Ambient ultraviolet-B radiation, supplements and other factors interact to impact vitamin D status differently depending on ethnicity: A cross-sectional study.

BACKGROUND & AIMS: Many determinants of vitamin D status have been well-described, yet supplementation guidelines largely follow a one-size-for-all model and deficiency remains common. We hypothesised that accounting accurately for ultraviolet-B (UVB) radiation and considering interactions could advance understanding of vitamin D status. METHODS: Asian, Black, and White participants from the UK Biobank cohort were included (N = 438,978). The Tropospheric Emission Monitoring Internet Service provided UVB data which we linked to participants' place of residence. UVB dose over 135 days prior to blood draw was weighted and added, yielding cumulative and weighted UVB (CW-D-UVB). The association between 25(OH)D and selected variables was assessed in multivariable linear regression models with and without interactions, stratified by ethnicity. Predictors were ranked using standardised ß-coefficients. RESULTS: Median 25(OH)D differed by ethnicity (Asian: 25.4 nmol/L (10.2 ng/mL), Black: 30.6 nmol/L (12.2 ng/mL), White: 47.9 nmol/L (19.2 ng/mL), p-value < 0.001). CW-D-UVB was strongly associated with 25(OH)D in all ethnicities. It was the most important predictor in White (ßAsian = 0.15, ßBlack = 0.20, ßWhite = 0.35), whereas supplementation was in Asian and Black participants (ßAsian = 0.30, ßBlack = 0.24, ßWhite = 0.21). We identified statistically significant interactions between BMI:supplementation (all), CW-D-UVB:sex (Asian and White), and CW-D-UVB:age (Black and White), and in White population between CW-D-UVB and supplementation, BMI, and cholesterol. CONCLUSION: Vitamin D deficiency was widespread, particularly among non-White individuals. UVB was a strong predictor of 25(OH)D and the effect was modified by other factors. Findings suggest that accurately measured ambient-UVB radiation and interactions could improve 25(OH)D prediction models, and support personalised approaches to vitamin D optimisation.

Comprehensive Analysis of Seasonal and Geographical Variation in UVB Radiation Relevant for Vitamin D Production in Europe.

Dermal synthesis, following sun exposure, is the main source of vitamin D. This study characterizes ambient UVB radiation relevant for vitamin D production in Europe. A biological weighing function was applied to data from the Tropospheric Emissions Monitoring Internet Service (TEMIS) for 46 capital cities over an 18-year period (2004-2021) to isolate wavelengths relevant for vitamin D production (D-UVB). Cumulative and weighted D-UVB (CW-D-UVB) were calculated to approximate seasonal vitamin D accumulation and diminution. Monthly 25(OH)D concentration measurements were extracted from published reports. All data were analyzed by location and time. Despite a moderate latitudinal range (35-64° N), we observed large-up to five-fold-regional differences: the highest mean diurnal D-UVB dose of 5.57 kJ/m2 (SD = 3.55 kJ/m2) was observed in Nicosia (Cyprus) and the lowest in Reykjavik (Iceland, 1.16 ± 1.29 kJ/m2). Seasonal differences in diurnal D-UVB dose were even more pronounced, with a median 36-fold difference between annual peak and trough depending on a location (range: 10- to 525-fold). The mean duration of "vitamin D winter" was 126 days but varied widely (4 to 215 days). Monthly CW-D-UVB and 25(OH)D changes were very strongly correlated: the changes in 25(OH)D concentration increased by 12.6 nmol/L for every 100 kJ/m2 increment of CW-D-UVB in population-based studies (r2 = 0.79, p-value = 1.16 × 10-37). Understanding the differences in D-UVB radiation can help understand determinants of vitamin D status and guide region- and season-specific safe and effective sunlight exposure recommendations and vitamin D supplementation guidelines.

The association between ambient UVB dose and ANCA-associated vasculitis relapse and onset.

BACKGROUND: The aetiology of ANCA-associated vasculitis (AAV) and triggers of relapse are poorly understood. Vitamin D (vitD) is an important immunomodulator, potentially responsible for the observed latitudinal differences between granulomatous and non-granulomatous AAV phenotypes. A narrow ultraviolet B spectrum induces vitD synthesis (vitD-UVB) via the skin. We hypothesised that prolonged periods of low ambient UVB (and by extension vitD deficiency) are associated with the granulomatous form of the disease and an increased risk of AAV relapse. METHODS: Patients with AAV recruited to the Irish Rare Kidney Disease (RKD) (n = 439) and UKIVAS (n = 1961) registries were studied. Exposure variables comprised latitude and measures of ambient vitD-UVB, including cumulative weighted UVB dose (CW-D-UVB), a well-validated vitD proxy. An n-of-1 study design was used to examine the relapse risk using only the RKD dataset. Multi-level models and logistic regression were used to examine the effect of predictors on AAV relapse risk, phenotype and serotype. RESULTS: Residential latitude was positively correlated (OR 1.41, 95% CI 1.14-1.74, p = 0.002) and average vitD-UVB negatively correlated (0.82, 0.70-0.99, p = 0.04) with relapse risk, with a stronger effect when restricting to winter measurements (0.71, 0.57-0.89, p = 0.002). However, these associations were not restricted to granulomatous phenotypes. We observed no clear relationship between latitude, vitD-UVB or CW-D-UVB and AAV phenotype or serotype. CONCLUSION: Our findings suggest that low winter ambient UVB and prolonged vitD status contribute to AAV relapse risk across all phenotypes. However, the development of a granulomatous phenotype does not appear to be directly vitD-mediated. Further research is needed to determine whether sufficient vitD status would reduce relapse propensity in AAV.

An observational and Mendelian randomisation study on vitamin D and COVID-19 risk in UK Biobank.

A growing body of evidence suggests that vitamin D deficiency has been associated with an increased susceptibility to viral and bacterial respiratory infections. In this study, we aimed to examine the association between vitamin D and COVID-19 risk and outcomes. We used logistic regression to identify associations between vitamin D variables and COVID-19 (risk of infection, hospitalisation and death) in 417,342 participants from UK Biobank. We subsequently performed a Mendelian Randomisation (MR) study to look for evidence of a causal effect. In total, 1746 COVID-19 cases (399 deaths) were registered between March and June 2020. We found no significant associations between COVID-19 infection risk and measured 25-OHD levels after adjusted for covariates, but this finding is limited by the fact that the vitamin D levels were measured on average 11 years before the pandemic. Ambient UVB was strongly and inversely associated with COVID-19 hospitalization and death overall and consistently after stratification by BMI and ethnicity. We also observed an interaction that suggested greater protective effect of genetically-predicted vitamin D levels when ambient UVB radiation is stronger. The main MR analysis did not show that genetically-predicted vitamin D levels are causally associated with COVID-19 risk (OR = 0.77, 95% CI 0.55-1.11, P = 0.160), but MR sensitivity analyses indicated a potential causal effect (weighted mode MR: OR = 0.72, 95% CI 0.55-0.95, P = 0.021; weighted median MR: OR = 0.61, 95% CI 0.42-0.92, P = 0.016). Analysis of MR-PRESSO did not find outliers for any instrumental variables and suggested a potential causal effect (OR = 0.80, 95% CI 0.66-0.98, p-val = 0.030). In conclusion, the effect of vitamin D levels on the risk or severity of COVID-19 remains controversial, further studies are needed to validate vitamin D supplementation as a means of protecting against worsened COVID-19.

Sunshine is an Important Determinant of Vitamin D Status Even Among High-dose Supplement Users: Secondary Analysis of a Randomized Controlled Trial in Crohn's Disease Patients.

Sunshine is considered to be the most important source of vitamin D. Due to an increased risk of skin cancer, sun avoidance is advised, but this directly contributes to the high prevalence of vitamin D deficiency. The simple solution is to advise vitamin D supplementation. The aim of this study was to examine the absolute and relative contribution of sunshine and supplementation to vitamin status. This study was a secondary analysis of an RCT of 92 Crohn's disease patients in remission (49% female, median age = 44). Participants were randomized to 2000 IU day-1 of vitamin D3 or placebo for 1 year, with 25-hydroxyvitamin D (25(OH)D) being measured at baseline and every 4 months. Based on participant's place of residence, daily ambient UVB dose at wavelengths that can induce vitamin D synthesis (D-UVB) was obtained. Cumulative and weighted ambient D-UVB (cw-D-UVB) exposure prior to each blood draw was calculated for each participant. Linear regression analysis and multilevel modeling were used to examine the association between UVB exposure, supplementation and 25(OH)D concentration. There was considerable annual variation in D-UVB, cw-D-UVB and 25(OH)D. Both supplementation and cw-D-UVB were found to be strongly associated with 25(OH)D: in multilevel model, an increase of approximately 6 nmol L-1 for every 100 kJ m-2 in cw-D-UVB was found, among those receiving placebo and supplementation (P < 0.0001). Treatment was associated with increase of 23 nmol L-1 (P < 0.0001). Sunshine is an important determinant of 25(OH)D concentration, even in those who are taking high-dose vitamin D supplements and reside at a higher mid-latitude location.

Annual Ambient UVB at Wavelengths that Induce Vitamin D Synthesis is Associated with Reduced Esophageal and Gastric Cancer Risk: A Nested Case-Control Study.

Vitamin D has been shown to be beneficial at reducing the risk of cancer; however, studies examining esophageal and gastric cancer have been scarce and findings inconsistent. The UK Biobank cohort was used for this nested case-control study (N = 3732). Primary, incident esophageal and gastric cancer cases diagnosed after recruitment were identified via linkage to National Cancer Registries. Tropospheric Emissions Monitoring Internet Service database was used to calculate ambient annual UVB dose (D-UVB). Conditional logistic regression was used to investigate the relationship between annual ambient D-UVB and risk of esophageal and gastric cancer, and odds ratios (ORs) are reported. In total, 373 esophageal and 249 gastric cancer cases and 3110 age- and gender-matched controls were included in the study. We found a strong inverse association between annual ambient D-UVB and odds of developing esophageal or gastric cancer: Compared to the lowest tertile, OR for the highest tertile was 0.64 (95%CI:0.51-0.79) in adjusted analysis. The association was strengthened when restricted to esophageal cancer (OR = 0.60; 95%CI:0.45-0.80) and esophageal adenocarcinoma cases (OR = 0.48; 95%CI: 0.34-0.68). Similar results were found in unadjusted and stratified analysis. In conclusion, ambient UVB radiation is inversely associated with the development of esophageal and gastric cancer, even in a high-latitude country.

Ambient UVB Dose and Sun Enjoyment Are Important Predictors of Vitamin D Status in an Older Population.

Background: UVB-induced skin synthesis is considered the key source of vitamin D, yet exposure to UVB is poorly accounted for in epidemiological studies.Objectives: The aim of this study was to examine the association of serum 25-hydroxyvitamin D [25(OH)D] concentration with accurately measured ambient UVB dose, sun enjoyment, supplements, and other factors.Methods: An all-Irish cohort of community-dwelling participants aged >60 y [median age: 73; 67% female; median 25(OH)D: 54.5 nmol/L] was used. Participants from this large, cross-sectional study completed a questionnaire to provide information on demographic factors and lifestyle (including supplement use and sun enjoyment). The Tropospheric Emission Monitoring Internet Service database was used to extract the daily ambient UVB dose at wavelengths that could induce vitamin D synthesis (D-UVB) over Ireland (latitude: 51°N-55°N). Blood sampling occurred throughout the year. Ambient exposure at the place of residence was calculated for each participant individually. Associations between determinants and serum 25(OH)D concentration were examined in a multivariate model. Random forest analysis was used to establish prediction models of vitamin D deficiency, and area under the curve (AUC) is shown.Results: In total, 5138 individuals were included. Median D-UVB was 63 mJ/cm2, which varied between seasons and latitudes, despite the small latitude differential. Vitamin D supplementation (ß = 27.7; P < 10 × 10-10), D-UVB (ß = 1.58 per 1000 mJ/cm2; P < 10 × 10-10), and sun enjoyment (ß = 6.6; P < 0.001) were strongly positively associated with serum 25(OH)D. Those who avoided sunshine were largely at risk of deficiency (<40 nmol/L), whereas those who enjoyed sunshine tended to be vitamin D sufficient (≥50 nmol/L). D-UVB and sun enjoyment improved prediction of deficiency in non-supplement-taking individuals; the overall AUC improved by 3.5%.Conclusion: D-UVB and sun enjoyment are important predictors of vitamin D status, even in this elderly population at northern latitudes. Accurate estimation of ambient UVB can help to further clarify the role of other determinants of vitamin D status and inform sunshine recommendation guidelines.