brand logo

Am Fam Physician. 2020;102(1):online

Author disclosure: No relevant financial affiliations.

Details for This Review

BenefitsHarms
1 in 274 did not die from cancer over a period of 1.2 yearsNot evaluated
No deaths from all causes were prevented
No cardiovascular deaths were prevented

Study Population: Adults taking vitamin D supplements

Efficacy End Points: Decrease in all-cause mortality, cancer mortality, or cardiovascular mortality

Harm End Points: None

Narrative: Vitamin D supplementation has been a topic of debate for many years. Vitamin D is essential to skeletal health and may also have other extraskeletal benefits. Observational studies have shown that those with low vitamin D levels have higher cancer and cardiovascular mortality. There is ongoing research to determine if vitamin D plays a role in decreasing all-cause mortality. Previous systematic reviews and meta-analyses have shown that oral vitamin D therapy was associated with small decreases in all-cause mortality. Recent trials with double the number of participants have shown no benefit of vitamin D supplementation on mortality.

This meta-analysis reviewed the effectiveness of vitamin D to reduce all-cause mortality, cancer mortality, cardiovascular mortality, noncancer or noncardiovascular mortality, cerebrovascular mortality, and ischemic heart disease mortality.1 It included 52 randomized controlled trials published before December 26, 2018 with a total of 75,454 participants. Intention-to-treat analysis was conducted to evaluate outcomes. Subgroup analyses were performed for dose (at least 2,000 IU per day and less than 2,000 IU per day), type of vitamin D (vitamin D2 and vitamin D3), timing of treatment (daily and intermittent), baseline serum 25-hydroxyvitamin D level (at least 20 ng per mL [49.92 nmol per L] and less than 20 ng per mL), and mean age at least 70 years and younger than 70 years). Retrospective subgroup analyses were also performed based on length of follow-up (at least three years and less than three years), year of publication (before 2014 or in/after 2014), sex (female and both sexes), residential status (community and institution), bolus (yes and no), intervention (vitamin D and vitamin D with calcium), and latitude (at least 40 degrees and less than 40 degrees).

For the primary outcome of all-cause mortality, there was no statistically significant difference between the vitamin D supplementation group and the control group (risk ratio = 0.98; 95% CI, 0.95 to 1.02). Several analyses showed a lack of publication bias or small group effect.

For the secondary outcomes of other mortality, the study found that vitamin D supplementation was associated with significant reduction in risk of cancer mortality (risk ratio = 0.84; 95% CI, 0.74 to 0.95; absolute risk reduction = 0.004; number needed to treat = 250). The study found no significant difference between groups in cardiovascular mortality, noncancer or noncardiovascular mortality, cerebrovascular mortality, or ischemic heart mortality.

Caveats: Vitamin D2 and vitamin D3 have differing effects in raising 25-hydroxy vitamin D levels. Most intervention trials comparing both have shown that vitamin D3 increased 25-hydroxyvitamin D levels more efficiently. Subgroup analyses found that all-cause mortality was significantly lower with vitamin D3 supplementation than vitamin D2 (P for interaction = .04). Similarly, vitamin D3 also reduced the risk of cancer mortality, but vitamin D2 did not (P for interaction = .11). Because subgroup analyses are observational by nature and not randomized comparisons, this effect on all-cause mortality requires additional evidence gathered by future large randomized controlled trials.

According to subgroup analysis, all-cause mortality was significantly lower in trials with longer follow-up (more than three years). Therefore, the length of vitamin D supplementation could affect the results on all-cause mortality.

In summary, high-quality evidence suggests that vitamin D supplementation does not decrease all-cause mortality, cardiovascular mortality, ischemic heart disease mortality, noncancer or noncardiovascular mortality, but it does decrease the risk of cancer mortality (number needed to treat = 274 for 1.2 years).

Copyright © 2020 MD Aware, LLC (theNNT.com). Used with permission.

This series is coordinated by Dean A. Seehusen, MD, MPH, AFP assistant medical editor, and Daniel Runde, MD, from the NNT Group.

A collection of Medicine by the Numbers published in AFP is available at https://www.aafp.org/afp/mbtn.

Copyright ©2022 MD Aware, LLC (theNNT.com). Used with permission.

This series is coordinated by Christopher W. Bunt, MD, AFP assistant medical editor, and the NNT Group.

A collection of Medicine by the Numbers published in AFP is available at https:// www.aafp.org/afp/mbtn.

Continue Reading


More in AFP

More in Pubmed

Copyright © 2020 by the American Academy of Family Physicians.

This content is owned by the AAFP. A person viewing it online may make one printout of the material and may use that printout only for his or her personal, non-commercial reference. This material may not otherwise be downloaded, copied, printed, stored, transmitted or reproduced in any medium, whether now known or later invented, except as authorized in writing by the AAFP.  See permissions for copyright questions and/or permission requests.