. ...
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ABSTRACT The review is reported the relation of some supplements against COVID-19 is reported in the review. The review summaries recent modifications in the field of treatment and prevention of COVID-19 by high dose of immune vitamins (C and D). The review covers the relation of these vitamins with maintaining immune system strong in the body. Finally, the review shows some recommendations about using vitamins (C and D) with regulating doses.
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Objective To systemically review and critically appraise published studies of the association between vitamin D supplementation or serum vitamin D level and susceptibility to SARS-CoV-2 infection or COVID-19, including clinical course, morbidity and mortality outcomes. Design Systematic review. Data sources MEDLINE (OVID), Embase (OVID), Cochrane Central Register of Controlled Trials, MedRxiv and BioRxiv preprint databases. COVID-19 databases of the WHO, Cochrane, CEBM Oxford and Bern University up to 10 June 2020. Study selection Studies that assessed vitamin D supplementation and/or low serum vitamin D in patients acutely ill with, or at risk of, severe betacoronavirus infection (SARS-CoV, MERS-CoV, SARS-CoV-2). Data extraction Two authors independently extracted data using a predefined data extraction form and assessed risk of bias using the Downs and Black Quality Assessment Checklist. Results Searches elicited 449 papers, 59 studies were eligible full-text assessment and 4 met the eligibility criteria of this review. The four studies were narratively synthesised and included (1) a cross-sectional study (n=107) suggesting an inverse association between serum vitamin D and SARS-CoV-2; (2) a retrospective cohort study (348 598 participants, 449 cases) in which univariable analysis showed that vitamin D protects against COVID-19; (3) an ecological country level study demonstrating a negative correlation between vitamin D and COVID-19 case numbers and mortality; and (4) a case–control survey (n=1486) showing cases with confirmed/probable COVID-19 reported lower vitamin D supplementation. All studies were at high/unclear risk of bias. Conclusion There is no robust evidence of a negative association between vitamin D and COVID-19. No relevant randomised controlled trials were identified and there is no robust peer-reviewed published evidence of association between vitamin D levels and severity of symptoms or mortality due to COVID-19. Guideline producers should acknowledge that benefits of vitamin D supplementation in COVID-19 are as yet unproven despite increasing interest.
Article
Molecular studies have demonstrated the importance of the exacerbated immune response to SARS-CoV-2 infection called cytokine storm in more severe patients with COVID-19. The pathophysiology is complex and involves several homeostatic factors; among them, the deficit of vitamin D draws attention because of the high frequency in the population. Some evidence suggests that patients with low serum vitamin D levels have a worse outcome, often requiring intensive care. This review analysed the studies available in the global literature that address the benefits of vitamin D in COVID-19, relate its serum levels to the severity of the disease, and indicate it as possible prophylaxis and therapeutic in infection.
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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.
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The world is in the grip of the COVID-19 pandemic. Public health measures that can reduce the risk of infection and death in addition to quarantines are desperately needed. This article reviews the roles of vitamin D in reducing the risk of respiratory tract infections, knowledge about the epidemiology of influenza and COVID-19, and how vitamin D supplementation might be a useful measure to reduce risk. Through several mechanisms, vitamin D can reduce risk of infections. Those mechanisms include inducing cathelicidins and defensins that can lower viral replication rates and reducing concentrations of pro-inflammatory cytokines that produce the inflammation that injures the lining of the lungs, leading to pneumonia, as well as increasing concentrations of anti-inflammatory cytokines. Several observational studies and clinical trials reported that vitamin D supplementation reduced the risk of influenza, whereas others did not. Evidence supporting the role of vitamin D in reducing risk of COVID-19 includes that the outbreak occurred in winter, a time when 25-hydroxyvitamin D (25(OH)D) concentrations are lowest; that the number of cases in the Southern Hemisphere near the end of summer are low; that vitamin D deficiency has been found to contribute to acute respiratory distress syndrome; and that case-fatality rates increase with age and with chronic disease comorbidity, both of which are associated with lower 25(OH)D concentration. To reduce the risk of infection, it is recommended that people at risk of influenza and/or COVID-19 consider taking 10,000 IU/d of vitamin D3 for a few weeks to rapidly raise 25(OH)D concentrations, followed by 5000 IU/d. The goal should be to raise 25(OH)D concentrations above 40–60 ng/mL (100–150 nmol/L). For treatment of people who become infected with COVID-19, higher vitamin D3 doses might be useful. Randomized controlled trials and large population studies should be conducted to evaluate these recommendations.
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Calcitriol [1,25(OH)2D3] is usually investigated in studies on the preventive effect of activated vitamin D against interstitial pneumonia. Although cholecalciferol (vitamin D3) can be easily obtained in the diet and has a longer half-life than calcitriol, there have been few investigations of its effect on interstitial pneumonia. We used human pulmonary fibroblast cell lines (HPFCs) and a mouse model of bleomycin-induced pulmonary fibrosis to evaluate whether vitamin D3 was activated in the lungs and had a preventive effect against interstitial pneumonia. Expression of the vitamin D receptor gene and genes for enzymes metabolizing vitamin D was evaluated in two HPFCs, and the suppressive effect of vitamin D3 on induction of inflammatory cytokines was also assessed. Gene expression of the vitamin D receptor and vitamin D-metabolizing enzymes was observed in both human pulmonary fibroblast cell lines. Vitamin D3 suppressed bleomycin-induced expression of inflammatory cytokines and fibrosis markers by the HPFCs. In mice, symptoms of bleomycin-induced pulmonary fibrosis were improved and expression of fibrosis markers/fibrosis inducers was decreased by a high vitamin D3 diet. Vitamin D3 is activated locally in lung tissues, suggesting that high dietary intake of vitamin D3 may have a preventive effect against interstitial pneumonia.
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Beyond vitamin D (VD) effect on bone homeostasis, numerous physiological functions in human health have been described for this versatile prohormone. In 2016, 95% of the world's population lived in areas where annual mean ambient particulate matter (< 2.5 μm) levels exceeded the World Health Organization guideline value (Shaddick et al., 2018). On the other hand, industries disperse thousands of chemicals continually into the environment. Further, considerable fraction of populations are exposed to tobacco smoke. All of these may disrupt biochemical pathways and cause detrimental consequences, such as VD deficiency (VDD). In spite of the remarkable number of studies conducted on the role of some of the above mentioned exposures on VDD, the literature suffers from two main shortcomings: (1) an overview of the impacts of environmental exposures on the levels of main VD metabolites, and (2) credible engaged mechanisms in VDD because of those exposures. To summarize explanations for these unclear topics, we conducted the present review, using relevant keywords in the PubMed database, to investigate the adverse effects of exposure to air pollution, some environmental chemicals , and smoking on the VD metabolism, and incorporate relevant potential pathways disrupting VD endo-crine system (VDES) leading to VDD. Air pollution may lead to the reduction of VD cutaneous production either directly by blocking ultraviolet B photons or indirectly by decreasing outdoor activity. Heavy metals may reduce VD serum levels by increasing renal tubular dysfunction, as well as downregulating the transcription of cyto-chrome P450 mixed-function oxidases (CYPs). Endocrine-disrupting chemicals (EDCs) may inhibit the activity and expression of CYPs, and indirectly cause VDD through weight gain and dysregulation of thyroid hormone, parathyroid hormone, and calcium homeostasis. Smoking through several pathways decreases serum 25(OH)D and 1,25(OH)2D levels, VD intake from diet, and the cutaneous production of VD through skin aging. In summary , disturbance in the cutaneous production of cholecalciferol, decreased intestinal intake of VD, the modulation of genes involved in VD homeostasis, and decreased local production of calcitriol in target tissues are the most likely mechanisms that involve in decreasing the serum VD levels.
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Vitamin D concentration is known to correlate with various parameters. A major source of vitamin D is synthesis in the skin; thus, the duration of sun exposure is known to correlate with serum vitamin D levels. We compared serum levels of vitamin D between 2 occupational groups in Korea: the fisherman group, the most sun-exposed, and the general occupation group, relatively less sun-exposed. This study was conducted on 140 healthy fishermen and 140 healthy residents with various occupations, all of whom resided in the southernmost region of Korea, from June to August 2016. We compared serum concentrations of 25-hydroxyvitamin D (25(OH)D) in both occupation groups by gender and age and suggested vitamin D reference interval for the region. Mean serum 25(OH)D concentrations in the general occupation and fisherman group were 13.60 ± 6.43 and 23.74 ± 8.88 ng/mL, respectively. Mean serum concentration of 25(OH)D was 1.7 times higher in the fisherman group compared with the general occupation group, which was statistically significant (P < .001). Approximately 98% of subjects in the general occupation group and 78% of subjects in the fisherman group demonstrated either vitamin D insufficiency or deficiency. Calculated serum 25(OH)D reference interval for all subjects in our study was 3.8 to 44.4 ng/mL. Despite exposure to a large amount of sunlight, 78% of subjects in the fisherman group presented with either vitamin D deficiency or insufficiency. By taking laboratory measurements of serum 25(OH)D concentrations in fisherman, who were expected to have the highest vitamin D concentrations in Korea, this study could be epidemiologically useful.
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Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are the clinical manifestations of severe lung damage and respiratory failure. ALI and ARDS result are associated with high mortality in patients. At present, no effective treatments for ALI and ARDS exist. It is established that vitamin D exhibits anti‑inflammatory effects, however, the specific effect of vitamin D on ALI remains largely unknown. The aim of the present study was to investigate whether, and by which mechanism, vitamin D alleviates lipopolysaccharide (LPS)‑induced ALI. The results demonstrated that a vitamin D agonist, calcitriol, exhibited a beneficial effect on LPS‑induced ALI in rats; calcitriol pretreatment significantly improved LPS‑induced lung permeability, as determined using Evans blue dye. Results from reverse transcription‑quantitative polymerase chain reaction, western blotting and ELISA analysis demonstrated that calcitriol also modulated the expression of members of the renin‑angiotensin system (RAS), including angiotensin (Ang) I‑converting enzymes (ACE and ACE2), renin and Ang II, which indicates that calcitriol may exert protective effects on LPS‑induced lung injury, at least partially, by regulating the balance between the expression of members of the RAS. The results of the present study may provide novel targets for the future treatment of ALI.
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Vitamin D deficiency and insufficiency is a global health issue that afflicts more than one billion children and adults worldwide. The consequences of vitamin D deficiency cannot be under estimated. There has been an association of vitamin D deficiency with a myriad of acute and chronic illnesses including preeclampsia, childhood dental caries, periodontitis, autoimmune disorders, infectious diseases, cardiovascular disease, deadly cancers, type 2 diabetes and neurological disorders. This review is to put into perspective the controversy surrounding the definition for vitamin D deficiency and insufficiency as well as providing guidance for how to treat and prevent vitamin D deficiency.
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The effects of urban living on health are becoming increasingly important, due to an increasing global population residing in urban areas. Concomitantly, due to immigration, there is a growing number of ethnic minority individuals (African, Asian or Middle Eastern descent) living in westernised Higher Latitude Countries (HLC) (e.g. Europe, Canada, New Zealand). Of concern is the fact that there is already a clear vitamin D deficiency epidemic in HLC, a problem which is likely to grow as the ethnic minority population in these countries increases. This is because 25-hydroxyvitamin D (25(OH)D) status of ethnic groups is significantly lower compared to native populations. Environmental factors contribute to a high prevalence of vitamin D deficiency in HLC, particularly during the winter months when there is no sunlight of appropriate wavelength for vitamin D synthesis via the skin. Also, climatic factors such as cloud cover may reduce vitamin D status even in the summer. This may be further worsened by factors related to urban living, including air pollution, which reduces UVB exposure to the skin, and less occupational sun exposure (may vary by individual HLC). Tall building height may reduce sun exposure by making areas more shaded. In addition, there are ethnicity-specific factors which further worsen vitamin D status in HLC urban dwellers, such as low dietary intake of vitamin D from foods, lower production of vitamin D in the skin due to increased melanin and reduced skin exposure to UVB due to cultural dress style and sun avoidance. A multidisciplinary approach applying knowledge from engineering, skin photobiology, nutrition, town planning and social science is required to prevent vitamin D deficiency in urban areas. Such an approach could include reduction of air pollution, modification of sun exposure advice to emphasise spending time each day in non-shaded urban areas (e.g. parks, away from tall buildings), and advice to ethnic minority groups to increase sun exposure, take vitamin D supplements and/or increase consumption of vitamin D rich foods in a way that is safe and culturally acceptable. This review hopes to stimulate further research to assess the impact of high latitude, urban environment and ethnicity on the risk of vitamin D deficiency.
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Background: Obesity is associated with vitamin D insufficiency and secondary hyperparathyroidism. Objective: This study assessed whether obesity alters the cutaneous production of vitamin D3 (cholecalciferol) or the intestinal absorption of vitamin D2 (ergocalciferol). Design: Healthy, white, obese [body mass index (BMI; in kg/m²) ≥ 30] and matched lean control subjects (BMI ≤ 25) received either whole-body ultraviolet radiation or a pharmacologic dose of vitamin D2 orally. Results: Obese subjects had significantly lower basal 25-hydroxyvitamin D concentrations and higher parathyroid hormone concentrations than did age-matched control subjects. Evaluation of blood vitamin D3 concentrations 24 h after whole-body irradiation showed that the incremental increase in vitamin D3 was 57% lower in obese than in nonobese subjects. The content of the vitamin D3 precursor 7-dehydrocholesterol in the skin of obese and nonobese subjects did not differ significantly between groups nor did its conversion to previtamin D3 after irradiation in vitro. The obese and nonobese subjects received an oral dose of 50000 IU (1.25 mg) vitamin D2. BMI was inversely correlated with serum vitamin D3 concentrations after irradiation (r = −0.55, P = 0.003) and with peak serum vitamin D2 concentrations after vitamin D2 intake (r = −0.56, P = 0.007). Conclusions: Obesity-associated vitamin D insufficiency is likely due to the decreased bioavailability of vitamin D3 from cutaneous and dietary sources because of its deposition in body fat compartments.
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Despite abundant sunshine throughout the year, vitamin D deficiency is endemic in the UAE. Solar radiation within the UVB range of the spectrum is required for the photosynthesis of vitamin D3 in the skin. Atmospheric transmission of UVB is strongly influenced by atmospheric conditions and solar zenith angle. We investigated the effects of diurnal and seasonal variation on the availability of sufficient UVB radiation for adequate vitamin D3 synthesis using an established in vitro model. Borosilicate ampoules of 7-dehydrocholesterol, the precursor of previtamin D3, in ethanol (50 µg/mL) were exposed to direct sunlight in an urban area of Abu Dhabi, at one hourly intervals between 0800 and 1700, on one day of each month over a period of one year. Conversion to previtamin D3, vitamin D3 and metabolically inactive photoisomers was analysed using high performance liquid chromatography. The efficiency of 7-dehydrocholesterol conversion to previtamin D3 varied estimated UVB intensity. At the latitude of Abu Dhabi (24.2 N) previtamin D3 synthesis can occur throughout the year. However very little if any previtamin D3 was produced before 0900 hrs.and after 1600 hrs. Local conditions in Abu Dhabi are likely sufficient to maintain vitamin D levels throughout the year given adequate sun exposure.