Vitamin D-Binding Protein, Bioavailable, and Free 25(OH)D, and Mortality: A Systematic Review and Meta-Analysis
Abstract
1. Introduction
2. Materials and Methods
2.1. Literature Search
2.2. Study Eligibility
2.3. Data Extraction and Quality Assessment
2.4. Data Synthesis
3. Results
3.1. Literature Search
3.2. Study Characteristics
3.3. Vitamin D Biomarkers and Mortality
3.4. Meta-Analyses
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
References
- Schöttker, B.; Jorde, R.; Peasey, A.; Thorand, B.; Jansen, E.H.J.M.; de Groot, L.; Streppel, M.; Gardiner, J.; Ordóñez-Mena, J.M.; Perna, L.P.; et al. Vitamin D and mortality: Meta-analysis of individual participant data from a large consortium of cohort studies from Europe and the United States. BMJ 2014, 348, g3656. [Google Scholar] [CrossRef] [PubMed]
- Gaksch, M.; Jorde, R.; Grimnes, G.; Joakimsen, R.; Schirmer, H.; Wilsgaard, T.; Mathiesen, E.B.; Njølstad, I.; Løchen, M.-L.; März, W.; et al. Vitamin D and mortality: Individual participant data meta-analysis of standardized 25-hydroxyvitamin D in 26916 individuals from a European consortium. PLoS ONE 2017, 12, e0170791. [Google Scholar] [CrossRef]
- Emerging Risk Factors Collaboration/EPIC-CVD/Vitamin D Studies Collaboration. Estimating dose-response relationships for vitamin D with coronary heart disease, stroke, and all-cause mortality: Observational and Mendelian randomisation analyses. Lancet Diabetes Endocrinol. 2021, 9, 837–846. [Google Scholar] [CrossRef]
- Bikle, D.D.; Schwartz, J. Vitamin D Binding Protein, Total and Free Vitamin D Levels in Different Physiological and Pathophysiological Conditions. Front. Endocrinol. 2019, 10, 317. [Google Scholar] [CrossRef] [PubMed]
- Bikle, D.; Bouillon, R.; Thadhani, R.; Schoenmakers, I. Vitamin D metabolites in captivity? Should we measure free or total 25 (OH) D to assess vitamin D status? J. Steroid Biochem. Mol. Biol. 2017, 173, 105–116. [Google Scholar] [CrossRef]
- Tsuprykov, O.; Chen, X.; Hocher, C.-F.; Skoblo, R.; Yin, L.; Hocher, B. Why should we measure free 25 (OH) vitamin D? J. Steroid Biochem. Mol. Biol. 2018, 180, 87–104. [Google Scholar] [CrossRef]
- Bikle, D.D.; Malmstroem, S.; Schwartz, J. Current Controversies: Are Free Vitamin Metabolite Levels a More Accurate Assessment of Vitamin D Status than Total Levels? Endocrinol. Metab. Clin. N. Am. 2017, 46, 901–918. [Google Scholar] [CrossRef]
- Powe, C.E.; Evans, M.K.; Wenger, J.; Zonderman, A.B.; Berg, A.H.; Nalls, M.; Tamez, H.; Zhang, D.; Bhan, I.; Karumanchi, S.A. Vitamin D–binding protein and vitamin D status of black Americans and white Americans. N. Engl. J. Med. 2013, 369, 1991–2000. [Google Scholar] [CrossRef]
- Page, M.J.; McKenzie, J.E.; Bossuyt, P.M.; Boutron, I.; Hoffmann, T.C.; Mulrow, C.D.; Shamseer, L.; Tetzlaff, J.M.; Akl, E.A.; Brennan, S.E.; et al. The PRISMA 2020 statement: An updated guideline for reporting systematic reviews. Syst. Rev. 2021, 10, 89. [Google Scholar] [CrossRef]
- Wells, G.; Shea, B.; O’Connell, D.; Peterson, J.; Welch, V.; Losos, M.; Tugwell, P. The Newcastle-Ottawa Scale (NOS) for Assessing the Quality of Nonrandomised Studies in Meta-Analyses. Available online: http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp (accessed on 10 June 2022).
- Dejaeger, M.; Antonio, L.; Bouillon, R.; Moors, H.; Wu, F.C.W.; O’Neill, T.W.; Huhtaniemi, I.T.; Rastrelli, G.; Forti, G.; Maggi, M.; et al. Ageing men with insufficient vitamin D have a higher mortality risk: No added value of its free fractions or active form. J. Clin. Endocrinol. Metab. 2021, 107, e1212–e1220. [Google Scholar] [CrossRef]
- Zhu, A.; Kuznia, S.; Niedermaier, T.; Holleczek, B.; Schöttker, B.; Brenner, H. Vitamin D-binding protein, total, “nonbioavailable,” bioavailable, and free 25-hydroxyvitamin D, and mortality in a large population-based cohort of older adults. J. Intern. Med. 2022, 292, 463–476. [Google Scholar] [CrossRef] [PubMed]
- Yang, L.; Chen, H.; Zhao, M.; Peng, P. Prognostic value of circulating vitamin D binding protein, total, free and bioavailable 25-hydroxy vitamin D in patients with colorectal cancer. Oncotarget 2017, 8, 40214–40221. [Google Scholar] [CrossRef] [PubMed]
- Yuan, C.; Song, M.; Zhang, Y.; Wolpin, B.M.; Meyerhardt, J.A.; Ogino, S.; Hollis, B.W.; Chan, A.T.; Fuchs, C.S.; Wu, K.; et al. Prediagnostic Circulating Concentrations of Vitamin D Binding Protein and Survival among Patients with Colorectal Cancer. Cancer Epidemiol. Biomark. Prev. 2020, 29, 2323–2331. [Google Scholar] [CrossRef] [PubMed]
- Fang, A.-P.; Long, J.-A.; Zhang, Y.-J.; Liu, Z.-Y.; Li, Q.-J.; Zhang, D.-M.; Luo, Y.; Zhong, R.-H.; Zhou, Z.-G.; Xu, Y.-J.; et al. Serum Bioavailable, Rather Than Total, 25-hydroxyvitamin D Levels Are Associated With Hepatocellular Carcinoma Survival. Hepatology 2020, 72, 169–182. [Google Scholar] [CrossRef]
- Turner, A.M.; McGowan, L.; Millen, A.; Rajesh, P.; Webster, C.; Langman, G.; Rock, G.; Tachibana, I.; Tomlinson, M.G.; Berditchevski, F.; et al. Circulating DBP level and prognosis in operated lung cancer: An exploration of pathophysiology. Eur. Respir. J. 2013, 41, 410–416. [Google Scholar] [CrossRef]
- Anic, G.M.; Weinstein, S.J.; Mondul, A.M.; Mannisto, S.; Albanes, D. Serum vitamin D, vitamin D binding protein, and lung cancer survival. Lung Cancer 2014, 86, 297–303. [Google Scholar] [CrossRef]
- Peng, S.M.; Yu, N.; Che, J.; Xu, J.Y.; Chen, G.C.; Li, D.P.; Zhang, Y.S.; Qin, L.Q. Total, bioavailable and free 25-hydroxyvitamin D are associated with the prognosis of patients with non-small cell lung cancer. Cancer Causes Control CCC 2022, 33, 983–993. [Google Scholar] [CrossRef]
- Chen, P.; Cao, Y.; Duan, X.; Li, J.; Zhao, W.; Wang, H. Bioavailable 25(OH)D level is associated with clinical outcomes of patients with diffuse large B-cell lymphoma: An exploratory study. Clin. Nutr. 2020, 40, 157–165. [Google Scholar] [CrossRef]
- Yu, C.; Xue, H.; Wang, L.; Chen, Q.; Chen, X.; Zhang, Y.; Hu, G.; Ling, W. Serum Bioavailable and Free 25-Hydroxyvitamin D Levels, but Not Its Total Level, Are Associated with the Risk of Mortality in Patients with Coronary Artery Disease. Circ. Res. 2018, 123, 996–1007. [Google Scholar] [CrossRef]
- Persson, L.J.; Aanerud, M.; Hiemstra, P.S.; Michelsen, A.E.; Ueland, T.; Hardie, J.A.; Aukrust, P.; Bakke, P.S.; Eagan, T.M. Vitamin D, vitamin D binding protein, and longitudinal outcomes in COPD. PLoS ONE 2015, 10, e0121622. [Google Scholar] [CrossRef]
- Subramanian, S.; Rhodes, J.M.; Taylor, J.M.; Milan, A.M.; Lane, S.; Hewison, M.; Chun, R.F.; Jorgensen, A.; Richardson, P.; Nitchingham, D.; et al. Vitamin D, vitamin D-binding protein, free vitamin D and COVID-19 mortality in hospitalized patients. Am. J. Clin. Nutr. 2022, 115, 1367–1377. [Google Scholar] [CrossRef] [PubMed]
- Zhu, A.; Kuznia, S.; Niedermaier, T.; Holleczek, B.; Schöttker, B.; Brenner, H. Distribution and Determinants of Vitamin D-Binding Protein, Total, “Non-Bioavailable”, Bioavailable, and Free 25-Hydroxyvitamin D Concentrations among Older Adults. Nutrients 2021, 13, 3982. [Google Scholar] [CrossRef] [PubMed]
- Oleröd, G.; Hultén, L.M.; Hammarsten, O.; Klingberg, E. The variation in free 25-hydroxy vitamin D and vitamin D-binding protein with season and vitamin D status. Endocr. Connect. 2017, 6, 111–120. [Google Scholar] [CrossRef] [PubMed]
- Heath, A.K.; Kim, I.Y.; Hodge, A.M.; English, D.R.; Muller, D.C. Vitamin D Status and Mortality: A Systematic Review of Observational Studies. Int. J. Environ. Res. Public Health 2019, 16, 383. [Google Scholar] [CrossRef]
Participants | First Author, Year | Country | Sample Size (Deaths/Total) | Age (Years) | Sex (% Fem) | Follow-Up (Years) | Predictor | Covariates Adjusted for | |||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Range | Mean | VDBP | 25(OH)D | Age | Sex | BMI | SMK | TIME | OTH | ||||||||
Total | BIO | Free | |||||||||||||||
General population | Dejaeger 2021 [11] | Europe | 469/1915 | NA | 60.1 | 0 | 12.3 a | √ | √ | √ | √ | √ | √ | √ | d | ||
Zhu 2022 [12] | Germany | 1739/5899 | 49–75 | 62.3 | 56.1 | 17.1 a | √ | √ | √ | √ | √ | √ | √ | √ | √ | e | |
Cancer patients | |||||||||||||||||
Colorectal | Yang 2017 [13] | China | 87/206 | 30–85 | 63.0 c | 36.4 | 3.8 a | √ | √ | √ | √ | √ | √ | √ | f | ||
Colorectal | Yuan 2020 [14] | US | 328/603 | 30–75 | 71.3 | 59.2 | 12.4 a | √ | √ | √ | √ | √ | √ | √ | g | ||
Liver | Fang 2020 [15] | China | 430/1031 | NA | 53.0 | 11.8 | 2.0 a | √ | √ | √ * | √ | √ | √ | √ | h | ||
Lung | Turner 2013 [16] | UK | 26/148 | NA | 66.8 | 41.4 | 4.1 b | √ | √ | √ | √ | i | |||||
Lung | Anic 2014 [17] | Finland | 428/500 | 50–69 | 68.4 | 0 | 20.0 c | √ | √ | √ | √ | √ | √ | √ | j | ||
Lung | Peng 2022 [18] | China | 179/395 | NA | 63.0 | 36.2 | 2.7 a | √ | √ | √ | √ * | √ | √ | √ | √ | k | |
DLBCL | Chen 2020 [19] | China | NA/332 | >60 years: 39.8% | 46.7 | 2.9 a | √ | √ | √ | l | |||||||
Other patients | |||||||||||||||||
CAD | Yu 2018 [20] | China | 205/1387 | 40–85 | 63.2 | 34.9 | 6.7 a | √ | √ | √ * | √ | √ | √ | √ | √ | m | |
COPD | Persson 2015 [21] | Norway | 69/426 | 40–76 | 63.5 | 39.9 | 5.0 b | √ | √ | √ | √ | √ | √ | n | |||
COVID-19 | Subramanian 2022 [22] | UK | 112/472 | 19–98 | 66.9 | 43.2 | NA | √ | √ | √ | √ | √ | √ | o |
Study | Cause of Mortality | VDBP | Total 25(OH)D | Bioavailable 25(OH)D | Free 25(OH)D | ||||
---|---|---|---|---|---|---|---|---|---|
(μg/mL) | HR (95% CI) | (ng/mL) | HR (95% CI) | (ng/mL) | HR (95% CI) | (pg/mL) | HR (95% CI) | ||
Dejaeger 2021 [11] | All-cause | 293.6 (36.7) a | Qi1: Ref b | 16.8 (8.9) a | Qi1: Ref b | NA | NA | 4.3 (2.3) a | Qi1: Ref b |
Qi2: 0.99 (0.70, 1.40) | Qi2: 0.77 (0.53, 1.12) | Qi2: 0.94 (0.61, 1.47) | |||||||
Qi3: 0.94 (0.67, 1.33) | Qi3: 0.82 (0.56, 1.19) | Qi3: 0.93 (0.60, 1.45) | |||||||
Qi4: 0.94 (0.67, 1.33) | Qi4: 0.56 (0.38, 0.81) | Qi4: 0.65 (0.42, 1.01) | |||||||
Qi5: 1.23 (0.88, 1.75) | Qi5: 0.49 (0.34, 0.72) | Qi5: 0.48 (0.31, 0.75) | |||||||
Zhu 2022 [12] | All-cause | Q1: 37.8–283.9 Q2: 283.9–314.3 Q3: 314.4–349.6 Q4: 349.7–600.0 | Q1: Ref | Q1: 2.8–13.4 Q2: 13.4–17.8 Q3: 17.8–24.0 Q4: 24.0–50.0 | Q1: Ref | Q1: 0.3–1.6 Q2: 1.6–2.2 Q3: 2.2–3.1 Q4: 3.1–7.0 | Q1: Ref | Q1: 0.6–3.6 Q2: 3.6–4.9 Q3: 4.9–6.9 Q4: 6.9–14.0 | Q1: Ref |
Q2: 0.90 (0.79, 1.02) | Q2: 0.80 (0.70, 0.90) | Q2: 0.87 (0.76, 0.99) | Q2: 0.86 (0.76, 0.98) | ||||||
Q3: 0.90 (0.79, 1.03) | Q3: 0.72 (0.63, 0.82) | Q3: 0.74 (0.64, 0.84) | Q3: 0.74 (0.65, 0.85) | ||||||
Q4: 0.95 (0.83, 1.09) | Q4: 0.64 (0.55, 0.73) | Q4: 0.67 (0.58, 0.77) | Q4: 0.70 (0.60, 0.80) | ||||||
CVD | Q1: Ref | Q1: Ref | Q1: Ref | Q1: Ref | |||||
Q2: 0.84 (0.67, 1.06) | Q2: 0.90 (0.72, 1.12) | Q2: 0.91 (0.73, 1.14) | Q2: 0.99 (0.79, 1.24) | ||||||
Q3: 0.94 (0.75, 1.18) | Q3: 0.77 (0.61, 0.97) | Q3: 0.80 (0.63, 1.01) | Q3: 0.84 (0.66, 1.06) | ||||||
Q4: 0.92 (0.73, 1.17) | Q4: 0.64 (0.50, 0.83) | Q4: 0.64 (0.49, 0.82) | Q4: 0.71 (0.55, 0.91) | ||||||
Cancer | Q1: Ref | Q1: Ref | Q1: Ref | Q1: Ref | |||||
Q2: 0.85 (0.68, 1.07) | Q2: 0.76 (0.61, 0.96) | Q2: 0.76 (0.60, 0.96) | Q2: 0.71 (0.56, 0.90) | ||||||
Q3: 0.89 (0.70, 1.11) | Q3: 0.82 (0.65, 1.03) | Q3: 0.72 (0.57, 0.91) | Q3: 0.67 (0.53, 0.85) | ||||||
Q4: 0.99 (0.79, 1.24) | Q4: 0.76 (0.60, 0.97) | Q4: 0.80 (0.63, 1.02) | Q4: 0.81 (0.64, 1.02) | ||||||
Respiratory disease | Q1: Ref | Q1: Ref | Q1: Ref | Q1: Ref | |||||
Q2: 0.73 (0.41, 1.30) | Q2: 0.60 (0.35, 1.04) | Q2: 0.60 (0.34, 1.04) | Q2: 0.61 (0.35, 1.07) | ||||||
Q3: 0.67 (0.37, 1.22) | Q3: 0.53 (0.29, 0.94) | Q3: 0.49 (0.28, 0.87) | Q3: 0.54 (0.31, 0.96) | ||||||
Q4: 1.08 (0.62, 1.86) | Q4: 0.39 (0.20, 0.74) | Q4: 0.35 (0.18, 0.67) | Q4: 0.37 (0.19, 0.70) |
Study | Cause of Mortality | VDBP | Total 25(OH)D | Bioavailable 25(OH)D | Free 25(OH)D | ||||
---|---|---|---|---|---|---|---|---|---|
(μg/mL) | HR (95% CI) | (ng/mL) | HR (95% CI) | (ng/mL) | HR (95% CI) | (pg/mL) | HR (95% CI) | ||
Patients with colorectal cancer | |||||||||
Yang 2017 [13] | CRC | L: <159 | L: Ref | L: <6.2 | L: Ref | L: <0.58 | L: Ref | L: <0.01 | L: Ref |
M: 159–310 | M: 1.46 (0.81, 2.66) | M: 6.2–29.9 | M: 1.18 (0.72, 1.94) | M: 0.58–1.03 | M: 0.81 (0.33, 1.99) | M: 0.01–0.02 | M: 0.24 (0.12, 0.50) | ||
H: >310 | H: 2.01 (0.92, 4.42) | H: >29.9 | H: 1.79 (0.90, 3.56) | H: >1.03 | H: 0.40 (0.082, 1.93) | H:>0.02 | H: 0.44 (0.24, 0.82) | ||
Yuan 2020 [14] | All-cause | Q1: 125.2 Q2: 213.5 Q3: 274.6 Q4: 383.5 a | Q1: Ref | Q1: 15.6 Q2: 23.7 Q3: 29.4 Q4: 40.5 a | Q1: Ref | Q1: 1.8 Q2: 2.9 Q3: 3.9 Q4: 6.5 a | Q1: Ref | Q1: 4.5 Q2: 7.0 Q3: 9.4 Q4: 15.8 a | Q1: Ref |
Q2: 0.77 (0.57, 1.06) | Q2: 1.18 (0.84, 1.65) | Q2: 1.11 (0.78, 1.59) | Q2: 1.18 (0.82, 1.69) | ||||||
Q3: 0.69 (0.50, 0.96) | Q3: 1.13 (0.80, 1.59) | Q3: 1.12 (0.78, 1.61) | Q3: 1.11 (0.77, 1.59) | ||||||
Q4: 0.58 (0.41, 0.80) | Q4: 0.72 (0.49, 1.05) | Q4: 1.19 (0.82, 1.73) | Q4: 1.36 (0.94, 1.95) | ||||||
CRC | Q1: Ref | Q1: Ref | Q1: Ref | Q1: Ref | |||||
Q2: 0.76 (0.50, 1.15) | Q2: 1.22 (0.77, 1.93) | Q2: 1.07 (0.66, 1.71) | Q2: 1.18 (0.73, 1.90) | ||||||
Q3: 0.73 (0.48, 1.11) | Q3: 1.45 (0.92, 2.30) | Q3: 1.01 (0.61, 1.65) | Q3: 1.05 (0.64, 1.70) | ||||||
Q4: 0.58 (0.37, 0.91) | Q4: 0.57 (0.34, 0.97) | Q4: 1.26 (0.77, 2.06) | Q4: 1.35 (0.83, 2.18) | ||||||
5-year overall survival | Q1: Ref | Q1: Ref | Q1: Ref | Q1: Ref | |||||
Q2: 0.74 (0.50, 1.10) | Q2: 0.92 (0.60, 1.40) | Q2: 1.07 (0.68, 1.69) | Q2: 1.03 (0.65, 1.64) | ||||||
Q3: 0.68 (0.46, 1.01) | Q3: 1.05 (0.69, 1.59) | Q3: 1.03 (0.65, 1.63) | Q3: 0.97 (0.61, 1.53) | ||||||
Q4: 0.50 (0.32, 0.76) | Q4: 0.48 (0.30, 0.78) | Q4: 1.14 (0.71, 1.82) | Q4: 1.29 (0.82, 2.02) | ||||||
Patients with liver cancer | |||||||||
Fang 2020 [15] | All-cause | NA | NA | Q1: ≤27.3 Q2: 27.3–34.6 Q3: 34.6–43.6 Q4: >43.6 | Q1: Ref | Q1: ≤1.73 Q2: 1.73–2.12 Q3: 2.12–2.56 Q4: >2.56 b | Q1: Ref | Q1: ≤4.62 Q2: 4.62–5.58 Q3: 5.58–6.71 Q4: >6.71 b | Q1: Ref |
Q2: 0.88 (0.66, 1.18) | Q2: 0.85 (0.66, 1.11) | Q2: 0.83 (0.63, 1.09) | |||||||
Q3: 0.97 (0.73, 1.29) | Q3: 0.77 (0.59, 1.00) | Q3: 0.83 (0.63, 1.09) | |||||||
Q4: 0.95 (0.72, 1.26) | Q4: 0.71 (0.53, 0.94) | Q4: 0.89 (0.68, 1.18) | |||||||
Liver cancer | NA | Q1: Ref | Q1: Ref | Q1: Ref | |||||
Q2: 0.90 (0.66, 1.22) | Q2: 0.80 (0.61, 1.05) | Q2: 0.83 (0.63, 1.10) | |||||||
Q3: 0.99 (0.73, 1.32) | Q3: 0.75 (0.57, 0.98) | Q3: 0.79 (0.59, 1.05) | |||||||
Q4: 0.97 (0.72, 1.31) | Q4: 0.69 (0.51, 0.93) | Q4: 0.90 (0.68, 1.20) | |||||||
Patients with lung cancer | |||||||||
Turner 2013 [16] | Lung cancer | Q1: <199 | Q1: Ref c | NA | NA | NA | NA | NA | NA |
Q2: 199–332 | Q2: 0.55 (0.046, 5.60) | ||||||||
Q3: 332–430 | Q3: 0.53 (0.044, 5.33) | ||||||||
Q4: ≥430 | Q4: 0.096 (0.0080, 0.97) | ||||||||
Anic 2014 [17] | Lung cancer | Q1: <274 | Q1: Ref | Season specific quartiles d | Q1: Ref | NA | NA | NA | NA |
Q2: 274–342 | Q2: 0.79 (0.59, 1.06) | Q2: 1.08 (0.81, 1.43) | |||||||
Q3: 342–417 | Q3: 1.02 (0.76, 1.35) | Q3: 0.97 (0.72, 1.29) | |||||||
Q4: ≥417 | Q4: 0.95 (0.71, 1.26) | Q4: 1.18 (0.89, 1.56) | |||||||
Peng 2022 [18] | All-cause | T1: ≤181.5 T2: 181.5–222.7 T3: >222.7 | T1: Ref | T1: ≤ 16.4 T2: 16.4–23.9 T3: >23.9 | T1: Ref | T1: ≤2.21 T2: 2.22–3.40 T3: >3.41 | T1: Ref | T1: ≤6.04 T2: 6.05–9.12 T3: >9.13 | T1: Ref |
T2: 0.67 (0.46, 0.99) | T2: 0.83 (0.57, 1.21) | T2: 0.63 (0.43, 0.92) | T2: 0.68 (0.47, 1.00) | ||||||
T3: 0.74 (0.51, 1.08) | T3: 0.58 (0.40, 0.87) | T3: 0.45 (0.30, 0.67) | T3: 0.49 (0.33, 0.73) | ||||||
PFS | T1: Ref | T1: Ref | T1: Ref | T1: Ref | |||||
T2: 0.73 (0.52, 1.02) | T2: 0.69 (0.49, 0.98) | T2: 0.79 (0.56, 1.10) | T2: 0.74 (0.52, 1.05) | ||||||
T3: 0.84 (0.60, 1.17) | T3: 0.61 (0.43, 0.86) | T3: 0.56 (0.40, 0.80) | T3: 0.60 (0.42, 0.85) | ||||||
Patients with diffuse large B-cell lymphoma | |||||||||
Chen 2020 [19] | All-cause | T1: <371 T2: 371–534 T3: >534 | T1: Ref e | T1: 0.3–11.4 T2: 11.5–18.6 T3: 18.7–37.8 | T1: Ref | T1: 0.094–0.66 T2: 0.66–1.11 T3: 1.11–3.44 | T1: Ref | NA | NA |
T2: 0.79 (0.37, 1.66) | T2: 0.90 (0.40, 2.03) | T2: 0.89 (0.39, 2.02) | |||||||
T3: 0.69 (0.33, 1.46) | T3: 0.40 (0.16, 1.03) | T3: 0.21 (0.07, 0.65) | |||||||
PFS | T1: Ref e | T1: Ref | T1: Ref | NA | |||||
T2: 0.75 (0.44, 1.29) | T2: 0.61 (0.34, 1.11) | T2: 0.72 (0.38, 1.35) | |||||||
T3: 0.51 (0.28, 0.91) | T3: 0.27 (0.13, 0.57) | T3: 0.39 (0.20, 0.79) |
Study | Cause of Mortality | VDBP | Total 25(OH)D | Bioavailable 25(OH)D | Free 25(OH)D | ||||
---|---|---|---|---|---|---|---|---|---|
(μg/mL) | HR (95% CI) | (ng/mL) | HR (95% CI) | (ng/mL) | HR (95% CI) | (pg/mL) | HR (95% CI) | ||
Patients with coronary artery disease | |||||||||
Yu 2018 [20] | All-cause | Q1: 285 Q2: 210 Q3: 139 Q4: 77 a | NA | Q1: 16.8 Q2: 20.4 Q3: 21.3 Q4: 23.2 a | Q1: Ref b | Q1: ≤2.11 Q2: 2.12–3.17 Q3: 3.18–4.87 Q4: ≥4.88 | Q1: Ref b | Q1: 3.17 Q2: 4.19 Q3: 5.14 Q4: 7.41 a | Q1: Ref b |
Q2: 0.67 (0.43, 1.04) | Q2: 0.76 (0.50, 1.15) | Q2: 0.82 (0.54, 1.26) | |||||||
Q3: 0.73 (0.47, 1.13) | Q3: 0.76 (0.50, 1.16) | Q3: 0.75 (0.49, 1.14) | |||||||
Q4: 0.74 (0.47, 1.14) | Q4: 0.56 (0.37, 0.85) | Q4: 0.61 (0.40, 0.93) | |||||||
CAD | NA | Q1: Ref b | Q1: Ref b | Q1: Ref b | |||||
Q2: 0.56 (0.33, 0.97) | Q2: 0.72 (0.41, 1.26) | Q2: 0.81 (0.48, 1.38) | |||||||
Q3: 0.66 (0.38, 1.13) | Q3: 0.67 (0.38, 1.18) | Q3: 0.71 (0.42, 1.22) | |||||||
Q4: 0.67 (0.39, 1.15) | Q4: 0.39 (0.22, 0.68) | Q4: 0.51 (0.30, 0.87) | |||||||
Patients with chronic obstructive pulmonary disease | |||||||||
Persson 2015 [21] | All-cause | L: <200 | L: Ref | Per 10 ng/mL decrease | 0.95 (0.71, 1.26) | NA | NA | NA | NA |
M: 200–299 | M: 1.03 (0.60, 1.75) | ||||||||
H: ≥300 | H: 0.76 (0.28, 2.02) | ||||||||
Patients with coronavirus disease 2019 | |||||||||
Subramanian 2022 [22] | COVID-19 | Per 100 μg/mL increase | 1.00 (0.97, 1.04) | Qi1: <10 | Qi1: Ref b | Qi1: <0.18 | Qi1: Ref b | Qi1: <0.62 | Qi1: Ref b |
Qi2: 10–19.6 | Qi2: 0.79 (0.39, 1.59) | Qi2: 0.18–0.32 | Qi2: 0.40 (0.18, 0.86) | Qi2: 0.62–1.08 | Qi2: 0.59 (0.28, 1.24) | ||||
Qi3: 20–29.6 | Qi3: 0.42 (0.21, 0.85) | Qi3: 0.32–0.52 | Qi3: 0.91 (0.42, 1.98) | Qi3: 1.08–1.65 | Qi3: 0.87 (0.41, 1.83) | ||||
Qi4: 30–39.6 | Qi4: 0.92 (0.46, 1.86) | Qi4: 0.52–0.81 | Qi4: 0.59 (0.27, 1.27) | Qi4: 1.65–2.46 | Qi4: 0.78 (0.37, 1.63) | ||||
Qi5: ≥40 | Qi5: 1.95 (0.98, 3.95) | Qi5: >0.81 | Qi5: 0.78 (0.36, 1.69) | Qi5: >2.46 | Qi5: 1.16 (0.55, 2.44) |
Participants | Study | VDBP | Total 25(OH)D | Bioavailable 25(OH)D | Free 25(OH)D |
---|---|---|---|---|---|
HR (95% CI) | HR (95% CI) | HR (95% CI) | HR (95% CI) | ||
General population | Dejaeger 2021 [11] | 1.23 (0.87, 1.73) | 0.49 (0.34, 0.71) | - | 0.48 (0.31, 0.75) |
Zhu 2022 [12] | 0.95 (0.83, 1.09) | 0.64 (0.56, 0.74) | 0.67 (0.58, 0.77) | 0.70 (0.61, 0.81) | |
Subtotal | 1.03 (0.81, 1.30) | 0.59 (0.47, 0.75) | - | 0.62 (0.43, 0.87) | |
Cancer patients | |||||
Colorectal | Yuan 2020 [14] | 0.58 (0.42, 0.81) | 0.72 (0.49, 1.05) | 1.19 (0.82, 1.73) | 1.36 (0.94, 1.96) |
Liver | Fang 2020 [15] | - | 0.95 (0.72, 1.26) | 0.71 (0.53, 0.95) | 0.89 (0.68, 1.17) |
Lung | Peng 2022 [18] | 0.74 (0.51, 1.08) | 0.58 (0.39, 0.86) | 0.45 (0.30, 0.67) | 0.49 (0.33, 0.73) |
DLBCL | Chen 2020 [19] | 0.69 (0.33, 1.45) | 0.40 (0.16, 1.01) | 0.21 (0.07, 0.64) | - |
Subtotal | 0.65 (0.51, 0.82) | 0.71 (0.53, 0.96) | 0.60 (0.33, 1.10) | 0.84 (0.48, 1.49) | |
Other patients | |||||
CAD | Yu 2018 [20] | - | 0.74 (0.48, 1.15) | 0.56 (0.37, 0.85) | 0.61 (0.40, 0.93) |
COPD | Persson 2015 [21] | 0.76 (0.28, 2.04) | - | - | - |
Subtotal | - | - | - | - | |
All studies | 0.83 (0.65, 1.07) | 0.67 (0.56, 0.80) | 0.63 (0.46, 0.87) | 0.71 (0.53, 0.97) |
Participants | Study | VDBP | Total 25(OH)D | Bioavailable 25(OH)D | Free 25(OH)D |
---|---|---|---|---|---|
HR (95% CI) | HR (95% CI) | HR (95% CI) | HR (95% CI) | ||
General population | Zhu 2022 [12] | 0.99 (0.79, 1.24) | 0.76 (0.60, 0.97) | 0.80 (0.63, 1.02) | 0.81 (0.64, 1.02) |
Cancer patients | |||||
Colorectal | Yang 2017 [13] | 2.01 (0.92, 4.41) | 1.79 (0.90, 3.56) | 0.40 (0.08, 1.94) | 0.44 (0.24, 0.81) |
Colorectal | Yuan 2020 [14] | 0.58 (0.37, 0.91) | 0.57 (0.34, 0.96) | 1.26 (0.77, 2.06) | 0.90 (0.68, 1.20) |
Liver | Fang 2020 [15] | - | 0.97 (0.72, 1.31) | 0.69 (0.51, 0.93) | 1.35 (0.83, 2.19) |
Lung | Turner 2013 [16] | 0.10 (0.01, 1.06) | - | - | - |
Lung | Anic 2014 [17] | 0.95 (0.71, 1.27) | 1.18 (0.89, 1.56) | - | - |
Subtotal | 0.84 (0.42, 1.67) | 1.02 (0.70, 1.48) | 0.83 (0.49, 1.41) | 0.84 (0.46, 1.51) | |
Other patients | |||||
All studies | 0.90 (0.63, 1.30) | 0.94 (0.70, 1.26) | 0.81 (0.63, 1.05) | 0.84 (0.59, 1.19) |
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. |
© 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Zhu, A.; Kuznia, S.; Boakye, D.; Schöttker, B.; Brenner, H. Vitamin D-Binding Protein, Bioavailable, and Free 25(OH)D, and Mortality: A Systematic Review and Meta-Analysis. Nutrients 2022, 14, 3894. https://doi.org/10.3390/nu14193894
Zhu A, Kuznia S, Boakye D, Schöttker B, Brenner H. Vitamin D-Binding Protein, Bioavailable, and Free 25(OH)D, and Mortality: A Systematic Review and Meta-Analysis. Nutrients. 2022; 14(19):3894. https://doi.org/10.3390/nu14193894
Chicago/Turabian StyleZhu, Anna, Sabine Kuznia, Daniel Boakye, Ben Schöttker, and Hermann Brenner. 2022. "Vitamin D-Binding Protein, Bioavailable, and Free 25(OH)D, and Mortality: A Systematic Review and Meta-Analysis" Nutrients 14, no. 19: 3894. https://doi.org/10.3390/nu14193894
APA StyleZhu, A., Kuznia, S., Boakye, D., Schöttker, B., & Brenner, H. (2022). Vitamin D-Binding Protein, Bioavailable, and Free 25(OH)D, and Mortality: A Systematic Review and Meta-Analysis. Nutrients, 14(19), 3894. https://doi.org/10.3390/nu14193894