TY  - GEN
CY  - Heidelberg
TI  - The associations of serum 25-hydroxyvitamin D levels and vitamin D supplement use with inflammation, mortality, and low back pain
Y1  - 2025///
AV  - public
N2  - Vitamin D insufficiency and deficiency are highly prevalent in the general population of European countries. Meta-analyses of observational studies and randomized controlled trials (RCT) generally concur that the effect of vitamin D extends well beyond bone health. However, it is imperative to underscore the persisting limitations in many current studies, particularly the paucity of real-world evidence. This dissertation aimed to investigate the associations of vitamin D deficiency (defined by serum 25-hydroxyvitamin D levels (25(OH)D) < 30 nmol/L), insufficiency (25(OH)D 30 - < 50 nmol/L) and self-reported regular intake of vitamin D supplements with a range of mortality outcomes and low back pain (LBP). Furthermore, it aimed to explore whether the associations of vitamin D exposures with mortality outcomes are mediated by biomarkers of systemic inflammatory responses (SIR) to diseases (e.g. cancer). Data from the large, prospective United Kingdom (UK) Biobank were used to address these aims.
Of the included 445,601 participants, 4.3% and 20.4% of the participants reported regularly taking vitamin D or multivitamin supplements, respectively. The majority of the population had either vitamin D deficiency (21.0%) or insufficiency (34.3%). Overall, 49 independent determinants of vitamin D deficiency and also 49 independent determinants of vitamin D supplement use were detected. Cox regression models adjusting for all of these determinants showed that both vitamin D deficiency and insufficiency were strongly associated with all-cause mortality, cardiovascular disease (CVD) mortality, cancer mortality and respiratory disease mortality. Furthermore, self-reported vitamin D supplement use was significantly associated with 10%, 11%, and 29% lower all-cause mortality, cancer, and respiratory disease mortality compared non-users, respectively. An 11% decreased CVD mortality risk by vitamin D supplementation was not statistically significant. Compared to RCTs or meta-analyses of RCTs, the efficacy of vitamin D supplements in reducing mortality in this real-world evidence study was at least as good as observed in RCTs.
In the investigation for the association of vitamin D status and vitamin D supplement use with mortality from 18 cancers, vitamin D deficiency was observed to be associated with significantly increased mortality from 4 cancers: stomach, colorectal, lung, and prostate cancer. Vitamin D insufficiency was associated with increased colorectal and lung cancer mortality. Compared to non-users, vitamin D use was associated with lower lung cancer mortality. The findings indicate that vitamin D supplement use for maintaining sufficient 25(OH)D levels may be a potential approach to reduce lung cancer mortality.
Furthermore, it was observed that vitamin D deficiency was associated with disadvantageous levels of all the investigated 6 blood cell count-based biomarkers of SIR, but not with the 3 C-reactive protein-based biomarkers of SIR. Although both vitamin D deficiency and all blood cell count-based biomarkers of SIR were significantly associated with all mortality outcomes the strength of these associations was unaltered if vitamin D deficiency and biomarkers of SIR were put in the same model. Thus, vitamin D deficiency and a SIR are independently associated with all-cause and cause-specific mortality and there is no evidence for the hypothesis that systemic inflammation is on the pathway from vitamin D deficiency to mortality. 
In another objective of the dissertation, I addressed the hypothesis that a low vitamin D status plays a role in LBP. Vitamin D deficiency and vitamin D supplement use were cross-sectionally associated with LBP in age- and sex-adjusted models, but these associations were not evident in comprehensively adjusted models. In longitudinal analyses, both vitamin D deficiency and vitamin D supplement use were not associated with LBP in any model after correction for multiple testing. This speaks against a role of vitamin D in the etiology of LBP.
In summary, this dissertation used data from the large UK Biobank and showed associations of vitamin D status and vitamin D supplement use with blood cell count based biomarkers of SIR, all-cause mortality, and cause-specific mortality (due to CVD, respiratory disease, total cancer as well as lung cancer), whereas the findings provide no evidence to support their association with LBP. The independent association of vitamin D deficiency and biomarkers of SIR with the mortality outcomes indicate that clinical interventions against both vitamin D deficiency and causes of systemic inflammation are needed if both conditions are present. Regarding vitamin D deficiency, routine testing of 25(OH)D concentrations by general practitioners and the appropriate intake of vitamin D supplement for those identified as vitamin D deficient or insufficient (25(OH)D < 50 nmol/L) is being recommended.
UR  - https://archiv.ub.uni-heidelberg.de/volltextserver/36433/
ID  - heidok36433
A1  - Sha, Sha
ER  -