Notable Developments for Vitamin D Amid the COVID-19 Pandemic, but Caution Warranted Overall: A Narrative Review

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel contagion that has infected over 113 million people worldwide. It is responsible for the coronavirus disease (COVID-19), which has cost the lives of 2.5 million people. Ergo, the global scientific community has been scrambling to repurpose or develop therapeutics to treat COVID-19. Dietary supplements and nutraceuticals are among those under consideration due to the link between nutritional status and patient outcomes. Overall, poor vitamin D status seems to be associated with an increased risk of COVID-19. Severely ill COVID-19 patients appear to be deficient or have suboptimal levels of serum 25-hydroxyvitamin D, a measure of vitamin D status. Consequently, vitamin D is now the subject of several prophylactic and therapeutic clinical trials. In this review, the general status of nutraceuticals and dietary supplements amid the pandemic is appraised, with a particular focus on vitamin D. Consumers should be aware of misinformation and unsubstantiated promises for products marketed for COVID-19 protection. However, maintaining a healthy diet and lifestyle will likely maintain health including optimum immune function that may affect patient outcomes. Those who are deficient in key nutrients such as vitamin D should consider lifestyle changes and potentially supplementation in consultation with their physician and/or registered dieticians.

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COVID-19 Disease Severity and Death in Relation to Vitamin D Status among SARS-CoV-2-Positive UAE Residents

Nutrients ◽

10.3390/nu13051714 ◽

2021 ◽

Vol 13 (5) ◽

pp. 1714

Author(s):

Habiba AlSafar ◽

William B. Grant ◽

Rafiq Hijazi ◽

Maimunah Uddin ◽

Nawal Alkaabi ◽

...

Keyword(s):

Vitamin D ◽

United Arab Emirates ◽

Blood Levels ◽

Vitamin D Status ◽

Hospital Visit ◽

Serum Samples ◽

Hydroxyvitamin D ◽

Increased Risk ◽

Multiethnic Population ◽

25 Hydroxyvitamin D

Insufficient blood levels of the neurohormone vitamin D are associated with increased risk of COVID-19 severity and mortality. Despite the global rollout of vaccinations and promising preliminary results, the focus remains on additional preventive measures to manage COVID-19. Results conflict on vitamin D’s plausible role in preventing and treating COVID-19. We examined the relation between vitamin D status and COVID-19 severity and mortality among the multiethnic population of the United Arab Emirates. Our observational study used data for 522 participants who tested positive for SARS-CoV-2 at one of the main hospitals in Abu Dhabi and Dubai. Only 464 of those patients were included for data analysis. Demographic and clinical data were retrospectively analyzed. Serum samples immediately drawn at the first hospital visit were used to measure serum 25-hydroxyvitamin D [25(OH)D] concentrations through automated electrochemiluminescence. Levels < 12 ng/mL were significantly associated with higher risk of severe COVID-19 infection and of death. Age was the only other independent risk factor, whereas comorbidities and smoking did not contribute to the outcomes upon adjustment. Sex of patients was not an important predictor for severity or death. Our study is the first conducted in the UAE to measure 25(OH)D levels in SARS-CoV-2-positive patients and confirm the association of levels < 12 ng/mL with COVID-19 severity and mortality.

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Gestational vitamin D deficiency and autism spectrum disorder

BJPsych Open ◽

10.1192/bjpo.bp.116.004077 ◽

2017 ◽

Vol 3 (2) ◽

pp. 85-90 ◽

Cited By ~ 44

Author(s):

Anna A. E. Vinkhuyzen ◽

Darryl W. Eyles ◽

Thomas H. J. Burne ◽

Laura M. E. Blanken ◽

Claudia J. Kruithof ◽

...

Keyword(s):

Vitamin D ◽

Vitamin D Deficiency ◽

Critical Period ◽

Autism Spectrum ◽

Vitamin D Status ◽

Hydroxyvitamin D ◽

Increased Risk ◽

25 Hydroxyvitamin D ◽

Spectrum Disorders ◽

Clinical Records

BackgroundThere is growing interest in linking vitamin D deficiency with autism spectrum disorders (ASDs). The association between vitamin D deficiency during gestation, a critical period in neurodevelopment, and ASD is not well understood.AimsTo determine the association between gestational vitamin D status and ASD.MethodBased on a birth cohort (n=4334), we examined the association between 25-hydroxyvitamin D (25OHD), assessed from both maternal mid-gestation sera and neonatal sera, and ASD (defined by clinical records; n=68 cases).ResultsIndividuals in the 25OHD-deficient group at mid-gestation had more than twofold increased risk of ASD (odds ratio (OR)=2.42, 95% confidence interval (CI) 1.09 to 5.07, P=0.03) compared with the sufficient group. The findings persisted in analyses including children of European ethnicity only.ConclusionsMid-gestational vitamin D deficiency was associated with an increased risk of ASD. Because gestational vitamin D deficiency is readily preventable with safe, inexpensive and readily available supplementation, this risk factor warrants closer scrutiny.

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An evaluation of vitamin D status in individuals with systemic lupus erythematosus

Proceedings of The Nutrition Society ◽

10.1017/s0029665111001613 ◽

2011 ◽

Vol 70 (4) ◽

pp. 399-407 ◽

Cited By ~ 10

Author(s):

Leanne C. Breslin ◽

Pamela J. Magee ◽

Julie M. W. Wallace ◽

Emeir M. McSorley

Keyword(s):

Systemic Lupus Erythematosus ◽

Vitamin D ◽

Disease Activity ◽

Lupus Erythematosus ◽

Additional Stress ◽

Vitamin D Status ◽

Systemic Lupus ◽

Hydroxyvitamin D ◽

Increased Risk ◽

25 Hydroxyvitamin D

Systemic lupus erythematosus (SLE) is a multi-system inflammatory disease where genetic susceptibility coupled with largely undefined environmental factors is reported to underlie the aetiology of the disease. One such factor is low vitamin D status. The primary source of vitamin D is endogenous synthesis following exposure of the skin to UVB light. Photosensitivity, sunlight avoidance and the use of sun protection factor in combination with medications prescribed to treat the symptoms of the disease, puts SLE patients at increased risk of vitamin D deficiency. Decreased conversion of 25-hydroxyvitamin D to the metabolically active form, 1,25-dihydroxyvitamin D3, is possible, due to renal impairment common in SLE putting additional stress on vitamin D metabolism. The majority of studies have identified low 25-hydroxyvitamin D in SLE patients, albeit using varying cut-offs (<25 to <80 nmol/l). Of these studies, fifteen have investigated a link between status and disease activity with conflicting results. Variation with disease activity index measures used alongside methodological limitations within the study design may partially explain these findings. This review discusses the importance of optimal vitamin D status in SLE, critically evaluates research carried out to date that has investigated vitamin D in SLE, and highlights the need for a well-designed observational study that controls for diet, medication use, dietary supplements, UV exposure and seasonality, that uses sensitive methods for measuring vitamin D status and disease activity in SLE to conclusively establish the role of vitamin D in SLE.

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Preoperative Vitamin D Deficiency is a Risk Factor for Postthyroidectomy Hypoparathyroidism: A Systematic Review and Meta-Analysis of Observational Studies

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/clinem/dgab039 ◽

2021 ◽

Author(s):

Konstantina D Vaitsi ◽

Panagiotis Anagnostis ◽

Stavroula Veneti ◽

Theodosios S Papavramidis ◽

Dimitrios G Goulis

Keyword(s):

Vitamin D ◽

Vitamin D Deficiency ◽

Meta Analysis ◽

Vitamin D Status ◽

Pubmed Central ◽

Hydroxyvitamin D ◽

Study Selection ◽

Postoperative Hypoparathyroidism ◽

Increased Risk ◽

25 Hydroxyvitamin D

Abstract Context Whether preoperative vitamin D deficiency (VDD) contributes to postoperative hypoparathyroidism (hypoPT) risk is unknown. Objective This work aimed to meta-analyze the best available evidence regarding the association between preoperative vitamin D status and hypoPT risk. Methods A comprehensive literature search was conducted in PubMed, CENTRAL, and Scopus databases, up to October 31, 2020. Study selection included patients undergoing thyroidectomy with preoperative vitamin D status and postoperative hypoPT data. Two researchers independently extracted data from eligible studies. Data were expressed as risk ratio (RR) with 95% CI. The I2 index was employed for heterogeneity. Results Thirty-nine studies were included in the quantitative analysis (61 915 cases with transient and 5712 with permanent hypoPT). Patients with VDD demonstrated a higher risk for transient hypoPT compared with those with preoperative vitamin D sufficiency (RR 1.92, 95% CI, 1.50-2.45, I2 = 85%). These results remained significant for patients with preoperative 25-hydroxyvitamin D concentrations less than or equal to 20 ng/mL (mild VDD; RR 1.46, 95% CI, 1.10-1.94, I2 = 88%) and less than or equal to 10 ng/mL (severe VDD; RR 1.98, 95% CI 1.42-2.76, I2 = 85%). The risk of permanent hypoPT was increased only in cases with severe VDD (RR 2.45, 95% CI, 1.30-4.63, I2 = 45%). No difference was evident in subgroup analysis according to study design or quality. Conclusion Patients with preoperative VDD are at increased risk of transient hypoPT following thyroidectomy. The risk for permanent hypoPT is increased only for those with severe VDD.

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Skeletal and extra-skeletal consequences of vitamin D deficiency

Orvosi Hetilap ◽

10.1556/oh.2011.29186 ◽

2011 ◽

Vol 152 (33) ◽

pp. 1312-1319 ◽

Cited By ~ 7

Author(s):

András Szabó

Keyword(s):

Vitamin D ◽

Vitamin D Deficiency ◽

Health Care Professionals ◽

Active Form ◽

The Body ◽

Vitamin D Status ◽

Vitamin D Receptors ◽

Hydroxyvitamin D ◽

Increased Risk ◽

25 Hydroxyvitamin D

Vitamin D is obtained from cutaneous production when 7-dehydrocholesterol is converted to vitamin D(3) (cholecalciferol) by ultraviolet B radiation or by oral intake of vitamin D. Rickets appeared to have been conquered with vitamin D intake, and many health care professionals thought the major health problems resulting from vitamin D deficiency had been resolved. However, rickets can be considered the tip of the vitamin D deficiency iceberg. In fact, vitamin D deficiency remains common in children and adults. An individual’s vitamin D status is best evaluated by measuring the circulating 25-hydroxyvitamin D (25(OH)D3) concentration. There is increasing agreement that the optimal circulating 25(OH)D3 level should be approximately 30 ng/mL or above. Using this definition, it has been estimated that approximately three-quarters of all adults have low levels. In utero and during childhood, vitamin D deficiency can cause growth retardation and skeletal deformities and may increase the risk of hip fracture later in life. Vitamin D deficiency in adults can exacerbate osteopenia and osteoporosis, cause osteomalacia and muscle weakness, and increase the risk of fracture. More recently, associations between low vitamin D status and increased risk for various non-skeletal morbidities have been recognized; whether all of these associations are causally related to low vitamin D status remains to be determined. The discovery that most tissues and cells in the body have vitamin D receptors and that several possess the enzymatic machinery to convert the 25-hydroxyvitamin D3, to the active form, 1,25-dihydroxyvitamin D3, has provided new insights into the function of this vitamin. Of great interest is its role in decreasing the risk of many chronic illnesses, including common cancers, autoimmune diseases, infectious diseases, and cardiovascular disease. In this review I consider the nature of vitamin D deficiency, discuss its role in skeletal and non-skeletal health, and suggest strategies for prevention and treatment. Orv. Hetil., 2011, 152, 1312–1319.

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The relationship between 25-hydroxyvitamin D concentration in early pregnancy and pregnancy outcomes in a large, prospective cohort

British Journal Of Nutrition ◽

10.1017/s0007114516003202 ◽

2016 ◽

Vol 116 (8) ◽

pp. 1409-1415 ◽

Cited By ~ 33

Author(s):

Veronica T. Boyle ◽

Eric B. Thorstensen ◽

David Mourath ◽

M. Beatrix Jones ◽

Lesley M. E. McCowan ◽

...

Keyword(s):

Vitamin D ◽

Preterm Birth ◽

Gestational Diabetes ◽

Pregnancy Outcomes ◽

Vitamin D Status ◽

Spontaneous Preterm Birth ◽

Hydroxyvitamin D ◽

Increased Risk ◽

25 Hydroxyvitamin D ◽

The Relationship

AbstractVitamin D insufficiency and deficiency have been associated with an increased risk of adverse pregnancy outcomes. Controversy remains as findings have been inconsistent between disparate populations. The aim of this study was to investigate the relationship between vitamin D status and pregnancy outcomes in a large, prospective pregnancy cohort. 25-Hydroxyvitamin D concentration was analysed in serum samples collected at 15 weeks of gestation from 1710 New Zealand women participating in a large, observational study. Associations between vitamin D status and pre-eclampsia, preterm birth, small for gestational age (SGA) and gestational diabetes were investigated. The mean 25-hydroxyvitamin D concentration was 72·9 nmol/l. In all, 23 % had 25-hydroxyvitamin D concentrations <50 nmol/l, and 5 % of participants had concentrations <25 nmol/l. Women with 25-hydroxyvitamin D concentrations <75 nmol/l at 15 weeks of gestation were more likely to develop gestational diabetes mellitus than those with concentrations >75 nmol/l (OR 2·3; 95 % CI 1·1, 5·1). However, this effect was not significant when adjustments were made for BMI and ethnicity (OR 1·8; 95 % CI 0·8, 4·2). 25-Hydroxyvitamin D concentration at 15 weeks was not associated with development of pre-eclampsia, spontaneous preterm birth or SGA infants. Pregnancy complications were low in this largely vitamin D-replete population.

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Comparison of Vitamin D and 25-Hydroxyvitamin D Concentrations in Human Breast Milk between 1989 and 2016–2017

Nutrients ◽

10.3390/nu13020573 ◽

2021 ◽

Vol 13 (2) ◽

pp. 573

Author(s):

Naoko Tsugawa ◽

Mayu Nishino ◽

Akiko Kuwabara ◽

Honami Ogasawara ◽

Maya Kamao ◽

...

Keyword(s):

Vitamin D ◽

Breast Milk ◽

Sun Exposure ◽

Stepwise Multiple Regression ◽

Human Breast Milk ◽

Vitamin D Status ◽

Human Breast ◽

Hydroxyvitamin D ◽

Lactating Mothers ◽

25 Hydroxyvitamin D

Background: Breast milk is considered the optimal source of nutrition during infancy. Although the vitamin D concentration in human breast milk is generally considered poor for infants, vitamin D in breast milk is an important source for exclusively breastfed infants. Increases in vitamin D insufficiency and deficiency in lactating mothers may reduce vitamin D concentrations in breast milk. This study aimed to compare vitamin D and 25-hydroxyvitamin D (25OHD) concentrations in breast milk collected in 1989 and 2016–2017 and simultaneously analyze them with liquid chromatography-tandem mass spectrometry (LC-MS/MS); the association between the lifestyle of recent lactating mothers (2016–2017) and vitamin D status in human breast milk was also evaluated. Method: Lactating mothers were recruited from three regions of Japan in 1989 (n = 72) and 2016–2017 (n = 90), and milk from 3–4 months was collected in summer and winter. The samples were strictly sealed and stored at −80℃ until measurement. Breast milk vitamin D and 25OHD concentrations were analyzed by LC-MS/MS. Vitamin D intake, sun exposure, and sunscreen use of the lactating mothers in 2016–2017 were assessed. Results: Both vitamin D and 25OHD concentrations in breast milk were higher in the summer regardless of the survey year. Significantly lower vitamin D and 25OHD concentrations were observed in 2016–2017 compared with 1989 in summer, but no survey year difference was observed in winter. The stepwise multiple regression analyses identified season, daily outdoor activity, and suntan in the last 12 months as independent factors associated with vitamin D3 concentrations. Conclusion: The results suggest that low vitamin D status in recent lactating mothers may have decreased vitamin D and 25OHD concentrations in breast milk compared with the 1980s. These results are helpful for developing public health strategies to improve vitamin D status in lactating mothers and infants.

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Plasma 25-Hydroxyvitamin D Levels and Fracture Risk in a Community-Based Cohort of Elderly Men in Sweden

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2009-2699 ◽

2010 ◽

Vol 95 (6) ◽

pp. 2637-2645 ◽

Cited By ~ 63

Author(s):

Håkan Melhus ◽

Greta Snellman ◽

Rolf Gedeborg ◽

Liisa Byberg ◽

Lars Berglund ◽

...

Keyword(s):

Vitamin D ◽

Uv Light ◽

Winter Season ◽

Community Dwelling ◽

Reference Level ◽

Blood Levels ◽

Elderly Men ◽

Hydroxyvitamin D ◽

Increased Risk ◽

25 Hydroxyvitamin D

Abstract Context: Blood levels of 25-hydroxyvitamin D [25(OH)D] is the generally accepted indicator of vitamin D status, but no universal reference level has been reached. Objective: The objective of the study was to determine the threshold at which low plasma 25(OH)D levels are associated with fractures in elderly men and clarify the importance of low levels on total fracture burden. Design and Participants: In the Uppsala Longitudinal Study of Adult Men, a population-based cohort (mean age, 71 yr, n = 1194), we examined the relationship between 25(OH)D and risk for fracture. Plasma 25(OH)D levels were measured with high-pressure liquid chromatography-mass spectrometry. Setting: The study was conducted in the municipality of Uppsala in Sweden, a country with a high fracture incidence. Main Outcome Measure: Time to fracture was measured. Results: During follow-up (median 11 yr), 309 of the participants (26%) sustained a fracture. 25(OH)D levels below 40 nmol/liter, which corresponded to the fifth percentile of 25(OH)D, were associated with a modestly increased risk for fracture, multivariable-adjusted hazard ratio 1.65 (95% confidence interval 1.09–2.49). No risk difference was detected above this level. Approximately 3% of the fractures were attributable to low 25(OH)D levels in this population. Conclusions: Vitamin D insufficiency is not a major cause of fractures in community-dwelling elderly men in Sweden. Despite the fact that cutaneous synthesis of previtamin D during the winter season is undetectable at this northern latitude of 60°, only one in 20 had 25(OH)D levels below 40 nmol/liter, the threshold at which the risk for fracture started to increase. Genetic adaptations to limited UV light may be an explanation for our findings.

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Vitamin D Status and Seasonal Variation among Danish Children and Adults: A Descriptive Study

Nutrients ◽

10.3390/nu10111801 ◽

2018 ◽

Vol 10 (11) ◽

pp. 1801 ◽

Cited By ~ 20

Author(s):

Louise Hansen ◽

Anne Tjønneland ◽

Brian Køster ◽

Christine Brot ◽

Rikke Andersen ◽

...

Keyword(s):

Vitamin D ◽

Seasonal Variation ◽

Vitamin D Status ◽

Hydroxyvitamin D ◽

Supplement Use ◽

Wide Range ◽

Adults And Children ◽

25 Hydroxyvitamin D ◽

Vitamin D Supplement ◽

Very High

The aim of the present study was to describe vitamin D status and seasonal variation in the general Danish population. In this study, 3092 persons aged 2 to 69 years (2565 adults, 527 children) had blood drawn twice (spring and autumn) between 2012 and 2014. A sub-sample of participants had blood samples taken monthly over a year. Serum 25-hydroxyvitamin D (25(OH)D) concentrations were measured by liquid chromatography mass spectrometry, and information on supplement use was assessed from questionnaires. Seasonal variations in 25(OH)D concentrations were evaluated graphically and descriptively, and status according to age, sex, and supplement use was described. It was found that 86% of both adults and children were vitamin D-sufficient in either spring and or/autumn; however, many had a spring concentration below 50 nmol/L. A wide range of 25(OH)D concentrations were found in spring and autumn, with very low and very high values in both seasons. Among adults, women in general had higher median 25(OH)D concentrations than men. Furthermore, vitamin D supplement use was substantial and affected the median concentrations markedly, more so during spring than autumn. Seasonal variation was thus found to be substantial, and bi-seasonal measurements are vital in order to capture the sizable fluctuations in vitamin D status in this Nordic population.

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Weight and skin colour as predictors of vitamin D status: results of an epidemiological investigation using nationally representative data

Public Health Nutrition ◽

10.1017/s1368980016000173 ◽

2016 ◽

Vol 20 (10) ◽

pp. 1857-1864 ◽

Cited By ~ 5

Author(s):

Sonali Rajan ◽

Tom Weishaar ◽

Bryan Keller

Keyword(s):

Vitamin D ◽

Body Weight ◽

Skin Colour ◽

Vitamin D Status ◽

Epidemiological Investigation ◽

Dietary Recommendations ◽

Hydroxyvitamin D ◽

25 Hydroxyvitamin D ◽

Nationally Representative ◽

The Impact

AbstractObjectiveCurrent US dietary recommendations for vitamin D vary by age. Recent research suggests that body weight and skin colour are also major determinants of vitamin D status. The objective of the present epidemiological investigation was to clarify the role of age as a predictor of vitamin D status, while accounting for body weight and skin colour, among a nationally representative sample.DesignWe calculated the mean serum 25-hydroxyvitamin D levels for the US population by age and weight, as well as by weight and race/ethnicity group. Multiple regression analyses were utilized to evaluate age and weight as predictors of vitamin D status: serum 25-hydroxyvitamin D levels with age alone, age and body weight, and age, body weight and their two-way interaction were modelled for the entire sample and each age subgroup. Graphical data were developed using B-spline non-linear regression.SettingNational Health and Nutrition Examination Survey (31 934 unweighted cases).SubjectsIndividuals aged 1 year and older.ResultsThere were highly significant differences in mean vitamin D status among US residents by weight and skin colour, with those having darker skin colour or higher body weight having worse vitamin D status. Although a significant factor, the impact of age on vitamin D status was notably less than the impact of body weight.ConclusionsVitamin D status varied predominantly by body weight and skin colour. Recommendations by nutritionists for diet and supplementation needs should take this into account if vitamin D-related health disparities are to be meaningfully reduced across the USA.

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