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. 2019 Jan 29;16(3):383.
doi: 10.3390/ijerph16030383.

Vitamin D Status and Mortality: A Systematic Review of Observational Studies

Alicia K Heath  1 , Iris Y Kim  2   3 , Allison M Hodge  4   5 , Dallas R English  6   7 , David C Muller  8
Affiliations

Vitamin D Status and Mortality: A Systematic Review of Observational Studies

Alicia K Heath et al. Int J Environ Res Public Health. .

Abstract

Epidemiological evidence suggests that vitamin D deficiency is associated with increased mortality, but it is unclear whether this is explained by reverse causation, and if there are specific causes of death for which vitamin D might be important. We conducted a systematic review of observational studies investigating associations between circulating 25-hydroxyvitamin D (25(OH)D) concentration and all-cause or cause-specific mortality in generally healthy populations. Relevant studies were identified using PubMed and EMBASE searches. After screening 722 unique records and removing those that were ineligible, 84 articles were included in this review. The vast majority of studies reported inverse associations between 25(OH)D concentration and all-cause mortality. This association appeared to be non-linear, with progressively lower mortality with increasing 25(OH)D up to a point, beyond which there was no further decrease. There is moderate evidence that vitamin D status is inversely associated with cancer mortality and death due to respiratory diseases, while for cardiovascular mortality, there is weak evidence of an association in observational studies, which is not supported by the data from intervention or Mendelian randomization studies. The relationship between vitamin D status and other causes of death remains uncertain due to limited data. Larger long-term studies are required to clarify these associations.

Keywords: 25-hydroxyvitamin D; all-cause mortality; cancer mortality; cardiovascular mortality; cause-specific mortality; mortality; respiratory disease mortality; systematic review; vitamin D; vitamin D status.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Flow diagram of selection of studies included in the review.
Figure 2
Figure 2
Results from prospective studies investigating all-cause mortality in relation to 25-hydroxyvitamin D (25(OH)D) concentration: (a) comparing low versus high concentrations categorically; (b) continuously, for a decrement in 25(OH)D concentration; (c) low (black) and high (blue) concentrations compared with levels in the middle of the 25(OH)D distribution. The squares represent hazard ratios, and horizontal lines are the 95% confidence intervals. Studies that estimated odds ratios or relative risks are denoted by * and ^, respectively. Axes are scaled differently in each panel to maximize the visualization of effect estimates.
Figure 2
Figure 2
Results from prospective studies investigating all-cause mortality in relation to 25-hydroxyvitamin D (25(OH)D) concentration: (a) comparing low versus high concentrations categorically; (b) continuously, for a decrement in 25(OH)D concentration; (c) low (black) and high (blue) concentrations compared with levels in the middle of the 25(OH)D distribution. The squares represent hazard ratios, and horizontal lines are the 95% confidence intervals. Studies that estimated odds ratios or relative risks are denoted by * and ^, respectively. Axes are scaled differently in each panel to maximize the visualization of effect estimates.
Figure 3
Figure 3
Results from prospective studies investigating cardiovascular mortality in relation to 25-hydroxyvitamin D (25(OH)D) concentration: (a) comparing low versus high concentrations categorically; (b) continuously, for a decrement in 25(OH)D concentration; (c) low (black) and high (blue) concentrations compared with levels in the middle of the 25(OH)D distribution. The squares represent hazard ratios and horizontal lines are the 95% confidence intervals. Studies that estimated odds ratios or relative risks are denoted by * and ^, respectively. Axes are scaled differently in each panel to maximize the visualization of effect estimates.
Figure 4
Figure 4
Results from prospective studies investigating cancer mortality in relation to 25-hydroxyvitamin D (25(OH)D) concentration: (a) comparing low versus high concentrations categorically; (b) continuously, for a decrement in 25(OH)D concentration; (c) low (black) and high (blue) concentrations compared with levels in the middle of the 25(OH)D distribution. The squares represent hazard ratios and horizontal lines are the 95% confidence intervals. Studies that estimated odds ratios or relative risks are denoted by * and ^, respectively. Axes are scaled differently in each panel to maximize the visualization of effect estimates.
Figure 5
Figure 5
Results from prospective studies investigating respiratory disease mortality in relation to 25-hydroxyvitamin D (25(OH)D) concentration: (a) comparing low versus high concentrations categorically; (b) continuously, for a decrement in 25(OH)D concentration; (c) low (black) and high (blue) concentrations compared with levels in the middle of the 25(OH)D distribution. The squares represent hazard ratios and horizontal lines are the 95% confidence intervals. ^ Relative risk was estimated in the Whitehall study. Axes are scaled differently in each panel to maximize the visualization of effect estimates.
Figure 5
Figure 5
Results from prospective studies investigating respiratory disease mortality in relation to 25-hydroxyvitamin D (25(OH)D) concentration: (a) comparing low versus high concentrations categorically; (b) continuously, for a decrement in 25(OH)D concentration; (c) low (black) and high (blue) concentrations compared with levels in the middle of the 25(OH)D distribution. The squares represent hazard ratios and horizontal lines are the 95% confidence intervals. ^ Relative risk was estimated in the Whitehall study. Axes are scaled differently in each panel to maximize the visualization of effect estimates.
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