DOI

DOI

 * DOI: 10.3390/nu13020411     https://pubmed.ncbi.nlm.nih.gov/33525447/
 * DOI: 10.3390/nu12092663
 * DOI: 10.1111/febs.15495
 * DOI: 10.1007/s00508-021-01833-y
 * DOI: 10.1016/j.nut.2020.111106
 * DOI: 10.1186/s12967-021-02838-x
 * DOI: 10.1016/j.dsx.2021.03.006
 * DOI: 10.1080/13543784.2021.1901883
 * DOI: 10.1002/1878-0261.12924
 * DOI: 10.1016/S2213-8587(21)00051-6
 * DOI: 10.1016/B978-0-12-386960-9.00002-2
 * DOI: 10.1080/19381980.2017.1300213
 * DOI: 10.1007/s11154-017-9424-1
 * DOI: 10.1542/peds.2015-1669
 * DOI: 10.1017/S0007114511007161

DOI: 10.3390/nu12092663
'''Vitamin-D status in Ireland is 45 to 65 nmol/l by season. The immune system wants it over 125nmol/l'''

https://pubmed.ncbi.nlm.nih.gov/32878330/ Nutrients 2020 Aug 31;12(9):2663. doi: 10.3390/nu12092663. Geomapping Vitamin D Status in a Large City and Surrounding Population-Exploring the Impact of Location and Demographics Helena Scully 1, Eamon Laird  2 , Martin Healy  3 , James Bernard Walsh  1 , Vivion Crowley  3 , Kevin McCarroll  1 Affiliations PMID: 32878330 PMCID: PMC7551618 DOI: 10.3390/nu12092663

'''To determine the factor triggering the sudden surge of daily new COVID-19 cases arising in most European countries during the autumn of 2020. The dates of the surge were determined using a fitting of the two last months of reported daily new cases in 18 European countries with latitude ranging from 39° to 62°. The study proves no correlation between the country surge date and the 2 weeks preceding temperature or humidity but shows an impressive linear correlation with latitude. The country surge date corresponds to the time when its sun UV daily dose drops below ≈ 34% of that of 0° latitude. Introducing reported seasonal blood 25-hydroxyvitamin D (25(OH)D) concentration variation into the reported link between acute respiratory tract infection risk and 25(OH)D concentration quantitatively explains the surge dynamics. Several studies have already substantiated a 25(OH)D concentration impact on COVID-19 severity. However, by comparing different patient populations, discriminating whether a low 25(OH)D concentration is a real factor underlying COVID-19 severity or only a marker of another weakness that is the primary severity factor can be challenging. The date of the surge is an intrapopulation observation and has the benefit of being triggered only by a parameter globally affecting the population, i.e. decreases in the sun UV daily dose. The results indicate that a low 25(OH)D concentration is a contributing factor to COVID-19 severity, which, combined with previous studies, provides a convincing set of evidence.'''

https://pubmed.ncbi.nlm.nih.gov/33479261/

Sci Rep 2021 Jan 21;11(1):1981. doi: 10.1038/s41598-021-81419-w. Autumn COVID-19 surge dates in Europe correlated to latitudes, not to temperature-humidity, pointing to vitamin D as contributing factor Stephan Walrand 1 PMID: 33479261 PMCID: PMC7820009 DOI: 10.1038/s41598-021-81419-w

J Clin Endocrinol Metab. 2013 Dec; 98(12): 4619–4628. Published online 2013 Oct 8. doi: 10.1210/jc.2013-2653 PMCID: PMC3849670 PMID: 24106283 Clinical Review The Role of the Parent Compound Vitamin D with Respect to Metabolism and Function: Why Clinical Dose Intervals Can Affect Clinical Outcomes Bruce W. Holliscorresponding author and Carol L. Wagner

Indeed, any high-dose, long-interval dosing schedule can be considered pharmacological rather than physiological.

'''Circulating vitamin D, the parent compound for tissue vitamin D activation, likely has an important direct physiological role beyond what was originally anticipated through the local tissue autocrine system. Based on emerging data from the laboratory and from clinical trials and on available knowledge of vitamin D axis metabolism, it appears likely that for the optimal benefits of vitamin D supplementation, enough vitamin D should be provided on a daily basis to ensure that stable circulating concentrations are maintained over time. This view implies that schedules for vitamin D dosing could have profound effects on the outcomes of clinical trials, due to the short circulating half-life of vitamin D'''

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3849670/

FEBS J. 2020 Jul 23 : 10.1111/febs.15495. doi: 10.1111/febs.15495 [Epub ahead of print] PMCID: PMC7404739 PMID: 32700398 https://pubmed.ncbi.nlm.nih.gov/32700398/

Low plasma 25(OH) vitamin D level is associated with increased risk of COVID‐19 infection: an Israeli population‐based study Eugene Merzon,corresponding author 1, 2 Dmitry Tworowski, 3 Alessandro Gorohovski, 3 Shlomo Vinker, 1 , 2 Avivit Golan Cohen, 1 , 2 Ilan Green, 1 , 2 and Milana Frenkel Morgensterncorresponding author 3

'''Of 7,807 individuals, 782 (10.1%) were COVID‐19‐positive, and 7,025 (89.9%) COVID‐19‐negative. The mean plasma vitamin D level was significantly lower among those who tested positive than negative for COVID‐19 [19.00 ng/mL (95% confidence interval [CI] 18.41‐19.59) vs. 20.55 (95% CI 20.32‐20.78)]. Univariate analysis demonstrated an association between low plasma 25(OH)D level and increased likelihood of COVID‐19 infection [crude odds ratio (OR) of 1.58 (95% CI 1.24‐2.01, p<0.001)], and of hospitalization due to the SARS‐CoV‐2 virus [crude OR of 2.09 (95% CI 1.01‐ 4.30, p<0.05)]. In multivariate analyses that controlled for demographic variables, and psychiatric and somatic disorders, the adjusted OR of COVID‐19 infection [1.45 (95% CI 1.08‐1.95, p<0.001)], and of hospitalization due to the SARS‐CoV‐2 virus [1.95 (95% CI 0.98‐4.845, p=0.061)] were preserved. In the multivariate analyses, age over 50 years, male gender and low‐medium socioeconomic status were also positively associated with the risk of COVID‐19 infection; age over 50 years was positively associated with the likelihood of hospitalization due to COVID‐19. Conclusion

Low plasma 25(OH)D level appears to be an independent risk factor for COVID‐19 infection and hospitalization.'''

Wien Klin Wochenschr

. 2021 Mar 15;1-3. doi: 10.1007/s00508-021-01833-y. Online ahead of print. Strong correlation between prevalence of severe vitamin D deficiency and population mortality rate from COVID-19 in Europe Isaac Z Pugach 1, Sofya Pugach  2 Affiliations

PMID: 33721102 PMCID: PMC7957444 DOI: 10.1007/s00508-021-01833-y

'''Results: There were data sets from 10 countries that fitted the criteria and were analyzed. Severe vitamin D deficiency was defined as 25(OH)D less than 25 nmol/L (10 ng/dL). Pearson correlation analysis between death rate per million of population from coronavirus disease 2019 (COVID-19) and prevalence of severe vitamin D deficiency showed a strong correlation with r = 0.79, p = 0.007. Over time, correlation strengthened, and r coefficient asymptotically increased. After adjusting for countries' age structure and per capita health expenditures, multiple linear regression analysis showed that higher prevalence of severe vitamin D deficiency is associated with increased mortality. Each 1% increase in prevalence increased deaths by 55 per million (95% confidence interval, CI 8-102), p = 0.03.

Conclusion: The authors recommend universal screening for vitamin D deficiency, and further investigation of Vitamin D supplementation in randomized control studies, which may lead to possible treatment or prevention of COVID-19.'''

University of Copenhagen. "Vitamin D crucial to activating immune defenses." ScienceDaily. ScienceDaily, 8 March 2010. .

Vitamin D crucial to activating immune defenses Date:    March 8, 2010 Source:    University of Copenhagen

https://www.sciencedaily.com/releases/2010/03/100307215534.htm

For the research team, identifying the role of vitamin D in the activation of T cells has been a major breakthrough. "Scientists have known for a long time that vitamin D is important for calcium absorption and the vitamin has also been implicated in diseases such as cancer and multiple sclerosis, but what we didn't realize is how crucial vitamin D is for actually activating the immune system -- which we know now. "

https://www.nature.com/articles/ni.1851

http://enformtk.u-aizu.ac.jp/mailer/to_uoa/infection-measures.html

I am not alone in my opinion, which you may dismiss as quirky and unqualified. Thousands of scientists worldwide are fighting this misinformation, which is resulting in a human medical experiment on a scale we have not witnessed in our lives before.

These include Nobel prize winner Michael Levitt of Stanford University, Luc Montagnier the Nobel laureate virologist from France. These include professors from prestigious universities all around the world such as Martin Kulldorff, Jay Bhattacharya, and John Ioannidis of Stanford University, Carl Heneghan, Tom Jefferson, and Sunetra Gupta of Oxford University, and Sucharit Bhakdi and Karin Moelling from Germany.

Nutrition Volume 84, April 2021, 111106 Applied nutritional investigation Increased risk for COVID-19 in patients with vitamin D deficiency

https://doi.org/10.1016/j.nut.2020.111106 https://www.sciencedirect.com/science/article/pii/S0899900720303890

Vitamin D deficiency is strongly associated with increased risk for coronavirus disease 2019 (COVID-19). The odds ratio for COVID-19 increases with vitamin deficiency in black individuals. Diabetes, obesity, and periodontal disease are associated with an increased risk for both COVID-19 and vitamin D deficiency.

Is vitamin D deficiency associated with the COVID-19 epidemic in Europe? Dimitra Rafailia Bakaloudi, Michail Chourdakis

doi: https://doi.org/10.1101/2021.01.28.21250673 https://www.medrxiv.org/content/10.1101/2021.01.28.21250673v2

Abstract The authors have withdrawn this manuscript because, following comments received during the review process, they have updated the number of countries included in their study (and also changed from 5 to 10 years the limit for Vit-D information studies that they included), which led to non-significant correlations between mortality and infections and Vit D deficiency prevalence. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author. J Transl Med 2021 Apr 26;19(1):166. doi: 10.1186/s12967-021-02838-x.

Vitamin D status of Arab Gulf residents screened for SARS-CoV-2 and its association with COVID-19 infection: a multi-centre case-control study

Nasser M Al-Daghri 1, Osama E Amer  2 , Naif H Alotaibi  3 , Dara A Aldisi  4 , Mushira A Enani  5 , Eman Sheshah  6 , Naji J Aljohani  2   7 , Naemah Alshingetti  8 , Suliman Y Alomar  9 , Hanan Alfawaz  10 , Syed D Hussain  2 , Abdullah M Alnaami  2 , Shaun Sabico

PMID: 33902635 PMCID: PMC8072076 DOI: 10.1186/s12967-021-02838-x https://pubmed.ncbi.nlm.nih.gov/33902635/

Results: Serum 25(OH)D levels were significantly lower in the SARS-CoV-2 positive group compared to the negative group after adjustment for age and BMI (52.8 nmol/l ± 11.0 versus 64.5 nmol/l ± 11.1; p = 0.009). Being elderly (> 60 years) [Odds ratio 6 (95% Confidence Interval, CI 2-18; p = 0.001) as well as having type 2 diabetes (T2D) [OR 6 (95% CI 3-14); p < 0.001)] and low HDL cholesterol (HDL-c) [OR 6 (95% CI 3-14); p < 0.001)] were significant risk factors for COVID-19 infection independent of age, sex and obesity.

Conclusions: Among Arab Gulf residents screened for SARS-CoV-2, serum 25(OH) D levels were observed to be lower in those who tested positive than negative individuals, but it was the presence of old age, diabetes mellitus and low-HDL-c that were significantly associated with risk of COVID-19 infection. Large population-based randomized controlled trials should be conducted to assess the protective effects of vitamin D supplementation against COVID-19.

Diabetes Metab Syndr 2021 Mar 13;15(3):757-764. doi: 10.1016/j.dsx.2021.03.006. Online ahead of print. Impact of the vitamin D deficiency on COVID-19 infection and mortality in Asian countries Ranil Jayawardena 1, Dhanushya T Jeyakumar  2 , Tormalli V Francis  3 , Anoop Misra

PMID: 33823331 PMCID: PMC7955807 DOI: 10.1016/j.dsx.2021.03.006 https://pubmed.ncbi.nlm.nih.gov/33823331/

Results: Positive correlations were observed for prevalence of vitamin D deficiency with COVID-19 infections (r = 0.55; p = 0.01; R2 = 0.31) and mortalities (r = 0.50; p = 0.01; R2 = 0.25). Moreover, the associations for the COVID-19 infections and mortalities improved to r = 0.76 (p = 0.002; R2 = 0.58) and r = 0.65 (p = 0.03; R2 = 0.42), respectively, after predicting with confounding factors. Similarly, mean vitamin D level had a significant negative correlation with COVID-19 infections (r = -0.77; p = 0.04; R2 = 0.59) and mortalities (r = -0.80; p = 0.03; R2 = 0.63) when combining with confounders.

Conclusion: Prevalence of vitamin D deficiency is significantly positively associated whereas the mean vitamin D level is significantly negatively associated with both infection and mortality rate of COVID-19 among Asian countries upon predicting with all confounders. Expert Opin Investig Drugs 2021 Apr 23;1-14. doi: 10.1080/13543784.2021.1901883. Online ahead of print. The time to offer treatments for COVID-19 Binh T Ngo 1   2, Paul Marik  1 , Pierre Kory  3 , Leland Shapiro  4 , Raphael Thomadsen  5 , Jose Iglesias  6 , Stephen Ditmore  7 , Marc Rendell  2 , Joseph Varon  8 , Michael Dubé  1 , Neha Nanda  1 , Gino In  1 , Daniel Arkfeld  1 , Preet Chaudhary  1 , Vito M Campese  1 , Diana L Hanna  1 , David E Sawcer  1 , Glenn Ehresmann  1 , David Peng  1 , Miroslaw Smogorewski  1 , April Armstrong  1 , Rajkumar Dasgupta  1 , Fred Sattler  1 , Denise Brennan-Rieder  9 , Cristina Mussini  10 , Oriol Mitja  11 , Vicente Soriano  12 , Nicolas Peschanski  13 , Gilles Hayem  14 , Marco Confalonieri  15 , Maria Carmela Piccirillo  16 , Antonio Lobo-Ferreira  17 , Iraldo Bello Rivero  18 , Mika Turkia  19 , Eivind H Vinjevoll  20 , Daniel Griffin  4   21 , Ivan Fn Hung  4 Affiliations

PMID: 33721548 PMCID: PMC8074648 DOI: 10.1080/13543784.2021.1901883 https://pubmed.ncbi.nlm.nih.gov/33721548/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8074648/

COVID-19 has characteristic phases, beginning as a viral influenza like illness which may then deteriorate to an inflammatory phase with a subsequent hyperinflammatory reaction characterized by cytokine release; Acute respiratory distress syndrome and a coagulopathy are responsible for mortality.

The focus of treatment of COVID-19 has been on very ill hospitalized patients. Outpatients who do not require hospitalization are told to home quarantine with no effective treatment.

The public health authorities have pursued universal immunization to prevent the disease, and several vaccines are now being administered to the population of the entire world. However, vaccination alone may not be sufficient to stop the disease as the virus continues to propagate with newly developing variants.

We reviewed treatments now available to use in parallel with vaccination to fight COVID-19. We found a number of agents, some already approved and in use in a number of countries.

We recommend that agents with known safety profile and preliminary evidence of possible benefit be used together with universal vaccination, while long-term studies proceed in parallel to prove efficacy.

Nutrients 2021 Jan 28;13(2):411. doi: 10.3390/nu13020411. Vitamin D Supplementation to Prevent COVID-19 Infections and Deaths-Accumulating Evidence from Epidemiological and Intervention Studies Calls for Immediate Action Hermann Brenner Affiliations

PMID: 33525447 PMCID: PMC7911431 DOI: 10.3390/nu13020411 https://pubmed.ncbi.nlm.nih.gov/33525447/

Abstract

The COVID-19 pandemic poses an unprecedented threat to human health, health care systems, public life, and economy around the globe. The repertoire of effective therapies for severe courses of the disease has remained limited. '''A large proportion of the world population suffers from vitamin D insufficiency or deficiency, with prevalence being particularly high among the COVID-19 high-risk populations. Vitamin D supplementation has been suggested as a potential option to prevent COVID-19 infections, severe courses, and deaths from the disease, but is not widely practiced. This article provides an up-to-date summary of recent epidemiological and intervention studies on a possible role of vitamin D supplementation for preventing severe COVID-19 cases and deaths. Despite limitations and remaining uncertainties, accumulating evidence strongly supports widespread vitamin D supplementation, in particular of high-risk populations, as well as high-dose supplementation of those infected.''' Given the dynamics of the COVID-19 pandemic, the benefit-risk ratio of such supplementation calls for immediate action even before results of ongoing large-scale randomized trials become available.

Molecular Oncology Research Article Open Access Vitamin D supplementation to the older adult population in Germany has the cost‐saving potential of preventing almost 30 000 cancer deaths per year Tobias Niedermaier Thomas Gredner Sabine Kuznia Ben Schöttker Ute Mons Hermann Brenner First published: 04 February 2021 https://doi.org/10.1002/1878-0261.12924 https://febs.onlinelibrary.wiley.com/doi/10.1002/1878-0261.12924

Recent meta‐analyses of randomized controlled trials (RCTs) have demonstrated significant reduction in cancer mortality by vitamin D supplementation. We estimated costs and savings for preventing cancer deaths by vitamin D supplementation of the population aged 50+ years in Germany. Our analysis is based on national data on cancer mortality in 2016. The number of preventable cancer deaths was estimated by multiplying cancer deaths above age 50 with the estimated proportionate reduction in cancer mortality derived by vitamin D supplementation according to meta‐analyses of RCTs (13%). Saved costs were estimated by multiplying this number by estimated end‐of‐life cancer care costs (€40 000). Annual costs of vitamin D supplementation were estimated at 25€ per person above age 50. Comprehensive sensitivity analyses were conducted. In the main analysis, vitamin D supplementation was estimated to prevent almost 30 000 cancer deaths per year at approximate costs of €900 million and savings of €1.154 billion, suggesting net savings of €254 million. Our results support promotion of supplementation of vitamin D among older adults as a cost‐saving approach to substantially reduce cancer mortality.

The Lancet Diabetes and Endocrinology Articles| Volume 9, ISSUE 5, P276-292, May 01, 2021 Vitamin D supplementation to prevent acute respiratory infections: a systematic review and meta-analysis of aggregate data from randomised controlled trials

David A Jolliffe, PhD Prof Carlos A Camargo Jr, MD   John D Sluyter, PhD Mary Aglipay, MSc Prof John F Aloia, MD   Davaasambuu Ganmaa, PhD et al.

Published:March 30, 2021

DOI:https://doi.org/10.1016/S2213-8587(21)00051-6 https://www.thelancet.com/journals/landia/article/PIIS2213-8587(21)00051-6/fulltext

Interpretation Despite evidence of significant heterogeneity across trials, vitamin D supplementation was safe and overall reduced the risk of ARI compared with placebo, although the risk reduction was small. Protection was associated with administration of daily doses of 400–1000 IU for up to 12 months, and age at enrolment of 1·00–15·99 years. The relevance of these findings to COVID-19 is not known and requires further investigation.

Now accepted for publication in BMJ Nutrition Dietary supplements during the COVID-19 pandemic: insights from 1.4M users of the COVID Symptom Study app - a longitudinal app-based community survey Panayiotis Louca, Benjamin Murray, Kerstin Klaser, Mark S Graham, Mohsen Mazidi, Emily R Leeming, Ellen Thompson, Ruth Bowyer, David A Drew, Long H Nguyen, Jordi Merino, Maria Gomez, Olatz Mompeo, Ricardo Costeira, Carole H Sudre, Rachel Gibson, Claire J Steves, Jonathan Wolf, Paul W Franks, Sebastien Ourselin, Andrew T Chan, Sarah E Berry, Ana M Valdes, Philip C Calder, Tim D Spector, Cristina Menni

doi: https://doi.org/10.1101/2020.11.27.20239087 https://www.medrxiv.org/content/10.1101/2020.11.27.20239087v1

Conclusion We observed a modest but significant association between use of probiotics, omega-3 fatty acid, multivitamin or vitamin D supplements and lower risk of testing positive for SARS-CoV-2 in women. No clear benefits for men were observed nor any effect of vitamin C, garlic or zinc for men or women. Randomised controlled trials of selected supplements would be required to confirm these observational findings before any therapeutic recommendations can be made.

Journal ListJ Family Med Prim Carev.7(2); Mar-Apr 2018PMC6060930 J Family Med Prim Care. 2018 Mar-Apr; 7(2): 324–330. doi: 10.4103/jfmpc.jfmpc_78_18 PMCID: PMC6060930 PMID: 30090772 Vitamin D deficiency in India P Aparna,1 S Muthathal,1 Baridalyne Nongkynrih,1 and Sanjeev Kumar Gupta1

Abstract Vitamin D is a fat-soluble vitamin playing a vital role in human physiology. Vitamin D deficiency is prevalent worldwide. This deficiency has many consequences which are still being explored, apart from the well-known skeletal complications. With this review, we aim to summarize the existing literature on Vitamin D status in India and understand the enormity of the problem. The prevalence of Vitamin D deficiency ranged from 40% to 99%, with most of the studies reporting a prevalence of 80%–90%. It was prevalent in all the age groups and high-risk groups alike. With the consequences of Vitamin D deficiency, namely, autoimmune diseases, cardiovascular diseases, cancer, and tuberculosis being explored, we can imagine the burden it would cause in our country. We need to create awareness among the public and healthcare providers about the importance of Vitamin D and the consequences of deficiency. Our Indian diet generally fails to satisfy the daily requirement of Vitamin D for a normal adult. This stresses on the need for fortifying various food with Vitamin D, through the national programs. This silent epidemic should be addressed appropriately with concrete public health action.

Respir Res 2020 Nov 9;21(1):294. doi: 10.1186/s12931-020-01554-2. The association between serum vitamin D and obstructive sleep apnea: an updated meta-analysis Xiaoyan Li 1, Jie He  2 , Jie Yun  3

PMID: 33167989 PMCID: PMC7653837 DOI: 10.1186/s12931-020-01554-2

Results: Twenty-nine eligible studies compromising 6717 participants met the inclusion criteria of the meta-analysis. The results revealed that the serum 25(OH)D level was significantly lower in OSA patients than the controls. According to the severity of the disease, subgroup analysis was performed; the results demonstrated that the serum 25(OH)D level was not decreased in mild OSA patients compared with the controls, while the serum 25(OH)D level in moderate and severe OSA patients was lower than that in the controls. Furthermore, based on ethnicity, BMI, PSG type, study quality and latitude, the subjects were divided into different subgroups for meta-analysis. The results revealed that the serum 25(OH)D level in all OSA subgroups was decreased compared with that in the control group.

BMJ Open Respir Res 2021 Jan;8(1):e000845. doi: 10.1136/bmjresp-2020-000845. Sleep apnoea is a risk factor for severe COVID-19 Satu Strausz 1   2   3, Tuomo Kiiskinen  1   4 , Martin Broberg  1 , Sanni Ruotsalainen  1 , Jukka Koskela  1   5 , Adel Bachour  6 , FinnGen; Aarno Palotie  1   5   7 , Tuula Palotie  2   3 , Samuli Ripatti  1   5   8 , Hanna M Ollila  9   5   10 Collaborators, Affiliations

PMID: 33436406 PMCID: PMC7804843 DOI: 10.1136/bmjresp-2020-000845 https://pubmed.ncbi.nlm.nih.gov/33436406/

Results: We identified 445 individuals with COVID-19, and 38 (8.5%) of them with OSA of whom 19 out of 91 (20.9%) were hospitalised. OSA associated with COVID-19 hospitalisation independent from age, sex, BMI and comorbidities (p-unadjusted=5.13×10-5, OR-adjusted=2.93 (95% CI 1.02 to 8.39), p-adjusted=0.045). OSA was not associated with the risk of contracting COVID-19 (p=0.25). A meta-analysis of OSA and severe COVID-19 showed association across 15 835 COVID-19 positive controls, and n=1294 patients with OSA with severe COVID-19 (OR=2.37 (95% 1.14 to 4.95), p=0.021).

Conclusion: Risk for contracting COVID-19 was the same for patients with OSA and those without OSA. In contrast, among COVID-19 positive patients, OSA was associated with higher risk for hospitalisation. Our findings are in line with earlier works and suggest OSA as an independent risk factor for severe COVID-19.

Vitam Horm 2011;86:23-62. doi: 10.1016/B978-0-12-386960-9.00002-2. Vitamin D and innate and adaptive immunity Martin Hewison

PMID: 21419266 DOI: 10.1016/B978-0-12-386960-9.00002-2 https://pubmed.ncbi.nlm.nih.gov/21419266/

Abstract In the last 5 years there has been renewed interest in the health benefits of vitamin D. A central feature of this revival has been new information concerning the nonclassical effects of vitamin D. In particular, studies of the interaction between vitamin D and the immune system have highlighted the importance of localized conversion of precursor 25-hydroxyvitamin D (25OHD) to active 1,25-dihydroxyvitamin D (1,25(OH)(2)D) as a mechanism for maintaining antibacterial activity in humans. The clinical relevance of this has been endorsed by increasing evidence of suboptimal 25OHD status in populations across the globe. Collectively these observations support the hypothesis that vitamin D insufficiency may lead to dysregulation of human immune responses and may therefore be an underlying cause of infectious disease and immune disorders. The current review describes the key mechanisms associated with vitamin D metabolism and signaling for both innate immune (antimicrobial activity and antigen presentation) and adaptive immune (T and B lymphocyte function) responses. These include coordinated actions of the vitamin D-activating enzyme, 1α-hydroxylase (CYP27B1), and the vitamin D receptor (VDR) in mediating intracrine and paracrine actions of vitamin D. Finally, the review will consider the role of immunomodulatory vitamin D in human health, with specific emphasis on infectious and autoimmune disease.

Dermatoendocrinol

. 2017 Apr 13;9(1):e1300213. doi: 10.1080/19381980.2017.1300213. eCollection 2017. Evaluation of vitamin D3 intakes up to 15,000 international units/day and serum 25-hydroxyvitamin D concentrations up to 300 nmol/L on calcium metabolism in a community setting S M Kimball 1, N Mirhosseini  1 , M F Holick  2

PMID: 28458767 PMCID: PMC5402701 DOI: 10.1080/19381980.2017.1300213 https://pubmed.ncbi.nlm.nih.gov/28458767/

Abstract Supplementation by the general public with vitamin D at doses above the Tolerable Upper Level of Intake (UL) is becoming quite common. The objective of the current analysis was to characterize the effect of vitamin D supplementation at doses up to 15,000 IU/d in a community-based program on vitamin D status, calcium homeostasis as well as on kidney, liver and immune function. We evaluated data collected for 3,882 participants in a community program for whom there were blood measurements at program entry and at follow-up within 6-18 months between 2013 and 2015. '''Participants were supplemented with a wide range of vitamin D doses (1,000 - 15,000 IU/d) aimed at achieving serum 25-hydroxyvitamin D [25(OH)D] levels of at least 100 nmol/L. Serum 25(OH)D concentrations up to 300 nmol/L were achieved without perturbation of calcium homeostasis or incidence of toxicity. Hypercalcemia and hypercalciuria were not related to an increase in 25(OH)D concentrations nor vitamin D dose. To achieve serum 25(OH)D levels >100 nmol/L on average, required vitamin D intakes of 6,000 IU/d for normal Body Mass Index (BMI), 7,000 IU/d for overweight and 8,000 IU/d for obese.''' Doses of vitamin D in excess of 6,000 IU/d were required to achieve serum 25(OH)D concentrations above 100 nmol/L, especially in individuals who were overweight or obese without any evidence of toxicity. Serum 25(OH)D concentrations up to 300 nmol/L were found to be safe.

Rev Endocr Metab Disord 2017 Jun;18(2):153-165. doi: 10.1007/s11154-017-9424-1. The vitamin D deficiency pandemic: Approaches for diagnosis, treatment and prevention Michael F Holick

PMID: 28516265 DOI: 10.1007/s11154-017-9424-1 https://pubmed.ncbi.nlm.nih.gov/28516265/

Abstract 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.

Immun Inflamm Dis 2021 Mar;9(1):128-133. doi: 10.1002/iid3.367. Epub 2020 Dec 15. Evidence and implications of pre-existing humoral cross-reactive immunity to SARS-CoV-2 Amandine Mveang Nzoghe 1, Paulin N Essone  2   3 , Marielle Leboueny  1 , Anicet Christel Maloupazoa Siawaya  1 , Eliode Cyrien Bongho  1 , Ofilia Mvoundza Ndjindji  1 , Rotimi Myrabelle Avome Houechenou  1 , Selidji Todagbe Agnandji  2   3 , Joel Fleury Djoba Siawaya

PMID: 33320447 PMCID: PMC7860591 DOI: 10.1002/iid3.367 https://pubmed.ncbi.nlm.nih.gov/33320447/

Results: Sera from 32 subjects (out of 135 [23.7%]) were reactive to SARS-CoV-2 N-antigen, suggesting the presence of anti-SARS-CoV-2 N-antigen antibodies.'

Conclusion: Although the clinical relevance of the observed reactivity can only be speculated and needs to be investigated, the implication of this finding for coronavirus disease 2019 seroepidemiological survey and vaccines' clinical trials is critical.

Pediatrics 2015 Oct;136(4):625-34. doi: 10.1542/peds.2015-1669. Maternal Versus Infant Vitamin D Supplementation During Lactation: A Randomized Controlled Trial Bruce W Hollis 1, Carol L Wagner  2 , Cynthia R Howard  3 , Myla Ebeling  4 , Judy R Shary  2 , Pamela G Smith  2 , Sarah N Taylor  2 , Kristen Morella  4 , Ruth A Lawrence  3 , Thomas C Hulsey

PMID: 26416936 PMCID: PMC4586731 DOI: 10.1542/peds.2015-1669 https://pubmed.ncbi.nlm.nih.gov/26416936/

Results: Of the 334 mother-infant pairs in 400 IU and 6400 IU groups at enrollment, 216 (64.7%) were still breastfeeding at visit 1; 148 (44.3%) continued full breastfeeding to 4 months and 95 (28.4%) to 7 months. Vitamin D deficiency in breastfeeding infants was greatly affected by race. Compared with 400 IU vitamin D3 per day, 6400 IU/day safely and significantly increased maternal vitamin D and 25(OH)D from baseline (P < .0001). Compared with breastfeeding infant 25(OH)D in the 400 IU group receiving supplement, infants in the 6400 IU group whose mothers only received supplement did not differ.

Conclusions: Maternal vitamin D supplementation with 6400 IU/day safely supplies breast milk with adequate vitamin D to satisfy her nursing infant's requirement and offers an alternate strategy to direct infant supplementation.

Br J Nutr 2012 Nov 14;108(9):1557-61. doi: 10.1017/S0007114511007161. Epub 2012 Jan 23. Traditionally living populations in East Africa have a mean serum 25-hydroxyvitamin D concentration of 115 nmol/l Martine F Luxwolda 1, Remko S Kuipers, Ido P Kema, D A Janneke Dijck-Brouwer, Frits A J Muskiet

PMID: 22264449 DOI: 10.1017/S0007114511007161 https://pubmed.ncbi.nlm.nih.gov/22264449/

Abstract: Cutaneous synthesis of vitamin D by exposure to UVB is the principal source of vitamin D in the human body. Our current clothing habits and reduced time spent outdoors put us at risk of many insufficiency-related diseases that are associated with calcaemic and non-calcaemic functions of vitamin D. Populations with traditional lifestyles having lifelong, year-round exposure to tropical sunlight might provide us with information on optimal vitamin D status from an evolutionary perspective. We measured the sum of serum 25-hydroxyvitamin D₂ and D₃ (25(OH)D) concentrations of thirty-five pastoral Maasai (34 (SD 10) years, 43 % male) and twenty-five Hadzabe hunter-gatherers (35 (SD 12) years, 84 % male) living in Tanzania. They have skin type VI, have a moderate degree of clothing, spend the major part of the day outdoors, but avoid direct exposure to sunlight when possible. Their 25(OH)D concentrations were measured by liquid chromatography-MS/MS. The mean serum 25(OH)D concentrations of Maasai and Hadzabe were 119 (range 58-167) and 109 (range 71-171) nmol/l, respectively. These concentrations were not related to age, sex or BMI. People with traditional lifestyles, living in the cradle of mankind, have a mean circulating 25(OH)D concentration of 115 nmol/l. Whether this concentration is optimal under the conditions of the current Western lifestyle is uncertain, and should as a possible target be investigated with concomitant appreciation of other important factors in Ca homeostasis that we have changed since the agricultural revolution.

Proc Biol Sci

. 2015 Dec 22;282(1821):20143085. doi: 10.1098/rspb.2014.3085. Evolution of the immune system in humans from infancy to old age A Katharina Simon 1, Georg A Hollander  2 , Andrew McMichael

PMID: 26702035 PMCID: PMC4707740 DOI: 10.1098/rspb.2014.3085 https://pubmed.ncbi.nlm.nih.gov/26702035/

Abstract This article reviews the development of the immune response through neonatal, infant and adult life, including pregnancy, ending with the decline in old age. A picture emerges of a child born with an immature, innate and adaptive immune system, which matures and acquires memory as he or she grows. It then goes into decline in old age. These changes are considered alongside the risks of different types of infection, autoimmune disease and malignancy.

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Medical Articles by Dr. Ray

Collection of health news, health articles and useful medical information you can use in everyday life. Jul 25 2020 The Immune System Changes With Age By Ray Schilling | autoimmune disease, diet, fish oil, food, immune system, Infectious Disease, lifestyle, omega-3 fatty acids, vaccinations, Vitamins and supplements

https://www.askdrray.com/the-immune-system-changes-with-age/

Vitamin D

The immune system is very dependent on vitamin D as the immune cells all contain vitamin D receptors. People who have less than 10 ng/mL of vitamin D in the blood are vitamin D deficient. They have much higher death rates when they get infected with the Covid-19 coronavirus.

Vitamin D regulates the expression of target genes. At the center is the vitamin D receptor, which is a nuclear transcription factor. Together with the retinoic X receptor (from vitamin A) the vitamin D receptor binds small sequences of DNA. They have the name “vitamin D response elements” and are capable of initiating a cascade of molecular interactions. The result is a modulation of specific genes. Researchers identified thousands of vitamin D response elements that regulate between 100 and 1250 genes. You need enough vitamin D for your immune system

When enough vitamin D is present in the blood (more than 30 ng/mL) the immune system releases the peptides cathelicidins and defensins, which effectively destroy bacteria and viruses.

Vitamin D has mainly an inhibitory function regarding adaptive immunity. It inhibits antibody production from B cells and also dampens the effect of T cells. Researchers reported that vitamin D3 is useful in the treatment of autoimmune diseases.

I am a slow absorber of vitamin D3 as repeat blood vitamin D levels showed. I need 10,000 IU of vitamin D3 daily to get a blood level of 50-80 ng/mL (=125-200 nmol/L). This is the higher range of normal. Everybody is different. Ask your physician to check your blood level of vitamin D. Toxic vitamin D blood levels are only starting above 150 ng/mL (= 375 nmol/L).

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Da leert man den Briefkasten doch gerne!📬 Diese Woche gab es ein Überraschungspaket von unserer Personalvorständin Birgit Bohle. Neben netten und motivierenden Worten gab es auch ein wenig Sonnenschein für das Homeoffice ☀️ Wir folgen ihrer Inspiration gerne – und werden das Wochenende nutzen, um an der frischen Luft etwas Sonne zu tanken! 😊 Wie sehen eure Pläne aus? Und, ganz wichtig: Bleibt alle gesund!

You like to empty the mailbox! 📬 This week there was a surprise package from our staff chairman Birgit Bohle. In addition to nice and motivating words, there was also a little sunshine for the home office ☀️ We love to follow her inspiration - and will use the weekend to soak up some sunshine in the fresh air! 😊 What are your plans? And, very importantly, stay healthy everyone!

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