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Dose-Response Relationships of Vitamin D Status and Vitamin D Intake...
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Dose-Response Relationships of Vitamin D Status and Vitamin D Intake with Health Outcomes

A special issue of Nutrients (ISSN 2072-6643). This special issue belongs to the section "Nutrition and Metabolism".

Deadline for manuscript submissions: closed (21 October 2022) | Viewed by 15095

Special Issue Editor

Prof. Dr. Hermann Brenner

E-Mail Website
Guest Editor
Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany
Interests: aging research; cancer; epidemiology; prevention; screening; vitamin D
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Numerous observational and intervention studies have suggested adverse health effects of poor vitamin D status and health benefits of vitamin D intake. However, results have often been inconsistent. Plausible major explanations for such inconsistency include heterogeneity in consideration of dose–response relationships in observational studies and of the target populations and dosing schemes in intervention studies.

The goal of this Special Issue, “Dose–Response Relationships of Vitamin D Status and Vitamin D Intake with Health Outcomes”, is to contribute to a better understanding of health effects of vitamin D status and vitamin D intake by paying adequate attention to specific dose–response relationships of vitamin D status and vitamin D intake with a variety of health outcomes, including incidence and mortality of major acute and chronic diseases.

Prof. Dr. Hermann Brenner
Guest Editor

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Keywords

  • vitamin D
  • epidemiological studies
  • insufficiency
  • deficiency
  • randomized trials
  • supplementation
  • dose–response
  • incidence
  • mortality

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Published Papers (6 papers)

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Editorial

Jump to: Research, Review

5 pages, 222 KiB  
Editorial
The Role of Vitamin D for Human Health: The Challenge of the Right Study Designs and Interpretation
by Hermann Brenner
Nutrients 2023, 15(13), 2897; https://doi.org/10.3390/nu15132897 - 27 Jun 2023
Cited by 1 | Viewed by 2281
Abstract
Numerous observational and intervention studies have suggested adverse health effects of poor vitamin D status and health benefits of vitamin D intake [...] Full article
(This article belongs to the Special Issue Dose-Response Relationships of Vitamin D Status and Vitamin D Intake with Health Outcomes)

Research

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10 pages, 1525 KiB  
Article
Inverse Relationship between Serum 25-Hydroxyvitamin D and Elevated Intraocular Pressure
by Jun-Hyuk Lee, Yu-Jin Kwon, Hye Sun Lee, Jee Hye Han, Boyoung Joung and Sung Jin Kim
Nutrients 2023, 15(2), 423; https://doi.org/10.3390/nu15020423 - 13 Jan 2023
Cited by 3 | Viewed by 2204
Abstract
Elevated intraocular pressure (EIOP) is the only major modifiable risk factor of glaucoma. While low serum vitamin D levels are considered a potential risk factor for glaucoma, there is conflicting evidence on the relationship between vitamin D and EIOP despite the possible linkage [...] Read more.
Elevated intraocular pressure (EIOP) is the only major modifiable risk factor of glaucoma. While low serum vitamin D levels are considered a potential risk factor for glaucoma, there is conflicting evidence on the relationship between vitamin D and EIOP despite the possible linkage between vitamin D and intraocular pressure through oxidative stress and systemic inflammation. Therefore, the aim of this study is to verify the relationship between 25-hydroxyvitamin D [25(OH)D] and EIOP using data from 15,338 individuals who visited the health promotion center of an education hospital. The cubic spline curve revealed an inverse dose-dependent association between serum 25(OH)D level and EIOP. Using multiple logistic regression analysis, the fully adjusted odds ratio (OR) with 95% confidence interval (CI) for the EIOP of the serum 25(OH)D per increment was 0.97 (0.96–0.990). The fully adjusted ORs (95% CIs) for the EIOP of the 25(OH)D insufficiency and 25(OH)D sufficiency groups, compared to 25(OH)D deficiency group, were 0.72 (0.56–0.92) and 0.51 (0.34–0.78), respectively. The relationship remained significant in male and young age subgroups. In conclusion, the clinical assessment of intraocular pressure may prove helpful when treating patients with 25(OH)D deficiency, which may be a preventive strategy against the development of glaucoma. Full article
(This article belongs to the Special Issue Dose-Response Relationships of Vitamin D Status and Vitamin D Intake with Health Outcomes)
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15 pages, 2066 KiB  
Article
Efficacy and Safety of a Personalized Vitamin D3 Loading Dose Followed by Daily 2000 IU in Colorectal Cancer Patients with Vitamin D Insufficiency: Interim Analysis of a Randomized Controlled Trial
by Sabine Kuznia, David Czock, Annette Kopp-Schneider, Reiner Caspari, Harald Fischer, Dana Clarissa Laetsch, Marija Slavic, Hermann Brenner and Ben Schöttker
Nutrients 2022, 14(21), 4546; https://doi.org/10.3390/nu14214546 - 28 Oct 2022
Cited by 6 | Viewed by 2753
Abstract
A personalized vitamin D3 loading dose has not yet been tested in cancer patients. This interim analysis of the randomized, placebo-controlled VICTORIA trial analyzed the first recruited 74 German adults with nonmetastatic colorectal cancer, a tumor surgery within the past year, and [...] Read more.
A personalized vitamin D3 loading dose has not yet been tested in cancer patients. This interim analysis of the randomized, placebo-controlled VICTORIA trial analyzed the first recruited 74 German adults with nonmetastatic colorectal cancer, a tumor surgery within the past year, and 25-hydroxyvitamin D levels (25(OH)D) < 50 nmol/L. Study participants received a loading dose tailored for a baseline 25(OH)D level and BMI in the first 11 days, followed by a maintenance dose of 2000 IU of vitamin D3 daily until end of trial week 12. The mean 25(OH)D levels were 27.6, 31.0, and 34.1 nmol/L in the placebo group and 25.9, 63.1, and 75.5 nmol/L in the verum group during screening, visit 1 (end of loading dose), and visit 2 (end of maintenance dose), respectively. The prevalence of 25(OH)D) ≥ 50 nmol/L at visits 1 and 2 was 3.5% and 17.4% in the placebo group and 80.0% and 100% in the verum group. No events of 25(OH)D > 150 nmol/L or hypercalcemia were observed. Hypercalciuria events at visit 1 (n = 5 in verum and n = 1 in the placebo group; p = 0.209) receded after discontinuation of the study medication. The personalized loading dose effectively and safely increased the 25(OH)D levels, and 2000 IU of vitamin D3 daily sustained the achieved levels. Full article
(This article belongs to the Special Issue Dose-Response Relationships of Vitamin D Status and Vitamin D Intake with Health Outcomes)
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12 pages, 970 KiB  
Article
Higher Serum 25-Hydroxyvitamin D Is Associated with Lower All-Cause and Cardiovascular Mortality among US Adults with Nonalcoholic Fatty Liver Disease
by Yuxiong Chen, Siqin Feng, Zhen’ge Chang, Yakun Zhao, Yanbo Liu, Jia Fu, Yijie Liu, Siqi Tang, Yitao Han, Shuyang Zhang and Zhongjie Fan
Nutrients 2022, 14(19), 4013; https://doi.org/10.3390/nu14194013 - 27 Sep 2022
Cited by 8 | Viewed by 2591
Abstract
Aims: We aimed to assess the association between serum 25-hydroxyvitamin D (25(OH)D) levels with all-cause and cardiovascular mortality in patients with nonalcoholic fatty liver disease (NAFLD). Methods: We performed a retrospective cohort study based on the US National Health and Nutrition Examination Survey [...] Read more.
Aims: We aimed to assess the association between serum 25-hydroxyvitamin D (25(OH)D) levels with all-cause and cardiovascular mortality in patients with nonalcoholic fatty liver disease (NAFLD). Methods: We performed a retrospective cohort study based on the US National Health and Nutrition Examination Survey 2001–2016 on adults aged ≥20 years. NAFLD was determined as a US Fatty Liver Index score ≥ 30 in the absence of other liver conditions. Weighted Cox proportional hazards regression models were applied to explore the relationship between serum 25(OH)D levels and mortality. Results: 898 all-cause deaths and 305 cardiovascular deaths were recorded over a median follow-up of 8.7 years. Compared with those in the severe deficiency group (below 25.0 nmol/L), the fully adjusted HRs and 95% CIs of NAFLD patients with sufficient serum 25(OH)D concentrations (≥75.0 nmol/L) were 0.36 (0.22, 0.60) for all-cause mortality and 0.14 (0.07, 0.29) for cardiovascular mortality. Each one-unit increase in the natural log-transformed serum 25(OH)D concentration was related to a 41% lower risk for all-cause deaths (HR = 0.59, 95% CI: 0.46, 0.77) and a 65% lower risk for cardiovascular deaths (HR = 0.35, 95% CI: 0.22, 0.58). Conclusions: Among NAFLD patients, increased serum 25(OH)D levels were independently associated with reduced risk for all-cause and cardiovascular deaths. Full article
(This article belongs to the Special Issue Dose-Response Relationships of Vitamin D Status and Vitamin D Intake with Health Outcomes)
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13 pages, 635 KiB  
Article
Consistent Inverse Associations of Total, “Bioavailable”, Free, and “Non-Bioavailable” Vitamin D with Incidence of Diabetes among Older Adults with Lower Baseline HbA1c (≤6%) Levels
by Anna Zhu, Sabine Kuznia, Tobias Niedermaier, Bernd Holleczek, Ben Schöttker and Hermann Brenner
Nutrients 2022, 14(16), 3282; https://doi.org/10.3390/nu14163282 - 11 Aug 2022
Cited by 4 | Viewed by 2271
Abstract
Background: Serum 25-hydroxyvitamin (25(OH)D) levels are inversely associated with risk of diabetes. The “free hormone hypothesis” suggests potential effects to be mainly related to concentrations of “bioavailable” and free rather than total 25(OH)D. We assessed associations of serum concentrations of vitamin D-binding protein [...] Read more.
Background: Serum 25-hydroxyvitamin (25(OH)D) levels are inversely associated with risk of diabetes. The “free hormone hypothesis” suggests potential effects to be mainly related to concentrations of “bioavailable” and free rather than total 25(OH)D. We assessed associations of serum concentrations of vitamin D-binding protein (VDBP), as well as total “bioavailable”, complementary “non-bioavailable”, and free 25(OH)D, with the risk of developing diabetes among non-diabetic older adults in a large population-based cohort study in Germany. Methods: We included 4841 non-diabetic older adults aged 50–75 years at the baseline exam from the ESTHER cohort conducted in Saarland, Germany, in 2001–2002. Concentrations of “bioavailable” and free 25(OH)D were derived from serum concentrations of VDBP, total 25(OH)D, and albumin. Incidence of diabetes was ascertained during up to 14 years of follow-up. Associations were quantified by multivariable Cox proportional hazards regression models with comprehensive confounder adjustment. Results: During a median follow-up of 10.6 years, 837 non-diabetic participants developed diabetes. We observed similar inverse associations with developing diabetes for VDBP (hazard ratio (HR) for lowest versus highest quintile: 1.37, 95% confidence interval (CI): 1.09, 1.72), total 25(OH)D (HR: 1.31, 95% CI: 1.03, 1.66), and “non-bioavailable” 25(OH)D (HR: 1.30, 95% CI: 1.02, 1.65). Associations were smaller and statistically insignificant for “bioavailable” and free 25(OH)D. However, associations of total “non-bioavailable”, “bioavailable”, and free 25(OH)D with incidence of diabetes were much stronger among, and essentially restricted to, participants with lower baseline HbA1c (≤6%) levels. Conclusions: This large prospective cohort study of older Caucasian adults, in agreement with results from randomized trials and Mendelian randomization studies, supports a protective effect of vitamin D against development of diabetes. The “free hormone theory” may not be relevant in this context. However, our results underline the importance of adequate vitamin D status among those who have not yet shown any sign of impaired glucose tolerance. Full article
(This article belongs to the Special Issue Dose-Response Relationships of Vitamin D Status and Vitamin D Intake with Health Outcomes)
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Review

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15 pages, 674 KiB  
Review
Vitamin D-Binding Protein, Bioavailable, and Free 25(OH)D, and Mortality: A Systematic Review and Meta-Analysis
by Anna Zhu, Sabine Kuznia, Daniel Boakye, Ben Schöttker and Hermann Brenner
Nutrients 2022, 14(19), 3894; https://doi.org/10.3390/nu14193894 - 20 Sep 2022
Cited by 8 | Viewed by 2117
Abstract
Introduction: Observational studies reported inverse associations between serum total 25-hydroxyvitamin D (25(OH)D) concentrations and mortality. Evolving evidence indicated, however, that bioavailable or free 25(OH)D may be even better predictors of mortality. We conducted a systematic review and meta-analysis to summarize the epidemiological evidence [...] Read more.
Introduction: Observational studies reported inverse associations between serum total 25-hydroxyvitamin D (25(OH)D) concentrations and mortality. Evolving evidence indicated, however, that bioavailable or free 25(OH)D may be even better predictors of mortality. We conducted a systematic review and meta-analysis to summarize the epidemiological evidence on associations of vitamin D-binding protein (VDBP), albumin-bound, bioavailable, and free 25(OH)D, with mortality. Methods: We systematically searched PubMed and Web of Science, up to 27 May 2022. Predictors of interest included serum or plasma concentrations of VDBP, albumin-bound, bioavailable, and free 25(OH)D. Assessed health outcomes were all-cause and cause-specific mortality. We included studies reporting associations between these biomarkers and mortality outcomes. We applied random-effects models for meta-analyses to summarize results from studies assessing the same vitamin D biomarkers and mortality outcomes. Results: We identified twelve eligible studies, including ten on VDBP, eight on bioavailable 25(OH)D, and eight on free 25(OH)D. No study reported on albumin-bound 25(OH)D and mortality. In meta-analyses, the highest levels of bioavailable and free 25(OH)D were associated with 37% (hazard ratio (HR): 0.63, 95% confidence interval (CI): 0.46, 0.87), and 29% (HR: 0.71, 95% CI: 0.53, 0.97) decrease in all-cause mortality, respectively, compared with the lowest levels. These estimates were similar to those for total 25(OH)D (HR: 0.67, 95% CI: 0.56, 0.80) observed in the same studies. Higher VDBP levels were associated with lower all-cause mortality in cancer patient cohorts. However, no such association was observed in general population cohorts. Conclusions: Similar inverse associations of total, bioavailable, and free 25(OH)D with mortality suggest that bioavailable and free 25(OH)D do not provide incremental value in predicting mortality. Full article
(This article belongs to the Special Issue Dose-Response Relationships of Vitamin D Status and Vitamin D Intake with Health Outcomes)
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