Impact of Vitamin D Supplementation on Influenza Vaccine Response and Immune Functions in Deficient Elderly Persons: A Randomized Placebo-Controlled Trial

Goncalves-Mendès, Nicolas; Talvas, Jérémie; Dualé, Christian; Guttmann, Aline; Corbin, V.; Marceau, Geoffroy; Sapin, Vincent; Brachet, Patrick; Evrard, Bertrand; Laurichesse, H.; Vasson, Marie‐Paule

doi:10.3389/fimmu.2019.00065

Cited by 127 publications

(130 citation statements)

References 57 publications

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“…Specifically, these studies show that oral vitamin D in very large doses upregulates TLR2, TLR4, IL-17A, CCR4, CXCR4, IL12RB1, IL12RB2, and TGF beta. 107,109,112,113,115 The upregulation of each of these has also been observed in CD. 99,108,110,111,114 While the doses involved in these studies are very large, the direction of association suggests that in those whose plasma levels of 1,25(OH) 2 D are already elevated or are predisposed to elevation, more modest doses of oral vitamin D may induce a state of increased immune activation that puts such individuals at greater risk for onset of CD.…”

Section: Select Effects Of Vitamin D On the Immune Systemmentioning

confidence: 85%

<p>Elevated Levels of 1,25-Dihydroxyvitamin D in Plasma as a Missing Risk Factor for Celiac Disease</p>

Bittker¹

2020

CEG

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The prevalence of celiac disease (CD) has increased significantly in some developed countries in recent decades. Potential risk factors that have been considered in the literature do not appear to provide a convincing explanation for this increase. This has led some researchers to hypothesize that there is a "missing environmental factor" that increases the risk of CD. Based on evidence from the literature, the author proposes that elevation in plasma levels of 1,25-dihydroxyvitamin D [1,25(OH) 2 D] is a missing risk factor for CD, and relatedly that significant oral vitamin D exposure is a "missing environmental factor" for CD. First, elevated plasma levels of 1,25(OH) 2 D are common in CD, especially in the newly diagnosed. Second, nine distinct conditions that increase plasma levels of 1,25(OH) 2 D are either associated with CD or have indications of such an association in the literature. Third, a retrospective study shows that sustained oral vitamin D supplementation in infancy is associated with increased CD risk, and other studies on comorbid conditions support this association. Fourth, large doses of oral vitamin D upregulate many of the same cytokines, chemokines, and toll-like receptors that are upregulated in CD. Fifth, epidemiological evidence, such as the timing of the inception of a CD "epidemic" in Sweden, the increased prevalence of CD in Finland and the United States in recent decades, the unusually low prevalence of CD in Germany, and the differential in prevalence between Finnish Karelians and Russian Karelians, may all be explained by oral vitamin D exposure increasing CD risk. The same is true of some seemingly contradictory results in the literature on the effects of breastfeeding on CD risk. If future research validates this hypothesis, adjustments to oral vitamin D consumption among those who have genetic susceptibility may decrease the risk of CD in these individuals.

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Section: Select Effects Of Vitamin D On the Immune Systemmentioning

confidence: 85%

<p>Elevated Levels of 1,25-Dihydroxyvitamin D in Plasma as a Missing Risk Factor for Celiac Disease</p>

Bittker¹

2020

CEG

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“…Other studies have demonstrated the role of Vit D in regulating the immune system. Vit D may suppress cytokine production by simultaneously boosting the innate immune system and reducing the overactivation of the adaptive immune system in response to viral load [11,13]. Vit D deficiency may be more prevalent among the elderly and African-American [8] but it includes every population group.…”

Section: Discussionmentioning

confidence: 99%

“…Some researchers have suggested the potential role of Vit D in suppressing cytokine storm during the 1918-1919 viral influenza pandemic [12]. Moreover, the role of Vit D in enhancing immune response in flu and previous coronaviruses has been suggested [11,13]. It is this ability of Vit D in suppressing cytokine production [14,15]that motivated our focus on Vit D deficiency and its association with severe COVID-19.…”

Section: Introductionmentioning

confidence: 99%

The Possible Role of Vitamin D in Suppressing Cytokine Storm and Associated Mortality in COVID-19 Patients

Daneshkhah¹,

Agrawal²,

Eshein³

et al. 2020

Preprint

203

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Objectives To investigate the possible role of Vitamin D (Vit D) deficiency via unregulated inflammation in COVID-19 complications and associated mortality. Design The time-adjusted case mortality ratio (T-CMR) was estimated as the number of deceased patients on day N divided by the number of confirmed cases on day N-8. The adaptive average of T-CMR (A-CMR) was further calculated as a metric of COVID-19 associated mortality in different countries. A model based on positivity change (PC) and an estimated prevalence of COVID-19 was developed to determine countries with similar screening strategies. Mean concentration of 25-hydroxyvitamin D (25(OH)D) in elderly individuals in countries with similar screening strategies were compared to investigate the potential impact of Vit D on A-CMR. We analyzed data showing a possible association between high C-Reactive Protein (CRP) concentration (CRP greater than or equal to 1 mg/dL) and severe COVID-19. We estimated a link between Vit D status and high CRP in healthy subjects (CRP greater than or equal to 0.2 mg/dL) with an adjustment for age and income to explore the possible role of Vit D in reducing complications attributed to unregulated inflammation and cytokine production. Data Sources Daily admission, recovery, and deceased rate data for patients with COVID-19 were collected from Kaggle as of April 20, 2020. Screening data were collected from Our World in Data and official statements from public authorities. The mean concentration of 25(OH)D among the elderly for comparison with A-CMR was collected from previously published studies from different countries. Chronic factor data used in regression analysis was obtained from published articles. The correlation between Vit D and CRP was calculated based on 9,212 subject-level data from NHANES, 2009-2010. Results A link between 25(OH)D and A-CMR in the US, France, Iran and the UK (countries with similar screening status) may exist. We observed an inverse correlation (correlation coefficient ranging from -0.84 to -1) between high CRP and 25(OH)D. Age and the family income status also correlated to high CRP and subjects with higher age and lower family income presented more incidences of high CRP. Our analysis determined a possible link between high CRP and Vit D deficiency and calculated an OR of 1.8 with 95%CI (1.2 to 2.6) among the elderly (age greater than or equal to 60 yo) in low-income families and an OR of 1.9 with 95%CI (1.4 to 2.7) among the elderly (age greater than or equal to 60 yo) in high-income families. COVID-19 patient-level data shows a notable OR of 3.4 with 95%CI (2.15 to 5.4) for high CRP in severe COVID-19 patients. Conclusion Given that CRP is a surrogate marker for cytokine storm and is associated with Vit D deficiency, based on retrospective data and indirect evidence we see a possible role of Vit D in reducing complications attributed to unregulated inflammation and cytokine storm. Further research is needed to account for other factors through direct measurement of Vit D levels in COVID-19 patients.

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“…Related clinical research studies are warranted. Based on numerous studies of other viruses [45,46], it is reasonable to hypothesize that vitamins C and D supplementation may boost immunity and help human organism fight COVID-19 and its aggressive effects on all organ systems (Fig. 1).…”

Section: Manifestations Of Covid-19 Which May Mimic Rheumatic Diseasesmentioning

confidence: 99%

Rheumatologists’ perspective on coronavirus disease 19 (COVID-19) and potential therapeutic targets

et al. 2020

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Impact of Vitamin D Supplementation on Influenza Vaccine Response and Immune Functions in Deficient Elderly Persons: A Randomized Placebo-Controlled Trial

Cited by 127 publications

References 57 publications

<p>Elevated Levels of 1,25-Dihydroxyvitamin D in Plasma as a Missing Risk Factor for Celiac Disease</p>

<p>Elevated Levels of 1,25-Dihydroxyvitamin D in Plasma as a Missing Risk Factor for Celiac Disease</p>

The Possible Role of Vitamin D in Suppressing Cytokine Storm and Associated Mortality in COVID-19 Patients

Rheumatologists’ perspective on coronavirus disease 19 (COVID-19) and potential therapeutic targets

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