Vitamin D Status and Risk of All-Cause and Cause-Specific Mortality in a Large Cohort: Results From the UK Biobank

Abstract Context Although an inverse association between vitamin D status and mortality has been reported in observational studies, the precise association shape and optimal vitamin D status remain undetermined. Objective To investigate the association between vitamin D status and risk of all-cause and cause-specific mortality and estimate optimal serum 25-hydroxyvitamin D [25(OH)D] concentrations. Design Prospective cohort study. Setting UK Biobank. Participants 365 530 participants who had serum 25(OH)D measurements and no history of cardiovascular disease (CVD), cancer, or diabetes at baseline (2006-2010). Main outcome measures All-cause and cause-specific mortality. Results During a median follow-up of 8.9 (interquartile range: 8.3-9.5) years, 10 175 deaths occurred, including 1841 (18.1%) due to CVD and 5737 (56.4%) due to cancer. The multivariate analyses revealed nonlinear inverse associations, with a decrease in mortality risk appearing to level off at 60 nmol/L of 25(OH)D for all-cause and CVD deaths and at 45 nmol/L for cancer deaths. Compared to participants with 25(OH)D concentrations below the cutoffs, those with higher concentrations had a 17% lower risk for all-cause mortality (hazard ratio [HR]: 0.83, 95% confidence interval [CI]: 0.79-0.86), 23% lower risk for CVD mortality (HR: 0.77, 95% CI: 0.68-0.86), and 11% lower risk for cancer mortality (HR: 0.89, 95% CI: 0.84-0.95). Conclusions Higher 25(OH)D concentrations are nonlinearly associated with lower risk of all-cause, CVD, and cancer mortality. The thresholds of 45 to 60 nmol/L might represent an intervention target to reduce the overall risk of premature death, which needs further confirmation in large clinical trials.

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Association of Antioxidants Use with All-Cause and Cause-Specific Mortality: A Prospective Study of the UK Biobank

Antioxidants ◽

10.3390/antiox9121287 ◽

2020 ◽

Vol 9 (12) ◽

pp. 1287

Author(s):

Inken Behrendt ◽

Gerrit Eichner ◽

Mathias Fasshauer

Keyword(s):

Respiratory Disease ◽

Mortality Risk ◽

Cancer Mortality ◽

Primary Objective ◽

Inverse Association ◽

Uk Biobank ◽

Cancer Subtypes ◽

Specific Mortality ◽

The Uk ◽

The Impact

Prospective studies and randomized controlled trials elucidating the impact of antioxidants supplementation on mortality risk are inconclusive. The present analysis determined association between regular antioxidants use and all-cause (primary objective), as well as cause-specific, mortality in 345,626 participants of the UK Biobank cohort using Cox proportional hazard models. All models were adjusted for confounders and multiple testing. Antioxidants users were defined as participants who indicated to regularly use at least one of the following: multivitamins, vitamin C, vitamin E, selenium, and zinc. Median age of antioxidants users (n = 101,159) and non-users (n = 244,467) at baseline was 57 years. During 3.9 million person-years and a median follow-up of 11.5 years, 19,491 deaths occurred. Antioxidants use was not significantly associated with all-cause, cancer, and non-cancer mortality including several cancer and non-cancer subtypes. Interestingly, mortality risk from respiratory disease was significantly 21% lower among antioxidants users as compared to non-users (hazard ratio: 0.79; 95% confidence interval: 0.67, 0.92). In conclusion, the present study findings do not support recommendations for antioxidants supplementation to prevent all-cause, cancer, or non-cancer mortality on a population level. The significant inverse association between antioxidants use and respiratory disease mortality needs further study.

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Association of serum 25-hydroxyvitamin D concentrations with risk of dementia among individuals with type 2 diabetes: A cohort study in the UK Biobank

PLoS Medicine ◽

10.1371/journal.pmed.1003906 ◽

2022 ◽

Vol 19 (1) ◽

pp. e1003906

Author(s):

Tingting Geng ◽

Qi Lu ◽

Zhenzhen Wan ◽

Jingyu Guo ◽

Liegang Liu ◽

...

Keyword(s):

Type 2 Diabetes ◽

Vitamin D ◽

Lower Risk ◽

Uk Biobank ◽

Hydroxyvitamin D ◽

Patients With Diabetes ◽

25 Hydroxyvitamin D ◽

The Uk

Background Several epidemiological studies have suggested that vitamin D status is associated with risk of dementia in general populations. However, due to the synergistic effect between diabetic pathology and neuroinflammation, and the prothrombotic profile in patients with diabetes, whether vitamin D is associated with risk of dementia among patients with diabetes is unclear. This study aimed to investigate the associations of circulating vitamin D levels with risks of all-cause dementia, Alzheimer disease (AD), and vascular dementia (VD) among adults with type 2 diabetes (T2D). Methods and findings This study included 13,486 individuals (≥60 years) with T2D and free of dementia at recruitment (2006–2010) from the UK Biobank study. Serum 25-hydroxyvitamin D (25[OH]D) concentrations were measured using the chemiluminescent immunoassay method at recruitment. Serum 25(OH)D ≥ 75 nmol/L was considered sufficient, according to the Endocrine Society Clinical Practice Guidelines. Incidence of all-cause dementia, AD, and VD cases was ascertained using electronic health records (EHRs). Each participant’s person-years at risk were calculated from the date of recruitment to the date that dementia was reported, date of death, date of loss to follow-up, or 28 February 2018, whichever occurred first. Among the 13,486 individuals with T2D (mean age, 64.6 years; men, 64.3%), 38.3% had vitamin D ≥ 50 nmol/L and only 9.1% had vitamin D ≥ 75 nmol/L. During a mean follow-up of 8.5 years, we observed 283 cases of all-cause dementia, including 101 AD and 97 VD cases. Restricted cubic spline analysis demonstrated a nonlinear relationship between serum 25(OH)D and risk of all-cause dementia (Pnonlinearity < 0.001) and VD (Pnonlinearity = 0.007), and the nonlinear association reached borderline significance for AD (Pnonlinearity = 0.06), with a threshold at around a serum 25(OH)D value of 50 nmol/L for all the outcomes. Higher serum levels of 25(OH)D were significantly associated with a lower risk of all-cause dementia, AD, and VD. The multivariate hazard ratios and 95% confidence intervals for participants who had serum 25(OH)D ≥ 50 nmol/L, compared with those who were severely deficient (25[OH]D < 25 nmol/L), were 0.41 (0.29–0.60) for all-cause dementia (Ptrend < 0.001), 0.50 (0.27–0.92) for AD (Ptrend = 0.06), and 0.41 (0.22–0.77) for VD (Ptrend = 0.01). The main limitation of the current analysis was the potential underreporting of dementia cases, as the cases were identified via EHRs. Conclusions In this study, we observed that higher concentrations of serum 25(OH)D were significantly associated with a lower risk of all-cause dementia, AD, and VD among individuals with T2D. Our findings, if confirmed by replication, may have relevance for dementia prevention strategies that target improving or maintaining serum vitamin D concentrations among patients with T2D.

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Implementation Strategies for Improving Vitamin D Status and Increasing Vitamin D Intake in the UK: Current Controversies and Future Perspectives. Proceedings of the 2nd Rank Prize Funds Forum on Vitamin D

British Journal Of Nutrition ◽

10.1017/s0007114521002555 ◽

2021 ◽

pp. 1-60

Author(s):

J.L. Buttriss ◽

S.A. Lanham-New ◽

S. Steenson ◽

L. Levy ◽

G.E. Swan ◽

...

Keyword(s):

Vitamin D ◽

Age Groups ◽

Implementation Strategies ◽

Vitamin D Status ◽

Cost Information ◽

Hydroxyvitamin D ◽

Minority Ethnic Groups ◽

Modelling Studies ◽

Clinical Consequences ◽

The Uk

Abstract A multi-disciplinary expert group met to discuss vitamin D deficiency in the UK, and strategies for improving population intakes and status. Changes to UK Government advice since the 1st Rank Forum on Vitamin D (2009) were discussed, including rationale for setting a RNI (10µg/day;400IU/day) for adults and children (4+ years). Current UK data show inadequate intakes among all age groups, and high prevalence of low vitamin D status among specific groups (e.g. pregnant women and adolescent males/females). Evidence of widespread deficiency within some minority ethnic groups, resulting in nutritional rickets (particularly among Black and South Asian infants), raised particular concern. It is too early to establish whether population vitamin D status has altered since Government recommendations changed in 2016. Vitamin D food fortification was discussed as a potential strategy to increase population intakes. Data from dose-response and dietary modelling studies indicate dairy products, bread, hens’ eggs and some meats as potential fortification vehicles. Vitamin D3 appears more effective than vitamin D2 for raising serum 25-hydroxyvitamin D concentration, which has implications for choice of fortificant. Other considerations for successful fortification strategies include: i) need for ‘real-world’ cost information for use in modelling work; ii) supportive food legislation; iii) improved consumer and health professional understanding of vitamin D’s importance; iv) clinical consequences of inadequate vitamin D status; v) consistent communication of Government advice across health/social care professions, and via the food industry. These areas urgently require further research to enable universal improvement in vitamin D intakes and status in the UK population.

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925Ethnic differences and determinants of vitamin D deficiency in the UK Biobank

International Journal of Epidemiology ◽

10.1093/ije/dyab168.641 ◽

2021 ◽

Vol 50 (Supplement_1) ◽

Author(s):

Joshua Sutherland ◽

Ang Zhou ◽

Matthew Leach ◽

Elina Hyppönen

Keyword(s):

Vitamin D ◽

Vitamin D Deficiency ◽

Asian Population ◽

European Ancestry ◽

Uk Biobank ◽

Mixed Ancestry ◽

Black African ◽

Hydroxyvitamin D ◽

The Uk ◽

Summer Time

Abstract Background While controversy remains regarding optimal vitamin D status, the public health relevance of true vitamin D deficiency is undisputed. There are few contemporary cross-ethnic studies investigating the prevalence and determinants of very low 25-hydroxyvitamin D [25(OH)D] concentrations. Methods We used data from 440,581 UK Biobank participants, of which 415,903 identified as white European, 7,880 Asian, 7,602 black African, 1,383 Chinese, and 6,473 of mixed ancestry. 25(OH)D concentrations were measured by DiaSorin Liaison XL and deficiency defined as ≤ 25 nmol/L 25(OH)D. Results The prevalence of 25(OH)D deficiency was highest among participants of Asian ancestry (57.2% in winter/spring and 50.8% in summer/autumn; followed by black African [38.47%/30.78%], mixed ancestry [36.53%/22.48%], Chinese [33.12%/20.68%] and white European [17.45%/5.90%], P < 1.0E-300). Participants with higher socioeconomic deprivation were more likely to have 25(OH)D deficiency compared to less deprived (P < 1.0E-300 for all comparisons), with the pattern being more apparent among those of white European ancestry and in summer (Pinteraction<6.4E-5 for both). In fully-adjusted analyses, regular consumption of oily fish was effective in mitigating ≤25 nmol/L 25(OH)D deficiency across all ethnicities, whilst outdoor-summer time was less effective for black Africans than white Europeans (OR: 0.89; 95% CI: 0.70, 1.12 and OR: 0.40; 95% CI: 0.38, 0.42, respectively). Conclusions Vitamin D deficiency remains an issue throughout the UK, particularly in lower socioeconomic areas and the UK Asian population, half of whom have vitamin D deficiency across seasons. Key messages The prevalence of 25(OH)D deficiency in the UK is alarming, with certain ethnic and socioeconomic groups considered particularly vulnerable.

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Association of serum 25-hydroxyvitamin D concentrations with all-cause and cause-specific mortality among individuals with diabetes mellitus

10.2337/figshare.12863750.v1 ◽

2020 ◽

Author(s):

Zhenzhen Wan ◽

Jingyu Guo ◽

An Pan ◽

Chen Chen ◽

Liegang Liu ◽

...

Keyword(s):

Diabetes Mellitus ◽

Vitamin D ◽

Vitamin D Status ◽

Hydroxyvitamin D ◽

All Cause Mortality ◽

Specific Mortality ◽

25 Hydroxyvitamin D ◽

Nationally Representative ◽

Reduced Risk ◽

Cvd Mortality

Objective: The evidence regarding vitamin D status and mortality among diabetes is scarce. This study aimed to examine the association of serum 25-hydroxyvitamin D [25(OH)D] concentrations with all-cause and cause-specific mortality among adults with <a>diabetes mellitus</a>. Research Design and Methods: This study included 6329 adults with diabetes from the Third National Health and Nutrition Examination Survey (NHANES III) and NHANES 2001-2014. Death outcomes were ascertained by linkage to National Death Index records through 31 December 2015. Cox proportional hazard models were used to estimate hazard ratios (HR) and 95% confidence (CIs) for mortality from all causes, cardiovascular disease (CVD), and cancer. Results: The weighted mean (95% CI) level of serum 25(OH)D was 57.7 (56.6, 58.8) nmol/L, and 46.6% had deficient vitamin D (<50 nmol/L [20 ng/mL]). <a>Higher </a>serum 25(OH)D levels were significantly associated with lower levels of glucose, insulin, HOMA-IR, HbA1c, blood lipids, and C-reactive protein at baseline (all Ptrend<0.05). During 55126 person-years of follow-up, 2056 deaths were documented, including 605 CVD deaths and 309 cancer deaths. <a>After multivariate adjustment, higher </a>serum 25(OH)D levels were significantly and linearly associated with lower all-cause and CVD mortality: there was a 31% reduced risk of all-cause mortality and a 38% reduced risk of CVD mortality per one unit increment in natural log-transformed 25(OH)D (both P<0.001). Compared with participants with 25(OH)D <25 nmol/L, the multivariate-adjusted HRs and 95% CI for participants with 25(OH)D >75 nmol/L were 0.59 (0.43, 0.83) for all-cause mortality (Ptrend=0.003), 0.50 (0.29, 0.86) for CVD mortality (Ptrend=0.02), and 0.49 (0.23, 1.04) for cancer mortality (Ptrend=0.12). Conclusions: In a nationally representative sample of US adults with diabetes, higher serum 25(OH)D levels were significantly associated with lower all-cause and CVD mortality. These findings suggest that maintaining adequate vitamin D status may lower mortality risk in individuals with diabetes.

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Vitamin D status of British African-Caribbean residents: analysis of the UK Biobank cohort

10.26226/morressier.619bdac3be545488cfae50ff ◽

2021 ◽

Author(s):

Rebecca Vearing ◽

Kathryn Hart ◽

Karen Charlton ◽

Yasmine Probst ◽

David Blackbourn ◽

...

Keyword(s):

Vitamin D ◽

Vitamin D Status ◽

Uk Biobank ◽

African Caribbean ◽

The Uk

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Vitamin D Status of the British African-Caribbean Residents: Analysis of the UK Biobank Cohort

Nutrients ◽

10.3390/nu13114104 ◽

2021 ◽

Vol 13 (11) ◽

pp. 4104

Author(s):

Rebecca M. Vearing ◽

Kathryn H. Hart ◽

Karen Charlton ◽

Yasmine Probst ◽

David J. Blackbourn ◽

...

Keyword(s):

Vitamin D ◽

Vitamin D Deficiency ◽

Societal Implications ◽

Vitamin D Status ◽

Uk Biobank ◽

Blood Draw ◽

Cross Sectional ◽

Increased Risk ◽

African Caribbean ◽

The Uk

The vitamin D status of the United Kingdom (UK) African-Caribbean (AC) population remains under-researched, despite an increased risk of vitamin D deficiency due to darker skin phenotypes and living at a high latitude. This cross-sectional study explored the vitamin D status and intake of AC individuals (n = 4046 with a valid serum 25(OH)D measurement) from the UK Biobank Cohort, aged ≥40 years at baseline (2006–2010). Over one third of the population were deficient (<25 nmol/L), 41.1% were insufficient (25–50 nmol/L) and 15.9% were sufficient (>50 nmol/L). Median (IQR) 25(OH)D was 30.0 (20.9) nmol/L. Logistic regression showed that brown/black skin phenotype, winter blood draw, not consuming oily fish and not using vitamin D supplements predicted increased odds of vitamin D deficiency, whilst older age and a summer or autumn blood draw were significantly associated with reduced odds of vitamin D deficiency. Vitamin D deficiency and insufficiency were prevalent in this AC population and is of considerable concern given the individual and societal implications of increased morbidity. Public health messaging for this group should focus on year-round vitamin D supplementation and increasing intakes of culturally appropriate vitamin D-rich foods. These data also support the urgent requirement for a revised vitamin D RNI for ethnic groups.

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Proceedings of the Rank Forum on Vitamin D

British Journal Of Nutrition ◽

10.1017/s0007114510002576 ◽

2010 ◽

Vol 105 (1) ◽

pp. 144-156 ◽

Cited By ~ 65

Author(s):

S. A. Lanham-New ◽

J. L. Buttriss ◽

L. M. Miles ◽

M. Ashwell ◽

J. L. Berry ◽

...

Keyword(s):

Vitamin D ◽

Reference Values ◽

Age Groups ◽

Vitamin D Status ◽

Public Health Burden ◽

Hydroxyvitamin D ◽

Wide Range ◽

The Uk ◽

The University ◽

Risk Managers

The Rank Forum on Vitamin D was held on 2nd and 3rd July 2009 at the University of Surrey, Guildford, UK. The workshop consisted of a series of scene-setting presentations to address the current issues and challenges concerning vitamin D and health, and included an open discussion focusing on the identification of the concentrations of serum 25-hydroxyvitamin D (25(OH)D) (a marker of vitamin D status) that may be regarded as optimal, and the implications this process may have in the setting of future dietary reference values for vitamin D in the UK. The Forum was in agreement with the fact that it is desirable for all of the population to have a serum 25(OH)D concentration above 25 nmol/l, but it discussed some uncertainty about the strength of evidence for the need to aim for substantially higher concentrations (25(OH)D concentrations>75 nmol/l). Any discussion of ‘optimal’ concentration of serum 25(OH)D needs to define ‘optimal’ with care since it is important to consider the normal distribution of requirements and the vitamin D needs for a wide range of outcomes. Current UK reference values concentrate on the requirements of particular subgroups of the population; this differs from the approaches used in other European countries where a wider range of age groups tend to be covered. With the re-emergence of rickets and the public health burden of low vitamin D status being already apparent, there is a need for urgent action from policy makers and risk managers. The Forum highlighted concerns regarding the failure of implementation of existing strategies in the UK for achieving current vitamin D recommendations.

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Baseline vitamin D status, sleep patterns, and the risk of incident type 2 diabetes in data from the UK Biobank study

10.2337/figshare.12746681 ◽

2020 ◽

Author(s):

Mengying Wang ◽

Tao Zhou ◽

Xiang Li ◽

Hao Ma ◽

Zhaoxia Liang ◽

...

Keyword(s):

Type 2 Diabetes ◽

Vitamin D ◽

Daytime Sleepiness ◽

Lower Risk ◽

Uk Biobank ◽

Sleep Patterns ◽

Serum 25Ohd ◽

Sleep Behaviors ◽

The Uk

Background: Circulating vitamin D concentrations have been associated with the risk of type 2 diabetes (T2D), but the results are inconsistent. Emerging evidence suggests that vitamin D metabolism is linked to sleep behaviors. We investigated the prospective association between serum 25-hydroxyvitamin D (25OHD) and the risk of incident T2D, and whether such association was modified by sleep behaviors. Research design and methods: The study included 350 211 individuals free of diabetes in the UK Biobank. Serum 25OHD (nmol/L) concentrations were measured. Five sleep behaviors including sleep duration, insomnia, snoring, chronotype, and daytime sleepiness were included to generate overall sleep patterns, defined by healthy sleep scores. We also calculated genetic risk scores of sleep patterns. Results: During a median follow-up of 8.1 years, we documented 6940 incident T2D cases. We found that serum 25OHD were significantly associated with a lower risk of incident T2D, and the multivariate adjusted hazard ratio (HR; 95% confidence interval [CI]) for per 10 nmol/L increase was 0.88 (0.87-0.90). We found a significant interaction between 25OHD and overall sleep patterns on the risk of incident T2D (P for interaction=0.002). The inverse association between high 25OHD and T2D was more prominent among participants with healthier sleep patterns. Among the individual sleep behaviors, daytime sleepiness showed the strongest interaction with 25OHD (P for interaction=0.0006). The reduced HR of T2D associated with high 25OHD appeared to be more evident among participants with no frequent daytime sleepiness compared with those with excessive daytime sleepiness. The genetic variations of the sleep patterns did not modify the relation between 25OHD and T2D. Conclusions: Our study indicates that higher serum 25OHD concentrations are associated with a lower risk of incident T2D; and such relations are modified by overall sleep patterns, with daytime sleepiness being the major contributor.

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