Effect of Vitamin D<sub>3</sub>Supplementation on Upper Respiratory Tract Infections in Healthy Adults

Murdoch, David R.; Slow, Sandy; Chambers, Stephen T.; Jennings, Lance C.; Stewart, Alistair; Priest, Patricia; Florkowski, Christopher M; Livesey, J. H.; Camargo, Carlos A.; Scragg, Robert

doi:10.1001/jama.2012.12505

Cited by 205 publications

(177 citation statements)

References 28 publications

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“…We recognize that with well .4000 genes directly or indirectly regulated by vitamin D and its metabolites, additional mechanisms of regulation beyond those examined in this article are also likely to contribute to this differential activity. Carlberg et al (38) The benefits of aggressive vitamin D supplementation in vivo have recently become controversial (2,(39)(40)(41)(42). A commonly cited epidemiologic rationale for such supplementation is to enhance protective immune capacity and to decrease inflammation.…”

Section: Discussionmentioning

confidence: 99%

Vitamin D [1,25(OH)2D3] Differentially Regulates Human Innate Cytokine Responses to Bacterial versus Viral Pattern Recognition Receptor Stimuli

Fitch

Becker

HayGlass

2016

The Journal of Immunology

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Vitamin D plays multiple roles in regulation of protective and maladaptive immunity. Although epidemiologic studies link poor in vivo 25(OH)D status to increased viral respiratory infections, we poorly understand how vitamin D affects viral pattern recognition receptor (PRR)-driven cytokine production. In this study, we hypothesized that the biologically active metabolite of vitamin D, 1,25(OH)2D3, inhibits human proinflammatory and anti-inflammatory innate cytokine responses stimulated by representative bacterial or viral PRR ligands. Fresh PBMCs or CD14+ monocytes were stimulated with TLR4, TLR7/8-selective ligands, or respiratory syncytial virus (RSV) ± 1,25(OH)2D3. Proinflammatory and anti-inflammatory responses resulting from TLR4 stimulation were inhibited ∼50% in the presence of 1,25(OH)2D3. Conversely, its usage at physiologic through pharmacologic concentrations inhibited neither proinflammatory nor anti-inflammatory responses evoked by viral PRR ligands or infectious RSV. This differential responsiveness was attributed to the finding that TLR7/8, but not TLR4, stimulation markedly inhibited vitamin D receptor mRNA and protein expression, selectively reducing the sensitivity of viral PRR responses to modulation. 1,25(OH)2D3 also enhanced expression of IkBa, a potent negative regulator of NF-κB and cytokine production, in TLR4-stimulated monocytes while not doing so upon TLR7/8 stimulation. Thus, 1,25(OH)2D3 inhibits both proinflammatory and a broad panel of anti-inflammatory responses elicited by TLR4 stimulation, arguing that the common view of it as an anti-inflammatory immune response modifier is an oversimplification. In viral responses, it consistently fails to modify TLR7/8- or RSV-stimulated innate cytokine production, even at supraphysiologic concentrations. Collectively, the data call into question the rationale for increasingly widespread self-medication with vitamin D supplements.

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Section: Discussionmentioning

confidence: 99%

Vitamin D [1,25(OH)2D3] Differentially Regulates Human Innate Cytokine Responses to Bacterial versus Viral Pattern Recognition Receptor Stimuli

Fitch

Becker

HayGlass

2016

The Journal of Immunology

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“…The degree of gargling Other interventions A variety of other interventions have been studied for the prevention of the common cold. Studies of exercise, 41 garlic 42,43 and homeopathy 44−46 showed unclear evidence of benefit, whereas those of vitamin D 48,49 and echinacea 50 showed no evidence of benefit. Vitamin C 47 may provide some benefit in people under physical stress (e.g., marathon runners or soldiers in subarctic environments), but no meaningful benefit has been shown for the average patient.…”

Section: Garglingmentioning

confidence: 99%

Prevention and treatment of the common cold: making sense of the evidence

Allan

Arroll

2014

CMAJ

163

136

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“…A growing literature (1)(2)(3) suggests that vitamin D may be associated with reduced mortality (overall (4) and hospital-associated (5) ), incidence of cancer (6)(7)(8)(9)(10)(11)(12)(13) , CVD (14,15) , diabetes (16) , fractures (17,18) and ageing-related functional limitations (19) , although some studies find an unclear relationship (20,21) or a harmful association with disease (22) . Randomized controlled trials are underway to examine the potential role of vitamin D in the prevention of multiple diseases, including cancer, CVD and diabetes (20,23) .…”

Section: Introductionmentioning

confidence: 99%

Vitamin D deficiency in minority populations

Taksler

Cutler

Giovannucci

et al. 2014

Public Health Nutr.

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Objective: Black and Hispanic individuals synthesize less vitamin D per unit of sun exposure than white individuals. The relationship between UV radiation and vitamin D insufficiency in minorities has not been well explored. Design: Prospective cohort study. Setting: Using the National Health and Nutrition Examination Survey, we obtained serum vitamin D levels for non-Hispanic Whites, Hispanics and non-Hispanic Blacks aged ≥18 years from [2000][2001][2002][2003][2004][2005][2006]. We linked these data with the average monthly solar UV index by census tract and data on sun exposure, vitamin D supplementation, health and demographics. We used multivariable regression analyses to assess vitamin D deficiency (<15 ng/ml) and insufficiency (<20 ng/ml) in January (when the UV index was lowest) by race/ethnicity and geography. Subjects: Adults (n 14 319) aged ≥18 years. Results: A 1-point increase in the UV index was associated with a 0·51 ng/ml increase in vitamin D (95 % CI 0·35, 0·67 ng/ml; P < 0·001). Non-Hispanic Black race and Hispanic ethnicity were associated with a 7·47 and 3·41 ng/ml decrease in vitamin D, respectively (both P < 0·001). In January, an estimated 65·4 % of nonHispanic Blacks were deficient in vitamin D, compared with 28·9 % of Hispanics and 14·0 % of non-Hispanic Whites. An estimated 84·2 % of non-Hispanic Blacks were insufficient in vitamin D v. 56·3 % of Hispanics and 34·8 % of non-Hispanic Whites. More non-Hispanic Blacks were estimated to be deficient in vitamin D in January in the highest UV index quartile than were non-Hispanic Whites in the lowest UV index quartile (60·2 % v. 25·7 %). Conclusions: Wintertime vitamin D insufficiency is pervasive among minority populations, and not uncommon among non-Hispanic Whites. KeywordsVitamins Vitamin D Disparities Race SurvivalThe Institute of Medicine estimates that 54 % of non-Hispanic Blacks have very low levels of vitamin D (25-hydroxycholecalifierol (25(OH)D 3 ) < 16 ng/ml), v. 27 % of Mexican Americans and 11 % of non-Hispanic Whites (1,2) . A growing literature (1)(2)(3) suggests that vitamin D may be associated with reduced mortality (overall (4) and hospital-associated (5) ), incidence of cancer (6)(7)(8)(9)(10)(11)(12)(13) , CVD (14,15) , diabetes (16) , fractures (17,18) and ageing-related functional limitations (19) , although some studies find an unclear relationship (20,21) or a harmful association with disease (22) . Randomized controlled trials are underway to examine the potential role of vitamin D in the prevention of multiple diseases, including cancer, CVD and diabetes (20,23) .There are known racial and seasonal variations in vitamin D. Black individuals synthesize less vitamin D per unit of sun exposure than white individuals, because darker complexion acts as a natural sunscreen (24,25) .The majority of vitamin D is estimated to derive from sunshine for most people (26) , with the liver converting cholecalciferol into 25(OH)D 3 , the form of vitamin D typically measured in blood serum. 25(OH)D 3 has a reported half-lif...

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Effect of Vitamin D₃Supplementation on Upper Respiratory Tract Infections in Healthy Adults

Abstract: anzctr.org.au Identifier: ACTRN12609000486224.

Cited by 205 publications

References 28 publications

Vitamin D [1,25(OH)2D3] Differentially Regulates Human Innate Cytokine Responses to Bacterial versus Viral Pattern Recognition Receptor Stimuli

Vitamin D [1,25(OH)2D3] Differentially Regulates Human Innate Cytokine Responses to Bacterial versus Viral Pattern Recognition Receptor Stimuli

Prevention and treatment of the common cold: making sense of the evidence

Vitamin D deficiency in minority populations

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Effect of Vitamin D3Supplementation on Upper Respiratory Tract Infections in Healthy Adults

Abstract: anzctr.org.au Identifier: ACTRN12609000486224.

Cited by 205 publications

References 28 publications

Vitamin D [1,25(OH)2D3] Differentially Regulates Human Innate Cytokine Responses to Bacterial versus Viral Pattern Recognition Receptor Stimuli

Vitamin D [1,25(OH)2D3] Differentially Regulates Human Innate Cytokine Responses to Bacterial versus Viral Pattern Recognition Receptor Stimuli

Prevention and treatment of the common cold: making sense of the evidence

Vitamin D deficiency in minority populations

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Effect of Vitamin D₃Supplementation on Upper Respiratory Tract Infections in Healthy Adults