Do studies reporting ‘U’-shaped serum 25-hydroxyvitamin D–health outcome relationships reflect adverse effects?

Grant, William B.; Karras, Spyridon N.; Bischoff‐Ferrari, Heike A.; Annweiler, Cédric; Boucher, Barbara J; Juzeniene, Asta; Garland, Cedric F.; Holick, Michael F.

doi:10.1080/19381980.2016.1187349

Cited by 97 publications

(75 citation statements)

References 121 publications

(127 reference statements)

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“…This might explain why studies conducted in cohorts from countries at different latitudes find differences in ‘optimal’ levels of vitamin D such as studies conducted in the USA vs . in countries from northern Europe. These hypotheses remain to be tested.…”

Section: Discussionmentioning

confidence: 99%

Vitamin D levels and cancer incidence in 217,244 individuals from primary health care in Denmark

Vojdeman

Madsen

Frederiksen

et al. 2019

Intl Journal of Cancer

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Vitamin D has been linked to cancer development in both pre‐clinical and epidemiological studies. Our study examines the association between serum levels of vitamin D and cancer incidence in the Capital Region of Denmark. Individuals who had vitamin D analyzed at The Copenhagen General Practitioners Laboratory between April 2004 and January 2010 were linked to Danish registries with end of follow‐up date at Dec 31st 2014, excluding individuals with pre‐existing cancer. Cox regression models adjusted for age in one‐year intervals, sex, month of sampling, and Charlson Comorbidity Index were applied. The study population of 217,244 individuals had a median vitamin D level of 46 nmol/L (IQR 27–67 nmol/L). Non‐melanoma skin cancer was the most frequent form of cancer, followed by breast‐, lung‐, and prostate cancers. No associations were found between increments of 10 nmol/L vitamin D and incidence of breast, colorectal, urinary, ovary or corpus uteri cancer. However, higher levels of vitamin D were associated with higher incidence of non‐melanoma (HR 1.09 [1.09–1.1]) and melanoma skin cancer (HR 1.1 [1.08–1.13]) as well as prostate (HR 1.05 [1.03–1.07]) and hematological cancers (HR 1.03 [1.01–1.06]), but with lower incidence of lung cancer (HR 0.95 [0.93–0.97]). In our study, vitamin D levels are not associated with the incidence of several major cancer types, but higher levels are significantly associated with a higher incidence of skin, prostate, and hematological cancers as well as a lower incidence of lung cancer. These results do not support an overall protective effect against cancer by vitamin D.

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Section: Discussionmentioning

confidence: 99%

Vitamin D levels and cancer incidence in 217,244 individuals from primary health care in Denmark

Vojdeman

Madsen

Frederiksen

et al. 2019

Intl Journal of Cancer

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“…Our sensitivity analysis of vitamin D supplement as an adjustment variable did not meaningfully change our result. Furthermore, taking vitamin D supplementation may be too late to affect disease progression …”

Section: Discussionmentioning

confidence: 99%

Inverted U‐shaped relationship between vitamin D and ever‐reported eczema in US adults

Wei

Jaleel

MacLeod

et al. 2019

Allergy

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Background: Eczema is a skin condition which affects up to 10% to 20% of people worldwide. Previous literature finds that low vitamin D levels may be a risk factor for eczema, but the association is not clear. Methods: We used the cross-sectional data from U.S. National Health and Nutrition Examination Survey 2005-2006. Adults were defined as 20 years and older. The association between eczema and serum 25-hydroxyvitamin D [25(OH)D] was estimated using multivariate logistic regression models adjusted for patient demographics, lifestyle variables, stress, and medical comorbidities. Restricted cubic spline analyseswere performed to explore nonlinear relationship. We also stratified by race. Results:A total of 3921 adults were included in the analysis. The prevalence of ever-report of eczema was 7.94% in US adults. Reports of eczema were higher in people with higher socioeconomic status, depressive symptoms, previous history of asthma and hay fever, female, sampled in summer, and nonHispanic white. The logistic regression found higher odds ratio of eczema in vitamin D deficiency group (<50 nmol/L) compared to sufficiency group (>75 nmol/L) (OR = 1.81, 95% CI: 1.09-3.01, P = 0.02). The spline analysis found an inverted U-shaped relationship between eczema and serum 25(OH)D level. Eczema risk reached the highest at around 45 nmol/L, with decreasing risk in both directions away from this value. This relationship was absent in nonHispanic black population. Conclusion: Vitamin D is associated with reports of eczema in nonHispanic white population, but not in the nonHispanic black population in the United States. K E Y W O R D S eczema, immune system, NHANES, race, vitamin D 1 | INTRODUCTION Eczema is one of the most common dermatological issues, with a prevalence of up to 10% in adults and 20% in children. 1-4 Eczema is caused by epidermal barrier dysfunction and an overactive immune response. 5 Vitamin D is important in maintaining the structural integrity in the epidermis, as well as in modulating the immune system. 6 A number of studies have evaluated the association between vitamin D and eczema; however, the relationship is still unclear. A randomized, double-blinded, placebo-controlled study of 60 atopic dermatitis (AD) patients aged 14 and older found that the vitamin D supplementation resulted in significant improvements in AD severity. 7Interestingly, while one study found that low vitamin D was associated with eczema in Korean adult population, 8 the association was not found in the UK population cohort. 9 To date, there is a paucity of studies that assess the relationship between vitamin D and eczema in Abbreviations: 25(OH)D, 25-hydroxyvitamin D; IOM, Institute of Medicine.

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“…The institute recognized that no studies had reported adverse effects of supplementation with less than 10,000 IU/d of vitamin D, but set the upper intake level at 4000 IU/d, partly out of concerns stemming from observational studies that found U-shaped 25(OH)D concentration-health outcome relationships. However, later investigation determined that most reports of J-or U-shaped relationships were from observational studies that did not measure serum 25(OH)D concentrations and that the likely reason for those relationships was a result of enrolling some participants who had started taking vitamin D supplements shortly before enrolling [151].…”

Section: Proposed Actionsmentioning

confidence: 99%

Evidence that Vitamin D Supplementation Could Reduce Risk of Influenza and COVID-19 Infections and Deaths

et al. 2020

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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 D 3 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 D 3 doses might be useful. Randomized controlled trials and large population studies should be conducted to evaluate these recommendations.

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Do studies reporting ‘U’-shaped serum 25-hydroxyvitamin D–health outcome relationships reflect adverse effects?

Cited by 97 publications

References 121 publications

Vitamin D levels and cancer incidence in 217,244 individuals from primary health care in Denmark

Vitamin D levels and cancer incidence in 217,244 individuals from primary health care in Denmark

Inverted U‐shaped relationship between vitamin D and ever‐reported eczema in US adults

Evidence that Vitamin D Supplementation Could Reduce Risk of Influenza and COVID-19 Infections and Deaths

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